Following the Physical Activity Guidelines for Adults With Spinal Cord Injury for 16 Weeks Does Not Improve Vascular Health: A Randomized Controlled Trial.

PubMed

Totosy de Zepetnek, Julia O; Pelletier, Chelsea A; Hicks, Audrey L; MacDonald, Maureen J

2015-09-01

To evaluate the effects of following the physical activity guidelines (PAG) for adults with spinal cord injury (SCI) for 16 weeks. Randomized controlled trial. Community exercise program. Individuals with SCI (N=23; neurological level of injury, C3-T11; American Spinal Injury Association Impairment Scale A-C; time postinjury, 12.0±9.9 y; age, 41.4±11.6 y). Participants were randomly assigned to PAG training (n=12) or active control (n=11) groups. PAG training involved ≥20 minutes of moderate-vigorous aerobic exercise (rating of perceived exertion 3-6 on 10-point scale) and 3×10 repetitions of upper-body strengthening exercises (50%-70% 1 repetition maximum) 2 times per week. The control group maintained existing physical activity levels with no guidance on training intensity. Outcome measures were obtained pre- and postintervention. Vascular health indicators included arterial stiffness via carotid distensibility and pulse wave velocity, and endothelial function via flow-mediated-dilation. Fasted blood samples were analyzed for markers of cardiovascular disease (CVD) risk. Body composition was assessed via anthropometrics and with dual-energy x-ray absorptiometry. Twenty-one individuals completed the intervention (PAG=12, control=9). Group-by-time interactions were observed for whole-body mass (P=.03), whole-body fat (P=.04), visceral adipose tissue (P=.04), and carotid artery distensibility (P=.05), suggesting maintained body composition and carotid stiffness in the PAG group concurrent with declines in the control group. No changes were found in any other outcome measure. While 16 weeks of adherence to the PAG in adults with SCI is insufficient to improve many markers of CVD risk, it may prevent declines in others. The PAG should continue to be promoted as a means to increase physical fitness and maintain body composition in individuals with SCI, but changes may be needed to achieve other health outcomes. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Pediatric and adolescent gynecology learned via a Web-based computerized case series.

PubMed

De Silva, Nirupama K; Dietrich, Jennifer E; Young, Amy E

2010-04-01

To increase resident knowledge in pediatric and adolescent gynecology via a Web-based self-tutorial. Prospective cohort involving 11 third- and fourth-year residents in a large university program. Residents were asked to complete a Web-based teaching series of cases involving common topics of pediatric and adolescent gynecology (PAG). A pretest and a posttest were completed to assess knowledge gained. Residents were asked to give feedback regarding improvements to the Web-based series for future case development. University-affiliated residency program in a major metropolitan area. Resident physicians in the Department of Obstetrics and Gynecology. Introduction of a Web-based teaching series to enhance resident education. Improvement of resident knowledge in PAG. All residents improved their knowledge in PAG after reviewing the series of cases. The pretest group mean score was 50%. The posttest group score was 69% (P < .05). All (100%) of participants said that this tool was an effective way to improve resident knowledge in PAG. A computer-based self-tutorial in pediatric and adolescent gynecology is a feasible and satisfactory teaching adjunct to PAG. Copyright 2010 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Molecular Engineering of UV/Vis Light-Emitting Diode (LED)-Sensitive Donor-π-Acceptor-Type Sulfonium Salt Photoacid Generators: Design, Synthesis, and Study of Photochemical and Photophysical Properties.

PubMed

Wu, Xingyu; Jin, Ming; Xie, Jianchao; Malval, Jean-Pierre; Wan, Decheng

2017-11-07

A series of donor-π-acceptor-type sulfonium salt photoacid generators (PAGs) were designed and synthesized by systematically changing electron-donating groups, π-conjugated systems, electron-withdrawing groups, and the number of branches through molecular engineering. These PAGs can effectively decompose under UV/Vis irradiation from a light-emitting diode (LED) light source because of the matching absorption and emitting spectra of the LEDs. The absorption and acid-generation properties of these sulfonium salts were elucidated by UV/Vis spectroscopy and so forth. Results indicated that the PAG performance benefited from the introduction of strong electron-donating groups, specific π-conjugated structures, certain electron-withdrawing groups, or two-branched structures. Most sulfonium salts showed potential as photoinitiators under irradiation by a wide variety of UV and visible LEDs. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

fMRI functional connectivity of the periaqueductal gray in PTSD and its dissociative subtype.

PubMed

Harricharan, Sherain; Rabellino, Daniela; Frewen, Paul A; Densmore, Maria; Théberge, Jean; McKinnon, Margaret C; Schore, Allan N; Lanius, Ruth A

2016-12-01

Posttraumatic stress disorder (PTSD) is associated with hyperarousal and active fight or flight defensive responses. By contrast, the dissociative subtype of PTSD, characterized by depersonalization and derealization symptoms, is frequently accompanied by additional passive or submissive defensive responses associated with autonomic blunting. Here, the periaqueductal gray (PAG) plays a central role in defensive responses, where the dorsolateral (DL-PAG) and ventrolateral PAG (VL-PAG) are thought to mediate active and passive defensive responses, respectively. We examined PAG subregion (dorsolateral and ventrolateral) resting-state functional connectivity in three groups: PTSD patients without the dissociative subtype ( n  = 60); PTSD patients with the dissociative subtype ( n  = 37); and healthy controls ( n  = 40) using a seed-based approach via PickAtlas and SPM12. All PTSD patients showed extensive DL- and VL-PAG functional connectivity at rest with areas associated with emotional reactivity and defensive action as compared to controls ( n  = 40). Although all PTSD patients demonstrated DL-PAG functional connectivity with areas associated with initiation of active coping strategies and hyperarousal (e.g., dorsal anterior cingulate; anterior insula), only dissociative PTSD patients exhibited greater VL-PAG functional connectivity with brain regions linked to passive coping strategies and increased levels of depersonalization (e.g., temporoparietal junction; rolandic operculum). These findings suggest greater defensive posturing in PTSD patients even at rest and demonstrate that those with the dissociative subtype show unique patterns of PAG functional connectivity when compared to those without the subtype. Taken together, these findings represent an important first step toward identifying neural and behavioral targets for therapeutic interventions that address defensive strategies in trauma-related disorders.

Endometriosis Is Associated With a Shift in MU Opioid and NMDA Receptor Expression in the Brain Periaqueductal Gray

PubMed Central

Torres-Reverón, Annelyn; Palermo, Karylane; Hernández-López, Anixa; Hernández, Siomara; Cruz, Myrella L.; Thompson, Kenira J.; Flores, Idhaliz; Appleyard, Caroline B.

2016-01-01

Studies have examined how endometriosis interacts with the nervous system, but little attention has been paid to opioidergic systems, which are relevant to pain signaling. We used the autotransplantation rat model of endometriosis and allowed to progress for 60 days. The brain was collected and examined for changes in endogenous opioid peptides, mu opioid receptors (MORs), and the N-methyl-d-aspartate subunit receptor (NR1) in the periaqueductal gray (PAG), since both of these receptors can regulate PAG activity. No changes in endogenous opioid peptides in met- and leu-enkephalin or β-endorphin levels were observed within the PAG. However, MOR immunoreactivity was significantly decreased in the ventral PAG in the endometriosis group. Endometriosis reduced by 20% the number of neuronal profiles expressing MOR and reduced by 40% the NR1 profiles. Our results suggest that endometriosis is associated with subtle variations in opioidergic and glutamatergic activity within the PAG, which may have implications for pain processing. PMID:27089914

Significance of hydrogen sulfide in sepsis-induced myocardial injury in rats

PubMed Central

Li, Xiaoqing; Cheng, Qinghong; Li, Jianhua; He, Yonglai; Tian, Peigang; Xu, Chao

2017-01-01

Sepsis-induced myocardial injury is a detrimental disorder for intensive care medicine due to its high rates of morbidity and mortality. Data suggest that nuclear factor (NF)-κB serves a critical role in the pathogenesis of myocardial injury. Hydrogen sulfide (H2S) serves an important role in the physiology and pathophysiology of regulatory mechanisms, particularly during an inflammatory reaction. However, the relationship between NF-κB and H2S in sepsis-induced myocardial injury is not well understood, and the underlying mechanisms remain unclear. In the present study, 60 male Sprague Dawley rats were randomly divided into the following six groups: A sham group, cecal ligation and puncture (CLP) group, sham + propargylglycine (PAG) group, CLP + PAG group, sham + sodium hydrosulfide (NaHS) group and CLP + NaHS group, with 10 rats in each group. The rats in all groups were sacrificed 12 h after surgery for sample collection. Compared with the sham group, it was observed that the concentrations of Creatine Kinase-MB (CK-MB) and cardiac troponin I (cTnI) in the serum, and pathological scores of myocardial tissue were significantly increased in the CLP, CLP + NaHS and CLP + PAG groups (P<0.05). The pathological scores and concentrations of CK-MB and cTnI were significantly higher in the CLP + PAG group (P<0.05) and significantly lower in the CLP + NaHS group (P<0.05) when compared with the CLP group. The expression of cystathionine-γ-lyase (CSE) mRNA and content of interleukin (IL)-10 were significantly higher in the CLP group compared with the CLP + PAG group (P<0.05), while the expression of myocardial NF-κB and content of tumor necrosis factor (TNF)-α in the CLP group were significantly lowered compared with the CLP + PAG group (P<0.05). The expression of NF-κB and content of TNF-α were significantly increased in the CLP group when compared with the CLP + NaHS group (P<0.05), while the content of myocardial IL-10 in the CLP group was significantly lower than in the CLP + NaHS group (P<0.05). In conclusion, H2S acted as an anti-inflammatory cytokine and biomarker in sepsis-induced myocardial injury. Furthermore, H2S may downregulate the NF-κB subunit p65 to mediate inflammatory responses. The present data suggest that myocardial injury in sepsis may be relieved through the regulation of H2S expression, and provide an experimental basis for the treatment of sepsis patients presenting with myocardial injury. In addition, myocardial injury in sepsis may be identified by monitoring changes in the expression of H2S. PMID:28962136

Targeted Technology Transfer to US Independents

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

Donald F. Duttlinger; E. Lance Cole

2006-09-29

The Petroleum Technology Transfer Council (PTTC) was established by domestic crude oil and natural gas producers in 1994 as a national not-for-profit organization to address the increasingly urgent need to improve the technology-transfer process in the U.S. upstream petroleum industry. Coordinated from a Headquarters (HQ) office in Houston, PTTC maintains an active grassroots program executed by 10 Regional Lead Organizations (RLOs) and two satellite offices (Figure 1). Regional Directors interact with domestic oil and gas producers through technology workshops, resource centers, websites, newsletters, technical publications and cooperative outreach efforts. HQ facilitates inter-regional technology transfer and implements a comprehensive communications program.more » Active volunteers on the National Board and in Producer Advisory Groups (PAGs) in each of the 10 regions focus effort in areas that will create the most impact for domestic producers. Focused effort by dedicated individuals across the country has enabled PTTC to achieve the milestones outlined in Appendix A.« less

Anatomical study of the final common pathway for vocalization in the cat

NASA Technical Reports Server (NTRS)

Holstege, Gert

1989-01-01

Results are presented of an anatomical study of the neuronal pathways in the cat, via which the periaqueductal gray (PAG) produces excitation of motoneurons involved in vocalization. It is shown that a specific cell group in the lateral part of the caudal PAG and in the tegmentum just lateral to it projects bilaterally to the nucleus retroambiguus (NRA) in the caudal medulla oblongata. Neurons in the NRA in turn project, via a contralateral pathway through the ventral funiculus of the spinal cord, to the motoneuronal cell groups innervating intercostal and abdominal muscles. In the brainstem, the NRA neurons project to the motoneuronal cell groups innervating mouth-opening and perioral muscles as well as to motoneurons innervating the pharynx, soft palate, and tongue. These results indicate that the projections from PAG via NRA to vocalization motoneurons form the final common pathway in vocalization.

Disrupted functional connectivity of the periaqueductal gray in chronic low back pain

PubMed Central

Yu, Rongjun; Gollub, Randy L.; Spaeth, Rosa; Napadow, Vitaly; Wasan, Ajay; Kong, Jian

2014-01-01

Chronic low back pain is a common neurological disorder. The periaqueductal gray (PAG) plays a key role in the descending modulation of pain. In this study, we investigated brain resting state PAG functional connectivity (FC) differences between patients with chronic low back pain (cLBP) in low pain or high pain condition and matched healthy controls (HCs). PAG seed based functional connectivity (FC) analysis of the functional MR imaging data was performed to investigate the difference among the connectivity maps in the cLBP in the low or high pain condition and HC groups as well as within the cLBP at differing endogenous back pain intensities. Results showed that FC between the PAG and the ventral medial prefrontal cortex (vmPFC)/rostral anterior cingulate cortex (rACC) increased in cLBP patients compared to matched controls. In addition, we also found significant negative correlations between pain ratings and PAG–vmPFC/rACC FC in cLBP patients after pain-inducing maneuver. The duration of cLBP was negatively correlated with PAG–insula and PAG–amygdala FC before pain-inducing maneuver in the patient group. These findings are in line with the impairments of the descending pain modulation reported in patients with cLBP. Our results provide evidence showing that cLBP patients have abnormal FC in PAG centered pain modulation network during rest. PMID:25379421

PERIAQUEDUCTAL GRAY NEUROPLASTICITY FOLLOWING CHRONIC MORPHINE VARIES WITH AGE: ROLE OF OXIDATIVE STRESS

PubMed Central

Bajic, Dusica; Berde, Charles B.; Commons, Kathryn G.

2012-01-01

The development of tolerance to the antinociceptive effects of morphine has been associated with networks within ventrolateral periaqueductal gray (vlPAG) and separately, nitric oxide signaling. Furthermore, it is known that the mechanisms that underlie tolerance differ with age. In this study, we used a rat model of antinociceptive tolerance to morphine at two ages, postnatal day (PD) 7 and adult, to determine if changes in the vlPAG related to nitric oxide signaling produced by chronic morphine exposure were age-dependent. Three pharmacological groups were analyzed: control, acute morphine, and chronic morphine group. Either morphine (10 mg/kg) or equal volume of normal saline was given subcutaneously twice daily for 6 ½ days. Animals were analyzed for morphine dose-response using Hot Plate test, and for the expression of several genes associated with nitric oxide metabolism was evaluated using rtPCR. In addition, the effect of morphine exposure on immunohistochemistry for Fos, and nNOS as well as nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) reaction at the vlPAG were measured. In both age groups acute morphine activated Fos in the vlPAG, and this effect was attenuated by chronic morphine, specifically in the vlPAG at the level of the laterodorsal tegmental nucleus (LDTg). In adults, but not PD7 rats, chronic morphine administration was associated with activation of nitric oxide function. In contrast, changes in the gene expression of PD7 rats suggested superoxide and peroxide metabolisms may be engaged. These data indicate that there is supraspinal neuroplasticity following morphine administration as early as PD7. Furthermore, oxidative stress pathways associated with chronic morphine exposure appear age-specific. PMID:22999971

Reflecting on the Postgraduate Experience: Teaching Research Methods and Statistics: Review of the DART-P Sponsored Workshop at PsyPAG 2013

ERIC Educational Resources Information Center

Jackson, Emma J.; Davies, Emma. L.

2014-01-01

Following the success of last year's teaching and career development workshop, this year's DART-P sponsored workshop at the Psychology Postgraduate Affairs Group (PsyPAG) Annual Conference held at Lancaster University focused on postgraduate's experiences of teaching research methods. This article provides a review of the invited speakers…

Effect of polaprezinc on oral mucositis, irradiation period, and time to discharge in patients with head and neck cancer.

PubMed

Suzuki, Akio; Kobayashi, Ryo; Shakui, Toshinobu; Kubota, Yukimasa; Fukita, Masaharu; Kuze, Bunya; Aoki, Mitsuhiro; Sugiyama, Tadashi; Mizuta, Keisuke; Itoh, Yoshinori

2016-09-01

The purpose of the present study was to determine whether polaprezinc suspension in sodium alginate (P-AG) reduces the irradiation period and time to discharge after completion of radiotherapy in patients with head and neck cancer. The incidence and severity of oral mucositis, the irradiation period, and the time to discharge in patients who received radiotherapy with head and neck cancer were investigated retrospectively from the medical records. The incidence of grade 3 oral mucositis was significantly lower in the P-AG group than in the control group (16.5% vs 52.0%; p = .0003). P-AG also significantly reduced median duration of radiotherapy (hazard ratio [HR] = 0.557; 95% confidence interval [CI] = 0.357-0.871; p = .0149) and median time to discharge after completion of radiotherapy (HR = 0.604; 95% CI = 0.386-0.946; p = .028). P-AG reduced the irradiation period and the time to discharge after completion of radiotherapy by preventing oral mucositis in patients with head and neck cancer. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1387-1392, 2016. © 2016 Wiley Periodicals, Inc.

Role of dorsolateral periaqueductal grey in the coordinated regulation of cardiovascular and respiratory function.

PubMed

Dampney, Roger A L; Furlong, Teri M; Horiuchi, Jouji; Iigaya, Kamon

2013-04-01

The midbrain periaqueductal grey (PAG) contains four longitudinal columns, referred to as the dorsomedial (dmPAG), dorsolateral (dlPAG), lateral (lPAG) and ventrolateral (vlPAG) subdivisions, which collectively have a pivotal role in integrating behavioural and physiological responses to external stressors as well as other functions. This review is focussed on the dlPAG, which is believed to be an important component of the central mechanisms that generate the defensive response to acute psychological stressors, such as the presence of a predator or other immediate threat. The anatomical connections of the dlPAG are highly specific and distinctly different from those of the other PAG subregions. The chemical properties of the dlPAG are also distinctly different from the other PAG subregions (e.g. there is a very high density of neurons that synthesize nitric oxide in the dlPAG but very few such neurons in the other PAG subregions). Recent functional studies have demonstrated that neurons in the dlPAG exert a powerful control over both sympathetic and respiratory activity, and that the pattern of the evoked respiratory changes is also distinctly different from those evoked from other PAG subregions. These studies also showed that the sympathetic and respiratory changes evoked from the dlPAG are highly correlated, suggesting the possibility that a common population of "command neurons" within this region may generate the sympathetic and respiratory changes that accompany defensive behavioural responses to acute psychological stressors. Finally, although the anatomical connections and functional properties of the dlPAG are distinctly different from the other PAG subregions, they have many similarities with adjacent parts of the superior colliculus, suggesting that the dlPAG and deep layers of the superior colliculus may be part of a common defence system in the midbrain. Copyright © 2013 Elsevier B.V. All rights reserved.

Dorsal periaqueductal gray-amygdala pathway conveys both innate and learned fear responses in rats

PubMed Central

Kim, Eun Joo; Horovitz, Omer; Pellman, Blake A.; Tan, Lancy Mimi; Li, Qiuling; Richter-Levin, Gal; Kim, Jeansok J.

2013-01-01

The periaqueductal gray (PAG) and amygdala are known to be important for defensive responses, and many contemporary fear-conditioning models present the PAG as downstream of the amygdala, directing the appropriate behavior (i.e., freezing or fleeing). However, empirical studies of this circuitry are inconsistent and warrant further examination. Hence, the present study investigated the functional relationship between the PAG and amygdala in two different settings, fear conditioning and naturalistic foraging, in rats. In fear conditioning, electrical stimulation of the dorsal PAG (dPAG) produced unconditional responses (URs) composed of brief activity bursts followed by freezing and 22-kHz ultrasonic vocalization. In contrast, stimulation of ventral PAG and the basolateral amygdalar complex (BLA) evoked freezing and/or ultrasonic vocalization. Whereas dPAG stimulation served as an effective unconditional stimulus for fear conditioning to tone and context conditional stimuli, neither ventral PAG nor BLA stimulation supported fear conditioning. The conditioning effect of dPAG, however, was abolished by inactivation of the BLA. In a foraging task, dPAG and BLA stimulation evoked only fleeing toward the nest. Amygdalar lesion/inactivation blocked the UR of dPAG stimulation, but dPAG lesions did not block the UR of BLA stimulation. Furthermore, in vivo recordings demonstrated that electrical priming of the dPAG can modulate plasticity of subiculum–BLA synapses, providing additional evidence that the amygdala is downstream of the dPAG. These results suggest that the dPAG conveys unconditional stimulus information to the BLA, which directs both innate and learned fear responses, and that brain stimulation-evoked behaviors are modulated by context. PMID:23959880

Activation of reciprocal pathways between arcuate nucleus and ventrolateral periaqueductal gray during electroacupuncture: involvement of VGLUT3

PubMed Central

Guo, Zhi-Ling; Longhurst, John C.

2010-01-01

Electroacupuncture (EA) at the Jianshi-Neiguan acupoints (P5-P6, overlying the median nerve) attenuates sympathoexcitatory responses through activation of the arcuate nucleus (ARC) and ventrolateral periaqueductal gray (vlPAG). Activation of the ARC or vlPAG respectively leads to neuronal excitation of the both nuclei during EA. However, direct projections between these two nuclei that could participate in central neural processing during EA have not been identified. The vesicular glutamate transporter 3 (VGLUT3) marks glutamatergic neurons. Thus, the present study evaluated direct neuronal projections between the ARC and vlPAG during EA, focusing on neurons containing VGLUT3. Seven to ten days after unilateral microinjection of a rodamine-conjugated microsphere retrograde tracer (100 nl) into the vlPAG or ARC, rats were subjected to EA or served as a sham-operated control. Low frequency (2 Hz) EA was performed bilaterally for 30 min at the P5-P6 acupoints. Perikarya containing the microsphere tracer were found in the ARC and vlPAG of both groups. Compared to controls (needle placement without electrical stimulation), c-Fos immunoreactivity and neurons double-labeled with c-Fos, an immediate early gene and the tracer were increased significantly in the ARC and vlPAG of EA-treated rats (both P<0.01). Moreover, some neurons were triple-labeled with c-Fos, the retrograde tracer and VGLUT3 in the two nuclei following EA stimulation (P<0.01, both nuclei). These results suggest that direct reciprocal projections between the ARC and vlPAG are available to participate in prolonged modulation by EA of sympathetic activity and that VGLUT3-containing neurons are an important neuronal phenotype involved in this process. PMID:20836994

A Case of Mistaken Identity? A Comparison of Professional and Amateur Problem Gamblers.

PubMed

Hing, Nerilee; Russell, Alex M T; Gainsbury, Sally M; Blaszczynski, Alex

2016-03-01

Professional gamblers are more likely than amateur gamblers to meet criteria for problem gambling but minimal research has examined their gambling behavior and its consequences. This study compared gambling behavior, problem gambling symptoms, related harms, recognition, and help-seeking among problem semi/professional gamblers (PPGs/PSPGs) and problem amateur gamblers (PAGs). Surveys completed by 57 self-identified professional gamblers, 311 semi-professional gamblers and 4226 amateur gamblers were analysed. PPGs/PSPGs were significantly more likely than PAGs to be male, younger, never married, speak a language other than English at home, and have higher psychological distress, compared to PAGs. PPGs/PSPGs were more likely to gamble more frequently on many skills-based forms, but most also participated in several chance-based forms. PPGs'/PSPGs' most common problematic gambling form was electronic gaming machines and they were more likely to have problems with sports betting than PAGs. Most PPGs/PSPGs reported coming out behind on all gambling forms over the previous year. PPGs/PSPGs were more likely than PAGs to report chasing losses and numerous detrimental financial gambling consequences. This group's self-identification as PPGs/PSPGs is clearly inaccurate and perhaps a means to avoid stigma, elevate status and support problem denial. PPGs/PSPGs may represent an extreme example of gamblers with erroneous cognitions and beliefs who lack the required discipline and skill to be successful professional gamblers. The findings identify a group of problem gamblers who may benefit from interventions to dispel their mistaken self-identity, and emphasize the need for more rigorous confirmation of professional gambler status in future research.

Factors related to meeting physical activity guidelines in active college students: A social cognitive perspective.

PubMed

Farren, G L; Zhang, T; Martin, S B; Thomas, K T

2017-01-01

To examine the relations of sex, exercise self-efficacy, outcome expectations, and social support with meeting physical activity guidelines (PAGs). Three hundred ninety-six college students participated in this study in the summer 2013. Students completed online questionnaires that assessed physical activity behaviors and psychosocial factors (ie, self-efficacy, outcome expectancies, and social support). Students' physical activity profile was categorized as meeting no PAGs, meeting aerobic PAGs only, meeting muscle-strengthening PAGs only, or meeting both PAGs. A multinomial logistic regression revealed that students' sex and psychosocial factors significantly affected the odds of meeting any and all PAGs. Sex significantly moderated the relationship between outcome expectancy and meeting aerobic PAGs and between outcome expectancy meeting muscle-strengthening PAGs. Results indicate that interventions designed to increase psychosocial factors may increase the likelihood of students meeting any and all PAGs. Social support may be especially beneficial for increasing muscle-strengthening activity.

[Effect of dizocilpine maleate and taurine on the circuitry of glutamate and glutamine in rat striatum exposed by manganese].

PubMed

Jia, Ke; Xu, Zhaofa; Xu, Bin

2008-01-01

To observe the effect of MK-801 and taurine on the activities of GS and PAG and the glutamatic neuron content in the rat striatum exposed by manganese. 40 Wistar rats were random divided into four groups. The first group was the control group which was subcutaneously injected at the content of 0.9% NaCl. The second group was MnCl2 group which was subcutaneously injected at the content of 0.9% NaCl. The third and fourth groups were pretreatment groups which were subcutaneously injected of 0.3 micromol/kg MK-801 and 1 mmol/kg taurine. After 2h, the first group was peritoneally injected at the content of 0.9% NaCl, the 2nd-4th group were peritoneally injected at the dose of 200 micromol/kg MnCl2. All administration was given at the dose of 5 ml/kg for 25d, the pretreatment groups were given for every other day. At the 24h after the administration of MnCl2, the 4 rats brain tissue in every groups were removed after the rats were perfused from the left ventricles to with 4% ploymerisatum. The glutamatic neuron content were determined by immunohistochemical method (SABC). The activities of GS and PAG in the residual rat striatum were determined. In comparison with control group, the percentage of positive area and integral optical densities of glutamate immunocreative cell increased significantly in MnCl2 group (P < 0.01), the activity of GS decreased significantly in MnCl2 group, the activity of PAG increased significantly in MnCl2 group. In comparison with MnCl2 group, the percentage of positive area and integral optical density of glutamate immunocreative cell decreased significantly in MK-801 and taurine pretreatment group, the activity of GS increased significantly in MK-801 and taurine pretreatment group , the activity of PAG decreased significantly in MK-801 pretreatment group. MK-801 and taurine have a certain protective effect on "the circuitry of glutamate and glutamine" disrupted with Mn.

Ancestral genetic diversity associated with the rapid spread of stress-tolerant coral symbionts in response to Holocene climate change.

PubMed

Hume, Benjamin C C; Voolstra, Christian R; Arif, Chatchanit; D'Angelo, Cecilia; Burt, John A; Eyal, Gal; Loya, Yossi; Wiedenmann, Jörg

2016-04-19

Coral communities in the Persian/Arabian Gulf (PAG) withstand unusually high salinity levels and regular summer temperature maxima of up to ∼35 °C that kill conspecifics elsewhere. Due to the recent formation of the PAG and its subsequent shift to a hot climate, these corals have had only <6,000 y to adapt to these extreme conditions and can therefore inform on how coral reefs may respond to global warming. One key to coral survival in the world's warmest reefs are symbioses with a newly discovered alga,Symbiodinium thermophilum Currently, it is unknown whether this symbiont originated elsewhere or emerged from unexpectedly fast evolution catalyzed by the extreme environment. Analyzing genetic diversity of symbiotic algae across >5,000 km of the PAG, the Gulf of Oman, and the Red Sea coastline, we show thatS. thermophilumis a member of a highly diverse, ancient group of symbionts cryptically distributed outside the PAG. We argue that the adjustment to temperature extremes by PAG corals was facilitated by the positive selection of preadapted symbionts. Our findings suggest that maintaining the largest possible pool of potentially stress-tolerant genotypes by protecting existing biodiversity is crucial to promote rapid adaptation to present-day climate change, not only for coral reefs, but for ecosystems in general.

Design, synthesis, and characterization of fluorine-free PAGs for 193-nm lithography

NASA Astrophysics Data System (ADS)

Liu, Sen; Glodde, Martin; Varanasi, Pushkara R.

2010-04-01

Photoacid generators (PAGs) are a key component in chemically amplified resists used in photolithography. Perfluorooctanesulfonates (PFOS) and other perfluoroalkylsulfonates (PFAS) have been well adopted as PAGs in 193 nm photoresist. Recently, concerns have been raised about their environmental impact due to their chemical persistency, bioaccumulation and toxicity. It is a general interest to find environmentally benign PAGs that are free of fluorine atoms. Here we describe the design, synthesis and characterization of a series of novel fluorine-free onium salts as PAGs for 193 nm photoresists. These PAGs demonstrated desirable physical and lithography properties when compared with PFAS-based PAGs for both dry and immersion exposures.

Endocannabinoids control vesicle release mode at midbrain periaqueductal grey inhibitory synapses.

PubMed

Aubrey, Karin R; Drew, Geoffrey M; Jeong, Hyo-Jin; Lau, Benjamin K; Vaughan, Christopher W

2017-01-01

The midbrain periaqueductal grey (PAG) forms part of an endogenous analgesic system which is tightly regulated by the neurotransmitter GABA. The role of endocannabinoids in regulating GABAergic control of this system was examined in rat PAG slices. Under basal conditions GABAergic neurotransmission onto PAG output neurons was multivesicular. Activation of the endocannabinoid system reduced GABAergic inhibition by reducing the probability of release and by shifting release to a univesicular mode. Blockade of endocannabinoid system unmasked a tonic control over the probability and mode of GABA release. These findings provides a mechanistic foundation for the control of the PAG analgesic system by disinhibition. The midbrain periaqueductal grey (PAG) has a crucial role in coordinating endogenous analgesic responses to physiological and psychological stressors. Endocannabinoids are thought to mediate a form of stress-induced analgesia within the PAG by relieving GABAergic inhibition of output neurons, a process known as disinhibition. This disinhibition is thought to be achieved by a presynaptic reduction in GABA release probability. We examined whether other mechanisms have a role in endocannabinoid modulation of GABAergic synaptic transmission within the rat PAG. The group I mGluR agonist DHPG ((R,S)-3,5-dihydroxyphenylglycine) inhibited evoked IPSCs and increased their paired pulse ratio in normal external Ca 2+ , and when release probability was reduced by lowering Ca 2+ . However, the effect of DHPG on the coefficient of variation and kinetics of evoked IPSCs differed between normal and low Ca 2+ . Lowering external Ca 2+ had a similar effect on evoked IPSCs to that observed for DHPG in normal external Ca 2+ . The low affinity GABA A receptor antagonist TPMPA ((1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid) inhibited evoked IPSCs to a greater extent in low than in normal Ca 2+ . Together these findings indicate that the normal mode of GABA release is multivesicular within the PAG, and that DHPG and lowering external Ca 2+ switch this to a univesicular mode. The effects of DHPG were mediated by mGlu5 receptor engagement of the retrograde endocannabinoid system. Blockade of endocannabinoid breakdown produced a similar shift in the mode of release. We conclude that endocannabinoids control both the mode and the probability of GABA release within the PAG. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Prevalence and trends in physical activity among older adults in the United States: A comparison across three national surveys.

PubMed

Keadle, Sarah Kozey; McKinnon, Robin; Graubard, Barry I; Troiano, Richard P

2016-08-01

This paper examined how many older adults (65+years) are meeting physical activity (PA) Guidelines (PAG; 150min/week of moderate-to-vigorous PA) using data from three leading national surveys (NHANES, BRFSS and NHIS). The proportion of individuals meeting aerobic PAG was determined for the most recent cycle available for each survey (NHANES 2011-12, NHIS and BRFSS 2013). We also assessed whether PAG adherence has changed over time. Predicted margins from multinomial logistic regression were computed after adjusting for age, race/ethnicity and gender and sample weights. The proportion of older adults meeting PAG was 27.3% for NHANES, 35.8% for NHIS and 44.3% for BRFSS. Across all surveys, men reported higher levels of activity than women, Non-Hispanic whites reported higher levels than Non-Hispanic blacks and Hispanics, activity declined with age and was lower in those with functional limitations, all P<0.05. The proportion of older adults meeting PAG in the NHIS survey, the only survey where PA questions remained the same over time, increased from 25.7% in 1998 to 35.8% in 2013 (P<0.01). Point-estimates for activity levels are different between surveys but they consistently identify sub-groups who are less active. Although older adults are reporting more activity over time, adherence to aerobic and strength training PAG remains low in this population and there is a need for effective interventions to prevent age-related declines in PA and address health disparities among older adults. Published by Elsevier Inc.

Prevalence and trends in physical activity among older adults in the United States: A comparison across three national surveys

PubMed Central

Keadle, Sarah Kozey; McKinnon, Robin; Graubard, Barry I; Troiano, Richard P

2016-01-01

This paper examined how many older adults (65+ yrs) are meeting physical activity (PA) Guidelines (PAG; 150 min/wk of moderate-to-vigorous PA) using data from three leading national surveys (NHANES, BRFSS and NHIS). The proportion of individuals meeting aerobic PAG was determined for the most recent cycle available for each survey (NHANES 2011–12, NHIS and BRFSS 2013). We also assessed whether PAG adherence has changed over time. Predicted margins from multinomial logistic regression were computed after adjusting for age, race/ethnicity and gender and sample weights. The proportion of older adults meeting PAG was 27.3% for NHANES, 35.8% for NHIS and 44.3% for BRFSS. Across all surveys, men reported higher levels of activity than women, Non-Hispanic Whites reported higher levels than Non-Hispanic Blacks and Hispanics, activity declined with age and was lower in those with functional limitations, all P<0.05. The proportion of older adults meeting PAG in the NHIS survey, the only survey where PA questions remained the same over time, increased from 25.7% in 1998 to 35.8% in 2013 (P<0.01). Point-estimates for activity levels are different between surveys but they consistently identify sub-groups who are less active. Although older adults are reporting more activity over time, adherence to aerobic and strength training PAG remains low in this population and there is a need for effective interventions are needed to prevent age-related declines in PA and address health disparities among older adults. PMID:27196146

Identification of pregnancy-associated glycoproteins and alpha-fetoprotein in fallow deer (Dama dama) placenta

PubMed Central

2014-01-01

Background This paper describes the isolation and characterization of pregnancy-associated glycoproteins (PAG) from fetal cotyledonary tissue (FCT) and maternal caruncular tissue (MCT) collected from fallow deer (Dama dama) pregnant females. Proteins issued from FCT and MCT were submitted to affinity chromatographies by using Vicia villosa agarose (VVA) or anti-bovine PAG-2 (R#438) coupled to Sepharose 4B gel. Finally, they were characterized by SDS-PAGE and N-terminal microsequencing. Results Four distinct fallow deer PAG (fdPAG) sequences were identified and submitted to Swiss-Prot database. Comparison of fdPAG with PAG sequences identified in other ruminant species exhibited 64 to 83% identity. Additionally, alpha-fetoprotein was identified in fetal and maternal tissues. Conclusion Our results demonstrate the efficacy of VVA and bovine PAG-2 affinity chromatographies for the isolation of PAG molecules expressed in deer placenta. This is the first report giving four specific amino acid sequences of PAG isolated from feto-maternal junction (FCT and MCT) in the Cervidae family. PMID:24410890

Factors associated with pregnancy-associated glycoprotein (PAG) levels in plasma and milk of Holstein cows during early pregnancy and their effect on the accuracy of pregnancy diagnosis.

PubMed

Ricci, A; Carvalho, P D; Amundson, M C; Fourdraine, R H; Vincenti, L; Fricke, P M

2015-04-01

Lactating Holstein cows (n = 141) were synchronized to receive their first timed artificial insemination (TAI). Blood and milk samples were collected 25 and 32 d after TAI, and pregnancy status was determined 32 d after TAI using transrectal ultrasonography. Cows diagnosed pregnant with singletons (n = 48) continued the experiment in which blood and milk samples were collected and pregnancy status was assessed weekly using transrectal ultrasonography from 39 to 102 d after TAI. Plasma and milk samples were assayed for pregnancy-associated glycoprotein (PAG) levels using commercial ELISA kits. Compared to ultrasonography, accuracy was 92% for the plasma PAG ELISA test and 89% for the milk PAG ELISA test 32 d after TAI. Plasma and milk PAG levels for pregnant cows increased from 25 d to an early peak 32 d after TAI. Plasma and milk PAG levels then decreased from 32 d after TAI to a nadir from 53 to 60 d after TAI for the plasma PAG assay and from 46 to 67 d after TAI for the milk PAG assay followed by an increase from 74 to 102 d after TAI. Overall, plasma PAG levels were approximately 2-fold greater compared with milk PAG levels, and primiparous cows had greater PAG levels in plasma and milk compared with multiparous cows. The incidence of pregnancy loss from 32 to 102 d after TAI based on ultrasonography was 13% for cows diagnosed with singleton pregnancies, and plasma and milk PAG levels decreased to nonpregnant levels within 7 to 14 d after pregnancy loss. Both plasma and milk PAG levels were negatively correlated with milk production for both primiparous and multiparous cows. We conclude that stage of gestation, parity, pregnancy loss, and milk production were associated with plasma and milk PAG levels after TAI similarly. Based on plasma and milk PAG profiles, the optimal time to conduct a first pregnancy diagnosis is around 32 d after AI, coinciding with an early peak in PAG levels. Because of the occurrence of pregnancy loss, all pregnant cows should be retested 74 d after AI or later when plasma and milk PAG levels in pregnant cows have rebounded from their nadir. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Gauging a Hydrocarbon Ruler by an Intrinsic Exciton Probe†

PubMed Central

Khan, M. Adil; Neale, Chris; Michaux, Catherine; Pomés, Régis; Privé, Gilbert G.; Woody, Robert W.; Bishop, Russell E.

2016-01-01

The structural basis of lipid acyl-chain selection by membrane-intrinsic enzymes is poorly understood because most integral membrane enzymes of lipid metabolism have proven refractory to structure determination; however, robust enzymes from the outer membranes of Gram-negative bacteria are now providing a first glimpse at the underlying mechanisms. The methylene unit resolution of the phospholipid: lipid A palmitoyltransferase PagP is determined by the hydrocarbon ruler, a 16-carbon saturated acyl-chain-binding pocket buried within the transmembrane β-barrel structure. Substitution of Gly88 lining the floor of the hydrocarbon ruler with Ala or Met makes the enzyme select specifically 15- or 12-carbon saturated acyl chains, respectively, indicating that hydrocarbon ruler depth determines acyl-chain selection. However, the Gly88Cys PagP resolution does not diminish linearly because it selects both 14- and 15-carbon saturated acyl chains. We discovered that an exciton, emanating from a buried Tyr26–Trp66 phenol–indole interaction, is extinguished by a local structural perturbation arising from the proximal Gly88Cys PagP sulfhydryl group. Site-specific S-methylation of the single Cys afforded Gly88Cys-S-methyl PagP, which reasserted both the exciton and methylene unit resolution by specifically selecting 13-carbon saturated acyl chains for transfer to lipid A. Unlike the other Gly88 substitutions, the Cys sulfhydryl group recedes from the hydrocarbon ruler floor and locally perturbs the subjacent Tyr26 and Trp66 aromatic rings. The resulting hydrocarbon ruler expansion thus occurs at the exciton’s expense and accommodates an extra methylene unit in the selected acyl chain. The hydrocarbon ruler–exciton juxtaposition endows PagP with a molecular gauge for probing the structural basis of lipid acyl-chain selection in a membrane-intrinsic environment. PMID:17375935

Comparison of a commercial bovine pregnancy-associated glycoprotein ELISA test and a pregnancy-associated glycoprotein radiomimmunoassay test for early pregnancy diagnosis in dairy cattle.

PubMed

Karen, Aly; Sousa, Noelita Melo De; Beckers, Jean-François; Bajcsy, Árpád Csaba; Tibold, János; Mádl, István; Szenci, Ottó

2015-08-01

The present study aimed to compare the accuracy of a commercial PAG-ELISA test (Bovine Preg Test 29) and bovine pregnancy-associated glycoprotein radioimmunoassay (PAG-RIA) for diagnosing pregnancy at Day 28 after insemination in dairy cows. Transrectal ultrasonography (TRUS) was performed in 100 Holstein-Friesian cows at Day 28 after artificial insemination (AI; Day 0) to diagnose pregnancy. After TRUS examination, blood sample was collected from the coccygeal vessels of each cow to measure the concentrations of bPAGs by PAG-RIA test and Bovine Preg Test 29. Milk samples were collected at Days 0, 21 and 28 for measurement of progesterone (P4) by ELISA test. The cows were re-examined by TRUS at Day 42 to confirm the pregnancy diagnoses. The actual gold standard was based on TRUS outcomes at Day 28 that agreed with the outcomes of PAG-RIA test or PAG-ELISA test. If the outcomes of TRUS at Day 28 and PAG-RIA test and PAG-ELISA test did not agree, the gold standard was based on the outcome of TRUS at Day 42. Out of 100 inseminated cows, 41 were confirmed pregnant at Day 28 after AI. Based on the actual gold standard, the sensitivity of TRUS, PAG-ELISA and PAG-RIA tests for diagnosing pregnant cows at Day 28 were 92.7%, 90.2% and 100%, while the specificity of the three tests for diagnosing non-pregnant cows were 91.5%, 98.3% and 94.4%, respectively. The overall accuracy of the three tests were 92%, 95% and 97%, respectively. The degree of agreement (Kappa±S.E.) between PAG-RIA and PAG-ELISA test was 0.90 ±0.04. The degrees of agreement between PAG-RIA and PAG-ELISA and TRUS at Day 28 were 0.80±0.05 and 0.76±0.06, respectively. In conclusion, the commercial PAG-ELISA test is a highly accurate method for diagnosing early pregnancy in dairy cows on Day 28 after AI and may be used as an alternative method to the TRUS and the PAG-RIA test. Copyright © 2015 Elsevier B.V. All rights reserved.

Ancestral genetic diversity associated with the rapid spread of stress-tolerant coral symbionts in response to Holocene climate change

PubMed Central

Hume, Benjamin C. C.; Voolstra, Christian R.; Arif, Chatchanit; D’Angelo, Cecilia; Burt, John A.; Eyal, Gal; Loya, Yossi; Wiedenmann, Jörg

2016-01-01

Coral communities in the Persian/Arabian Gulf (PAG) withstand unusually high salinity levels and regular summer temperature maxima of up to ∼35 °C that kill conspecifics elsewhere. Due to the recent formation of the PAG and its subsequent shift to a hot climate, these corals have had only <6,000 y to adapt to these extreme conditions and can therefore inform on how coral reefs may respond to global warming. One key to coral survival in the world’s warmest reefs are symbioses with a newly discovered alga, Symbiodinium thermophilum. Currently, it is unknown whether this symbiont originated elsewhere or emerged from unexpectedly fast evolution catalyzed by the extreme environment. Analyzing genetic diversity of symbiotic algae across >5,000 km of the PAG, the Gulf of Oman, and the Red Sea coastline, we show that S. thermophilum is a member of a highly diverse, ancient group of symbionts cryptically distributed outside the PAG. We argue that the adjustment to temperature extremes by PAG corals was facilitated by the positive selection of preadapted symbionts. Our findings suggest that maintaining the largest possible pool of potentially stress-tolerant genotypes by protecting existing biodiversity is crucial to promote rapid adaptation to present-day climate change, not only for coral reefs, but for ecosystems in general. PMID:27044109

Influence of native plasmids to fitness of Pantoea vagans strain C9-1

USDA-ARS?s Scientific Manuscript database

Pantoea vagans strain C9-1 is a biological control agent for fire blight caused by Erwinia amylovora. We cured C9-1 of two of its three plasmids: pPag2, pPag3, and both pPag2 and pPag3, tested phenotypes of the derivatives, and evaluated blossom colonization in the field. pPag2 (166 kb) encodes for ...

Lesion of the Ventral Periaqueductal Gray Reduces Conditioned Fear but Does Not Change Freezing Induced by Stimulation of the Dorsal Periaqueductal Gray

PubMed Central

Vianna, Daniel M.L.; Graeff, Frederico G.; Landeira-Fernandez, Jesus; Brandão, Marcus L.

2001-01-01

Previously-reported evidence showed that freezing to a context previously associated with footshock is impaired by lesion of the ventral periaqueductal gray (vPAG). It has also been shown that stepwise increase in the intensity of the electrical stimulation of the dorsal periaqueductal gray (dPAG) produces alertness, then freezing, and finally escape. These aversive responses are mimicked by microinjections of GABA receptor antagonists, such as bicuculline, or blockers of the glutamic acid decarboxylase (GAD), such as semicarbazide, into the dPAG. In this work, we examined whether the expression of these defensive responses could be the result of activation of ventral portion of the periaqueductal gray. Sham- or vPAG electrolytic–lesioned rats were implanted with an electrode in the dPAG for the determination of the thresholds of freezing and escape responses. The vPAG electrolytic lesions were behaviorally verified through a context-conditioned fear paradigm. Results indicated that lesion of the vPAG disrupted conditioned freezing response to contextual cues associated with footshocks but did not change the dPAG electrical stimulation for freezing and escape responses. In a second experiment, lesion of the vPAG also did not change the amount of freezing and escape behavior produced by microinjections of semicarbazide into the dPAG. These findings indicate that freezing and escape defensive responses induced by dPAG stimulation do not depend on the integrity of the vPAG. A discussion on different neural circuitries that might underlie different inhibitory and active defensive behavioral patterns that animals display during threatening situations is presented. PMID:11390636

Connections from the rat dorsal column nuclei (DCN) to the periaqueductal gray matter (PAG).

PubMed

Barbaresi, Paolo; Mensà, Emanuela

2016-08-01

Electrical stimulation of the dorsal columns (DCs; spinal cord stimulation; SCS) has been proposed to treat chronic neuropathic pain. SCS may activate a dual mechanism that would affect both the spinal cord and supraspinal levels. Stimulation of DCs or DC nuclei (DCN) in animals where neuropathic pain has been induced causes activation of brainstem centers including the periaqueductal gray (PAG), which is involved in the endogenous pain suppression system. Biotinylated dextran-amine (BDA) was iontophoretically injected into the DCN to analyze the ascending projection directed to the PAG. Separate injections into the gracile nucleus (GrN) and the cuneate nucleus (CunN) showed BDA-positive fibers terminating in different regions of the contralateral PAG. GrN-PAG afferents terminated in the caudal and middle portions of PAG-l, whereas CunN-PAG fibers terminated in the middle and rostral portions of PAG-l. Based on the DCN somatotopic map, the GrN sends information to the PAG from the contralateral hindlimb and the tail and the CunN from the contralateral forelimb, shoulder, neck and ear. This somatotopic organization is consistent with earlier electrophysiological and PAG stimulation studies. These fibers could form part of the DCs-brainstem-spinal cord loop, which may be involved in the inhibitory effects of SCS on neuropathic pain. Copyright © 2016. Published by Elsevier Ireland Ltd.

Updating Dosimetry for Emergency Response Dose Projections.

PubMed

DeCair, Sara

2016-02-01

In 2013, the U.S. Environmental Protection Agency (EPA) proposed an update to the 1992 Protective Action Guides (PAG) Manual. The PAG Manual provides guidance to state and local officials planning for radiological emergencies. EPA requested public comment on the proposed revisions, while making them available for interim use by officials faced with an emergency situation. Developed with interagency partners, EPA's proposal incorporates newer dosimetric methods, identifies tools and guidelines developed since the current document was issued, and extends the scope of the PAGs to all significant radiological incidents, including radiological dispersal devices or improvised nuclear devices. In order to best serve the emergency management community, scientific policy direction had to be set on how to use International Commission on Radiological Protection Publication 60 age groups in dose assessment when implementing emergency guidelines. Certain guidelines that lend themselves to different PAGs for different subpopulations are the PAGs for potassium iodide (KI), food, and water. These guidelines provide age-specific recommendations because of the radiosensitivity of the thyroid and young children with respect to ingestion and inhalation doses in particular. Taking protective actions like using KI, avoiding certain foods or using alternative sources of drinking water can be relatively simple to implement by the parents of young children. Clear public messages can convey which age groups should take which action, unlike how an evacuation or relocation order should apply to entire households or neighborhoods. New in the PAG Manual is planning guidance for the late phase of an incident, after the situation is stabilized and efforts turn toward recovery. Because the late phase can take years to complete, decision makers are faced with managing public exposures in areas not fully remediated. The proposal includes quick-reference operational guidelines to inform re-entry to the contaminated zone. Broad guidance on approaches to wide-area cleanup and cleanup goals is also provided. EPA adapted the cleanup process from the 2008 U.S. Department of Homeland Security (DHS) Planning Guidance for Protection and Recovery Following Radiological Dispersal Device (RDD) and Improvised Nuclear Device (IND) Incidents, and the final PAG Manual will supersede that DHS guidance. Waste management guidance is also provided. Recognizing that an incident could result in radioactive waste volumes that severely strain or exceed available resources and capacity, officials may consider alternatives for disposal of waste that is relatively lightly contaminated. Waste management, including treatment, staging, and interim and long-term storage, must be an integral part of recovery.

Ebf2 is required for development of dopamine neurons in the midbrain periaqueductal gray matter of mouse.

PubMed

Yang, Qiaoqiao; Liu, Shuxi; Yin, Min; Yin, Yanqing; Zhou, Guomin; Zhou, Jiawei

2015-11-01

Dopaminergic (DA) neurons in the midbrain ventral periaqueductal gray matter (PAG) play critical roles in various physiological and pathophysiological processes including sleep-wake rhyme, antinociception, and drug addiction. However, the molecular mechanisms underlying their development are poorly understood. Here, we showed that PAG DA neurons arose as early as E15.5 in mouse embryos. During the prenatal period, the majority of PAG DA neurons was distributed in the intermediate and caudal regions of the PAG. In the postnatal brain, ∼50% of PAG DA neurons were preferentially located in the caudal portion of the PAG. Moreover, transcription factor early B-cell factor 2 (Ebf2) was transiently expressed in a subset of DA neurons in embryonic ventral mesencephalon. Functional analysis revealed that loss of Ebf2 in vivo caused a marked reduction in the number of DA neurons in the midbrain PAG but not in the substantia nigra and ventral tegmental area. Thus, Ebf2 is identified as a novel and important regulator selectively required for midbrain PAG DA neuron development. © 2015 Wiley Periodicals, Inc.

Periaqueductal Gray Afferents Synapse onto Dopamine and GABA Neurons In the Rat Ventral Tegmental Area

PubMed Central

Omelchenko, Natalia; Sesack, Susan R.

2009-01-01

The midbrain central gray (periaqueductal gray; PAG) mediates defensive behaviors and is implicated in the rewarding effects of opiate drugs. Projections from the PAG to the ventral tegmental area (VTA) suggest that this region might also regulate behaviors involving motivation and cognition. However, studies have not yet examined the morphological features of PAG axons in the VTA or whether they synapse onto dopamine (DA) or GABA neurons. In this study, we injected anterograde tracers into the rat PAG and used immunoperoxidase to visualize the projections to the VTA. Immunogold-silver labeling for tyrosine hydroxylase (TH) or GABA was then used to identify the phenotype of innervated cells. Electron microscopic examination of the VTA revealed axons labeled anterogradely from the PAG, including myelinated and unmyelinated fibers and axon varicosities, some of which formed identifiable synapses. Approximately 55% of these synaptic contacts were of the symmetric (presumably inhibitory) type; the rest were asymmetric (presumably excitatory). These findings are consistent with the presence of both GABA and glutamate projection neurons in the PAG. Some PAG axons contained dense-cored vesicles indicating the presence of neuropeptides in addition to classical neurotransmitters. PAG projections synapsed onto both DA and GABA cells with no obvious selectivity, providing the first anatomical evidence for these direct connections. The results suggest a diverse nature of PAG physiological actions on midbrain neurons. Moreover, as both the VTA and PAG are implicated in the reinforcing actions of opiates, our findings provide a potential substrate for some of the rewarding effects of these drugs. PMID:19885830

Genetic structure of coral-Symbiodinium symbioses on the world's warmest reefs.

PubMed

Smith, Edward G; Hume, Benjamin C C; Delaney, Patrice; Wiedenmann, Jörg; Burt, John A

2017-01-01

Corals in the Arabian/Persian Gulf (PAG) survive extreme sea temperatures (summer mean: >34°C), and it is unclear whether these corals have genetically adapted or physiologically acclimated to these conditions. In order to elucidate the processes involved in the thermal tolerance of PAG corals, it is essential to understand the connectivity between reefs within and outside of the PAG. To this end, this study set out to investigate the genetic structure of the coral, Platygyra daedalea, and its symbiotic algae in the PAG and neighbouring Gulf of Oman. Using nuclear markers (the ITS region and an intron of the Pax-C gene), this study demonstrates genetic divergence of P. daedalea on reefs within the thermally extreme PAG compared with those in the neighbouring Gulf of Oman. Isolation by distance of P. daedalea was supported by the ITS dataset but not the Pax-C intron. In addition, the symbiont community within the PAG was dominated by C3 symbionts, while the purportedly thermotolerant clade D was extremely rare and was common only at sites outside of the PAG. Analysis of the psbAncr indicates that the C3 variant hosted by P. daedalea in the PAG belongs to the newly described species, Symbiodinium thermophilum. The structuring of the coral and symbiont populations suggests that both partners of the symbiosis may contribute to the high bleaching thresholds of PAG corals. While limited gene flow has likely played a role in local adaptation within the PAG, it also indicates limited potential for natural export of thermal tolerance traits to reefs elsewhere in the Indian Ocean threatened by climate change.

Transmembrane adaptor protein PAG1 is a novel tumor suppressor in neuroblastoma

PubMed Central

Agarwal, Saurabh; Ghosh, Rajib; Chen, Zaowen; Lakoma, Anna; Gunaratne, Preethi H.; Kim, Eugene S.; Shohet, Jason M.

2016-01-01

(NB) is the most common extracranial pediatric solid tumor with high mortality rates. The tyrosine kinase c-Src has been known to play an important role in differentiation of NB cells, but the mechanism of c-Src regulation has not been defined. Here, we characterize PAG1 (Cbp, Csk binding protein), a central inhibitor of c-Src and other Src family kinases, as a novel tumor suppressor in NB. Clinical cohort analysis demonstrate that low expression of PAG1 is a significant prognostic factor for high stage disease, increased relapse, and worse overall survival for children with NB. PAG1 knockdown in NB cells promotes proliferation and anchorage-independent colony formation with increased activation of AKT and ERK downstream of c-Src, while PAG1 overexpression significantly rescues these effects. In vivo, PAG1 overexpression significantly inhibits NB tumorigenicity in an orthotopic xenograft model. Our results establish PAG1 as a potent tumor suppressor in NB by inhibiting c-Src and downstream effector pathways. Thus, reactivation of PAG1 and inhibition of c-Src kinase activity represents an important novel therapeutic approach for high-risk NB. PMID:26993602

Interaction between two adapter proteins, PAG and EBP50: a possible link between membrane rafts and actin cytoskeleton.

PubMed

Brdicková, N; Brdicka, T; Andera, L; Spicka, J; Angelisová, P; Milgram, S L; Horejsí, V

2001-10-26

Phosphoprotein associated with GEMs (PAG), also known as Csk-binding protein (Cbp), is a broadly expressed palmitoylated transmembrane adapter protein found in membrane rafts, also called GEMs (glycosphingolipid-enriched membrane microdomains). PAG is known to bind and activate the essential regulator of Src-family kinases, cytoplasmic protein tyrosine kinase Csk. In the present study we used the yeast 2-hybrid system to search for additional proteins which might bind to PAG. We have identified the abundant cytoplasmic adapter protein EBP50 (ezrin/radixin/moesin (ERM)-binding phosphoprotein of 50 kDa), also known as NHERF (Na(+)/H(+) exchanger regulatory factor), as a specific PAG-binding partner. The interaction involves the C-terminal sequence (TRL) of PAG and N-terminal PDZ domain(s) of EBP50. As EBP50 is known to interact via its C-terminal domain with the ERM-family proteins, which in turn bind to actin cytoskeleton, the PAG-EBP50 interaction may be important for connecting membrane rafts to the actin cytoskeleton.

Recovering low-turbidity cutting liquid from silicon slurry waste.

PubMed

Tsai, Tzu-Hsuan; Shih, Yu-Pei

2014-04-30

In order to recover a low-turbidity polyalkylene glycol (PAG) liquid from silicon slurry waste by sedimentation, temperatures were adjusted, and acetone, ethanol or water was used as a diluent. The experimental results show that the particles in the waste would aggregate and settle readily by using water as a diluent. This is because particle surfaces had lower surface potential value and weaker steric stabilization in PAG-water than in PAG-ethanol or PAG-acetone solutions. Therefore, water is the suggested diluent for recovering a low-turbidity PAG (<100 NTU) by sedimentation. After 50 wt.% water-assisted sedimentation for 21 days, the solid content of the upper liquid reduced to 0.122 g/L, and the turbidity decreased to 44 NTU. The obtained upper liquid was then vacuum-distillated to remove water. The final recovered PAG with 0.37 NTU had similar viscosity and density to the unused PAG and could be reused in the cutting process. Copyright © 2014 Elsevier B.V. All rights reserved.

Subspecies differences in early fetal development and plasma pregnancy-associated glycoprotein concentrations in cattle.

PubMed

Mercadante, P M; Waters, K M; Mercadante, V R G; Lamb, G C; Elzo, M A; Johnson, S E; Rae, D O; Yelich, J V; Ealy, A D

2013-08-01

Inclusion of Bos indicus genetics improves production traits of cattle maintained in hot climates. Limited information exists detailing pregnancy-specific events as influenced by variable amounts of Bos indicus genetics. Three experiments were completed to examine the effect of Bos taurus and Bos indicus genotypes on fetal size and plasma pregnancy-associated glycoprotein (PAG) concentrations. In all experiments, cows were bred by AI after synchronization of ovulation. Fetal measurements were completed by transrectal ultrasonography and plasma PAG concentrations were quantified from plasma harvested the day of each fetal measurement. In Exp. 1, fetal size and plasma PAG concentrations were measured at d 53 of pregnancy in cows composed of various fractions of Angus and Brahman (n = 9 to 21 cows/group). Fetus size was greater in cows containing >80% Angus genetics compared with cows containing <80% Angus influence (3.40 ± 0.28 vs. 2.86 ± 0.28 cm crown-rump length; P < 0.01). Plasma PAG concentrations were reduced (P < 0.01) in cows containing >80% Angus genetics when compared with their contemporaries (6.0 ± 1.5 ng/mL vs. 9.4 ± 1.5 ng/mL). In Exp. 2, fetal measurements and plasma PAG concentrations were determined at d 35 and 62 of pregnancy in Angus and Brangus cows. Breed did not affect fetus size at d 35, but Angus cows contained larger fetuses than Brangus cows at d 62 [3.0 ± 0.03 vs. 2.8 ± 0.03 cm crown-nose length (CNL; P > 0.01)]. Plasma PAG concentrations were not different between breed at d 35 and 62 (P > 0.1). In Exp. 3, fetal measurements and plasma samples were collected at d 33/34, 40/41, 47/48, and 54/55 post-AI in Angus and Brangus cows. Fetus size was not different (P > 0.05) between genotypes on d 33/34, 40/41, and 47/48. Angus fetuses were larger than Brangus fetuses at d 54/55 (2.1 ± 0.03 vs. 1.9 ± 0.03 cm CNL; P = 0.001). Plasma PAG concentrations were less in Angus than Brangus cows at each time point (average 4.9 ± 0.9 vs. 8.2 ± 0.9 ng/mL; P = 0.005). In conclusion, these studies determined that the Bos taurus × Bos indicus genotype impacts fetal size and rate of fetal development by 7 wk of gestation. Plasma PAG concentrations were increased in cattle with Bos indicus genetics in 2 of 3 studies, suggesting that genotype is one of several determinants of PAG production and secretion in cattle.

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

Noh, Seol Ah, E-mail: s6022029@korea.ac.kr; Choi, Young-Im, E-mail: yichoi99@forest.go.kr; Cho, Jin-Seong, E-mail: jinsung3932@gmail.com

Brassinosteroids (BRs) play important roles in many aspects of plant growth and development, including regulation of vascular cambium activities and cell elongation. BR-induced BEE3 (brassinosteroid enhanced expression 3) is required for a proper BR response. Here, we identified a poplar (Populus alba × Populus glandulosa) BEE3-like gene, PagBEE3L, encoding a putative basic helix-loop-helix (bHLH)-type transcription factor. Expression of PagBEE3L was induced by brassinolide (BL). Transcripts of PagBEE3L were mainly detected in stems, with the internode having a low level of transcription and the node having a relatively higher level. The function of the PagBEE3L gene was investigated through phenotypic analyses with PagBEE3L-overexpressingmore » (ox) transgenic lines. This work particularly focused on a potential role of PagBEE3L in stem growth and development of polar. The PagBEE3L-ox poplar showed thicker and longer stems than wild-type plants. The xylem cells from the stems of PagBEE3L-ox plants revealed remarkably enhanced proliferation, resulting in an earlier thickening growth than wild-type plants. Therefore, this work suggests that xylem development of poplar is accelerated in PagBEE3L-ox plants and PagBEE3L plays a role in stem growth by increasing the proliferation of xylem cells to promote the initial thickening growth of poplar stems. - Highlights: • We identify the BEE3-like gene form hybrid poplar (Populus alba × Populus glandulosa). • We examine effects of overexpression of PagBEE3L on growth in poplar. • We found that 35S:BEE3L transgenic plants showed more rapid growth than wild-type plants. • BEE3L protein plays an important role in the development of plant stem.« less

On the verge of a respiratory-type panic attack: Selective activations of rostrolateral and caudoventrolateral periaqueductal gray matter following short-lasting escape to a low dose of potassium cyanide.

PubMed

Müller, Cláudia Janaina Torres; Quintino-Dos-Santos, Jeyce Willig; Schimitel, Fagna Giacomin; Tufik, Sérgio; Beijamini, Vanessa; Canteras, Newton Sabino; Schenberg, Luiz Carlos

2017-04-21

Intravenous injections of potassium cyanide (KCN) both elicit escape by its own and facilitate escape to electrical stimulation of the periaqueductal gray matter (PAG). Moreover, whereas the KCN-evoked escape is potentiated by CO 2 , it is suppressed by both lesions of PAG and clinically effective treatments with panicolytics. These and other data suggest that the PAG harbors a hypoxia-sensitive alarm system the activation of which could both precipitate panic and render the subject hypersensitive to CO 2 . Although prior c-Fos immunohistochemistry studies reported widespread activations of PAG following KCN injections, the employment of repeated injections of high doses of KCN (>60µg) in anesthetized rats compromised both the localization of KCN-responsive areas and their correlation with escape behavior. Accordingly, here we compared the brainstem activations of saline-injected controls (air/saline) with those produced by a single intravenous injection of 40-µg KCN (air/KCN), a 2-min exposure to 13% CO 2 (CO 2 /saline), or a combined stimulus (CO 2 /KCN). Behavioral effects of KCN microinjections into the PAG were assessed as well. Data showed that whereas the KCN microinjections were ineffective, KCN intravenous injections elicited escape in all tested rats. Moreover, whereas the CO 2 alone was ineffective, it potentiated the KCN-evoked escape. Compared to controls, the nucleus tractus solitarius was significantly activated in both CO 2 /saline and CO 2 /KCN groups. Additionally, whereas the laterodorsal tegmental nucleus was activated by all treatments, the rostrolateral and caudoventrolateral PAG were activated by air/KCN only. Data suggest that the latter structures are key components of a hypoxia-sensitive suffocation alarm which activation may trigger a panic attack. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Pediatric and Adolescent Gynecology in Europe: Clinical Services, Standards of Care, and Training.

PubMed

Richmond, Anna; Priyanka, Sweta; Mahmood, Tahir; MacDougall, Jane; Wood, Paul

2016-06-01

To identify current clinical services and training available across Europe within pediatric and adolescent gynecology (PAG) and establish the extent to which PAG services meet current European Board and College of Obstetrics and Gynecology (EBCOG) standards. Quantitative and qualitative questionnaire. European countries that are members of the EBCOG and the European Association of Pediatric and Adolescent Gynecology. Thirty-six countries that were approached beginning in September 2013; data were obtained from 27 countries. Questionnaires with 28 stems were sent to clinical leaders in 36 European countries. National society, national standards, legislation for female genital mutilation, protocols for transition to adult services, human papilloma virus vaccination programs, sex and contraception education, safeguarding, clinical leads for PAG, delivery of PAG services, and training available for PAG. Of 36 countries, 27 responded. Seventy-seven percent had a national PAG society but only 44% had national standards in PAG. There was agreement that PAG cases should be multidisciplinary but not all have clinical networks in place to facilitate this. Human papilloma virus programs are available in some European countries and not all have legislation against female genital mutilation. A significant proportion of cases continue to be seen in adult gynecology clinics as opposed to designated PAG clinics with only 41% with processes to transfer patients into adult care. In this article we provide a framework to explore areas for improvement within PAG services and training across Europe. The EBCOG standards of care are not being adhered to in many countries because processes and clinical networks are not in place to facilitate them. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

Influence of endogenous plasmids on phenotypes of Pantoea vagans strain C9-1 associated with epiphytic fitness

USDA-ARS?s Scientific Manuscript database

Pantoea vagans strain C9-1 is an effective biological control agent for fire blight of pear and apple. C9-1 carries three circular plasmids: pPag1 (168 kb), pPag2 (166 kb), and pPag3 (530 kb). Of these, pPag3, a member of the large Pantoea plasmid family, was proposed to contribute to epiphytic fitn...

Specific induction of PAG608 in cranial and spinal motor neurons of L-DOPA-treated parkinsonian rats.

PubMed

Shimizu, Masako; Miyazaki, Ikuko; Higashi, Youichirou; Eslava-Alva, Maria J; Diaz-Corrales, Francisco J; Asanuma, Masato; Ogawa, Norio

2008-04-01

We identified p53-activated gene 608 (PAG608) as a specifically induced gene in striatal tissue of L-DOPA (100mg/kg)-injected hemi-parkinsonian rats using differential display assay. In the present study, we further examined morphological distribution of PAG608 in the central nervous system of L-DOPA-treated hemi-parkinsonian rats. PAG608 expression was markedly induced in fibers and neuronal cells of the lateral globus pallidus and reticular thalamic nucleus adjacent to internal capsule, specifically in the parkinsonian side of L-DOPA-treated models. The protein was also constitutively expressed in motor neurons specifically in either side of the pontine nucleus and motor nuclei of trigeminal and facial nerves. Furthermore, L-DOPA-induced PAG608 expression on motor neurons in the contralateral side of the ventral horn of the spinal cord and the lateral corticospinal tract without cell loss. The specific induction of PAG608 6-48h after L-DOPA injection in the extrapyramidal tracts, pyramidal tracts and corresponding lower motor neurons of the spinal cords suggests its involvement in molecular events in stimulated motor neurons. Taken together with the constitutive expression of PAG608 in the motor nuclei of cranial nerves, PAG608 may be a useful marker of stressed or activated lower motor neurons.

Study on dissolution behavior of polymer-bound and polymer-blended photo-acid generator (PAG) resists

NASA Astrophysics Data System (ADS)

Yamamoto, Hiroki; Kozawa, Takahiro; Tagawa, Seiichi

2013-03-01

The requirements for the next generation resist materials are so challenging that it is indispensable for feasibility of EUV lithography to grasp basic chemistry of resist matrices in all stage of resist processes. Under such circumstances, it is very important to know dissolution characteristics of the resist film into alkaline developer though the dissolution of exposed area of resist films in alkaline developer to form a pattern is a complex reactive process. In this study, the influence of EUV and KrF exposure on the dissolution behavior of polymer bound PAG and polymer blended PAG was studied in detail using quartz crystal microbalance (QCM) methods. The difference in swelling formation between KrF and EUV exposure was observed. It is likely that difference of reaction mechanism induces the difference of these swelling. Also, it is observed that the swelling of polymer-bound PAG is less than that of polymer blended PAG in both KrF and EUV exposure. This result indicates that polymer-bound PAG suppresses swelling very well and showed an excellent performance. Actually, the developed polymer bound-PAG resist showed an excellent performance (half pitch 50 nm line and space pattern). Thus, polymer bound PAG is one of the promising candidate for 16 nm EUV resist.

Biosorption of Cu(II) by powdered anaerobic granular sludge from aqueous medium.

PubMed

Zhou, Xu; Chen, Chuan; Wang, Aijie; Jiang, Guangming; Liu, Lihong; Xu, Xijun; Yuan, Ye; Lee, Duu-Jung; Ren, Nanqi

2013-01-01

Copper(II) biosorption processes by two pre-treated powdered anaerobic granular sludges (PAGS) (original sludges were methanogenic anaerobic granules and denitrifying sulfide removal (DSR) anaerobic granules) were investigated through batch tests. Factors affecting the biosorption process, such as pH, temperature and initial copper concentrations, were examined. Also, the physico-chemical characteristics of the anaerobic sludge were analyzed by Fourier transform infrared spectroscopy, scanning electron microscopy image, surface area and elemental analysis. A second-order kinetic model was applied to describe the biosorption process, and the model could fit the biosorption process. The Freundlich model was used for describing the adsorption equilibrium data and could fit the equilibrium data well. It was found that the methanogenic PAGS was more effective in Copper(II) biosorption process than the DSR PAGS, whose maximum biosorption capacity was 39.6% lower. The mechanisms of the biosorption capacities for different PAGS were discussed, and the conclusion suggested that the environment and biochemical reactions during the growth of biomass may have affected the structure of the PAGS. The methanogenic PAGS had larger specific surface area and more biosorption capacity than the DSR PAGS.

Distinct Structural Elements Govern the Folding, Stability, and Catalysis in the Outer Membrane Enzyme PagP.

PubMed

Iyer, Bharat Ramasubramanian; Mahalakshmi, Radhakrishnan

2016-09-06

The outer membrane enzyme PagP is indispensable for lipid A palmitoylation in Gram-negative bacteria and has been implicated in resistance to host immune defenses. PagP possesses an unusual structure for an integral membrane protein, with a highly dynamic barrel domain that is tilted with respect to the membrane normal. In addition, it contains an N-terminal amphipathic helix. Recent functional and structural studies have shown that these molecular factors are critical for PagP to carry out its function in the challenging environment of the bacterial outer membrane. However, the precise contributions of the N-helix to folding and stability and residues that can influence catalytic rates remain to be addressed. Here, we identify a sequence-dependent stabilizing role for the N-terminal helix of PagP in the measured thermodynamic stability of the barrel. Using chimeric barrel sequences, we show that the Escherichia coli PagP N-terminal helix confers 2-fold greater stability to the Salmonella typhimurium barrel. Further, we find that the W78F substitution in S. typhimurium causes a nearly 20-fold increase in the specific activity in vitro for the phospholipase reaction, compared to that of E. coli PagP. Here, phenylalanine serves as a key regulator of catalysis, possibly by increasing the reaction rate. Through coevolution analysis, we detect an interaction network between seemingly unrelated segments of this membrane protein. Exchanging the structural and functional features between homologous PagP enzymes from E. coli and S. typhimurium has provided us with an understanding of the molecular factors governing PagP stability and function.

Local connections between the columns of the periaqueductal gray matter: a case for intrinsic neuromodulation.

PubMed

Jansen, A S; Farkas, E; Mac Sams, J; Loewy, A D

1998-02-16

Chemical stimulation of the lateral or ventrolateral columns of the midbrain periaqueductal gray matter (PAG) in conscious animals produces opposite responses (viz., defensive behavior and pressor responses from the lateral column vs. quiescence and depressor responses from the ventrolateral column), raising the possibility that the two columns are interconnected. To test this hypothesis, two types of anatomical experiments were performed in rats. First, the anterograde axonal marker Phaseolus vulgaris leuco-agglutinin (PHA-L) was injected into individual PAG columns or adjoining regions which included the Edinger-Westphal, dorsal raphe, and precommissural nuclei. The results shows that each column projects bilaterally to all of the other PAG columns, and also provides local connections within its own column. Furthermore, the Edinger-Westphal and precommissural nuclei project to all four PAG columns, while the dorsal raphe nucleus projects only to the ventrolateral and lateral columns. In a second experiment, we found that cardiovascular-related PAG projection neurons of both the lateral and ventrolateral columns receive an input from the reciprocal PAG column. This was demonstrated by a double tracer neuroanatomical study in which PHA-L was first iontophoretically ejected into either the lateral or ventrolateral PAG columns and then, several days later the retrograde transneuronal viral tracer, pseudorabies virus, was injected into the stellate sympathetic ganglion. Intra-PAG circuits were visualized by a dual immunohistochemical procedure. These results suggest that during the fight-or-flight response when the 'fight' program is activated, inhibition of the 'flight' PAG network may occur and the converse situation may occur during the flight response. Copyright 1997 Elsevier Science B.V.

The benefits of magnetic resonance imaging methods to extend the knowledge of the anatomical organisation of the periaqueductal gray in mammals.

PubMed

Menant, Ophélie; Andersson, Frédéric; Zelena, Dóra; Chaillou, Elodie

2016-11-01

The periaqueductal gray (PAG) is a mesencephalic brain structure involved in the expression of numerous behaviours such as maternal, sexual and emotional. Histological approaches showed the PAG is composed by subdivisions with specific cell organisation, neurochemical composition and connections with the rest of the brain. The comparison of studies performed in rodents and cats as the most often examined species, suggests that PAG organisation differs between mammals. However, we should also consider the plurality of the methods used in these studies that makes difficult the comparison of the PAG organisation between species. Therefore, to study the PAG in all mammals including human, the most relevant in vivo imaging method seems to be the magnetic resonance imaging (MRI). The purpose of this review was to summarize the knowledge of the anatomical organisation of the PAG in mammals and highlights the benefits of MRI methods to extend this knowledge. Results obtained by MRI so far support the conclusions of ex vivo studies, especially to describe the subdivisions and the connections of the PAG. In these latter, diffusion-weighted MRI and functional connectivity seem the most appropriate methods. In conclusion firstly, the MRI seems to be the best judicious method to compare species and improve the comprehension of the role of the PAG. Secondly, MRI is an in vivo method aimed to manage repeated measures in the same cohort of subjects allowing to study the impact of aging and the development on the anatomical organisation of the PAG. Copyright © 2016 Elsevier B.V. All rights reserved.

Functional grouping and cortical–subcortical interactions in emotion: A meta-analysis of neuroimaging studies

PubMed Central

Kober, Hedy; Barrett, Lisa Feldman; Joseph, Josh; Bliss-Moreau, Eliza; Lindquist, Kristen; Wager, Tor D.

2009-01-01

We performed an updated quantitative meta-analysis of 162 neuroimaging studies of emotion using a novel multi-level kernel-based approach, focusing on locating brain regions consistently activated in emotional tasks and their functional organization into distributed functional groups, independent of semantically defined emotion category labels (e.g., “anger,” “fear”). Such brain-based analyses are critical if our ways of labeling emotions are to be evaluated and revised based on consistency with brain data. Consistent activations were limited to specific cortical sub-regions, including multiple functional areas within medial, orbital, and inferior lateral frontal cortices. Consistent with a wealth of animal literature, multiple subcortical activations were identified, including amygdala, ventral striatum, thalamus, hypothalamus, and periaqueductal gray. We used multivariate parcellation and clustering techniques to identify groups of co-activated brain regions across studies. These analyses identified six distributed functional groups, including medial and lateral frontal groups, two posterior cortical groups, and paralimbic and core limbic/brainstem groups. These functional groups provide information on potential organization of brain regions into large-scale networks. Specific follow-up analyses focused on amygdala, periaqueductal gray (PAG), and hypothalamic (Hy) activations, and identified frontal cortical areas co-activated with these core limbic structures. While multiple areas of frontal cortex co-activated with amygdala sub-regions, a specific region of dorsomedial prefrontal cortex (dmPFC, Brodmann’s Area 9/32) was the only area co-activated with both PAG and Hy. Subsequent mediation analyses were consistent with a pathway from dmPFC through PAG to Hy. These results suggest that medial frontal areas are more closely associated with core limbic activation than their lateral counterparts, and that dmPFC may play a particularly important role in the cognitive generation of emotional states. PMID:18579414

Processing cardiovascular information in the vlPAG during electroacupuncture in rats: roles of endocannabinoids and GABA

PubMed Central

Tjen-A-Looi, Stephanie C.; Li, Peng; Longhurst, John C.

2009-01-01

A long-loop pathway, involving the hypothalamic arcuate nucleus (ARC), ventrolateral periaqueductal gray (vlPAG), and the rostral ventrolateral medulla (rVLM), is essential in electroacupuncture (EA) attenuation of sympathoexcitatory cardiovascular reflex responses. The ARC provides excitatory input to the vlPAG, which, in turn, inhibits neuronal activity in the rVLM. Although previous studies have shown that endocannabinoid CB1 receptor activation modulates γ-aminobutyric acid (GABA)-ergic and glutamatergic neurotransmission in the dorsolateral PAG in stress-induced analgesia, an important role for endocannabinoids in the vlPAG has not yet been observed. We recently have shown (Fu LW, Longhurst JC. J Appl Physiol; doi:10.1152/japplphysiol.91648.2008) that EA reduces the local vlPAG concentration of GABA, but not glutamate, as measured with high-performance liquid chromatography from extracellular samples collected by microdialysis. We, therefore, hypothesized that, during EA, endocannabinoids, acting through CB1 receptors, presynaptically inhibit GABA release to disinhibit the vlPAG and ultimately modulate excitatory reflex blood pressure responses. Rats were anesthetized, ventilated, and instrumented to measure heart rate and blood pressure. Gastric distention-induced blood pressure responses of 18 ± 5 mmHg were reduced to 6 ± 1 mmHg by 30 min of low-current, low-frequency EA applied bilaterally at pericardial P 5–6 acupoints overlying the median nerves. Like EA, microinjection of the fatty acid amide hydrolase inhibitor URB597 (0.1 nmol, 50 nl) into the vlPAG to increase endocannabinoids locally reduced the gastric distention cardiovascular reflex response from 21 ± 5 to 3 ± 4 mmHg. This inhibition was reversed by pretreatment with the GABAA antagonist gabazine (27 mM, 50 nl), suggesting that endocannabinoids exert their action through a GABAergic receptor mechanism in the vlPAG. The EA-related inhibition from 18 ± 3 to 8 ± 2 mmHg was reversed to 14 ± 2 mmHg by microinjection of the CB1 receptor antagonist AM251 (2 nmol, 50 nl) into the vlPAG. Pretreatment with gabazine eliminated reversal following CB1-receptor blockade. Thus EA releases endocannabinoids and activates presynaptic CB1 receptors to inhibit GABA release in the vlPAG. Reduction of GABA release disinhibits vlPAG cells, which, in turn, modulate the activity of rVLM neurons to attenuate the sympathoexcitatory reflex responses. PMID:19325030

Behavioral meaningful opioidergic stimulation activates kappa receptor gene expression

PubMed Central

Teodorov, E.; Ferrari, M.F.R.; Fior-Chadi, D.R.; Camarini, R.; Felício, L.F.

2012-01-01

The periaqueductal gray (PAG) has been reported to be a location for opioid regulation of pain and a potential site for behavioral selection in females. Opioid-mediated behavioral and physiological responses differ according to the activity of opioid receptor subtypes. The present study investigated the effects of the peripheral injection of the kappa-opioid receptor agonist U69593 into the dorsal subcutaneous region of animals on maternal behavior and on Oprk1 gene activity in the PAG of female rats. Female Wistar rats weighing 200-250 g at the beginning of the study were randomly divided into 2 groups for maternal behavior and gene expression experiments. On day 5, pups were removed at 7:00 am and placed in another home cage that was distant from their mother. Thirty minutes after removing the pups, the dams were treated with U69593 (0.15 mg/kg, sc) or 0.9% saline (up to 1 mL/kg) and after 30 min were evaluated in the maternal behavior test. Latencies in seconds for pup retrieval, grouping, crouching, and full maternal behavior were scored. The results showed that U69593 administration inhibited maternal behavior (P < 0.05) because a lower percentage of U69593 group dams showed retrieval of first pup, retrieving all pups, grouping, crouching and displaying full maternal behavior compared to the saline group. Opioid gene expression was evaluated using real-time reverse-transcription polymerase chain reaction (RT-PCR). A single injection of U69593 increased Oprk1 PAG expression in both virgin (P < 0.05) and lactating female rats (P < 0.01), with no significant effect on Oprm1 or Oprd1 gene activity. Thus, the expression of kappa-opioid receptors in the PAG may be modulated by single opioid receptor stimulation and behavioral meaningful opioidergic transmission in the adult female might occur simultaneously to specific changes in gene expression of kappa-opioid receptor subtype. This is yet another alert for the complex role of the opioid system in female reproduction. PMID:22641418

Involvement of TRPV1 channels in the periaqueductal grey on the modulation of innate fear responses.

PubMed

Aguiar, Daniele C; Almeida-Santos, Ana F; Moreira, Fabricio A; Guimarães, Francisco S

2015-04-01

The transient receptor potential vanilloid type-1 channel (TRPV1) is expressed in the midbrain periaqueductal grey (PAG), a region of the brain related to aversive responses. TRPV1 antagonism in the dorsolateral PAG (dlPAG) induces anxiolytic-like effects in models based on conflict situations. No study, however, has investigated whether these receptors could contribute to fear responses to proximal threat. Thus, we tested the hypothesis that TRPV1 in the PAG could mediate fear response in rats exposed to a predator. We verified whether exposure to a live cat (a natural predator) would activate TRPV1-expressing neurons in the PAG. Double-staining immunohistochemistry was used as a technique to detect c-Fos, a marker of neuronal activation, and TRPV1 expression. We also investigated whether intra-dlPAG injections of the TRPV1 antagonist, capsazepine (CPZ), would attenuate the behavioural consequences of predator exposure. Exposure to a cat increased c-Fos expression in TRPV1-positive neurons, mainly in the dorsal columns of the PAG, suggesting that TRPV1-expressing neurons are activated by threatening stimuli. Accordingly, local injection of CPZ inhibited the fear responses. These data support the hypothesis that TRPV1 channels mediate fear reactions in the dlPAG. This may have an implication for the development of TRPV1-antagonists as potential drugs for the treatment of certain psychiatric disorders.

Predatory hunting and exposure to a live predator induce opposite patterns of Fos immunoreactivity in the PAG.

PubMed

Comoli, E; Ribeiro-Barbosa, E R; Canteras, Newton Sabino

2003-01-06

Considering the periaqueductal gray's (PAG) general roles in mediating motivational responses, in the present study, we compared the Fos expression pattern in the PAG induced by innate behaviors underlain by opposite motivational drivers, in rats, namely, insect predation and defensive behavior evoked by the confrontation with a live predator (a cat). Exposure to the predator was associated with a striking Fos expression in the PAG, where, at rostral levels, an intense Fos expression was found largely distributed in the dorsomedial and dorsolateral regions, whereas, at caudal levels, Fos-labeled cells tended to be mostly found in the lateral and ventrolateral columns, as well as in the dorsal raphe nucleus. Quite the opposite, insect predation was associated with increased Fos expression predominantly in the rostral two thirds of the lateral PAG, where the majority of the Fos-immunoreactive cells were found at the oculomotor nucleus levels. Remarkably, both exposure to the cat and insect predation upregulated Fos expression in the supraoculomotor region and the laterodorsal tegmental nucleus. Overall, the present results clearly suggest that the PAG activation pattern appears to reflect, at least partly, the animal's motivational status. It is well established that the PAG is critical for the expression of defensive responses, and, considering the present findings, it will be important to investigate how the PAG contributes to the expression of the predatory behavior, as well.

PAGER 2.0: an update to the pathway, annotated-list and gene-signature electronic repository for Human Network Biology

PubMed Central

Yue, Zongliang; Zheng, Qi; Neylon, Michael T; Yoo, Minjae; Shin, Jimin; Zhao, Zhiying; Tan, Aik Choon

2018-01-01

Abstract Integrative Gene-set, Network and Pathway Analysis (GNPA) is a powerful data analysis approach developed to help interpret high-throughput omics data. In PAGER 1.0, we demonstrated that researchers can gain unbiased and reproducible biological insights with the introduction of PAGs (Pathways, Annotated-lists and Gene-signatures) as the basic data representation elements. In PAGER 2.0, we improve the utility of integrative GNPA by significantly expanding the coverage of PAGs and PAG-to-PAG relationships in the database, defining a new metric to quantify PAG data qualities, and developing new software features to simplify online integrative GNPA. Specifically, we included 84 282 PAGs spanning 24 different data sources that cover human diseases, published gene-expression signatures, drug–gene, miRNA–gene interactions, pathways and tissue-specific gene expressions. We introduced a new normalized Cohesion Coefficient (nCoCo) score to assess the biological relevance of genes inside a PAG, and RP-score to rank genes and assign gene-specific weights inside a PAG. The companion web interface contains numerous features to help users query and navigate the database content. The database content can be freely downloaded and is compatible with third-party Gene Set Enrichment Analysis tools. We expect PAGER 2.0 to become a major resource in integrative GNPA. PAGER 2.0 is available at http://discovery.informatics.uab.edu/PAGER/. PMID:29126216

Results of the independent verification of radiological remedial action at 397 East 3rd South Street, Monticello, Utah (MS00168)

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

Wilson, M.J.; Crutcher, J.W.

1991-07-01

In 1980 the site of a vanadium and uranium mill at Monticello, Utah, was accepted into the US Department of Energy's (DOE's) Surplus Facilities Management Program, with the objectives of restoring the government-owned mill site to safe levels of radioactivity, disposing of or containing the tailings in an environmentally safe manner, and performing remedial actions on off-site (vicinity) properties that had been contaminated by radioactive material resulting from mill operations. During 1987 and 1988, UNC Geotech, the remedial action contractor designated by DOE, performed remedial action on the vicinity property at 397 East 3rd South Street, Monticello, Utah. The Pollutantmore » Assessments Group (PAG) of Oak Ridge National Laboratory was assigned the responsibility of verifying the data supporting the adequacy of remedial action and confirming the site's compliance with DOE guidelines. The PAG found that the site successfully meets the DOE remedial action objectives. Procedures used by PAG are described. 3 refs., 2 tabs.« less

Results of the independent verification of radiological remedial action at 464 South 1st East Street, Monticello, Utah (MS00071)

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

Wilson, M.J.; Crutcher, J.W.

1991-07-01

In 1980 the site of a vanadium and uranium mill at Monticello, Utah, was accepted into the US Department of Energy's (DOE's) Surplus Facilities Management Program, with the objectives of restoring the government-owned mill site to safe levels of radioactivity, disposing of or containing the tailings in an environmentally safe manner, and performing remedial actions on off-site (vicinity) properties that had been contaminated by radioactive material resulting from mill operations. During 1986 and 1987, UNC Geotech, the remedial action contractor designated by DOE, performed remedial action on the vicinity property at 464 South 1st East Street, Monticello, Utah. The Pollutantmore » Assessments Group (PAG) of Oak Ridge National Laboratory was assigned the responsibility of verifying the data supporting the adequacy of remedial action and confirming the site's compliance with DOE guidelines. The PAG found that the site successfully meets the DOE remedial action objectives. Procedures used by PAG are described. 3 refs., 2 tabs.« less

Results of the independent verification of radiological remedial action at 87 East 500 South Street, Monticello, Utah (MS00153)

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

Wilson, M.J.; Crutcher, J.W.

1991-07-01

In 1980 the iste of a vanadium and uranium mill at Monticello, Utah, was accepted into the US Department of Energy's (DOE's) Surplus Facilities Management Program, with the objectives of restoring the government-owned mill site to safe levels of radioactivity, disposing of or containing the tailings in an environmentally safe manner, and performing remedial actions on off-site (vicinity) properties that had been contaminated by radioactive material resulting from mill operations. During 1987 and 1988, UNC Geotech, the remedial action contractor designated by DOE, performed remedial action on the vicinity property at 87 East 500 South Street, Monticello, Utah. The Pollutantmore » Assessments Group (PAG) of Oak Ridge National Laboratory was assigned the responsibility of verifying the data supporting the adequacy of remedial action and confirming the site's compliance with DOE guidelines. The PAG found that the site successfully meets the DOE remedial action objectives. Procedures used by PAG are described. 3 refs., 2 tabs.« less

Acellular pertussis vaccine based on outer membrane vesicles capable of conferring both long-lasting immunity and protection against different strain genotypes.

PubMed

Gaillard, María Emilia; Bottero, Daniela; Errea, Agustina; Ormazábal, Maximiliano; Zurita, M Eugenia; Moreno, Griselda; Rumbo, Martin; Castuma, Celina; Bartel, Erika; Flores, Dario; van der Ley, Peter; van der Ark, Arno; F Hozbor, Daniela

2014-02-12

Despite high vaccination coverage rates, pertussis continues to be a global concern, with increased incidence widely noted. The current pertussis epidemiologic situation has been mainly attributed to waning immunity and pathogen adaptation. To improve the disease control, a new generation of vaccines capable to overcome those weaknesses associated to the current vaccines need to be developed. Previously we have demonstrated that the outer membrane vesicles obtained from the recombinant Bordetella pertussis strain expressing PagL enzyme (OMVs(BpPagL)) are good vaccine candidates to protect against pertussis. In this work the OMVs(BpPagL) formulated with diphtheria and tetanus toxoids (Tdap(OMVsBpPagL)) was used to evaluate its capacity to offer protection against Argentinean clinical isolates and to induce long-term immunity. To these aims BALB/c mice were immunized with Tdap(OMVsBpPagL) and challenged with sublethal doses of the clinical isolate Bp106 selected as a representative circulating isolate. Comparisons with a current commercial Tdap vaccine used at a dose in which pertussis toxin level was equivalent to that of Tdap(OMVsBpPagL) were performed. With the normalized doses of both vaccines we observed that Tdap(OMVsBpPagL) protected against the clinical isolate infection, whereas current commercial Tdap vaccine showed little protection against such pathogen. Regarding long-term immunity we observed that the Tdap(OMVsBpPagL) protective capacity against the recommended WHO reference strain persisted at least 9 months. In agreement with these results Tdap(OMVsBpPagL) induced Th1 and Th2 immune response. In contrast, commercial Tdap induced Th2 but weak Th1 responses. All results presented here showed that Tdap(OMVsBpPagL) is an interesting formulation to be considered for the development of novel acellular multi-antigen vaccine. Copyright © 2013 Elsevier Ltd. All rights reserved.

Studying electron-PAG interactions using electron-induced fluorescence

NASA Astrophysics Data System (ADS)

Narasimhan, Amrit; Grzeskowiak, Steven; Ostrander, Jonathan; Schad, Jonathon; Rebeyev, Eliran; Neisser, Mark; Ocola, Leonidas E.; Denbeaux, Gregory; Brainard, Robert L.

2016-03-01

In extreme ultraviolet (EUV) lithography, 92 eV photons are used to expose photoresists. Typical EUV resists are organic-based and chemically amplified using photoacid generators (PAGs). Upon exposure, PAGs produce acids which catalyze reactions that result in changes in solubility. In EUV lithography, photo- and secondary electrons (energies of 10- 80 eV) play a large role in PAG acid-production. Several mechanisms for electron-PAG interactions (e.g. electron trapping, and hole-initiated chemistry) have been proposed. The aim of this study is to explore another mechanism - internal excitation - in which a bound PAG electron can be excited by receiving energy from another energetic electron, causing a reaction that produces acid. This paper explores the mechanism of internal excitation through the analogous process of electron-induced fluorescence, in which an electron loses energy by transferring that energy to a molecule and that molecule emits a photon rather than decomposing. We will show and quantify electron-induced fluorescence of several fluorophores in polymer films to mimic resist materials, and use this information to refine our proposed mechanism. Relationships between the molecular structure of fluorophores and fluorescent quantum yield may aid in the development of novel PAGs for EUV lithography.

Does the North American Society for Pediatric and Adolescent Gynecology Short Curriculum Increase Resident Knowledge in Pediatric and Adolescent Gynecology?

PubMed

Huguelet, P S; Browner-Elhanan, K J; Fleming, N; Karjane, N W; Loveless, M; Sheeder, J; Talib, H J; Wheeler, C; Kaul, P

2016-12-01

To determine if the North American Society for Pediatric and Adolescent Gynecology (NASPAG) Short Curriculum improves self-reported knowledge in pediatric and adolescent gynecology (PAG) among obstetrics and gynecology (Ob/Gyn) residents, at programs without PAG-trained faculty. Prospective, cross-sectional exposure to the NASPAG short curriculum with a follow-up questionnaire. Ob/Gyn residency training programs without PAG faculty. Ob/Gyn residents in training from February 2015 to June 2015. Exposure to the NASPAG Short Curriculum. Improvement in self-perceived knowledge after completion of curriculum. Two hundred twenty-seven residents met inclusion criteria; 34 completed the study (15% response). Less than 50% of residents reported adequate knowledge in the areas of prepubertal vaginal bleeding, vulvovaginitis, precocious and delayed puberty, Home environment, Education and Employment, Eating, peer-related Activities, Drugs, Sexuality, Suicide/depression, Safety from injury and violence (HEEADSSS) interview, pelvic pain, and bleeding management in teens with developmental delay. After completion of the curriculum, self-reported knowledge improved in 8 of 10 learning objectives, with no significant improvement in bleeding disorders or Müllerian anomalies. There was no association between pretest knowledge and level of residency training, type of residency program, previous exposure to PAG lectures, and previous exposure to patients with PAG complaints. Significant deficiencies exist regarding self-reported knowledge of core PAG topics among Ob/Gyn residents at programs without PAG-trained faculty. Use of the NASPAG Short Curriculum by residents without access to PAG-trained faculty resulted in improved self-reported knowledge in PAG. Copyright © 2016 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Stimulation of the dorsal periaqueductal gray enhances spontaneous recovery of a conditioned taste aversion

PubMed Central

Mickley, G. Andrew; Ketchesin, Kyle D.; Ramos, Linnet; Luchsinger, Joseph R.; Rogers, Morgan M.; Wiles, Nathanael R.; Hoxha, Nita

2012-01-01

Due to its relevance to clinical practice, extinction of learned fears has been a major focus of recent research. However, less is known about the means by which conditioned fears re-emerge (i.e., spontaneously recover) as time passes or contexts change following extinction. The periaqueductal gray represents the final common pathway mediating defensive reactions to fear and we have reported previously that the dorsolateral PAG (dlPAG) exhibits a small but reliable increase in neural activity (as measured by c-fos protein immunoreactivity) when spontaneous recovery (SR) of a conditioned taste aversion (CTA) is reduced. Here we extend these correlational studies to determine if inducing dlPAG c-fos expression through electrical brain stimulation could cause a reduction in SR of a CTA. Male Sprague-Dawley rats acquired a strong aversion to saccharin (conditioned stimulus; CS) and then underwent CTA extinction through multiple non-reinforced exposures to the CS. Following a 30-day latency period after asymptotic extinction was achieved; rats either received stimulation of the dorsal PAG (dPAG) or stimulation of closely adjacent structures. Sixty minutes following the stimulation, rats were again presented with the saccharin solution as we tested for SR of the CTA. The brain stimulation evoked c-fos expression around the tip of the electrodes. However, stimulation of the dPAG failed to reduce SR of the previously extinguished CTA. In fact, dPAG stimulation caused rats to significantly suppress their saccharin drinking (relative to controls) – indicating an enhanced SR. These data refute a cause-and-effect relationship between enhanced dPAG c-fos expression and a reduction in SR. However, they highlight a role for the dPAG in modulating SR of extinguished CTAs. PMID:23183042

Pregnancy-associated glycoprotein (PAG) concentration in plasma and milk samples for early pregnancy diagnosis in Lacaune dairy sheep.

PubMed

El Amiri, B; Sousa, N M; Alvarez Oxiley, A; Hadarbach, D; Beckers, J F

2015-04-01

In the present study, four RIA systems (RIA-1 to -4) based on two antisera raised against ovine pregnancy-associated glycoproteins (ovPAGs), combined with an ovine or a bovine PAG tracer were used to measure PAG concentrations in plasma and milk samples of dairy ewes. Blood and milk samples were collected on different days of gestation: 0, 18, 20, 22, 25, 28, 32, 42, and 49. From day 20 onward, the PAG in plasma could be detected in all pregnant ewes using the four RIA systems. By using milk, except for RIA-1, the other systems showed a sensitivity of 100% from day 28 of gestation onward. In plasma, PAG concentrations were higher in multiple than in single pregnancies, while no clear relationship was observed in milk. In conclusion, milk is a good alternative to plasma for early pregnancy diagnosis in sheep from day 28 to day 42. Copyright © 2014 Elsevier Ltd. All rights reserved.

Detergent-mediated protein aggregation

PubMed Central

Neale, Chris; Ghanei, Hamed; Holyoake, John; Bishop, Russell E.; Privé, Gilbert G.; Pomès, Régis

2016-01-01

Because detergents are commonly used to solvate membrane proteins for structural evaluation, much attention has been devoted to assessing the conformational bias imparted by detergent micelles in comparison to the native environment of the lipid bilayer. Here, we conduct six 500-ns simulations of a system with >600,000 atoms to investigate the spontaneous self assembly of dodecylphosphocholine detergent around multiple molecules of the integral membrane protein PagP. This detergent formed equatorial micelles in which acyl chains surround the protein’s hydrophobic belt, confirming existing models of the detergent solvation of membrane proteins. In addition, unexpectedly, the extracellular and periplasmic apical surfaces of PagP interacted with the headgroups of detergents in other micelles 85 and 60% of the time, respectively, forming complexes that were stable for hundreds of nanoseconds. In some cases, an apical surface of one molecule of PagP interacted with an equatorial micelle surrounding another molecule of PagP. In other cases, the apical surfaces of two molecules of PagP simultaneously bound a neat detergent micelle. In these ways, detergents mediated the non-specific aggregation of folded PagP. These simulation results are consistent with dynamic light scattering experiments, which show that, at detergent concentrations ≥600 mM, PagP induces the formation of large scattering species that are likely to contain many copies of the PagP protein. Together, these simulation and experimental results point to a potentially generic mechanism of detergent-mediated protein aggregation. PMID:23466535

Comparison of accuracy of pregnancy-associated glycoprotein (PAG) concentration in blood and milk for early pregnancy diagnosis in cows.

PubMed

Gajewski, Z; Petrajtis-Gołobów, M; Melo de Sousa, N; Beckers, J F; Pawliński, B; Wehrend, A

2014-12-01

The aim of this study was to compare two methods of early pregnancy diagnosis by determining pregnancy-associated glycoprotein (PAG) concentration in blood and PAG concentration in milk. Blood and milk samples were obtained on days 0 (AI day), 14, 21, 28, 35, 49, 63, 77, 91 and 105 of gestation from 60 lactating Holstein Frisian cows from one herd, carrying live fetuses. To determine PAG concentration a specific RIA system (RIA-706) was used. PAG concentration in blood and milk increased after 28 days of pregnancy, with blood concentrations being significantly higher than in milk. However, the accuracy of both tests at this time point was similar (sensitivity: 92 % in blood, 93 % in milk; specificity 53 % and 60 % respectively). None of the tests were able to detect open cows properly at this stage. On day 35 of gestation sensitivity (100 % for blood, 97 % for milk) and specificity (100 % for blood, 100 % for milk) were high enough to be used for reliable pregnancy diagnosis. The accuracy (sensitivity and specificity) for PAG concentrations in blood and milk for the rest of the study was 100 %. Our investigation shows that PAG determination in milk is a stress-free and non-invasive method for early pregnancy diagnosis in cattle.

Neural substrates underlying fear-evoked freezing: the periaqueductal grey–cerebellar link

PubMed Central

Koutsikou, Stella; Crook, Jonathan J; Earl, Emma V; Leith, J Lianne; Watson, Thomas C; Lumb, Bridget M; Apps, Richard

2014-01-01

The central neural pathways involved in fear-evoked behaviour are highly conserved across mammalian species, and there is a consensus that understanding them is a fundamental step towards developing effective treatments for emotional disorders in man. The ventrolateral periaqueductal grey (vlPAG) has a well-established role in fear-evoked freezing behaviour. The neural pathways underlying autonomic and sensory consequences of vlPAG activation in fearful situations are well understood, but much less is known about the pathways that link vlPAG activity to distinct fear-evoked motor patterns essential for survival. In adult rats, we have identified a pathway linking the vlPAG to cerebellar cortex, which terminates as climbing fibres in lateral vermal lobule VIII (pyramis). Lesion of pyramis input–output pathways disrupted innate and fear-conditioned freezing behaviour. The disruption in freezing behaviour was strongly correlated to the reduction in the vlPAG-induced facilitation of α-motoneurone excitability observed after lesions of the pyramis. The increased excitability of α-motoneurones during vlPAG activation may therefore drive the increase in muscle tone that underlies expression of freezing behaviour. By identifying the cerebellar pyramis as a critical component of the neural network subserving emotionally related freezing behaviour, the present study identifies novel neural pathways that link the PAG to fear-evoked motor responses. PMID:24639484

Aryl sulfonates as neutral photoacid generators (PAGs) for EUV lithography

NASA Astrophysics Data System (ADS)

Sulc, Robert; Blackwell, James M.; Younkin, Todd R.; Putna, E. Steve; Esswein, Katherine; DiPasquale, Antonio G.; Callahan, Ryan; Tsubaki, Hideaki; Tsuchihashi, Tooru

2009-03-01

EUV lithography (EUVL) is a leading candidate for printing sub-32 nm hp patterns. In order for EUVL to be commercially viable at these dimensions, a continuous evolution of the photoresist material set is required to simultaneously meet the aggressive specifications for resolution, resist sensitivity, LWR, and outgassing rate. Alternative PAG designs, especially if tailored for EUVL, may aid in the formation of a material set that helps achieve these aggressive targets. We describe the preparation, characterization, and lithographic evaluation of aryl sulfonates as non-ionic or neutral photoacid generators (PAGs) for EUVL. Full lithographic characterization is reported for our first generation resist formulation using compound H, MAP-1H-2.5. It is benchmarked against MAP-1P-5.0, which contains the well-known sulfonium PAG, triphenylsulfonium triflate (compound P). Z-factor analysis indicates nZ32 = 81.4 and 16.8 respectively, indicating that our first generation aryl sulfonate formulations require about 4.8x improvement to match the results achieved with a model onium PAG. Improving the acid generation efficiency and use of the generated byproducts is key to the continued optimization of this class of PAGs. To that end, we believe EI-MS fragmentation patterns and molecular simulations can be used to understand and optimize the nature and efficiency of electron-induced PAG fragmentation.

The path to successful commercialization of cell and gene therapies: empowering patient advocates.

PubMed

Bauer, Gerhard; Abou-El-Enein, Mohamed; Kent, Alastair; Poole, Brian; Forte, Miguel

2017-02-01

Often, novel gene and cell therapies provide hope for many people living with incurable diseases. To facilitate and accelerate a successful regulatory approval and commercialization path for effective, safe and affordable cell and gene therapies, the involvement of patient advocacy groups (PAGs) should be considered early in the development process. This report provides a thorough overview of the various roles PAGs play in the clinical translation of cell and gene therapies and how they can bring about positive changes in the regulatory process, infrastructure improvements and market stability. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Role played by periaqueductal gray neurons in parasympathetically mediated fear bradycardia in conscious rats.

PubMed

Koba, Satoshi; Inoue, Ryo; Watanabe, Tatsuo

2016-06-01

Freezing, a characteristic pattern of defensive behavior elicited by fear, is associated with a decrease in the heart rate. Central mechanisms underlying fear bradycardia are poorly understood. The periaqueductal gray (PAG) in the midbrain is known to contribute to autonomic cardiovascular adjustments associated with various emotional behaviors observed during active or passive defense reactions. The purpose of this study was to elucidate the role played by PAG neurons in eliciting fear bradycardia. White noise sound (WNS) exposure at 90 dB induced freezing behavior and elicited bradycardia in conscious rats. The WNS exposure-elicited bradycardia was mediated parasympathetically because intravenous administration of atropine abolished the bradycardia (P < 0.05). Moreover, WNS exposure-elicited bradycardia was mediated by neuronal activation of the lateral/ventrolateral PAG (l/vlPAG) because bilateral microinjection of muscimol, a GABAA agonist, into the l/vlPAG significantly suppressed the bradycardia. It is noted that muscimol microinjected bilaterally into the dorsolateral PAG had no effect on WNS exposure-elicited bradycardia. Furthermore, retrograde neuronal tracing experiments combined with immunohistochemistry demonstrated that a number of l/vlPAG neurons that send direct projections to the nucleus ambiguus (NA) in the medulla, a major origin of parasympathetic preganglionic neurons to the heart, were activated by WNS exposure. Based on these findings, we propose that the l/vlPAG-NA monosynaptic pathway transmits fear-driven central signals, which elicit bradycardia through parasympathetic outflow. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Destruction of a distal hypoxia response element abolishes trans-activation of the PAG1 gene mediated by HIF-independent chromatin looping

PubMed Central

Schörg, Alexandra; Santambrogio, Sara; Platt, James L.; Schödel, Johannes; Lindenmeyer, Maja T.; Cohen, Clemens D.; Schrödter, Katrin; Mole, David R.; Wenger, Roland H.; Hoogewijs, David

2015-01-01

A crucial step in the cellular adaptation to oxygen deficiency is the binding of hypoxia-inducible factors (HIFs) to hypoxia response elements (HREs) of oxygen-regulated genes. Genome-wide HIF-1α/2α/β DNA-binding studies revealed that the majority of HREs reside distant to the promoter regions, but the function of these distal HREs has only been marginally studied in the genomic context. We used chromatin immunoprecipitation (ChIP), gene editing (TALEN) and chromosome conformation capture (3C) to localize and functionally characterize a 82 kb upstream HRE that solely drives oxygen-regulated expression of the newly identified HIF target gene PAG1. PAG1, a transmembrane adaptor protein involved in Src signalling, was hypoxically induced in various cell lines and mouse tissues. ChIP and reporter gene assays demonstrated that the −82 kb HRE regulates PAG1, but not an equally distant gene further upstream, by direct interaction with HIF. Ablation of the consensus HRE motif abolished the hypoxic induction of PAG1 but not general oxygen signalling. 3C assays revealed that the −82 kb HRE physically associates with the PAG1 promoter region, independent of HIF-DNA interaction. These results demonstrate a constitutive interaction between the −82 kb HRE and the PAG1 promoter, suggesting a physiologically important rapid response to hypoxia. PMID:26007655

Identification of Novel Placentally Expressed Aspartic Proteinase in Humans

PubMed Central

Majewska, Marta; Lipka, Aleksandra; Panasiewicz, Grzegorz; Gowkielewicz, Marek; Jozwik, Marcin; Majewski, Mariusz Krzysztof; Szafranska, Bozena

2017-01-01

This study presents pioneering data concerning the human pregnancy-associated glycoprotein-Like family, identified in the genome, of the term placental transcriptome and proteome. RNA-seq allowed the identification of 1364 bp hPAG-L/pep cDNA with at least 56.5% homology with other aspartic proteinases (APs). In silico analyses revealed 388 amino acids (aa) of full-length hPAG-L polypeptide precursor, with 15 aa-signal peptide, 47 aa-blocking peptide and 326 aa-mature protein, and two Asp residues (D), specific for a catalytic cleft of the APs (VVFDTGSSNLWV91-102 and AIVDTGTSLLTG274-285). Capillary sequencing identified 9330 bp of the hPAG-L gene (Gen Bank Acc. No. KX533473), composed of nine exons and eight introns. Heterologous Western blotting revealed the presence of one dominant 60 kDa isoform of the hPAG-L amongst cellular placental proteins. Detection with anti-pPAG-P and anti-Rec pPAG2 polyclonals allowed identification of the hPAG-L proteins located within regions of chorionic villi, especially within the syncytiotrophoblast of term singleton placentas. Our novel data extend the present knowledge about the human genome, as well as placental transcriptome and proteome during term pregnancy. Presumably, this may contribute to establishing a new diagnostic tool for examination of some disturbances during human pregnancy, as well as growing interest from both scientific and clinical perspectives. PMID:28594357

Effects of chemogenetic excitation or inhibition of the ventrolateral periaqueductal gray on the acquisition and extinction of Pavlovian fear conditioning.

PubMed

Arico, Carolyn; Bagley, Elena E; Carrive, Pascal; Assareh, Neda; McNally, Gavan P

2017-10-01

The midbrain periaqueductal gray (PAG) has been implicated in the generation and transmission of a prediction error signal that instructs amygdala-based fear and extinction learning. However, the PAG also plays a key role in the expression of conditioned fear responses. The evidence for a role of the PAG in fear learning and extinction learning has been obtained almost exclusively using PAG-dependent fear responses. It is less clear whether the PAG regulates fear learning when other measures of learned fear are used. Here we combined a chemogenetic approach, permitting excitation or inhibition of neurons in the ventrolateral PAG (VLPAG), with conditioned suppression as the measure of learned fear to assess the role of VLPAG in the acquisition and extinction of fear learning. We show that chemogenetic excitation of VLPAG (with some encroachment on lateral PAG [LPAG]) impairs acquisition of fear and, conversely, chemogenetic inhibition impairs extinction of fear. These effects on fear and extinction learning were specific to the combination of DREADD expression and injection of CNO because they were observed relative to both eYFP controls injected with CNO as well as DREADD expressing controls injected with vehicle. Taken together, these results show that activity of L/VLPAG neurons regulates both the acquisition and extinction of Pavlovian fear learning. Copyright © 2017 Elsevier Inc. All rights reserved.

Identification of Novel Placentally Expressed Aspartic Proteinase in Humans.

PubMed

Majewska, Marta; Lipka, Aleksandra; Panasiewicz, Grzegorz; Gowkielewicz, Marek; Jozwik, Marcin; Majewski, Mariusz Krzysztof; Szafranska, Bozena

2017-06-08

This study presents pioneering data concerning the human pregnancy-associated glycoprotein-Like family, identified in the genome, of the term placental transcriptome and proteome. RNA-seq allowed the identification of 1364 bp hPAG-L/pep cDNA with at least 56.5% homology with other aspartic proteinases (APs). In silico analyses revealed 388 amino acids (aa) of full-length hPAG-L polypeptide precursor, with 15 aa-signal peptide, 47 aa-blocking peptide and 326 aa-mature protein, and two Asp residues (D), specific for a catalytic cleft of the APs (VVFDTGSSNLWV91-102 and AIVDTGTSLLTG274-285). Capillary sequencing identified 9330 bp of the hPAG-L gene (Gen Bank Acc. No. KX533473), composed of nine exons and eight introns. Heterologous Western blotting revealed the presence of one dominant 60 kDa isoform of the hPAG-L amongst cellular placental proteins. Detection with anti-pPAG-P and anti-Rec pPAG2 polyclonals allowed identification of the hPAG-L proteins located within regions of chorionic villi, especially within the syncytiotrophoblast of term singleton placentas. Our novel data extend the present knowledge about the human genome, as well as placental transcriptome and proteome during term pregnancy. Presumably, this may contribute to establishing a new diagnostic tool for examination of some disturbances during human pregnancy, as well as growing interest from both scientific and clinical perspectives.

Results of the independent verification of radiological remedial action at 600 South Clayhill Drive (AKA 600 South Cemetery Road), Monticello, Utah (MS00145)

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

Wilson, M.J.; Crutcher, J.W.

1991-07-01

In 1980 the site of a vanadium and uranium mill at Monticello, Utah, was accepted into the US Department of Energy's (DOE's) Surplus Facilities Management Program, with the objectives of restoring the government-owned mill site to safe levels of radioactivity, disposing of or containing the tailings in an environmentally safe manner, and performing remedial actions on off-site (vicinity) properties that had been contaminated by radioactive material resulting from mill operations. During 1986 and 1987, UNC Geotech, the remedial action contractor designated by DOE, performed remedial action on the vicinity property at 600 South Cemetery Road (updated by San Juan Countymore » and the state of Utah to 600 South Clayhill Drive), Monticello, Utah. The Pollutant Assessments Group (PAG) of Oak Ridge National Laboratory was assigned the responsibility of verifying the data supporting the adequacy of remedial action and confirming the site's compliance with DOE guidelines. The PAG found that the site successfully meets the DOE remedial action objectives. Procedures used by PAG are described. 3 refs., 2 tabs.« less

Opiate anti-nociception is attenuated following lesion of large dopamine neurons of the periaqueductal grey: critical role for D1 (not D2) dopamine receptors.

PubMed

Flores, Juan A; El Banoua, Fadwa; Galán-Rodríguez, Beatriz; Fernandez-Espejo, Emilio

2004-07-01

The periaqueductal grey (PAG) area is involved in pain modulation as well as in opiate-induced anti-nociceptive effects. The PAG possess dopamine neurons, and it is likely that this dopaminergic network participates in anti-nociception. The objective was to further study the morphology of the PAG dopaminergic network, along with its role in nociception and opiate-induced analgesia in rats, following either dopamine depletion with the toxin 6-hydroxydopamine or local injection of dopaminergic antagonists. Nociceptive responses were studied through the tail-immersion (spinal reflex) and the hot-plate tests (integrated supraspinal response), establishing a cut-off time to further minimize animal suffering. Heroin and morphine were employed as opiates. Histological data indicated that the dopaminergic network of the PAG is composed of two types of neurons: small rounded cells, and large multipolar neurons. Following dopamine depletion of the PAG, large neurons (not small ones) were selectively affected by the toxin (61.9% dopamine cell loss, 80.7% reduction of in vitro dopaminergic peak), and opiate-induced analgesia in the hot-plate test (not the tail-immersion test) was reliably attenuated in lesioned rats (P < 0.01). After infusions of dopaminergic ligands into the PAG, D(1) (not D(2)) receptor antagonism attenuated opiate-induced analgesia in a dose-dependent manner in the hot-plate test. The present study provides evidence that large neurons of the dopaminergic network of the PAG participate in supraspinal (not spinal) nociceptive responses after opiates through the involvement of D(1) dopamine receptors. This dopaminergic system should be included as another network within the PAG involved in opiate-induced anti-nociception.

Role of IL-1 beta and 5-HT2 receptors in midbrain periaqueductal gray (PAG) in potentiating defensive rage behavior in cat.

PubMed

Bhatt, Suresh; Bhatt, Rekha; Zalcman, Steven S; Siegel, Allan

2008-02-01

Feline defensive rage, a form of aggressive behavior that occurs in response to a threat can be elicited by electrical stimulation of the medial hypothalamus or midbrain periaqueductal gray (PAG). Our laboratory has recently begun a systematic examination of the role of cytokines in the regulation of rage and aggressive behavior. It was shown that the cytokine, interleukin-2 (IL-2), differentially modulates defensive rage when microinjected into the medial hypothalamus and PAG by acting through separate neurotransmitter systems. The present study sought to determine whether a similar relationship exists with respect to interleukin 1-beta (IL-1 beta), whose receptor activation in the medial hypothalamus potentiates defensive rage. Thus, the present study identified the effects of administration of IL-1 beta into the PAG upon defensive rage elicited from the medial hypothalamus. Microinjections of IL-1 beta into the dorsal PAG significantly facilitated defensive rage behavior elicited from the medial hypothalamus in a dose and time dependent manner. In addition, the facilitative effects of IL-1 beta were blocked by pre-treatment with anti-IL-1 beta receptor antibody, while IL-1 beta administration into the PAG had no effect upon predatory attack elicited from the lateral hypothalamus. The findings further demonstrated that IL-1 beta's effects were mediated through 5-HT(2) receptors since pretreatment with a 5-HT(2C) receptors antagonist blocked the facilitating effects of IL-1 beta. An extensive pattern of labeling of IL-1 beta and 5-HT(2C) receptors in the dorsal PAG supported these findings. The present study demonstrates that IL-beta in the dorsal PAG, similar to the medial hypothalamus, potentiates defensive rage behavior and is mediated through a 5-HT(2C) receptor mechanism.

Evaluating correlates of adolescent physical activity duration towards National Health Objectives: analysis of the Colorado Youth Risk Behavioral Survey, 2005.

PubMed

Nkansah-Amankra, Stephen; Diedhiou, Abdoulaye; Agbanu, Harry L K; Toma-Drane, Mariana; Dhawan, Ashish

2011-06-01

While numerous studies have examined the relationships among correlates of physical activity (PA), less attention has been given to identifying the correlates of low PA duration. The main objective of the current study was to examine correlates of low PA duration, team sports participation and smoking behaviors among adolescents. Data from the 2005 Colorado Youth Behavioral Risk Survey were analyzed using Cox proportional hazard models. We evaluated associations between two measures of low PA duration, assessed as per Healthy People 2010 (HP2010) objectives and 2008 Physical Activity Guidelines (PAG) for Americans, and smoking behaviors, participation in the physical education (PE) and team sports, controlling for age, gender and other behavioral characteristics. Forty percent and 70%, respectively, of adolescents did not meet the 2008 PAG and HP2010 objectives. After adjustment, smoking remained associated with failure to meet the 2008 PAG. However, no significant relationship was found with low PA duration as per the HP2010 objectives. The risk of low PA was higher among girls for both outcome measures. Likewise, adolescents who reported no participation in team sports presented a 7-fold higher risk of low PA as per the 2008 PAG and 51% higher risk of low PA as per the HP2010 objectives compared with the group with team sports participation. Regular participation in school PE and team sports may represent an important avenue for increasing PA duration and reducing smoking behaviors among adolescents.

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

Gangopadhyay, Arup; McWatt, D. G.; Zdrodowski, R. J.

Engine oils play a critical role in friction reduction. Improvements in engine oil technology steadily improved fuel economy as the industry moved through ILSAC GF-1 to GF-5 specifications. These improvements were influenced by changes in base oil chemistry, development of new friction modifiers and their treat levels, and the total additive package consisting of various other components. However, the improvements are incremental and further fuel consumption reduction opportunities are becoming more challenging. Polyalkylene glycol (PAG) based engine oils are being explored as a step forward for significant fuel consumption reduction. Although PAG fluids are used in many industrial applications, itsmore » application as an engine oil has been explored in a limited way. The objective of this project is to deep dive in exploring the applicability of PAG technology in engine oil, understanding the benefits, and limitations, elucidating the mechanism(s) for friction benefits, if any, and finally recommending how to address any limitations. The project was designed in four steps, starting with selection of lubricant technology, followed by friction and wear evaluations in laboratory bench tests which are relatively simple and inexpensive and also served as a screener for further evaluation. Selected formulations were chosen for more complex engine component level tests i.e., motored valvetrain friction and wear, piston ring friction using a motored single cylinder, and motored engine tests. A couple of formulations were further selected based on component level tests for engine dyno tests i.e., Sequence VID (ASTM D6709) for fuel economy, Sequence IVA (ASTM D6891) for valvetrain wear, and Sequence VG (ASTM D6593) for sludge and varnish protection. These are some of the industry standard tests required for qualifying engine oils. Out of these tests, a single PAG oil was selected for chassis roll dynamometer tests for fuel economy and emission measurements using FTP (Federal Test Procedure) metro/highway cycles. Five different PAG chemistries were selected by varying the starting alcohol, the oxide monomers (ethylene oxide, propylene oxide, or butylene oxide), capped or uncapped, homopolymer or random copolymer. All formulations contained a proprietary additive package and one which contained additional antiwear and friction modifier additives. Laboratory bench tests (Pin-on-Disk, High Frequency Reciprocating Rig (HFRR), Block-on-Ring, Mini-Traction Machine (MTM) identified formulations having friction, wear, and load carrying characteristics similar to or better than baseline GF-5 SAE 5W-20 oil. Motored valvetrain and motored piston ring friction tests showed nearly 50% friction reduction for some of the PAG formulations compared to GF-5 SAE 5W-20 oil. Motored engine tests showed up to 15% friction benefit over GF-5 SAE 5W-20 oil. It was observed that friction benefits are more related to PAG base oil chemistry than their lower viscosity compared to GF-5 SAE 5W-20 oil. Analysis of wear surfaces from laboratory bench tests and bucket tappets from motored valvetrain tests confirmed the presence of PAG molecules. The adsorption of these polar molecules is believed to be reason for friction reduction. However, the wear surfaces also had thin tribo-film derived from additive components. The tribo-film consisting of phosphates, sulfides, and molybdenum disulfide (when molybdenum additive was present) were observed for both GF-5 SAE 5W-20 and PAG fluids. However, when using PAG fluids, motored valvetrain tests showed high initial wear, which is believed to be due to delay in protective tribo-film formation. After the initial wear, the wear rate of PAG fluids was comparable to GF-5 SAE 5W-20 oil. The PAG oil containing additional antiwear and friction reducing additives showed low initial wear as expected. However, when this oil was evaluated in Sequence IVA test, it showed initially low wear comparable to GF-5 oil but wear accelerated with oil aging indicating rapid deterioration of additive components. ASTM Sequence VG test showed good sludge protection capability but failed to meet varnish rating for GF-5 requirement. Chassis roll dynamometer tests with PAG oil 15-1 showed about 1% fuel economy benefit over GF-5 SAE 5W-20 oil in EPA city cycles only and when the oil was slightly aged (500 miles). No fuel economy benefits could be observed in combined EPA metro/highway cycles. Also, no fuel economy benefit could be observed with continued (500- 10000 miles) oil aging. However, the emission level was comparable to the reference oil and was within EPA limits. Analysis of the PAG oil following tests showed low iron content although additive components were significantly degraded. The results indicate that PAG fluids have significant friction reduction potential but there are challenges with wear and varnish protection capabilities. These limitations are primarily because the selected additive components were chosen to provide a fluid with no metal content that forms little or no sulphated ash. Significant development work is needed to identify additive components compatible with PAG chemistry including their solubility in PAG oil. Miscibility of PAG fluids with mineral base oil is another challenge for oil change service. There is PAG chemistry (oil soluble PAG, OSP) which is soluble in mineral oils but the formulation explored in this investigation did not show significant friction reduction in motored engine tests. Again, highlighting the need for additive development for specific PAG chemistry. The thermal oxidation behavior of these oils has not been explored in this investigation and needs attention.« less

Destruction of a distal hypoxia response element abolishes trans-activation of the PAG1 gene mediated by HIF-independent chromatin looping.

PubMed

Schörg, Alexandra; Santambrogio, Sara; Platt, James L; Schödel, Johannes; Lindenmeyer, Maja T; Cohen, Clemens D; Schrödter, Katrin; Mole, David R; Wenger, Roland H; Hoogewijs, David

2015-07-13

A crucial step in the cellular adaptation to oxygen deficiency is the binding of hypoxia-inducible factors (HIFs) to hypoxia response elements (HREs) of oxygen-regulated genes. Genome-wide HIF-1α/2α/β DNA-binding studies revealed that the majority of HREs reside distant to the promoter regions, but the function of these distal HREs has only been marginally studied in the genomic context. We used chromatin immunoprecipitation (ChIP), gene editing (TALEN) and chromosome conformation capture (3C) to localize and functionally characterize a 82 kb upstream HRE that solely drives oxygen-regulated expression of the newly identified HIF target gene PAG1. PAG1, a transmembrane adaptor protein involved in Src signalling, was hypoxically induced in various cell lines and mouse tissues. ChIP and reporter gene assays demonstrated that the -82 kb HRE regulates PAG1, but not an equally distant gene further upstream, by direct interaction with HIF. Ablation of the consensus HRE motif abolished the hypoxic induction of PAG1 but not general oxygen signalling. 3C assays revealed that the -82 kb HRE physically associates with the PAG1 promoter region, independent of HIF-DNA interaction. These results demonstrate a constitutive interaction between the -82 kb HRE and the PAG1 promoter, suggesting a physiologically important rapid response to hypoxia. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Impact of a Pediatric and Adolescent Gynecology Curriculum on an Obstetrics and Gynecology Residency.

PubMed

Palaszewski, Dawn M; Miladinovic, Branko; Caselnova, Petra M; Holmström, Shelly W

2016-12-01

To determine the effectiveness of a new pediatric and adolescent gynecology (PAG) curriculum for improving obstetrics/gynecology resident physician knowledge and comfort level in patient management and to describe the current deficiencies in resident physician knowledge and comfort level in PAG. A PAG curriculum was implemented for the obstetrics/gynecology resident physicians (n = 20) at the University of South Florida in July 2013. Before and after the curriculum was introduced, resident physicians and recent graduates of the residency program completed a survey to assess their comfort level and a knowledge assessment consisting of 20 case-based questions. University-based residency program. Resident physicians and recent resident physician graduates in the Department of Obstetrics and Gynecology. Introduction of a PAG curriculum during the 2013-2014 academic year. Improvement in resident physicians' comfort level and knowledge in PAG. After the curriculum was introduced, comfort increased in examining the genitals of a pediatric gynecology patient (median difference = 1.5; P = .003) and history-taking, physical examination skills, and management (median difference = 1; P = .002) compared with before the curriculum. There was no significant difference in overall quiz score (15.5 ± 1.87 vs 15.8 ± 1.3; P = .78). A curriculum in PAG did improve resident comfort level in managing PAG patients, but did not significantly improve knowledge of this topic. Copyright © 2016.

Connexions between the dorsomedial division of the ventromedial hypothalamus and the dorsal periaqueductal grey matter are critical in the elaboration of hypothalamically mediated panic-like behaviour.

PubMed

Ullah, Farhad; Dos Anjos-Garcia, Tayllon; Mendes-Gomes, Joyce; Elias-Filho, Daoud Hibrahim; Falconi-Sobrinho, Luiz Luciano; Freitas, Renato Leonardo de; Khan, Asmat Ullah; Oliveira, Ricardo de; Coimbra, Norberto Cysne

2017-02-15

The electrical and chemical stimulation of the dorsal periaqueductal grey matter (dPAG) elicits panic-like explosive escape behaviour. Although neurons of the ventromedial hypothalamus (VMH) seem to organise oriented escape behaviour, when stimulated with excitatory amino acids at higher doses, non-oriented/explosive escape reactions can also be displayed. The aim of this work was to examine the importance of reciprocal projections between the VMH and the dPAG for the organisation of this panic-like behaviour. The chemical stimulation of the VMH with 9nmol of N-methyl-d-aspartic acid (NMDA) elicited oriented and non-oriented escape behaviours. The pretreatment of the dPAG with a non-selective blocker of synaptic contacts, cobalt chloride (CoCl 2 ), followed by stimulation of the dorsomedial part of the ventromedial hypothalamus (dmVMH) with 9nmol of NMDA, abolished the non-oriented/explosive escape and freezing responses elicited by the stimulation of the dmVMH. Nonetheless, the rats still showed oriented escape to the burrow. On the other hand, when the blockade of the dmVMH with CoCl 2 was followed by stimulation of the dPAG with 6nmol of NMDA, no effect was observed either on the non-oriented/explosive escape or on the freezing behaviour organised by the dPAG. Furthermore, Fos protein-labelled neurons were observed in the dPAG after the stimulation of the dmVMH with 9nmol of NMDA. Additionally, when the anterograde neurotracer biotinylated dextran amine (BDA) was deposited in the dmVMH subsequent stimulation of the dmVMH produced BDA-labelled neural fibres with terminal boutons surrounding Fos-labelled neurons in the dPAG, suggesting synaptic contacts between dmVMH and dPAG neurons for eliciting panic-like behavioural responses. The current data suggest that the dPAG is the key structure that organises non-oriented/explosive escape reactions associated with panic attack-like behaviours. Copyright © 2016 Elsevier B.V. All rights reserved.

The endocannabinoid system in the rat dorsolateral periaqueductal grey mediates fear-conditioned analgesia and controls fear expression in the presence of nociceptive tone

PubMed Central

Olango, WM; Roche, M; Ford, GK; Harhen, B; Finn, DP

2012-01-01

BACKGROUND AND PURPOSE Endocannabinoids in the midbrain periaqueductal grey (PAG) modulate nociception and unconditioned stress-induced analgesia; however, their role in fear-conditioned analgesia (FCA) has not been examined. The present study examined the role of the endocannabinoid system in the dorsolateral (dl) PAG in formalin-evoked nociceptive behaviour, conditioned fear and FCA in rats. EXPERIMENTAL APPROACH Rats received intra-dlPAG administration of the CB1 receptor antagonist/inverse agonist rimonabant, or vehicle, before re-exposure to a context paired 24 h previously with foot shock. Formalin-evoked nociceptive behaviour and fear-related behaviours (freezing and 22 kHz ultrasonic vocalization) were assessed. In a separate cohort, levels of endocannabinoids [2-arachidonoyl glycerol (2-AG) and N-arachidonoyl ethanolamide (anandamide; AEA)] and the related N-acylethanolamines (NAEs) [N-palmitoyl ethanolamide (PEA) and N-oleoyl ethanolamide (OEA)] were measured in dlPAG tissue following re-exposure to conditioned context in the presence or absence of formalin-evoked nociceptive tone. KEY RESULTS Re-exposure of rats to the context previously associated with foot shock resulted in FCA. Intra-dlPAG administration of rimonabant significantly attenuated FCA and fear-related behaviours expressed in the presence of nociceptive tone. Conditioned fear without formalin-evoked nociceptive tone was associated with increased levels of 2-AG, AEA, PEA and OEA in the dlPAG. FCA was specifically associated with an increase in AEA levels in the dlPAG. CONCLUSIONS AND IMPLICATIONS Conditioned fear to context mobilises endocannabinoids and NAEs in the dlPAG. These data support a role for endocannabinoids in the dlPAG in mediating the potent suppression of pain responding which occurs during exposure to conditioned aversive contexts. LINKED ARTICLES This article is part of a themed section on Cannabinoids in Biology and Medicine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-8. To view Part I of Cannabinoids in Biology and Medicine visit http://dx.doi.org/10.1111/bph.2011.163.issue-7 PMID:21564082

Endocrine Profiles, Haematology and Pregnancy Outcomes of Late Pregnant Holstein Dairy Heifers Sired by Bulls Giving a High or Low Incidence of Stillbirth

PubMed Central

Kornmatitsuk, B; Dahl, E; Ropstad, E; Beckers, JF; Gustafsson, H; Kindahl, H

2004-01-01

The high incidence of stillbirth in Swedish Holstein heifers has increased continuously during the last 15 years to an average of 11% today. The pathological reasons behind the increased incidence of stillbirth are unknown. The present experiment was undertaken to investigate possible causes of stillbirth and to study possible physiological markers for predicting stillbirth. Twenty Swedish Holstein dairy heifers sired by bulls with breeding values for a high risk of stillbirth (n = 12) (experimental group) and a low risk of stillbirth (n = 8) (control group, group B) were selected based on information in the Swedish AI-data base. The experimental group consisted of 2 subgroups of heifers (groups A1 and A2) inseminated with 2 different bulls with 3.5% and 9% higher stillbirth rates than the average, and the control group consisted of heifers pregnant with 5 different bulls with 0%–6% lower stillbirth rates than the average. The bull used for group A1 had also calving difficulties due to large calves as compared to the bull in group A2 showing no calving difficulties. The heifers were supervised from 6–7 months of pregnancy up to birth, and the pregnancies and parturitions were compared between groups regarding hormonal levels, haematology, placental characteristics and calf viability. In group A1, 1 stillborn, 1 weak and 4 normal calves were recorded. In group A2, 2 stillborn and 4 normal calves were registered. All animals in the control group gave birth to a normal living calf without any assistance. The weak calf showed deviating profiles of body temperature, saturated oxygen and heart rates, compared with the normal living calves. No differences of the placentome thickness, measured in vivo by ultrasonography were seen between the groups. The number of leukocytes and differential cell counts in groups A1 and A2 followed the profiles found in the control group. In group A1, a slight decrease of oestrone sulphate (E1SO4) levels was found in the animal delivering a stillborn calf from the first 24-h blood sampling at 6 weeks to the second at 3 weeks prior to delivery, while the levels of E1SO4 at both periods in the animal delivering a weak calf followed the profile in animals delivering a normal living calf. During late pregnancy and at the time of parturition, the levels of E1SO4 and PAGs in animals delivering a stillborn or weak calf (from group A1) followed the normal profiles found in animals delivering a normal living calf. In group A2, low levels of E1SO4 and pregnancy associated glycoproteins (PAGs) over 24 h at both 3 and 6 weeks prior to parturition (<1.5 nmol/L) were recorded in animals delivering a stillborn calf. During late pregnancy and parturition, the levels of E1SO4 and PAGs were slightly lower during 30–50 days prior to delivery and increased with a lower magnitude at the time of parturition. In conclusion, our results indicate that the aetiology behind stillbirth varies depending on the AI-bulls used and is associated with dystocia or low viability of the calves. Deviating profiles of oestrone sulphate (E1SO4) and pregnancy associated glycoproteins (PAGs) in animals delivering a stillborn calf not caused by dystocia were observed, suggesting placental dysfunction as a possible factor. The finding suggests that the analyses of E1SO4 and PAGs could be used for monitoring foetal well-being in animals with a high risk of stillbirth at term. PMID:15535086

Comparative effects of 12 weeks of equipment based and mat Pilates in patients with Chronic Low Back Pain on pain, function and transversus abdominis activation. A randomized controlled trial.

PubMed

Cruz-Díaz, David; Bergamin, M; Gobbo, S; Martínez-Amat, Antonio; Hita-Contreras, Fidel

2017-08-01

Pilates method has been recommended for patients with chronic low back pain (CLBP) and the activation of transversus abdominis has been deemed to play an important role in the improvement of these patients. Nevertheless, the evidence of the activation of TrA in Pilates practitioners remains unclear. To assess the effectiveness of 12 weeks of Pilates practice in disability, pain, kinesiophobia and transversus abdominis activation in patients with chronic nonspecific Low Back Pain. A randomized controlled trial was carried out. A single-blind randomized controlled trial with repeated measures at 6 and 12 weeks was carried out. A total of ninety eight patients with low back pain were included and randomly allocated to a Pilates Mat group (PMG) equipment based with apparatus Pilates (PAG) or control group (CG). Roland Morris Disability Questionnaire (RMDQ), visual analog scale (VAS) Tampa Scale of Kinesiophobia (TSK), and transversus abdominis (TrA) activation assessed by real time ultrasound measurement (US) were assessed as outcome measures. Improvement were observed in both intervention groups in all the included variables at 6 and 12 weeks (p<0.001). Faster enhancement was observed in the equipment based Pilates group (p=0.007). Equipment based and mat Pilates modalities are both effective in the improvement of TaA activation in patients with CLBP with associate improvement on pain, function and kinesiophobia. Significant differences were observed after 12 weeks of intervention in PMG and PAG with faster improvement in PAG suggesting that, feedback provided by equipment could help in the interiorization of Pilates principles. Copyright © 2017 Elsevier Ltd. All rights reserved.

A leptin-regulated circuit controls glucose mobilization during noxious stimuli.

PubMed

Flak, Jonathan N; Arble, Deanna; Pan, Warren; Patterson, Christa; Lanigan, Thomas; Goforth, Paulette B; Sacksner, Jamie; Joosten, Maja; Morgan, Donald A; Allison, Margaret B; Hayes, John; Feldman, Eva; Seeley, Randy J; Olson, David P; Rahmouni, Kamal; Myers, Martin G

2017-08-01

Adipocytes secrete the hormone leptin to signal the sufficiency of energy stores. Reductions in circulating leptin concentrations reflect a negative energy balance, which augments sympathetic nervous system (SNS) activation in response to metabolically demanding emergencies. This process ensures adequate glucose mobilization despite low energy stores. We report that leptin receptor-expressing neurons (LepRb neurons) in the periaqueductal gray (PAG), the largest population of LepRb neurons in the brain stem, mediate this process. Application of noxious stimuli, which often signal the need to mobilize glucose to support an appropriate response, activated PAG LepRb neurons, which project to and activate parabrachial nucleus (PBN) neurons that control SNS activation and glucose mobilization. Furthermore, activating PAG LepRb neurons increased SNS activity and blood glucose concentrations, while ablating LepRb in PAG neurons augmented glucose mobilization in response to noxious stimuli. Thus, decreased leptin action on PAG LepRb neurons augments the autonomic response to noxious stimuli, ensuring sufficient glucose mobilization during periods of acute demand in the face of diminished energy stores.

Simulation Comparisons of Three Different Meander Line Dipoles

DTIC Science & Technology

2015-01-01

Paez C I. Design formulas for a meandered dipole. IEEE Xplore Digital Library, 2014: n. pag. Web. 2 September 2014. 2. Nguyen, VH, Phan, HP, Hoang...MH. Improving radiation characteristics of UHF RFID antennas by zigzag structures. IEEE Xplore Digital Library, 2014: n. pag. Web. 2 September 2014...geometry-based, frequency-independent lumped element model. IEEE Xplore Digital Library, 2014: n. pag. Web. 2 September 2014. 5. Olaode OO, Palmer WD

Brain circuits mediating baroreflex bradycardia inhibition in rats: an anatomical and functional link between the cuneiform nucleus and the periaqueductal grey

PubMed Central

Netzer, Florence; Bernard, Jean-François; Verberne, Anthony J M; Hamon, Michel; Camus, Françoise; Benoliel, Jean-Jacques; Sévoz-Couche, Caroline

2011-01-01

Abstract Defence responses triggered experimentally in rats by stimulation of the dorsomedial nucleus of the hypothalamus (DMH) and the dorsolateral periaqueductal grey matter (PAG) inhibit the cardiac baroreflex response (i.e. bradycardia). It has also been proposed that the midbrain cuneiform nucleus (CnF) is involved in active responses. Our aim was to identify the neurocircuitry involved in defence-induced baroreflex inhibition, with a particular focus on the link between DMH, CnF and dorsolateral PAG. Microinjection of the anterograde tracer Phaseolus vulgaris leucoaggutinin into the CnF revealed a dense projection to the dorsolateral PAG. Moreover, activation of neurons in the CnF induced increased expression of Fos protein in the dorsolateral PAG. Inhibition of neurons of the CnF or dorsolateral PAG prevented the inhibition of baroreflex bradycardia induced by DMH or CnF stimulation, respectively. These results provide a detailed description of the brain circuitry underlying acute baroreflex modulation by neurons of the DMH. Our data have shown for the first time that the CnF plays a key role in defence reaction-associated cardiovascular changes; its stimulation, from the DMH, activates the dorsolateral PAG, which, in turn, inhibits baroreflex bradycardia. PMID:21486808

Effect of Dorsal and Ventral Hippocampal Lesions on Contextual Fear Conditioning and Unconditioned Defensive Behavior Induced by Electrical Stimulation of the Dorsal Periaqueductal Gray

PubMed Central

Ballesteros, Carolina Irurita; de Oliveira Galvão, Bruno; Maisonette, Silvia; Landeira-Fernandez, J.

2014-01-01

The dorsal (DH) and ventral (VH) subregions of the hippocampus are involved in contextual fear conditioning. However, it is still unknown whether these two brain areas also play a role in defensive behavior induced by electrical stimulation of the dorsal periaqueductal gray (dPAG). In the present study, rats were implanted with electrodes into the dPAG to determine freezing and escape response thresholds after sham or bilateral electrolytic lesions of the DH or VH. The duration of freezing behavior that outlasted electrical stimulation of the dPAG was also measured. The next day, these animals were subjected to contextual fear conditioning using footshock as an unconditioned stimulus. Electrolytic lesions of the DH and VH impaired contextual fear conditioning. Only VH lesions disrupted conditioned freezing immediately after footshock and increased the thresholds of aversive freezing and escape responses to dPAG electrical stimulation. Neither DH nor VH lesions disrupted post-dPAG stimulation freezing. These results indicate that the VH but not DH plays an important role in aversively defensive behavior induced by dPAG electrical stimulation. Interpretations of these findings should be made with caution because of the fact that a non-fiber-sparing lesion method was employed. PMID:24404134

Echolocation calls and communication calls are controlled differentially in the brainstem of the bat Phyllostomus discolor

PubMed Central

Fenzl, Thomas; Schuller, Gerd

2005-01-01

Background Echolocating bats emit vocalizations that can be classified either as echolocation calls or communication calls. Neural control of both types of calls must govern the same pool of motoneurons responsible for vocalizations. Electrical microstimulation in the periaqueductal gray matter (PAG) elicits both communication and echolocation calls, whereas stimulation of the paralemniscal area (PLA) induces only echolocation calls. In both the PAG and the PLA, the current thresholds for triggering natural vocalizations do not habituate to stimuli and remain low even for long stimulation periods, indicating that these structures have relative direct access to the final common pathway for vocalization. This study intended to clarify whether echolocation calls and communication calls are controlled differentially below the level of the PAG via separate vocal pathways before converging on the motoneurons used in vocalization. Results Both structures were probed simultaneously in a single experimental approach. Two stimulation electrodes were chronically implanted within the PAG in order to elicit either echolocation or communication calls. Blockade of the ipsilateral PLA site with iontophoretically application of the glutamate antagonist kynurenic acid did not impede either echolocation or communication calls elicited from the PAG. However, blockade of the contralateral PLA suppresses PAG-elicited echolocation calls but not communication calls. In both cases the blockade was reversible. Conclusion The neural control of echolocation and communication calls seems to be differentially organized below the level of the PAG. The PLA is an essential functional unit for echolocation call control before the descending pathways share again the final common pathway for vocalization. PMID:16053533

Using Polymer Alternating Gas to Enhance Oil Recovery in Heavy Oil

NASA Astrophysics Data System (ADS)

Yang, Yongzhi; Li, Weirong; Zhou, Tiyao; Dong, Zhenzhen

2018-02-01

CO2 has been used to recover oil for more than 40 years. Currently, about 43% of EOR production in U.S. is from CO2 flooding. CO2 flooding is a well-established EOR technique, but its density and viscosity nature are challenges for CO2 projects. Low density (0.5 to 0.8 g/cm3) causes gas to rise upward in reservoirs and bypass many lower portions of the reservoir. Low viscosity (0.02 to 0.08 cp) leads to poor volumetric sweep efficiency. So water-alternating-gas (WAG) method was used to control the mobility of CO2 and improve sweep efficiency. However, WAG process has some other problems in heavy oil reservoir, such as poor mobility ratio and gravity overriding. To examine the applicability of carbon dioxide to recover viscous oil from highly heterogeneous reservoirs, this study suggests a new EOR method--polymer-alternating gas (PAG) process. The process involves a combination of polymer flooding and CO2 injection. To confirm the effectiveness of PAG process in heavy oils, a reservoir model from Liaohe Oilfield is used to compare the technical and economic performance among PAG, WAG and polymer flooding. Simulation results show that PAG method would increase oil recovery over 10% compared with other EOR methods and PAG would be economically success based on assumption in this study. This study is the first to apply PAG to enhance oil recovery in heavy oil reservoir with highly heterogeneous. Besides, this paper provides detailed discussions and comparison about PAG with other EOR methods in this heavy oil reservoir.

Protective Action Guides (PAGs)

EPA Pesticide Factsheets

The Protective Action Guide (PAG) manual contains radiation dose guidelines that would trigger public safety measures. EPA developed Protective Action Guides to help responders plan for radiation emergencies.

Determination of properties of PVE lubricants with HFC refrigerants[PolyVinylEther

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

Kaneko, Masato; Sakanoue, Shuichi; Tazaki, Toshihiro

1999-07-01

Polyalkyleneglycol (PAG) and polyol ester (POE) have been developed as refrigeration lubricants, used with HFC134a. PAG is used for automotive air conditioning systems and POE is used for domestic reciprocating refrigerators and for A/C systems. Although PAG exhibits good lubricity performance, it is difficult to use for domestic reciprocating refrigerators due to its low dielectric property. POE is difficult to use for automotive A/C systems, due to hydrolysis and poor lubricity performance. Polyvinylether (PVE) can be used in place of PAG and POE with HFC refrigerants. PVE is used for A/C systems as well as refrigerator and freezer applications. PVEmore » is an ideal lubricant for use with HFCs.« less

Panicolytic-like action of bradykinin in the dorsal periaqueductal gray through μ-opioid and B2-kinin receptors.

PubMed

Sestile, Caio César; Maraschin, Jhonatan Christian; Gama, Vanessa Scalco; Zangrossi, Hélio; Graeff, Frederico Guilherme; Audi, Elisabeth Aparecida

2017-09-01

A wealth of evidence has shown that opioid and kinin systems may control proximal defense in the dorsal periaqueductal gray matter (dPAG), a critical panic-associated area. Studies with drugs that interfere with serotonin-mediated neurotransmission suggest that the μ-opioid receptor (MOR) synergistically interacts with the 5-HT 1A receptor in the dPAG to inhibit escape, a panic-related behavior. A similar inhibitory effect has also been reported after local administration of bradykinin (BK), which is blocked by the non-selective opioid receptor antagonist naloxone. The latter evidence, points to an interaction between BK and opioids in the dPAG. We further explored the existence of this interaction through the dPAG electrical stimulation model of panic. We also investigated whether intra-dPAG injection of captopril, an inhibitor of the angiotensin-converting enzyme (ACE) that also degrades BK, causes a panicolytic-like effect. Our results showed that intra-dPAG injection of BK inhibited escape performance in a dose-dependent way, and this panicolytic-like effect was blocked by the BK type 2 receptor (B2R) antagonist HOE-140, and by the selective MOR antagonist CTOP. Conversely, the panicolytic-like effect caused by local administration of the selective MOR agonist DAMGO was antagonized by pre-treatment with either CTOP or HOE-140, indicating cross-antagonism between MOR and B2R. Finally, intra-dPAG injection of captopril also impaired escape in a dose-dependent way, and this panicolytic-like effect was blocked by pretreatment with HOE-140, suggesting mediation by endogenous BK. The panicolytic-like effect of captopril indicates that the use of ACE inhibitors in the clinical management of panic disorder may be worth exploring. Copyright © 2017 Elsevier Ltd. All rights reserved.

A novel uPAg-KPI fusion protein inhibits the growth and invasion of human ovarian cancer cells in vitro.

PubMed

Zhao, Li-Ping; Xu, Tian-Min; Kan, Mu-Jie; Xiao, Ye-Chen; Cui, Man-Hua

2016-05-01

Urokinase-type plasminogen activator (uPA) acts by breaking down the basement membrane and is involved in cell proliferation, migration and invasion. These actions are mediated by binding to the uPA receptor (uPAR) via its growth factor domain (GFD). The present study evaluated the effects of uPAg-KPI, a fusion protein of uPA-GFD and a kunitz protease inhibitor (KPI) domain that is present in the amyloid β-protein precursor. Using SKOV-3 cells, an ovarian cancer cell line, we examined cell viability, migration, invasion and also protein expression. Furthermore, we examined wound healing, and migration and invasion using a Transwell assay. Our data showed that uPAg-KPI treatment reduced the viability of ovarian cancer SKOV-3 cells in both a concentration and time-dependent manner by arresting tumor cells at G1/G0 phase of the cell cycle. The IC50 of uPAg-KPI was 0.5 µg/µl after 48 h treatment. At this concentration, uPAg-KPI also inhibited tumor cell colony formation, wound closure, as well as cell migration and invasion capacity. At the protein level, western blot analysis demonstrated that uPAg-KPI exerted no significant effect on the expression of total extracellular signal-regulated kinase (ERK)1/ERK2 and AKT, whereas it suppressed levels of phosphorylated ERK1/ERK2 and AKT. Thus, we suggest that this novel uPAg-KPI fusion protein reduced cell viability, colony formation, wound healing and the invasive ability of human ovarian cancer SKOV-3 cells in vitro by regulating ERK and AKT signaling. Further studies using other cell lines will confirm these findings.

A novel uPAg-KPI fusion protein inhibits the growth and invasion of human ovarian cancer cells in vitro

PubMed Central

ZHAO, LI-PING; XU, TIAN-MIN; KAN, MU-JIE; XIAO, YE-CHEN; CUI, MAN-HUA

2016-01-01

Urokinase-type plasminogen activator (uPA) acts by breaking down the basement membrane and is involved in cell proliferation, migration and invasion. These actions are mediated by binding to the uPA receptor (uPAR) via its growth factor domain (GFD). The present study evaluated the effects of uPAg-KPI, a fusion protein of uPA-GFD and a kunitz protease inhibitor (KPI) domain that is present in the amyloid β-protein precursor. Using SKOV-3 cells, an ovarian cancer cell line, we examined cell viability, migration, invasion and also protein expression. Furthermore, we examined wound healing, and migration and invasion using a Transwell assay. Our data showed that uPAg-KPI treatment reduced the viability of ovarian cancer SKOV-3 cells in both a concentration and time-dependent manner by arresting tumor cells at G1/G0 phase of the cell cycle. The IC50 of uPAg-KPI was 0.5 µg/µl after 48 h treatment. At this concentration, uPAg-KPI also inhibited tumor cell colony formation, wound closure, as well as cell migration and invasion capacity. At the protein level, western blot analysis demonstrated that uPAg-KPI exerted no significant effect on the expression of total extracellular signal-regulated kinase (ERK)1/ERK2 and AKT, whereas it suppressed levels of phosphorylated ERK1/ERK2 and AKT. Thus, we suggest that this novel uPAg-KPI fusion protein reduced cell viability, colony formation, wound healing and the invasive ability of human ovarian cancer SKOV-3 cells in vitro by regulating ERK and AKT signaling. Further studies using other cell lines will confirm these findings. PMID:27035617

Polysaccharide isolated from Aloe vera gel suppresses ovalbumin-induced food allergy through inhibition of Th2 immunity in mice.

PubMed

Lee, Dajeong; Kim, Hyuk Soon; Shin, Eunju; Do, Seon-Gil; Lee, Chong-Kil; Kim, Young Mi; Lee, Min Bum; Min, Keun Young; Koo, Jimo; Kim, Su Jeong; Nam, Seung Taek; Kim, Hyun Woo; Park, Young Hwan; Choi, Wahn Soo

2018-05-01

An allergic reaction occurs when the immune system overreacts to harmless substance called allergen that gains access to the body. Food allergy is a hypersensitive immune reaction to food proteins and the number of patients with food allergy has recently increased. Aloe Vera is used for wellness and medicinal purposes. In particular, Aloe vera has been reported to enhance immunity. However, the effect of Aloe vera on food allergy is not yet known. In this study, we investigated the effects of processed Aloe vera gel (PAG) containing low molecular weight Aloe polysaccharide (AP) on ovalbumin (OVA)-induced food allergy in mice. Allergic symptoms, rectal temperature, and diarrhea were measured in OVA-induced food allergy mice. Other allergic parameters were also analyzed by RT-PCR, ELISA, flow cytometry, and other biochemical methods. As the results, PAG suppressed the decrease of body temperature, diarrhea, and allergic symptoms in OVA-induced food allergy mice. PAG also reduced serum concentrations of type 2 helper T cell (Th2) cytokines (Interleukin-(IL)-4, IL-5, and IL-13) as well as histamine, mast cell protease-1 (MCP-1), and immunoglobulin (Ig)E. PAG blocked the degranulation of mast cells and infiltration of eosinophils in intestine. Furthermore, PAG suppressed the population of Th2 cells in spleen and mesenteric lymph nodes. PAG also increased the production of IL-10 and population of type 1 regulatory T (Tr1) cells in mice with food allergy. Taken together, our findings suggest that PAG suppressed Th2 immune responses through, at least partially, stimulating the secretion of IL-10 in food allergy mice. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Emotion and the Cardiovascular System: Postulated Role of Inputs From the Medial Prefrontal Cortex to the Dorsolateral Periaqueductal Gray.

PubMed

Dampney, Roger

2018-01-01

The midbrain periaqueductal gray (PAG) plays a major role in generating different types of behavioral responses to emotional stressors. This review focuses on the role of the dorsolateral (dl) portion of the PAG, which on the basis of anatomical and functional studies, appears to have a unique and distinctive role in generating behavioral, cardiovascular and respiratory responses to real and perceived emotional stressors. In particular, the dlPAG, but not other parts of the PAG, receives direct inputs from the primary auditory cortex and from the secondary visual cortex. In addition, there are strong direct inputs to the dlPAG, but not other parts of the PAG, from regions within the medial prefrontal cortex that in primates correspond to cortical areas 10 m, 25 and 32. I first summarise the evidence that the inputs to the dlPAG arising from visual, auditory and olfactory signals trigger defensive behavioral responses supported by appropriate cardiovascular and respiratory effects, when such signals indicate the presence of a real external threat, such as the presence of a predator. I then consider the functional roles of the direct inputs from the medial prefrontal cortex, and propose the hypothesis that these inputs are activated by perceived threats, that are generated as a consequence of complex cognitive processes. I further propose that the inputs from areas 10 m, 25 and 32 are activated under different circumstances. The input from cortical area 10 m is of special interest, because this cortical area exists only in primates and is much larger in the brain of humans than in all other primates.

Emotion and the Cardiovascular System: Postulated Role of Inputs From the Medial Prefrontal Cortex to the Dorsolateral Periaqueductal Gray

PubMed Central

Dampney, Roger

2018-01-01

The midbrain periaqueductal gray (PAG) plays a major role in generating different types of behavioral responses to emotional stressors. This review focuses on the role of the dorsolateral (dl) portion of the PAG, which on the basis of anatomical and functional studies, appears to have a unique and distinctive role in generating behavioral, cardiovascular and respiratory responses to real and perceived emotional stressors. In particular, the dlPAG, but not other parts of the PAG, receives direct inputs from the primary auditory cortex and from the secondary visual cortex. In addition, there are strong direct inputs to the dlPAG, but not other parts of the PAG, from regions within the medial prefrontal cortex that in primates correspond to cortical areas 10 m, 25 and 32. I first summarise the evidence that the inputs to the dlPAG arising from visual, auditory and olfactory signals trigger defensive behavioral responses supported by appropriate cardiovascular and respiratory effects, when such signals indicate the presence of a real external threat, such as the presence of a predator. I then consider the functional roles of the direct inputs from the medial prefrontal cortex, and propose the hypothesis that these inputs are activated by perceived threats, that are generated as a consequence of complex cognitive processes. I further propose that the inputs from areas 10 m, 25 and 32 are activated under different circumstances. The input from cortical area 10 m is of special interest, because this cortical area exists only in primates and is much larger in the brain of humans than in all other primates. PMID:29881334

Angiotensin AT1 receptors modulate the anxiogenic effects of angiotensin (5-8) injected into the rat ventrolateral periaqueductal gray.

PubMed

Genaro, Karina; Fabris, Débora; Fachim, Helene A; Prado, Wiliam A

2017-10-01

Losartan and PD 123,319 are non-peptide angiotensin (Ang) receptor antagonists for the AT1 and AT2 subtypes of Ang II receptors, respectively. The tetrapeptide Ang (5-8) is the smallest Ang-peptide that elicits anxiogenic effects on unconditioned and conditioned experimental models upon injection into the ventrolateral column of the periaqueductal gray (vlPAG), and Ang (5-8) can be synthesized (from Ang II or Ang III) and inactivated in this mesencephalic structure. The vlPAG is also known to play a central role in mechanisms of fear and anxiety. We therefore utilized male Wistar rats to examine the effects of losartan and PD 123,319 injections, selective antagonists of the AT1 and AT2 receptors, respectively, into the vlPAG in the elevated plus-maze, a classic rat model of anxiety, and against the anxiogenic effect of Ang (5-8) (0.4 nmol/0.25μL) upon injection into the same region. The anxiolytic profile was dependent on the dose of intra-vlPAG losartan, whereas no effects on experimental anxiety were observed in the plus-maze following PD 123,319 injection. The anxiogenic effect of Ang (5-8) injection into the vlPAG remained unchanged in the PD 123,319-pretreated rats, but the effect did not occur in losartan-pretreated rats. The results led us to suggest that the anxiogenic effect of Ang (5-8) injection into the vlPAG may depend on the local activation of AT1, but not AT2 receptors. Activation of AT1 receptors in structures nearby vlPAG may be tonically involved in fear and experimental anxiety. Copyright © 2017. Published by Elsevier Inc.

Periaqueductal gray knockdown of V2, not V1a and V1b receptor influences nociception in the rat. yj6676@yahoo.com.

PubMed

Yang, Jun; Yang, Yu; Chen, Jian-Min; Wang, Gen; Xu, Hong-Tao; Liu, Wen-Yan; Lin, Bao-Cheng

2007-01-01

Our pervious study has proved that arginine vasopressin (AVP) in periaqueductal gray (PAG) plays a role in antinociception. After establishing a model of local special gene knockdown, the nociceptive effect of vasopressin receptor subunit in PAG was investigated in the rat. Microinjection of short-interfering RNA (siRNA) into PAG, which targeted vasopressin receptor subtypes (V(1a), V(1b) and V(2)), locally weakened the associated mRNA expression and depressed the related receptor synthesis in a dose-dependent manner, in which the significant inhibitive effect occurred on from 7th day to 14th day following 1microg or 2microg siRNA administration. PAG knockdown of V(2) receptor gene markedly decreased pain threshold in from 6th day to 13th day after siRNA administration, whereas local knockdown of either V(1a) or V(1b) receptor gene could not influence pain threshold. The data suggest that V(2) rather than V(1a) and V(1b) receptor in PAG involves in nociception.

Inward-rectifying K+ (Kir2) leak conductance dampens the excitability of lamina I projection neurons in the neonatal rat

PubMed Central

Ford, Neil C.; Baccei, Mark L.

2016-01-01

Spinal lamina I projection neurons serve as a major conduit by which noxious stimuli detected in the periphery are transmitted to nociceptive circuits in the brain, including the parabrachial nucleus (PB) and the periaqueductal gray (PAG). While neonatal spino-PB neurons are more than twice as likely to exhibit spontaneous activity compared to spino-PAG neurons, the underlying mechanisms remain unclear since nothing is known about the voltage-independent (i.e. ‘leak’) ion channels expressed by these distinct populations during early life. To begin identifying these key leak conductances, the present study investigated the role of classical inward-rectifying K+ (Kir2) channels in the regulation of intrinsic excitability in neonatal rat spino-PB and spino-PAG neurons. The data demonstrate that a reduction in Kir2-mediated conductance by external BaCl2 significantly enhanced intrinsic membrane excitability in both groups. Similar results were observed in spino-PB neurons following Kir2 channel block with the selective antagonist ML133. In addition, voltage-clamp experiments showed that spino-PB and spino-PAG neurons express similar amounts of Kir2 current during the early postnatal period, suggesting that the differences in the prevalence of spontaneous activity between the two populations are not explained by differential expression of Kir2 channels. Overall, the results indicate that Kir2-mediated conductance tonically dampens the firing of multiple subpopulations of lamina I projection neurons during early life. Therefore, Kir2 channels are positioned to tightly shape the output of the immature spinal nociceptive circuit and thus regulate the ascending flow of nociceptive information to the developing brain, which has important functional implications for pediatric pain. PMID:27751963

Resting Functional Connectivity of the Periaqueductal Gray Is Associated With Normal Inhibition and Pathological Facilitation in Conditioned Pain Modulation.

PubMed

Harper, Daniel E; Ichesco, Eric; Schrepf, Andrew; Hampson, Johnson P; Clauw, Daniel J; Schmidt-Wilcke, Tobias; Harris, Richard E; Harte, Steven E

2018-06-01

Conditioned pain modulation (CPM), a psychophysical paradigm that is commonly used to infer the integrity of endogenous pain-altering systems by observation of the effect of one noxious stimulus on another, has previously identified deficient endogenous analgesia in fibromyalgia (FM) and other chronic pain conditions. The mechanisms underlying this deficiency, be they insufficient inhibition and/or active facilitation, are largely unknown. The present cross-sectional study used a combination of behavioral CPM testing, voxel-based morphometry, and resting state functional connectivity to identify neural correlates of CPM in healthy controls (HC; n = 14) and FM patients (n = 15), and to probe for differences that could explain the pain-facilitative CPM that was observed in our patient sample. Voxel-based morphometry identified a cluster encompassing the periaqueductal gray (PAG) that contained significantly less gray matter volume in FM patients. Higher resting connectivity between this cluster and cortical pain processing regions was associated with more efficient inhibitory CPM in both groups, whereas PAG connectivity with the dorsal pons was associated with greater CPM inhibition only in HC. Greater PAG connectivity to the caudal pons/rostral medulla, which was pain-inhibitory in HC, was associated with pain facilitation in FM patients. These findings indicate that variation in the strength of the PAG resting functional connectivity can explain some of the normal variability in CPM. In addition, pain-facilitative CPM observed in FM patients likely involves attenuation of pain inhibitory as well as amplification of pain facilitative processes in the central nervous system. Copyright © 2018 The American Pain Society. Published by Elsevier Inc. All rights reserved.

Chronic Neuropathic Pain in Mice Reduces μ-Opioid Receptor-Mediated G-protein Activity in the Thalamus

PubMed Central

Hoot, Michelle R.; Sim-Selley, Laura J.; Selley, Dana E.; Scoggins, Krista L.; Dewey, William L.

2011-01-01

Neuropathic pain is a debilitating condition that is often difficult to treat using conventional pharmacological interventions and the exact mechanisms involved in the establishment and maintenance of this type of chronic pain have yet to be fully elucidated. The present studies examined the effect of chronic nerve injury on μ-opioid receptors and receptor-mediated G-protein activity within the supraspinal brain regions involved in pain processing of mice. Chronic constriction injury (CCI) reduced paw withdrawal latency, which was maximal at 10 days post-injury. [d-Ala2,(N-Me)Phe4, Gly5-OH] enkephalin (DAMGO)-stimulated [35S]GTPγS binding was then conducted at this time point in membranes prepared from the rostral ACC (rACC), thalamus and periaqueductal grey (PAG) of CCI and sham-operated mice. Results showed reduced DAMGO-stimulated [35S]GTPγS binding in the thalamus and PAG of CCI mice, with no change in the rACC. In thalamus, this reduction was due to decreased maximal stimulation by DAMGO, with no difference in EC50 values. In PAG, however, DAMGO Emax values did not significantly differ between groups, possibly due to the small magnitude of the main effect. [3H]Naloxone binding in membranes of the thalamus showed no significant differences in Bmax values between CCI and sham-operated mice, indicating that the difference in G-protein activation did not result from differences in μ-opioid receptor levels. These results suggest that CCI induced a region-specific adaptation of μ-opioid receptor-mediated G-protein activity, with apparent desensitization of the μ-opioid receptor in the thalamus and PAG and could have implications for treatment of neuropathic pain. PMID:21762883

The effect of altered 5-hydroxytryptamine levels on beta-endorphin

NASA Technical Reports Server (NTRS)

Soliman, Karam F. A.; Mash, Deborah C.; Walker, Charles A.

1986-01-01

The purpose of the present study was to examine the effect of altering the concentration of 5-hydroxytryptamine (5-HT) on beta-endorphin (beta-Ep) content in the hypothalamus, thalamus, and periaqueductal gray (PAG)-rostral pons regions of the rat brain. The selective 5-HT reuptake inhibitor, fluoxetine (10 mg/kg), significantly lowered beta-Ep content in the hypothalamus and the PAG. Parachlorophenylalanine, which inhibits 5-HT synthesis, significantly elevated beta-Ep in all brain parts studied. Intracisternal injections of the neurotoxin 5-prime, 7-prime-dihydroxytryptamine with desmethylimipramine pretreatment significantly increased beta-Ep content in the hypothalamus and the PAG. In adrenalectomized rats, fluoxetine significantly decreased beta-Ep levels in the hypothalamus and increased the levels in the PAG. The results indicate that 5-HT may modulate the levels of brain beta-Ep.

Opiorphin causes a panicolytic-like effect in rat panic models mediated by μ-opioid receptors in the dorsal periaqueductal gray.

PubMed

Maraschin, Jhonatan Christian; Rangel, Marcel Pereira; Bonfim, Antonio Joaquim; Kitayama, Mariana; Graeff, Frederico Guilherme; Zangrossi, Hélio; Audi, Elisabeth Aparecida

2016-02-01

Reported evidence indicates that endogenous opioid peptides regulate the expression of escape behavior in rats, a panic-related defensive response, through μ-opioid receptors (MORs) in the dorsal periaqueductal gray (dPAG). These peptides are rapidly catabolized by degrading enzymes, including neutral endopeptidase (NEP) and aminopeptidase N (APN). Opiorphin is a peptide inhibitor of both NEP and APN and potentiates the action of endogenous enkephalins. This study evaluated the effects of intravenous and intra-dPAG administration of opiorphin on escape responses in the elevated T-maze and in a dPAG electrical stimulation test in rats. We also evaluated the involvement of MORs in the effects of opiorphin using the selective MOR antagonist CTOP. A dose of 2.0 mg/kg, i.v., of opiorphin impaired escape performance in both tests. Similar effects were observed with intra-dPAG administration of 5.0 nmol of opiorphin. Local pretreatment with 1.0 nmol CTOP antagonized the anti-escape effects of intra-dPAG opiorphin in both tests, as well as the effect of systemically administered opiorphin (2.0 mg/kg, i.v.) in the electrical stimulation test. These results indicate that opiorphin has an antipanic-like effect that is mediated by MORs in the dPAG. They may open new perspectives for the development of opiorphin analogues with greater bioavailability and physicochemical characteristics in the pursuit of new medications for the treatment of panic disorder. Copyright © 2015 Elsevier Ltd. All rights reserved.

Rapid detection of food-borne Salmonella contamination using IMBs-qPCR method based on pagC gene.

PubMed

Wang, Jiashun; Li, Yi; Chen, Jia; Hua, Deping; Li, Yi; Deng, Hui; Li, Ying; Liang, Zhixuan; Huang, Jinhai

Detection of Salmonella is very important to minimize the food safety risk. In this study, the recombinant PagC protein and PagC antibody were prepared and coupled with immunomagnetic beads (IMBs) to capture Salmonella cells from pork and milk samples. And then the SYBR Green qualitative PCR was developed to detect the pathogenic Salmonella. The results showed that the PagC polyclonal antiserum is of good specificity and the capture rate of 0.1mg IMBs for Salmonella tended to be stable at the range of 70-74% corresponding to the concentrations between 10 1 and 10 4 CFU/mL. The method developed demonstrated high specificity for the positive Salmonella samples when compared to non-specific DNA samples, such as Escherichia coli, Staphylococcus aureus, Yersinia enterocolitica, and Yersinia pseudotuberculosis. The limit of detection of this assay was 18CFU/mL. Detection and quantitative enumeration of Salmonella in samples of pork or milk shows good recoveries of 54.34% and 52.07%. In conclusion, the polyclonal antibody of recombinant PagC protein is effective to capture Salmonella from detected samples. The developed pagC antibody IMBs-qPCR method showed efficiency, sensitivity and specificity for 30 Salmonella detection, enabling detection within 10h, which is a promising rapid method to detect Salmonella in emergency. Copyright © 2017 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. All rights reserved.

Evidence of Pavlovian conditioned fear following electrical stimulation of the periaqueductal grey in the rat.

PubMed

Di Scala, G; Mana, M J; Jacobs, W J; Phillips, A G

1987-01-01

Stimulation of the periaqueductal grey (PAG) has been used to support aversive conditioning in a variety of species with several experimental paradigms. However, it has not been clearly demonstrated whether the behavioral changes produced by PAG stimulation in these paradigms are mediated by associative or nonassociative mechanisms. The present studies demonstrate that electrical stimulation of the PAG in the rat may be used to support associative learning in a Pavlovian paradigm. In each experiment, a fully controlled conditional emotional response (CER) procedure was used to examine the unconditional aversive properties of PAG stimulation. In Experiment 1a, weak associative conditioning was observed when a light CS was paired with PAG stimulation over 6 conditioning trials. In Experiment 1b, robust associative conditioning was obtained with a light CS when 18 conditioning trials were used. In Experiment 2, robust associative conditioning was demonstrated with a tone CS when 6 conditioning trials were used. The results parallel those found when other aversive stimuli are used as a UCS (e.g., footshock or intraorbital air puff), and because the present experiments included the proper control procedures the results clearly indicate that the behavioral changes produced by PAG stimulation are mediated by associative Pavlovian learning mechanisms rather than nonassociative mechanisms such as sensitization or pseudoconditioning. The present technique may be useful for assessing the neuroanatomical and neurochemical substrates underlying the aversive effects of brain-stimulation, and for screening the effects of drugs on the conditional and unconditional responses produced by such stimulation.

Hydrogen sulfide upregulated mRNA expressions of sodium bicarbonate cotransporter1, trefoil factor1 and trefoil factor2 in gastric mucosa in rats.

PubMed

Cheraghi, Parisa; Mard, Seyyed Ali; Nagi, Tahereh

2016-01-01

Hydrogen sulfide (H 2 S) has been shown to protect the gastric mucosa through several protective mechanisms but till now its effect on mRNA expression of sodium bicarbonate cotransporter 1 (NBC1), trefoil factor1 (TFF1) and trefoil factor2 (TFF2) was not investigated. This study was aimed to evaluate the effect of H 2 S on mRNA expression of NBC1, TFF1 and TFF2 in rat gastric mucosa in response to gastric distention. Thirty two rats were randomly assigned into four equal groups. They were control (C), distention (D), propargylglycine (PAG)-, and NaHS-treated groups. To evaluate the effect of exogenous and endogenous H 2 S on gene expression of NBC1, TFF1 and TFF2, two groups of rats were received H 2 S donor, intra-peritoneal NaHS (80 µg Kg -1 ), and PAG (50 mg kg -1 ), accompanied to stimulate the gastric acid secretion, respectively. Under general anesthesia and laparotomy, a catheter was inserted into the stomach through duodenum for instillation of isotonic saline for gastric distention. Ninety min after beginning the experiment, animals were sacrificed and the gastric mucosa was collected to determine total acid content of gastric effluents and to quantify the mRNA expression of studied genes by quantitative real-time polymerase chain reaction (qRT-PCR). Results showed that A) gastric distention increased the level of mRNA expressions of NBC1, TFF1 and TFF2; B) these levels in NaHS-treated rats were significantly higher than those in Distention group; and C) PAG decreased the expression levels of NBC1 and TFF1. The Findings showed H 2 S upregulated gene expression of NBC1, TFF1 and TFF2 in gastric mucosa.

Participation of dorsal periaqueductal gray 5-HT1A receptors in the panicolytic-like effect of the κ-opioid receptor antagonist Nor-BNI.

PubMed

Maraschin, Jhonatan Christian; Almeida, Camila Biesdorf; Rangel, Marcel Pereira; Roncon, Camila Marroni; Sestile, Caio César; Zangrossi, Hélio; Graeff, Frederico Guilherme; Audi, Elisabeth Aparecida

2017-06-01

Panic patients may have abnormalities in serotonergic and opioidergic neurotransmission. The dorsal periaqueductal gray (dPAG) plays an important role in organizing proximal defense, related to panic attacks. The 5-HT 1A receptor (5-HT 1A -R) is involved in regulating escape behavior that is organized in the dPAG. Activation of κ-opioid receptor (KOR) in this region causes anxiogenic effects. In this study, we investigated the involvement of KOR in regulating escape behavior, using systemic and intra-dPAG injection of the KOR antagonist Nor-BNI. As panic models, we used the elevated T-maze (ETM) and the dPAG electrical stimulation test (EST). We also evaluated whether activation of the 5-HT 1A -R or the μ-opioid receptor (MOR) in the dPAG contributes to the Nor-BNI effects. The results showed that systemic administration of Nor-BNI, either subcutaneously (2.0 and 4.0mg/kg) or intraperitoneally (2.0mg/kg), impaired escape in the EST, indicating a panicolytic-like effect. Intra-dPAG injection of this antagonist (6.8nmol) caused the same effect in the EST and in the ETM. Association of ineffective doses of Nor-BNI and the 5-HT 1A -R agonist 8-OH-DPAT caused panicolytic-like effect in these two tests. Previous administration of the 5-HT 1A -R antagonist WAY-100635, but not of the MOR antagonist CTOP, blocked the panicolytic-like effect of Nor-BNI. These results indicate that KOR enhances proximal defense in the dPAG through 5-HT 1A -R modulation, independently of MOR. Because former results indicate that the 5-HT 1A -R is involved in the antipanic action of antidepressants, KOR antagonists may be useful as adjunctive or alternative drug treatment of panic disorder. Copyright © 2017 Elsevier B.V. All rights reserved.

Does an Advanced Pelvic Simulation Curriculum Improve Resident Performance on a Pediatric and Adolescent Gynecology Focused Objective Structured Clinical Examination? A Cohort Study.

PubMed

Dumont, Tania; Hakim, Julie; Black, Amanda; Fleming, Nathalie

2016-06-01

To determine the effect of an advanced pelvic simulation curriculum on resident performance on a pediatric and adolescent gynecology (PAG) focused objective structured clinical examination (OSCE). Obstetrics and gynecology residents in a single academic Canadian center participated in a PAG simulation curriculum. An OSCE on prepubertal vaginal bleeding was administered at the biannual OSCE examination 2 months before the simulation curriculum and again 3 months after the simulation curriculum. Academic half-day at the University of Ottawa Skills and Simulation Centre. Obstetrics and gynecology residents from the University of Ottawa. Participants completed 4 stations teaching PAG-appropriate history-taking, genital examination, Tanner staging, vaginal sampling and flushing, hymenectomy, vaginoscopy, laparoscopic adnexal detorsion, and approach to the child and/or adolescent. Advanced pelvic models were used for procedure-specific stations. The primary outcome measure was change in mean score on a prepubertal vaginal bleeding OSCE station. Secondary outcome measures were changes in individual component scores. Fourteen residents completed the simulation curriculum and the PAG OSCE at the 2 separate time points (before and after simulation curriculum). The mean OSCE score before the simulation curriculum was 54.6% (20.5 of 37) and mean score after the curriculum was 78.1% (28.9 of 37; P < .001). Significant score increases were found in history-taking, examination, differential diagnosis, identification of organism, surgical procedures, and identification of foreign body (P < .01 for all). This innovative PAG simulation curriculum significantly increased residents' knowledge in PAG history-taking, examination skills, operative procedures, and approach to the child and/or adolescent. Obstetrics and Gynecology Program Directors should consider incorporating PAG simulation training into their curriculum to ensure that residents meet their learning objectives and increase their knowledge and confidence, which will ultimately benefit patient care. Copyright © 2015 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Effect of endogenous hydrogen sulfide inhibition on structural and functional renal disturbances induced by gentamicin

PubMed Central

Francescato, H.D.C.; Chierice, J.R.A.; Marin, E.C.S.; Cunha, F.Q.; Costa, R.S.; Silva, C.G.A.; Coimbra, T.M.

2012-01-01

Animal models of gentamicin nephrotoxicity present acute tubular necrosis associated with inflammation, which can contribute to intensify the renal damage. Hydrogen sulfide (H2S) is a signaling molecule involved in inflammation. We evaluated the effect of DL-propargylglycine (PAG), an inhibitor of endogenous H2S formation, on the renal damage induced by gentamicin. Male Wistar rats (N = 8) were injected with 40 mg/kg gentamicin (im) twice a day for 9 days, some of them also received PAG (N = 8, 10 mg·kg−1·day−1, ip). Control rats (N = 6) were treated with saline or PAG only (N = 4). Twenty-four-hour urine samples were collected one day after the end of these treatments, blood samples were collected, the animals were sacrificed, and the kidneys were removed for quantification of H2S formation and histological and immunohistochemical studies. Gentamicin-treated rats presented higher sodium and potassium fractional excretion, increased plasma creatinine [4.06 (3.00; 5.87) mg%] and urea levels, a greater number of macrophages/monocytes, and a higher score for tubular interstitial lesions [3.50 (3.00; 4.00)] in the renal cortex. These changes were associated with increased H2S formation in the kidneys from gentamicin-treated rats (230.60 ± 38.62 µg·mg protein−1·h−1) compared to control (21.12 ± 1.63) and PAG (11.44 ± 3.08). Treatment with PAG reduced this increase (171.60 ± 18.34), the disturbances in plasma creatinine levels [2.20 (1.92; 4.60) mg%], macrophage infiltration, and score for tubular interstitial lesions [2.00 (2.00; 3.00)]. However, PAG did not interfere with the increase in fractional sodium excretion provoked by gentamicin. The protective effect of PAG on gentamicin nephrotoxicity was related, at least in part, to decreased H2S formation. PMID:22331137

Effect of endogenous hydrogen sulfide inhibition on structural and functional renal disturbances induced by gentamicin.

PubMed

Francescato, H D C; Chierice, J R A; Marin, E C S; Cunha, F Q; Costa, R S; Silva, C G A; Coimbra, T M

2012-03-01

Animal models of gentamicin nephrotoxicity present acute tubular necrosis associated with inflammation, which can contribute to intensify the renal damage. Hydrogen sulfide (H2S) is a signaling molecule involved in inflammation. We evaluated the effect of DL-propargylglycine (PAG), an inhibitor of endogenous H2S formation, on the renal damage induced by gentamicin. Male Wistar rats (N = 8) were injected with 40 mg/kg gentamicin (im) twice a day for 9 days, some of them also received PAG (N = 8, 10 mg·kg-1·day-1, ip). Control rats (N = 6) were treated with saline or PAG only (N = 4). Twenty-four-hour urine samples were collected one day after the end of these treatments, blood samples were collected, the animals were sacrificed, and the kidneys were removed for quantification of H2S formation and histological and immunohistochemical studies. Gentamicin-treated rats presented higher sodium and potassium fractional excretion, increased plasma creatinine [4.06 (3.00; 5.87) mg%] and urea levels, a greater number of macrophages/monocytes, and a higher score for tubular interstitial lesions [3.50 (3.00; 4.00)] in the renal cortex. These changes were associated with increased H2S formation in the kidneys from gentamicin-treated rats (230.60 ± 38.62 µg·mg protein-1·h-1) compared to control (21.12 ± 1.63) and PAG (11.44 ± 3.08). Treatment with PAG reduced this increase (171.60 ± 18.34), the disturbances in plasma creatinine levels [2.20 (1.92; 4.60) mg%], macrophage infiltration, and score for tubular interstitial lesions [2.00 (2.00; 3.00)]. However, PAG did not interfere with the increase in fractional sodium excretion provoked by gentamicin. The protective effect of PAG on gentamicin nephrotoxicity was related, at least in part, to decreased H2S formation.

Resident Education Curriculum in Pediatric and Adolescent Gynecology: The Short Curriculum 2.0.

PubMed

Talib, Hina J; Karjane, Nicole; Teelin, Karen; Abraham, Margaret; Holt, Stephanie; Chelvakumar, Gayaythri; Dumont, Tania; Huguelet, Patricia S; Conner, Lindsay; Wheeler, Carol; Fleming, Nathalie

2018-04-01

The degree of exposure to pediatric and adolescent gynecology (PAG) varies across residency programs in obstetrics and gynecology and pediatrics. Nevertheless, these programs are responsible for training residents and providing opportunities within their programs to fulfill PAG learning objectives. To that end, the North American Society for Pediatric and Adolescent Gynecology has taken a leadership role in PAG resident education by creating and systematically updating the Short Curriculum. This curriculum outlines specific learning objectives that are central to PAG education and lists essential resources for learners' reference. This updated curriculum replaces the previous 2014 publication with added content, resources, and updated references. Additionally, attention to the needs of learners in pediatrics and adolescent medicine is given greater emphasis in this revised North American Society for Pediatric and Adolescent Gynecology Short Curriculum 2.0. Copyright © 2017 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Identification of phenylpropanoids in fig (Ficus carica L.) leaves.

PubMed

Takahashi, Toru; Okiura, Aya; Saito, Keita; Kohno, Masahiro

2014-10-15

In this study, the phenylpropanoid composition and antioxidant activity of identified components in fig (Ficus carica L.) leaves were examined. Known polyphenols rutin, isoschaftoside, isoquercetin, and chlorogenic acid were identified. Furthermore, caffeoylmalic acid (CMA) was the most abundant polyphenol and was identified for the first time. CMA exhibited antioxidant activity similar to that of vitamin C or catechin. Psoralen and bergapten were identified as known furanocoumarins, with psoralen being the most abundant. Moreover, psoralic acid glucoside (PAG) was identified for the first time. As a precursor of psoralen, PAG content was equivalent to the psoralen content in moles. Notably, the content of these compounds varied between the five fig varieties, and the furanocoumarin and PAG contents varied more than that of the polyphenols. Further investigations concerning the influence of CMA and PAG on human health are necessary to elucidate functionalities of fig leaves.

Clinical features and hormonal profiles of cloprostenol-induced early abortions in heifers monitored by ultrasonography

PubMed Central

Lobago, Fikre; Gustafsson, Hans; Bekana, Merga; Beckers, Jean-François; Kindahl, Hans

2006-01-01

Background The present study describes the clinical features and plasma profiles of bovine pregnancy-associated glycoprotein 1 (bPAG1), the main metabolite of prostaglandin F2α (PG metabolite) and progesterone (P4) in heifers in which early abortions were induced. Methods Early abortions were induced in four heifers with cloprostenol and monitored by ultrasonography. Blood samples were collected and the plasma were analyzed for bPAG 1, P4 and PG metabolite. Results The foetal heartbeat rates varied from 170–186 beats per minute for all foetuses up to the date of cloprostenol treatment. Foetal death was confirmed within two days after cloprostenol treatment. Prior to cloprostenol injection, blood plasma concentrations of bPAG1, PG metabolite and P4 varied from 8.4 – 40.0 ng/mL, 158 – 275 pmol/L and 20.7 – 46.9 nmol/L, respectively. After the foetus expelled, the plasma level of bPAG1 began to decrease but the decrease was small and gradual. The estimated half-life of bPAG1 was 1.8 – 6.6 days. The plasma level of the PG metabolite started to have short lasting peaks (above 300 pmol/L) within three hours after cloprostenol treatment. The plasma concentrations of P4 dropped sharply to less than 4 nmol/L after 24 hours of cloprostenol injection. Conclusion The current findings indicated that after early closprostenol-induced foetal death, the plasma concentration of bPAG1 decreased gradually and showed a tendency of variation with the stages of pregnancy. PMID:17121683

The HSP90 inhibitor 17-PAG effectively inhibits the proliferation and migration of androgen-independent prostate cancer cells

PubMed Central

Peng, Ruixian; Li, Zhenyu; Lin, Zhiyuan; Wang, Yang; Wang, Wei; Hu, Bo; Wang, Xilong; Zhang, Jun; Wang, Yangyun; Zhou, Renyuan; Lu, Chunhua; Shen, Yuemao; Wang, Jifeng; Shi, Guowei

2015-01-01

Castration-resistant prostate cancer (CRPC) ultimately occurs after a period of treatment with androgen deprivation therapy. Furthermore, CRPC patients can only derive limited survival benefits from traditional cytotoxic drugs. HSP90, which is a molecular chaperone, plays a vital role in client protein processing and maintaining the function of cells. HSP90 is usually overexpressed in prostate cancer tissues, which makes it a potential target for managing prostate cancer. Geldanamycin (GA), which was recognized as the first natural HSP90 inhibitor, has demonstrated potent anti-tumor efficacy in large-scale pre-clinical studies, but its application in the clinic is not permitted due to its liver toxicity and unstable physical properties. In this study, we report a new GA derivative, 17-PAG (17-(propynylamino)-17-demethoxygeldanamycin), which demonstrates highly effective anti-tumor activity against androgen-independent prostate cancer cells. Treating cells with 17-PAG dose-dependently suppressed proliferation, reduced colony formation and induced apoptosis of DU-145/C4-2B cells. Moreover, 17-PAG suppressed the migration and invasion of DU-145/C4-2B cells by regulating epithelial mesenchymal transition (EMT). 17-PAG also downregulated the HSP90 client proteins, including Her2, EGFR, C-Raf, AKT, p-AKT, and CDK4. Animal assays confirmed that 17-PAG shows strong anti-tumor effects with no obvious organ toxicity in DU-145 cell xenografted nude mice. These results provide us with a potential target for treating androgen-independent prostate cancer in a safe and effective manner. PMID:26693070

Opioid tolerance in periaqueductal gray neurons isolated from mice chronically treated with morphine

PubMed Central

Bagley, Elena E; Chieng, Billy C H; Christie, MacDonald J; Connor, Mark

2005-01-01

The midbrain periaqueductal gray (PAG) is a major site of opioid analgesic action, and a significant site of cellular adaptations to chronic morphine treatment (CMT). We examined μ-opioid receptor (MOP) regulation of voltage-gated calcium channel currents (ICa) and G-protein-activated K channel currents (GIRK) in PAG neurons from CMT mice. Mice were injected s.c. with 300 mg kg−1 of morphine base in a slow release emulsion three times over 5 days, or with emulsion alone (vehicles). This protocol produced significant tolerance to the antinociceptive effects of morphine in a test of thermal nociception. Voltage clamp recordings were made of ICa in acutely isolated PAG neurons and GIRK in PAG slices. The MOP agonist DAMGO (Tyr-D-Ala-Gly-N-Me-Phe-Gly-ol enkephalin) inhibited ICa in neurons from CMT mice (230 nM) with a similar potency to vehicle (150 nM), but with a reduced maximal effectiveness (37% inhibition in vehicle neurons, 27% in CMT neurons). Inhibition of ICa by the GABAB agonist baclofen was not altered by CMT. Met-enkephalin-activated GIRK currents recorded in PAG slices were significantly smaller in neurons from CMT mice than vehicles, while GIRK currents activated by baclofen were unaltered. These data demonstrate that CMT-induced antinociceptive tolerance is accompanied by homologous reduction in the effectiveness of MOP agonists to inhibit ICa and activate GIRK. Thus, a reduction in MOP number and/or functional coupling to G proteins accompanies the characteristic cellular adaptations to CMT previously described in PAG neurons. PMID:15980868

Opioid tolerance in periaqueductal gray neurons isolated from mice chronically treated with morphine.

PubMed

Bagley, Elena E; Chieng, Billy C H; Christie, MacDonald J; Connor, Mark

2005-09-01

The midbrain periaqueductal gray (PAG) is a major site of opioid analgesic action, and a significant site of cellular adaptations to chronic morphine treatment (CMT). We examined mu-opioid receptor (MOP) regulation of voltage-gated calcium channel currents (I(Ca)) and G-protein-activated K channel currents (GIRK) in PAG neurons from CMT mice. Mice were injected s.c. with 300 mg kg(-1) of morphine base in a slow release emulsion three times over 5 days, or with emulsion alone (vehicles). This protocol produced significant tolerance to the antinociceptive effects of morphine in a test of thermal nociception. Voltage clamp recordings were made of I(Ca) in acutely isolated PAG neurons and GIRK in PAG slices. The MOP agonist DAMGO (Tyr-D-Ala-Gly-N-Me-Phe-Gly-ol enkephalin) inhibited I(Ca) in neurons from CMT mice (230 nM) with a similar potency to vehicle (150 nM), but with a reduced maximal effectiveness (37% inhibition in vehicle neurons, 27% in CMT neurons). Inhibition of I(Ca) by the GABA(B) agonist baclofen was not altered by CMT. Met-enkephalin-activated GIRK currents recorded in PAG slices were significantly smaller in neurons from CMT mice than vehicles, while GIRK currents activated by baclofen were unaltered. These data demonstrate that CMT-induced antinociceptive tolerance is accompanied by homologous reduction in the effectiveness of MOP agonists to inhibit I(Ca) and activate GIRK. Thus, a reduction in MOP number and/or functional coupling to G proteins accompanies the characteristic cellular adaptations to CMT previously described in PAG neurons.

Microinjection of muscimol into caudal periaqueductal gray lowers body temperature and attenuates increases in temperature and activity evoked from the dorsomedial hypothalamus.

PubMed

de Menezes, Rodrigo C A; Zaretsky, Dmitry V; Fontes, Marco A P; DiMicco, Joseph A

2006-05-30

Microinjection of the neuronal inhibitor muscimol into the midbrain lateral/dorsolateral periaqueductal gray (l/dlPAG) suppresses increases in heart rate (HR) and mean arterial pressure (MAP) evoked by microinjection of the GABA(A) receptor antagonist bicuculline methiodide (BMI) into the dorsomedial hypothalamus (DMH) in rats. Injection of BMI into the DMH also increases body temperature (Tco) and motor activity. Here, our goal was to extend previous findings by examining the effect of microinjection of muscimol into the PAG on these thermogenic and behavioral responses in conscious freely moving rats. Microinjection of muscimol (300 pmol and 1 nmol) alone into the l/dlPAG reduced baseline Tco without affecting activity, HR, or MAP. Similar injection of a dose that failed to alter baseline Tco (100 pmol) suppressed the increases in Tco evoked from the DMH and significantly attenuated DMH-induced increases in locomotor activity. Whereas microinjection of 1 nmol muscimol into the ldlPAG abolished the increases in Tco evoked from the DMH and in fact lowered body temperature to a degree similar to that seen after this dose of muscimol alone, 1 nmol muscimol at adjacent sites outside the targeted region of the PAG had no significant effect on DMH-induced increases in Tco or any other parameter. These results indicate a role for neuronal activity in the l/dlPAG in (1) the temperature and behavioral responses to disinhibition of neurons in the DMH, and (2) the maintenance of basal body temperature in conscious freely moving rats.

Glutamate and GABA-metabolizing enzymes in post-mortem cerebellum in Alzheimer's disease: phosphate-activated glutaminase and glutamic acid decarboxylase.

PubMed

Burbaeva, G Sh; Boksha, I S; Tereshkina, E B; Savushkina, O K; Prokhorova, T A; Vorobyeva, E A

2014-10-01

Enzymes of glutamate and GABA metabolism in postmortem cerebellum from patients with Alzheimer's disease (AD) have not been comprehensively studied. The present work reports results of original comparative study on levels of phosphate-activated glutaminase (PAG) and glutamic acid decarboxylase isoenzymes (GAD65/67) in autopsied cerebellum samples from AD patients and matched controls (13 cases in each group) as well as summarizes published evidence for altered levels of PAG and GAD65/67 in AD brain. Altered (decreased) levels of these enzymes and changes in links between amounts of these enzymes and other glutamate-metabolizing enzymes (such as glutamate dehydrogenase and glutamine synthetase-like protein) in AD cerebella suggest significantly impaired glutamate and GABA metabolism in this brain region, which was previously regarded as not substantially involved in AD pathogenesis.

Bayesian estimation of sensitivity and specificity of a milk pregnancy-associated glycoprotein-based ELISA and of transrectal ultrasonographic exam for diagnosis of pregnancy at 28-45 days following breeding in dairy cows.

PubMed

Dufour, Simon; Durocher, Jean; Dubuc, Jocelyn; Dendukuri, Nandini; Hassan, Shereen; Buczinski, Sébastien

2017-05-01

Using a milk sample for pregnancy diagnosis in dairy cattle is extremely convenient due to the low technical inputs required for collection of biological materials. Determining accuracy of a novel pregnancy diagnostic test that relies on a milk sample is, however, difficult since no gold standard test is available for comparison. The objective of the current study was to estimate diagnostic accuracy of the milk PAG-based ELISA and of transrectal ultrasonographic (TUS) exam for determining pregnancy status of individual dairy cows using a methodology suited for test validation in the absence of gold standard. Secondary objectives were to evaluate whether test accuracy varies with cow's characteristics and to identify the optimal ELISA optical density threshold for PAG test interpretation. Cows (n=519) from 18 commercial dairies tested with both TUS and PAG between 28 and 45days following breeding were included in the study. Other covariates (number of days since breeding, parity, and daily milk production) hypothesized to affect TUS or PAG test accuracy were measured. A Bayesian hierarchical latent class model (LCM) methodology assuming conditional independence between tests was used to obtain estimates of tests' sensitivities (Se) and specificities (Sp), to evaluate impact of covariates on these, and to compute misclassification costs across a range of ELISA thresholds. Very little disagreement was observed between tests with only 23 cows yielding discordant results. Using the LCM model with non-informative priors for tests accuracy parameters, median (95% credibility intervals [CI]) TUS Se and Sp estimates of 0.96 (0.91, 1.00) and 0.99 (0.97, 1.0) were obtained. For the PAG test, median (95% CI) Se of 0.99 (0.98, 1.00) and Sp of 0.95 (0.89, 1.0) were observed. The impact of adjusting for conditional dependence between tests was negligible. Test accuracy of the PAG test varied slightly by parity number. When assuming false negative to false positive costs ratio≥3:1, the optimal ELISA optical density threshold allowing minimization of misclassification costs was 0.25. In conclusion, both TUS and PAG showed excellent accuracy for pregnancy diagnosis in dairy cows. When using the PAG test, a threshold of 0.25 could be used for test interpretation. Copyright © 2017 Elsevier B.V. All rights reserved.

Network Confinement and Heterogeneity Slows Nanoparticle Diffusion in Polymer Gels

NASA Astrophysics Data System (ADS)

Parrish, Emmabeth; Caporizzo, Matthew; Composto, Russell

Nanoparticle (NP) diffusion was measured in polyacrylamide gels (PAG) with a mesh size comparable to NP size, 20nm. The confinement ratio (CR), NP diameter/mesh, increased from 0.4 to 3.8 by increasing crosslinker density and 0.4 to 2 by adding acetone, which collapsed PAG. In all gels, NPs either became localized (<200nm) or diffused microns, as measured by single particle tracking. Mean squared displacements (MSD) of mobile NPs decreased as CR increased. In collapsed gels, the localized NP population increased and MSD of mobile NPs decreased compared to crosslinked PAG. For all CRs, van Hove distributions exhibited non-Gaussian displacements consistent with intermittent localization of NPs. The non-Gaussian parameter increased from a maximum of 1.5 for crosslinked PAG to 5 for collapsed PAG, consistent with greater network heterogeneity. Diffusion coefficients, D, decreased exponentially as CR increased for crosslinked gels, but in collapsed gels D decreased more strongly, suggesting CR alone was insufficient to capture diffusion. Collapsing the gel resulted in an increasingly tortuous pathway for NPs, slowing diffusion at a given CR. Understanding how gel structure affects NP mobility will allow the design of gels with improved ability to separate and release molecules. ACS/PRF 54028-ND7, NSF/MWN DMR-1210379.

Defining the neurocircuitry of exercise hyperpnoea

PubMed Central

Paterson, David J

2014-01-01

One hundred years ago in this journal, Krogh and Lindhard published a seminal paper highlighting the importance of the brain in the control of breathing during exercise. This symposium report reviews the historical developments that have taken place since 1913, and attempts to place the detailed neurocircuitry thought to underpin exercise hyperpnoea into context by focusing on key structures that might form the command network. With the advent of enhanced neuroimaging and functional neurosurgical techniques, a unique window of opportunity has recently arisen to target potential circuits in humans. Animal studies have identified a priori sites of interest in mid-brain structures, in particular the subthalamic locomotor region (subthalamic nucleus, STN) and the periaqueductal grey (PAG), which have now been recorded from in humans during exercise. When all data are viewed in an integrative manner, the PAG, in particular the lateral PAG, and aspects of the dorsal lateral PAG, appear to be key communicating circuitry for ‘central command’. Moreover, the PAG also fulfils many requirements of a command centre. It has functional connectivity to higher centres (dorsal lateral prefrontal cortex) and the basal ganglia (in particular, the STN), and receives a sensory input from contracting muscle, but, importantly, it sends efferent information to brainstem nuclei involved in cardiorespiratory control. PMID:23918772

75 FR 8310 - Federal Advisory Committee; Transformation Advisory Group; Closed Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-24

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77 FR 61581 - Notice of Advisory Committee Closed Meeting; U.S. Strategic Command Strategic Advisory Group

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2012-10-10

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Panicolytic-like effect of tramadol is mediated by opioid receptors in the dorsal periaqueductal grey.

PubMed

Fiaes, Gislaine Cardoso de Souza; Roncon, Camila Marroni; Sestile, Caio Cesar; Maraschin, Jhonatan Christian; Souza, Rodolfo Luis Silva; Porcu, Mauro; Audi, Elisabeth Aparecida

2017-05-30

Tramadol is a synthetic opioid prescribed for the treatment of moderate to severe pain, acting as agonist of μ-opioid receptors and serotonin (5-HT) and noradrenaline (NE) reuptake inhibitor. This study evaluated the effects of tramadol in rats submitted to the elevated T-maze (ETM), an animal model that evaluates behavioural parameters such as anxiety and panic. Male Wistar rats were intraperitoneally (i.p.) treated acutely with tramadol (16 and 32mg/kg) and were submitted to the ETM. Tramadol (32mg/kg) promoted a panicolytic-like effect. Considering that dorsal periaqueductal grey (dPAG) is the main brain structure related to the pathophysiology of panic disorder (PD), this study also evaluated the participation of 5-HT and opioid receptors located in the dPAG in the panicolytic-like effect of tramadol. Seven days after stereotaxic surgery for implantation of a cannula in the dPAG, the animals were submitted to the test. To assess the involvement of 5-HT 1A receptors on the effect of tramadol, we combined the 5-HT 1A receptor antagonist, WAY100635 (0.37nmol), microinjected intra-dPAG, 10min prior to the administration of tramadol (32mg/kg, i.p.). WAY100635 did not block the panicolytic-like effect of tramadol. We also associated the non-selective opioid receptor antagonist, naloxone, systemically (1mg/kg, i.p.) or intra-dPAG (0.5nmol) administered 10min prior to tramadol (32mg/kg, i.p.). Naloxone blocked the panicolytic-like effect of tramadol in both routes of administrations, showing that tramadol modulates acute panic defensive behaviours through its interaction with opioid receptors located in the dPAG. Copyright © 2017 Elsevier B.V. All rights reserved.

Periaqueductal gray glutamatergic, cannabinoid and vanilloid receptor interplay in defensive behavior and aversive memory formation.

PubMed

Back, Franklin P; Carobrez, Antonio P

2018-06-01

Stimulation of the midbrain periaqueductal gray matter (PAG) in humans elicits sensations of fear and impending terror, and mediates predator defensive responses in rodents. In rats, pharmacological stimulation of the dorsolateral portion of the PAG (dlPAG) with N-Methyl-d-Aspartate (NMDA) induces aversive conditioning that acts as an unconditioned stimulus (US). In the present work, we investigated the interplay between the vanilloid TRPV1 and cannabinoid CB1 receptors in the NMDA-dlPAG defensive response and in subsequent aversive learning. Rats were subjected to dlPAG NMDA infusion in an olfactory conditioned stimulus (CS) task allowing the evaluation of immediate and long-term defensive behavioral responses during CS presentation. The results indicated that an intermediate dose of NMDA (50 pmol) induced both immediate and long-term effects. A sub-effective dose of NMDA (25 pmol) was potentiated by the TRPV1 receptor agonist capsaicin (CAP, 1 nmol) and the CB1 receptor antagonist, AM251 (200 pmol). CAP (10 nmol) or the combination of CAP (1 nmol) and AM251 (200 pmol) induced long-term effects without increasing immediate defensive responses. The glutamate release inhibitor riluzole (2 or 4 nmol) and the AMPA/kainate receptor antagonist DNQX (2 or 4 nmol) potentiated the immediate effects but blocked the long-term effects. The results showed that immediate defensive responses rely on NMDA receptors, and aversive learning on the fine-tuning of TRPV1, CB1, metabotropic glutamate and AMPA receptors located in pre- and postsynaptic membranes. In conclusion, the activity of the dlPAG determines core affective aspects of aversive memory formation controlled by local TRPV1/CB1 balance. Copyright © 2018 Elsevier Ltd. All rights reserved.

Identification of neural circuits involved in female genital responses in the rat: A dual virus and anterograde tracing study

PubMed Central

Marson, L.; Murphy, A Z

2010-01-01

The spinal and peripheral innervation of the clitoris and vagina are fairly well understood. However, little is known regarding supraspinal control of these pelvic structures. The multisynaptic tracer pseudorabies virus (PRV) was used to map the brain neurons that innervate the clitoris and vagina. In order to delineate forebrain input onto PRV labeled cells, the anterograde tracer biotinylated dextran amine (BDA) was injected into the medial preoptic nucleus (MPO), ventromedial nucleus of the hypothalamus (VMN) or the midbrain periaqueductal gray (PAG) 10 days prior to viral injections. These brain regions have been intimately linked to various aspects of female reproductive behavior. Four days after viral injections, into the vagina and clitoris PRV labeled cells were observed in the paraventricular nucleus, Barrington’s nucleus, the A5 region, and the nucleus paragigantocellularis. At 5 days post-viral administration, additional PRV labeled cells were observed within the preoptic region, VMN, PAG and lateral hypothalamus. Anterograde labeling from the MPO terminated among PRV positive cells primarily within the dorsal paraventricular nucleus of the hypothalamus (PVN), ventrolateral VMN (VMNvl), caudal PAG and nucleus paragigantocellularis (nPGi). Anterograde labeling from the VMN terminated among PRV positive cells in the MPO and lateral/ventrolateral PAG. Anterograde labeling from the PAG terminated among PRV positive cells in the PVN, ventral hypothalamus and nPGi. Transynaptically labeled cells in the lateral hypothalamus, Barrington's nucleus and ventromedial medulla received innervation from all three sources. These studies, together, identify several CNS sites participating in the neural control of female sexual responses. They also provide the first data demonstrating a link between the MPO, VMNvl and PAG and CNS regions innervating the clitoris and vagina, providing support that these areas play a major role in female genital responses. PMID:16914428

Analgesia induced by localized injection of opiate peptides into the brain of infant rats.

PubMed

Barr, G A; Wang, S

2013-05-01

Stimulation of a variety of brain sites electrically or by opiates activates descending inhibitory pathways to attenuate noxious input to the spinal cord dorsal horn and produce analgesia. Analgesia induced by electrical stimulation of the periaqueductal grey (PAG) of the midbrain or medial rostral ventral medulla (RVM) matures late, towards the end or past the pre-weaning period. Descending facilitation takes precedence over inhibition. Yet opiates injected intracerebroventricularly or directly into the PAG induce analgesia relatively early in development. Our goal was to re-examine the role of opiates specific to individual receptor types in analgesia at several supraspinal sites. Antinociception was tested following microinjection of DAMGO (μ-opiate agonist), DPDPE (∂-opiate agonist) or U50,488 (κ-opiate agonist) into the PAG, RVM or dorsal lateral pons (DLP) in 3-, 10- and 14-day-old rats. DAMGO produced analgesia at 3 days of age at each brain area; the RVM was the most effective and the dorsal PAG was the least effective site. DPDPE produced modest analgesia at 10 and 14 days of age at the ventral PAG, RVM or DLP, but not the dorsal PAG. U50,488H was ineffective at all sites and all ages. Antinociception could be elicited at all three sites by DAMGO as early as 3 days of age and DPDPE at 10 and 14 days of age. The degree of analgesia increased gradually during the first 2 weeks of life, and likely reflects the maturation of connections within the brain and of descending inhibitory paths from these sites. © 2012 European Federation of International Association for the Study of Pain Chapters.

Drug-induced GABA transporter currents enhance GABA release to induce opioid withdrawal behaviors.

PubMed

Bagley, Elena E; Hacker, Jennifer; Chefer, Vladimir I; Mallet, Christophe; McNally, Gavan P; Chieng, Billy C H; Perroud, Julie; Shippenberg, Toni S; Christie, MacDonald J

2011-10-30

Neurotransmitter transporters can affect neuronal excitability indirectly via modulation of neurotransmitter concentrations or directly via transporter currents. A physiological or pathophysiological role for transporter currents has not been described. We found that GABA transporter 1 (GAT-1) cation currents directly increased GABAergic neuronal excitability and synaptic GABA release in the periaqueductal gray (PAG) during opioid withdrawal in rodents. In contrast, GAT-1 did not indirectly alter GABA receptor responses via modulation of extracellular GABA concentrations. Notably, we found that GAT-1-induced increases in GABAergic activity contributed to many PAG-mediated signs of opioid withdrawal. Together, these data support the hypothesis that GAT-1 activity directly produces opioid withdrawal signs through direct hyperexcitation of GABAergic PAG neurons and nerve terminals, which presumably enhances GABAergic inhibition of PAG output neurons. These data provide, to the best of our knowledge, the first evidence that dysregulation of a neurotransmitter transporter current is important for the maladaptive plasticity that underlies opiate withdrawal.

Hypothalamic Circuits for Predation and Evasion.

PubMed

Li, Yi; Zeng, Jiawei; Zhang, Juen; Yue, Chenyu; Zhong, Weixin; Liu, Zhixiang; Feng, Qiru; Luo, Minmin

2018-02-21

The interactions between predator and prey represent some of the most dramatic events in nature and constitute a matter of life and death for both sides. The hypothalamus has been implicated in driving predation and evasion; however, the exact hypothalamic neural circuits underlying these behaviors remain poorly defined. Here, we demonstrate that inhibitory and excitatory projections from the mouse lateral hypothalamus (LH) to the periaqueductal gray (PAG) in the midbrain drive, respectively, predation and evasion. LH GABA neurons were activated during predation. Optogenetically stimulating PAG-projecting LH GABA neurons drove strong predatory attack, and inhibiting these cells reversibly blocked predation. In contrast, LH glutamate neurons were activated during evasion. Stimulating PAG-projecting LH glutamate neurons drove evasion and inhibiting them impeded predictive evasion. Therefore, the seemingly opposite behaviors of predation and evasion are tightly regulated by two dissociable modular command systems within a single neural projection from the LH to the PAG. VIDEO ABSTRACT. Copyright © 2018 Elsevier Inc. All rights reserved.

76 FR 60811 - Notice of Advisory Committee Closed Meeting; U.S. Strategic Command Strategic Advisory Group...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-30

... DEPARTMENT OF DEFENSE Notice of Advisory Committee Closed Meeting; U.S. Strategic Command Strategic Advisory Group; Correction AGENCY: Department of Defense. ACTION: Notice of Advisory Committee... Command Strategic Advisory Group gave notice of a meeting to be held on November 1, 2011, from 8 a.m. to 5...

Role of benzodiazepine and serotonergic mechanisms in conditioned freezing and antinociception using electrical stimulation of the dorsal periaqueductal gray as unconditioned stimulus in rats.

PubMed

Castilho, V M; Macedo, C E; Brandão, M L

2002-12-01

The dorsal periaqueductal gray matter (dPAG) has been implicated in the modulation of defensive behavior. Electrical stimulation of this structure can be used as an unconditioned stimulus to produce a conditioned fear reaction expressed by freezing, antinociception, and autonomic responses. This study investigated the influence of benzodiazepine, serotonergic, and opioid mechanisms on these conditioned responses. Animals implanted with an electrode and a guide cannula into the dPAG were submitted to two conditioning sessions. Each session consisted of ten pairings of the light in a distinctive chamber (CS) with the electrical stimulation of this structure at the escape threshold. On the next day, each animal was exposed only to the CS (testing) and the duration of freezing, number of rearing and grooming episodes were recorded for 5 min. Before and after the testing session, animals were submitted to the tail-flick test. Fifteen minutes before the exposure to the CS, animals received injections into the dPAG of midazolam (a positive modulator of benzodiazepine sites), alpha-methyl-5-hydroxytryptamine (alpha-Me-5-HT; an agonist of 5-HT(2) receptors), naltrexone (an opioid antagonist), or vehicle. Conditioning with dPAG electrical stimulation caused significant increases in the time of freezing and conditioned antinociception. Injections of midazolam into the dPAG significantly inhibited freezing behavior and antinociception due to conditioning. Injections of alpha-Me-5-HT inhibited the effects of conditioning on freezing without affecting conditioned antinociception. Injections of naltrexone (13 nmol/0.2 micro l) did not change any of the conditioned responses studied. (1) Conditioned freezing and antinociception are modulated by benzodiazepine mechanisms into dPAG. (2) 5-HT(2) receptors seem to regulate conditioned freezing behavior. However, conditioned antinociception was not affected by 13 nmol naltrexone. (3) Opioid mechanisms do not seem to be involved in the conditioned responses using electrical stimulation of the dPAG as unconditioned stimulus. Further studies with other opioid and 5-HT(2) receptor antagonists are still needed to confirm the conclusions drawn from the present work.

Non-exercise Estimation of V02max Using a Dichotomy of Meeting or Not Meeting DHHS Physical Activity Recommendations

NASA Technical Reports Server (NTRS)

Wier, Larry T.; Jackson, Allen W.; Jackson, Andrew S.

2009-01-01

The physical activity guidelines (PAG) established by the US Dept. of Health and Human Services in 2008 is consistent with a rating of >/= 6 on the 11-point NASA Physical Activity Status Scale (PASS). Wier, et. al. developed non-exercise models for estimating VO2(sub max) from a combination of PASS, age, gender and either waist girth (WG) (R = 0.810, SEE= 4.799 ml/kg/min), %Fat (R = 0. 817, SEE = 4.716 ml/kg/min) or BMI (R = 0.802, SEE = 4.900 ml . kg-1. min -1 ). PURPOSE: to develop non-exercise models to estimate VO2max from age, gender, body composition (WG, %Fat, BMI) and PASS dichotomized at meets or does not meet the PAG (PAG-PASS), and to compare the accuracy of the PAG-PASS models with the models using the 11-point PASS. METHODS: 2417 men and 384 women were measured for VO2max by indirect calorimetry (RER >1.1); age (yr), gender by M = 1, W = 0; WG at the umbilicus; %fat by skin-folds, BMI by weight (kg) divided by height squared (m 2 ) , and PAGPASS by PASS < 6 = 0 and =/> 6 = 1. RESULTS: Three models were developed by multiple regression to estimate VO2(sub max) from age, gender, PAG-PASS and either WG (R = 0.790, SEE=5.019 ml/kg/min), %FAT (R= 0.080, SEE = 4.915 ml/kg/min) or BMI (R = 0.777, SEE = 5.162ml/kg/min). Cross-validation by the PRESS technique confirmed these statistics. Simple correlations between measured VO2(sub max) and estimates from the PAG-PASS models with WG, %Fat and BMI were 0.790, 0.800 and 0.777, minimally different from the correlations obtained with the PASS models (0.810, 0.810, and 0.802). PAG-PASS and PASS model constant errors were also similar: < 1 ml/kg/min for subsamples of age, gender, PASS and for VO2(sub max) between 30 and 50 ml/kg/min (70% of the sample) but > 1 ml/kg/min for VO2(sub max) <30 and >50 ml/kg/min. CONCLUSIONS: Non-exercise models using the combined effects of age, gender, body composition and the dichotomized PAG-PASS provide estimates of VO2(sub max) that are accurate for most adults, and the accuracy of these models are similar to previously published models using the 11-point PASS.

Pharmacological evidence for the mediation of the panicolytic effect of fluoxetine by dorsal periaqueductal gray matter μ-opioid receptors.

PubMed

Roncon, Camila Marroni; Almada, Rafael Carvalho; Maraschin, Jhonatan Christian; Audi, Elisabeth Aparecida; Zangrossi, Hélio; Graeff, Frederico Guilherme; Coimbra, Norberto Cysne

2015-12-01

Previously reported results have shown that the inhibitory effect of fluoxetine on escape behavior, interpreted as a panicolytic-like effect, is blocked by pretreatment with either the opioid receptor antagonist naloxone or the 5-HT1A receptor (5-HT1A-R) antagonist WAY100635 via injection into the dorsal periaqueductal gray matter (dPAG). Additionally, reported evidence indicates that the μ-opioid receptor (MOR) interacts with the 5-HT1A-R in the dPAG. In the present work, pretreatment of the dPAG with the selective MOR blocker CTOP antagonized the anti-escape effect of chronic fluoxetine (10 mg/kg, i.p., daily, for 21 days), as measured in the elevated T-maze (ETM) test, indicating mediation of this effect by the MOR. In addition, the combined administration of sub-effective doses of the selective MOR agonist DAMGO (intra-dPAG) and sub-effective doses of chronic as well as subchronic (7 days) fluoxetine increased avoidance and escape latencies, suggesting that the activation of MORs may facilitate and accelerate the effects of fluoxetine. The current observation that MORs located in the dPAG mediate the anti-escape effect of fluoxetine may open new perspectives for the development of more efficient and fast-acting panic-alleviating drugs. Copyright © 2015 Elsevier Ltd. All rights reserved.

Network confinement and heterogeneity slows nanoparticle diffusion in polymer gels

NASA Astrophysics Data System (ADS)

Parrish, Emmabeth; Caporizzo, Matthew A.; Composto, Russell J.

2017-05-01

Nanoparticle (NP) diffusion was measured in polyacrylamide gels (PAGs) with a mesh size comparable to the NP size, 21 nm. The confinement ratio (CR), NP diameter/mesh size, increased from 0.4 to 3.8 by increasing crosslinker density and from 0.4 to 2.1 by adding acetone, which collapsed the PAGs. In all gels, NPs either became localized, moving less than 200 nm, diffused microns, or exhibited a combination of these behaviors, as measured by single particle tracking. Mean squared displacements (MSDs) of mobile NPs decreased as CR increased. In collapsed gels, the localized NP population increased and MSD of mobile NPs decreased compared to crosslinked PAGs. For all CRs, van Hove distributions exhibited non-Gaussian displacements, consistent with intermittent localization of NPs. The non-Gaussian parameter increased from a maximum of 1.5 for crosslinked PAG to 5 for collapsed PAG, consistent with greater network heterogeneity in these gels. Diffusion coefficients decreased exponentially as CR increased for crosslinked gels; however, in collapsed gels, the diffusion coefficients decreased more strongly, which was attributed to network heterogeneity. Collapsing the gel resulted in an increasingly tortuous pathway for NPs, slowing diffusion at a given CR. Understanding how gel structure affects NP mobility will allow the design and enhanced performance of gels that separate and release molecules in membranes and drug delivery platforms.

Self-reported dietary adherence, disease-specific symptoms, and quality of life are associated with healthcare provider follow-up in celiac disease.

PubMed

Hughey, Jacob J; Ray, Bonnie K; Lee, Anne R; Voorhees, Kristin N; Kelly, Ciaran P; Schuppan, Detlef

2017-12-11

The only treatment for celiac disease (CeD) is a lifelong gluten-free diet (GFD). The restrictive nature of the GFD makes adherence a challenge. As an integral part of CeD management, multiple professional organizations recommend regular follow-up with a healthcare provider (HCP). Many CeD patients also participate in patient advocacy groups (PAGs) for education and support. Previous work found that follow-up of CeD patients is highly variable. Here we investigated the self-reported factors associated with HCP follow-up among individuals diagnosed with CeD who participate in a PAG. We conducted a survey of members of Beyond Celiac (a PAG), collecting responses from 1832 U.S. adults ages 19-65 who reported having CeD. The survey queried HCP follow-up related to CeD and included validated instruments for dietary adherence (CDAT), disease-specific symptoms (CSI), and quality of life (CD-QOL). Overall, 27% of respondents diagnosed with CeD at least five years ago reported that they had not visited an HCP about CeD in the last five years. The most frequent reason for not visiting an HCP was "doing fine on my own" (47.6%). Using multiple logistic regression, we identified significant associations between whether a respondent reported visiting an HCP about CeD in the last five years and the scores for all three validated instruments. In particular, as disease-specific symptoms and quality of life worsened, the probability of having visited an HCP increased. Conversely, as dietary adherence worsened, the probability decreased. Our results suggest that many individuals with CeD manage their disease without ongoing support from an HCP. Our results thus emphasize the need for greater access to high quality CeD care, and highlight an opportunity for PAGs to bring together patients and HCPs to improve management of CeD.

Elastohydrodynamics of oil-soluble PAGs, high-oleic sunflower oil and their blends

USDA-ARS?s Scientific Manuscript database

Recent reports indicate that the oxidative stability of vegetable oils can be improved for lubrication purposes by mixing them with oil-soluble polyalkyl glycols (OS-PAG). This inspired a study of other lubrication-related properties of their blends. The viscosity, density, and elastohydrodynamic fi...

78 FR 42071 - Updates to Protective Action Guides Manual: Protective Action Guides (PAGs) and Planning Guidance...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-15

... ENVIRONMENTAL PROTECTION AGENCY [EPA-HQ-OAR-2007-0268; FRL-9833-5] Updates to Protective Action Guides Manual: Protective Action Guides (PAGs) and Planning Guidance for Radiological Incidents AGENCY: Environmental Protection Agency (EPA). ACTION: Proposed guidance; extension of comment period. SUMMARY: The U.S...

78 FR 22257 - Updates to Protective Action Guides Manual: Protective Action Guides (PAGs) and Planning Guidance...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-15

... ENVIRONMENTAL PROTECTION AGENCY [EPA-HQ-OAR-2007-0268; FRL-9707-2] Updates to Protective Action Guides Manual: Protective Action Guides (PAGs) and Planning Guidance for Radiological Incidents AGENCY: Environmental Protection Agency (EPA). ACTION: Notice of document availability for interim use and public...

45 CFR 1222.4 - Advisory group responsibilities.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 45 Public Welfare 4 2014-10-01 2014-10-01 false Advisory group responsibilities. 1222.4 Section... COMMUNITY SERVICE PARTICIPATION OF PROJECT BENEFICIARIES § 1222.4 Advisory group responsibilities. The advisory group shall have the following responsibilities for the intent and purposes of these requirements...

45 CFR 1222.4 - Advisory group responsibilities.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 45 Public Welfare 4 2013-10-01 2013-10-01 false Advisory group responsibilities. 1222.4 Section... COMMUNITY SERVICE PARTICIPATION OF PROJECT BENEFICIARIES § 1222.4 Advisory group responsibilities. The advisory group shall have the following responsibilities for the intent and purposes of these requirements...

45 CFR 1222.4 - Advisory group responsibilities.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 45 Public Welfare 4 2012-10-01 2012-10-01 false Advisory group responsibilities. 1222.4 Section... COMMUNITY SERVICE PARTICIPATION OF PROJECT BENEFICIARIES § 1222.4 Advisory group responsibilities. The advisory group shall have the following responsibilities for the intent and purposes of these requirements...

45 CFR 1222.4 - Advisory group responsibilities.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 4 2010-10-01 2010-10-01 false Advisory group responsibilities. 1222.4 Section... COMMUNITY SERVICE PARTICIPATION OF PROJECT BENEFICIARIES § 1222.4 Advisory group responsibilities. The advisory group shall have the following responsibilities for the intent and purposes of these requirements...

78 FR 17924 - U.S. Strategic Command Strategic Advisory Group; Notice of Federal Advisory Committee Closed Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-25

... DEPARTMENT OF DEFENSE Office of the Secretary U.S. Strategic Command Strategic Advisory Group... following federal advisory committee: U.S. Strategic Command Strategic Advisory Group. DATES: April 18, 2013..., intelligence, and policy-related issues to the Commander, U.S. Strategic Command, during the development of the...

A recombinant Bacillus anthracis strain producing the Clostridium perfringens Ib component induces protection against iota toxins.

PubMed

Sirard, J C; Weber, M; Duflot, E; Popoff, M R; Mock, M

1997-06-01

The Bacillus anthracis toxinogenic Sterne strain is currently used as a live veterinary vaccine against anthrax. The capacity of a toxin-deficient derivative strain to produce a heterologous antigen by using the strong inducible promoter of the B. anthracis pag gene was investigated. The expression of the foreign gene ibp, encoding the Ib component of iota toxin from Clostridium perfringens, was analyzed. A pag-ibp fusion was introduced by allelic exchange into a toxin-deficient Sterne strain, thereby replacing the wild-type pag gene. This recombinant strain, called BAIB, was stable and secreted large quantities of Ib protein in induced culture conditions. Mice given injections of live BAIB spores developed an antibody response specific to the Ib protein. The pag-ibp fusion was therefore functional both in vitro and in vivo. Moreover, the immunized animals were protected against a challenge with C. perfringens iota toxin or with the homologous Clostridium spiroforme toxin. The protective immunity was mediated by neutralizing antibodies. In conclusion, B. anthracis is promising for the development of live veterinary vaccines.

A recombinant Bacillus anthracis strain producing the Clostridium perfringens Ib component induces protection against iota toxins.

PubMed Central

Sirard, J C; Weber, M; Duflot, E; Popoff, M R; Mock, M

1997-01-01

The Bacillus anthracis toxinogenic Sterne strain is currently used as a live veterinary vaccine against anthrax. The capacity of a toxin-deficient derivative strain to produce a heterologous antigen by using the strong inducible promoter of the B. anthracis pag gene was investigated. The expression of the foreign gene ibp, encoding the Ib component of iota toxin from Clostridium perfringens, was analyzed. A pag-ibp fusion was introduced by allelic exchange into a toxin-deficient Sterne strain, thereby replacing the wild-type pag gene. This recombinant strain, called BAIB, was stable and secreted large quantities of Ib protein in induced culture conditions. Mice given injections of live BAIB spores developed an antibody response specific to the Ib protein. The pag-ibp fusion was therefore functional both in vitro and in vivo. Moreover, the immunized animals were protected against a challenge with C. perfringens iota toxin or with the homologous Clostridium spiroforme toxin. The protective immunity was mediated by neutralizing antibodies. In conclusion, B. anthracis is promising for the development of live veterinary vaccines. PMID:9169728

Development of the Updated Environmental Protection Agency Manual of Protective Action Guides (PAGS) and Protective Actions for Nuclear Incidents

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

Carter, L.M.

2008-07-01

As a student intern with the United States Environmental Protection Agency (EPA) Headquarters, the author was trained in the National Response Plan (NRP) and assisted in the editing of the new (unpublished) EPA Protective Action Guides (PAGs) [1] which has been revised in light of the perceived post 9/11 potential for 'Dirty Bomb' and 'Improvised Nuclear Device' attacks on civilian areas. Technical aspects and the public policy aspects of developing the new guides are discussed. Early Phase initial responses discussed include: Notification of state and/or local authorities, immediate evacuation/sheltering prior to release information or measurements, monitoring of releases and exposuremore » rate measurements, estimation of dose consequences, implementation of protective actions in other areas. The new PAG clarifies the use of 1992 PAGs [2] for incidents other than nuclear power plant accidents, lowers projected thyroid dose for potassium iodine (KI), provides drinking water guidance, includes guidance for long-term site restoration, and updates dosimetry from ICRP 26 to ICRP 60. (authors)« less

Neuroimaging of the Periaqueductal Gray: State of the Field

PubMed Central

Linnman, Clas; Moulton, Eric A.; Barmettler, Gabi; Becerra, Lino; Borsook, David

2011-01-01

This review and meta-analysis aims at summarizing and integrating the human neuroimaging studies that report periaqueductal gray (PAG) involvement; 250 original manuscripts on human neuroimaging of the PAG were identified. A narrative review and meta-analysis using activation likelihood estimates is included. Behaviors covered include pain and pain modulation, anxiety, bladder and bowel function and autonomic regulation. Methods include structural and functional magnetic resonance imaging, functional connectivity measures, diffusion weighted imaging and positron emission tomography. Human neuroimaging studies in healthy and clinical populations largely confirm the animal literature indicating that the PAG is involved in homeostatic regulation of salient functions such as pain, anxiety and autonomic function. Methodological concerns in the current literature, including resolution constraints, imaging artifacts and imprecise neuroanatomical labeling are discussed, and future directions are proposed. A general conclusion is that PAG neuroimaging is a field with enormous potential to translate animal data onto human behaviors, but with some growing pains that can and need to be addressed in order to add to our understanding of the neurobiology of this key region. PMID:22197740

Right mesial temporal lobe epilepsy impairs empathy-related brain responses to dynamic fearful faces.

PubMed

Toller, Gianina; Adhimoolam, Babu; Grunwald, Thomas; Huppertz, Hans-Jürgen; Kurthen, Martin; Rankin, Katherine P; Jokeit, Hennric

2015-03-01

Unilateral mesial temporal lobe epilepsy (MTLE) has been associated with reduced amygdala responsiveness to fearful faces. However, the effect of unilateral MTLE on empathy-related brain responses in extra-amygdalar regions has not been investigated. Using functional magnetic resonance imaging, we measured empathy-related brain responses to dynamic fearful faces in 34 patients with unilateral MTLE (18 right sided), in an epilepsy (extra-MTLE; n = 16) and in a healthy control group (n = 30). The primary finding was that right MTLE (RMTLE) was associated with decreased activity predominantly in the right amygdala and also in bilateral periaqueductal gray (PAG) but normal activity in the right anterior insula. The results of the extra-MTLE group demonstrate that these reduced amygdala and PAG responses go beyond the attenuation caused by antiepileptic and antidepressant medication. These findings clearly indicate that RMTLE affects the function of mesial temporal and midbrain structures that mediate basic interoceptive input necessary for the emotional awareness of empathic experiences of fear. Together with the decreased empathic concern found in the RMTLE group, this study provides neurobehavioral evidence that patients with RMTLE are at increased risk for reduced empathy towards others' internal states and sheds new light on the nature of social-cognitive impairments frequently accompanying MTLE.

Ventrolateral orbital cortex oxytocin attenuates neuropathic pain through periaqueductal gray opioid receptor.

PubMed

Taati, Mina; Tamaddonfard, Esmaeal

2018-06-01

Oxytocin plays an important role in supraspinal modulation of pain. In the present study, we investigated the effects of ventrolateral orbital cortex (VLOC) microinjection of oxytocin on neuropathic pain after blockade of opioid receptors in this area and ventrolateral periaqueductal gray (vlPAG). Neuropathic pain was induced by complete transcection of preoneal and tibial branches of sciatic nerve. The VLOC and vlPAG were unilaterally (contralateral to the sciatic nerve-injured side) and bilaterally implanted with guide cannulas, respectively. Mechanical paw withdrawal threshold (PWT) was measured using von Frey filaments. Area under curve (AUC) was also calculated. Microinjection of oxytocin (5, 10 and 20 ng/site) into the VLOC increased PWT. Antiallodynia induced by oxytocin (20 ng/site) was inhibited by prior intra-VLOC administration of atosiban (an oxytocin receptor antagonist, 100 ng/site) and naloxone (an opioid receptor antagonist, 500 ng/site). Prior microinjection of naloxone (500 ng/site) into the vlPAG also inhibited antiallodynia induced by intra-VLOC microinjection of oxytocin (20 ng/site). All the VLOC and vlPAG microinjected drugs did not alter locomotor activity. It is concluded that oxytocin and its receptor may be involved in modulation of neuropathic pain at the VLOC level. Opioid receptors of VLOC and vlPAG might be involved in the antiallodynic effect of the VLOC-microinjected oxytocin. Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.

Order of multiphoton excitation of sulfonium photo-acid generators used in photoresists based on SU-8

NASA Astrophysics Data System (ADS)

Williams, Henry E.; Diaz, Carlos; Padilla, Gabriel; Hernandez, Florencio E.; Kuebler, Stephen M.

2017-06-01

Multiphoton lithography (MPL), Z-scan spectroscopy, and quantum chemical calculations were employed to investigate the order of multiphoton excitation that occurs when femtosecond laser pulses are used to excite two sulfonium photo-acid generators (PAGs) commonly used in photoresists based on the cross-linkable epoxide SU-8. The mole-fractions of the mono- and bis-sulfonium forms of these PAGs were determined for the commercially available photoresist SU-8 2075 and for the PAGs alone from a separate source. Both were found to contain similar fractions of the mono- and bis-forms, with the mono form present in the majority. Reichert's method was used to determine the solvatochromic strength of the SU-8 matrix, so that results obtained for the PAGs in SU-8 and in solution could be reliably compared. The PAGs were found to exhibit a minimal solvatochromic shift for a series of solvents that span across the solvatochromic strength of SU-8 itself. Sub-micron-sized features were fabricated in SU-8 2075 by MPL using amplified and continuous-wave mode-locked laser pulses. Analysis of the features as a function of average laser power, scan speed, and excitation wavelength shows that the PAGs can be activated by both two- and three-photon absorption (2PA and 3PA). Which activation mode dominates depends principally upon the excitation wavelength because the average laser powers that can be used with the photoresist are limited by practical considerations. The power must be high enough to effect sufficient cross-linking, yet not so high as to exceed the damage threshold of the material. When the laser pulses have a duration on the order of 100 fs, 3PA dominates at wavelengths near 800 nm, whereas 2PA becomes dominant at wavelengths below 700 nm. These findings are corroborated by open-aperture Z-scan measurements and quantum chemical calculations of the cross-sections for 2PA and 3PA as a function of wavelength.

Opioid and GABAB receptors differentially couple to an adenylyl cyclase/protein kinase A downstream effector after chronic morphine treatment

PubMed Central

Bagley, Elena E.

2014-01-01

Opioids are intensely addictive, and cessation of their chronic use is associated with a highly aversive withdrawal syndrome. A cellular hallmark of withdrawal is an opioid sensitive protein kinase A-dependent increase in GABA transporter-1 (GAT-1) currents in periaqueductal gray (PAG) neurons. Elevated GAT-1 activity directly increases GABAergic neuronal excitability and synaptic GABA release, which will enhance GABAergic inhibition of PAG output neurons. This reduced activity of PAG output neurons to several brain regions, including the hypothalamus and medulla, contributes to many of the PAG-mediated signs of opioid withdrawal. The GABAB receptor agonist baclofen reduces some of the PAG mediated signs of opioid withdrawal. Like the opioid receptors the GABAB receptor is a Gi/Go coupled G-protein coupled receptor. This suggests it could be modulating GAT-1 activity in PAG neurons through its inhibition of the adenylyl cyclase/protein kinase A pathway. Opioid modulation of the GAT-1 activity can be detected by changes in the reversal potential of opioid membrane currents. We found that when opioids are reducing the GAT-1 cation conductance and increasing the GIRK conductance the opioid agonist reversal potential is much more negative than Ek. Using this approach for GABAB receptors we show that the GABAB receptor agonist, baclofen, does not couple to inhibition of GAT-1 currents during opioid withdrawal. It is possible this differential signaling of the two Gi/Go coupled G-protein coupled receptors is due to the strong compartmentalization of the GABAB receptor that does not favor signaling to the adenylyl cyclase/protein kinase A/GAT-1 pathway. This highlights the importance of studying the effects of G-protein coupled receptors in native tissue with endogenous G-protein coupled receptors and the full complement of relevant proteins and signaling molecules. This study suggests that baclofen reduces opioid withdrawal symptoms through a non-GAT-1 effector. PMID:25009497

Opioid and GABAB receptors differentially couple to an adenylyl cyclase/protein kinase A downstream effector after chronic morphine treatment.

PubMed

Bagley, Elena E

2014-01-01

Opioids are intensely addictive, and cessation of their chronic use is associated with a highly aversive withdrawal syndrome. A cellular hallmark of withdrawal is an opioid sensitive protein kinase A-dependent increase in GABA transporter-1 (GAT-1) currents in periaqueductal gray (PAG) neurons. Elevated GAT-1 activity directly increases GABAergic neuronal excitability and synaptic GABA release, which will enhance GABAergic inhibition of PAG output neurons. This reduced activity of PAG output neurons to several brain regions, including the hypothalamus and medulla, contributes to many of the PAG-mediated signs of opioid withdrawal. The GABAB receptor agonist baclofen reduces some of the PAG mediated signs of opioid withdrawal. Like the opioid receptors the GABAB receptor is a Gi/Go coupled G-protein coupled receptor. This suggests it could be modulating GAT-1 activity in PAG neurons through its inhibition of the adenylyl cyclase/protein kinase A pathway. Opioid modulation of the GAT-1 activity can be detected by changes in the reversal potential of opioid membrane currents. We found that when opioids are reducing the GAT-1 cation conductance and increasing the GIRK conductance the opioid agonist reversal potential is much more negative than E k . Using this approach for GABAB receptors we show that the GABAB receptor agonist, baclofen, does not couple to inhibition of GAT-1 currents during opioid withdrawal. It is possible this differential signaling of the two Gi/Go coupled G-protein coupled receptors is due to the strong compartmentalization of the GABAB receptor that does not favor signaling to the adenylyl cyclase/protein kinase A/GAT-1 pathway. This highlights the importance of studying the effects of G-protein coupled receptors in native tissue with endogenous G-protein coupled receptors and the full complement of relevant proteins and signaling molecules. This study suggests that baclofen reduces opioid withdrawal symptoms through a non-GAT-1 effector.

75 FR 22561 - Federal Advisory Committee; United States Strategic Command Strategic Advisory Group; Charter...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-29

... Command Strategic Advisory Group; Charter Renewal AGENCY: Department of Defense (DoD). ACTION: Renewal of... Command Strategic Advisory Group (hereafter referred to as the Group). FOR FURTHER INFORMATION CONTACT... Chairman of the Joint Chiefs of Staff and the Commander of the U.S. Strategic Command independent advice...

77 FR 55863 - NASA Advisory Council; Science Committee; Earth Science Subcommittee; Applied Sciences Advisory...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-11

... NATIONAL AERONAUTICS AND SPACE ADMINISTRATION [Notice (12-072)] NASA Advisory Council; Science Committee; Earth Science Subcommittee; Applied Sciences Advisory Group Meeting AGENCY: National Aeronautics... the Applied Science Advisory Group. This Subcommittee reports to the Earth Science Subcommittee...

GABA transporter currents activated by protein kinase A excite midbrain neurons during opioid withdrawal.

PubMed

Bagley, Elena E; Gerke, Michelle B; Vaughan, Christopher W; Hack, Stephen P; Christie, MacDonald J

2005-02-03

Adaptations in neurons of the midbrain periaqueductal gray (PAG) induced by chronic morphine treatment mediate expression of many signs of opioid withdrawal. The abnormally elevated action potential rate of opioid-sensitive PAG neurons is a likely cellular mechanism for withdrawal expression. We report here that opioid withdrawal in vitro induced an opioid-sensitive cation current that was mediated by the GABA transporter-1 (GAT-1) and required activation of protein kinase A (PKA) for its expression. Inhibition of GAT-1 or PKA also prevented withdrawal-induced hyperexcitation of PAG neurons. Our findings indicate that GAT-1 currents can directly increase the action potential rates of neurons and that GAT-1 may be a target for therapy to alleviate opioid-withdrawal symptoms.

Substance P-induced release of Met5-enkephalin from striatal and periaqueductal gray slices.

PubMed

Del Río, J; Naranjo, J R; Yang, H Y; Costa, E

1983-11-21

Substance P(SP), the heptapeptide SP and the stable analogue (p-Glu5-MePhe8-MeGly9) SP (DiMe-C7) induce a Ca2+-dependent release of Met5-enkephalin (MET) from slices of periaqueductal gray matter (PAG) and striatum of rats. The MET release from striatal slices is greater than that from PAG slices because of the higher MET content of striatum. Intraventricular injection of SP and of the two related peptides induce analgesia in the rat, and their analgesic potency is in line with their capacity to release MET. Other neuropeptides which possess antinociceptive activity such as bombesin, neurotensin, vasopressin and somatostatin fail to release MET from PAG slices.

75 FR 60484 - NASA Advisory Council; Science Committee; Earth Science Subcommittee; Applied Sciences Advisory...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-30

... NATIONAL AERONAUTICS AND SPACE ADMINISTRATION [Notice: (10-115)] NASA Advisory Council; Science Committee; Earth Science Subcommittee; Applied Sciences Advisory Group Meeting AGENCY: National Aeronautics...) announces a meeting of the Applied Science Advisory Group. This Subcommittee reports to the Earth Science...

76 FR 27388 - Special Medical Advisory Group; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-11

... DEPARTMENT OF VETERANS AFFAIRS Special Medical Advisory Group; Notice of Meeting The Department of Veterans Affairs (VA) gives notice under Public Law 92-463 (Federal Advisory Committee Act) that the Special Medical Advisory Group will meet on May 26, 2011, in Room 830 at VA Central Office, 810 Vermont...

77 FR 25706 - Notice of Advisory Committee Closed Meeting; U.S. Strategic Command Strategic Advisory Group

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-01

..., Command and Control, Science and Technology, Missile Defense. Meeting Accessibility: Pursuant to 5 U.S.C... DEPARTMENT OF DEFENSE Notice of Advisory Committee Closed Meeting; U.S. Strategic Command Strategic Advisory Group AGENCY: Department of Defense. ACTION: Notice of Advisory Committee closed meeting...

77 FR 74099 - Reestablishment of Advisory Group

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-12

..., Health Promotion, and Integrative and Public Health. The Advisory Group on Prevention, Health Promotion, and Integrative and Public Health (Advisory Group), as set forth under the provisions of Executive...

A serotonergic deficit in the dorsal periaqueductal gray matter may underpin enhanced panic-like behavior in diabetic rats.

PubMed

Gambeta, Eder; Sestile, Caio C; Fogaça, Manoela V; Guimarães, Francisco S; Audi, Elisabeth A; da Cunha, Joice M; Zangrossi, Hélio; Shimene de Melo Yamashita, Paula; Zanoveli, Janaina M

2017-10-01

It is known that diabetic (DBT) animals present dysregulation on the serotonergic system in several brain areas associated with anxiety-like responses. The aim of this study was to investigate the involvement of 5-HT1A receptors on dorsal periaqueductal gray (dPAG) in the behavioral response related to panic disorder in type-1 DBT animals. For this, the escape response by electric stimulation (ES) of dPAG in DBT and normoglycemic (NGL) animals was assessed. Both NGL and DBT animals were exposed to an open-field test (OFT) 28 days after DBT confirmation. The current threshold to induce escape behavior in DBT animals was reduced compared with NGL animals. No impairment in locomotor activity was observed when DBT animals were compared with NGL animals. An intra-dPAG injection of the 5-HT1A receptor agonist (±)-8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) increased the [INCREMENT] threshold in both DBT and NGL, suggesting a panicolytic-like effect. DBT animals presented a more pronounced panicolytic-like response compared with NGL as a higher [INCREMENT] threshold was observed after 8-OH-DPAT treatment, which could be a consequence of the increased expression of the 5-HT1A receptor in the dPAG from DBT animals. Our results are in line with the proposal that a deficiency in serotonergic modulation of the dPAG is involved in triggering the panic attack and the 5-HT1A receptors might be essential for the panicolytic-like response.

Differential development of antinociceptive tolerance to morphine and fentanyl is not linked to efficacy in the ventrolateral periaqueductal gray of the rat

PubMed Central

Bobeck, Erin N.; Haseman, Rachel A.; Hong, Dana; Ingram, Susan L.; Morgan, Michael M.

2012-01-01

Systemic administration of morphine typically produces greater tolerance than higher efficacy mu-opioid receptor (MOPr) agonists, such as fentanyl. The objective of the present study was to test this relationship by measuring antinociceptive efficacy and tolerance to morphine and fentanyl microinjected into the ventrolateral periaqueductal gray (vlPAG). MOPr agonist efficacy was evaluated by microinjecting the irreversible opioid receptor antagonist β-funaltrexamine hydrochloride (β-FNA) into the vlPAG prior to a dose-response analysis of morphine and fentanyl antinociception. In contrast to systemic administration of morphine and fentanyl, microinjection of these drugs into the vlPAG had similar efficacy as measured by similar reductions in maximal antinociception following β-FNA administration. Analysis of tolerance revealed a rightward shift in the dose-response curve to a single pretreatment with morphine, but not fentanyl. Moreover, the magnitude of tolerance to morphine was comparable following one, four, or eight pretreatments. Tolerance to fentanyl also was evident following four or eight microinjections. These data are surprising in that antinociceptive efficacy appears to vary depending on the site of administration. Moreover, the similar efficacy following microinjection of morphine and fentanyl into the vlPAG was associated with comparable tolerance, with the one exception of no tolerance to acute administration of fentanyl. Perspective These data reveal that antinociceptive tolerance following vlPAG administration of opioids develops rapidly, is evident with both morphine and fentanyl, and the magnitude is relatively consistent regardless of the number of pretreatments. PMID:22766006

78 FR 23333 - Special Medical Advisory Group, Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-18

... DEPARTMENT OF VETERANS AFFAIRS Special Medical Advisory Group, Notice of Meeting The Department of Veterans Affairs (VA) gives notice under the Federal Advisory Committee Act, 5 U.S.C. App. 2, that the Special Medical Advisory Group will meet on May 1, 2013, in Room 830 at VA Central Office, 810 Vermont...

Circulating bovine pregnancy associated glycoproteins (bPAGs) are associated with late embryonic/fetal survival but not ovulatory follicle size in suckled beef cows

USDA-ARS?s Scientific Manuscript database

GnRH-induced ovulation of small dominant follicles resulted in increased late embryonic/fetal mortality. The objective of this study was to examine the relationship between ovulatory follicle size, embryo/fetal survival, and circulating concentrations of bPAGs (detects presence of an embryo/fetus a...

Full expression of Bacillus anthracis toxin gene in the presence of bicarbonate requires a 2.7-kb-long atxA mRNA that contains a terminator structure.

PubMed

Bertin, Marine; Château, Alice; Fouet, Agnès

2010-05-01

Bacillus anthracis toxin gene expression requires AtxA, a virulence regulator that also activates capsule gene transcription and controls expression of more than a hundred genes. Here we report that atxA mRNA is 2.7-kb-long and ends, after a 500 nt-long 3' untranslated region, with a stem loop structure followed by a run of U's. The presence of this structure stabilizes atxA mRNA and is necessary for AtxA maximal accumulation, full expression of the PA toxin gene, pagA and optimal PA accumulation. This structure displays terminator activity independently of its orientation when cloned between an inducible promoter and a reporter gene. The 3.6-kb-long DNA fragment carrying both AtxA promoters and the terminator is sufficient for full expression of pagA in the presence of bicarbonate. No pXO1-encoded element other than the DNA fragment encompassing the 2.7 kb atxA transcript and the pagA promoter is required for bicarbonate induction of pagA transcription. (c) 2010 Elsevier Masson SAS. All rights reserved.

Facilitation of the arterial baroreflex by the preoptic area in anaesthetized rats.

PubMed Central

Inui, K; Nomura, J; Murase, S; Nosaka, S

1995-01-01

1. Activation of cell bodies in the ventrolateral part of the midbrain periaqueductal grey matter (PAG) facilitates the arterial baroreflex via the nucleus raphe magnus. The facilitatory effects of stimulation within the hypothalamus on the arterial baroreflex and their relation to the PAG and nucleus raphe magnus were studied in urethane- and chloralose-anaesthetized rats. 2. Systematic mapping experiments revealed that the preoptic area (POA) is the principal location in the hypothalamus of neuronal cell bodies that are responsible for the potentiation of the baroreflex. In addition to provoking hypotension and vagal bradycardia, both electrical and chemical stimulation of the POA produced facilitation of baroreflex vagal bradycardia (BVB) that was evoked by electrical stimulation of the aortic depressor nerve. Baroreflex hypotension was slightly augmented during activation of the POA in vagotomized rats. 3. Selective destruction of cell bodies either in the ventrolateral PAG or in the nucleus raphe magnus reduced facilitation of BVB by the POA. Hypotension and bradycardia due to POA stimulation were also markedly attenuated after such selective destruction. 4. In conclusion, the POA, the ventrolateral PAG and the nucleus raphe magnus constitute a functional complex that produces cardiovascular trophotropic effects including hypotension, vagal bradycardia and baroreflex facilitation. PMID:8568691

The Influence of Lath, Block and Prior Austenite Grain (PAG) Size on the Tensile, Creep and Fatigue Properties of Novel Maraging Steel

PubMed Central

McAdam, Steven; Hill, Paul; Rawson, Martin; Perkins, Karen

2017-01-01

The influence of martensitic microstructure and prior austenite grain (PAG) size on the mechanical properties of novel maraging steel was studied. This was achieved by looking at two different martensitic structures with PAG sizes of approximately 40 µm and 80 µm, produced by hot rolling to different reductions. Two ageing heat-treatments were considered: both heat-treatments consisted of austenisation at 960 °C, then aging at 560 °C for 5 h, but while one was rapidly cooled the other was slow cooled and then extended aged at 480 °C for 64 h. It is shown that for the shorter ageing treatment the smaller PAG size resulted in significant improvements in strength (increase of more than 150 MPa), ductility (four times increase), creep life (almost four times increase in creep life) and fatigue life (almost doubled). Whereas, the extended aged sample showed similar changes in the fatigue life, elongation and hardness it displayed yet showed no difference in tensile strength and creep. These results display the complexity of microstructural contributions to mechanical properties in maraging steels. PMID:28773086

Pregnancy-associated glycoprotein, chymosin and pepsinogen immunoreactivity of proteins extracted from fetal gastric tissue in bovine species.

PubMed

Bella, A; Sousa, N M; Dehimi, M L; Beckers, J F

2012-06-01

The objective of this work was to investigate the expression of gastric aspartic proteinases in fundic and pyloric mucosa removed from bovine fetuses. For this purpose, fractions issued from classical biochemical protocols were analyzed by proteolytic method, by PAG-RIA and by Western blot with the use of antisera raised against both pepsinogens and PAG. A strong reaction of proteins extracted from the fundic mucosa collected at the beginning of pregnancy was revealed with both anti-bPAG-I and anti-bPAG-II antisera, suggesting the expression of pepsinogen F in bovine species. Concerning pyloric mucosa, the analysis by Western blot highlighted a very strong immunoreaction with the anti-bovine chymosin serum. Amino-terminal sequencing allowed to identify bovine fetuin and albumin in fundic extracts, chymosin in the pyloric mucosa extracts, as well as some unknown proteins in both mucosa. Despite no N-terminal microsequence corresponding to the hypothetical pepsinogen F could be identified, it cannot be excluded that an existing bovine pepsinogen F-like molecule could be degraded during the purification procedure or that co-purified proteins could be responsible for masking its N-terminal microsequence. Copyright © 2011 Elsevier Ltd. All rights reserved.

Assessing the work of medical audit advisory groups in promoting audit in general practice.

PubMed

Baker, R; Hearnshaw, H; Cooper, A; Cheater, F; Robertson, N

1995-12-01

Objectives--To determine the role of medical audit advisory groups in audit activities in general practice. Design--Postal questionnaire survey. Subjects--All 104 advisory groups in England and Wales in 1994. Main measures--Monitoring audit: the methods used to classify audits, the methods used by the advisory group to collect data on audits from general practices, the proportion of practices undertaking audit. Directing and coordinating audits: topics and number of practices participating in multipractice audits. Results--The response rate was 86-5%. In 1993-4, 54% of the advisory groups used the Oxfordshire or Kirklees methods for classifying audits, or modifications of them. 99% of the advisory groups collected data on audit activities at least once between 1991-2 and 1993-4. Visits, questionnaires, and other methods were used to collect information from all or samples of practices in each of the advisory group's areas. Some advisory groups used different methods in different years. In 1991-2, 57% of all practices participated in some audit, in 1992-3, 78%, and in 1993-4, 86%. 428 multipractice audits were identified. The most popular topic was diabetes. Conclusions--Advisory groups have been active in monitoring audit in general practice. However, the methods used to classify and collect information about audits in general practices varied widely. The number of practices undertaking audit increased between 1991-2 and 1993 1. The large number of multipractice audits supports the view that the advisory groups have directed and coordinated audit activities. This example of a national audit programme for general practice may be helpful in other countries in which the introduction of quality assurance is being considered.

Glutamate spillover modulates GABAergic synaptic transmission in the rat midbrain periaqueductal grey via metabotropic glutamate receptors and endocannabinoid signaling.

PubMed

Drew, Geoffrey M; Mitchell, Vanessa A; Vaughan, Christopher W

2008-01-23

Glutamate spillover regulates GABAergic synaptic transmission at several CNS synapses via presynaptic ionotropic and metabotropic glutamate receptors (mGluRs). We have previously demonstrated that activation of group I-III mGluRs inhibits GABAergic transmission in the midbrain periaqueductal gray (PAG), a region involved in organizing behavioral responses to threat, stress, and pain. Here, we examined the role of glutamate spillover in the modulation of GABAergic transmission in the PAG. Using whole-cell recordings from rat PAG slices, we found that evoked IPSCs were reduced by the nonspecific glutamate transport blockers DL-threo-beta-benzyloxyaspartic acid (TBOA) and L-trans-pyrrolidine-2,4-dicarboxylic acid, but not by the glial GLT1-specific blocker dihydrokainate. In contrast, TBOA had no effect on evoked IPSCs when glutamate uptake into the postsynaptic neuron was selectively impaired. TBOA increased the paired-pulse ratio of evoked IPSCs and reduced the rate but not the amplitude of spontaneous miniature IPSCs. The effect of TBOA on evoked IPSCs was abolished by the broad-spectrum mGluR antagonist (2S)-2-amino-2-[(1S,2S)-2-carboxycycloprop-1-yl]-3-(xanth-9-yl) propanoic acid (100 microM), reduced by the mGluR5-specific antagonist 2-methyl-6-(phenylethynyl)pyridine hydrochloride (MPEP) and mimicked by the mGluR1/5 agonist (RS)-3,5-dihydroxyphenylglycine (DHPG). Furthermore, the effects of both TBOA and DHPG were reduced by the cannabinoid CB1 receptor antagonist 1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-1-piperidinyl-1H-pyrazole-3-carboxamide (AM251). Finally, although MPEP and AM251 had no effect on single evoked IPSCs, they increased evoked IPSCs during repetitive stimulation. These results indicate that neuronal glutamate transporters limit mGluR5 activation and endocannabinoid signaling, but may be overwhelmed during conditions of elevated glutamate release. Thus, neuronal glutamate transporters play a key role in regulating endocannabinoid-mediated cross talk between glutamatergic and GABAergic synapses within the PAG.

CosmicSIG science and plans

NASA Astrophysics Data System (ADS)

Olinto, Angela V.

2014-03-01

Recent activities of the Cosmic Ray Science Interest Group (CosmicSIG) of the Physics of the Cosmos PAG will be reviewed. CosmicSIG was formed to provide an assessment to NASA HQ and the PCOS program office of the status of current and future missions in the area of cosmic-ray astrophysics. CosmicSIG also strives to act as a focal point and forum for the cosmic ray community.

Altered Excitability and Local Connectivity of mPFC-PAG Neurons in a Mouse Model of Neuropathic Pain.

PubMed

Cheriyan, John; Sheets, Patrick L

2018-05-16

The medial prefrontal cortex (mPFC) plays a major role in both sensory and affective aspects of pain. There is extensive evidence that chronic pain produces functional changes within the mPFC. However, our understanding of local circuit changes to defined subpopulations of mPFC neurons in chronic pain models remains unclear. A major subpopulation of mPFC neurons project to the periaqueductal gray (PAG), which is a key midbrain structure involved in endogenous pain suppression and facilitation. Here, we used laser scanning photostimulation of caged glutamate to map cortical circuits of retrogradely labeled cortico-PAG (CP) neurons in layer 5 (L5) of mPFC in brain slices prepared from male mice having undergone chronic constriction injury (CCI) of the sciatic nerve. Whole-cell recordings revealed a significant reduction in excitability for L5 CP neurons contralateral to CCI in the prelimbic (PL), but not infralimbic (IL), region of mPFC. Circuit mapping showed that excitatory inputs to L5 CP neurons in both PL and IL arose primarily from layer 2/3 (L2/3) and were significantly reduced in CCI mice. Glutamate stimulation of L2/3 and L5 elicited inhibitory inputs to CP neurons in both PL and IL, but only L2/3 input was significantly reduced in CP neurons of CCI mice. We also observed significant reduction in excitability and L2/3 inhibitory input to CP neurons ipsilateral to CCI. These results demonstrating region and laminar specific changes to mPFC-PAG neurons suggest that a unilateral CCI bilaterally alters cortical circuits upstream of the endogenous analgesic network, which may contribute to persistence of chronic pain. SIGNIFICANCE STATEMENT Chronic pain is a significant unresolved medical problem that is refractory to traditional analgesics and can negatively affect emotional health. The role of central circuits in mediating the persistent nature of chronic pain remains unclear. Local circuits within the medial prefrontal cortex (mPFC) process ascending pain inputs and can modulate endogenous analgesia via direct projections to the periaqueductal gray (PAG). However, the mechanisms by which chronic pain alters intracortical circuitry of mPFC-PAG neurons are unknown. Here, we report specific changes to local circuits of mPFC-PAG neurons in mice displaying chronic pain behavior after nerve injury. These findings provide evidence for a neural mechanism by which chronic pain disrupts the descending analgesic system via functional changes to cortical circuits. Copyright © 2018 the authors 0270-6474/18/384829-11$15.00/0.

45 CFR 1222.5 - Advisory group expenses.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 45 Public Welfare 4 2013-10-01 2013-10-01 false Advisory group expenses. 1222.5 Section 1222.5... SERVICE PARTICIPATION OF PROJECT BENEFICIARIES § 1222.5 Advisory group expenses. As permitted by law... group in connection with its responsibilities under § 1222.4. ...

45 CFR 1222.5 - Advisory group expenses.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 45 Public Welfare 4 2012-10-01 2012-10-01 false Advisory group expenses. 1222.5 Section 1222.5... SERVICE PARTICIPATION OF PROJECT BENEFICIARIES § 1222.5 Advisory group expenses. As permitted by law... group in connection with its responsibilities under § 1222.4. ...

45 CFR 1222.5 - Advisory group expenses.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 45 Public Welfare 4 2014-10-01 2014-10-01 false Advisory group expenses. 1222.5 Section 1222.5... SERVICE PARTICIPATION OF PROJECT BENEFICIARIES § 1222.5 Advisory group expenses. As permitted by law... group in connection with its responsibilities under § 1222.4. ...

45 CFR 1222.5 - Advisory group expenses.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 4 2010-10-01 2010-10-01 false Advisory group expenses. 1222.5 Section 1222.5... SERVICE PARTICIPATION OF PROJECT BENEFICIARIES § 1222.5 Advisory group expenses. As permitted by law... group in connection with its responsibilities under § 1222.4. ...

Nanoscale inhomogeneity and photoacid generation dynamics in extreme ultraviolet resist materials

NASA Astrophysics Data System (ADS)

Wu, Ping-Jui; Wang, Yu-Fu; Chen, Wei-Chi; Wang, Chien-Wei; Cheng, Joy; Chang, Vencent; Chang, Ching-Yu; Lin, John; Cheng, Yuan-Chung

2018-03-01

The development of extreme ultraviolet (EUV) lithography towards the 22 nm node and beyond depends critically on the availability of resist materials that meet stringent control requirements in resolution, line edge roughness, and sensitivity. However, the molecular mechanisms that govern the structure-function relationships in current EUV resist systems are not well understood. In particular, the nanoscale structures of the polymer base and the distributions of photoacid generators (PAGs) should play a critical roles in the performance of a resist system, yet currently available models for photochemical reactions in EUV resist systems are exclusively based on homogeneous bulk models that ignore molecular-level details of solid resist films. In this work, we investigate how microscopic molecular organizations in EUV resist affect photoacid generations in a bottom-up approach that describes structure-dependent electron-transfer dynamics in a solid film model. To this end, molecular dynamics simulations and stimulated annealing are used to obtain structures of a large simulation box containing poly(4-hydroxystyrene) (PHS) base polymers and triphenylsulfonium based PAGs. Our calculations reveal that ion-pair interactions govern the microscopic distributions of the polymer base and PAG molecules, resulting in a highly inhomogeneous system with nonuniform nanoscale chemical domains. Furthermore, the theoretical structures were used in combination of quantum chemical calculations and the Marcus theory to evaluate electron transfer rates between molecular sites, and then kinetic Monte Carlo simulations were carried out to model electron transfer dynamics with molecular structure details taken into consideration. As a result, the portion of thermalized electrons that are absorbed by the PAGs and the nanoscale spatial distribution of generated acids can be estimated. Our data reveal that the nanoscale inhomogeneous distributions of base polymers and PAGs strongly affect the electron transfer and the performance of the resist system. The implications to the performances of EUV resists and key engineering requirements for improved resist systems will also be discussed in this work. Our results shed light on the fundamental structure dependence of photoacid generation and the control of the nanoscale structures as well as base polymer-PAG interactions in EVU resist systems, and we expect these knowledge will be useful for the future development of improved EUV resist systems.

Neuroethological validation of an experimental apparatus to evaluate oriented and non-oriented escape behaviours: Comparison between the polygonal arena with a burrow and the circular enclosure of an open-field test.

PubMed

Biagioni, Audrey Francisco; dos Anjos-Garcia, Tayllon; Ullah, Farhad; Fisher, Isaac René; Falconi-Sobrinho, Luiz Luciano; de Freitas, Renato Leonardo; Felippotti, Tatiana Tocchini; Coimbra, Norberto Cysne

2016-02-01

Inhibition of GABAergic neural inputs to dorsal columns of the periaqueductal grey matter (dPAG), posterior (PH) and dorsomedial (DMH) hypothalamic nuclei elicits distinct types of escape behavioural reactions. To differentiate between the variety and intensity of panic-related behaviours, the pattern of defensive behaviours evoked by blockade of GABAA receptors in the DMH, PH and dPAG were compared in a circular open-field test and in a recently designed polygonal arena. In the circular open-field, the defensive behaviours induced by microinjection of bicuculline into DMH and PH were characterised by defensive alertness behaviour and vertical jumps preceded by rearing exploratory behaviour. On the other hand, explosive escape responses interspersed with horizontal jumps and freezing were observed after the blockade of GABAA receptors on dPAG neurons. In the polygonal arena apparatus, the escape response produced by GABAergic inhibition of DMH and PH neurons was directed towards the burrow. In contrast, the blockade of GABAA receptors in dPAG evoked non-oriented escape behaviour characterised by vigorous running and horizontal jumps in the arena. Our findings support the hypothesis that the hypothalamic nuclei organise oriented escape behavioural responses whereas non-oriented escape is elaborated by dPAG neurons. Additionally, the polygonal arena with a burrow made it easy to discriminate and characterise these two different patterns of escape behavioural responses. In this sense, the polygonal arena with a burrow can be considered a good methodological tool to discriminate between these two different patterns of escape behavioural responses and is very useful as a new experimental animal model of panic attacks. Copyright © 2015 Elsevier B.V. All rights reserved.

78 FR 78513 - Bank Secrecy Act Advisory Group; Solicitation of Application for Membership

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-26

... DEPARTMENT OF THE TREASURY Financial Crimes Enforcement Network Bank Secrecy Act Advisory Group; Solicitation of Application for Membership AGENCY: Financial Crimes Enforcement Network (``FinCEN''), Treasury... institutions and trade groups for membership on the Bank Secrecy Act Advisory Group. New members will be...

Early pregnancy diagnosis in sheep using near-infrared spectroscopy on blood plasma.

PubMed

Andueza, Donato; Alabart, José L; Lahoz, Belén; Muñoz, Fernando; Folch, José

2014-02-01

The objective of this study was to evaluate the ability of near-infrared reflectance spectroscopy (NIRS) to discriminate between pregnant and nonpregnant ewes in early stages of pregnancy after artificial insemination (AI) from blood plasma. Samples were collected using jugular puncture at 18 and 25 days after AI from 188 Rasa Aragonesa and Ansotana ewes. Plasma samples were analyzed for pregnancy-associated glycoprotein (PAG) and progesterone (P4) using ELISA commercial kits. The spectra of plasma samples were recorded in the visible and near-infrared ranges. The performance of these tests were compared, using as criterion standard the pregnancy status determined using transabdominal ultrasonography at 45 days after AI. Pregnancy rate was 47.9% (90/188). At Day 18, sensitivity was similar in NIRS and P4 tests (98.9% vs. 100%; not significant) and greater than PAG (32.2%; both P < 0.001). Specificity was similar in NIRS and PAG tests (both 100%) and greater than that of P4 (84.7%; P < 0.001). At Day 25, sensitivity and specificity of NIRS and PAG were both 100%. It can be concluded that NIRS was an accurate method of diagnosis of pregnancy at Days 18 and 25 after AI in ewes. Copyright © 2014 Elsevier Inc. All rights reserved.

National Space Council Users' Advisory Group

NASA Image and Video Library

2018-06-19

Users' Advisory Group member Faith Ozmen, CEO of the Sierra Nevada Corporation is seen durring the first meeting of the National Space Council Users' Advisory Group, Tuesday, June 19, 2018 at NASA Headquarters in Washington. The Users' Advisory Group will advise and inform the National Space Council on a broad range of aerospace topics, including the impacts of U.S. and international laws and regulations, national security space priorities, scientific and human space exploration priorities, and ways to bolster support. Photo Credit: (NASA/Joel Kowsky)

Morphine administration during low ovarian hormone stage results in transient over expression of fear memories in females.

PubMed

Perez-Torres, Emily M; Ramos-Ortolaza, Dinah L; Morales, Roberto; Santini, Edwin; Rios-Ruiz, Efrain J; Torres-Reveron, Annelyn

2015-01-01

Acute exposure to morphine after a traumatic event reduces trauma related symptoms in humans and conditioned fear expression in male rats. We aimed to determine whether acute administration of morphine alters consolidation of fear learning and extinction. Male and female rats in proestrus and metaestrus (high and low ovarian hormones respectively) underwent fear conditioning and received saline or morphine (2.5 mg/kg s.c.). The next day they underwent extinction. Results showed increased freezing during extinction only in the morphine metaestrus group while morphine did not affect males or proestrus females. Recall of extinction was similar on all groups. On a second experiment, a subset of rats conditioned during metaestrus was administered morphine prior to extinction producing no effects. We then measured mu opioid receptor (MOR) expression in the amygdala and periaqueductal gray (PAG) at the end of extinction (day 2). In males and proestrus females, morphine caused an increase in MOR in the amygdala but no in the PAG. In metaestrus females, morphine did not change MOR expression in either structure. These data suggests that ovarian hormones may interact with MORs in the amygdala to transiently alter memory consolidation. Morphine given after trauma to females with low ovarian hormones might increase the recall of fear responses, making recovery harder.

75 FR 23848 - Special Medical Advisory Group; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-04

... DEPARTMENT OF VETERANS AFFAIRS Special Medical Advisory Group; Notice of Meeting The Department of... Special Medical Advisory Group will meet on May 14, 2010, in Room 830 at VA Central Office, 810 Vermont... the Group is to advise the Secretary of Veterans Affairs and the Under Secretary for Health on the...

Plasma-anode electron gun

NASA Astrophysics Data System (ADS)

Santoru, Joseph; Schumacher, Robert W.; Gregoire, Daniel J.

1994-11-01

The plasma-anode electron gun (PAG) is an electron source in which the thermionic cathode is replaced with a cold, secondary-electron-emitting electrode. Electron emission is stimulated by bombarding the cathode with high-energy ions. Ions are injected into the high-voltage gap through a gridded structure from a plasma source (gas pressure less than or equal to 50 mTorr) that is embedded in the anode electrode. The gridded structure serves as both a cathode for the plasma discharge and as an anode for the PAG. The beam current is modulated at near ground potential by modulating the plasma source, eliminating the need for a high-voltage modulator system. During laboratory tests, the PAG has demonstrated square-wave, 17-microsecond-long beam pulses at 100 kV and 10 A, and it has operated stably at 70 kV and 2.5 A for 210 microsecond pulse lengths without gap closure.

Site-directed antibody immobilization using a protein A-gold binding domain fusion protein for enhanced SPR immunosensing.

PubMed

de Juan-Franco, Elena; Caruz, Antonio; Pedrajas, J R; Lechuga, Laura M

2013-04-07

We have implemented a novel strategy for the oriented immobilization of antibodies onto a gold surface based on the use of a fusion protein, the protein A-gold binding domain (PAG). PAG consists of a gold binding peptide (GBP) coupled to the immunoglobulin-binding domains of staphylococcal protein A. This fusion protein provides an easy and fast oriented immobilization of antibodies preserving its native structure, while leaving the antigen binding sites (Fab) freely exposed. Using this immobilization strategy, we have demonstrated the performance of the immunosensing of the human Growth Hormone by SPR. A limit of detection of 90 ng mL(-1) was obtained with an inter-chip variability lower than 7%. The comparison of this method with other strategies for the direct immobilization of antibodies over gold surfaces has showed the enhanced sensitivity provided by the PAG approach.

Creating the Southern Region 4-H Volunteer Advisory Group

ERIC Educational Resources Information Center

Culp, Ken, III; Edwards, Harriett C.; Jordan, Jenny W.

2014-01-01

The SR4-HVAG combines the efforts of states to provide quality educational programming for volunteers and Extension professionals using an advisory group system. An advisory group rather than a council was created because the group provides programmatic input rather than sets policy. The purposes of the SR4-HVAG are to: provide a mechanism for…

78 FR 10618 - Re-Establishment of the Advisory Group on Prevention, Health Promotion, and Integrative and...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-14

..., Health Promotion, and Integrative and Public Health AGENCY: Office of the Assistant Secretary for Health..., Health Promotion, and Integrative and Public Health (hereafter referred to as ``the Advisory Group... Advisory Group provides recommendations and advice to the National Prevention, Health Promotion, and Public...

75 FR 48723 - Meeting Announcement: Neotropical Migratory Bird Conservation Advisory Group

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-11

...] Meeting Announcement: Neotropical Migratory Bird Conservation Advisory Group AGENCY: Fish and Wildlife... Bird Conservation Act (NMBCA) grants program (Advisory Group) will meet in person and via conference...: Recognizing the importance of conserving migratory birds, the U.S. Congress passed the NMBCA (Pub. L. 106-247...

75 FR 70971 - Special Medical Advisory Group; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-19

... DEPARTMENT OF VETERANS AFFAIRS Special Medical Advisory Group; Notice of Meeting The Department of... Special Medical Advisory Group will meet on December 1, 2010, in Room 830 at VA Central Office, 810... on the Blue Ribbon Panel on VA-Medical School Affiliations Report. Any member of the public wishing...

78 FR 67436 - Defense Trade Advisory Group; Notice of Open Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-12

... DEPARTMENT OF STATE [Public Notice 8515] Defense Trade Advisory Group; Notice of Open Meeting AGENCY: Department of State. ACTION: Notice of meeting. SUMMARY: The Defense Trade Advisory Group (DTAG.... Specific agenda topics will be posted on the Directorate of Defense Trade Controls Web site, at www.pmddtc...

78 FR 71022 - Defense Trade Advisory Group; Notice of Open Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-27

... DEPARTMENT OF STATE [Public Notice 8534] Defense Trade Advisory Group; Notice of Open Meeting AGENCY: Department of State. ACTION: Notice of meeting. SUMMARY: The Defense Trade Advisory Group (DTAG... consequences of the Export Control Reform Initiatives on industry and provide recommendation on how to overcome...

Spatiotemporal control of synergistic gel disintegration consisting of boroxole- and glyco-based polymers via photoinduced proton transfer.

PubMed

Kotsuchibashi, Yohei; Ebara, Mitsuhiro; Sato, Takeshi; Wang, Yinan; Rajender, Rajender; Hall, Dennis G; Narain, Ravin; Aoyagi, Takao

2015-02-12

We demonstrate here a local- and remote-control of gel disintegration by using photoinduced proton transfer chemistry of photoacid generator (PAG). The gels were prepared by simply mixing two polymers, poly(N-isopropylacrylamide-co-5-methacrylamido-1,2-benzoxaborole) (P(NIPAAm-co-MAAmBO)) and poly(3-gluconamidopropyl methacrylamide) (PGAPMA) via the synergistic interaction of benzoxaborole and diol groups. The o-nitrobenzaldehyde (o-NBA) was then loaded into the gel as a PAG. The benzoxaborole-diol interaction was successfully disintegrated upon UV irradiation due to the local pH decrease inside the gel. When the gel was irradiated to a specific gel region, the synergistic interactions were disintegrated only at the exposed region. Of special interest is that the whole material eventually transitioned from gel to sol state, as the generated protons diffused gradually toward the nonilluminated region. The ability of the proposed gel-sol transition system via photoinduced proton diffusion may be beneficial for not only prompt pH changes within the gel but also the design of predictive and programmable devices for drug delivery.

76 FR 52642 - Notice of Advisory Committee Closed Meeting; U.S. Strategic Command Strategic Advisory Group

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-23

... DEPARTMENT OF DEFENSE Notice of Advisory Committee Closed Meeting; U.S. Strategic Command.... Strategic Command Strategic Advisory Group. DATES: November 1, 2011, from 8 a.m. to 5 p.m. and November 2..., intelligence, and policy-related issues to the Commander, U.S. Strategic Command, during the development of the...

A randomized controlled trial to test the efficacy of the SCI Get Fit Toolkit on leisure-time physical activity behaviour and social-cognitive processes in adults with spinal cord injury.

PubMed

Arbour-Nicitopoulos, Kelly P; Sweet, Shane N; Lamontagne, Marie-Eve; Ginis, Kathleen A Martin; Jeske, Samantha; Routhier, François; Latimer-Cheung, Amy E

2017-01-01

Single blind, two-group randomized controlled trial. To evaluate the efficacy of the SCI Get Fit Toolkit delivered online on theoretical constructs and moderate-to-vigorous physical activity (MVPA) among adults with SCI. Ontario and Quebec, Canada. Inactive, English- and French-speaking Canadian adults with traumatic SCI with Internet access, and no self-reported cognitive or memory impairments. Participants ( N =90 M age =48.12±11.29 years; 79% male) were randomized to view the SCI Get Fit Toolkit or the Physical Activity Guidelines for adults with SCI (PAG-SCI) online. Primary (intentions) and secondary (outcome expectancies, self-efficacy, planning and MVPA behaviour) outcomes were assessed over a 1-month period. Of the 90 participants randomized, 77 were included in the analyses. Participants viewed the experimental stimuli only briefly, reading the 4-page toolkit for approximately 2.5 min longer than the 1-page guideline document. No condition effects were found for intentions, outcome expectancies, self-efficacy, and planning (ΔR 2 ⩽0.03). Individuals in the toolkit condition were more likely to participate in at least one bout of 20 min of MVPA behaviour at 1-week post-intervention compared to individuals in the guidelines condition (OR=3.54, 95% CI=0.95, 13.17). However, no differences were found when examining change in weekly minutes of MVPA or comparing whether participants met the PAG-SCI. No firm conclusions can be made regarding the impact of the SCI Get Fit Toolkit in comparison to the PAG-SCI on social cognitions and MVPA behaviour. The limited online access to this resource may partially explain these null findings.

The neural mobilization technique modulates the expression of endogenous opioids in the periaqueductal gray and improves muscle strength and mobility in rats with neuropathic pain

PubMed Central

2014-01-01

Background The neural mobilization (NM) technique is a noninvasive method that has been proven to be clinically effective in reducing pain; however, the molecular mechanisms involved remain poorly understood. The aim of this study was to analyze whether NM alters the expression of the mu-opioid receptor (MOR), the delta-opioid receptor (DOR) and the Kappa-opioid receptor (KOR) in the periaqueductal gray (PAG) and improves locomotion and muscle force after chronic constriction injury (CCI) in rats. Methods The CCI was imposed on adult male rats followed by 10 sessions of NM every other day, starting 14 days after the CCI injury. At the end of the sessions, the PAG was analyzed using Western blot assays for opioid receptors. Locomotion was analyzed by the Sciatic functional index (SFI), and muscle force was analyzed by the BIOPAC system. Results An improvement in locomotion was observed in animals treated with NM compared with injured animals. Animals treated with NM showed an increase in maximal tetanic force of the tibialis anterior muscle of 172% (p < 0.001) compared with the CCI group. We also observed a decrease of 53% (p < 0.001) and 23% (p < 0.05) in DOR and KOR levels, respectively, after CCI injury compared to those from naive animals and an increase of 17% (p < 0.05) in KOR expression only after NM treatment compared to naive animals. There were no significant changes in MOR expression in the PAG. Conclusion These data provide evidence that a non-pharmacological NM technique facilitates pain relief by endogenous analgesic modulation. PMID:24884961

Energetics of side-chain partitioning of β-signal residues in unassisted folding of a transmembrane β-barrel protein

PubMed Central

Iyer, Bharat Ramasubramanian; Zadafiya, Punit; Vetal, Pallavi Vijay

2017-01-01

The free energy of water-to-interface amino acid partitioning is a major contributing factor in membrane protein folding and stability. The interface residues at the C terminus of transmembrane β-barrels form the β-signal motif required for assisted β-barrel assembly in vivo but are believed to be less important for β-barrel assembly in vitro. Here, we experimentally measured the thermodynamic contribution of all 20 amino acids at the β-signal motif to the unassisted folding of the model β-barrel protein PagP. We obtained the partitioning free energy for all 20 amino acids at the lipid-facing interface (ΔΔG0w,i(φ)) and the protein-facing interface (ΔΔG0w,i(π)) residues and found that hydrophobic amino acids are most favorably transferred to the lipid-facing interface, whereas charged and polar groups display the highest partitioning energy. Furthermore, the change in non-polar surface area correlated directly with the partitioning free energy for the lipid-facing residue and inversely with the protein-facing residue. We also demonstrate that the interface residues of the β-signal motif are vital for in vitro barrel assembly, because they exhibit a side chain–specific energetic contribution determined by the change in nonpolar accessible surface. We further establish that folding cooperativity and hydrophobic collapse are balanced at the membrane interface for optimal stability of the PagP β-barrel scaffold. We conclude that the PagP C-terminal β-signal motif influences the folding cooperativity and stability of the folded β-barrel and that the thermodynamic contributions of the lipid- and protein-facing residues in the transmembrane protein β-signal motif depend on the nature of the amino acid side chain. PMID:28592485

Effects of (S)-3,4-DCPG, an mGlu8 receptor agonist, on inflammatory and neuropathic pain in mice.

PubMed

Marabese, I; de Novellis, V; Palazzo, E; Scafuro, M A; Vita, D; Rossi, F; Maione, S

2007-02-01

In this study, the effect of (S)-3,4-dicarboxyphenylglycine (DCPG), a selective mGlu8 receptor agonist, has been investigated in inflammatory and neuropathic pain models in order to elucidate the role of mGlu8 receptor in modulating pain perception. Inflammatory pain was induced by the peripheral injection of formalin or carrageenan in awake mice. Systemic administration of (S)-3,4-DCPG, performed 15 min before formalin, decreased both early and delayed nociceptive responses of the formalin test. When this treatment was carried out 15 min after the peripheral injection of formalin it still reduced the late hyperalgesic phase. Similarly, systemic (S)-3,4-DCPG reduced carrageenan-induced thermal hyperalgesia and mechanical allodynia when administered 15 min before carrageenan, but no effect on pain behaviour was observed when (S)-3,4-DCPG was given after the development of carrageenan-induced inflammatory pain. When microinjected into the lateral PAG (RS)-alpha-methylserine-O-phoshate (MSOP), a group III receptor antagonist, antagonised the analgesic effect induced by systemic administration of (S)-3,4-DCPG in both of the inflammatory pain models. Intra-lateral PAG (S)-3,4-DCPG reduced pain behaviour when administered 10 min before formalin or carrageenan; both the effects were blocked by intra-lateral PAG MSOP. (S)-3,4-DCPG was ineffective in alleviating thermal hyperalgesia and mechanical allodynia 7 days after the chronic constriction injury of the sciatic nerve, whereas it proved effective 3 days after surgery. Taken together these results suggest that stimulation of mGlu8 receptors relieve formalin and carrageenan-induced hyperalgesia in inflammatory pain, whereas it would seem less effective in established inflammatory or neuropathic pain.

77 FR 6796 - Notification of Three Public Teleconferences of a Work Group of the Chartered Science Advisory Board

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-09

... Work Group of the Chartered Science Advisory Board AGENCY: Environmental Protection Agency (EPA... teleconferences of a work group of the Chartered Science Advisory Board to discuss the President's FY 2013 Budget...), 5 U.S.C., App. 2. Pursuant to FACA and EPA policy, notice is hereby given that a work group of the...

Laterally Versus Medially Projecting Spinothalamic Neurons and their Axon Collaterals to the Periaqueductal Gray and Medullary Reticular Formation in the Rat

DTIC Science & Technology

1987-06-30

nucleus reticularis gigantocellularis. No distinct tracts were reported in the brainstem as far rostral as the superior olivary complex. At the level...that stimulation of the PAG 12 activates neurons which project to the MRF, specifically the nucleus reticularis gigantocellularis, nucleus ... reticularis magnocellularis and the nucleus raphe magnus. Neurons in the raphe magnus receive convergent input from the PAG and other MRF regions and, via

TECHNOLOGY TRANSFER TO U.S. INDEPENDENT OIL AND NATURAL GAS PRODUCERS

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

Unknown

2000-11-01

The Petroleum Technology Transfer Council (PTTC) continued pursuing its mission of helping U.S. independent oil and gas producers make timely, informed technology decisions during Fiscal Year 2000 (FY00). Functioning as a cohesive national organization, PTTC has active grassroots programs through its ten Regional Lead Organizations (RLOs) who bring research and academia to the table via their association with geological surveys and engineering departments. The regional directors connect with independent oil and gas producers through technology workshops, resource centers, websites, newsletters, various technical publications and other outreach efforts. These are guided by regional Producer Advisory Groups (PAGs), who are area operatorsmore » and service companies working with the Regional Lead Organizations. The role of the national headquarters (HQ) staff includes planning and managing the PTTC program, conducting nation-wide technology transfer activities, and implementing a comprehensive communications effort. The organization effectively combines federal, state, and industry funding to achieve important goals for all of these sectors. This integrated funding base, combined with industry volunteers guiding PTTC's activities and the dedication of national and regional staff, are achieving notable results. PTTC is increasingly recognized as a critical resource for information and access to technologies, especially for smaller companies. This technical progress report summarizes PTTC's accomplishments during FY00, which lays the groundwork for further growth in the future. At a time of many industry changes and market movements, the organization has built a reputation and expectation to address industry needs of getting information distributed quickly which can impact the bottom line immediately.« less

78 FR 29787 - ALPS ETF Trust, et al.;

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-21

... under common control with the Fund of Funds Sub-Adviser (``Fund of Funds Sub-Advisory Group''). 12...) Relief 1. The members of the Fund of Funds Advisory Group will not control (individually or in the...-Advisory Group will not control (individually or in the aggregate) a Fund within the meaning of section 2(a...

76 FR 66775 - Defense Trade Advisory Group; Notice of Open Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-27

... DEPARTMENT OF STATE [Public Notice: 7666] Defense Trade Advisory Group; Notice of Open Meeting Summary: The Defense Trade Advisory Group (DTAG) will meet in open session from 1 p.m. until 4 p.m. on Wednesday, November 9, 2011, in the East Auditorium, U.S. Department of State, Harry S. Truman Building...

A Bayesian latent class model to estimate the accuracy of pregnancy diagnosis by transrectal ultrasonography and laboratory detection of pregnancy-associated glycoproteins in dairy cows.

PubMed

Fosgate, G T; Motimele, B; Ganswindt, A; Irons, P C

2017-09-15

Accurate diagnosis of pregnancy is an essential component of an effective reproductive management plan for dairy cattle. Indirect methods of pregnancy detection can be performed soon after breeding and offer an advantage over traditional direct methods in not requiring an experienced veterinarian and having potential for automation. The objective of this study was to estimate the sensitivity and specificity of pregnancy-associated glycoprotein (PAG) detection ELISA and transrectal ultrasound (TRUS) in dairy cows of South Africa using a Bayesian latent class approach. Commercial dairy cattle from the five important dairy regions in South Africa were enrolled in a short-term prospective cohort study. Cattle were examined at 28-35days after artificial insemination (AI) and then followed up 14days later. At both sampling times, TRUS was performed to detect pregnancy and commercially available PAG detection ELISAs were performed on collected serum and milk. A total of 1236 cows were sampled and 1006 had complete test information for use in the Bayesian latent class model. The estimated sensitivity (95% probability interval) and specificity for PAG detection serum ELISA were 99.4% (98.5, 99.9) and 97.4% (94.7, 99.2), respectively. The estimated sensitivity and specificity for PAG detection milk ELISA were 99.2% (98.2, 99.8) and 93.4% (89.7, 96.1), respectively. Sensitivity of veterinarian performed TRUS at 28-35days post-AI varied between 77.8% and 90.5% and specificity varied between 94.7% and 99.8%. In summary, indirect detection of pregnancy using PAG ELISA is an accurate method for use in dairy cattle. The method is descriptively more sensitive than veterinarian-performed TRUS and therefore could be an economically viable addition to a reproductive management plan. Copyright © 2017 Elsevier B.V. All rights reserved.

Neuropeptide glutamic acid-isoleucine (NEI)-induced paradoxical sleep in rats.

PubMed

Fujimoto, Moe; Fukuda, Satoru; Sakamoto, Hidetoshi; Takata, Junko; Sawamura, Shigehito

2017-01-01

Neuropeptideglutamic acid-isoleucine (NEI) as well as melanin concentrating hormone (MCH) is cleaved from the 165 amino acid protein, prepro-melanin concentrating hormone (prepro-MCH). Among many physiological roles of MCH, we demonstrated that intracerebroventricular (icv) injection of MCH induced increases in REM sleep episodes as well as in non REM sleep episodes. However, there are no studies on the effect of NEI on the sleep-wake cycle. As for the sites of action of MCH for induction of REM sleep, the ventrolateral periaqueductal gray (vlPAG) has been reported to be one of its site of action. Although MCH neurons contain NEI, GABA, MCH, and other neuropeptides, we do not know which transmitter(s) might induce REM sleep by acting on the vlPAG. Thus, we first examined the effect of icv injection of NEI on the sleep-wake cycle, and investigated how microinjection of either NEI, MCH, or GABA into the vlPAG affected REM sleep in rats. Icv injection of NEI (0.61μg/5μl: n=7) significantly increased the time spent in REM episodes compared to control (saline: 5μl; n=6). Microinjection of either NEI (61ng/0.2μl: n=7), MCH (100ng/0.2μl: n=6) or GABA (250mM/0.2μl: n=7) into the vlPAG significantly increased the time spent in REM episodes and the AUC. Precise hourly analysis of REM sleep also revealed that after those microinjections, NEI and MCH increased REM episodes at the latter phase, compared to GABA which increased REM episodes at the earlier phase. This result suggests that NEI and MCH may induce sustained REM sleep, while GABA may initiate REM sleep. In conclusion, our findings demonstrate that NEI, a cleaved peptide from the same precursor, prepro-MCH, as MCH, induce REM sleep at least in part through acting on the vlPAG. Copyright © 2016 Elsevier Inc. All rights reserved.

Unraveling the role of secondary electrons upon their interaction with photoresist during EUV exposure

NASA Astrophysics Data System (ADS)

Pollentier, Ivan; Vesters, Yannick; Jiang, Jing; Vanelderen, Pieter; de Simone, Danilo

2017-10-01

The interaction of 91.6eV EUV photons with photoresist is very different to that of optical lithography at DUV wavelength. The latter is understood quite well and it is known that photons interact with the resist in a molecular way through the photoacid generator (PAG) of the chemically amplified resist (CAR). In EUV however, the high energy photons interact with the matter on atomic scale, resulting in the generation of secondary electrons. It is believed that these secondary electrons in their turn are responsible in chemical modification and lead to switching reactions that enable resist local dissolution. However, details of the interaction are still unclear, e.g. which reaction an electron with a given energy can initiate. In this work we have introduced a method to measure the chemical interaction of the secondary electrons with the EUV resist. The method is based on electron gun exposures of low energy electrons (range 1eV to 80eV) in the photoresist. The chemical interaction is then measured by Residual Gas Analysis (RGA), which can analyze out of the outgassing which and how much reaction products are generated. In this way a `chemical yield' can be quantified as function of electron energy. This method has been successfully applied to understand the interaction of secondary electrons on the traditional CAR materials. The understanding was facilitated by testing different compositions of an advanced EUV CAR, where resp. polymer only, polymer+PAG, and polymer+PAG+quencher are tested with the electron gun. It was found that low energy electrons down to 3-4eV can activate PAG dissociation, which can lead to polymer deprotection. However it was observed too that energy electrons of 12eV and higher can do direct deprotection even in absence of the PAG. In addition, testing suggests that electrons can generate also other chemical changes on the polymer chain that could lead to cross-linking.

IL-17 is not essential for inflammation and chronic pelvic pain development in an experimental model of chronic prostatitis/chronic pelvic pain syndrome.

PubMed

Motrich, Ruben D; Breser, María L; Sánchez, Leonardo R; Godoy, Gloria J; Prinz, Immo; Rivero, Virginia E

2016-03-01

Pain and inflammation in the absence of infection are hallmarks in chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS) patients. The etiology of CP/CPPS is unclear, and autoimmunity has been proposed as a cause. Experimental autoimmune prostatitis (EAP) models have long been used for studying CP/CPPS. Herein, we studied prostate inflammation induction and chronic pelvic pain development in EAP using IL-12p40-KO, IL-4-KO, IL-17-KO, and wild-type (C57BL/6) mice. Prostate antigen (PAg) immunization in C57BL/6 mice induced specific Th1 and Th17 immune responses and severe prostate inflammation and cell infiltration, mainly composed of CD4 T cells and macrophages. Moreover, chronic pelvic pain was evidenced by increased allodynia responses. In immunized IL-17-KO mice, the presence of a prominent PAg-specific Th1 immune response caused similar prostate inflammation and chronic pelvic pain. Furthermore, markedly high PAg-specific Th1 immune responses, exacerbated prostate inflammation, and chronic pelvic pain were detected in immunized IL-4-KO mice. Conversely, immunized IL-12p40-KO mice developed PAg-specific Th2 immune responses, characterized by high IL-4 secretion and neither infiltration nor damage in the prostate. As observed in wild-type control animals, IL12p40-KO mice did not evidence tactile allodynia responses. Our results suggest that, as in patients, chronic pelvic pain is a consequence of prostate inflammation. After PAg immunization, a Th1-associated immune response develops and induces prostate inflammation and chronic pelvic pain. The absence of Th1 or Th2 cytokines, respectively, diminishes or enhances EAP susceptibility. In addition, IL-17 showed not to be essential for pathology induction and chronic pelvic pain development.

78 FR 66086 - DBX ETF Trust, et al.; Notice of Application

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-04

... common control with the Fund of Funds Sub-Adviser (``Fund of Funds Sub-Advisory Group''). 12. Applicants... members of the Fund of Funds Advisory Group will not control (individually or in the aggregate) a Fund (or... of Funds Sub-Advisory Group will not control (individually or in the aggregate) a Fund (or its...

77 FR 67438 - Defense Trade Advisory Group; Notice of Open Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-09

... DEPARTMENT OF STATE [Public Notice 8084] Defense Trade Advisory Group; Notice of Open Meeting SUMMARY: The Defense Trade Advisory Group (DTAG) will meet in open session from 1:00 p.m. until 5:00 p.m. on Wednesday, November 28, 2012, in the East Auditorium, U.S. Department of State, Harry S. Truman...

76 FR 16652 - Defense Trade Advisory Group; Notice of Open Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-24

... DEPARTMENT OF STATE [Public Notice 7328] Defense Trade Advisory Group; Notice of Open Meeting Summary: The Defense Trade Advisory Group (DTAG) will meet in open session from 10 a.m. to 1:30 p.m. on Tuesday, May 3, 2011, in the Dean Acheson Auditorium at the U.S. Department of State, Harry S. Truman...

Advisory Groups to Encourage Collaboration: A Case Study

ERIC Educational Resources Information Center

Stephens, Lisa A.; Glynn, Graham; Lavallee, David; Moreau, Joseph; Orzech, Mary Jo; Pence, Harry E.

2011-01-01

This article is a case study of how the provost and senior executive leadership of one large university system capitalized on a long-standing advisory group as a tool to support communication and collaboration across a broad constituency. These advisory efforts help guide both future directions and investment. It is the story of how this group has…

Shipboard Sewage Treatment System for Great Lakes Vessels

DTIC Science & Technology

1979-09-01

practical and economical method available today for large-scale 03 production is by the electrical, or corona , discharge principle. 7 In this method...2-L2 corona generator.* It required a standard, grounded 120-V, 10-A, 60-Hz electrical source for power. Compressed air at 75 psig (517 kPag) for the...from 50 to 100 psig (340 to 690 kPag). Electrical power supplied to the corona cell was adjusted manually with a variable resistor. In general, for a

Mechanisms of EUV exposure: electrons and holes

NASA Astrophysics Data System (ADS)

Narasimhan, Amrit; Grzeskowiak, Steven; Ackerman, Christian; Flynn, Tracy; Denbeaux, Greg; Brainard, Robert L.

2017-03-01

In extreme ultraviolet (EUV) lithography, 92 eV photons are used to expose photoresists. Current EUV photoresists are composed of photoacid generators (PAGs) in polymer matrices. Secondary electrons (2 - 80 eV) created in resists during EUV exposure play large role in acid-production. There are several proposed mechanisms for electron-resist interactions: internal excitation, electron trapping, and hole-initiated chemistry. Here, we will address two central questions in EUV resist research: (1) How many electrons are generated per EUV photon absorption? (2) By which mechanisms do these electrons interact and react with molecules in the resist? We will use this framework to evaluate the contributions of electron trapping and hole initiated chemistry to acid production in chemically amplified photoresists, with specific emphasis on the interdependence of these mechanisms. We will show measurements of acid yield from direct bulk electrolysis of PAGs and EUV exposures of PAGs in phenolic and nonphenolic polymers to narrow down the mechanistic possibilities in chemically amplified resists.

Results of the independent verification of radiological remedial action at 16 East 5th South Street, Monticello, Utah (MS00075)

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

Wilson, M.J.; Crutcher, J.W.

1991-07-01

In 1980 the site of a vanadium and uranium mill at Monticello, Utah, was accepted into the US Department of Energy's (DOE's) Surplus Facilities Management Program, with the objectives of restoring the government-owned mill site to safe levels of radioactivity, disposing of or containing the tailings in an environmentally safe manner, and performing remedial actions on off-site (vicinity) properties that had been contaminated by radioactive material resulting from mill operations. During 1984 UNC Geotech, the remedial action contractor designated by DOE, performed remedial action on the vicinity property at 16 East 5th South Street, Monticello, Utah. The Pollutant Assessments Groupmore » (PAG) of Oak Ridge National Laboratory was assigned the responsibility of verifying the data supporting the adequacy of remedial action and confirming the site's compliance with DOE guidelines. The PAG found that the site successfully meets the DOE remedial action objectives. Procedures used by PAG are described. 3 refs., 2 tabs.« less

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

Fedynyshyn, J.P.

The opioid binding characteristics of the rat (PAG) and the signal transduction mechanisms of the opioid receptors were examined with in vitro radioligand binding, GTPase, adenylyl cyclase, and inositol phosphate assays. The nonselective ligand {sup 3}H-ethylketocyclazocine (EKC), the {mu} and {delta} selective ligand {sup 3}H-(D-Ala{sup 2}, D-Leu{sup 5}) enkephalin (DADLE), the {mu} selective ligand {sup 3}H-(D-Ala{sup 2}, N-methyl Phe{sup 4}, Glyol{sup 5}) enkephalin (DAGO), and the {delta} selective ligand {sup 3}H-(D-Pen{sup 2}, D-Pen{sup 5}) enkephalin (DPDPE) were separately used as tracer ligands to label opioid binding sites in rat PAG enriched P{sub 2} membrane in competition with unlabeled DADLE, DAGO,more » DPDPE, or the {kappa} selective ligand trans-3,4-dichloro-N-(2-(1-pyrrolidinyl)cyclohexyl)benzeneacetamide, methane sulfonate, hydrate (U50, 488H). Only {mu} selective high affinity opioid binding was observed. No high affinity {delta} or {kappa} selective binding was detected. {sup 3}H-DAGO was used as a tracer ligand to label {mu} selective high affinity opioid binding sites in PAG enriched P{sub 2} membrane in competition with unlabeled {beta}-endorphin, dynorphin A (1-17), BAM-18, methionine enkephalin, dynorphin A (1-8), and leucine enkephalin. Of these endogenous opioid peptides only those with previously reported high affinity {mu} type opioid binding activity competed with {sup 3}H-DAGO for binding sites in rat PAG enriched P{sub 2} membrane with affinities similar to that of unlabeled DAGO.« less

NMD3 regulates both mRNA and rRNA nuclear export in African trypanosomes via an XPOI-linked pathway

PubMed Central

Bühlmann, Melanie; Walrad, Pegine; Rico, Eva; Ivens, Alasdair; Capewell, Paul; Naguleswaran, Arunasalam; Roditi, Isabel; Matthews, Keith R.

2015-01-01

Trypanosomes mostly regulate gene expression through post-transcriptional mechanisms, particularly mRNA stability. However, much mRNA degradation is cytoplasmic such that mRNA nuclear export must represent an important level of regulation. Ribosomal RNAs must also be exported from the nucleus and the trypanosome orthologue of NMD3 has been confirmed to be involved in rRNA processing and export, matching its function in other organisms. Surprisingly, we found that TbNMD3 depletion also generates mRNA accumulation of procyclin-associated genes (PAGs), these being co-transcribed by RNA polymerase I with the procyclin surface antigen genes expressed on trypanosome insect forms. By whole transcriptome RNA-seq analysis of TbNMD3-depleted cells we confirm the regulation of the PAG transcripts by TbNMD3 and using reporter constructs reveal that PAG1 regulation is mediated by its 5′UTR. Dissection of the mechanism of regulation demonstrates that it is not dependent upon translational inhibition mediated by TbNMD3 depletion nor enhanced transcription. However, depletion of the nuclear export factors XPO1 or MEX67 recapitulates the effects of TbNMD3 depletion on PAG mRNAs and mRNAs accumulated in the nucleus of TbNMD3-depleted cells. These results invoke a novel RNA regulatory mechanism involving the NMD3-dependent nuclear export of mRNA cargos, suggesting a shared platform for mRNA and rRNA export. PMID:25873624

Antioxidant proteins TSA and PAG interact synergistically with Presenilin to modulate Notch signaling in Drosophila.

PubMed

Wangler, Michael F; Reiter, Lawrence T; Zimm, Georgianna; Trimble-Morgan, Jennifer; Wu, Jane; Bier, Ethan

2011-07-01

Alzheimer's disease (AD) pathogenesis is characterized by senile plaques in the brain and evidence of oxidative damage. Oxidative stress may precede plaque formation in AD; however, the link between oxidative damage and plaque formation remains unknown. Presenilins are transmembrane proteins in which mutations lead to accelerated plaque formation and early-onset familial Alzheimer's disease. Presenilins physically interact with two antioxidant enzymes thiol-specific antioxidant (TSA) and proliferation-associated gene (PAG) of the peroxiredoxin family. The functional consequences of these interactions are unclear. In the current study we expressed a presenilin transgene in Drosophila wing and sensory organ precursors of the fly. This caused phenotypes typical of Notch signaling loss-of-function mutations. We found that while expression of TSA or PAG alone produced no phenotype, co-expression of TSA and PAG with presenilin led to an enhanced Notch loss-of-function phenotype. This phenotype was more severe and more penetrant than that caused by the expression of Psn alone. In order to determine whether these phenotypes were indeed affecting Notch signaling, this experiment was performed in a genetic background carrying an activated Notch (Abruptex) allele. The phenotypes were almost completely rescued by this activated Notch allele. These results link peroxiredoxins with the in vivo function of Presenilin, which ultimately connects two key pathogenetic mechanisms in AD, namely, antioxidant activity and plaque formation, and raises the possibility of a role for peroxiredoxin family members in Alzheimer's pathogenesis.

OCLC and Its Advisory Committees.

ERIC Educational Resources Information Center

Baker, Shirley K.

1998-01-01

Describes the Online Computer Library Center (OCLC) advisory committees in terms of research, public, college and university, and special libraries. All four of the type-of-library advisory groups work to shape OCLC policies and programs, according to the particular needs of each group. OCLC's financial and programmatic success depends upon…

ENHANCING RESERVOIR MANAGEMENT IN THE APPALACHIAN BASIN BY IDENTIFYING TECHNICAL BARRIER AND PREFERRED PRACTICES

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

Ronald R. McDowell; Khashayar Aminian; Katharine L. Avary

2003-09-01

The Preferred Upstream Management Practices (PUMP) project, a two-year study sponsored by the United States Department of Energy (USDOE), had three primary objectives: (1) the identification of problems, problematic issues, potential solutions and preferred practices related to oil production; (2) the creation of an Appalachian Regional Council to oversee and continue this investigation beyond the end of the project; and (3) the dissemination of investigative results to the widest possible audience, primarily by means of an interactive website. Investigation and identification of oil production problems and preferred management practices began with a Problem Identification Workshop in January of 2002. Threemore » general issues were selected by participants for discussion: Data Management; Reservoir Engineering; and Drilling Practices. At the same meeting, the concept of the creation of an oversight organization to evaluate and disseminated preferred management practices (PMP's) after the end of the project was put forth and volunteers were solicited. In-depth interviews were arranged with oil producers to gain more insight into problems and potential solutions. Project members encountered considerable reticence on the part of interviewees when it came to revealing company-specific production problems or company-specific solutions. This was the case even though interviewees were assured that all responses would be held in confidence. Nevertheless, the following production issues were identified and ranked in order of decreasing importance: Water production including brine disposal; Management of production and business data; Oil field power costs; Paraffin accumulation; Production practices including cementing. An number of secondary issues were also noted: Problems associated with Enhanced Oil Recovery (EOR) and Waterflooding; Reservoir characterization; Employee availability, training, and safety; and Sale and Purchase problems. One item was mentioned both in interviews and in the Workshop, as, perhaps, the key issue related to oil production in the Appalachian region - the price of a barrel of oil. Project members sought solutions to production problems from a number of sources. In general, the Petroleum Technology Transfer Council (PTTC) website, both regional and national, proved to be a fertile source of information. Technical issues included water production, paraffin accumulation, production practices, EOR and waterflooding were addressed in a number of SPE papers. Articles on reservoir characterization were found in both the AAPG Bulletin and in SPE papers. Project members extracted topical and keyword information from pertinent articles and websites and combined them in a database that was placed on the PUMP website. Because of difficulties finding potential members with the qualifications, interests, and flexibility of schedule to allow a long-term commitment, it was decided to implement the PMP Regional Council as a subcommittee of the Producer Advisory Group (PAG) sponsored by Appalachian Region PTTC. The advantages of this decision are that the PAG is in already in existence as a volunteer group interested in problem identification and implementation of solutions and that PAG members are unpaid, so no outside funds will be required to sustain the group. The PUMP website became active in October of 2002. The site is designed to evolve; as new information becomes available, it can be readily added to the site or the site can be modified to accommodate it. The site is interactive allowing users to search within the PUMP site, within the Appalachian Region PTTC site, or within the whole internet through the input of user-supplied key words for information on oil production problems and solutions. Since its inception in the Fall of 2002, the PUMP site has experienced a growing number of users of increasingly diverse nature and from an increasing geographic area. This indicates that the site is reaching its target audience in the Appalachian region and beyond. Following up on a commitment to technology transfer, a total of eight focused-technology workshops were sponsored by the Appalachian Region PTTC center at the request of the PUMP project. Five Welltender Operations and Safety seminars were held in Kentucky, West Virginia, Ohio, and Pennsylvania. A two-day Applied Reservoir Characterization seminar and a one-day course on Paraffin, Asphaltene, and Scale problems were held in Pennsylvania. A one-day workshop on Produced Water was held in OH. In addition to workshops and the PUMP website, the project also generated several topical reports available to the public through the website and through USDOE.« less

How Does The Universe Work? The Physics Of The Cosmos Program (PCOS)

NASA Astrophysics Data System (ADS)

Sambruna, Rita M.

2011-09-01

The Physics of the Cosmos (PCOS) program incorporates cosmology, high-energy astrophysics, and fundamental physics projects aimed at addressing central questions about the nature of complex astrophysical phenomena such as black holes, neutron stars, dark energy, and gravitational waves. Its overarching theme is, How does the Universe work? PCOS includes a suite of operating (Chandra, Fermi, Planck, XMM-Newton, INTEGRAL) and future missions across the electromagnetic spectrum and beyond, which are in concept development and/or formulation. The PCOS program directly supports development of intermediate TRL (4-6) technology relevant to future missions through the Strategic Astrophysics Technology (SAT) program, as well as data analysis, theory, and experimental astrophysics via other R&A avenues (e.g., ADAP, ATP). The Einstein Fellowship is a vital and vibrant PCOS component funded by the program. PCOS receives community input via its Program Analysis Group, the PhysPAG (www.pcos.gsfc.nasa.gov/physpag.php), whose membership and meetings are open to the community at large. In this poster, we describe the detailed science questions addressed within PCOS, with special emphasis on future opportunities. Details about the PhysPAG operations and functions will be provided, as well as an update on future meetings.

Pain modulation is affected differently in medication-overuse headache and chronic myofascial pain - A multimodal MRI study.

PubMed

Michels, Lars; Christidi, Foteini; Steiger, Vivian R; Sándor, Peter S; Gantenbein, Andreas R; Landmann, Gunther; Schreglmann, Sebastian R; Kollias, Spyros; Riederer, Franz

2017-07-01

Background Neuroimaging studies revealed structural and functional changes in medication-overuse headache (MOH), but it remains unclear whether similar changes could be observed in other chronic pain disorders. Methods In this cross-sectional study, we investigated functional connectivity (FC) with resting-state functional magnetic resonance imaging (fMRI) and white matter integrity using diffusion tensor imaging (DTI) to measure fractional anisotropy (FA) and mean diffusivity (MD) in patients with MOH ( N = 12) relative to two control groups: patients with chronic myofascial pain (MYO; N = 11) and healthy controls (CN; N = 16). Results In a data-driven approach we found hypoconnectivity in the fronto-parietal attention network in both pain groups relative to CN (i.e. MOH < CN and MYO < CN). In contrast, hyperconnectivity in the saliency network (SN) was detected only in MOH, which correlated with FA in the insula. In a seed-based analysis we investigated FC between the periaqueductal grey (PAG) and all other brain regions. In addition to overlapping hyperconnectivity seen in patient groups (relative to CN), MOH had a distinct connectivity pattern with lower FC to parieto-occipital regions and higher FC to orbitofrontal regions compared to controls. FA and MD abnormalities were mostly observed in MOH, involving the insula. Conclusions Hyperconnectivity within the SN along with associated white matter changes therein suggest a particular role of this network in MOH. In addition, abnormal connectivity between the PAG and other pain modulatory (frontal) regions in MOH are consistent with dysfunctional central pain control.

Identification and Characterization of Intercritical Heat-Affected Zone in As-Welded Grade 91 Weldment

NASA Astrophysics Data System (ADS)

Wang, Yiyu; Kannan, Rangasayee; Li, Leijun

2016-12-01

A metallurgical method is proposed for locating the intercritical heat-affected zone in the as-welded Grade 91 steel. New austenitic grains, preferentially formed along the original prior austenite grain boundaries, are characterized to contain finer M23C6 carbides and higher strain levels than the original prior austenite grains. Kurdjumov-Sachs Group 1 variant pairs, with a low misorientation of 7 deg within a martensitic block, are identified as the dominant variants in the new PAGs.

75 FR 67695 - U.S. Strategic Command Strategic Advisory Group Closed Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-03

... DEPARTMENT OF DEFENSE Office of the Secretary of Defense U.S. Strategic Command Strategic Advisory... meeting notice of the U.S. Strategic Command Strategic Advisory Group. DATES: December 9, 2010: 8 a.m. to..., intelligence, and policy-related issues to the Commander, U.S. Strategic Command, during the development of the...

77 FR 45653 - Yakima River Basin Conservation Advisory Group; Yakima River Basin Water Enhancement Project...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-01

... 4 p.m. ADDRESSES: The meeting will be held at the Bureau of Reclamation, Yakima Field Office, 1917... DEPARTMENT OF THE INTERIOR Bureau of Reclamation Yakima River Basin Conservation Advisory Group...: Notice of public meeting. SUMMARY: As required by the Federal Advisory Committee Act, the Yakima River...

75 FR 54871 - National Drinking Water Advisory Council's Climate Ready Water Utilities Working Group Meeting...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-09

... ENVIRONMENTAL PROTECTION AGENCY [FRL-9198-8] National Drinking Water Advisory Council's Climate... final in-person meeting of the Climate Ready Water Utilities (CRWU) Working Group of the National Drinking Water Advisory Council (NDWAC). The purpose of this meeting is to review and discuss final changes...

Effect of early or late resynchronization based on different methods of pregnancy diagnosis on reproductive performance of dairy cows.

PubMed

Sinedino, L D P; Lima, F S; Bisinotto, R S; Cerri, R L A; Santos, J E P

2014-01-01

The aim of this study was to compare the reproductive performance of dairy cows subjected to early (ER) or late (LR) resynchronization programs after nonpregnancy diagnoses based on either pregnancy-associated glycoproteins (PAG) ELISA or transrectal palpation, respectively. In addition, the accuracy of the PAG ELISA for early pregnancy diagnosis was assessed. Lactating Holstein cows were subjected to a Presynch-Ovsynch protocol with timed artificial insemination (AI) performed between 61 and 74 DIM. On the day of the first postpartum AI, 1,093 cows were blocked by parity and assigned randomly to treatments; however, because of attrition, 452 ER and 520 LR cows were considered for the statistical analyses. After the first postpartum AI, cows were observed daily for signs of estrus and inseminated on the same day of detected estrus. Cows from ER that were not reinseminated in estrus received the first GnRH injection of the Ovsynch protocol for resynchronization 2d before pregnancy diagnosis. On d 28 after the previous AI (d 27 to 34), pregnancy status was determined by PAG ELISA, and nonpregnant cows continued on the Ovsynch protocol for reinsemination. Pregnant cows had pregnancy status reconfirmed on d 46 after AI (d 35 to 52) by transrectal palpation, and those that lost the pregnancies were resynchronized. Cows assigned to LR had pregnancy diagnosed by transrectal palpation on d 46 after AI (d 35 to 52) and nonpregnant cows were resynchronized with the Ovsynch protocol. Blood was sampled on d 28 after AI (d 27 to 34) from cows in both treatments that had not been reinseminated on estrus and again on d 46 after AI (d 35 to 52) for assessment of PAG ELISA to determine the accuracy of the test. Cows were subjected to treatments for 72d after the first insemination. Pregnancy per AI (P/AI) at first postpartum timed AI did not differ between treatments and averaged 28.9%. The proportion of nonpregnant cows that were resynchronized and received timed AI was greater for ER than for LR (30.0 vs. 7.6%). Cows in ER had a shorter interval between inseminations when inseminated following spontaneous estrus (21.7±1.1 vs. 27.8±0.8d) or after timed AI (35.3±1.2 vs. 55.2±1.4d). Nevertheless, the ER did not affect the rate of pregnancy (adjusted hazard ratio=1.23; 95% confidence interval=0.94 to 1.61) or the median days postpartum to pregnancy (ER=132 vs. LR=140). A total of 2,129 PAG ELISA were evaluated. Overall, sensitivity, specificity, and positive and negative predictive values averaged 95.1, 89.0, 90.1, and 94.5%, respectively, and the accuracy was 92.1%. In conclusion, PAG ELISA for early diagnosis of pregnancy had acceptable accuracy, but early resynchronization after nonpregnancy diagnosis with PAG ELISA did not improve the rate of pregnancy or reduce days open in dairy cows continuously observed for estrus. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Auditing audits: use and development of the Oxfordshire Medical Audit Advisory Group rating system.

PubMed Central

Lawrence, M.; Griew, K.; Derry, J.; Anderson, J.; Humphreys, J.

1994-01-01

OBJECTIVES--To assess the value of the Oxfordshire Medical Audit Advisory Group rating system in monitoring and stimulating audit activity, and to implement a development of the system. DESIGN--Use of the rating system for assessment of practice audits on three annual visits in Oxfordshire; development and use of an "audit grid" as a refinement of the system; questionnaire to all medical audit advisory groups in England and Wales. SETTING--All 85 general practices in Oxfordshire; all 95 medical audit advisory groups in England and Wales. MAIN OUTCOME MEASURES--Level of practices' audit activity as measured by rating scale and grid. Use of scale nationally together with perceptions of strengths and weaknesses as perceived by chairs of medical audit advisory groups. RESULTS--After one year Oxfordshire practices more than attained the target standards set in 1991, with 72% doing audit involving setting target standards or implementing change; by 1993 this had risen to 78%. Most audits were confined to chronic disease management, preventive care, and appointments. 38 of 92 medical audit advisory groups used the Oxfordshire group's rating scale. Its main weaknesses were insensitivity in assessing the quality of audits and failure to measure team involvement. CONCLUSIONS--The rating system is effective educationally in helping practices improve and summatively for providing feedback to family health service authorities. The grid showed up weakness in the breadth of audit topics studied. IMPLICATIONS AND ACTION--Oxfordshire practices achieved targets set for 1991-2 but need to broaden the scope of their audits and the topics studied. The advisory group's targets for 1994-5 are for 50% of practices to achieve an audit in each of the areas of clinical care, access, communication, and professional values and for 80% of audits to include setting targets or implementing change. PMID:8086911

75 FR 76070 - Railroad Safety Advisory Committee (RSAC); Working Group Activity Update

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-07

.... 65] Railroad Safety Advisory Committee (RSAC); Working Group Activity Update AGENCY: Federal Railroad... Committee (RSAC) Working Group Activities. SUMMARY: The FRA is updating its announcement of RSAC's Working.... [[Page 76071

Efferent connections of the parvalbumin-positive (PV1) nucleus in the lateral hypothalamus of rodents.

PubMed

Celio, Marco R; Babalian, Alexandre; Ha, Quan Hue; Eichenberger, Simone; Clément, Laurence; Marti, Christiane; Saper, Clifford B

2013-10-01

A solitary cluster of parvalbumin-positive neurons--the PV1 nucleus--has been observed in the lateral hypothalamus of rodents. In the present study, we mapped the efferent connections of the PV1 nucleus using nonspecific antero- and retrograde tracers in rats, and chemoselective, Cre-dependent viral constructs in parvalbumin-Cre mice. In both species, the PV1 nucleus was found to project mainly to the periaqueductal grey matter (PAG), predominantly ipsilaterally. Indirectly in rats and directly in mice, a discrete, longitudinally oriented cylindrical column of terminal fields (PV1-CTF) was identified ventrolateral to the aqueduct on the edge of the PAG. The PV1-CTF is particularly dense in the rostral portion, which is located in the supraoculomotor nucleus (Su3). It is spatially interrupted over a short stretch at the level of the trochlear nucleus and abuts caudally on a second parvalbumin-positive (PV2) nucleus. The rostral and the caudal portions of the PV1-CTF consist of axonal endings, which stem from neurons scattered throughout the PV1 nucleus. Topographically, the longitudinal orientation of the PV1-CTF accords with that of the likewise longitudinally oriented functional modules of the PAG, but overlaps none of them. Minor terminal fields were identified in a crescentic column of the lateral PAG, as well as in the Edinger-Westphal, the lateral habenular, and the laterodorsal tegmental nuclei. So far, no obvious functions have been attributed to this small, circumscribed column ventrolateral to the aqueduct, the prime target of the PV1 nucleus. © 2013 Wiley Periodicals, Inc.

Doping in Two Elite Athletics Competitions Assessed by Randomized-Response Surveys.

PubMed

Ulrich, Rolf; Pope, Harrison G; Cléret, Léa; Petróczi, Andrea; Nepusz, Tamás; Schaffer, Jay; Kanayama, Gen; Comstock, R Dawn; Simon, Perikles

2018-01-01

Doping in sports compromises fair play and endangers health. To deter doping among elite athletes, the World Anti-Doping Agency (WADA) oversees testing of several hundred thousand athletic blood and urine samples annually, of which 1-2% test positive. Measures using the Athlete Biological Passport suggest a higher mean prevalence of about 14% positive tests. Biological testing, however, likely fails to detect many cutting-edge doping techniques, and thus the true prevalence of doping remains unknown. We surveyed 2167 athletes at two sporting events: the 13th International Association of Athletics Federations Word Championships in Athletics (WCA) in Daegu, South Korea in August 2011 and the 12th Quadrennial Pan-Arab Games (PAG) in Doha, Qatar in December 2011. To estimate the prevalence of doping, we utilized a "randomized response technique," which guarantees anonymity for individuals when answering a sensitive question. We also administered a control question at PAG assessing past-year use of supplements. The estimated prevalence of past-year doping was 43.6% (95% confidence interval 39.4-47.9) at WCA and 57.1% (52.4-61.8) at PAG. The estimated prevalence of past-year supplement use at PAG was 70.1% (65.6-74.7%). Sensitivity analyses, assessing the robustness of these estimates under numerous hypothetical scenarios of intentional or unintentional noncompliance by respondents, suggested that we were unlikely to have overestimated the true prevalence of doping. Doping appears remarkably widespread among elite athletes, and remains largely unchecked despite current biological testing. The survey technique presented here will allow future investigators to generate continued reference estimates of the prevalence of doping.

An NMR relaxometry and gravimetric study of gelatin-free aqueous polyacrylamide dosimeters

NASA Astrophysics Data System (ADS)

Babic, Steven; Schreiner, L. John

2006-09-01

In conformal radiation therapy, a high dose of radiation is given to a target volume to increase the probability of cure, and care is taken to minimize the dose to surrounding healthy tissue. The techniques used to achieve this are very complicated and the precise verification of the resulting three-dimensional (3D) dose distribution is required. Polyacrylamide gelatin (PAG) dosimeters with magnetic resonance imaging and optical computed tomography scanning provide the required 3D dosimetry with high spatial resolution. Many basic studies have characterized these chemical dosimeters that polymerize under irradiation. However, the investigation of the fundamental properties of the radiation-induced polymerization in PAG dosimeters is complicated by the presence of the background gelatin matrix. In this work, a gelatin-free model system for the study of the basic radiation-induced polymerization in PAG dosimeters has been developed. Experiments were performed on gelatin-free dosimeters, named aqueous polyacrylamide (APA) dosimeters, containing equal amounts of acrylamide and N,N'-methylene-bisacrylamide. The APA dosimeters were prepared with four different total monomer concentrations (2, 4, 6 and 8% by weight). Nuclear magnetic resonance (NMR) spin-spin and spin-lattice proton relaxation measurements at 20 MHz, and gravimetric analyses performed on all four dosimeters, show a continuous degree of polymerization over the dose range of 0-25 Gy. The developed NMR model explains the relationship observed between the relaxation data and the amount of crosslinked polymer formed at each dose. This model can be extended with gelatin relaxation data to provide a fundamental understanding of radiation-induced polymerization in the conventional PAG dosimeters.

An NMR relaxometry and gravimetric study of gelatin-free aqueous polyacrylamide dosimeters.

PubMed

Babic, Steven; Schreiner, L John

2006-09-07

In conformal radiation therapy, a high dose of radiation is given to a target volume to increase the probability of cure, and care is taken to minimize the dose to surrounding healthy tissue. The techniques used to achieve this are very complicated and the precise verification of the resulting three-dimensional (3D) dose distribution is required. Polyacrylamide gelatin (PAG) dosimeters with magnetic resonance imaging and optical computed tomography scanning provide the required 3D dosimetry with high spatial resolution. Many basic studies have characterized these chemical dosimeters that polymerize under irradiation. However, the investigation of the fundamental properties of the radiation-induced polymerization in PAG dosimeters is complicated by the presence of the background gelatin matrix. In this work, a gelatin-free model system for the study of the basic radiation-induced polymerization in PAG dosimeters has been developed. Experiments were performed on gelatin-free dosimeters, named aqueous polyacrylamide (APA) dosimeters, containing equal amounts of acrylamide and N,N'-methylene-bisacrylamide. The APA dosimeters were prepared with four different total monomer concentrations (2, 4, 6 and 8% by weight). Nuclear magnetic resonance (NMR) spin-spin and spin-lattice proton relaxation measurements at 20 MHz, and gravimetric analyses performed on all four dosimeters, show a continuous degree of polymerization over the dose range of 0-25 Gy. The developed NMR model explains the relationship observed between the relaxation data and the amount of crosslinked polymer formed at each dose. This model can be extended with gelatin relaxation data to provide a fundamental understanding of radiation-induced polymerization in the conventional PAG dosimeters.

Brain circuits for mating behavior in cats and brain activations and de-activations during sexual stimulation and ejaculation and orgasm in humans.

PubMed

Holstege, Gert; Huynh, Hieu K

2011-05-01

In cats, there exists a descending system that controls the posture necessary for mating behavior. A key role is played by the mesencephalic periaqueductal gray (PAG), which maintains strong specific projections to the nucleus retroambiguus located laterally in the most caudal medulla. The NRA, in turn, has direct access to motoneurons in the lumbosacral cord that produce the mating posture. This pathway is slightly different in males and females, but in females its strength fluctuates strongly depending on whether or not the cat is in heat. This way the PAG determines whether or not mating can take place. Via the PAG many other regions in the limbic system as well as in the prefrontal cortex and insula can influence mating behavior. In humans, the brain also controls responses to sexual stimulation as well as ejaculation in men and orgasm in women. Neuroimaging techniques show activations and de-activations but are not able to verify whether the PAG has a similar effect as in cats. PET-scanning results revealed that there is activation in the upper brainstem and cerebellum, as well as insula in men and in the somatomotor and somatosensory cortex in women. During sexual stimulation, but especially during ejaculation and orgasm there was strong de-activation mainly on the left side in the temporal lobe and ventral prefrontal cortex. These neuroimaging results show the importance of lowering the level of alertness regarding your immediate environment (left hemisphere) to have proper sexual behavior. Copyright © 2011 Elsevier Inc. All rights reserved.

Photopatterned free-standing polyacrylamide gels for microfluidic protein electrophoresis.

PubMed

Duncombe, Todd A; Herr, Amy E

2013-06-07

Designed for compatibility with slab-gel polyacrylamide gel electrophoresis (PAGE) reagents and instruments, we detail development of free-standing polyacrylamide gel (fsPAG) microstructures supporting electrophoretic performance rivalling that of microfluidic platforms. For the protein electrophoresis study described here, fsPAGE lanes are comprised of a sample reservoir and contiguous separation gel. No enclosed microfluidic channels are employed. The fsPAG devices (120 μm tall) are directly photopatterned atop of and covalently attached to planar polymer or glass surfaces. Leveraging the fast <1 h design-prototype-test cycle - significantly faster than mold based fabrication techniques - we optimize the fsPAG architecture to minimize injection dispersion for rapid (<1 min) and short (1 mm) protein separations. The facile fabrication and prototyping of the fsPAGE provides researchers a powerful tool for developing custom analytical assays. We highlight the utility of assay customization by fabricating a polyacrylamide gel with a spatial pore-size distribution and demonstrate the resulting enhancement in separation performance over a uniform gel. Further, we up-scale from a unit separation to an array of 96 concurrent fsPAGE assays in 10 min run time driven by one electrode pair. The fsPAG array layout matches that of a 96-well plate to facilitate integration of the planar free standing gel array with multi-channel pipettes while remaining compatible with conventional slab-gel PAGE reagents, such as staining for label-free protein detection. Notably, the entire fsPAGE workflow from fabrication, to operation, and readout uses readily available materials and instruments - making this technique highly accessible.

Punishing Unfairness: Rewarding or the Organization of a Reactively Aggressive Response?

PubMed Central

White, Stuart F.; Brislin, Sarah J.; Sinclair, Stephen; Blair, James R.

2014-01-01

Objectives The neural correlates of human cooperative behavior remain poorly understood. Previous work has suggested that increases in striatal activation while punishing unfair offers represents reward signaling. However, other regions are also implicated when punishing others, for example dorsomedial frontal cortex (dmFC), anterior insula cortex (AIC), and periaqueductal gray (PAG). Moreover, the response of other regions implicated in signaling reward, for example ventromedial prefrontal cortex (vmPFC) or posterior cingulate cortex (PCC), has not been systematically examined. Experimental Design Functional magnetic resonance imaging utilizing parametric modulation was conducted on 21 healthy adults participating in a social exchange paradigm. Principal Observations Participants showed significant positive modulation of activity as a function of delivered punishment in caudate, dmFC, AIC, and PAG; that is, higher punishments by participants of unsatisfactory offers were associated with increasing activity within these regions. However, participants showed significant negative modulation of activity as a function of delivered punishment in vmPFC and PCC; increases in punishment level by participants were associated with decreases in activity within these regions. Conclusions The current data question whether caudate activity when punishing unfair offers should be considered to indicate the reward value of this punishment. Instead, this activity, in conjunction with activity within dmFC, AIC, and PAG, may represent the organization of an untypical, punishing response that represents a reactive aggressive response to provocation. Notably, an inverse, regulatory relationship between vmPFC and PAG activity has been previously implicated in the context of another stimulus for reactive aggression; looming threat (Mobbs et al. [2007]: Science 317:1079–1083). PMID:23868733

Overlapping topics in advisory reports issued by five well-established European National Immunization Technical Advisory Groups from 2011 to 2014.

PubMed

Nijsten, Daniëlle; Houweling, Hans; Durupt, Antoine; Adjagba, Alex

2016-12-07

National Immunization Technical Advisory Groups (NITAGs) are facing increasingly complex vaccination issues together with a lack of human resources for evidence assessment and data analysis. One way to reduce these burdens could be to share some of the preparatory work across NITAGs. We conducted an inventory of all the advisory reports issued by five well-established European NITAGs from 2011 to 2014 to assess overlaps in issues and activities. A total of 104 advisory reports were retrieved. Advisory reports on the same issues were compared to identify overlapping activities and processes. Advisory reports issued by the five NITAGs showed little overlap in issues and processes. A first step towards efficient collaboration would be to establish an independent platform to provide insight into each NITAG's work and to facilitate the exchange of agendas, assessment frameworks and evidence. Copyright © 2016 Elsevier Ltd. All rights reserved.

77 FR 15372 - Meeting of the Advisory Group on Prevention, Health Promotion, and Integrative and Public Health

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-15

... Promotion, and Integrative and Public Health AGENCY: Department of Health and Human Services, Office of the... Public Health Service. ACTION: Notice. SUMMARY: In accordance with Section 10(a) of the Federal Advisory... scheduled to be held for the Advisory Group on Prevention, Health Promotion, and Integrative and Public...

76 FR 67731 - Meeting of the Advisory Group on Prevention, Health Promotion, and Integrative and Public Health

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-02

... Promotion, and Integrative and Public Health AGENCY: Department of Health and Human Services, Office of the... Public Health Service. ACTION: Notice. SUMMARY: In accordance with Section 10(a) of the Federal Advisory... scheduled to be held for the Advisory Group on Prevention, Health Promotion, and Integrative and Public...

76 FR 26300 - Meeting of the Advisory Group on Prevention, Health Promotion, and Integrative and Public Health

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-06

... Promotion, and Integrative and Public Health AGENCY: Department of Health and Human Services, Office of the... Public Health Service. ACTION: Notice. SUMMARY: In accordance with Section 10(a) of the Federal Advisory... scheduled to be held for the Advisory Group on Prevention, Health Promotion, and Integrative and Public...

78 FR 14798 - Meeting of the Advisory Group on Prevention, Health Promotion, and Integrative and Public Health

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-07

... Promotion, and Integrative and Public Health AGENCY: Department of Health and Human Services, Office of the... Public Health Service. ACTION: Notice. SUMMARY: In accordance with Section 10(a) of the Federal Advisory... and Public Health (the ``Advisory Group''). The meeting will be open to the public. Information about...

76 FR 58007 - Meeting of the Advisory Group on Prevention, Health Promotion, and Integrative and Public Health

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-19

... Promotion, and Integrative and Public Health AGENCY: Department of Health and Human Services, Office of the... Public Health Service. ACTION: Notice. SUMMARY: In accordance with Section 10(a) of the Federal Advisory... scheduled to be held for the Advisory Group on Prevention, Health Promotion, and Integrative and Public...

Role of Advisory Groups. Instructor Guide. Working for Clean Water: An Information Program for Advisory Committees.

ERIC Educational Resources Information Center

Pennsylvania State Univ., Middletown. Inst. of State and Regional Affairs.

Presented is an instructor's manual for conducting a learning session about public participation in water quality planning. Participants in the session learn about the purpose, organization, and activities of citizen advisory groups. The manual, a component of the Working for Clean Water Project, is designed for use in conjunction with a…

Structuring unbreakable hydrophobic barriers in paper

NASA Astrophysics Data System (ADS)

Nargang, Tobias M.; Kotz, Frederik; Rapp, Bastian E.

2018-02-01

Hydrophobic barriers are one of the key elements of microfluidic paper based analytical devices (μPADs).μPADs are simple and cost efficient and they can be carried out without the need of high standard laboratories. To carry out such a test a method is needed to create stable hydrophobic barriers. Commonly used methods like printing wax or polystyrene have the major drawback that these barriers are stiff and break if bended which means they will no longer be able to retain a liquid sample. Here we present silanes to structure hydrophobic barriers via polycondensation and show a silanization method which combines the advantages of flexible silane/siloxane layers with the short processing times of UV-light based structuring. The barriers are created by using methoxy silanes which are mixed with a photo acid generator (PAG) as photoinitiator. Also a photosensitizer was given to the mixture to increase the effectiveness of the PAG. After the PAG is activated by UV-light the silane is hydrolyzed and coupled to the cellulose via polycondensation. The created hydrophobic barriers are highly stable and do not break if being bended.

Unraveling the role of photons and electrons upon their chemical interaction with photoresist during EUV exposure

NASA Astrophysics Data System (ADS)

Pollentier, Ivan; Vesters, Yannick; Petersen, John S.; Vanelderen, Pieter; Rathore, Atish; de Simone, Danilo; Vandenberghe, Geert

2018-03-01

The interaction of 91.6 eV EUV photons with photoresist - in particular chemically amplified resist (CAR) - is different than exposure at 193 nm and 248 nm wavelengths. The latter is understood well and it is known that photons interact with electrons in the resist's molecular valence orbitals (for chemically amplified resist (CAR) the photon interacts with the photo acid generator (PAG), which leads to a deprotection reaction on a polymer after a thermal catalytic reaction during a post-exposure-bake.). At EUV however, more steps are involved in the radiolysis process between the absorption of the photon and the final chemical modification. These are related to the generation of primary electrons and their decay to lower energy secondary electrons, and most of this steps are not well understood. In this paper, the reaction products from EUV and low energy electron exposure are examined using Residual Gas Analysis (RGA), which measures and analyzes the outgassing products related to the ongoing reactions. This investigation is applied firstly on a model CAR where details of the resist chemical constituents were known prior to testing. The measurement not only resolved information on the expected acid related reactions from the PAG and protection groups, but also exhibited direct scission reactions of the polymer, where some of them lead to polymerization reactions. Moreover, the measurement quantifies the balance between the different ongoing reactions, which were confirmed by contrast curve measurements. Based on learnings on the model resist, applied the measurement technique to commercial resists, where actual resist chemistry composition is not known. Despite that, it was found that information could be deduced to distinguish between acid related ongoing reactions and direct scission of reaction on the base polymer and quantify their relation. Moreover, different generations of commercial resists based on similar chemistry platform were investigated, which revealed that improvements in printing performance could be explained by PAG reaction yield increase.

Advisory: Definitions, Descriptions, Decisions, Directions.

ERIC Educational Resources Information Center

Galassi, John P.; Gulledge, Suzanne A.; Cox, Nancy D.

Advisory groups have played an essential role in improving the school climate and conditions for young adolescents in schools. How middle school decision makers go about the process of designing or re-designing an advisory program needs to be considered. A discussion is presented of the background information that helps define advisories. It…

76 FR 1187 - Application for Recertification of Prince William Sound Regional Citizens' Advisory Council

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-07

... Prince William Sound Regional Citizens' Advisory Council AGENCY: Coast Guard, DHS. ACTION: Notice of... on, the application for recertification submitted by the Prince William Sound Regional Citizen's... advisory group in lieu of a Regional Citizens' Advisory Council for Prince William Sound, Alaska. This...

75 FR 51525 - Railroad Safety Advisory Committee (RSAC); Working Group Activity Update

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-20

.... 63] Railroad Safety Advisory Committee (RSAC); Working Group Activity Update AGENCY: Federal Railroad... Committee (RSAC) Working Group Activities. SUMMARY: The FRA is updating its announcement of RSAC's Working.... SUPPLEMENTARY INFORMATION: This notice serves to update FRA's last announcement of working group activities and...

National Space Council Users' Advisory Group

NASA Image and Video Library

2018-06-19

James Uthmeier, of the Department of Commerce, speaks about deregulation and space traffic management initiatives at the first meeting of the National Space Council Users' Advisory Group, Tuesday, June 19, 2018 at NASA Headquarters in Washington. The Users' Advisory Group will advise and inform the National Space Council on a broad range of aerospace topics, including the impacts of U.S. and international laws and regulations, national security space priorities, scientific and human space exploration priorities, and ways to bolster support. Photo Credit: (NASA/Joel Kowsky)

75 FR 4904 - Railroad Safety Advisory Committee (RSAC); Working Group Activity Update

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-29

...-7257] Railroad Safety Advisory Committee (RSAC); Working Group Activity Update AGENCY: Federal Railroad... Committee (RSAC) Working Group Activities. SUMMARY: The FRA is updating its announcement of RSAC's Working... notice serves to update FRA's last announcement of working group activities and status reports of August...

77 FR 24257 - Railroad Safety Advisory Committee (RSAC); Working Group Activity Update

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-23

.... 69] Railroad Safety Advisory Committee (RSAC); Working Group Activity Update AGENCY: Federal Railroad... Committee (RSAC) Working Group Activities. SUMMARY: The FRA is updating its announcement of the RSAC Working.... SUPPLEMENTARY INFORMATION: This notice serves to update FRA's last announcement of working group activities and...

75 FR 18824 - Federal Advisory Committee; U.S. Strategic Command Strategic Advisory Group; Closed Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-13

... DEPARTMENT OF DEFENSE Office of the Secretary Federal Advisory Committee; U.S. Strategic Command... 102-3.150, the Department of Defense announces that the U.S. Strategic Command Strategic Advisory... Commander, U.S. Strategic Command, during the development of the Nation's strategic war plans. Agenda Topics...

Hypoxic pulmonary vasoconstriction in isolated rat pulmonary arteries is not inhibited by antagonists of H2S-synthesizing pathways

PubMed Central

Prieto-Lloret, Jesus; Shaifta, Yasin; Ward, Jeremy P T; Aaronson, Philip I

2015-01-01

An increase in the H2S (hydrogen sulphide, hereafter sulphide) concentration in pulmonary artery smooth muscle cells (PASMCs) has been proposed to mediate hypoxic pulmonary vasoconstriction (HPV). We evaluated this hypothesis in isolated rat intrapulmonary arteries (IPAs) by examining the effects of the sulphide precursor cysteine and sulphide-synthesis blockers on HPV and also on normoxic pulmonary vasoconstriction (NPV) stimulated by prostaglandin F2α (PGF2α) and by the drug LY83583, which causes contraction in IPAs by increasing cellular reactive oxygen species levels. Experiments with several blockers of cystathionine γ-lyase (CSE), the enzyme responsible for sulphide synthesis in the vasculature, demonstrated that propargylglycine (PAG, 1 mm) had little or no effect on the NPV caused by PGF2α or LY83583. Conversely, other CSE antagonists tested, aminooxyacetic acid (AOAA, 100 μm), β-cyanoalanine (BCA, 500 μm) and hydroxylamine (HA, 100 μm), altered the NPV to PGF2α (BCA increased, HA inhibited) and/or LY83583 (BCA increased, AOAA and HA inhibited). Preincubating IPAs in physiological saline solution (PSS) containing 1 mm cysteine increased the amplitude of the NPV to PGF2α by ∼50%, and had a similar effect on HPV elicited by hypoxic challenge with 0% O2. The enhancement of both responses by cysteine was abolished by pretreatment with 1 mm PAG. Measurements carried out with an amperometric electrode demonstrated that incubation with 1 mm cysteine under anoxic conditions (to minimize sulphide oxidation) greatly potentiated the release of sulphide from pieces of rat liver and that this release was strongly antagonized by PAG, indicating that at this concentration PAG could enter cells intact and antagonize CSE. PAG at 1 mm had no effect on HPV recorded in control PSS, or in PSS supplemented with physiological concentrations of cysteine (10 μm), cystine (50 μm) and glutamate (100 μm) in order to prevent the possible depletion of intracellular cysteine during experiments. Application of a combination of 1 mm cysteine and 1 mm α-ketoglutarate to promote sulphide synthesis via the cysteine aminotransferase/mercaptopyruvate sulphurtransferase (CAT/MST) pathway caused an increase in HPV similar to that observed for cysteine. This was partially blocked by the CAT antagonist aspartate (1 mm) and also by PAG. However, HPV was not increased by 1 mm α-ketoglutarate alone, and HPV in the absence of α-ketoglutarate and cysteine was not attenuated by aspartate. Pretreatment of IPAs with dithiothreitol (DTT, 1 mm), proposed to promote the conversion of mitochondrial thiosulphate to sulphide, did not increase the release of sulphide from pieces of rat liver in either the presence or the absence of 1 mm cysteine, and virtually abolished HPV. The results provide evidence that the sulphide precursor cysteine can promote both NPV and HPV in rat IPA by generating sulphide via a PAG-sensitive pathway, presumably CSE. However, HPV evoked under control conditions was unaffected by the blockade of CSE. Moreover, HPV was not affected by the CAT antagonist aspartate and was blocked rather than enhanced by DTT. The data therefore indicate that sulphide generated by CSE or CAT/MST or from thiosulphate is unlikely to contribute to O2 sensing during HPV in these arteries. PMID:25630260

78 FR 1917 - Commercial Space Transportation Advisory Committee-Public Teleconference

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-09

... DEPARTMENT OF TRANSPORTATION Federal Aviation Administration Commercial Space Transportation...: Notice of Commercial Space Transportation Advisory Committee Teleconference. SUMMARY: Pursuant to the... Group (BLWG) of the Commercial Space Transportation Advisory Committee (COMSTAC). DATES: The...

B2-kinin receptors in the dorsal periaqueductal gray are implicated in the panicolytic-like effect of opiorphin.

PubMed

Sestile, Caio César; Maraschin, Jhonatan Christian; Rangel, Marcel Pereira; Santana, Rosangela Getirana; Zangrossi, Hélio; Graeff, Frederico Guilherme; Audi, Elisabeth Aparecida

2017-10-03

Reported results have shown that the pentapeptide opiorphin inhibits oligopeptidases that degrade brain neuropeptides, and has analgesic and antidepressant effects in experimental animals, without either tolerance or dependency after chronic administration. In a previous study we showed that opiorphin has a panicolytic-like effect in the dorsal periaqueductal gray (dPAG) electrical stimulation test (EST), mediated by the μ-opioid receptor (MOR). This study further analyzes the mechanism of opiorphin panicolytic action, using the EST and drug injection inside the dPAG. The obtained results showed that blockade of the 5-HT 1A receptors with WAY-100635 did not change the escape-impairing effect of opiorphin, and combined injection of sub-effective doses of opiorphin and the 5-HT 1A -agonist 8-OH-DPAT did not have a significant anti-escape effect. In contrast, the anti-escape effect of opiorphin was antagonized by pretreatment with the kinin B2 receptor blocker HOE-140, and association of sub-effective doses of opiorphin and bradykinin caused a significant anti-escape effect. The anti-escape effect of bradykinin was not affected by previous administration of WAY-100635. Therefore, the anti-escape effect of opiorphin in the dPAG seems to be mediated by endogenous bradykinin, acting on kinin B2 receptors, which previous results have shown to interact synergistically with MOR in the dPAG to restrain escape in two animal models of panic. Chemical compounds: Opiorphin (PubChem CID: 25195667); WAY100635 maleate salt (PubChem CID: 11957721); 8-OH-DPAT hydrobromide (PubChem CID: 6917794); Bradykinin (PubChem CID: 439201); HOE-140 (Icatibant) (PubChem CID: 6918173). Copyright © 2017 Elsevier Inc. All rights reserved.

Inhibition of endogenous hydrogen sulfide formation reduces the organ injury caused by endotoxemia

PubMed Central

Collin, Marika; Anuar, Farhana B M; Murch, Oliver; Bhatia, Madhav; Moore, Philip K; Thiemermann, Christoph

2005-01-01

Hydrogen sulfide (H2S) is a naturally occurring gaseous transmitter, which may play important roles in normal physiology and disease. Here, we investigated the role of H2S in the organ injury caused by severe endotoxemia in the rat. Male Wistar rats were subjected to acute endotoxemia (Escherichia coli lipopolysaccharide (LPS) 6 mg kg−1 intravenously (i.v.) for 6 h) and treated with vehicle (saline, 1 ml kg−1 i.v.) or DL-propargylglycine (PAG, 10–100 mg kg−1 i.v.), an inhibitor of the H2S-synthesizing enzyme cystathionine-γ-lyase (CSE). PAG was administered either 30 min prior to or 60 min after the induction of endotoxemia. Endotoxemia resulted in circulatory failure (hypotension and tachycardia) and an increase in serum levels of alanine aminotransferase and aspartate aminotransferase (markers for hepatic injury), lipase (indicator of pancreatic injury) and creatine kinase (indicator of neuromuscular injury). In the liver, endotoxemia induced a significant increase in the myeloperoxidase (MPO) activity, and in the expression and activity of the H2S-synthesizing enzymes CSE and cystathionine-β-synthase. Administration of PAG either prior to or after the injection of LPS dose-dependently reduced the hepatocellular, pancreatic and neuromuscular injury caused by endotoxemia, but not the circulatory failure. Pretreatment of rats with PAG abolished the LPS-induced increase in the MPO activity and in the formation of H2S and in the liver. These findings support the view that an enhanced formation of H2S contributes to the pathophysiology of the organ injury in endotoxemia. We propose that inhibition of H2S synthesis may be a useful therapeutic strategy against the organ injury associated with sepsis and shock. PMID:16100527

Evaluating the ParticipACTION "Think Again" Campaign.

PubMed

Gainforth, Heather L; Jarvis, Jocelyn W; Berry, Tanya R; Chulak-Bozzer, Tala; Deshpande, Sameer; Faulkner, Guy; Rhodes, Ryan E; Spence, John C; Tremblay, Mark S; Latimer-Cheung, Amy E

2016-08-01

Introduction ParticipACTION's 2011 "Think Again" campaign aimed to draw parents', and specifically mothers', attention to the amount of physical activity (PA) their children do relative to the national guidelines (physical activity guidelines [PAG]). Purpose To evaluate ParticipACTION's "Think Again" campaign in the context of the hierarchy of effects model. Methods Data were drawn from "Think Again" campaign evaluations conducted among two cohorts of parents with children ages 5 to 11 years (3 months postcampaign launch [T1], n = 702; 15 months postlaunch [T2], n = 670). Results At T2, campaign awareness was weakly associated with parents agreeing that their children were not active enough (p = .01, d = .18). Parents who were aware of the campaign showed greater knowledge of PAG (ps < .01, ϕs > .14), had higher outcome expectations about their children engaging in PA (p < .01, d = .16), had stronger intentions to help their child meet the guidelines (p < .01, d = .18), and engaged in more parental support behaviors (p < .001, d = .31) as compared with parents who were not aware. At T1, parents aware of the campaign had greater perceived behavioral control (PBC) to influence their child's PA participation (p < .01, d = .22), whereas parents not aware of the campaign had greater PBC to find practical ways to help their child be active (p < .01, d = .26). Parental awareness of the campaign was not associated with children meeting the PAG at either time point (ps > .05). Conclusions The campaign appeared marginally effective for increasing parental knowledge of PAG and for creating realistic awareness of children's PA levels. Additional intervention strategies are needed to produce larger effects and to change parental behavior. © 2015 Society for Public Health Education.

Cat odour-induced anxiety--a study of the involvement of the endocannabinoid system.

PubMed

Sütt, Silva; Raud, Sirli; Areda, Tarmo; Reimets, Ain; Kõks, Sulev; Vasar, Eero

2008-07-01

Recent evidence suggests the involvement of the endocannabinoid (EC) system in the regulation of anxiety. The aim of present work was to study the role of the EC system in cat odour-induced anxiety in rats. Materials and methods Male Wistar rats were exposed to cat odour in home and motility cages. Exposure of rats to elevated zero-maze was used to determine changes in anxiety. Effect of rimonabant (0.3-3 mg/kg), antagonist of CB1 receptors, was studied on cat odour-induced alterations in exploratory behaviour. Real-time PCR was used to determine gene expression levels of EC-related genes in the brain. Anxiogenic-like action of cat odour was evident in the elevated zero-maze. Cat odour increased the expression of FAAH, the enzyme responsible for the degradation of anandamide, in the mesolimbic area. By contrast, in the amygdala and periaqueductal grey (PAG) levels of NAPE-PLD, the enzyme related to the synthesis of anandamide, and FAAH were remarkably decreased. Cat odour also decreased the expression of enzymes related to metabolism of 2-archidonoyl-glycerol in the amygdala and PAG. Pre-treatment of rats with rimonabant (0.3-3 mg/kg) reduced the exploratory behaviour of rats, but did not affect cat odour-induced changes. Exposure to cat odour induces anxiogenic-like effect on the behaviour in rats. Cat odour also causes moderate increase in expression of EC-related genes in the mesolimbic area, whereas significant down-regulation is established in the amygdala and PAG. Relation of predator odour-induced anxiety to the inhibition of the EC system in the amygdala and PAG is supported by behavioural studies where blockade of CB1 receptors by rimonabant induces anxiogenic-like action.

Increase in local protein concentration by field-inversion gel electrophoresis.

PubMed

Tsai, Henghang; Low, Teck Yew; Freeby, Steve; Paulus, Aran; Ramnarayanan, Kalpana; Cheng, Chung-Pui Paul; Leung, Hon-Chiu Eastwood

2007-09-26

Proteins that migrate through cross-linked polyacrylamide gels (PAGs) under the influence of a constant electric field experience negative factors, such as diffusion and non-specific trapping in the gel matrix. These negative factors reduce protein concentrations within a defined gel volume with increasing migration distance and, therefore, decrease protein separation efficiency. Enhancement of protein separation efficiency was investigated by implementing pulsed field-inversion gel electrophoresis (FIGE). Separation of model protein species and large protein complexes was compared between FIGE and constant field electrophoresis (CFE) in different percentages of PAGs. Band intensities of proteins in FIGE with appropriate ratios of forward and backward pulse times were superior to CFE despite longer running times. These results revealed an increase in band intensity per defined gel volume. A biphasic protein relative mobility shift was observed in percentages of PAGs up to 14%. However, the effect of FIGE on protein separation was stochastic at higher PAG percentage. Rat liver lysates subjected to FIGE in the second-dimension separation of two-dimensional polyarcylamide gel electrophoresis (2D PAGE) showed a 20% increase in the number of discernible spots compared with CFE. Nine common spots from both FIGE and CFE were selected for peptide sequencing by mass spectrometry (MS), which revealed higher final ion scores of all nine protein spots from FIGE. Native protein complexes ranging from 800 kDa to larger than 2000 kDa became apparent using FIGE compared with CFE. The present investigation suggests that FIGE under appropriate conditions improves protein separation efficiency during PAGE as a result of increased local protein concentration. FIGE can be implemented with minimal additional instrumentation in any laboratory setting. Despite the tradeoff of longer running times, FIGE can be a powerful protein separation tool.

Disrupted functional connectivity of the pain network in fibromyalgia.

PubMed

Cifre, Ignacio; Sitges, Carolina; Fraiman, Daniel; Muñoz, Miguel Ángel; Balenzuela, Pablo; González-Roldán, Ana; Martínez-Jauand, Mercedes; Birbaumer, Niels; Chialvo, Dante R; Montoya, Pedro

2012-01-01

To investigate the impact of chronic pain on brain dynamics at rest. Functional connectivity was examined in patients with fibromyalgia (FM) (n = 9) and healthy controls (n = 11) by calculating partial correlations between low-frequency blood oxygen level-dependent fluctuations extracted from 15 brain regions. Patients with FM had more positive and negative correlations within the pain network than healthy controls. Patients with FM displayed enhanced functional connectivity of the anterior cingulate cortex (ACC) with the insula (INS) and basal ganglia (p values between .01 and .05), the secondary somatosensory area with the caudate (CAU) (p = .012), the primary motor cortex with the supplementary motor area (p = .007), the globus pallidus with the amygdala and superior temporal sulcus (both p values < .05), and the medial prefrontal cortex with the posterior cingulate cortex (PCC) and CAU (both p values < .05). Functional connectivity of the ACC with the amygdala and periaqueductal gray (PAG) matter (p values between .001 and .05), the thalamus with the INS and PAG (both p values < .01), the INS with the putamen (p = .038), the PAG with the CAU (p = .038), the secondary somatosensory area with the motor cortex and PCC (both p values < .05), and the PCC with the superior temporal sulcus (p = .002) was also reduced in FM. In addition, significant negative correlations were observed between depression and PAG connectivity strength with the thalamus (r = -0.64, p = .003) and ACC (r = -0.60, p = .004). These findings demonstrate that patients with FM display a substantial imbalance of the connectivity within the pain network during rest, suggesting that chronic pain may also lead to changes in brain activity during internally generated thought processes such as occur at rest.

75 FR 1380 - National Drinking Water Advisory Council's Climate Ready Water Utilities Working Group Meeting...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-11

... Ready Water Utilities Working Group Meeting Announcement AGENCY: Environmental Protection Agency. ACTION... meeting of the Climate Ready Water Utilities (CRWU) Working Group of the National Drinking Water Advisory Council (NDWAC). The purpose of this meeting is for the Working Group to discuss the attributes and...

75 FR 20352 - National Drinking Water Advisory Council's Climate Ready Water Utilities Working Group Meeting...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-19

... Ready Water Utilities Working Group Meeting Announcement AGENCY: Environmental Protection Agency. ACTION...-person meeting of the Climate Ready Water Utilities (CRWU) Working Group of the National Drinking Water Advisory Council (NDWAC). The purpose of this meeting is for the Working Group to discuss key findings, the...

Percutaneous treatment of transplant renal artery stenosis in children.

PubMed

Repetto, Horacio A; Rodríguez-Rilo, Laila; Mendaro, Esteban; Basso, Laura; Galvez, Hugo; Morrone, Gabriela; Vazquez, Luis A

2004-12-01

Percutaneous treatment of renal artery stenosis (RAS) is an accepted procedure and numerous reports have been published. However, experience with its use in RAS in the transplanted kidney in children is scarce. Since 1994 we have diagnosed RAS in seven children with the use of Doppler ultrasonography (US), confirming it with percutaneous angiography (PAG). In six of the seven patients percutaneous transluminal angioplasty (PTA) was performed. In one patient a metallic stent was placed due to the extension of the arterial lesion, and a second stent was placed in another child when a re-stenosis was diagnosed 1 month after the PTA. All patients presented with hypertension (de novo or 30% increase over previous values). After ruling out acute rejection, calcineurin inhibitor toxicity, and urinary obstruction, US was performed and, when an increase in arterial flux velocity was registered, PAG was also performed. Six children showed an increase in serum creatinine (Cr) and proteinuria. Blood pressure decreased after the procedure and Cr returned to previous levels in all children. One of the grafts was lost due to chronic transplant rejection 7 years later. The other children have a functioning kidney. Although this is a small group of patients, the consistently good results and the lack of reported experience prompted us to communicate our preliminary observation.

"Freedom to go where I want": improving access to sexual and reproductive health for women with disabilities in the Philippines.

PubMed

Devine, Alexandra; Ignacio, Raquel; Prenter, Krystle; Temminghoff, Lauren; Gill-Atkinson, Liz; Zayas, Jerome; Marco, Ma Jesusa; Vaughan, Cathy

2017-05-01

Women with disabilities experience a range of violations of their sexual and reproductive rights. The Philippines ratified the United Nations Convention on the Rights of Persons with Disabilities and have laws in place to promote the rights to sexual and reproductive health and protection from violence. However, limited resourcing, and opposition to such laws undermine access to these rights for all women. Inadequate disability inclusion within policy and programming, and limited disability awareness of services, further impedes women with disabilities from attaining these rights. The W-DARE project (Women with Disability taking Action on REproductive and sexual health) was a three-year participatory action research program designed to (1) understand the sexual and reproductive health experiences and needs of women with disabilities; and (2) improve access to quality sexual and reproductive health, including violence response services, for women with disabilities in the Philippines. In response to the highlighted need for more information about sexual and reproductive health and greater access to services, the W-DARE team developed and implemented a pilot intervention focused on peer-facilitated Participatory Action Groups (PAGs) for women with disabilities. This paper focuses on the qualitative findings from the evaluation of this PAG intervention.

Final Report of the Advanced Coal Technology Work Group

EPA Pesticide Factsheets

The Advanced Coal Technology workgroup reported to the Clean Air Act Advisory Committee. This page includes the final report of the Advanced Coal Technology Work Group to the Clean Air Act Advisory Committee.

78 FR 3402 - Marine Fisheries Advisory Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-16

... Fisheries Advisory Committee AGENCY: National Marine Fisheries Service (NMFS), National Oceanic and... forth the schedule and proposed agenda of a forthcoming meeting of the Marine Fisheries Advisory... the Recreational Fisheries Working Group for submission to the NOAA Fisheries Assistant Administrator...

OPERATION SUN BEAM, SHOT SMALL BOY. Project Officer’s Report - Project 7.1.4. Transient Radiation Effects Measurements on Guidance System Circuits

DTIC Science & Technology

1985-09-01

131 3.28 Small Boy results, diode detector 132 3.29...r. ■»".",.«.. i *• • % s ■ • r-.•’WN v. i. > » • V »l ■> ills m ^ \\’ tj^ jCi "T^^^^^-^^^^^v^^ ^^^^ TEST SPECIMEN CIRCUIT TEST BOARD S...8217 % "." ■." ■. Jl ." •’ ." ." ■.’ •h k. ^ s; u a u Ü 0) •a 0) 1 s IN ä .6« 130 pag^s 131 through 132 deleted

FINE GRAIN NUCLEAR EMULSION

DOEpatents

Oliver, A.J.

1962-04-24

A method of preparing nuclear track emulsions having mean grain sizes less than 0.1 microns is described. The method comprises adding silver nitrate to potassium bromide at a rate at which there is always a constant, critical excess of silver ions. For minimum size grains, the silver ion concentration is maintained at the critical level of about pAg 2.0 to 5.0 during prectpitation, pAg being defined as the negative logarithm of the silver ion concentration. It is preferred to eliminate the excess silver at the conclusion of the precipitation steps. The emulsion is processed by methods in all other respects generally similar to the methods of the prior art. (AEC)

Heliothis zea nudivirus 1 gene hhi1 induces apoptosis which is blocked by the Hz-iap2 gene and a noncoding gene, pag1.

PubMed

Wu, Yueh-Lung; Wu, Carol P; Liu, Catherine Y Y; Lee, Song-Tay; Lee, Hsiao-Ping; Chao, Yu-Chan

2011-07-01

Heliothis zea nudivirus 1 (HzNV-1 or Hz-1 virus), previously regarded as a nonoccluded baculovirus, recently has been placed in the Nudivirus genus. This virus generates HzNV-1 HindIII-I 1 (hhi1) and many other transcripts during productive viral infection; during latent viral infection, however, persistency-associated gene 1 (pag1) is the only gene expressed. In this report, we used transient expression assays to show that hhi1 can trigger strong apoptosis in transfected cells, which can be blocked, at least partially, by the inhibitor of apoptosis genes Autographa californica iap2 (Ac-iap2) and H. zea iap2 (Hz-iap2). In addition to these two genes, unexpectedly, pag1, which encodes a noncoding RNA with no detectable protein product, was found to efficiently suppress hhi1-induced apoptosis. The assay of pro-Sf-caspase-1 processing by hhi1 transfection did not detect the small P12 subunit at any of the time intervals tested, suggesting that hhi1 of HzNV-1 induces apoptosis through alternative caspase pathways.

Antinociception induced by intravenous dipyrone (metamizol) upon dorsal horn neurons: involvement of endogenous opioids at the periaqueductal gray matter, the nucleus raphe magnus, and the spinal cord in rats.

PubMed

Vazquez, Enrique; Hernandez, Norma; Escobar, William; Vanegas, Horacio

2005-06-28

Microinjection of dipyrone (metamizol) into the periaqueductal gray matter (PAG) in rats causes antinociception. This is mediated by endogenous opioidergic circuits located in the PAG itself, in the nucleus raphe magnus and adjacent structures, and in the spinal cord. The clinical relevance of these findings, however, is unclear. Therefore, in the present study, dipyrone was administered intravenously, and the involvement of endogenous opioidergic circuits in the so-induced antinociception was investigated. In rats, responses of dorsal spinal wide-dynamic range neurons to mechanical noxious stimulation of a hindpaw were strongly inhibited by intravenous dipyrone (200 mg/kg). This effect was abolished by microinjection of naloxone (0.5 microg/0.5 microl) into the ventrolateral and lateral PAG or into the nucleus raphe magnus or by direct application of naloxone (50 microg/50 microl) onto the spinal cord surface above the recorded neuron. These results show that dipyrone, a non-opioid analgesic with widespread use in Europe and Latin America, when administered in a clinically relevant fashion causes antinociception by activating endogenous opioidergic circuits along the descending pain control system.

Complementary roles for amygdala and periaqueductal gray in temporal-difference fear learning.

PubMed

Cole, Sindy; McNally, Gavan P

2009-01-01

Pavlovian fear conditioning is not a unitary process. At the neurobiological level multiple brain regions and neurotransmitters contribute to fear learning. At the behavioral level many variables contribute to fear learning including the physical salience of the events being learned about, the direction and magnitude of predictive error, and the rate at which these are learned about. These experiments used a serial compound conditioning design to determine the roles of basolateral amygdala (BLA) NMDA receptors and ventrolateral midbrain periaqueductal gray (vlPAG) mu-opioid receptors (MOR) in predictive fear learning. Rats received a three-stage design, which arranged for both positive and negative prediction errors producing bidirectional changes in fear learning within the same subjects during the test stage. Intra-BLA infusion of the NR2B receptor antagonist Ifenprodil prevented all learning. In contrast, intra-vlPAG infusion of the MOR antagonist CTAP enhanced learning in response to positive predictive error but impaired learning in response to negative predictive error--a pattern similar to Hebbian learning and an indication that fear learning had been divorced from predictive error. These findings identify complementary but dissociable roles for amygdala NMDA receptors and vlPAG MOR in temporal-difference predictive fear learning.

Toward a more precise, clinically--informed pathophysiology of pathological laughing and crying.

PubMed

Lauterbach, Edward C; Cummings, Jeffrey L; Kuppuswamy, Preetha Sharone

2013-09-01

Involuntary emotional expression disorder (IEED) includes the syndromes of pathological laughing and crying (PLC) and emotional lability (EL). Review of the lesion, epilepsy, and brain stimulation literature leads to an updated pathophysiology of IEED. A volitional system involving frontoparietal (primary motor, premotor, supplementary motor, posterior insular, dorsal anterior cingulate gyrus (ACG), primary sensory and related parietal) corticopontine projections inhibits an emotionally-controlled system involving frontotemporal (orbitofrontal, ventral ACG, anterior insular, inferior temporal, and parahippocampal) projections targeting the amygdala-hypothalamus-periaqueductal gray (PAG)-dorsal tegmentum (dTg) complex that regulates emotional displays. PAG activity is regulated by glutamatergic NMDA, muscarinic M1-3, GABA-A, dopamine D2, norepinephrine alpha-1,2, serotonin 5HT1a, 5HT1b/d, and sigma-1 receptors, with an acetylcholine/GABA balance mediating volitional inhibition of the PAG. Lesions of the volitional corticopontine projections (or of their feedback or processing circuits) can produce PLC. Direct activation of the emotional pathway can result in EL and the laughing or crying of gelastic and dacrystic epilepsy. A criterion-based nosology of PLC and EL subtypes is offered. Copyright © 2013 Elsevier Ltd. All rights reserved.

Depression-like behavior in rat: Involvement of galanin receptor subtype 1 in the ventral periaqueductal gray

PubMed Central

Wang, Peng; Li, Hui; Barde, Swapnali; Zhang, Ming-Dong; Sun, Jing; Wang, Tong; Zhang, Pan; Luo, Hanjiang; Wang, Yongjun; Yang, Yutao; Wang, Chuanyue; Svenningsson, Per; Theodorsson, Elvar; Hökfelt, Tomas G. M.; Xu, Zhi-Qing David

2016-01-01

The neuropeptide galanin coexists in rat brain with serotonin in the dorsal raphe nucleus and with noradrenaline in the locus coeruleus (LC), and it has been suggested to be involved in depression. We studied rats exposed to chronic mild stress (CMS), a rodent model of depression. As expected, these rats showed several endophenotypes relevant to depression-like behavior compared with controls. All these endophenotypes were normalized after administration of a selective serotonin reuptake inhibitor. The transcripts for galanin and two of its receptors, galanin receptor 1 (GALR1) and GALR2, were analyzed with quantitative real-time PCR using laser capture microdissection in the following brain regions: the hippocampal formation, LC, and ventral periaqueductal gray (vPAG). Only Galr1 mRNA levels were significantly increased, and only in the latter region. After knocking down Galr1 in the vPAG with an siRNA technique, all parameters of the depressive behavioral phenotype were similar to controls. Thus, the depression-like behavior in rats exposed to CMS is likely related to an elevated expression of Galr1 in the vPAG, suggesting that a GALR1 antagonist could have antidepressant effects. PMID:27457954

The Vγ9Vδ2 T Cell Antigen Receptor and Butyrophilin-3 A1: Models of Interaction, the Possibility of Co-Evolution, and the Case of Dendritic Epidermal T Cells

PubMed Central

Karunakaran, Mohindar M.; Herrmann, Thomas

2014-01-01

Most circulating human gamma delta T cells are Vγ9Vδ2 T cells. Their hallmark is the expression of T cell antigen receptors (TCR) whose γ-chains show a Vγ9-JP (Vγ2-Jγ1.2) rearrangement and are paired with Vδ2-containing δ-chains, a dominant TCR configuration, which until recently seemed to occur in primates only. Vγ9Vδ2 T cells respond to phosphoantigens (PAg) such as (E)-4-Hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP), which is produced by many pathogens and isopentenyl pyrophosphate (IPP), which accumulates in certain tumors or cells treated with aminobisphosphonates such as zoledronate. A prerequisite for PAg-induced activation is the contact of Vγ9Vδ2 T cells with cells expressing butyrophilin-3 A1 (BTN3A1). We will first critically review models of how BTN3 might act in PAg-mediated Vγ9Vδ2 T cell activation and then address putative co-evolution of Vγ9, Vδ2, and BTN3 genes. In those rodent and lagomorphs used as animal models, all three genes are lost but a data-base analysis showed that they emerged together with placental mammals. A strong concomitant conservation of functional Vγ9, Vδ2, and BTN3 genes in other species suggests co-evolution of these three genes. A detailed analysis was performed for the new world camelid alpaca (Vicugna pacos). It provides an excellent candidate for a non-primate species with presumably functional Vγ9Vδ2 T cells since TCR rearrangements share features characteristic for PAg-reactive primate Vγ9Vδ2 TCR and proposed PAg-binding sites of BTN3A1 have been conserved. Finally, we analyze the possible functional relationship between the butyrophilin-family member Skint1 and the γδ TCR-V genes used by murine dendritic epithelial T cells (DETC). Among placental mammals, we identify five rodents, the cow, a bat, and the cape golden mole as the only species concomitantly possessing potentially functional homologs of murine Vγ3, Vδ4 genes, and Skint1 gene and suggest to search for DETC like cells in these species. PMID:25566259

75 FR 51473 - Houston/Galveston Navigation Safety Advisory Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-20

... Houston/Galveston Navigation Safety Advisory Committee (HOGANSAC) and its working groups will meet in... noon. The Committee's working groups will meet on September 9, 2010, from 9 a.m. to noon. These... materials distributed to each member of the Committee or working group should reach the Coast Guard on or...

78 FR 24289 - Aviation Rulemaking Advisory Committee (ARAC) Airman Testing Standards and Training Working Group...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-24

... Rulemaking Advisory Committee (ARAC) Airman Testing Standards and Training Working Group (ATSTWG) AGENCY... FAA will post all comments it receives, without change, to http://www.regulations.gov , including any... several draft documents developed by the Airman Testing Standards and Training Working Group. The...

Synthesis of novel fluorene-based two-photon absorbing molecules and their applications in optical data storage, microfabrication, and stimulated emission depletion

NASA Astrophysics Data System (ADS)

Yanez, Ciceron

2009-12-01

Two-photon absorption (2PA) has been used for a number of scientific and technological applications, exploiting the fact that the 2PA probability is directly proportional to the square of the incident light intensity (while one-photon absorption bears a linear relation to the incident light intensity). This intrinsic property of 2PA leads to 3D spatial localization, important in fields such as optical data storage, fluorescence microscopy, and 3D microfabrication. The spatial confinement that 2PA enables has been used to induce photochemical and photophysical events in increasingly smaller volumes and allowed nonlinear, 2PA-based, technologies to reach sub-diffraction limit resolutions. The primary focus of this dissertation is the development of novel, efficient 2PA, fluorene-based molecules to be used either as photoacid generators (PAGs) or fluorophores. A second aim is to develop more effective methods of synthesizing these compounds. As a third and final objective, the new molecules were used to develop a write-once-read many (WORM) optical data storage system, and stimulated emission depletion probes for bioimaging. In Chapter I, the microwave-assisted synthesis of triarylsulfonium salt photoacid generators (PAGs) from their diphenyliodonium counterparts is reported. The microwave-assisted synthesis of these novel sulfonium salts afforded reaction times 90 to 420 times faster than conventional thermal conditions, with photoacid quantum yields of new sulfonium PAGs ranging from 0.01 to 0.4. These PAGs were used to develop a fluorescence readout-based, nonlinear three-dimensional (3D) optical data storage system (Chapter II). In this system, writing was achieved by acid generation upon two-photon absorption (2PA) of a PAG (at 710 or 730 nm). Readout was then performed by interrogating two-photon absorbing dyes, after protonation, at 860 nm. Two-photon recording and readout of voxels was demonstrated in five and eight consecutive, crosstalk-free layers within a polymer matrix, generating a data storage capacity of up to 1.8 x 1013 bits/cm3. The possibility of using these PAGs in microfabrication is described in Chapter III, where two-photon induced cationic ring-opening polymerization (CROP) crosslinking of an SU8 resin is employed to produce free-standing microstructures. Chapter IV describes the investigation of one- and two-photon stimulated emission transitions by the fluorescence quenching of a sulfonyl-containing fluorene compound in solution at room temperate using a picosecond pump-probe technique. The nature of stimulated transitions under various fluorescence excitation and quenching conditions were analyzed theoretically, and good agreement with experimental data was demonstrated. Two-photon stimulated transitions S1 → S0 were shown at lambdaq = 1064 nm. The two-photon stimulated emission cross section of the sulfonyl fluorophore was estimated as delta2PE (lambda q) ≈ 240--280 GM, making this compound a good candidate for use in two-photon stimulated emission depletion (STED) microscopy.

76 FR 25702 - National Maritime Security Advisory Committee; Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-05

... DEPARTMENT OF HOMELAND SECURITY Coast Guard [USCG-2011-0310] National Maritime Security Advisory... Maritime Security Advisory Committee (NMSAC) will meet by teleconference to discuss the results of the... Maritime Organization (IMO). Agenda (1) Results of Seafarer Access Working Group's review and...

76 FR 22910 - ACHP Quarterly Business Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-25

... ADVISORY COUNCIL ON HISTORIC PRESERVATION ACHP Quarterly Business Meeting AGENCY: Advisory Council on Historic Preservation. ACTION: Notice. SUMMARY: Notice is hereby given that the Advisory Council... Historic Preservation Working Group IX. New Business X. Adjourn Note: The meetings of the ACHP are open to...

76 FR 7816 - Civil Nuclear Trade Advisory Committee Public Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-11

... U.S. Japan Global Nuclear Energy Cooperation Working Group, U.S. industry program at the... submitted to the Civil Nuclear Trade Advisory Committee, Office of Energy & Environmental Industries, Room... DEPARTMENT OF COMMERCE International Trade Administration Civil Nuclear Trade Advisory Committee...

Korean Military Advisory Group (KMAG): A Model for Success

DTIC Science & Technology

2010-05-15

43-45. 16 Alan Millett, The War in Korea, 1945-1950: A House Burning, ( Lawrence : University Press of Kansas, 2005), 172 17 Ibid., 75 18...A great step forward for the advisory effort came in the form of US Army Captain James H. Hausman . Captain Hausman came to Korea in 1946 as one of...group that Hausman joined in 1946 was an organization in crisis, run with limited resources. His mandate from the nascent advisory group’s commander

75 FR 51840 - State of Arizona Resource Advisory Council Meeting

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2010-08-23

... Policy and Management Act of 1976 and the Federal Advisory Committee Act of 1972, the U.S. Department of... implemented; RAC questions on BLM District Managers' Reports; and reports by RAC working groups. A public...) Working Group Report, REA Working Group meeting schedule and future BLM/FS recreation fee proposals. The...

78 FR 5242 - Membership in the National Parks Overflights Advisory Group Aviation Rulemaking Committee

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2013-01-24

... commercial air tour operator interests due to an incumbent member's completion of a three-year term... environmental concerns and commercial air tour operator interests need to apply by February 22, 2013. FOR... advisory group is comprised of a balanced group of representatives of general aviation, commercial air tour...

77 FR 66856 - Merchant Marine Personnel Advisory Committee: Intercessional Meeting AGENCY: Coast Guard, DHS

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-07

... Committee Working Group Meeting. SUMMARY: A working group of the Merchant Marine Personnel Advisory Committee (MERPAC) will meet to work on Task Statement 77 concerning the development of new performance...-Technical Ratings. This meeting will be open to the public. DATES: A MERPAC working group will meet on...

Phase I Recommendations by the Air Quality Management Work Group to the Clean Air Act Advisory Committee

EPA Pesticide Factsheets

Recommendations to the Clean Air Act Advisory Committee by Air Quality Management Work Group addressing the recommendations made by the National Research Council to improve the U.S. air quality management system.

Audit in general practice: factors influencing participation.

PubMed Central

Baker, R.; Robertson, N.; Farooqi, A.

1995-01-01

OBJECTIVE--To identify the factors influencing participation in a single topic audit initiated by a medical audit advisory group. DESIGN--Interview and questionnaire survey of general practitioners who had been invited to take part in an audit of vitamin B-12. SETTING--All 147 general practices in Leicestershire. MAIN OUTCOME MEASURES--Aspects of structure, attitude, and behaviour that influenced participation or non-participation. RESULTS--75 practices completed the audit, 49 withdrew after initial agreement, and 23 refused to take part at the outset. Participants were more likely than those who refused to view the advisory group as useful or a threat and to have positive thoughts about audit but less likely to have previously undertaken audit entailing implementation of change. Participants were more likely than those who withdrew to have positive thoughts about audit and to have discussed whether to take part within the practice but were less likely to view the advisory group as useful. The most common reason given for withdrawal was lack of time. CONCLUSIONS--Participation was influenced by attitudes towards audit in general and the advisory group in particular and by aspects of behaviour such as communication within the practice. Practical support and resources may help some practices undertake audit, but advisory groups must also deal with attitudes and unsatisfactory communication in practice teams. PMID:7613323

77 FR 19301 - Prince William Sound Regional Citizens' Advisory Council Charter Renewal

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-30

... DEPARTMENT OF HOMELAND SECURITY Coast Guard [USCG-2012-0099] Prince William Sound Regional... Prince William Sound Regional Citizens' Advisory Council (PWSRCAC) as an alternative voluntary advisory group for Prince William Sound, Alaska. This certification allows the PWSRCAC to monitor the activities...

16 CFR 1018.4 - Applicability.

Code of Federal Regulations, 2012 CFR

2012-01-01

... organizations: (1) Any local civic group whose primary function is that of rendering a public service with... non-statutory) subject to the jurisdiction of the Commission. This part also shall apply to ad hoc advisory committees and non-Commission established advisory committees when they are performing advisory...

16 CFR 1018.4 - Applicability.

Code of Federal Regulations, 2014 CFR

2014-01-01

... organizations: (1) Any local civic group whose primary function is that of rendering a public service with... non-statutory) subject to the jurisdiction of the Commission. This part also shall apply to ad hoc advisory committees and non-Commission established advisory committees when they are performing advisory...

16 CFR 1018.4 - Applicability.

Code of Federal Regulations, 2011 CFR

2011-01-01

... organizations: (1) Any local civic group whose primary function is that of rendering a public service with... non-statutory) subject to the jurisdiction of the Commission. This part also shall apply to ad hoc advisory committees and non-Commission established advisory committees when they are performing advisory...

16 CFR § 1018.4 - Applicability.

Code of Federal Regulations, 2013 CFR

2013-01-01

... organizations: (1) Any local civic group whose primary function is that of rendering a public service with... non-statutory) subject to the jurisdiction of the Commission. This part also shall apply to ad hoc advisory committees and non-Commission established advisory committees when they are performing advisory...

16 CFR 1018.4 - Applicability.

Code of Federal Regulations, 2010 CFR

2010-01-01

... organizations: (1) Any local civic group whose primary function is that of rendering a public service with... non-statutory) subject to the jurisdiction of the Commission. This part also shall apply to ad hoc advisory committees and non-Commission established advisory committees when they are performing advisory...

Advances in biotechnology and linking outputs to variation in complex traits: Plant and Animal Genome meeting January 2012.

PubMed

Appels, R; Barrero, R; Bellgard, M

2012-03-01

The Plant and Animal Genome (PAG, held annually) meeting in January 2012 provided insights into the advances in plant, animal, and microbe genome studies particularly as they impact on our understanding of complex biological systems. The diverse areas of biology covered included the advances in technologies, variation in complex traits, genome change in evolution, and targeting phenotypic changes, across the broad spectrum of life forms. This overview aims to summarize the major advances in research areas presented in the plenary lectures and does not attempt to summarize the diverse research activities covered throughout the PAG in workshops, posters, presentations, and displays by suppliers of cutting-edge technologies.

78 FR 55336 - Membership in the National Parks Overflights Advisory Group Aviation Rulemaking Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-10

... DEPARTMENT OF TRANSPORTATION Federal Aviation Administration Membership in the National Parks Overflights Advisory Group Aviation Rulemaking Committee AGENCY: Federal Aviation Administration... Park Service (NPS) and the Federal Aviation Administration (FAA) invited interested persons to apply to...

78 FR 25338 - Membership in the National Parks Overflights Advisory Group Aviation Rulemaking Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-30

... DEPARTMENT OF TRANSPORTATION Federal Aviation Administration Membership in the National Parks Overflights Advisory Group Aviation Rulemaking Committee AGENCY: Federal Aviation Administration... the Federal Aviation Administration (FAA) invited interested persons to apply to fill one opening on...

77 FR 30304 - Merchant Marine Personnel Advisory Committee: Intercessional Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-22

... Committee Working Group Meeting. SUMMARY: A working group of the Merchant Marine Personnel Advisory Committee (MERPAC) will meet to discuss Task Statement 76, ``Review of Performance Measures (Assessment Criteria);'' and Task Statement 77, ``Development of Performance Measures (Assessment Criteria).'' This...

77 FR 5031 - Notice of a Meeting of a Working Group of the Advisory Committee to the Director

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-01

... the public about a meeting of the Advisory Committee to the Director (ACD) Working Group on Diversity in the Biomedical Research Workforce (WGBDRW). DATES: The meeting will be held on Tuesday, February...

78 FR 18616 - Prince William Sound Regional Citizens' Advisory Council (PWSRCAC) Charter Renewal

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-27

... DEPARTMENT OF HOMELAND SECURITY Coast Guard [Docket No. USCG-2013-0088] Prince William Sound... the Prince William Sound Regional Citizens' Advisory Council (PWSRCAC) as an alternative voluntary advisory group for Prince William Sound, Alaska. This certification allows the PWSRCAC to monitor the...

75 FR 16159 - Prince William Sound Regional Citizens' Advisory Council (PWSRCAC) Charter Renewal

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-31

... DEPARTMENT OF HOMELAND SECURITY Coast Guard [USCG-2010-0121] Prince William Sound Regional... the Prince William Sound Regional Citizens' Advisory Council (PWSRCAC) as an alternative voluntary advisory group for Prince William Sound, Alaska. This certification allows the PWSRCAC to monitor the...

76 FR 24506 - Prince William Sound Regional Citizens' Advisory Council (PWSRCAC) Charter Renewal

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-02

... DEPARTMENT OF HOMELAND SECURITY Coast Guard [Docket No. USCG-2011-0142] Prince William Sound... the Prince William Sound Regional Citizens' Advisory Council (PWSRCAC) as an alternative voluntary advisory group for Prince William Sound, Alaska. This certification allows the PWSRCAC to monitor the...

Endangered Species Day | Endangered Species Coalition

Science.gov Websites

Skip to content About Us Staff Board Advisory Board Scientific Advisory Committee Endangered Species Day Advisory Board Member Groups Blog Campaigns Endangered Species Day Southern Resident Orcas Species Education Program Vanishing Endangered Species Take Action Join the Activist Network Become a

Technical Evaluation Report on the Fluid Dynamics Panel Specialists’ Meeting on Effects of Adverse Weather on Aerodynamics (Les Effets des Conditions Meteorologiques Adverses sur l’Aerodynamique)

DTIC Science & Technology

1991-11-01

AD-A245 117 III~i~IIiiIiIIi~ifhII _________________________AGARD-R306 0 AGARD ADVISORY GROUP FOR AEROSPACE RESEARCH & DEVELOPMENT 4 7 RUE ANCELLE...REPRODUCE LEGIBLY. AGARD-AR-306 ADVISORY GROUP FOR AEROSPACE RESEARCH & DEVELOPMENT 7 RUE ANCELLE 92200 NEUILLY SUR SEINE FRANCE AGARD ADVISORY RIEPORT...Conditions NMeleorolovioiue,, Adverscs sur rAerodynarminiuc) - J.J. Reinrnann National ,\\cronautico and Space .\\drmintration L eip Research (Center

75 FR 28649 - State of Arizona Resource Advisory Council Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-21

... Policy and Management Act of 1976 and the Federal Advisory Committee Act of 1972, the U.S. Department of... Managers' Reports; and reports by RAC working groups. A public comment period will be provided at 11:30 a.m... brief review of the Recreation Enhancement Act (REA) Working Group Report, REA Working Group meeting...

Public Participation. Instructor Guide. Working for Clean Water: An Information Program for Advisory Groups.

ERIC Educational Resources Information Center

Buskirk, E. Drannon, Jr.; Auker, Dennis

Participants in the learning session described will become familiar with successful public participation strategies and learn about the role of advisory groups in developing public participation programs. The manual is designed to guide instructors who will facilitate the 65-minute session for citizen groups. A slide-tape program is available to…

78 FR 54668 - Cook Inlet Regional Citizens' Advisory Council (CIRCAC) Charter Renewal

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-05

... DEPARTMENT OF HOMELAND SECURITY Coast Guard [USCG-2013-0720] Cook Inlet Regional Citizens.... SUMMARY: The purpose of this notice is to inform the public that the Coast Guard has recertified the Cook Inlet Regional Citizens' Advisory Council (CIRCAC) as an alternative voluntary advisory group for Cook...

76 FR 62428 - Cook Inlet Regional Citizens' Advisory Council (CIRCAC) Charter Renewal

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-07

... DEPARTMENT OF HOMELAND SECURITY Coast Guard [USCG-2011-0852] Cook Inlet Regional Citizens.... SUMMARY: The purpose of this notice is to inform the public that the Coast Guard has recertified the Cook Inlet Regional Citizens' Advisory Council (CIRCAC) as an alternative voluntary advisory group for Cook...

Maritime security report. May 2000 [Organization of American States Tactical Advisory Group on Port Security

DOT National Transportation Integrated Search

2000-05-01

The member countries of the Organization of American States (OAS) have recognized that a coordinated multilateral approach to improving port security in the Western Hemisphere is needed and has established a Technical Advisory Group on Port Security ...

Developments of the studies on the polymerization under microgravity

NASA Astrophysics Data System (ADS)

Li, Ping; Yi, Zongchun

Microgravity has been recognized as a new and useful way of processing materials for pharmacology biology and microelectronic In microgravity there is no direction for gravity sensitive processes which take part in crystal growth convection sedimentation physical--chemical processes in biological objects The absent of gravity leads to the possibility of synthesis of new materials which cannot be prepared on Earth The perspective for possible biotechnological applications gave an impetus to a series of experiments on polymerization in space by NASA Rocket-Space Corporation RSC ENERGIYA the Institute of Bioorganic Chemistry Uzbekistan and so on The influence of microgravity on polymerization is based on the exclusion of convection and sedimentation processes in curing polymer Under microgravity condition a frontal polymerization process and creation of high homogeneous polyacrilamide gel were observed 1 Thus a much better resolution result of proteins by electrophoresis on orbital PAG matrices was obtained than that on terrestrial PAG matrices A deeper understanding of conditions responsible for generation of physical properties of PAG synthesized on the Earth was a strong motivation for seeking gravity-sensitive mechanisms of polymerization The polymerization under microgravity can potentially applied on functional polymer The conductive polymer such as polypyrrole is usually utilized especially for microelectronics The polymerization of pyrrole in microgravity conditions was made to prepare polymer particles having shapes

Anti-wear additive content in fully synthetic PAO and PAG base oils and its effect on electrostatic and tribological phenomena in a rotating shaft-oil-lip seal system

NASA Astrophysics Data System (ADS)

Gajewski, Juliusz B.; Głogowski, Marek J.

2013-03-01

The paper presents the results of experiments on electrostatic and tribological aspects of different anti-wear additive's contents when an additive is blended with different fully synthetic (poly-α-olefin) and PAG (polyalkylene glycol) base oils in a rotating shaft-oil and oil-lip seal interfacial system. The experimental results are the relationships of electric potential induced in a lip seal's stiffening ring to angular velocity of a rotating metal shaft and to temperature of the oils tested. The braking torque of a shaft is measured with a torquemeter sensor connected directly with a microprocessor-based system for controlling the rotational speed and for measuring the shaft's braking torque and oil temperature. The beneficial and promising results are obtained for PAG when an external DC electric field is applied to the system and the braking torque is then reduced for a certain combination of the base oil and additive's contents. On the basis of the former and present research results an analysis is made to permit one to show how the type of the oils and additives tested can affect both interfaces: rotating shaft-oil and oil-lip of the lip seal and especially the braking torque.

Transformation of an edible crop with the pagA gene of Bacillus anthracis.

PubMed

Aziz, Mohammad Azhar; Sikriwal, Deepa; Singh, Samer; Jarugula, Sridhar; Kumar, P Anand; Bhatnagar, Rakesh

2005-09-01

Vaccination against anthrax is the most important strategy to combat the disease. This study describes a generation of edible transgenic crop expressing, functional protective antigen (PA). In vitro studies showed that the plant-expressed antigen is qualitatively similar to recombinant PA. Immunization studies in mouse animal models indicated the generation of PA-specific neutralizing antibodies and stressed the need for improving expression levels to generate higher antibody titers. Genetic engineering of a plant organelle offers immense scope for increasing levels of antigen expression. An AT-rich PA gene (pagA) coding for the 83-kDa PA molecule was thus cloned and expressed in tobacco chloroplasts. Biolistics was used for the transformation of a chloroplast genome under a set of optimized conditions. The expression of the pagA gene with 69% AT content was highly favored by an AT-rich chloroplast genome. A multifold expression level of functional PA was obtained as compared with the nuclear transgenic tobacco plants. This report describes for the first time a comprehensive study on generating transgenic plants expressing PA, which may serve as a source of an edible vaccine against anthrax. Two important achievements of expressing PA in an edible crop and use of chloroplast technology to enhance the expression levels are discussed here.

Methionine biosynthesis in higher plants. I. Purification and characterization of cystathionine gamma-synthase from spinach chloroplasts.

PubMed

Ravanel, S; Droux, M; Douce, R

1995-01-10

Cystathionine gamma-synthase, the first enzyme specific for the methionine biosynthetic pathway, was purified to apparent homogeneity from spinach leaf chloroplasts. A nonradioactive assay based on O-phthaldialdehyde derivatization of L-cystathionine and fluorescence detection was developed to determine the cystathionine gamma-synthase activity. A unique cystathionine gamma-synthase activity was located in the stromal fraction of chloroplasts while cystathionine beta-lyase, the second enzyme of the transsulfuration pathway, was associated with both the chloroplastic and cytosolic compartments (see companion manuscript). The purified enzyme exhibited a specific activity of 13 U mg-1. As estimated by gel filtration and polyacrylamide gel electrophoresis (PAGE) under nondenaturing conditions followed by activity staining, the native enzyme had an apparent M(r) of 215,000. On the basis of sodium dodecyl sulfate-PAGE, purified cystathionine gamma-synthase migrated as two molecular species of M(r) 53,000 and 50,000 that are identical in their N-termini. The absorption spectrum obtained at pH 7.5 exhibited a peak at 425 nm due to pyridoxal 5'-phosphate (PLP). The purified enzyme catalyzed the formation of L-cystathionine or L-homocysteine depending on the sulfur-containing substrate, L-cysteine or sulfide. Maximal cystathionine gamma-synthase activity was found at pH 7.4. The apparent Km values for O-phospho-L-homoserine (the unique homoserine ester synthesized in the chloroplast), L-cysteine, and sulfide were 1.4, 0.18, and 0.6 mM, respectively. Inactivation of cystathionine gamma-synthase by DL-propargylglycine (PAG) showed pseudo-first-order kinetics and data were consistent with the existence of an intermediate reversible enzyme-inhibitor complex (Kappi = 140 microM) preceding the formation of a final enzyme-inhibitor complex (kd = 24 x 10(-3) s-1). The irreversibility of the inhibition and the partial restoration of the activity by pyridoxal-phosphate suggest that PAG interacts with the PLP prosthetic group of the enzyme. Kinetic and equilibrium binding studies showed that PAG binding to PLP was considerably enhanced in the enzyme binding pocket compared to that with PLP free in solution.

The cholinergic agonist carbachol increases the frequency of spontaneous GABAergic synaptic currents in dorsal raphe serotonergic neurons in the mouse.

PubMed

Yang, C; Brown, R E

2014-01-31

Dorsal raphe nucleus (DRN) serotonin (5-HT) neurons play an important role in feeding, mood control and stress responses. One important feature of their activity across the sleep-wake cycle is their reduced firing during rapid-eye-movement (REM) sleep which stands in stark contrast to the wake/REM-on discharge pattern of brainstem cholinergic neurons. A prominent model of REM sleep control posits a reciprocal interaction between these cell groups. 5-HT inhibits cholinergic neurons, and activation of nicotinic receptors can excite DRN 5-HT neurons but the cholinergic effect on inhibitory inputs is incompletely understood. Here, in vitro, in DRN brain slices prepared from GAD67-GFP knock-in mice, a brief (3 min) bath application of carbachol (50 μM) increased the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) in GFP-negative, putative 5-HT neurons but did not affect miniature (tetrodotoxin-insensitive) IPSCs. Carbachol had no direct postsynaptic effect. Thus, carbachol likely increases the activity of local GABAergic neurons which synapse on 5-HT neurons. Removal of dorsal regions of the slice including the ventrolateral periaqueductal gray (vlPAG) region where GABAergic neurons projecting to the DRN have been identified, abolished the effect of carbachol on sIPSCs whereas the removal of ventral regions containing the oral region of the pontine reticular nucleus (PnO) did not. In addition, carbachol directly excited GFP-positive, GABAergic vlPAG neurons. Antagonism of both muscarinic and nicotinic receptors completely abolished the effects of carbachol. We suggest cholinergic neurons inhibit DRN 5-HT neurons when acetylcholine levels are lower i.e. during quiet wakefulness and the beginning of REM sleep periods, in part via excitation of muscarinic and nicotinic receptors located on local vlPAG and DRN GABAergic neurons. Higher firing rates or burst firing of cholinergic neurons associated with attentive wakefulness or phasic REM sleep periods leads to excitation of 5-HT neurons via the activation of nicotinic receptors located postsynaptically and presynaptically on excitatory afferents. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

The Cholinergic Agonist Carbachol Increases the Frequency of Spontaneous GABAergic Synaptic Currents in Dorsal Raphe Serotonergic Neurons in the Mouse

PubMed Central

Yang, Chun; Brown, Ritchie E.

2013-01-01

Dorsal raphe nucleus (DRN) serotonin (5-HT) neurons play an important role in feeding, mood control and stress responses. One important feature of their activity across the sleep-wake cycle is their reduced firing during rapid-eye-movement (REM) sleep which stands in stark contrast to the wake/REM-on discharge pattern of brainstem cholinergic neurons. A prominent model of REM sleep control posits a reciprocal interaction between these cell groups. 5-HT inhibits cholinergic neurons, and activation of nicotinic receptors can excite DRN 5-HT neurons but the cholinergic effect on inhibitory inputs is incompletely understood. Here, in vitro, in DRN brain slices prepared from GAD67-GFP knock-in mice, a brief (3 min) bath application of carbachol (50 μM) increased the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) in GFP-negative, putative serotonin neurons but did not affect miniature (tetrodotoxin-insensitive) IPSCs. Carbachol had no direct postsynaptic effect. Thus, carbachol likely increases the activity of local GABAergic neurons which synapse on 5-HT neurons. Removal of dorsal regions of the slice including the ventrolateral periaqueductal gray (vlPAG) region where GABAergic neurons projecting to the DRN have been identified, abolished the effect of carbachol on sIPSCs whereas removal of ventral regions containing the oral region of the pontine reticular nucleus (PnO) did not. In addition, carbachol directly excited GFP-positive, GABAergic vlPAG neurons. Antagonism of both muscarinic and nicotinic receptors completely abolished the effects of carbachol. We suggest cholinergic neurons inhibit DRN 5-HT neurons when acetylcholine levels are lower i.e. during quiet wakefulness and the beginning of REM sleep periods, in part via excitation of muscarinic and nicotinic receptors located on local vlPAG and DRN GABAergic neurons. Higher firing rates or burst firing of cholinergic neurons associated with attentive wakefulness or phasic REM sleep periods leads to excitation of 5-HT neurons via activation of nicotinic receptors located postsynaptically and presynaptically on excitatory afferents. PMID:24231737

Cooperative regulation of anxiety and panic-related defensive behaviors in the rat periaqueductal grey matter by 5-HT1A and μ-receptors.

PubMed

Roncon, Camila M; Biesdorf, Carla; Coimbra, Norberto C; Audi, Elisabeth A; Zangrossi, Hélio; Graeff, Frederico G

2013-12-01

Previous results with the elevated T-maze (ETM) test indicate that the antipanic action of serotonin (5-HT) in the dorsal periaqueductal grey (dPAG) depends on the activation endogenous opioid peptides. The aim of the present work was to investigate the interaction between opioid- and serotonin-mediated neurotransmission in the modulation of defensive responses in rats submitted to the ETM. The obtained results showed that intra-dPAG administration of morphine significantly increased escape latency, a panicolytic-like effect that was blocked by pre-treatment with intra-dPAG injection of either naloxone or the 5-HT1A antagonist N-[2-[4-(2-methoxyphenyl)-1 piperazinyl] ethyl] -N- 2- pyridinyl-ciclohexanecarboxamide maleate (WAY-100635). In addition, previous administration of naloxone antagonized both the anti-escape and the anti-avoidance (anxiolytic-like) effect of the 5-HT1A agonist (±)-8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide (8-OH-DPAT), but did not affect the anti-escape effect of the 5-HT2A agonist (±)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI). Moreover, the combination of sub-effective doses of locally administered 5-HT and morphine significantly impaired ETM escape performance. Finally, the µ-antagonist D-PHE-CYS-TYR-D-TRP-ORN-THR-PEN (CTOP) blocked the anti-avoidance as well as the anti-escape effect of 8-OHDPAT, and the association of sub-effective doses of the µ-opioid receptor agonist [D-Ala(2), N-Me-Phe(4), Gly(5)-ol]-enkephalin acetate salt (DAMGO) and of 8-OHDPAT had anti-escape and anti-avoidance effects in the ETM. These results suggest a synergic interaction between the 5-HT1A and the µ-opioid receptor at post-synaptic level on neurons of the dPAG that regulate proximal defense, theoretically related to panic attacks.

Revealing the inventory of type III effectors in Pantoea agglomerans gall-forming pathovars using draft genome sequences and a machine-learning approach.

PubMed

Nissan, Gal; Gershovits, Michael; Morozov, Michael; Chalupowicz, Laura; Sessa, Guido; Manulis-Sasson, Shulamit; Barash, Isaac; Pupko, Tal

2018-02-01

Pantoea agglomerans, a widespread epiphytic bacterium, has evolved into a hypersensitive response and pathogenicity (hrp)-dependent and host-specific gall-forming pathogen by the acquisition of a pathogenicity plasmid containing a type III secretion system (T3SS) and its effectors (T3Es). Pantoea agglomerans pv. betae (Pab) elicits galls on beet (Beta vulgaris) and gypsophila (Gypsophila paniculata), whereas P. agglomerans pv. gypsophilae (Pag) incites galls on gypsophila and a hypersensitive response (HR) on beet. Draft genome sequences were generated and employed in combination with a machine-learning approach and a translocation assay into beet roots to identify the pools of T3Es in the two pathovars. The genomes of the sequenced Pab4188 and Pag824-1 strains have a similar size (∼5 MB) and GC content (∼55%). Mutational analysis revealed that, in Pab4188, eight T3Es (HsvB, HsvG, PseB, DspA/E, HopAY1, HopX2, HopAF1 and HrpK) contribute to pathogenicity on beet and gypsophila. In Pag824-1, nine T3Es (HsvG, HsvB, PthG, DspA/E, HopAY1, HopD1, HopX2, HopAF1 and HrpK) contribute to pathogenicity on gypsophila, whereas the PthG effector triggers HR on beet. HsvB, HsvG, PthG and PseB appear to endow pathovar specificities to Pab and Pag, and no homologous T3Es were identified for these proteins in other phytopathogenic bacteria. Conversely, the remaining T3Es contribute to the virulence of both pathovars, and homologous T3Es were found in other phytopathogenic bacteria. Remarkably, HsvG and HsvB, which act as host-specific transcription factors, displayed the largest contribution to disease development. © 2016 BSPP AND JOHN WILEY & SONS LTD.

Modification of splenic stiffness on acoustic radiation force impulse parallels the variation of portal pressure induced by transjugular intrahepatic portosystemic shunt.

PubMed

De Santis, Adriano; Nardelli, Silvia; Bassanelli, Chiara; Lupo, Marinella; Iegri, Claudia; Di Ciesco, Carmela Anna; Forlino, Mariana; Farcomeni, Alessio; Riggio, Oliviero

2018-03-01

Spleen and liver stiffness (LS) measured by acoustic radiation force impulse (ARFI) imaging has been shown to be useful in identifying patients with portal hypertension. The study aims to establish if the modification of portal pressure induced by a transjugular intrahepatic portosystemic shunt (TIPS) parallels the modification of spleen or LS measured by ARFI in order to understand if ARFI may be used to monitor the modification of portal pressure in patients with cirrhosis. Thirty-eight patients with severe portal hypertension underwent LS and spleen stiffness (SS) before TIPS and 1 week after TIPS. Portal atrial gradient (PAG) was measured before and after the shunt opening. Portal atrial gradient decreased significantly from 19.5 to 6 mmHg (P < 0.001). SS decreased significantly after TIPS (pre-TIPS 3.7 m/s vs post-TIPS 3. 1 m/s; P < 0.001), and LS was also significantly modified by TIPS (pre-TIPS 2.8 m/s vs post-TIPS 2.4 m/s; P = 0.003). PAG and SS values measured before and after TIPS were significantly correlated (r = 0.56; P < 0.001); on the other hand, PAG and LS were not (r = 0.19; P = 0.27). Two patients developed a persistent hepatic encephalopathy refractory to medical treatment and were submitted to the reduction of the stent diameter. The modification of SS was parallel to the modification of PAG. Spleen stiffness is superior to LS in detecting the modification of portal pressure induced by TIPS. This makes SS a potential non-invasive method to monitor the modification of portal hypertension. Further investigations are needed to establish applicability and clinical utility of this promising tool in the treatment of portal hypertension. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Evidence that NMDA-dependent limbic neural plasticity in the right hemisphere mediates pharmacological stressor (FG-7142)-induced lasting increases in anxiety-like behavior: study 3--the effects on amygdala efferent physiology of block of NMDA receptors prior to injection of FG-7142 and its relationship to behavioral change.

PubMed

Adamec, R E

1998-01-01

The findings of this study support the hypothesis that N-methyl-D-aspartate (NMDA) receptors mediate the initiation of long-term potentiation (LTP) and behavioral changes induced by the anxiogenic beta-carboline, FG-7142. Unlike previous work, this study examined the effects of FG-7142 on LTP of amygdala efferents in both hemispheres. 7-amino-phosphono-heptanoic acid (AP7), a competitive NMDA receptor blocker, given prior to administration of FG-7142, prevented LTP in amygdala efferent transmission to the medial hypothalamus and periacqueductal gray (PAG). When given FG-7142 alone, cats showed lasting behavioral changes accompanied by LTP in all pathways studied. Duration of LTP, and its relationship to behavioral change, depended on the pathway and the hemisphere of the pathway. Correlation and covariance analyses indicate that LTP in the left amygdalo-ventromedial hypothalamic pathway mediates initiation, but not maintenance, of increased defensiveness. This finding replicates previous work. A new finding is that increased local excitability in the right basal amygdala (reduced threshold for evoked response), and LTP in the right amygdalo-PAG pathway, may be important for maintenance of increases in defensive behavior. Furthermore, the effects of flumazenil, a benzodiazepine receptor antagonist, on behavior and physiology single out the importance of right amygdalo-PAG LTP as a critical mediator of increased defensiveness. Flumazenil reversed the increase in defensiveness produced by FG-7142 in a drug-dependent manner as described in Adamec (1998a). Moreover, flumazenil reversed LTP only in the right amygdalo-PAG pathway. The findings of the present study suggest that response to FG-7142 may be a useful model of the effects of traumatic stressors on limbic system function in anxiety, especially in view of the recent data in humans implicating right hemispheric function in persisting negative affective states.

Evidence that long-lasting potentiation in limbic circuits mediating defensive behaviour in the right hemisphere underlies pharmacological stressor (FG-7142) induced lasting increases in anxiety-like behaviour: role of benzodiazepine receptors.

PubMed

Adamec, R E

2000-01-01

The hypothesis that benzodiazepine receptors mediate initiation of lasting behavioural changes induced by FG-7142 was supported in this study. Behavioural changes normally induced by FG-7142 were blocked by prior administration of the competitive benzodiazepine receptor blocker, Flumazenil. When cats were subsequently given FG-7142 alone, the drug produced lasting behavioural changes in species characteristic defensive responses to rodent and cat vocal threat. FG-7142 also induced long-lasting potentiation (LLP) of evoked potentials in a number of efferent pathways from the amygdala in both hemispheres. Flumazenil given prior to FG-7142 blocked LLP in all but one of the amygdala efferent pathways, suggesting benzodiazepine receptor dependence of initiation of LLP. Three physiological changes were most closely correlated with behavioural changes. LLP in the right amygdalo-ventromedial hypothalamic (VMH) and amygdalo-periacqueductal gray (PAG) pathways coincided closely with behavioural changes, as did a reduced threshold for the right amygdalo-VMH evoked potential. Administration of Flumazenil after FG-7142 returned defensive behaviour to pre FG-7142 baseline levels in a drug-dependent manner. At the same time LLP only in the right amygdalo-PAG pathway was reduced by Flumazenil. LLP in other pathways and amygdalo-VMH threshold were unaltered by Flumazenil. Moreover, covariance analyses indicated that increased defensiveness depended solely on LLP in the right amygdalo-PAG. These findings support the view that maintenance of lasting increases in defensive behaviour depend upon LLP of excitatory neural transmission between amygdala and lateral column of the PAG in the right hemisphere. Moreover, FG-7142 may be a useful model of the effects of traumatic stressors on limbic system function in anxiety, especially in view of the recent data in humans implicating right hemispheric function in persisting negative affective states in post-traumatic stress disorder.

77 FR 3030 - Membership in the National Parks Overflights Advisory Group Aviation Rulemaking Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-20

... DEPARTMENT OF TRANSPORTATION Federal Aviation Administration Membership in the National Parks Overflights Advisory Group Aviation Rulemaking Committee ACTION: Notice. SUMMARY: By Federal Register notice (See 76 FR 65319; October 20, 2011) the National Park Service (NPS) and the Federal Aviation...

77 FR 1944 - Merchant Marine Personnel Advisory Committee: Intercessional Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-12

... Performance Measures (Assessment Criteria).'' This meeting will be open to the public. DATES: A MERPAC working..., working group meeting is as follows: (1) Review existing performance measures and develop new performance... Committee Working Group Meeting. SUMMARY: The Merchant Marine Personnel Advisory Committee (MERPAC) will...

77 FR 11142 - Merchant Marine Personnel Advisory Committee: Intercessional Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-24

... Committee working group meeting. SUMMARY: The Merchant Marine Personnel Advisory Committee (MERPAC) will conduct an intercessional meeting so that a working group may discuss Task Statement 76, entitled ``Review of Performance Measures (Assessment Criteria).'' This meeting will be open to the public. DATES: A...

75 FR 68023 - Membership Availability in the National Parks Overflights Advisory Group Aviation Rulemaking...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-04

... National Parks Overflights Advisory Group Aviation Rulemaking Committee To Represent Environmental Concerns... NPOAG Aviation Rulemaking Committee (ARC) for a member representing environmental concerns and invites... operations, environmental concerns, and Native American Tribes. The Administrator of the FAA and the Director...

77 FR 59243 - Aviation Rulemaking Advisory Committee Meeting on Transport Airplane and Engine Issues

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-26

... Committee Meeting on Transport Airplane and Engine Issues AGENCY: Federal Aviation Administration (FAA), DOT... Rulemaking Advisory Committee (ARAC) to discuss transport airplane and engine (TAE) issues. DATES: The... Prioritization Working Group Transport Canada Report Materials Flammability Working Group Report Avionics...

Public Education Policy Issues in Montana.

ERIC Educational Resources Information Center

Hitz, Randy, Ed.; Chambers, Keith, Ed.

This document contains articles that address six major issues affecting Montana public education. The issues were selected by an advisory group comprised of representatives from professional education organizations, state agencies, the legislature, and business. Each of the articles, written by members of the advisory group, contains an executive…

Peroxisome Degradation by Microautophagy in Pichia pastoris: Identification of Specific Steps and Morphological Intermediates

PubMed Central

Sakai, Yasuyoshi; Koller, Antonius; Rangell, Linda K.; Keller, Gilbert A.; Subramani, Suresh

1998-01-01

We used the dye N-(3-triethylammoniumpropyl)-4-(p-diethylaminophenylhexatrienyl) pyridinium dibromide (FM4-64) and a fusion protein, consisting of the green fluorescent protein appended to the peroxisomal targeting signal, Ser-Lys-Leu (SKL), to label the vacuolar membrane and the peroxisomal matrix, respectively, in living Pichia pastoris cells and followed by fluorescence microscopy the morphological and kinetic intermediates in the vacuolar degradation of peroxisomes by microautophagy and macroautophagy. Structures corresponding to the intermediates were also identified by electron microscopy. The kinetics of appearance and disappearance of these intermediates is consistent with a precursor–product relationship between intermediates, which form the basis of a model for microautophagy. Inhibitors affecting different steps of microautophagy did not impair peroxisome delivery to the vacuole via macroautophagy, although inhibition of vacuolar proteases affected the final vacuolar degradation of green fluorescent protein (S65T mutant version [GFP])-SKL via both autophagic pathways. P. pastoris mutants defective in peroxisome microautophagy (pag mutants) were isolated and characterized for the presence or absence of the intermediates. These mutants, comprising 6 complementation groups, support the model for microautophagy. Our studies indicate that the microautophagic degradation of peroxisomes proceeds via specific intermediates, whose generation and/or processing is controlled by PAG gene products, and shed light on the poorly understood phenomenon of peroxisome homeostasis. PMID:9566964

Some peace of mind: assessing a pilot intervention to promote mental health among widows of injecting drug users in north-east India

PubMed Central

Kermode, Michelle; Devine, Alexandra; Chandra, Prabha; Dzuvichu, Bernice; Gilbert, Thomhood; Herrman, Helen

2008-01-01

Background HIV prevalence in north-east India is high and injecting drug use (IDU) is common. Due to HIV-related deaths there are increasing numbers of IDU widows, many of whom are HIV infected, and experiencing poor health, social isolation, discrimination and poverty, all factors likely to be compromising their mental health. There is increasing recognition of the links between HIV and mental health. Methods The aim of this study was to pilot a peer-facilitated, participatory action group (PAG) process and assess the impact of the intervention on the mental health of participants. The intervention consisted of 10 PAG meetings involving 74 IDU widows. Changes in quality of life (WHOQOL-BREF), mental health (GHQ12) and somatic symptoms were assessed. The value of the intervention from the perspective of the participants was captured using a qualitative evaluation method (Most Significant Change). Results Participants' quality of life, mental health and experience of somatic symptoms improved significantly over the course of the intervention, and the women told stories reflecting a range of 'significant changes'. Conclusion This pilot intervention study demonstrated that a participatory approach to mental health promotion can have a positive impact on the lives of vulnerable women, and the potential to contribute to HIV prevention. Further investigation is warranted. PMID:18718027

76 FR 78281 - Medicare Program; First Semi-Annual Meeting of the Advisory Panel on Hospital Outpatient Payment...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-16

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Medicare & Medicaid Services [CMS-1586-N] Medicare Program; First Semi-Annual Meeting of the Advisory Panel on Hospital Outpatient Payment (HOP--Formerly Known as the Advisory Panel on Ambulatory Payment Classification Groups--APC Panel)--February 27...

76 FR 20051 - Advisory Committee for International Science & Engineering; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-11

... NATIONAL SCIENCE FOUNDATION Advisory Committee for International Science & Engineering; Notice of... Engineering ( 25104). Date/Time: April 25, 2011; 8:30 a.m. to 5 p.m. April 26, 2011; 8:30 a.m. to 12 p.m... International Science and Engineering, Reports from Advisory Committee Working Groups. April 26, 2011 AM...

75 FR 22607 - Advisory Board on Radiation and Worker Health (ABRWH or Advisory Board), National Institute for...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-29

... on Radiation and Worker Health (ABRWH or Advisory Board), National Institute for Occupational Safety... the Energy Employees Occupational Illness Compensation Program (EEOICP) Act of 2000 to advise the... Petition Status Updates; Subcommittee and Work Group Reports; and Board Working Time. The agenda is subject...

78 FR 58543 - Advisory Board on Radiation and Worker Health (ABRWH or Advisory Board), National Institute for...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-24

... on Radiation and Worker Health (ABRWH or Advisory Board), National Institute for Occupational Safety... the Energy Employees Occupational Illness Compensation Program Act of 2000 to advise the President on... Subcommittee Report; SEC Issues Work Group Report on ``Sufficient Accuracy''/Co-Worker Dose Modeling; SEC...

75 FR 43180 - Advisory Board on Radiation and Worker Health (ABRWH or Advisory Board), National Institute for...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-23

... on Radiation and Worker Health (ABRWH or Advisory Board), National Institute for Occupational Safety... established under the Energy Employees Occupational Illness Compensation Program (EEOICP) Act of 2000 to... Petition Status Updates; Subcommittee and Work Group Reports; and Board Working Time. The agenda is subject...

78 FR 18624 - U.S. Extractive Industries Transparency Initiative Multi-Stakeholder Group (USEITI MSG) Advisory...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-27

... DEPARTMENT OF THE INTERIOR Office of the Secretary [Docket No. ONRR-2012-0003] U.S. Extractive Industries Transparency Initiative Multi- Stakeholder Group (USEITI MSG) Advisory Committee AGENCY: Policy..., teleconference and the May 1-2, 2013, meeting of the United States Extractive Industries Transparency Initiative...

77 FR 32594 - Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-01

... Advisors). The Bureau seeks to collect selection-related information from nominees to the CAB, such as... for other Advisory Groups, members of other Advisory Groups, and Special Advisors to CAB and other... obtain information on the qualifications of individuals nominated to the CAB and will aid the Bureau in...

An Advisory Advantage

ERIC Educational Resources Information Center

Gewertz, Catherine

2007-01-01

Teachers are trained to be mentors, counselors, and friends to a group of advisees, shepherding them through the term papers and broken hearts of adolescence. Each advisory group of about a dozen students stays together, with the same adviser, until graduation. By creating that kind of culture, with promising indicators that it is paying off…

78 FR 32306 - Advisory Group to the Commissioner of Internal Revenue; Renewal of Charter

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-29

... DEPARTMENT OF THE TREASURY Internal Revenue Service Advisory Group to the Commissioner of Internal Revenue; Renewal of Charter AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice. SUMMARY: The... Communications and Liaison, 202-283-8868 (not a toll-free number). SUPPLEMENTARY INFORMATION: Notice is hereby...

78 FR 37495 - Appliance Standards and Rulemaking Federal Advisory Committee: Notice of Open Meetings for the...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-21

... Rulemaking Federal Advisory Committee: Notice of Open Meetings for the Commercial HVAC, WH, and Refrigeration... Requirements for Commercial HVAC, WH, and Refrigeration Equipment AGENCY: Office of Energy Efficiency and... Heating (WH), and Refrigeration Certification Working Group (Commercial Certification Group). The purpose...

78 FR 69172 - Defense Trade Advisory Group; Notice of Cancellation of Open Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-18

... DEPARTMENT OF STATE [Public Notice 8525] Defense Trade Advisory Group; Notice of Cancellation of Open Meeting AGENCY: Department of State. ACTION: Notice of Cancellation of meeting. SUMMARY: The notice references Public Notice 8515 published in the November 12, 2013 Federal Register, announcing the...

76 FR 72745 - Defense Trade Advisory Group; Notice of Membership

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-25

...: Department of State. ACTION: Notice. The U.S. Department of State's Bureau of Political-Military Affairs' Defense Trade Advisory Group (DTAG) is accepting membership applications. The Bureau of Political-Military...-Military Affairs with a formal channel for regular consultation and coordination with U.S. private sector...

77 FR 66583 - Solicitation of Nominations for Membership on the Civil Nuclear Trade Advisory Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-06

... the Department as chair of the Civil Nuclear Trade Working Group (CINTWG) of the Trade Promotion... of the Civil Nuclear Trade Working Group of the Trade Promotion Coordinating Committee. In particular... Membership on the Civil Nuclear Trade Advisory Committee AGENCY: International Trade Administration, Commerce...

76 FR 26771 - NASA Advisory Council; Task Group of the Science Committee; Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-09

... of the Science Committee; Meeting AGENCY: National Aeronautics and Space Administration. ACTION... the NASA Advisory Council (NAC) Science Committee. This Task Group reports to the Science Committee of the NAC. The Meeting will be held for the purpose of soliciting from the scientific community and...

76 FR 21073 - NASA Advisory Council; Task Group of the Science Committee; Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-14

... of the Science Committee; Meeting AGENCY: National Aeronautics and Space Administration. ACTION... the NASA Advisory Council (NAC) Science Committee. This Task Group reports to the Science Committee of the NAC. The Meeting will be held for the purpose of soliciting from the scientific community and...

77 FR 46112 - Call for Nominations for Advisory Groups, Oregon/Washington

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-02

... Steens Mountain Advisory Council. Citizens who serve on these groups provide advice and recommendations to the BLM on land use planning and management of the National System of Public Lands within their geographic areas and management options for a specific National Landscape Conservation System site. The BLM...

The mesencephalic GCt-ICo complex and tonic immobility in pigeons (Columba livia): a c-Fos study.

PubMed

Melleu, Fernando Falkenburger; Lino-de-Oliveira, C; Marino-Neto, J

2017-04-01

Tonic immobility (TI) is a response to a predator attack, or other inescapable danger, characterized by immobility, analgesia and unresponsiveness to external stimuli. In mammals, the periaqueductal gray (PAG) and deep tectal regions control the expression of TI as well as other defensive behaviors. In birds, little is known about the mesencephalic circuitry involved in the control of TI. Here, adult pigeons (both sex, n = 4/group), randomly assigned to non-handled, handled or TI groups, were killed 90 min after manipulations and the brains processed for detection of c-Fos immunoreactive cells (c-Fos-ir, marker for neural activity) in the mesencephalic central gray (GCt) and the adjacent nucleus intercollicularis (ICo). The NADPH-diaphorase staining delineated the boundaries of the sub nuclei in the ICo-GCt complex. Compared to non-handled, TI (but not handling) induced c-Fos-ir in NADPH-diaphorase-rich and -poor regions. After TI, the number of c-Fos-ir increased in the caudal and intermediate areas of the ICo (but not in the GCt), throughout the rostrocaudal axis of the dorsal stratum griseum periventriculare (SGPd) of the optic tectum and in the n. mesencephalicus lateralis pars dorsalis (MLd), which is part of the ascending auditory pathway. These data suggest that inescapable threatening stimuli such as TI may recruit neurons in discrete areas of ICo-GCt complex, deep tectal layer and in ascending auditory circuits that may control the expression of defensive behaviors in pigeons. Additionally, data indicate that the contiguous deep tectal SCPd (but not GCt) in birds may be functionally comparable to the mammalian dorsal PAG.

FoxP2 brainstem neurons project to sodium appetite regulatory sites.

PubMed

Shin, Jung-Won; Geerling, Joel C; Stein, Matthew K; Miller, Rebecca L; Loewy, Arthur D

2011-09-01

The transcription factor Forkhead box protein 2 (FoxP2) is expressed in two cell groups of the brainstem that have been implicated in sodium appetite regulation: the pre-locus coeruleus (pre-LC) and parabrachial nucleus--external lateral-inner subdivision (PBel-inner). Because the connections of these two groups are unknown, neuroanatomical tracing methods were used to define their central projections. The pre-LC outputs were first analyzed using an anterograde axonal tracer--Phaseolus vulgaris leucoagglutinin (PHAL) to construct a brain map. Next, we examined whether the FoxP2 immunoreactive (FoxP2+) neurons of the pre-LC contribute to these projections using a retrograde neuronal tracer--cholera toxin β-subunit (CTb). CTb was injected into selected brain regions identified in the anterograde tracing study. One week later the rats were killed, and brainstem sections were processed by a double immunohistochemical procedure to determine whether the FoxP2+ neurons in the pre-LC and/or PBel-inner contained CTb. FoxP2+ pre-LC neurons project to: (1) ventral pallidum; (2) substantia innominata and bed nucleus of the stria terminalis; (3) paraventricular, central medial, parafascicular, and subparafascicular parvicellular thalamic nuclei; (4) paraventricular (PVH), lateral, perifornical, dorsomedial (DMH), and parasubthalamic hypothalamic nuclei; and (5) ventral tegmental area (VTA), periaqueductal gray matter (PAG), dorsal and central linear raphe nuclei. FoxP2+ PBel-inner neurons project to the PVH and DMH, with weaker connections to the LHA, VTA, and PAG. Both the pre-LC and PBel-inner project to central sites implicated in sodium appetite, and related issues, including foraging behavior, hedonic responses to salt intake, sodium balance, and cardiovascular regulation, are discussed. Copyright © 2011 Elsevier B.V. All rights reserved.

78 FR 7434 - Medicare Program: Notice of Two Membership Appointments to the Advisory Panel on Hospital...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-01

... Panel on Hospital Outpatient Payment (HOP, the Panel). The two new appointments to the Panel will each... Classification groups and weights. The Advisory Panel on Hospital Outpatient Payment (HOP, the Panel) is governed... members to the Advisory Panel on Hospital Outpatient Payment (HOP, the Panel) to fill two vacancies on the...

Distribution of haptoglobins in different dialect groups of Chinese, Malays and Indians in Singapore.

PubMed

Saha, N; Ong, Y W

1984-07-01

A total of 870 subjects comprising 524 Chinese (from different dialect groups), 231 Malays and 115 Tamil Indians were investigated for the distribution of haptoglobin types and ABO blood groups. Haptoglobins were typed by PAG electrophoresis using discontinuous buffer system. The frequencies of Hp,1 Hp2 and Hp0 were found to be 0.330, 0.670 and 0.029 in Chinese; 0.298, 0.702 and 0.004 in Malays; and 0.167, 0.833 and 0.009 in Indians. The Hainanese had the highest frequency of Hp1 (0.375) followed by Cantonese (0.348), Teochew (0.333) and Hakkas (0.288). The distribution of all the phenotypes of haptoglobin was at equilibrium in all the population groups studied. No association of ABO blood groups was detected with the haptoglobin types. However, there was an excess of AB blood group in persons carrying Hp2 compared with those with Hp1.

Working for Clean Water, 2: Citizen Handbooks. An Information Program for Advisory Groups.

ERIC Educational Resources Information Center

Stoltzfus, Lorna Chr., Ed.

Presented is material from an information program designed to help citizen advisory groups and local officials improve decision-making in water quality planning. This program is aimed at helping people focus on essential issues and questions by providing materials suitable for persons with non-technical backgrounds. The following chapters are…

77 FR 42313 - Recharter of the Advisory Group on Prevention, Health Promotion, and Integrative and Public Health

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-18

... Promotion, and Integrative and Public Health AGENCY: Office of the Assistant Secretary for Health, Office of... Promotion, and Integrative and Public Health. FOR FURTHER INFORMATION CONTACT: Corinne Graffunder... Integrative and Public Health (the ``Advisory Group'') within the Department of Health and Human Services. To...

Environmental Assessment. Instructor Guide. Working for Clean Water: An Information Program for Advisory Groups.

ERIC Educational Resources Information Center

Buskirk, E. Drannon, Jr.

Described is an hour-long learning session on environmental assessment that is designed to help citizen advisory groups improve decision making in water quality planning. The instructor's guide addresses: (1) environmental considerations in water quality planning, and (2) the identification of primary and secondary impacts of wastewater projects.…

77 FR 70482 - Notice of Establishment of a NASA Federal Advisory Committee; Applied Sciences Advisory Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-26

... Analysis Group (ASAG) as a task group under the auspices of the Earth Science Subcommittee of the NASA... and prioritizing the Earth Science Division's Applied Sciences Program activities and has served as a... recommendations to the Director, Earth Science Division, Science Mission Directorate, NASA Headquarters, on...

Groundwater Contamination. Instructor Guide. Working for Clean Water: An Information Program for Advisory Groups.

ERIC Educational Resources Information Center

Cole, Charles A.

Described is a presentation and learning session on groundwater, which is intended to educate advisory groups interested in improving water quality decision making. Among the areas addressed are the importance of groundwater, sources of contamination, and groundwater pollution control programs. These materials are part of the Working for Clean…

75 FR 69154 - Notice of Meeting of the National Parks Overflights Advisory Group Aviation Rulemaking Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-10

... Parks Air Tour Management Act of 2000 (NPATMA), enacted on April 5, 2000, as Public Law 106-181... Parks Overflights Advisory Group Aviation Rulemaking Committee ACTION: Notice of meeting. SUMMARY: The Federal Aviation Administration (FAA) and the National Park Service (NPS), in accordance with the National...

Sensory trigeminal ULF-TENS stimulation reduces HRV response to experimentally induced arithmetic stress: A randomized clinical trial.

PubMed

Monaco, Annalisa; Cattaneo, Ruggero; Ortu, Eleonora; Constantinescu, Marian Vladimir; Pietropaoli, Davide

2017-05-01

Ultra Low Frequency Transcutaneous Electric Nervous Stimulation (ULF-TENS) is extensively used for pain relief and for the diagnosis and treatment of temporomandibular disorders (TMD). In addition to its local effects, ULF-TENS acts on the autonomic nervous system (ANS), with particular reference to the periaqueductal gray (PAG), promoting the release of endogenous opioids and modulating descending pain systems. It has been suggested that the PAG participates in the coupling between the emotional stimulus and the appropriate behavioral autonomic response. This function is successfully investigated by HRV. Therefore, our goal is to investigate the effects of trigeminal ULF-TENS stimulation on autonomic behavior in terms of HRV and respiratory parameters during an experimentally-induced arithmetic stress test in healthy subjects. Thirty healthy women between 25 and 35years of age were enrolled and randomly assigned to either the control (TENS stimulation off) or test group (TENS stimulation on). Heart (HR, LF, HF, LF/HF ratio, DET, RMSSD, PNN50, RR) and respiratory (BR) rate were evaluated under basal, T1 (TENS off/on), and stress (mathematical task) conditions. Results showed that HRV parameters and BR significantly changed during the arithmetic stress paradigm (p<0.01). Independently of stress conditions, TENS and control group could be discriminated only by non-linear HRV data, namely RR and DET (p=0.038 and p=0.027, respectively). During the arithmetic task, LF/HF ratio was the most sensitive parameter to discriminate between groups (p=0.019). Our data suggest that trigeminal sensory ULF-TENS reduces the autonomic response in terms of HRV and BR during acute mental stress in healthy subjects. Future directions of our work aim at applying the HRV and BR analysis, with and without TENS stimulation, to individuals with dysfunctional ANS among those with TMD. Copyright © 2017 Elsevier Inc. All rights reserved.

Towards Deciphering the Hidden Mechanisms That Contribute to the Antigenic Activation Process of Human Vγ9Vδ2 T Cells.

PubMed

Boutin, Lola; Scotet, Emmanuel

2018-01-01

Vγ9Vδ2 T cells represent a major unconventional γδ T cell subset located in the peripheral blood of adults in humans and several non-human primates. Lymphocytes that constitute this transitional subset can sense subtle level changes of intracellular phosphorylated intermediates of the isoprenoid biosynthesis pathway (phosphoantigens, pAg), such as isopentenyl pyrophosphate, during cell stress events. This unique antigenic activation process operates in a rigorous framework that requires the expression of butyrophilin 3A1 (BTN3A1/CD277) molecules, which are type I glycoproteins that belong to the B7 family. Several studies have further shown that pAg specifically bind to the intracellular B30.2 domain of BTN3A1 linked to the antigenic activation of Vγ9Vδ2 T cells. Here, we highlight the recent advances in BTN3A1 dynamics induced upon the binding of pAg and the contribution of the different subunits to this activation process. Recent reports support that conformational modifications of BTN3A1 might represent a key step in the detection of infection or tumorigenesis by Vγ9Vδ2 T cells. A better understanding of this mechanism will help optimize novel immunotherapeutical approaches that target defined functions of this unique γδ T cell subset.

Towards Deciphering the Hidden Mechanisms That Contribute to the Antigenic Activation Process of Human Vγ9Vδ2 T Cells

PubMed Central

Boutin, Lola; Scotet, Emmanuel

2018-01-01

Vγ9Vδ2 T cells represent a major unconventional γδ T cell subset located in the peripheral blood of adults in humans and several non-human primates. Lymphocytes that constitute this transitional subset can sense subtle level changes of intracellular phosphorylated intermediates of the isoprenoid biosynthesis pathway (phosphoantigens, pAg), such as isopentenyl pyrophosphate, during cell stress events. This unique antigenic activation process operates in a rigorous framework that requires the expression of butyrophilin 3A1 (BTN3A1/CD277) molecules, which are type I glycoproteins that belong to the B7 family. Several studies have further shown that pAg specifically bind to the intracellular B30.2 domain of BTN3A1 linked to the antigenic activation of Vγ9Vδ2 T cells. Here, we highlight the recent advances in BTN3A1 dynamics induced upon the binding of pAg and the contribution of the different subunits to this activation process. Recent reports support that conformational modifications of BTN3A1 might represent a key step in the detection of infection or tumorigenesis by Vγ9Vδ2 T cells. A better understanding of this mechanism will help optimize novel immunotherapeutical approaches that target defined functions of this unique γδ T cell subset. PMID:29731756

Interaction between μ-opioid and 5-HT1A receptors in the regulation of panic-related defensive responses in the rat dorsal periaqueductal grey.

PubMed

Rangel, Marcel P; Zangrossi, Hélio; Roncon, Camila M; Graeff, Frederico G; Audi, Elisabeth A

2014-12-01

A wealth of evidence indicates that the activation of 5-HT1A and 5-HT2A receptors in the dorsal periaqueductal grey matter (dPAG) inhibits escape, a panic-related defensive behaviour. Results that were previously obtained with the elevated T-maze test of anxiety/panic suggest that 5-HT1A and μ-opioid receptors in this midbrain area work together to regulate this response. To investigate the generality of this finding, we assessed whether the same cooperative mechanism is engaged when escape is evoked by a different aversive stimulus electrical stimulation of the dPAG. Administration of the μ-receptor blocker CTOP into the dPAG did not change the escape threshold, but microinjection of the μ-receptor agonist DAMGO (0.3 and 0.5 nmol) or the 5-HT1A receptor agonist 8-OHDPAT (1.6 nmol) increased this index, indicating a panicolytic-like effect. Pretreatment with CTOP antagonised the anti-escape effect of 8-OHDPAT. Additionally, combined administration of subeffective doses of DAMGO and 8-OHDPAT increased the escape threshold, indicating drug synergism. Therefore, regardless of the aversive nature of the stimulus, μ-opioid and 5-HT1A receptors cooperatively act to regulate escape behaviour. A better comprehension of this mechanism might allow for new therapeutic strategies for panic disorder. © The Author(s) 2014.

Involvement of the pagR gene of pXO2 in anthrax pathogenesis

PubMed Central

Liang, Xudong; Zhang, Enmin; Zhang, Huijuan; Wei, Jianchun; Li, Wei; Zhu, Jin; Wang, Bingxiang; Dong, Shulin

2016-01-01

Anthrax is a disease caused by Bacillus anthracis. Specifically, the anthrax toxins and capsules encoded by the pXO1 and pXO2 plasmids, respectively, are the major virulence factors. We previously reported that the pXO1 plasmid was retained in the attenuated strain of B. anthracis vaccine strains even after subculturing at high temperatures. In the present study, we reinvestigate the attenuation mechanism of Pasteur II. Sequencing of pXO1 and pXO2 from Pasteur II strain revealed mutations in these plasmids as compared to the reference sequences. Two deletions on these plasmids, one each on pXO1 and pXO2, were confirmed to be unique to the Pasteur II strain as compared to the wild-type strains. Gene replacement with homologous recombination revealed that the mutation in the promoter region of the pagR gene on pXO2, but not the mutation on pXO1, contributes to lethal levels of toxin production. This result was further confirmed by RT-PCR, western blot, and animal toxicity assays. Taken together, our results signify that the attenuation of the Pasteur II vaccine strain is caused by a mutation in the pagR gene on its pXO2 plasmid. Moreover, these data suggest that pXO2 plasmid encoded proteins are involved in the virulence of B. anthracis. PMID:27363681

Serotonergic lesions of the periaqueductal gray, a primary source of serotonin to the nucleus paragigantocellularis, facilitate sexual behavior in male rats.

PubMed

Normandin, Joseph J; Murphy, Anne Z

2011-05-01

While selective serotonin reuptake inhibitors (SSRIs) are widely used to treat anxiety and depression, they also produce profound disruptions of sexual function including delayed orgasm/ejaculation. The nucleus paragigantocellularis (nPGi), a primary source of inhibition of ejaculation in male rats, contains receptors for serotonin (5-HT). The ventrolateral periaqueductal gray (vlPAG) provides serotonin to this region, thus providing an anatomical and neurochemical basis for serotonergic regulation of the nPGi. We hypothesize that 5-HT acting at the nPGi could underlie the SSRI-induced inhibition of ejaculation in rodents. To this end, we produced 5-HT lesions of the source of 5-HT to the nPGi (the vlPAG) and examined sexual behavior. Removing the source of 5-HT to the nPGi facilitated genital reflexes, but not other aspects of sexual behavior, consistent with our hypothesis. Namely, 5-HT lesions produced a significant increase in the mean number of ejaculations and a significant decrease in ejaculation latency as compared to sham lesioned animals, while latency to mating and the post-ejaculatory interval did not differ. These data suggest that the serotonergic vlPAG-nPGi pathway is an important regulatory mechanism for the inhibition of ejaculation in rats and supports the hypothesis that this circuit contributes to SSRI-induced inhibition of ejaculation. Copyright © 2011 Elsevier Inc. All rights reserved.

Serotonergic lesions of the periaqueductal gray, a primary source of serotonin to the nucleus paragigantocellularis, facilitate sexual behavior in male rats

PubMed Central

Normandin, Joseph J.; Murphy, Anne Z.

2011-01-01

While selective serotonin reuptake inhibitors (SSRIs) are widely used to treat anxiety and depression, they also produce profound disruptions of sexual function including delayed orgasm/ejaculation. The nucleus paragigantocellularis (nPGi), a primary source of inhibition of ejaculation in male rats, contains receptors for serotonin (5-HT). The ventrolateral periaqueductal gray (vlPAG) provides serotonin to this region, thus providing an anatomical and neurochemical basis for serotonergic regulation of the nPGi. We hypothesize that 5-HT acting at the nPGi could underlie the SSRI-induced inhibition of ejaculation in rodents. To this end, we produced 5-HT lesions of the source of 5-HT to the nPGi (the vlPAG) and examined sexual behavior. Removing the source of 5-HT to the nPGi facilitated genital reflexes, but not other aspects of sexual behavior, consistent with our hypothesis. Namely, 5-HT lesions produced a significant increase in the mean number of ejaculations and a significant decrease in ejaculation latency as compared to sham lesioned animals, while latency to mating and the post-ejaculatory interval did not differ. These data suggest that the serotonergic vlPAG-nPGi pathway is an important regulatory mechanism for the inhibition of ejaculation in rats, and supports the hypothesis that this circuit contributes to SSRI-induced inhibition of ejaculation. PMID:21296106

Efferent connections of the parvalbumin-positive (PV1) nucleus in the lateral hypothalamus of rodents

PubMed Central

Celio, Marco R.; Babalian, Alexander; Ha, Quan Hue; Eichenberger, Simone; Clément, Laurence; Marti, Christiane; Saper, Clifford B.

2013-01-01

A solitary cluster of parvalbumin-positive neurons - the PV1-nucleus - has been observed in the lateral hypothalamus of rodents. In the present study, we mapped the efferent connections of the rodent PV1-nucleus using non-specific antero- and retrograde tracers in rats, and chemoselective, Cre-dependent viral constructs in parvalbumin-Cre mice. In both species, the PV1-nucleus was found to project mainly to the periaqueductal grey matter (PAG), preponderantly ipsilateral. Indirectly in rats and directly in mice, a discrete, longitudinally- orientated cylindrical column of terminal fields (PV1-CTF) was identified ventrolateral to the aqueduct on the edge of the PAG. The PV1-CTF, which is particularly dense in the rostral portion, located in the supraoculomotor nucleus (Su3), is spatially interrupted over a short stretch at the level of the trochlear nucleus and abuts caudally on a second parvalbum in-positive (PV2) nucleus. The rostral and the caudal portions of the PV1-CTF consist of axonal endings that stem from scattered neurons throughout the PV1-nucleus. Minor terminal fields were identified in a crescentic column of the lateral PAG, as well as in the Edinger-Westphal-, the lateral habenular- and the laterodorsal tegmental nuclei. So far no obvious functions can be attributed to this small, circumscribed column ventrolateral to the aqueduct, the prime target of the PV1-nucleus. PMID:23787784

TECHNOLOGY TRANSFER TO U.S. INDEPENDENT OIL AND NATURAL GAS PRODUCERS

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

Donald Duttlinger

2001-11-01

The Petroleum Technology Transfer Council (PTTC) continued pursuing its mission of helping U.S. independent oil and gas producers make timely, informed technology decisions during Fiscal Year 2001 (FY01). Functioning as a cohesive national organization, PTTC has active grassroots programs through its ten Regional Lead Organizations (RLOs). They bring research and academia to the table via their association with geological surveys and engineering departments. The regional directors interact with independent oil and gas producers through technology workshops, resource centers, websites, newsletters, various technical publications and other outreach efforts. These are guided by regional Producer Advisory Groups (PAGs), who are area operatorsmore » and service companies working with the regional networks. The role of the national Headquarters (HQ) staff includes planning and managing the PTTC program, conducting nation wide technology transfer activities, and implementing a comprehensive communications effort. The organization effectively combines federal funding through the Department of Energy's (DOE) Office of Fossil Energy, state, and industry funding to achieve important goals for all of these sectors. This integrated funding base, combined with industry volunteers guiding PTTC's activities and the dedication of national and regional staff, are achieving notable results. PTTC is increasingly recognized as a critical resource for information and access to technologies, especially for smaller companies without direct contact to R&D efforts. This technical progress report summarizes PTTC's accomplishments during FY01, which lays the groundwork for further growth in the future. At a time of many industry changes and wide market movements, the organization itself is adapting to change. PTTC has built a reputation and expectation among producers and other industry participants to quickly distribute information addressing technical needs. The organization efficiently has an impact on business economics as the focus remains on proven applicable technologies, which target cost reduction and efficiency gains.« less

78 FR 38345 - Meeting of the Advisory Group on Prevention, Health Promotion, and Integrative and Public Health

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-26

... Promotion, and Integrative and Public Health AGENCY: Office of the Surgeon General of the United States Public Health Service, Office of the Assistant Secretary for Health, Office of the Secretary, Department... Integrative and Public Health (the ``Advisory Group''). The meeting will be open to the public. [[Page 38346...

75 FR 38099 - Establishment of the Advisory Group on Prevention, Health Promotion, and Integrative and Public...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-01

... Promotion, and Integrative and Public Health AGENCY: Department of Health and Human Services, Office of the Secretary, Office of Public Health and Science. ACTION: Notice. AUTHORITY: Executive Order 13544, dated June... Act, Public Law 111-148, dated March 23, 2010. The Advisory Group on Prevention, Health Promotion, and...

78 FR 69853 - Meeting of the Advisory Group on Prevention, Health Promotion, and Integrative and Public Health

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-21

... Promotion, and Integrative and Public Health AGENCY: Office of the Surgeon General of the United States Public Health Service, Office of the Assistant Secretary for Health, Office of the Secretary, Department... Integrative and Public Health (the ``Advisory Group''). The meeting will be open to the public. Information...

77 FR 33220 - Advisory Group on Prevention, Health Promotion, and Integrative and Public Health; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-05

... Integrative and Public Health; Notice of Meeting AGENCY: Office of the Surgeon General of the United States Public Health Service, Office of the Assistant Secretary for Health, Office of the Secretary, Department... Integrative and Public Health (the ``Advisory Group''). The web meeting will be open to the public. The agenda...

78 FR 48877 - Meeting of the Advisory Group on Prevention, Health Promotion, and Integrative and Public Health

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-12

... Promotion, and Integrative and Public Health AGENCY: Office of the Surgeon General of the United States Public Health Service, Office of the Assistant Secretary for Health, Office of the Secretary, Department... Integrative and Public Health (the ``Advisory Group''). The meeting will be open to the public. Information...

76 FR 47237 - Notice of Public Meeting for the Glen Canyon Dam Adaptive Management Work Group Federal Advisory...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-04

... . SUPPLEMENTARY INFORMATION: The Glen Canyon Dam Adaptive Management Program (AMP) was implemented as a result of... AMP includes a Federal advisory committee, the AMWG, a technical work group (TWG), a Grand Canyon... other administrative and resource issues pertaining to the AMP. To view a copy of the agenda and...

Working for Clean Water, 3: Citizen Handbooks. An Information Program for Advisory Groups.

ERIC Educational Resources Information Center

Stoltzfus, Lorna Chr., Ed.

Presented is material from an information program designed to help citizen advisory groups and local officials improve decision-making in water quality planning. The program is designed to help people focus on essential issues and questions by providing materials suitable for people with non-technical backgrounds. Chapter topics include: (1)…

Urban Stormwater Runoff. Instructor Guide. Working for Clean Water: An Information Program for Advisory Groups.

ERIC Educational Resources Information Center

Simko, Robert A.

Urban stormwater runoff collects pollutants from many parts of a city and is an important consideration in water quality planning. Presented is an instructor's guide for a learning session covering various aspects of urban runoff including pollutant sources, management practices, and regulatory programs. Intended for citizen advisory groups, this…

76 FR 14950 - Closed Meeting of the U.S. Strategic Command Strategic Advisory Group

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-18

... DEPARTMENT OF DEFENSE Office of the Secretary Closed Meeting of the U.S. Strategic Command.... Strategic Command Strategic Advisory Group. DATES: April 7, 2011, from 8 a.m. to 5 p.m. and April 8, 2011... policy-related issues to the Commander, U.S. Strategic Command, during the development of the Nation's...

75 FR 1834 - Membership Availability in the National Parks Overflights Advisory Group Aviation; Rulemaking...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-13

... Parks Air Tour Management Act of 2000 (the Act) was enacted on April 5, 2000, as Public Law 106-181. The... National Parks Overflights Advisory Group Aviation; Rulemaking Committee To Represent Commercial Air Tour... (FAA), as required by the National Parks Air Tour Management Act of 2000, established the National...

78 FR 64259 - U.S. Department of State Advisory Committee on Private International Law (ACPIL)-Online Dispute...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-28

... DEPARTMENT OF STATE [Public Notice 8508] U.S. Department of State Advisory Committee on Private International Law (ACPIL)--Online Dispute Resolution (ODR) Study Group The Office of the Assistant Legal Adviser for Private International Law, Department of State, hereby gives notice that the ACPIL ODR Study Group...

21 CFR 14.84 - Nominations and selection of nonvoting members of standing technical advisory committees.

Code of Federal Regulations, 2011 CFR

2011-04-01

... one person selected by consumer groups and organizations and one person selected by industry groups... subcommittees may be made at any time. All nominations are to be submitted in writing to Advisory Committee Oversight and Management Staff, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 32, rm. 1503...

Wastewater Facilities Operation and Management. Instructor Guide. Working for Clean Water: An Information Program for Advisory Groups.

ERIC Educational Resources Information Center

Long, David A.

Local communities must be willing to spend funds to assure the proper operation and management of wastewater treatment facilities. Designed for citizen advisory groups, the one-hour learning session described in this instructor's manual covers problem areas, federal requirements, and responsibilities for wastewater plant operations and management.…

Improvement of Morphine-Mediated Analgesia by Inhibition of β-Arrestin 2 Expression in Mice Periaqueductal Gray Matter

PubMed Central

Li, Yuting; Liu, Xing; Liu, Chang; Kang, Jiuhong; Yang, Jingyu; Pei, Gang; Wu, Chunfu

2009-01-01

Morphine is a well-known μ-opioid receptor (MOR) agonist and an efficient analgesic, but its long-term use inevitably leads to drug addiction and tolerance. Here, we show that specific inhibition of β-arrestin2 with its siRNA lentivirus microinjected in mice periaqueductal gray matter (PAG) significantly improved both acute and chronic morphine analgesia and delayed the tolerance in the hotplate test. The specific effect of β-arrestin2 was proven by overexpression or knockdown of its homology β-arrestin1 in PAG, which showed no significant effects on morphine analgesia. These findings suggest that specific siRNA targeting β-arrestin2 may constitute a new approach to morphine therapy and other MOR agonist-mediated analgesia and tolerance. PMID:19399231

Resist development status for immersion lithography

NASA Astrophysics Data System (ADS)

Tsuji, Hiromitsu; Yoshida, Masaaki; Ishizuka, Keita; Hirano, Tomoyuki; Endo, Kotaro; Sato, Mitsuru

2005-05-01

Immersion lithography has already demonstrated superior performance for next generation semiconductor manufacturing, while some challenges with contact immersion fluids and resist still remain. There are many interactions to be considered with regards to the solid and liquid interface. Resist elusion in particular requires very careful attention since the impact on the lens and fluid supply system in exposure tool could pose a significant risk at the manufacturing stage. TOK developed a screening procedure to detect resist elution of ion species down to ppb levels during non and post exposure steps. It was found that the PAG cation elution is affected by molecular weight and structure while the PAG anion elution was dependent on the molecular structure and mobility. In this paper, lithographic performance is also discussed with the low elution type resist.

75 FR 10328 - Advisory Committee for Mathematical and Physical Sciences; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-05

... Person: Dr. Morris L. Aizenman, Senior Science Associate, Directorate for Mathematical and Physical... Directorate; Report of NSF Advisory Working Groups; Meeting of MPSAC with Divisions within MPS Directorate...

76 FR 14996 - Advisory Committee for Mathematical and Physical Sciences; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-18

.... Aizenman, Senior Science Associate, Directorate for Mathematical and Physical Sciences, Room 1005, National... Committee of Visitors Report of NSF Advisory Working Groups Meeting of MPSAC with Divisions within MPS...

Prevention of red cell storage lesion: a comparison of five different additive solutions.

PubMed

Lagerberg, Johan W; Korsten, Herbert; Van Der Meer, Pieter F; De Korte, Dirk

2017-09-01

In Europe, red cell concentrates (RCC) are usually stored in SAGM (saline-adenine-glucose-mannitol). During storage, in vitro red cell quality declines, including lowered energy status and increased cell lysis. Recently, several additive solutions (ASs), designed to diminish the decline in in vitro quality during storage, have been developed. These new solutions have mainly been developed to better maintain red blood cell (RBC) 2,3-biphosphoglycerate (2,3 BPG) levels and energy status during storage. High levels of 2,3 BPG allow for better oxygen release while high energy status is necessary for function and survival of RBC in vivo. In a paired study design, RBC ASs were compared for their ability to provide improved in vitro quality during hypothermic storage. For each experiment, 5 whole blood units held overnight were pooled and split. The whole blood units were processed according to the buffy coat method. RBCs were resuspended in either SAGM, PAGGSM, PAG3M, E-Sol 5 or AS-7 and leucoreduced by filtration. RCCs were stored for eight weeks at 2-6 °C and sampled weekly for analysis of in vitro quality parameters. Red cell concentrates stored in PAG3M, E-Sol 5 and AS-7 showed significantly higher lactate production and higher levels of intracellular adenosine triphosphate (ATP) and total adenylate. 2,3 BPG levels rapidly declined during storage in SAGM and PAGGSM. The decline in 2,3 BPG was inhibited during storage in E-Sol 5 and AS-7, while in PAG3M, 2,3 BPG level increased above the initial level till day 35 and remained detectable till day 56. Haemolysis was comparable for all ASs until day 35, upon prolonged storage, haemolysis in SAGM was higher than with the other ASs. As compared to SAGM, storage in PAGGSM, PAG3M, E-Sol 5 and AS-7 better maintained morphological properties. Storage of RBCs in the new generation ASs yield RBCs with more stable metabolite levels and improved overall quality during storage as compared with RBCs stored in SAGM.

Financial Management. Working for Clean Water: An Information Program for Advisory Groups. Instructor Guide.

ERIC Educational Resources Information Center

Auker, Dennis; And Others

The implementation of water quality programs in the face of rising costs raises many questions for states and local communities, including: How much can taxpayers afford to pay? Who will pay? How can they pay? Described is an hour-long learning session on financial management that is designed to help citizen advisory groups play an integral role…

Facility Planning in the Construction Grants Program. Instructor Guide. Working for Clean Water: An Information Program for Advisory Groups.

ERIC Educational Resources Information Center

Buskirk, E. Drannon, Jr.; Cole, Charles A.

Wastewater facility planning is an essential component of the federal construction grants process. Presented in this instructor's guide is a one-hour presentation on facility planning intended for citizen advisory groups. The guide is part of the Working for Clean Water Project, which also includes a supplementary audiovisual presentation.…

76 FR 31626 - Notice of Arizona Recreation Resource Advisory Council Workgroup Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-01

... 24 hours a day, 7 days a week, to leave a message or question with the above individuals. You will...), Arizona Recreation Resource Advisory Council (RRAC) Work Group will meet in Sedona, Arizona, as indicated below. DATES: June 29, 2011. The RRAC Work Group meeting will be held on June 29 (8 a.m.-5:30 p.m...

75 FR 56533 - Public Safety and Homeland Security Bureau; Federal Advisory Committee Act; Communications...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-16

... working groups will be presenting their proposed recommendations on issues such as public safety... regarding the CSRIC can be found at: http://www.fcc.gov/pshs/advisory/csric/ . Federal Communications...

Preoperative DTI and probabilistic tractography in an amputee with deep brain stimulation for lower limb stump pain.

PubMed

Owen, S L F; Heath, J; Kringelbach, M L; Stein, J F; Aziz, T Z

2007-10-01

This study aimed to find out whether preoperative diffusion tensor imaging (DTI) and probabilistic tractography could help with surgical planning for deep brain stimulation in the periaqueductal/periventricular grey area (PAG/PVG) in a patient with lower leg stump pain. A preoperative DTI was obtained from the patient, who then received DBS surgery in the PAG/PVG area with good pain relief. The postoperative MRI scan showing electrode placement was used to calculate four seed areas to represent the contacts on the Medtronic 3387 electrode. Probabilistic tractography was then performed from the pre-operative DTI image. Tracts were seen to connect to many areas within the pain network from the four different contacts. These initial findings suggest that preoperative DTI scanning and probabilistic tractography may be able to assist surgical planning in the future.

Representation of aversive prediction errors in the human periaqueductal gray

PubMed Central

Roy, Mathieu; Shohamy, Daphna; Daw, Nathaniel; Jepma, Marieke; Wimmer, Elliott; Wager, Tor D.

2014-01-01

Pain is a primary driver of learning and motivated action. It is also a target of learning, as nociceptive brain responses are shaped by learning processes. We combined an instrumental pain avoidance task with an axiomatic approach to assessing fMRI signals related to prediction errors (PEs), which drive reinforcement-based learning. We found that pain PEs were encoded in the periaqueductal gray (PAG), an important structure for pain control and learning in animal models. Axiomatic tests combined with dynamic causal modeling suggested that ventromedial prefrontal cortex, supported by putamen, provides an expected value-related input to the PAG, which then conveys PE signals to prefrontal regions important for behavioral regulation, including orbitofrontal, anterior mid-cingulate, and dorsomedial prefrontal cortices. Thus, pain-related learning involves distinct neural circuitry, with implications for behavior and pain dynamics. PMID:25282614

Pegylated and nanoparticle-conjugated sulfonium salt photo triggers necrotic cell death.

PubMed

Fadhel, Alaa A; Yue, Xiling; Ghazvini Zadeh, Ebrahim H; Bondar, Mykhailo V; Belfield, Kevin D

Photodynamic therapy (PDT) processes involving the production of singlet oxygen face the issue of oxygen concentration dependency. Despite high oxygen delivery, a variety of properties related to metabolism and vascular morphology in cancer cells result in hypoxic environments, resulting in limited effectiveness of such therapies. An alternative oxygen-independent agent whose cell cytotoxicity can be remotely controlled by light may allow access to treatment of hypoxic tumors. Toward that end, we developed and tested both polyethylene glycol (PEG)-functionalized and hydrophilic silica nanoparticle (SiNP)-enriched photoacid generator (PAG) as a nontraditional PDT agent to effectively induce necrotic cell death in HCT-116 cells. Already known for applications in lithography and cationic polymerization, our developed oxygen-independent PDT, whether free or highly monodispersed on SiNPs, generates acid when a one-photon (1P) or two-photon (2P) excitation source is used, thus potentially permitting deep tissue treatment. Our study shows that when conjugated to SiNPs with protruding amine functionalities (SiNP-PAG9), such atypical PDT agents can be effectively delivered into HCT-116 cells and compartmentalize exclusively in lysosomes and endosomes. Loss of cell adhesion and cell swelling are detected when an excitation source is applied, suggesting that SiNP-PAG9, when excited via near-infrared 2P absorption (a subject of future investigation), can be used as a delivery system to selectively induce cell death in oxygen-deprived optically thick tissue.

Mind wandering away from pain dynamically engages antinociceptive and default mode brain networks.

PubMed

Kucyi, Aaron; Salomons, Tim V; Davis, Karen D

2013-11-12

Human minds often wander away from their immediate sensory environment. It remains unknown whether such mind wandering is unsystematic or whether it lawfully relates to an individual's tendency to attend to salient stimuli such as pain and their associated brain structure/function. Studies of pain-cognition interactions typically examine explicit manipulation of attention rather than spontaneous mind wandering. Here we sought to better represent natural fluctuations in pain in daily life, so we assessed behavioral and neural aspects of spontaneous disengagement of attention from pain. We found that an individual's tendency to attend to pain related to the disruptive effect of pain on his or her cognitive task performance. Next, we linked behavioral findings to neural networks with strikingly convergent evidence from functional magnetic resonance imaging during pain coupled with thought probes of mind wandering, dynamic resting state activity fluctuations, and diffusion MRI. We found that (i) pain-induced default mode network (DMN) deactivations were attenuated during mind wandering away from pain; (ii) functional connectivity fluctuations between the DMN and periaqueductal gray (PAG) dynamically tracked spontaneous attention away from pain; and (iii) across individuals, stronger PAG-DMN structural connectivity and more dynamic resting state PAG-DMN functional connectivity were associated with the tendency to mind wander away from pain. These data demonstrate that individual tendencies to mind wander away from pain, in the absence of explicit manipulation, are subserved by functional and structural connectivity within and between default mode and antinociceptive descending modulation networks.

78 FR 52818 - Notice of Meeting of the National Parks Overflights Advisory Group Aviation Rulemaking Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-26

... conference call. The meeting will be held from 10:00 a.m. to 12:00 p.m. Pacific Daylight Time. This NPOAG meeting will be open to the public. Interested persons may listen in on the conference call (see Public... Administrator and Director serve alternating 1-year terms as chairman of the advisory group. The duties of the...

77 FR 39321 - Air Traffic Procedures Advisory Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-02

... DEPARTMENT OF TRANSPORTATION Federal Aviation Administration Air Traffic Procedures Advisory... INFORMATION CONTACT: Ms. Lee Kyker, Environmental Specialist, Air Traffic Eastern Service Center, Operations... Manager, Operations Support Group, FAA, Air Traffic, Eastern Service Center. [FR Doc. 2012-16100 Filed 6...

75 FR 71791 - Commercial Space Transportation Advisory Committee-Public Teleconference

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-24

... DEPARTMENT OF TRANSPORTATION Federal Aviation Administration Commercial Space Transportation...: Notice of Commercial Space Transportation Advisory Committee Teleconference. SUMMARY: Pursuant to Section... given of a teleconference of the Space Transportation Operations Working Group (STOWG) of the Commercial...

Progress in Military Airlift (Les Progres Realises dans le Domaine du Transport Aerien Militaire)

DTIC Science & Technology

1991-05-01

transformation of the flight deck, with both visible and concealed changes. This crew/ airplane interface modification has resulted in an evolution of ...300 ADVISORY GROUP FOR AEROSPACE RESEARCH & DEVELOPMENT 7 RUE ANCELLE 92200 NEUILLY SUR SEINE FRANCE AGARD ADVISORY REPOW 300 Technical Evaluation...Advisory Report was prepared at the request of the ’ Flight Mechanics Panel of AGARD. _ North Atlantic Treaty Organization Organisation du Trait de

76 FR 82031 - Commercial Space Transportation Advisory Committee; Public Teleconference

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-29

... conducted by AST because of its knowledge and resources in the commercial space industry. The purpose of the... DEPARTMENT OF TRANSPORTATION Federal Aviation Administration Commercial Space Transportation...: Notice of Commercial Space Transportation Advisory Committee Risk Management Working Group Teleconference...

75 FR 21046 - Advisory Committee on Reactor Safeguards

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-22

... NUCLEAR REGULATORY COMMISSION Advisory Committee on Reactor Safeguards In accordance with the... on Reactor Safeguards (ACRS) will hold a meeting on May 6-8, 2010, 11545 Rockville Pike, Rockville....: Boiling Water Reactor (BWR) Owners Group (BWROG) Topical Report NEDC-33347P, ``Containment Overpressure...

76 FR 72967 - Aviation Security Advisory Committee (ASAC) Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-28

...The Transportation Security Administration (TSA) will hold a meeting of the Aviation Security Advisory Committee (ASAC) via telephone conference on December 15, 2011, to establish working groups and set the agenda for future activity. This meeting will be open to the public.

The proposed tier 2 medaka extended one generation reproduction test (MEOGRT)

EPA Science Inventory

The Food Quality Protection Act of 1996 requires EPA to develop and implement a program using valid tests for determining the potential endocrine effects from pesticides. The EPA established advisory group, the Endocrine Disruptor Screening and Testing Advisory Committee (EDSTAC)...

77 FR 24178 - Information Systems Technical Advisory Committee; Notice of Partially Closed Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-23

... and Introductions 2. Working Group Reports 3. Industry Presentation: E-beam Lithography 4. Industry Presentation: ENC Threshold for Satellite Modem 5. Industry Presentation: Semiconductor Manufacturing Equipment... DEPARTMENT OF COMMERCE Bureau of Industry and Security Information Systems Technical Advisory...

Vision Hampton Roads : public responsiveness summary.

DOT National Transportation Integrated Search

2010-02-23

All comments submitted to Vision Hampton Roads were reviewed prior to addition to the final : document. Using this Public Responsiveness Summary, citizens will be able to see and track how : their engagement has impacted results. On the following pag...

Blood-alcohol proficiency test program

DOT National Transportation Integrated Search

1975-01-01

A preliminary survey has been performed to ascertain the validity of the blood alcohol analysis performed by a number of laboratories on a voluntary basis. Values of accuracy and precision of the tests are presented. /Abstract from report summary pag...

Photoactivated and patternable charge transport materials and their use in organic light-emitting devices

NASA Astrophysics Data System (ADS)

Liu, Jie; Lewis, Larry N.; Duggal, Anil R.

2007-06-01

Organic light-emitting devices (OLEDs) usually employ at least one organic semiconductor layer that acts as a hole-injection material. The prototypical example is a conjugated polymer such as poly(3,4-ethylenedioxythiophene) heavily p doped with polystyrene sulfonic acid. Here, the authors describe a chemical doping strategy for hole injection material formulation that enables spatial patterning of the material conductivity through optical activation. The strategy utilizes an organic photoacid generator (PAG) dispersed in a polymeric organic semiconductor host. Upon UV irradiation, the PAG decomposes and generates a strong protonic acid that subsequently p dopes the host. The authors demonstrate an OLED made with such a light-activated hole-injection material and show that arbitrary emission patterning can be accomplished. This approach may provide a simple, low cost path toward specialty lighting and signage applications for OLED technology.

77 FR 10798 - Aviation Rulemaking Advisory Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-23

... assigned to the Aviation Rulemaking Advisory Committee (ARAC) concerning all weather operations. This... Weather Operations Harmonization Working Group. Over the years since assigning this task to ARAC, the... the All Weather Operations Manual for ICAO. These efforts are important to the FAA and other civil...

76 FR 2916 - Houston/Galveston Navigation Safety Advisory Committee; Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-18

... DEPARTMENT OF HOMELAND SECURITY Coast Guard [USCG-2010-1116] Houston/Galveston Navigation Safety.../Galveston Navigation Safety Advisory Committee (``HOGANSAC'' or ``the Committee'') and its working groups will meet in Texas City, Texas and Houston, Texas to discuss waterway improvements, aids to navigation...

The Payload Advisory Panel and the Data and Information System Advisory Panel of the Investigators Working Group of the Earth Observing System: A joint report

NASA Technical Reports Server (NTRS)

Moore, Berrien, III; Dozier, Jeff; Barron, Eric J.; Batista, Getulio; Brewer, Peter; Grose, William; Harris, Graham; Hartmann, Dennis; Lau, William; Lemarshall, John

1993-01-01

The Payload Advisory Panel of the Investigators Working Group (IWG) for the Earth Observing System (EOS) met 4 to 6 October 1993 in Herndon, Virginia. The Panel, originally composed of the Interdisciplinary Science Principal Investigators, was expanded to include all Principal Investigators and as such is now the IWG itself. The meeting also addressed directly a report from the EOS Data and Information System (EOSDIS) Advisory Panel. The meeting focused on payload issues in the years 2000 to 2005; however, some subjects in the nearer-term, most significantly EOSDIS, were considered. The overarching theme of convergence in Earth observations set a backdrop for the entire meeting. Other themes included: atmospheric chemistry; remote sensing of the global cycles of energy, water, and carbon in EOS; ocean and land-ice altimetry; and the EOSDIS. The Totol Solar Irradiance Monitoring Report and results from the Accelerated Canopy Chemistry Program are included as appendices.

Confirmatory radiological survey of the BORAX-V turbine building Idaho National Engineering Laboratory, Idaho Falls, Idaho

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

Stevens, G.H.; Coleman, R.L.; Jensen, M.K.

1993-07-01

An independent assessment of the remediation of the BORAX-V (Boiling Water Reactor Experiment) turbine building at the Idaho National Engineering Laboratory (INEL), Idaho Falls, Idaho, was accomplished by the Oak Ridge National Laboratory Pollutant Assessments Group (ORNL/PAG). The purpose of the assessment was to confirm the site`s compliance with applicable Department of Energy guidelines. The assessment included reviews of both the decontamination and decommissioning Plan and data provided from the pre- and post-remedial action surveys and an independent verification survey of the facility. The independent verification survey included determination of background exposure rates and soil concentrations, beta-gamma and gamma radiationmore » scans, smears for detection of removable contamination, and direct measurements for alpha and beta-gamma radiation activity on the basement and mezzanine floors and the building`s interior and exterior walls. Soil samples were taken, and beta-gamma and gamma radiation exposure rates were measured on areas adjacent to the building. Results of measurements on building surfaces at this facility were within established contamination guidelines except for elevated beta-gamma radiation levels located on three isolated areas of the basement floor. Following remediation of these areas, ORNL/PAG reviewed the remedial action contractor`s report and agreed that remediation was effective in removing the source of the elevated direct radiation. Results of all independent soil analyses for {sup 60}Co were below the detection limit. The highest {sup 137}Cs analysis result was 4.6 pCi/g; this value is below the INEL site-specific guideline of 10 pCi/g.« less

Customer advisory groups: another way to listen to the marketplace.

PubMed

Gombeski, William R; Taylor, Jan; Britt, Jason; Riggs, Karen; Wray, Tanya; Springate, Suzanne; Blair, Geoff; Bernard, Phil

2010-01-01

Customer advisory groups (CAGs) are formal groups of customers (referring physicians, patients, health insurance brokers, etc.) who meet regularly to share their ideas and to provide feedback to proposed or existing marketing strategies, programs, and activities. While CAGs are very prevalent in other industries they appear to be relatively underutilized in health care. This article provides an overview of how CAGs work, their advantages and disadvantages, tips on how to make them work better, and insights from interviews with 39 healthcare chief marketing officers on their use of CAGs.

Neonatal Sleep Restriction Increases Nociceptive Sensitivity in Adolescent Mice.

PubMed

Araujo, Paula; Coelho, Cesar A; Oliveira, Maria G; Tufik, Sergio; Andersen, Monica L

2018-03-01

Sleep loss in infants may have a negative effect on the functional and structural development of the nociceptive system. We tested the hypothesis that neonatal sleep restriction induces a long-term increase of pain-related behaviors in mice and that this hypersensitivity occurs due to changes in the neuronal activity of nociceptive pathways. We aim to investigate the effects of sleep loss in neonatal mice on pain behaviors of adolescent and adult mice in a sex-dependent manner. We also analyzed neuroanatomical and functional changes in pain pathways associated with behavioral changes. An experimental animal study. A basic sleep research laboratory at Universidade Federal de São Paulo in Brazil. Neonatal mice at postnatal day (PND) 12 were randomly assigned to either control (CTRL), maternal separation (MS), or sleep restriction (SR) groups. MS and SR were performed 2 hours a day for 10 days (PND 12 until PND 21). The gentle handling method was used to prevent sleep. At PND 21, PND 35, or PND 90, the mice were tested for pain-related behaviors. Their brains were harvested and immunohistochemically stained for c-Fos protein in the anterior cingulate cortex, primary somatosensory cortex, and periaqueductal gray (PAG). Neonatal SR significantly increased nociceptive sensitivity in the hot plate test in adolescent mice (-23.5% of pain threshold). This alteration in nociceptive response was accompanied by a decrease in c-Fos expression in PAG (-40% of c-Fos positive cells compared to the CTRL group). The hypersensitivity found in adolescent mice was not present in adult animals, and all mice showed a comparable nociceptive response. Even using a mild manipulation method, in which a minimal amount of handling was applied to maintain wakefulness, sleep deprivation was a stressful event evidenced by higher corticosterone levels. Repeated exposures to sleep loss during early life were able to induce changes in the nociceptive response associated with alterations in neural activity in descending control of pain. Brain maturation, hypersensitivity, neuronal activity, nociception, pain, periaqueductal gray, postnatal development, sleep, sleep deprivation.

Response of the μ-opioid system to social rejection and acceptance.

PubMed

Hsu, D T; Sanford, B J; Meyers, K K; Love, T M; Hazlett, K E; Wang, H; Ni, L; Walker, S J; Mickey, B J; Korycinski, S T; Koeppe, R A; Crocker, J K; Langenecker, S A; Zubieta, J-K

2013-11-01

The endogenous opioid system, which alleviates physical pain, is also known to regulate social distress and reward in animal models. To test this hypothesis in humans (n=18), we used an μ-opioid receptor (MOR) radiotracer to measure changes in MOR availability in vivo with positron emission tomography during social rejection (not being liked by others) and acceptance (being liked by others). Social rejection significantly activated the MOR system (i.e., reduced receptor availability relative to baseline) in the ventral striatum, amygdala, midline thalamus and periaqueductal gray (PAG). This pattern of activation is consistent with the hypothesis that the endogenous opioids have a role in reducing the experience of social pain. Greater trait resiliency was positively correlated with MOR activation during rejection in the amygdala, PAG and subgenual anterior cingulate cortex (sgACC), suggesting that MOR activation in these areas is protective or adaptive. In addition, MOR activation in the pregenual ACC was correlated with reduced negative affect during rejection. In contrast, social acceptance resulted in MOR activation in the amygdala and anterior insula, and MOR deactivation in the midline thalamus and sgACC. In the left ventral striatum, MOR activation during acceptance predicted a greater desire for social interaction, suggesting a role for the MOR system in social reward. The ventral striatum, amygdala, midline thalamus, PAG, anterior insula and ACC are rich in MORs and comprise a pathway by which social cues may influence mood and motivation. MOR regulation of this pathway may preserve and promote emotional well being in the social environment.

Metabolic effect of alkaline additives and guanosine/gluconate in storage solutions for red blood cells.

PubMed

D'Alessandro, Angelo; Reisz, Julie A; Culp-Hill, Rachel; Korsten, Herbert; van Bruggen, Robin; de Korte, Dirk

2018-04-06

Over a century of advancements in the field of additive solutions for red blood cell (RBC) storage has made transfusion therapy a safe and effective practice for millions of recipients worldwide. Still, storage in the blood bank results in the progressive accumulation of metabolic alterations, a phenomenon that is mitigated by storage in novel storage additives, such as alkaline additive solutions. While novel alkaline additive formulations have been proposed, no metabolomics characterization has been performed to date. We performed UHPLC-MS metabolomics analyses of red blood cells stored in SAGM (standard additive in Europe), (PAGGSM), or alkaline additives SOLX, E-SOL 5 and PAG3M for either 1, 21, 35 (end of shelf-life in the Netherlands), or 56 days. Alkaline additives (especially PAG3M) better preserved 2,3-diphosphoglycerate and adenosine triphosphate (ATP). Deaminated purines such as hypoxanthine were predictive of hemolysis and morphological alterations. Guanosine supplementation in PAGGSM and PAG3M fueled ATP generation by feeding into the nonoxidative pentose phosphate pathway via phosphoribolysis. Decreased urate to hypoxanthine ratios were observed in alkaline additives, suggestive of decreased generation of urate and hydrogen peroxide. Despite the many benefits observed in purine and redox metabolism, alkaline additives did not prevent accumulation of free fatty acids and oxidized byproducts, opening a window for future alkaline formulations including (lipophilic) antioxidants. Alkalinization via different strategies (replacement of chloride anions with either high bicarbonate, high citrate/phosphate, or membrane impermeant gluconate) results in different metabolic outcomes, which are superior to current canonical additives in all cases. © 2018 AABB.

Toll-Like Receptor Activation by Generalized Modules for Membrane Antigens from Lipid A Mutants of Salmonella enterica Serovars Typhimurium and Enteritidis.

PubMed

Rossi, Omar; Caboni, Mariaelena; Negrea, Aurel; Necchi, Francesca; Alfini, Renzo; Micoli, Francesca; Saul, Allan; MacLennan, Calman A; Rondini, Simona; Gerke, Christiane

2016-04-01

Invasive nontyphoidal Salmonella (iNTS) disease is a neglected disease with high mortality in children and HIV-positive individuals in sub-Saharan Africa, caused primarily by Africa-specific strains of Salmonella enterica serovars Typhimurium and Enteritidis. A vaccine using GMMA (generalized modules for membrane antigens) fromS.Typhimurium andS.Enteritidis containing lipid A modifications to reduce potential in vivo reactogenicity is under development. GMMA with penta-acylated lipid A showed the greatest reduction in the level of cytokine release from human peripheral blood monocytes from that for GMMA with wild-type lipid A. Deletion of the lipid A modification genes msbB and pagP was required to achieve pure penta-acylation. Interestingly, ΔmsbBΔ pagP GMMA from S. Enteritidis had a slightly higher stimulatory potential than those from S. Typhimurium, a finding consistent with the higher lipopolysaccharide (LPS) content and Toll-like receptor 2 (TLR2) stimulatory potential of the former. Also, TLR5 ligand flagellin was found in Salmonella GMMA. No relevant contribution to the stimulatory potential of GMMA was detected even when the flagellin protein FliC from S. Typhimurium was added at a concentration as high as 10% of total protein, suggesting that flagellin impurities are not a major factor for GMMA-mediated immune stimulation. Overall, the stimulatory potential of S. Typhimurium and S. Enteritidis ΔmsbB ΔpagP GMMA was close to that of Shigella sonnei GMMA, which are currently in phase I clinical trials. Copyright © 2016 Rossi et al.

Age-dependent plasticity in endocannabinoid modulation of pain processing through postnatal development.

PubMed

Kwok, Charlie H-T; Devonshire, Ian M; Imraish, Amer; Greenspon, Charles M; Lockwood, Stevie; Fielden, Catherine; Cooper, Andrew; Woodhams, Stephen; Sarmad, Sarir; Ortori, Catherine A; Barrett, David A; Kendall, David; Bennett, Andrew J; Chapman, Victoria; Hathway, Gareth J

2017-11-01

Significant age- and experience-dependent remodelling of spinal and supraspinal neural networks occur, resulting in altered pain responses in early life. In adults, endogenous opioid peptide and endocannabinoid (ECs) pain control systems exist which modify pain responses, but the role they play in acute responses to pain and postnatal neurodevelopment is unknown. Here, we have studied the changing role of the ECs in the brainstem nuclei essential for the control of nociception from birth to adulthood in both rats and humans. Using in vivo electrophysiology, we show that substantial functional changes occur in the effect of microinjection of ECs receptor agonists and antagonists in the periaqueductal grey (PAG) and rostroventral medulla (RVM), both of which play central roles in the supraspinal control of pain and the maintenance of chronic pain states in adulthood. We show that in immature PAG and RVM, the orphan receptor, GPR55, is able to mediate profound analgesia which is absent in adults. We show that tissue levels of endocannabinoid neurotransmitters, anandamide and 2-arachidonoylglycerol, within the PAG and RVM are developmentally regulated (using mass spectrometry). The expression patterns and levels of ECs enzymes and receptors were assessed using quantitative PCR and immunohistochemistry. In human brainstem, we show age-related alterations in the expression of key enzymes and receptors involved in ECs function using PCR and in situ hybridisation. These data reveal that significant changes on ECs that to this point have been unknown and which shed new light into the complex neurochemical changes that permit normal, mature responses to pain.

Activation patterns of cells in selected brain stem nuclei of more and less stress responsive rats in two animal models of PTSD - predator exposure and submersion stress.

PubMed

Adamec, Robert; Toth, Mate; Haller, Jozsef; Halasz, Jozsef; Blundell, Jacqueline

2012-02-01

This study had two purposes. First: compare predator and water submersion stress cFos activation patterns in dorsal raphe (DR), locus coeruleus (LC) and periaqueductal gray (PAG). Second: identify markers of vulnerability to stressors within these areas. Rats were either predator or submersion stressed and tested 1.75 h later for anxiety-like behavior. Immediately thereafter, rats were sacrificed and cFos expression examined. In DR, serotonergic cells expressing or not expressing cFos were also counted. Predator and submersion stress increased anxiety-like behavior (in the elevated plus maze- EPM) equally over controls. Moreover, stressed rats spent equally less time in the center of the hole board than handled controls, another indication of increased anxiety-like behavior. To examine vulnerability, rats which were less anxious (LA) and more (highly) anxious (MA) in the EPM were selected from among handled control and stressed animals. LA rats in the stressed groups were considered stress non-responsive and MA stressed rats were considered stress responsive. LA and MA rats did not differ in cFos expression in any brain area, though stressors did increase cFos cell counts in all areas over controls. Intriguingly, the number of serotonergic DR neurons not activated by stress predicted degree of anxiety response to submersion stress only. LA submersion stressed rats had more serotonergic cells than all other groups, and MA submersion stressed rats had fewer serotonergic cells than all other groups, which did not differ. Moreover, these cell counts correlated with EPM anxiety. We conclude that a surplus of such cells protects against anxiogenic effects of submersion, while a paucity of such cells enhances vulnerability to submersion stress. Other data suggest serotonergic cells may exert their effects via inhibition of dorsolateral PAG cells during submersion stress. Findings are discussed with respect to serotonergic transmission in vulnerability to predator stress and relevance of findings for post traumatic stress disorder (PTSD). This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'. Copyright © 2010 Elsevier Ltd. All rights reserved.

The process of developing evidence-based guidance in medicine and public health: a qualitative study of views from the inside

PubMed Central

2013-01-01

Background There has been significant investment in developing guidelines to improve clinical and public health practice. Though much is known about the processes of evidence synthesis and evidence-based guidelines implementation, we know little about how evidence presented to advisory groups is interpreted and used to form practice recommendations or what happens where evidence is lacking. This study investigates how members of advisory groups of NICE (National Institute of Health and Clinical Excellence) conceptualize evidence and experience the process. Methods Members of three advisory groups for acute physical, mental and public health were interviewed at the beginning and end of the life of the group. Seventeen were interviewed at both time points; five were interviewed just once at time one; and 17 were interviewed only once after guidance completion. Using thematic and content analysis, interview transcripts were analysed to identify the main themes. Results Three themes were identified: 1. What is the task? Different members conceptualized the task differently; some emphasized the importance of evidence at the top of the quality hierarchy while others emphasized the importance of personal experience. 2. Who gets heard? Managing the diversity of opinion and vested interests was a challenge for the groups; service users were valued and as was the importance of fostering good working relationships between group members. 3. What is the process? Group members valued debate and recognized the need to marshal discussion; most members were satisfied with the process and output. Conclusions Evidence doesn’t form recommendations on its own, but requires human judgement. Diversity of opinion within advisory groups was seen as key to making well-informed judgments relevant to forming recommendations. However, that diversity can bring tensions in the evaluation of evidence and its translation into practice recommendations. PMID:24006933

77 FR 67367 - Announcement of Physical Activity Guidelines Mid-Course Report Availability and Public Comment...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-09

... Council on Fitness, Sports and Nutrition (PCFSN) was convened to complete the PAG Mid- course Report. The... INFORMATION: A subcommittee of the President's Council on Fitness, Sports and Nutrition (PCFSN) was created...

Hartmannella vermiformis inhibition of Legionella pneumophila cultivability

EPA Science Inventory

Hartmannella vermiformis is frequently isolated from drinking water (DW) and is permissive to Legionella pneumophila intracellular replication. Thus, H. vermiformis may play an important role in the growth and survival potential of such environmental pathogens. In this study, Pag...

West Valley College Vocational and Technical Advisory Committees.

ERIC Educational Resources Information Center

West Valley Coll., Saratoga, CA.

This brochure describes junior college advisory committees as groups of persons who represent industry and assist in organizing curriculum, advise on material procurement, keep the college current on industry practices, coordinate programs with the community, assist in student selection, guide instructors, provide moral support and public…

77 FR 74341 - Establishing the Hurricane Sandy Rebuilding Task Force

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-14

... Economic Advisers; (xxii) the White House Office of Public Engagement and Intergovernmental Affairs; (xxiii... their official capacity, may designate employees with authority to act on their behalf. The Advisory... Advisory Group members and elected officials, or their designated employees, as necessary to provide advice...

78 FR 62002 - Railroad Safety Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-10

... Working Groups. Status reports will also be provided by the Engineering Task Force. This agenda is subject... CONTACT: Larry Woolverton, RSAC Administrative Officer/Coordinator, FRA, 1200 New Jersey Avenue SE... perspectives. In addition, there are non-voting advisory representatives from the agencies with railroad safety...

77 FR 31398 - National Advisory Committee on Occupational Safety and Health (NACOSH)

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-25

... DEPARTMENT OF LABOR Occupational Safety and Health Administration [Docket No. OSHA-2012-0019] National Advisory Committee on Occupational Safety and Health (NACOSH) AGENCY: Occupational Safety and... on Occupational Safety and Health (NACOSH) and NACOSH Work Groups. SUMMARY: NACOSH will meet June 20...

AGARD Flight Test Instrumentation Series. Volume 7. Strain Gauge Measurements on Aircraft

DTIC Science & Technology

1976-04-01

U.S. DEPARTMENT OF CRY11ERCE Natioal Techaical Infnaitm Soice AD-A026 838 AGARD FLIGHT TEST INSTRUMENTATION SERIES VOLUME 7. STRAIN GUAGE...MEASUREMENTS ON AIRCRAFT ADVISORY GROUP FOR AEROSPACE RESEARCH AND DEVELOPMENT PREPARED FOR.I NORTH ATLANTIC TREATY ORGANIZATION APRIL 1976 • • ,. h VI -i• d...INFORMATION DOCUMENT PROCESSING WORKSHEET ,5.RVICE USCOMM-DC 41420.P7I AGARD-AG-160 Volume 7 NORTH ATLANTIC TREATY ORGANIZATION ADVISORY GROUP FOR AEROSPACE

77 FR 11557 - National Advisory Council on the National Health Service Corps; Request for Nominations

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-27

... sets forth standards for the formation and use of advisory committees. The NAC on the NHSC is a group..., recruitment and retention, site administration, customer service, marketing, organizational partnerships... specific attributes, perspectives, and/or skills does the individual possess that would benefit the...

78 FR 66425 - Advisory Group to the Commissioner of Internal Revenue; Renewal of Charter

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-05

... Charter for the Information Reporting Program Advisory Committee (IRPAC), has been renewed for a two-year period beginning October 29, 2013. FOR FURTHER INFORMATION CONTACT: Ms. Caryl Grant, National Public Liaison, at [email protected] . SUPPLEMENTARY INFORMATION: Notice is hereby given under section 10(a...

76 FR 67556 - Advisory Group to the Commissioner of Internal Revenue; Renewal of Charter

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-01

... Charter for the Information Reporting Program Advisory Committee (IRPAC), has been renewed for a two-year period beginning October 20, 2011. FOR FURTHER INFORMATION CONTACT: Ms.Caryl Grant, National Public Liaison, at [email protected] . SUPPLEMENTARY INFORMATION: Notice is hereby given under section 10(a...

75 FR 49508 - Navigation Safety Advisory Council; Vacancies

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-13

... having an active interest in the Rules of the Road and vessel and port safety (Group One); three persons... active interest in the Rules of the Road and vessel and port safety'' includes: Organizations that... DEPARTMENT OF HOMELAND SECURITY Coast Guard [Docket No. USCG-2010-0708] Navigation Safety Advisory...

77 FR 12839 - Federal Advisory Committee Act; Technological Advisory Council

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-02

... 12th Street SW., Washington, DC 20554. DATES: March 28, 2012. ADDRESSES: Federal Communications Commission, 445 12th Street SW., Washington, DC 20554. FOR FURTHER INFORMATION CONTACT: Walter Johnston... groups to support planned work. The FCC will attempt to accommodate as many people as possible. However...

78 FR 66425 - Advisory Group to the Commissioner of Internal Revenue; Renewal of Charter

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-05

... officials and representatives of the public to discuss relevant tax administration issues. As an advisory body designed to focus on broad policy matters, the IRSAC reviews existing tax policy and/or makes recommendations with respect to emerging federal tax administration issues. The IRSAC suggests operational...

76 FR 67256 - Advisory Group to the Commissioner of Internal Revenue; Renewal of Charter

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-31

... public, the tax professional community, small and large businesses, international, wage and investment... Revenue Service officials and representatives of the public to discuss relevant tax administration issues. As an advisory body designed to focus on broad policy matters, the IRSAC reviews existing tax policy...

Student Success: The Case for Establishing Prerequisites through Content Review

ERIC Educational Resources Information Center

Academic Senate for California Community Colleges, 2010

2010-01-01

In the 1990s, the Academic Senate collaborated with the Chancellor's Office and other leadership groups in the state to revise Title 5 regulations, to draft "The Model District Policy on Prerequisites, Corequisites, and Advisories on Recommended Preparation" (Board of Governors, 1993) and "Prerequisites, Corequisites, Advisories, And Limitations…

An examination of women's representation and participation in bicycle advisory committees in California : [research brief].

DOT National Transportation Integrated Search

2012-04-01

In the United States, women bicycle at significantly lower rates than men. One method of remedying this disparity is to ensure that women are engaged in bicycle planning and policy making. A bicycle advisory committee is one type of group that undert...

78 FR 27866 - Appliance Standards and Rulemaking Federal Advisory Committee: Notice of Open Meeting for the...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-13

... Federal Advisory Committee: Notice of Open Meeting for the Commercial HVAC, WH, and Refrigeration..., Ventilation, and Air-conditioning (HVAC), Water Heating (WH), and Refrigeration Certification Working Group... requirements for commercial HVAC, WH, and refrigeration equipment, as authorized by the Energy Policy and...

Reclaiming Advisory: Advocacy in Action

ERIC Educational Resources Information Center

Bennett, Cory A.; Martin, Kathryn

2018-01-01

Exemplary middle schools have a variety of programs that support students' needs and help them adjust socially and emotionally; advisory programs can be one structure to effectively provide some of this support. This article shares the story of how a group of middle level teachers and teacher leaders within a culturally diverse school reclaimed…

77 FR 44707 - Commercial Space Transportation Advisory Committee-Public Teleconference

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-30

... statements should contact Susan Lender, DFO, (the Contact Person listed below) in writing (mail or email) by... Susan Lender, Designated Federal Officer (DFO), (the Contact Person listed below) by phone or email for... relevant written statements for the COMSTAC working group members to consider under the advisory process...

Science Advisory Panel Meets to Discuss HLB/ACP

USDA-ARS?s Scientific Manuscript database

A group of scientists met in December 2013 as a Science Advisory Panel (SAP) to listen to presentations by the Citrus Research Board (CRB) and the California Department of Food and Agriculture (CDFA) and to respond to questions posed by CDFA personnel and the general public. The goal of the meeting ...

Sequential Nitrification/Denitrification in Subsurface Flow Constructed Wetlands. A Literature Review

DTIC Science & Technology

1992-12-01

I I I I I iii I I I 3 TABLE OF CONTENTS SIG NATURE PAG E...3 SECTION I1. CONSTRUCTED WETLANDS: AN OVERVIEW ......................................... 4 A. Natural W...pollutants from secondary effluent in natural w etlands

[Report of the Ninth meeting of the WHO Technical Advisory Group of Leprosy Control].

PubMed

Ishii, Norihisa; Mori, Shuichi; Nagaoka, Yuzuru; Suzuki, Koichi

2009-02-01

The Ninth meeting of the WHO Technical Advisory Group (TAG) on Leprosy Control was held in Cairo, Egypt on 6th and 7th March 2008. The meeting was chaired by Professor W.C.S. Smith and attended by national leprosy programme managers from Brazil, the Democratic Republic of Congo, Cambodia, Egypt, Iran, India, Nigeria and Thailand. In addition, several experts and members of the Technical Commission of the International Federation ofAnti-Leprosy Associations (ILEP) also attended the meeting.

Water Conservation and Reuse. Instructor Guide. Working for Clean Water: An Information Program for Advisory Committees.

ERIC Educational Resources Information Center

Pennsylvania State Univ., Middletown. Inst. of State and Regional Affairs.

Described is a learning session on water conservation intended for citizen advisory groups interested in water quality planning. Topics addressed in this instructor's manual include water conservation needs, benefits, programs, technology, and problems. These materials are components of the Working for Clean Water Project. (Author/WB)

Formation and Uses of Lay Advisory Groups for the Humanities. Project Report No. 14.

ERIC Educational Resources Information Center

Beckwith, Miriam M.

Based on the experiences of several community colleges, this report examines successful and unsuccessful strategies utilized in the formation of lay advisory committees for the humanities. The report first presents brief descriptions of successful committee organization efforts at five institutions: Clark College (Vancouver, WA), Brevard Community…

The Heart of School

ERIC Educational Resources Information Center

DiMartino, Joseph; Clarke, John H.

2008-01-01

Successful advisory programs have a number of things in common across a wide variety of schools. They all divide the student body into small groups, usually of 20 or fewer students, that meet regularly with an adult in the school community. In addition to this basic element, successful advisory programs have five other elements in common: (1) They…

National Mathematics Advisory Panel Reports of the Task Groups and Subcommittees

ERIC Educational Resources Information Center

US Department of Education, 2008

2008-01-01

For students to compete in the 21st-century global economy, knowledge of and proficiency in mathematics are critical. Whether headed to college or to the workforce, today's high school graduates need solid mathematics skill. The National Mathematics Advisory Panel was created in 2006 and charged with reviewing the best available scientific…

78 FR 22550 - Solicitation of Nomination for Appointment to the Advisory Committee on Minority Health

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-16

... groups; (6) ensure that the National Center for Health Statistics collects data on the health status of... DEPARTMENT OF HEALTH AND HUMAN SERVICES Solicitation of Nomination for Appointment to the Advisory Committee on Minority Health AGENCY: Office of Minority Health, Office of the Assistant Secretary for Health...

76 FR 27059 - Solicitation of Written Comments on the Draft Report and Draft Recommendations of the Vaccine...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-10

... Draft Recommendations of the Vaccine Safety Working Group for Consideration by the National Vaccine Advisory Committee on the Federal Vaccine Safety System AGENCY: National Vaccine Program Office, Office of.... ACTION: Notice. SUMMARY: The National Vaccine Advisory Committee (NVAC) was established in 1987 to comply...

National VET Equity Advisory Taskforce. Final Report

ERIC Educational Resources Information Center

Australian Government Department of Education, Employment and Workplace Relations, 2009

2009-01-01

The purview of the National VET (Vocational Education and Training) Equity Advisory Taskforce (NVEAT) encompasses a range of clients and issues across the full spectrum of the VET sector. NVEAT has undertaken a number of activities to gain a better understanding of the range of issues affecting all learners and particular disadvantaged groups of…

75 FR 7483 - Center for Substance Abuse Prevention; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-19

... working groups; and a comparison of HHS and DOT urine collection requirements. DTAB members and invited... ensure that advisory committee meetings proceed in an orderly fashion, are conducted in a safe and secure environment, that the right of free speech is protected, and that the ability of SAMHSA Advisory Committees to...

76 FR 76740 - Secretary's Advisory Committee on Heritable Disorders in Newborns and Children; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-08

...), notice is hereby given of the following meeting: Name: Secretary's Advisory Committee on Heritable... than Tuesday, January 24, 2012. All comments, whether oral or written, should contain the name, address, telephone number, and any professional or business affiliation of the author. Groups having similar...

A-Okay: A Middle School Advisory Program.

ERIC Educational Resources Information Center

Robinson, Bonnie

This guide presents an advisory program for middle schools. The program is designed for groups of 10 to 15 students meeting twice a week; the advisors should be adults from within the school (teachers, guidance counselors, administrators, etc.). The program has four goals: (1) to promote students' sense of belonging within the school; (2) to…

The President's Advisory Council: A Seminar for College CEOs.

ERIC Educational Resources Information Center

Scott, Robert A.

The purpose of the President's Advisory Council at Ramapo College of New Jersey is discussed by the college's president. The Council consists of a small group of experienced executives who discuss with the president strategic issues inherent in managing a sizeable enterprise. The four members of the Council are a marketing expert, a strategic…

Teacher's Guide for "Tightrope," a Simulation Game in Economics.

ERIC Educational Resources Information Center

Baskind, Larry; And Others

"Tightrope" is a simulation based on economic stability and growth in a country. Several small groups of students, acting as Economic Advisory Councils, make fiscal and monetary policy decisions for their country based on their knowledge of business cycles, monetary policy, and fiscal policy. In each of the four rounds the Advisory Councils study…

Urodynamic function during sleep-like brain states in urethane anesthetized rats.

PubMed

Crook, J; Lovick, T

2016-01-28

The aim was to investigate urodynamic parameters and functional excitability of the periaqueductal gray matter (PAG) during changes in sleep-like brain states in urethane anesthetized rats. Simultaneous recordings of detrusor pressure, external urethral sphincter (EUS) electromyogram (EMG), cortical electroencephalogram (EEG), and single-unit activity in the PAG were made during repeated voiding induced by continuous infusion of saline into the bladder. The EEG cycled between synchronized, high-amplitude slow wave activity (SWA) and desynchronized low-amplitude fast activity similar to slow wave and 'activated' sleep-like brain states. During (SWA, 0.5-1.5 Hz synchronized oscillation of the EEG waveform) voiding became more irregular than in the 'activated' brain state (2-5 Hz low-amplitude desynchronized EEG waveform) and detrusor void pressure threshold, void volume threshold and the duration of bursting activity in the external urethral sphincter EMG were raised. The spontaneous firing rate of 23/52 neurons recorded within the caudal PAG and adjacent tegmentum was linked to the EEG state, with the majority of responsive cells (92%) firing more slowly during SWA. Almost a quarter of the cells recorded (12/52) showed phasic changes in firing rate that were linked to the occurrence of voids. Inhibition (n=6), excitation (n=4) or excitation/inhibition (n=2) was seen. The spontaneous firing rate of 83% of the micturition-responsive cells was sensitive to changes in EEG state. In nine of the 12 responsive cells (75%) the responses were reduced during SWA. We propose that during different sleep-like brain states changes in urodynamic properties occur which may be linked to changing excitability of the micturition circuitry in the periaqueductal gray. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

A potential role for the midbrain in integrating fat-free mass determined energy needs: An H2 (15) O PET study.

PubMed

Weise, Christopher M; Thiyyagura, Pradeep; Reiman, Eric M; Chen, Kewei; Krakoff, Jonathan

2015-06-01

Little is known on how sensing of energy needs is centrally represented, integrated, and translated into the behavioral aspects of energy homeostasis. Fat free mass (FFM) is the major determinant of energy expenditure. We investigated how interindividual variances in FFM relate to neuronal activity in humans. Healthy adults (n = 64, 21F/43M; age 31.3 ± 9.1y; percentage of body fat [PFAT] 25.6 ± 10.7%; BMI 30.4 ± 9) underwent a 36h fast and subsequent H(2) (15) O positron emission tomographic (PET) measurement of regional cerebral blood flow (rCBF). Multiple variable regression analysis revealed significant associations of FFM with rCBF within the midbrain [including parts of the periaqueductal gray (PAG), ventral tegmental area (VTA), thalamic and hypothalamic regions], the bilateral parahippocampal region, left anterior cingulate, left insular cortex, right cerebellum, and distinct regions within the temporal and occipital cortex. In contrast, no significant associations were found for fat mass (FM). We investigated the potential functional-anatomical link between FFM and central regulation of food intake by performing a conjunction analysis of FFM and the perceived hunger feelings. This showed a significant overlap within the midbrain PAG. Mediation analysis demonstrated a significant indirect effect of FFM on hunger with PAG rCBF as mediator. Most regions we found to be associated with FFM form part in ascending homeostatic pathways and cortical circuitries implicated in the regulation of basic bodily functions indicating a potential role of these central networks in the integration of FFM determined energy needs. © 2015 Wiley Periodicals, Inc.

Tolerance to the antinociceptive effect of morphine in the absence of short-term presynaptic desensitization in rat periaqueductal gray neurons.

PubMed

Fyfe, Leon W; Cleary, Daniel R; Macey, Tara A; Morgan, Michael M; Ingram, Susan L

2010-12-01

Opioids activate the descending antinociceptive pathway from the ventrolateral periaqueductal gray (vlPAG) by both pre- and postsynaptic inhibition of tonically active GABAergic neurons (i.e., disinhibition). Previous research has shown that short-term desensitization of postsynaptic μ-opioid receptors (MOPrs) in the vlPAG is increased with the development of opioid tolerance. Given that pre- and postsynaptic MOPrs are coupled to different signaling mechanisms, the present study tested the hypothesis that short-term desensitization of presynaptic MOPrs also contributes to opioid tolerance. Twice-daily injections of morphine (5 mg/kg s.c.) for 2 days caused a rightward shift in the morphine dose-response curve on the hot plate test (D(50) = 9.9 mg/kg) compared with saline-pretreated (5.3 mg/kg) male Sprague-Dawley rats. In vitro whole-cell patch-clamp recordings from vlPAG slices revealed that inhibition of evoked inhibitory postsynaptic currents (eIPSCs) by the MOPr-selective agonist [d-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin was decreased in morphine-tolerant (EC(50) = 708 nM) compared with saline-pretreated rats (EC(50) = 163 nM). However, short-term desensitization of MOPr inhibition of eIPSCs was not observed in either saline- or morphine-pretreated rats. Reducing the number of available MOPrs with the irreversible opioid receptor antagonist, β-chlornaltrexamine decreased maximal MOPr inhibition with no evidence of desensitization, indicating that the lack of observed desensitization is not caused by receptor reserve. These results demonstrate that tolerance to the antinociceptive effect of morphine is associated with a decrease in presynaptic MOPr sensitivity or coupling to effectors, but this change is independent of short-term MOPr desensitization.

Tolerance to the Antinociceptive Effect of Morphine in the Absence of Short-Term Presynaptic Desensitization in Rat Periaqueductal Gray Neurons

PubMed Central

Fyfe, Leon W.; Cleary, Daniel R.; Macey, Tara A.; Morgan, Michael M.

2010-01-01

Opioids activate the descending antinociceptive pathway from the ventrolateral periaqueductal gray (vlPAG) by both pre- and postsynaptic inhibition of tonically active GABAergic neurons (i.e., disinhibition). Previous research has shown that short-term desensitization of postsynaptic μ-opioid receptors (MOPrs) in the vlPAG is increased with the development of opioid tolerance. Given that pre- and postsynaptic MOPrs are coupled to different signaling mechanisms, the present study tested the hypothesis that short-term desensitization of presynaptic MOPrs also contributes to opioid tolerance. Twice-daily injections of morphine (5 mg/kg s.c.) for 2 days caused a rightward shift in the morphine dose-response curve on the hot plate test (D50 = 9.9 mg/kg) compared with saline-pretreated (5.3 mg/kg) male Sprague-Dawley rats. In vitro whole-cell patch-clamp recordings from vlPAG slices revealed that inhibition of evoked inhibitory postsynaptic currents (eIPSCs) by the MOPr-selective agonist [d-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin was decreased in morphine-tolerant (EC50 = 708 nM) compared with saline-pretreated rats (EC50 = 163 nM). However, short-term desensitization of MOPr inhibition of eIPSCs was not observed in either saline- or morphine-pretreated rats. Reducing the number of available MOPrs with the irreversible opioid receptor antagonist, β-chlornaltrexamine decreased maximal MOPr inhibition with no evidence of desensitization, indicating that the lack of observed desensitization is not caused by receptor reserve. These results demonstrate that tolerance to the antinociceptive effect of morphine is associated with a decrease in presynaptic MOPr sensitivity or coupling to effectors, but this change is independent of short-term MOPr desensitization. PMID:20739455

Song-associated reward correlates with endocannabinoid-related gene expression in male European starlings (Sturnus vulgaris).

PubMed

Hahn, Allison H; Merullo, Devin P; Spool, Jeremy A; Angyal, Caroline S; Stevenson, Sharon A; Riters, Lauren V

2017-03-27

Vocal communication is required for successful social interactions in numerous species. During the breeding season, songbirds produce songs that are reinforced by behavioral consequences (e.g., copulation). However, some songbirds also produce songs not obviously directed at other individuals. The consequences maintaining or reinforcing these songs are less obvious and the neural mechanisms associated with undirected communication are not well-understood. Previous studies indicate that undirected singing is intrinsically rewarding and mediated by opioid or dopaminergic systems; however, endocannabinoids are also involved in regulating reward and singing behavior. We used a conditioned place preference paradigm to examine song-associated reward in European starlings and quantitative real-time PCR to measure expression of endocannabinoid-related neural markers (CB 1 , FABP7, FABP5, FAAH, DAGLα), in brain regions involved in social behavior, reward and motivation (ventral tegmental area [VTA], periaqueductal gray [PAG], and medial preoptic nucleus [POM]), and a song control region (Area X). Our results indicate that starlings producing high rates of song developed a conditioned place preference, suggesting that undirected song is associated with a positive affective state. We found a significant positive relationship between song-associated reward and CB 1 receptors in VTA and a significant negative relationship between song-associated reward and CB 1 in PAG. There was a significant positive relationship between reward and the cannabinoid transporter FABP7 in POM and a significant negative relationship between reward and FABP7 in PAG. In Area X, FABP5 and DAGLα correlated positively with singing. These results suggest a role for endocannabinoid signaling in vocal production and reward associated with undirected communication. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Impact of ambiguity and risk on decision making in mild Alzheimer's disease.

PubMed

Sinz, H; Zamarian, L; Benke, T; Wenning, G K; Delazer, M

2008-01-01

Decisions under ambiguity and decisions under risk are crucial types of decision making in daily living at any age. This is the first study assessing these two types of decisions in patients with mild dementia of Alzheimer's type (DAT) by means of the Iowa Gambling Task (IGT) and a newly developed, Probability-Associated Gambling (PAG) task. While rules for gains and losses are implicit in the IGT, in the PAG task rules are explicit and winning probabilities, which change from trial to trial, can be estimated. Results of the IGT indicated that DAT patients made more disadvantageous decisions than healthy controls. Patients also shifted more frequently among decks, i.e. under ambiguity decisions were taken randomly and no advantageous strategy was established over time by DAT patients. Thus, not only actual choices but also development of advantageous strategies may be revealing about decision making in the IGT. Compared to controls, patients demonstrated less advantageous choices in the PAG task as well. They gambled more often in the low winning probabilities and less frequently in the high probabilities than healthy participants. Patients' performance on both tasks correlated with measures of executive functions. Findings of the present investigation are consistent with the early pathological cerebral changes and related (cognitive, emotional) deficits reported for DAT. As suggested by our study, decisions under ambiguity as well as decisions under risk are impaired in mild DAT. It may thus be expected that patients with mild DAT have difficulties in taking decisions in every-day life situations, both in cases of ambiguity (information on probability is missing or conflicting, and the expected utility of the different options is incalculable) and in cases of risk (outcomes can be predicted by well-defined or estimable probabilities).

Song-associated reward correlates with endocannabinoid-related gene expression in male European starlings (Sturnus vulgaris)

PubMed Central

Hahn, Allison H.; Merullo, Devin P.; Spool, Jeremy A.; Angyal, Caroline S.; Stevenson, Sharon A.; Riters, Lauren V.

2017-01-01

Vocal communication is required for successful social interactions in numerous species. During the breeding season, songbirds produce songs that are reinforced by behavioral consequences (e.g., copulation). However, some songbirds also produce songs not obviously directed at other individuals. The consequences maintaining or reinforcing these songs are less obvious and the neural mechanisms associated with undirected communication are not well-understood. Previous studies indicate that undirected singing is intrinsically rewarding and mediated by opioid or dopaminergic systems; however, endocannabinoids are also involved in regulating reward and singing behavior. We used a conditioned place preference paradigm to examine song-associated reward in European starlings and quantitative real-time PCR to measure expression of endocannabinoid-related neural markers (CB1, FABP7, FABP5, FAAH, DAGLα), in brain regions involved in social behavior, reward and motivation (ventral tegmental area [VTA], periaqueductal gray [PAG], and medial preoptic nucleus [POM]), and a song control region (Area X). Our results indicate that starlings producing high rates of song developed a conditioned place preference, suggesting that undirected song is associated with a positive affective state. We found a significant positive relationship between song-associated reward and CB1 receptors in VTA and a significant negative relationship between song-associated reward and CB1 in PAG. There was a significant positive relationship between reward and the cannabinoid transporter FABP7 in POM and a significant negative relationship between reward and FABP7 in PAG. In Area X, FABP5 and DAGLα correlated positively with singing. These results suggest a role for endocannabinoid signaling in vocal production and reward associated with undirected communication. PMID:28147243

Menthol enhances phasic and tonic GABAA receptor-mediated currents in midbrain periaqueductal grey neurons

PubMed Central

Lau, Benjamin K; Karim, Shafinaz; Goodchild, Ann K; Vaughan, Christopher W; Drew, Geoffrey M

2014-01-01

Background and Purpose Menthol, a naturally occurring compound in the essential oil of mint leaves, is used for its medicinal, sensory and fragrant properties. Menthol acts via transient receptor potential (TRPM8 and TRPA1) channels and as a positive allosteric modulator of recombinant GABAA receptors. Here, we examined the actions of menthol on GABAA receptor-mediated currents in intact midbrain slices. Experimental Approach Whole-cell voltage-clamp recordings were made from periaqueductal grey (PAG) neurons in midbrain slices from rats to determine the effects of menthol on GABAA receptor-mediated phasic IPSCs and tonic currents. Key Results Menthol (150–750 μM) produced a concentration-dependent prolongation of spontaneous GABAA receptor-mediated IPSCs, but not non-NMDA receptor-mediated EPSCs throughout the PAG. Menthol actions were unaffected by TRPM8 and TRPA1 antagonists, tetrodotoxin and the benzodiazepine antagonist, flumazenil. Menthol also enhanced a tonic current, which was sensitive to the GABAA receptor antagonists, picrotoxin (100 μM), bicuculline (30 μM) and Zn2+ (100 μM), but unaffected by gabazine (10 μM) and a GABAC receptor antagonist, 1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid hydrate (TPMPA; 50 μM). In addition, menthol potentiated currents induced by the extrasynaptic GABAA receptor agonist THIP/gaboxadol (10 μM). Conclusions and Implications These results suggest that menthol positively modulates both synaptic and extrasynaptic populations of GABAA receptors in native PAG neurons. The development of agents that potentiate GABAA-mediated tonic currents and phasic IPSCs in a manner similar to menthol could provide a basis for novel GABAA-related pharmacotherapies. PMID:24460753

Hydrogen sulfide accelerates the recovery of kidney tubules after renal ischemia/reperfusion injury.

PubMed

Han, Sang Jun; Kim, Jee In; Park, Jeen-Woo; Park, Kwon Moo

2015-09-01

Progression of acute kidney injury to chronic kidney disease (CKD) is associated with inadequate recovery of damaged kidney. Hydrogen sulfide (H2S) regulates a variety of cellular signals involved in cell death, differentiation and proliferation. This study aimed to identify the role of H2S and its producing enzymes in the recovery of kidney following ischemia/reperfusion (I/R) injury. Mice were subjected to 30 min of bilateral renal ischemia. Some mice were administered daily NaHS, an H2S donor, and propargylglycine (PAG), an inhibitor of the H2S-producing enzyme cystathionine gamma-lyase (CSE), during the recovery phase. Cell proliferation was assessed via 5'-bromo-2'-deoxyuridine (BrdU) incorporation assay. Ischemia resulted in decreases in CSE and cystathionine beta-synthase (CBS) expression and activity, and H2S level in the kidney. These decreases did not return to sham level until 8 days after ischemia when kidney had fibrotic lesions. NaHS administration to I/R-injured mice accelerated the recovery of renal function and tubule morphology, whereas PAG delayed that. Furthermore, PAG increased mortality after ischemia. NaHS administration to I/R-injured mice accelerated tubular cell proliferation, whereas it inhibited interstitial cell proliferation. In addition, NaHS treatment reduced post-I/R superoxide formation, lipid peroxidation, level of GSSG/GSH and Nox4 expression, whereas it increased catalase and MnSOD expression. Our findings demonstrate that H2S accelerates the recovery of I/R-induced kidney damage, suggesting that the H2S-producing transsulfuration pathway plays an important role in kidney repair after acute injury. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Mental Health Advisory Team-Korea (8th Army) Technical Report

DTIC Science & Technology

2016-06-30

10 2.3 Comparison Groups for Analyses...10 2.4 Focus Groups ............................................................................................................... 11...46 8.7 Perceptions of Staffing Challenges: Survey and Focus Group Data .............................. 48 9 SOLDIER FOCUS GROUP SUMMARY

Evaluating the ParticipACTION "Think Again" Campaign

ERIC Educational Resources Information Center

Gainforth, Heather L.; Jarvis, Jocelyn W.; Berry, Tanya R.; Chulak-Bozzer, Tala; Deshpande, Sameer; Faulkner, Guy; Rhodes, Ryan E.; Spence, John C.; Tremblay, Mark S.; Latimer-Cheung, Amy E.

2016-01-01

Introduction: ParticipACTION's 2011 "Think Again" campaign aimed to draw parents', and specifically mothers', attention to the amount of physical activity (PA) their children do relative to the national guidelines (physical activity guidelines [PAG]). Purpose: To evaluate ParticipACTION's "Think Again" campaign in the context…

Whole-Genome Sequences of Variants of Bacillus anthracis Sterne and Their Toxin Gene Deletion Mutants

PubMed Central

Staab, A.; Plaut, R. D.; Pratt, C.; Lovett, S. P.; Wiley, M. R.; Biggs, T. D.; Bernhards, R. C.; Beck, L. C.; Palacios, G. F.; Stibitz, S.; Jones, K. L.; Goodwin, B. G.; Smith, M. A.

2017-01-01

ABSTRACT Here, we report the draft genome sequences of three laboratory variants of Bacillus anthracis Sterne and their double (Δlef Δcya) and triple (Δpag Δlef Δcya) toxin gene deletion derivatives. PMID:29122874

Calculation of the Actual Cost of Engine Maintenance

DTIC Science & Technology

2003-03-01

Cost Estimating Integrated Tools ( ACEIT ) helps analysts store, retrieve, and analyze data; build cost models; analyze risk; time phase budgets; and...Tools ( ACEIT ).” n. pag. http://www.aceit.com/ 21 February 2003. • USAMC Logistics Support Activity (LOGSA). “Cost Analysis Strategy Assessment

Caffeine-water-polypeptide interaction in aqueous solution

NASA Astrophysics Data System (ADS)

Ghabi, Habib; Dhahbi, Mahmoud

1999-04-01

The interaction of caffeine monomer with the synthetic polypeptides polyasparagine (pAg) and polyaspartic acid (pAsp) was studied by UV spectrophotometry. The results show that different types of interactions are possible depending on the nature of polypeptide. The form of the complex was discussed.

Role of National Immunization Technical Advisory Group on improvement of immunization programmes in the Islamic Republic of Iran.

PubMed

Zahraei, Seyed Mohsen; Marandi, Alireza; Sadrizadeh, Bijan; Gouya, Mehdi Mohammad; Rezaei, Parviz; Vazirian, Parviz; Yaghini, Fatheme

2010-04-19

The National Immunization Technical Advisory Group (NITAG) was established in Iran in 1982 and has made many important technical recommendations (e.g., regarding polio eradication, introduction of new vaccines, organizing special studies) that have contributed to a dramatic decline in vaccine preventable disease burden. The NITAG consists of experts from the Ministry of Health and Medical Education (MOHME), vaccine manufacturers, and medical universities with national Expanded Program of Immunization (EPI) staff serving as the secretariat. It is not completely independent from MOHME or EPI. It meets on a quarterly basis, and publishes national guidelines and immunization schedules that are updated regularly. Although primarily an advisory body, representation from MOHME members, including the EPI manager, ensures almost universal implementation of NITAG recommendations. Copyright © 2010 Elsevier Ltd. All rights reserved.

Feasibility study using MRI and two optical CT scanners for readout of polymer gel and PresageTM

NASA Astrophysics Data System (ADS)

Svensson, H.; Skyt, P. S.; Ceberg, S.; Doran, S.; Muren, L. P.; Balling, P.; Petersen, J. B. B.; Bäck, S. Å. J.

2013-06-01

The aim of this study was to compare the conventional combination of three-dimensional dosimeter (nPAG gel) and readout method (MRI) with other combinations of three-dimensional dosimeters (nPAG gel/PresageTM) and readout methods (optical CT scanners). In the first experiment, the dose readout of a gel irradiated with a four field-box technique was performed with both an Octopus IQ scanner and MRI. It was seen that the MRI readout agreed slightly better to the TPS. In another experiment, a gel and a PresageTM sample were irradiated with a VMAT field and read out using MRI and a fast laser scanner, respectively. A comparison between the TPS and the volumes revealed that the MRI/gel readout had closer resemblance to the TPS than the optical CT/PresageTM readout. There are clearly potential in the evaluated optical CT scanners, but more time has to be invested in the particular scanning scenario than was possible in this study.

Response properties of nucleus reticularis lateralis neurons after electroacupuncture stimulation in rats.

PubMed

Moritaka, Kentaro; Zeredo, Jorge L; Kimoto, Mari; Nasution, Fajar H; Hirano, Takafumi; Toda, Kazuo

2010-01-01

A descending inhibitory mechanism from the periaqueductal gray (PAG) to the spinal cord through the nucleus raphe magnus (NRM) is strongly involved in endogenous analgesic system produced by acupuncture stimulation. In addition to the PAG to NRM system which descends in the medial pathway of the brain stem, the nucleus reticularis lateralis (NRL) situated in the lateral part of the brain stem is reported to play an important role in modulating centrifugal antinociceptive action. In the present study, to clarify the role of NRL in acupuncture analgesia, we investigated the response properties of NRL neurons to acupuncture stimulation. The majority of NRM-projecting NRL neurons were inhibited by electroacupuncture stimulation. This effect was antagonized by ionophoretic application of naloxone, indicating that endogenous opioids act directly onto these NRL neurons. By contrast, about half of spinal projecting NRL neurons were excited by electroacupuncture stimulation, suggesting that part of the NRL neurons may modulate pain transmission directly at the spinal level.

Effect of Oils on Kinematic Viscosity of R134a

NASA Astrophysics Data System (ADS)

Sato, Tomoaki; Takaishi, Yoshinori; Oguchi, Kosei

The kinematic viscosity defined as a ratio of viscosity to density is one of the key properties in producing technically important dimensionless numbers such as Prandtl and Reynolds numbers. We measured both viscosity and density of R134a/POE and R134a/PAG mixtures at saturation in the range of relatively low oilconcentrations. The density measurements for oil-concentrations up to 50 mass% were conducted with a densimeter making use of glass buoys within overall uncertainty of ±1.0%, and the viscosity measurements for oil-concentrations up to 16 mass% were carried out with an oscillating-cup viscometer making use of polarizer with overall uncertainty less than ±3.5%. The kinematic viscosities obtained from the experimental viscosity and density data are presented for both R134a/POE and R134a/PAG mixtures in the range of temperatures from 278 K to 288 K for oil-concentrations up to 15 mass%. The oil-concentration dependence of the kinematic viscosity for both mixtures is also reported.

Top-coatless 193nm positive-tone development immersion resist for logic application

NASA Astrophysics Data System (ADS)

Liu, Lian Cong; Yeh, Tsung Ju; Lin, Yeh-Sheng; Huang, Yu Chin; Kuo, Chien Wen; Huang, Wen Liang; Lin, Chia Hung; Yu, Chun Chi; Hsu, Ray; Wan, I.-Yuan; Lin, Jeff; Im, Kwang-Hwyi; Lim, Hae Jin; Jeon, Hyun K.; Suzuki, Yasuhiro; Xu, Cheng Bai

2015-03-01

In this paper, we summarize our development efforts for a top-coatless 193nm immersion positive tone development (PTD) contact hole (C/H) resist with improved litho and defect performances for logic application specifically with an advance node. The ultimate performance goal was to improve the depth of focus (DoF) margin, mask error enhancement factor (MEEF), critical dimension uniformity (CDU), contact edge roughness (CER), and defect performance. Also, the through pitch CD difference was supposed to be comparable to the previous control resist. Effects of polymer and PAG properties have been evaluated for this purpose. The material properties focused in the evaluation study were polymer activation energy (Ea), polymer solubility differentiated by polymerization process types, and diffusion length (DL) and acidity (pKa) of photoacid generator (PAG). Additionally, the impact of post exposure bake (PEB) temperature was investigated for process condition optimization. As a result of this study, a new resist formulation to satisfy all litho and defect performance was developed and production yield was further improved.

TARGETED TECHNOLOGY TRANSFER TO US INDEPENDENTS

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

Donald F. Duttlinger; E. Lance Cole

2005-01-01

The Petroleum Technology Transfer Council (PTTC) continued pursuing its mission of assisting U.S. independent oil and gas producers with timely, informed technology decisions during Fiscal Year 2004 (FY04). PTTC has active grassroots programs through its 10 Regional Lead Organizations (RLOs) and 2 satellite offices. They bring research and academia to the table via their association with geological surveys and engineering departments. The regional directors interact with independent oil and gas producers through technology workshops, resource centers, websites, newsletters, technical publications and other cooperative outreach efforts. PTTC's Headquarters (HQ) staff receives direction from a National Board of Directors predominantly comprised ofmore » American natural gas and oil producers to plan and manage the overall technology transfer program. PTTC HQ implements a comprehensive communications program by interconnecting the talents of the National Board, 10 Regional Producer Advisory Groups (PAG) and the RLOs with industry across the U.S. PTTC effectively combines federal funding through the Department of Energy's (DOE) Office of Fossil Energy, namely the Strategic Center for Natural Gas and Oil with state and industry contributions to share application of upstream technologies. Ultimately, these efforts factor in to provide a safe, secure and reliable energy supply for American consumers. This integrated resource base, combined with industry volunteers guiding PTTC's activities and the dedication of national and regional staff, are achieving notable results regarding domestic production figures. PTTC is increasingly recognized as a critical resource for information and access to technologies by providing direct contact with research, development and demonstration (RD&D) results. A key to the program is demonstrating proven technologies that can be applied broadly and rapidly. This technical progress report summarizes PTTC's accomplishments during FY04. Activities remained at high levels. Board and staff interaction has defined strategic thrusts to further outreach. Networking, involvement in technical activities and an active exhibit schedule are increasing PTTC's sphere of influence with both producers and the service sector. PTTC's reputation for unbiased bottom line information stimulates cooperative ventures with other organizations. Efforts to build the contact database and a growing E-mail Technology Alert service are expanding PTTC's audience.« less

Serving Boys through Readers' Advisory

ERIC Educational Resources Information Center

Sullivan, Michael

2010-01-01

Based on more than twenty years' experience working to get boys interested in reading, the author now offers his first readers' advisory volume. With an emphasis on nonfiction and the boy-friendly categories of genre fiction, the work offers a wealth of material including: (1) Suggestions for how to booktalk one-on-one as well as in large groups;…

Land Treatment. Instructor Guide. Working for Clean Water: An Information Program for Advisory Committees

ERIC Educational Resources Information Center

Pennsylvania State Univ., Middletown. Inst. of State and Regional Affairs.

Presented is an instructor's manual for a learning session centered on the methodology and feasibility of land treatment of municipal wastewater. A supplementary slide-tape program is available. These materials are components of the Working for Clean Water Project, which is intended to educate advisory groups who are interested in improving…

78 FR 64505 - Request for Nominations for Voting Members on a Public Advisory Committee; Tobacco Products...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-29

... Advisory Committee, Office of Science, Center for Tobacco Products. FDA seeks to include the views of women and men, members of all racial and ethnic groups, and individuals with and without disabilities on its... matters related to financial holdings, employment, and research grants and/or contracts to permit...

77 FR 61007 - Request for Nominations for Voting Members on a Public Advisory Committee; Tobacco Products...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-05

... Advisory Committee, Office of Science, Center for Tobacco Products. FDA seeks to include the views of women and men, members of all racial and ethnic groups, and individuals with and without disabilities on its... matters related to financial holdings, employment, and research grants and/or contracts to permit...

78 FR 36816 - U.S. Department of State Advisory Committee on Private International Law (ACPIL): Public Meeting...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-19

... DEPARTMENT OF STATE [Public Notice 8358] U.S. Department of State Advisory Committee on Private International Law (ACPIL): Public Meeting of the Study Group on Family Law The Office of the Assistant Legal Adviser for Private International Law, Department of State, hereby gives notice of a public meeting of the...

77 FR 75696 - U.S. Department of State Advisory Committee on Private International Law (ACPIL): Public Meeting...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-21

... DEPARTMENT OF STATE [Public Notice 8131] U.S. Department of State Advisory Committee on Private International Law (ACPIL): Public Meeting of the Study Group on Family Law The Office of the Assistant Legal Adviser for Private International Law, Department of State, hereby gives notice of a public meeting of the...

Functional and ultrastructural neuroanatomy of interactive intratectal/tectonigral mesencephalic opioid inhibitory links and nigrotectal GABAergic pathways: involvement of GABAA and mu1-opioid receptors in the modulation of panic-like reactions elicited by electrical stimulation of the dorsal midbrain.

PubMed

Ribeiro, S J; Ciscato, J G; de Oliveira, R; de Oliveira, R C; D'Angelo-Dias, R; Carvalho, A D; Felippotti, T T; Rebouças, E C C; Castellan-Baldan, L; Hoffmann, A; Corrêa, S A L; Moreira, J E; Coimbra, N C

2005-12-01

In the present study, the functional neuroanatomy of nigrotectal-tectonigral pathways as well as the effects of central administration of opioid antagonists on aversive stimuli-induced responses elicited by electrical stimulation of the midbrain tectum were determined. Central microinjections of naloxonazine, a selective mu(1)-opiod receptor antagonist, in the mesencephalic tectum (MT) caused a significant increase in the escape thresholds elicited by local electrical stimulation. Furthermore, either naltrexone or naloxonazine microinjected in the substantia nigra, pars reticulata (SNpr), caused a significant increase in the defensive thresholds elicited by electrical stimulation of the continuum comprised by dorsolateral aspects of the periaqueductal gray matter (dlPAG) and deep layers of the superior colliculus (dlSC), as compared with controls. These findings suggest an opioid modulation of GABAergic inhibitory inputs controlling the defensive behavior elicited by MT stimulation, in cranial aspects. In fact, iontophoretic microinjections of the neurotracer biodextran into the SNpr, a mesencephalic structure rich in GABA-containing neurons, show outputs to neural substrate of the dlSC/dlPAG involved with the generation and organization of fear- and panic-like reactions. Neurochemical lesion of the nigrotectal pathways increased the sensitivity of the MT to electrical (at alertness, freezing and escape thresholds) and chemical (blockade of GABA(A) receptors) stimulation, suggesting a tonic modulatory effect of the nigrotectal GABAergic outputs on the neural networks of the MT involved with the organization of the defensive behavior and panic-like reactions. Labeled neurons of the midbrain tectum send inputs with varicosities to ipsi and contralateral dlSC/dlPAG and ipsilateral substantia nigra, pars reticulata and compacta, in which the anterograde and retrograde tracing from a single injection indicates that the substantia nigra has reciprocal connections with the dlSC/dlPAG featuring close axo-somatic and axo-dendritic appositions in both locations. In addition, ultrastructural approaches show inhibitory axo-axonic synapses in MT and inhibitory axo-somatic/axo-axonic synapses in the SNpr. These findings, in addition to the psychopharmacological evidence for the interaction between opioid and GABAergic mechanisms in the cranial aspects of the MT as well as in the mesencephalic tegmentum, offer a neuroanatomical basis of a pre-synaptic opioid inhibition of GABAergic nigrotectal neurons modulating fear in defensive behavior-related structures of the cranial mesencephalon, in a short link, and through a major neural circuit, also in GABA-containing perikarya and axons of nigrotectal neurons.

Regulation of Human γδ T Cells by BTN3A1 Protein Stability and ATP-Binding Cassette Transporters

PubMed Central

Rhodes, David A.; Chen, Hung-Chang; Williamson, James C.; Hill, Alfred; Yuan, Jack; Smith, Sam; Rhodes, Harriet; Trowsdale, John; Lehner, Paul J.; Herrmann, Thomas; Eberl, Matthias

2018-01-01

Activation of human Vγ9/Vδ2 T cells by “phosphoantigens” (pAg), the microbial metabolite (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP) and the endogenous isoprenoid intermediate isopentenyl pyrophosphate, requires expression of butyrophilin BTN3A molecules by presenting cells. However, the precise mechanism of activation of Vγ9/Vδ2 T cells by BTN3A molecules remains elusive. It is not clear what conformation of the three BTN3A isoforms transmits activation signals nor how externally delivered pAg accesses the cytosolic B30.2 domain of BTN3A1. To approach these problems, we studied two HLA haplo-identical HeLa cell lines, termed HeLa-L and HeLa-M, which showed marked differences in pAg-dependent stimulation of Vγ9/Vδ2 T cells. Levels of IFN-γ secretion by Vγ9/Vδ2 T cells were profoundly increased by pAg loading, or by binding of the pan-BTN3A specific agonist antibody CD277 20.1, in HeLa-M compared to HeLa-L cells. IL-2 production from a murine hybridoma T cell line expressing human Vγ9/Vδ2 T cell receptor (TCR) transgenes confirmed that the differential responsiveness to HeLa-L and HeLa-M was TCR dependent. By tissue typing, both HeLa lines were shown to be genetically identical and full-length transcripts of the three BTN3A isoforms were detected in equal abundance with no sequence variation. Expression of BTN3A and interacting molecules, such as periplakin or RhoB, did not account for the functional variation between HeLa-L and HeLa-M cells. Instead, the data implicate a checkpoint controlling BTN3A1 stability and protein trafficking, acting at an early time point in its maturation. In addition, plasma membrane profiling was used to identify proteins upregulated in HMB-PP-treated HeLa-M. ABCG2, a member of the ATP-binding cassette (ABC) transporter family was the most significant candidate, which crucially showed reduced expression in HeLa-L. Expression of a subset of ABC transporters, including ABCA1 and ABCG1, correlated with efficiency of T cell activation by cytokine secretion, although direct evidence of a functional role was not obtained by knockdown experiments. Our findings indicate a link between members of the ABC protein superfamily and the BTN3A-dependent activation of γδ T cells by endogenous and exogenous pAg. PMID:29670629

Gears and Power Transmission Systems for Helicopters and Turboprops; Conference Proceedings: Propulsion and Energetics Panel Symposium (64th) Held at Lisbon, Portugal on 8-12 October 1984.

DTIC Science & Technology

1985-01-01

surface is a non -trivial problem of theoretical physics. Even so, the phenomenologi- cal description given earlier which is based on experimental findings...AGARD-CP-369 ISBN 92-835-0372-4 UNCLASSII-ILI1) -5. Originator Advisory Group tor Aerospace Research and Decvelopmtent North Atlantic Treaty...discussed in an AG;ARI~ographl to be published ri I97’ AGARD-CP-369 NORTH ATLANTIC TREATY ORGANIZATION ADVISORY GROUP FOR AEROSPACE RESEARCH AND

Company-College Links: Examples of What Works--A University Advisory Council Report.

ERIC Educational Resources Information Center

American Council of Life Insurance, Washington, DC. Education and Community Services.

A report is presented of a meeting sponsored by the University Advisory Council of the American Council of Life Insurance on company-college links. A brief outline is presented of each of five innovative programs developed and implemented by business groups and colleges. As background to the projects, attention is also directed to some of the main…

Report of Advisory Group on Assessing Means for Strengthening the Role of Labor in Education and Work Planning.

ERIC Educational Resources Information Center

Northwest Regional Educational Lab., Portland, OR.

As a part of research designed to determine how labor leaders perceive the current relationship between labor and education and to identify activities that could promote greater collaboration in education and work, an advisory committee composed of labor leaders met to analyze labor's role in planning educational activities. Central issues for the…

Moving forward on strengthening and sustaining National Immunization Technical Advisory Groups (NITAGs) globally: Recommendations from the 2nd global NITAG network meeting.

PubMed

MacDonald, Noni E; Duclos, Philippe; Wichmann, Ole; Henaff, Louise; Harnden, Anthony; Alshammary, Aisha; Tijerino, Roberto Arroba; Hall, Madeline; Sacarlal, Jahit; Singh, Rupa Rajbhandari

2017-12-15

National Immunization Technical Advisory Groups (NITAGs) provide independent, evidence-informed advice to assist their governments in immunization policy formation. This is complex work and many NITAGs face challenges in fulfilling their roles. Inter-country NITAG collaboration opportunities have the potential to enhance NITAG function and grow the quality of recommendations. Hence the many requests for formation of a network linking NITAGs together so they can learn from each other. The first Global NITAG Network (GNN) meeting, held in 2016, led to a push to launch the GNN and grow the network. At the second GNN meeting, held June 28-29, 2017 in Berlin, the GNN was formally inaugurated. Participants discussed GNN governance, reflected on the April 2017 Strategic Advisory Group of Experts (SAGE) on Immunization conclusions concerning strengthening of NITAGs and also shared NITAG experiences in evaluation and inter-country collaborations and independence. They also discussed the role of Regional Technical Advisory Groups on Immunization (RTAGs) and regional networks. A number of issues were raised including NITAGs and communications, dissemination of recommendations and vaccine implementation as well as implications of off-label recommendations. Participants were alerted to immunization evidence assessment sites and value of sharing of resources. They also discussed potential GNN funding opportunities, developed an action plan for 2017-18 and selected a Steering Committee to help move the GNN forward. All participants agreed on the importance of the GNN and the value in attracting more countries to join the GNN. Copyright © 2017.

Exploring SETAC's roles in the global dialogue on sustainability--an opening debate.

PubMed

McCormick, Ron; Kapustka, Larry; Stahl, Cynthia; Fava, Jim; Lavoie, Emma; Robertson, Cory; Sanderson, Hans; Scott, Heidi; Seager, Tom; Vigon, Bruce

2013-01-01

A combination platform-debate session was held at the Society of Environmental Toxicology and Chemistry (SETAC) North America annual meeting in Boston (November 2011). The session was organized by members of the Advisory Group on Sustainability, newly formed and approved as a global entity by the SETAC World Council just prior to the meeting. The platform portion of the session provided a historical backdrop for the debate that was designed to explore SETAC's role in the sustainability dialogue. The debate portion presented arguments for and against the proposition that "Science is the primary contribution of SETAC to the global dialogue on sustainability." Although the debate was not designed to achieve a definitive sustainability policy for SETAC, the audience clearly rejected the proposition, indicating a desire from the SETAC membership for an expanded role in global sustainability forums. This commentary details the key elements of the session, identifies the contribution the Advisory Group will have at the World Congress in Berlin (May 2012), and invites interested persons to become active in the Advisory Group. Copyright © 2012 SETAC.

Health governance--its introduction in Lanarkshire Health Board.

PubMed

Wrench, J G; Moir, D C

2002-01-01

To describe an approach to implementing the principles of clinical governance in a Health Board setting. Using guidance from the Scottish Executive and The Faculty of Public Health Medicine to set up a health governance structure at Health Board level. Auditing current work to identify areas that required to be progressed. Lanarkshire Health Board. A Health Governance Committee and a Health Governance Advisory Group, to support the work of the main committee, were set up at Board level. The Scottish Executive Governance Monitoring Template has been adapted to cover the main public health functions. Topics considered in the first year include qualifications, registration and CPD activity of Consultants in Public Health Medicine, audit of public health advice on gastro-intestinal illness, audit of DPH Annual Report and audit of items of business on Health Board agenda. The model developed in Lanarkshire has a Health Governance Advisory Group which works in support of the main Health Governance Committee. This model works well in practice with much of the routine work being done by the Advisory Group. This has streamlined the work of the Health Governance Committee and facilitated its introduction.