The Role of Social Relationships in PrEP Uptake and Use Among Transgender Women and Men Who Have Sex with Men.

PubMed

Mehrotra, Megha L; Rivet Amico, K; McMahan, Vanessa; Glidden, David V; Defechereux, Patricia; Guanira, Juan V; Grant, Robert M

2018-05-12

Qualitative studies suggest that social relationships play an important role in HIV pre-exposure prophylaxis (PrEP) use, but there have been few quantitative assessments of the role of social relationships in PrEP uptake or adherence. We examined the association between disclosure of study participation or LGBT identity and PrEP use in the 1603 HIV-negative participants enrolled in the iPrEx OLE study. We also evaluated the association between LGBT social group involvement and PrEP use. Study participation disclosure to parents and LGBT identity disclosure to anyone in a participant's social network were associated with greater PrEP uptake. Study participation disclosure to partners was associated with higher probability of having protective PrEP drug concentrations compared [risk difference 0.15 95% CI (0.01, 0.30)]. For each additional type of LGBT organization a participant was involved in, the probability of PrEP uptake and having protective drug concentrations increased by 0.04 [95% CI (0.03, 0.06)] and 0.04 (95% CI (0.02, 0.07)] respectively. Overall, social context was associated with PrEP use in iPrEx OLE, and should be taken into consideration when designing future PrEP implementation programs.

Understanding the Press Kit and Its Use by the Media: When PR Material Becomes News

ERIC Educational Resources Information Center

Weisgerber, Corinne

2006-01-01

This activity helps students understand the relationship between public relations (PR) writing and news writing by demonstrating how PR material gets used in the production of news stories. Considering that "more than 70 percent of daily newspaper copy emanates from PR-generated releases," it is important for students to learn how PR professionals…

ERK1/2 and p38 MAP kinases control prion protein fragment 90-231-induced astrocyte proliferation and microglia activation.

PubMed

Thellung, Stefano; Villa, Valentina; Corsaro, Alessandro; Pellistri, Francesca; Venezia, Valentina; Russo, Claudio; Aceto, Antonio; Robello, Mauro; Florio, Tullio

2007-11-01

Astrogliosis and microglial activation are a common feature during prion diseases, causing the release of chemoattractant and proinflammatory factors as well as reactive free radicals, involved in neuronal degeneration. The recombinant protease-resistant domain of the prion protein (PrP90-231) displays in vitro neurotoxic properties when refolded in a beta-sheet-rich conformer. Here, we report that PrP90-231 induces the secretion of several cytokines, chemokines, and nitric oxide (NO) release, in both type I astrocytes and microglial cells. PrP90-231 elicited in both cell types the activation of ERK1/2 MAP kinase that displays, in astrocytes, a rapid kinetics and a proliferative response. Conversely, in microglia, PrP90-231-dependent MAP kinase activation was delayed and long lasting, inducing functional activation and growth arrest. In microglial cells, NO release, dependent on the expression of the inducible NO synthase (iNOS), and the secretion of the chemokine CCL5 were Ca(2+) dependent and under the control of the MAP kinases ERK1/2 and p38: ERK1/2 inhibition, using PD98059, reduced iNOS expression, while p38 blockade by PD169316 inhibited CCL5 release. In summary, we demonstrate that glial cells are activated by extracellular misfolded PrP90-231 resulting in a proliferative/secretive response of astrocytes and functional activation of microglia, both dependent on MAP kinase activation. In particular, in microglia, PrP90-231 activated a complex signalling cascade involved in the regulation of NO and chemokine release. These data argue in favor of a causal role for misfolded prion protein in sustaining glial activation and, possibly, glia-mediated neuronal death.

Metabolism of hydroxypyruvate in a mutant of barley lacking NADH-dependent hydroxypyruvate reductase, an important photorespiratory enzyme activity

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

Murray, A.J.S.; Blackwell, R.D.; Lea, P.J.

1989-09-01

A mutant of barley (Hordeum vulgare L.), LaPr 88/29, deficient in NADH-dependent hydroxypyruvate reductase (HPR) activity has been isolated. The activities of both NADH (5%) and NADPH-dependent (19%) HPR were severely reduced in this mutant compared to the wild type. Although lacking an enzyme in the main carbon pathway of photorespiration, this mutant was capable of CO{sub 2} fixation rates equivalent to 75% of that of the wild type, in normal atmospheres and 50% O{sub 2}. There also appeared to be little disruption to the photorespiratory metabolism as ammonia release, CO{sub 2} efflux and {sup 14}CO{sub 2} release from L-(U-{supmore » 14}C)serine feeding were similar in both mutant and wild-type leaves. When leaves of LaPr 88/29 were fed either ({sup 14}C)serine or {sup 14}CO{sub 2}, the accumulation of radioactivity was in serine and not in hydroxypyruvate, although the mutant was still able to metabolize over 25% of the supplied ({sup 14}C)serine into sucrose. After 3 hours in air the soluble amino acid pool was almost totally dominated by serine and glycine. LaPr 88/29 has also been used to show that NADH-glyoxylate reductase and NADH-HPR are probably not catalyzed by the same enzyme in barley and that over 80% of the NADPH-dependent HPR activity is due to the NADH-dependent enzyme. We also suggest that the alternative NADPH activity can metabolize a proportion, but not all, of the hydroxypyruvate produced during photorespiration and may thus form a useful backup to the NADH-dependent enzyme under conditions of maximal photorespiration.« less

The neutral sphingomyelinase pathway regulates packaging of the prion protein into exosomes.

PubMed

Guo, Belinda B; Bellingham, Shayne A; Hill, Andrew F

2015-02-06

Prion diseases are a group of transmissible, fatal neurodegenerative disorders associated with the misfolding of the host-encoded prion protein, PrP(C), into a disease-associated form, PrP(Sc). The transmissible prion agent is principally formed of PrP(Sc) itself and is associated with extracellular vesicles known as exosomes. Exosomes are released from cells both in vitro and in vivo, and have been proposed as a mechanism by which prions spread intercellularly. The biogenesis of exosomes occurs within the endosomal system, through formation of intraluminal vesicles (ILVs), which are subsequently released from cells as exosomes. ILV formation is known to be regulated by the endosomal sorting complexes required for transport (ESCRT) machinery, although an alternative neutral sphingomyelinase (nSMase) pathway has been suggested to also regulate this process. Here, we investigate a role for the nSMase pathway in exosome biogenesis and packaging of PrP into these vesicles. Inhibition of the nSMase pathway using GW4869 revealed a role for the nSMase pathway in both exosome formation and PrP packaging. In agreement, targeted knockdown of nSMase1 and nSMase2 in mouse neurons using lentivirus-mediated RNAi also decreases exosome release, demonstrating the nSMase pathway regulates the biogenesis and release of exosomes. We also demonstrate that PrP(C) packaging is dependent on nSMase2, whereas the packaging of disease-associated PrP(Sc) into exosomes occurs independently of nSMase2. These findings provide further insight into prion transmission and identify a pathway which directly assists exosome-mediated transmission of prions. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Registration of PR0806-80 and PR0806-81 white bean germplasm lines with resistance to BGYMV, BCMV, BCMNV and rust

USDA-ARS?s Scientific Manuscript database

PR0806-80 (Reg. No. GP-___, PI ______) and PR0806-81 (Reg. No. GP-___, PI ______) are multiple disease resistant dry bean (Phaseolus vulgaris L.) germplasm lines, adapted to the humid tropics, that were developed and released cooperatively by the University of Puerto Rico Agricultural Experiment Sta...

Outcomes of percutaneous trigger finger release with concurrent steroid injection.

PubMed

Liu, Wen-Chih; Lu, Chun-Kuan; Lin, Yu-Chuan; Huang, Peng-Ju; Lin, Gau-Tyan; Fu, Yin-Chih

2016-12-01

Percutaneous release (PR) of the A1 pulley is a quick, safe, and minimally invasive procedure for treating trigger fingers. The purpose of this study is to identify if PR with additional steroid injections can shorten the recovery to reach unlimited range of motion. Between January 2013 and December 2013, we included 432 trigger fingers with actively correctable triggering or severer symptoms without previous surgical release or steroid injections from two hand clinic offices (A and B). The same experienced surgeon performed PR at the office. Patients from Clinic A received PR with steroid injections and those from Clinic B received PR without steroid injections. Patients returned for follow-up 1 week, 6 weeks, and 12 weeks after the procedure. Between the steroid group and the nonsteroid group, there is no significant difference in the mean time for patients to return to normal work and the rate of residual extensor lag. Middle fingers showed a 5.09-fold chance of having a residual extensor lag over that of the other fingers. High grade trigger fingers recovered more slowly than low grade ones. The success rate of a 12-week follow-up was 98.4%. There was no significant difference between the steroid group (97.5%) and the nonsteroid group (99.1%). PR can treat trigger fingers effectively, but additional steroid injection does not provide more benefit. Some fingers showed temporary extensor lag, especially in middle fingers and high grade trigger fingers, but 85% of those will eventually reach full recovery after self-rehabilitation without another surgical release. Copyright © 2016. Published by Elsevier Taiwan.

Public Relations in Special Libraries.

ERIC Educational Resources Information Center

Rutkowski, Hollace Ann; And Others

1991-01-01

This theme issue includes 11 articles on public relations (PR) in special libraries. Highlights include PR at the Special Libraries Association (SLA); sources for marketing research for libraries; developing a library image; sample PR releases; brand strategies for libraries; case studies; publicizing a consortium; and a bibliography of pertinent…

Prolonged-release fampridine and walking and balance in MS: randomised controlled MOBILE trial

PubMed Central

Hupperts, Raymond; Lycke, Jan; Short, Christine; Gasperini, Claudio; McNeill, Manjit; Medori, Rossella; Tofil-Kaluza, Agata; Hovenden, Maria; Mehta, Lahar R; Elkins, Jacob

2016-01-01

Background: Mobility impairment is a common disability in MS and negatively impacts patients’ lives. Objective: Evaluate the effect of prolonged-release (PR) fampridine (extended-release dalfampridine in the United States) on self-assessed walking disability, dynamic/static balance and safety in patients with MS. Methods: MOBILE was a randomised, double-blind, exploratory, placebo-controlled trial. Patients with progressive/relapsing-remitting MS and Expanded Disability Status Scale score of 4.0–7.0 were treated with PR-fampridine or placebo twice daily for 24 weeks. Efficacy endpoints included change from baseline in the 12-item MS Walking Scale (MSWS-12), Timed Up and Go (TUG) test and Berg Balance Scale (BBS). Results: 132 patients were randomised at 24 sites in six countries. PR-fampridine therapy resulted in greater median improvements from baseline in MSWS-12 score, TUG speed and BBS total score versus placebo over 24 weeks. A higher proportion of patients receiving PR-fampridine versus placebo experienced significant improvements at MSWS-12 improvement thresholds ⩾7 (p = 0.0275), ⩾8 (p = 0.0153) and ⩾9 points (p = 0.0088) and TUG speed thresholds ⩾10% (p = 0.0021) and ⩾15% (p = 0.0262). PR-fampridine was well tolerated. Conclusions: PR-fampridine therapy resulted in early and sustained improvements in broad measures of walking and balance over six months. PMID:25921050

Global gene expression profiles of Phytophthora ramorum strain pr102 in response to plant host and tissue differentiation

Treesearch

Caroline M. Press; Niklaus J. Grunwald

2008-01-01

The release of the draft genome sequence of P. ramorum strain Pr102, enabled the construction of an oligonucleotide microarray of the entire genome of Pr102. The array contains 344,680 features (oligos) that represent the transcriptome of Pr102. P. ramorum RNA was extracted from mycelium and sporangia and used to compare gene...

Pravastatin chitosan nanogels-loaded erythrocytes as a new delivery strategy for targeting liver cancer.

PubMed

Harisa, Gamaleldin I; Badran, Mohamed M; AlQahtani, Saeed A; Alanazi, Fars K; Attia, Sabry M

2016-01-01

Chitosan nanogels (CNG) are developed as one of the most promising carriers for cancer targeting. However, these carriers are rapidly eliminated from circulation by reticuloendothelial system (RES), which limits their application. Therefore, erythrocytes (ER) loaded CNG as multifunctional carrier may overcome the massive elimination of nanocarriers by RES. In this study, erythrocytes loaded pravastatin-chitosan nanogels (PR-CNG-ER) were utilized as a novel drug carrier to target liver cancer. Thus, PR-CNG formula was developed in nanosize, with good entrapment efficiency, drug loading and sustained release over 48 h. Then, PR-CNG loaded into ER were prepared by hypotonic preswelling technique. The resulting PR-CNG-ER showed 36.85% of entrapment efficiency, 66.82% of cell recovery and release consistent to that of hemoglobin over 48 h. Moreover, PR-CNG-ER exhibited negative zeta potential, increasing of hemolysis percent, marked phosphatidylserine exposure and stomatocytes shape compared to control unloaded erythrocytes. PR-CNG-ER reduced cells viability of HepG2 cells line by 28% compared to unloaded erythrocytes (UER). These results concluded that PR-CNG-ER are promising drug carriers to target liver cancer.

Replication and spread of CJD, kuru and scrapie agents in vivo and in cell culture

PubMed Central

Miyazawa, Kohtaro; Emmerling, Kaitlin

2011-01-01

Transmissible Spongiform Encephalopathy (TSE) agents are defined by their virulence for particular species, their spread in the population, their incubation time to cause disease, and their neuropathological sequelae. Murine adapted human agents, including sporadic CJD (sCJD), New Guinea kuru, and Japanese CJD agents, display particularly distinct incubation times and maximal infectious brain titers. They also induce agent-specific patterns of neurodegeneration. When these TSE agents are transmitted to cultured hypothalamic GT1 cells they maintain their unique identities. Nevertheless, the human kuru (kCJD) and Japanese FU-CJD agents, as well as the sheep 22L and 263K scrapie agents display doubling times that are 8× to 33× faster in cells than in brain, indicating release from complex innate immune responses. These data are most consistent with a foreign viral structure, rather than an infectious form of host prion protein (PrP-res). Profound agent-specific inhibitory effects are also apparent in GT1 cells, and maximal titer plateau in kCJD and FU-CJD differed by 1,000-fold in a cell-based assay. Remarkably, the lower titer kCJD agent rapidly induced de novo PrP-res in GT1 cells, whereas the high titer FU-CJD agent replicated silently for multiple passages. Although PrP-res is often considered to be toxic, PrP-res instead may be part of a primal defense and/or clearance mechanism against TSE environmental agents. Limited spread of particular TSE agents through nanotubes and cell-to-cell contacts probably underlies the long peripheral phase of human CJD. PMID:21527829

The effects of captive rearing on the behavior of newly-released whooping cranes (Grus americana)

USGS Publications Warehouse

Kreger, M.D.; Hatfield, J.S.; Estevez, I.; Gee, G.F.; Clugston, D.A.

2005-01-01

Rearing treatments used in captivity to prepare animals for reintroduction to the wild may have a profound effect on behavior and, possibly, affect their survival after reintroduction. This study examined the behaviors of captive-reared whooping cranes (Grus americana) upon their release in Florida to determine if rearing treatments may affect the behavior of the birds and how these affect their chances of survival in the wild. Individually tagged birds were observed at the rearing facility, the U.S. Geological Survey Patuxent Wildlife Research Center in Maryland, from hatch to 20 weeks of age and at the release site in Central Florida for up to 6 weeks post release. The rearing treatments were parent reared (PR), hand reared (HR), and hand reared with exercise (HRE). Observations at the rearing facility are described in a previous paper. At the release site, each bird was observed for 5 min every morning (0700?1000 h) and late afternoon (1500?1800 h) during the 6-week study period. Our results indicated that most of the time, the n = 34 birds were foraging (46.03 ? 1.48%), followed by nonvigilant (20.89 ? 0.73%), vigilant (19.21 ? 0.72%), or performing comfort behaviors (11.61 ? 1.28%). Data were analyzed using mixed models repeated measures ANOVA. There were no significant behavioral differences between HR and HRE birds. PR birds were found in larger groups than HR birds during the first 2 weeks post release and greater than HR and HRE birds afterwards. This may be interpreted as an antipredator strategy for birds that relied on parental guidance during rearing. HR and HRE birds foraged more than PR birds during the first 2 weeks post release and PR birds were more vigilant during the first 2 weeks post release. Across rearing treatments, the percentages of time spent foraging and engaged in vigilant behaviors during rearing were positively correlated with their behavior upon release. If any of these behaviors can be demonstrated to have relevance for the survival of the whooping cranes after release then it may be possible to establish behavioral interventions to increase the frequencies of such behavior, so that they are perpetuated after release.

Direct conversion from tramadol to tapentadol prolonged release for moderate to severe, chronic malignant tumour-related pain.

PubMed

Kress, H G; Koch, E D; Kosturski, H; Steup, A; Karcher, K; Dogan, C; Etropolski, M; Eerdekens, M

2016-10-01

A recent randomized-withdrawal, active- and placebo-controlled, double-blind phase 3 study showed that tapentadol prolonged release (PR) was effective and well tolerated for managing moderate to severe, chronic malignant tumour-related pain in patients who were opioid naive or dissatisfied with current treatment (Pain Physician, 2014, 17, 329-343). This post hoc, subgroup analysis evaluated the efficacy and tolerability of tapentadol PR in patients who previously received and were dissatisfied with tramadol for any reason and who had a pain intensity ≥5 (11-point numerical rating scale) before converting directly to tapentadol PR. In the original study, eligible patients had been randomized (2:1) and titrated to their optimal dose of tapentadol PR (100-250 mg bid) or morphine sulphate-controlled release (40-100 mg bid) over 2 weeks. The present report focuses on results during the titration period for a subgroup of patients randomized to tapentadol PR after having been on tramadol treatment prior to randomization in the study (n = 129). Results for this subgroup are compared with results for all 338 patients who received tapentadol PR during titration (overall tapentadol PR group). Responder rates (responders: completed titration, mean pain intensity <5 [0-10 scale] and ≤20 mg/day rescue medication during last 3 days) were slightly better for the tramadol/tapentadol PR subgroup (69.8% [90/129]) vs. the overall tapentadol PR group (63.9% [214/335]). Tolerability profiles were comparable for both groups. Results of this subgroup analysis indicate that patients with cancer pain could safely switch from prior treatment with the weak centrally acting analgesic tramadol directly to the strong centrally acting analgesic tapentadol PR, for an improved analgesic therapy for severe pain. WHAT DOES THIS STUDY ADD?: Results of this post hoc analysis show that patients who had received prior tramadol therapy could switch directly to tapentadol PR, with the majority (˜70%) experiencing improved efficacy. © 2016 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFIC®.

High probability neurotransmitter release sites represent an energy efficient design

PubMed Central

Lu, Zhongmin; Chouhan, Amit K.; Borycz, Jolanta A.; Lu, Zhiyuan; Rossano, Adam J; Brain, Keith L.; Zhou, You; Meinertzhagen, Ian A.; Macleod, Gregory T.

2016-01-01

Nerve terminals contain multiple sites specialized for the release of neurotransmitters. Release usually occurs with low probability, a design thought to confer many advantages. High probability release sites are not uncommon but their advantages are not well understood. Here we test the hypothesis that high probability release sites represent an energy efficient design. We examined release site probabilities and energy efficiency at the terminals of two glutamatergic motor neurons synapsing on the same muscle fiber in Drosophila larvae. Through electrophysiological and ultrastructural measurements we calculated release site probabilities to differ considerably between terminals (0.33 vs. 0.11). We estimated the energy required to release and recycle glutamate from the same measurements. The energy required to remove calcium and sodium ions subsequent to nerve excitation was estimated through microfluorimetric and morphological measurements. We calculated energy efficiency as the number of glutamate molecules released per ATP molecule hydrolyzed, and high probability release site terminals were found to be more efficient (0.13 vs. 0.06). Our analytical model indicates that energy efficiency is optimal (~0.15) at high release site probabilities (~0.76). As limitations in energy supply constrain neural function, high probability release sites might ameliorate such constraints by demanding less energy. Energy efficiency can be viewed as one aspect of nerve terminal function, in balance with others, because high efficiency terminals depress significantly during episodic bursts of activity. PMID:27593375

Stimulating the Release of Exosomes Increases the Intercellular Transfer of Prions.

PubMed

Guo, Belinda B; Bellingham, Shayne A; Hill, Andrew F

2016-03-04

Exosomes are small extracellular vesicles released by cells and play important roles in intercellular communication and pathogen transfer. Exosomes have been implicated in several neurodegenerative diseases, including prion disease and Alzheimer disease. Prion disease arises upon misfolding of the normal cellular prion protein, PrP(C), into the disease-associated isoform, PrP(Sc). The disease has a unique transmissible etiology, and exosomes represent a novel and efficient method for prion transmission. The precise mechanism by which prions are transmitted from cell to cell remains to be fully elucidated, although three hypotheses have been proposed: direct cell-cell contact, tunneling nanotubes, and exosomes. Given the reported presence of exosomes in biological fluids and in the lipid and nucleic acid contents of exosomes, these vesicles represent an ideal mechanism for encapsulating prions and potential cofactors to facilitate prion transmission. This study investigates the relationship between exosome release and intercellular prion dissemination. Stimulation of exosome release through treatment with an ionophore, monensin, revealed a corresponding increase in intercellular transfer of prion infectivity. Conversely, inhibition of exosome release using GW4869 to target the neutral sphingomyelinase pathway induced a decrease in intercellular prion transmission. Further examination of the effect of monensin on PrP conversion revealed that monensin also alters the conformational stability of PrP(C), leading to increased generation of proteinase K-resistant prion protein. The findings presented here provide support for a positive relationship between exosome release and intercellular transfer of prion infectivity, highlighting an integral role for exosomes in facilitating the unique transmissible nature of prions. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Sphingosine 1-phosphate (S1P) suppresses the collagen-induced activation of human platelets via S1P4 receptor.

PubMed

Onuma, Takashi; Tanabe, Kumiko; Kito, Yuko; Tsujimoto, Masanori; Uematsu, Kodai; Enomoto, Yukiko; Matsushima-Nishiwaki, Rie; Doi, Tomoaki; Nagase, Kiyoshi; Akamatsu, Shigeru; Tokuda, Haruhiko; Ogura, Shinji; Iwama, Toru; Kozawa, Osamu; Iida, Hiroki

2017-08-01

Sphingosine 1-phosphate (S1P) is as an extracellular factor that acts as a potent lipid mediator by binding to specific receptors, S1P receptors (S1PRs). However, the precise role of S1P in human platelets that express S1PRs has not yet been fully clarified. We previously reported that heat shock protein 27 (HSP27) is released from human platelets accompanied by its phosphorylation stimulated by collagen. In the present study, we investigated the effect of S1P on the collagen-induced platelet activation. S1P pretreatment markedly attenuated the collagen-induced aggregation. Co-stimulation with S1P and collagen suppressed collagen-induced platelet activation, but the effect was weaker than that of S1P-pretreatment. The collagen-stimulated secretion of platelet-derived growth factor (PDGF)-AB and the soluble CD40 ligand (sCD40L) release were significantly reduced by S1P. In addition, S1P suppressed the collagen-induced release of HSP27 as well as the phosphorylation of HSP27. S1P significantly suppressed the collagen-induced phosphorylation of p38 mitogen-activated protein kinase. S1P increased the levels of GTP-bound Gαi and GTP-bound Gα13 coupled to S1PPR1 and/or S1PR4. CYM50260, a selective S1PR4 agonist, but not SEW2871, a selective S1PR1 agonist, suppressed the collagen-stimulated platelet aggregation, PDGF-AB secretion and sCD40L release. In addition, CYM50260 reduced the release of phosphorylated-HSP27 by collagen as well as the phosphorylation of HSP27. The selective S1PR4 antagonist CYM50358, which failed to affect collagen-induced HSP27 phosphorylation, reversed the S1P-induced attenuation of HSP27 phosphorylation by collagen. These results strongly suggest that S1P inhibits the collagen-induced human platelet activation through S1PR4 but not S1PR1. Copyright © 2017 Elsevier Ltd. All rights reserved.

Prolonged-Release Oxycodone/Naloxone Improves Anal Sphincter Relaxation Compared to Oxycodone Plus Macrogol 3350.

PubMed

Poulsen, Jakob Lykke; Brock, Christina; Grønlund, Debbie; Liao, Donghua; Gregersen, Hans; Krogh, Klaus; Drewes, Asbjørn Mohr

2017-11-01

Opioid analgesics inhibit anal sphincter function and contribute to opioid-induced bowel dysfunction (OIBD). However, it is unknown whether the inhibition can be reduced by opioid antagonism with prolonged-release (PR) naloxone and how this compares to laxative treatment. To compare the effects of combined PR oxycodone/naloxone or PR oxycodone plus macrogol 3350 on anal sphincter function and gastrointestinal symptoms. A randomized, double-blind, crossover trial was conducted in 20 healthy men. Participants were treated for 5 days with combined PR oxycodone/naloxone or PR oxycodone plus macrogol 3350. Resting anal pressure, anal canal distensibility, and relaxation of the internal sphincter to rectal distension were evaluated before treatment (baseline) and on day 5. The Patient Assessment of Constipation Symptom (PAC-SYM) questionnaire, stool frequency, and stool consistency were assessed daily. Both PR oxycodone/naloxone and PR oxycodone plus macrogol treatment decreased sphincter relaxation compared to baseline (- 27.5%; P < 0.001 and - 14.7%; P = 0.01). However, sphincter relaxation was increased after PR naloxone/oxycodone treatment compared to macrogol (difference = + 17.6%; P < 0.001). Resting anal pressure and anal canal distensibility did not differ between treatments. PAC-SYM abdominal symptoms score was lower during PR naloxone compared to macrogol (0.2 vs. 3.2; P = 0.002). The number of bowel movements was lower during PR naloxone versus macrogol (4.2 vs. 5.4; P = 0.035). Relaxation of the internal anal sphincter was significantly better after PR oxycodone/naloxone treatment compared to PR oxycodone plus macrogol 3350. These findings highlight that OIBD may require specific therapy against the complex, pan-intestinal effects of opioids.

Surprisingly rich in H2O Soils of Mars: a Consequence of mild Degassing

NASA Astrophysics Data System (ADS)

Kochemasov, G. G.

2003-04-01

SURPRISINGLY RICH IN H2O SOILS OF MARS: A CONSEQUENCE OF MILD DEGASSING G.Kochemasov, IGEM RAS, 35 Staromonetny, Moscow 119017, kochem@igem.ru The wave planetology [1, 2] connects principal structural characteristics of celestial bodies with their orbital properties (ellipticities &orbital frequencies). In this respect terrestrial planets Venus, Earth, Mars are suitable for comparisons not only of solid bodies structures but also of their gaseous envelopes. Their atmospheric structures closely follow structures of their solid spheres [2]: tectonic granulations in all spheres depend on the planets' orbital frequencies: 1/0.62 y - 1/1 y - ? y. Granula sizes are pR/6, pR/4, pR/2, thus Venus is fine-grained, Earth medium-grained, Mars coarse-grained. Longer orbital periods -coarser tectonic granulas -slower wave oscillations. Finer tectonic structures -more frequent oscillations -more complete degassing. Three planets confirm this conclusion. Venus is covered with a thick dense atmosphere, Mars possesses very weak transparent one, Earth is in the middle. Venus is more thoroughly shaken out and released of its volatiles than Earth &Mars. This is proved also by a large amount if nitrogen in its CO2-atmosphere and by a very low ratio in it of radiogenic to primordial Ar (Venus 1, Earth 300, Mars 3000 [3]). Compare "sweeping" volatiles out of the planets. In a sphere of radius R there are 55.7 grains of radius pR/12 (Venus), 16.5 grains of radius pR/8 (Earth), 2.06 grains of radius pR/4 (Mars). Venus is 3.38 times finer-grained than Earth and 27.04 times than Mars. Venusian wavelength 6000 km (pR/3) gives frequency 0.07 khz, terrestrial wavelength 10000 km (pR/2) gives 0.03 khz, martian 10660 km (pR/1) 0.025 khz. Venusian oscillations 2.33 times more frequent than terrestrial ones and 2.8 times more frequent than martian ones. If planets outgassing is proportional to the square (outgassing goes through surface) of the production of granulation and oscillation frequency, then Venus is 62 times more outgassed than Earth [(3.38 x 2.33)2=62.1] and 5732 times more outgassed than Mars [(27.04 x 2.8)2=5732.3]. Taking into account the smaller martian mass (1/10 of E. &M.) one would expect this outgassing difference to be 5732 x 10=57320 times. Actually venusian atmosphere is 90 times more massive than terrestrial one and ~ 18000 times than martian one. A rather high discrepancy between V &M (actually 18000, calculated 57320) is probably due to high amounts of frozen CO2 &H2O (Odyssey data) in near-surface layers constantly supplying volatiles into atmosphere, but basic reason is probably in the higher ellipticity of the martian orbit promoting volatile sweeping. So, Mars is slighter degassed than Earth &Venus. Ref.: [1] Kochemasov G.G. (1999) Geophys. Res. Abstr., v.1, #3,700; [2] Ibid.(2002) 36th Vernadsky-Brown microsymp. "Topics in Comparative Planetology", Moscow, Abstr., CD-ROM; [3]Pollack J.B., Black D.C. (1979) Science, v. 205, # 4401, 56-59.

GABAB receptor-mediated frequency-dependent and circadian changes in synaptic plasticity modulate retinal input to the suprachiasmatic nucleus

PubMed Central

Moldavan, Mykhaylo G; Allen, Charles N

2013-01-01

Light is the most important environmental signal that entrains the circadian clock located in the hypothalamic suprachiasmatic nucleus (SCN). The retinohypothalamic tract (RHT) was stimulated to simulate the light intensity-dependent discharges of intrinsically photosensitive retinal ganglion cells projecting axons to the hypothalamus. EPSCs were evoked by paired-pulse stimulation or by application of stimulus trains, and recorded from SCN neurons in rat brain slices. Initial release probability (Pr) and synaptic plasticity changes depended on the strength of GABAB receptor (GABABR)-mediated presynaptic inhibition and could be different at the same GABABR agonist concentration. Facilitation caused by frequency-dependent relief of GABABR-mediated inhibition was observed when the initial Pr was decreased to less than 15% of control during strong activation of presynaptic GABAB receptors by (±)baclofen (10 μm), GABA (≥2 mm) or by GABA uptake inhibitor nipecotic acid (≥5 mm). In contrast, short-term synaptic depression appeared during baclofen (10 μm) application when initial Pr was greater than 30% of control. Block of 4-aminopyridine-sensitive K+ currents increased the amplitude and time constant of decay of evoked EPSCs (eEPSCs), and decreased the GABABR-mediated presynaptic inhibition. The GABAB receptor antagonist CGP55845 (3 μm) increased the eEPSCs amplitude 30% throughout the light−dark cycle. During light and dark phases the RHT inputs to 55% and 33% of recorded neurons, respectively, were under GABAB inhibitory control indicating that the tonic inhibition induced by local changes of endogenous GABA concentration contributes to the circadian variation of RHT transmitter release. We conclude that GABABR-mediated presynaptic inhibition decreased with increasing frequency and broadening of presynaptic action potentials, and depended on the sensitivity of RHT terminals to GABABR agonists, and diurnal changes of the extracellular GABA concentration around RHT axon terminals in the SCN. PMID:23401614

Combined statistical analysis of landslide release and propagation

NASA Astrophysics Data System (ADS)

Mergili, Martin; Rohmaneo, Mohammad; Chu, Hone-Jay

2016-04-01

Statistical methods - often coupled with stochastic concepts - are commonly employed to relate areas affected by landslides with environmental layers, and to estimate spatial landslide probabilities by applying these relationships. However, such methods only concern the release of landslides, disregarding their motion. Conceptual models for mass flow routing are used for estimating landslide travel distances and possible impact areas. Automated approaches combining release and impact probabilities are rare. The present work attempts to fill this gap by a fully automated procedure combining statistical and stochastic elements, building on the open source GRASS GIS software: (1) The landslide inventory is subset into release and deposition zones. (2) We employ a traditional statistical approach to estimate the spatial release probability of landslides. (3) We back-calculate the probability distribution of the angle of reach of the observed landslides, employing the software tool r.randomwalk. One set of random walks is routed downslope from each pixel defined as release area. Each random walk stops when leaving the observed impact area of the landslide. (4) The cumulative probability function (cdf) derived in (3) is used as input to route a set of random walks downslope from each pixel in the study area through the DEM, assigning the probability gained from the cdf to each pixel along the path (impact probability). The impact probability of a pixel is defined as the average impact probability of all sets of random walks impacting a pixel. Further, the average release probabilities of the release pixels of all sets of random walks impacting a given pixel are stored along with the area of the possible release zone. (5) We compute the zonal release probability by increasing the release probability according to the size of the release zone - the larger the zone, the larger the probability that a landslide will originate from at least one pixel within this zone. We quantify this relationship by a set of empirical curves. (6) Finally, we multiply the zonal release probability with the impact probability in order to estimate the combined impact probability for each pixel. We demonstrate the model with a 167 km² study area in Taiwan, using an inventory of landslides triggered by the typhoon Morakot. Analyzing the model results leads us to a set of key conclusions: (i) The average composite impact probability over the entire study area corresponds well to the density of observed landside pixels. Therefore we conclude that the method is valid in general, even though the concept of the zonal release probability bears some conceptual issues that have to be kept in mind. (ii) The parameters used as predictors cannot fully explain the observed distribution of landslides. The size of the release zone influences the composite impact probability to a larger degree than the pixel-based release probability. (iii) The prediction rate increases considerably when excluding the largest, deep-seated, landslides from the analysis. We conclude that such landslides are mainly related to geological features hardly reflected in the predictor layers used.

Gender differences in the association between lifestyle behaviors and diabetes distress in a community sample of adults with type 2 diabetes.

PubMed

Lipscombe, Carla; Smith, Kimberley J; Gariepy, Geneviève; Schmitz, Norbert

2016-03-01

The present study examined the association between moderate and severe diabetes distress (DD) and lifestyle behaviors (physical activity, smoking, alcohol consumption) in a community sample of adults with type 2 diabetes mellitus (T2DM). A total of 1971 adults with T2DM were recruited using mixed methods sampling. Participants were considered eligible if they had a doctor diagnosis of T2DM (≤10 years), were insulin naïve, aged 40-75 years, and were from Quebec, Canada. Participants provided information on DD, lifestyle behaviors, sociodemographic, and diabetes-related factors. Multinomial logistic regressions examined the association between moderate and severe DD and each lifestyle behavior, according to gender. Effect estimates can be interpreted as probability ratios (PR). In females, physical inactivity was associated with an increased likelihood of moderate distress (PR 2.2; 95% confidence interval [CI] 1.49-3.24) and severe distress (PR 1.80; 95% CI 1.00-3.24). In males, only severe distress was associated with physical inactivity (PR 1.92; 95% CI 1.00-3.66). Current smoking was associated with a greater probability of severe distress in males (PR 3.0; 95% CI 1.54-5.84) and females (PR 1.32; 95% CI 0.67-2.60); however this effect was stronger in males. No association was found between alcohol consumption and DD in females. In males, frequent alcohol consumption was associated with a reduced probability of moderate (PR 0.56; 95% CI 0.34-0.91) and severe distress (PR 0.47; 95% CI 0.21-1.06). The findings of this study suggest important gender differences in the association between DD and lifestyle behaviors. © 2015 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

Evaluation of critical distances for energy transfer between Pr3+ and Ce3+ in yttrium aluminium garnet

NASA Astrophysics Data System (ADS)

Zeng, Peng; Wei, Xiantao; Zhou, Shaoshuai; Yin, Min; Chen, Yonghu

2016-09-01

A series of Pr3+/Ce3+ doped yttrium aluminium garnet (Y3Al5O12 or simply YAG) phosphors were synthesized to investigate the energy transfer between Pr3+ and Ce3+ for their potential application in a white light-emitting diode and quantum information storage and processing. The excitation and emission spectra of YAG:Pr3+/Ce3+ were measured and analyzed, and it revealed that the reabsorption between Pr3+ and Ce3+ was so weak that it can be ignored, and the energy transfer from Pr3+ (5d) to Ce3+ (5d) and Ce3+ (5d) to Pr3+ (1D2) did occur. By analyzing the excitation and the emission spectra, the energy transfer from Pr3+ (5d) to Ce3+ (5d) and Ce3+ (5d) to Pr3+ (1D2) was examined in detail with an original strategy deduced from fluorescence dynamics and the Dexter energy transfer theory, and the critical distances of energy transfer were derived to be 7.9 Å and 4.0 Å for Pr3+ (5d) to Ce3+ (5d) and Ce3+ (5d) to Pr3+ (1D2), respectively. The energy transfer rates of the two processes of various concentrations were discussed and evaluated. Furthermore, for the purpose of sensing a single Pr3+ state with a Ce3+ ion, the optimal distance of Ce3+ from Pr3+ was evaluated as 5.60 Å, where the probability of success reaches its maximum value of 78.66%, and meanwhile the probabilities were evaluated for a series of Y3+ sites in a YAG lattice. These results will be of valuable reference for achievement of the optimal energy transfer efficiency in Pr3+/Ce3+ doped YAG and other similar systems.

Multiple Instance Fuzzy Inference

DTIC Science & Technology

2015-12-02

very small probabilities. To compute Pr(t | Bi) for a given bag Bi, a conjunction measure of all its instances Bij , j = 1, . . . ,M is computed using...the noisy-or operator Pr(t | Bi) = 1− ∏ 1≤ j ≤M (1− Pr(Bij ∈ t)), (2.5) where Pr(Bij ∈ t) is computed from a Gaussian distribution centred at the concept...Xnk to target concept Ci, and its computed using Pr(Xnk ∈ Ci) = e−( ∑D j =1 sij(xnkj−cij)2) (2.9) In (4.5), sij is a scaling parameter that weights the

Prolactin-releasing peptide is a potent mediator of the innate immune response in leukocytes from Salmo salar.

PubMed

Romero, Alex; Manríquez, René; Alvarez, Claudio; Gajardo, Cristina; Vásquez, Jorge; Kausel, Gudrun; Monrás, Mónica; Olavarría, Víctor H; Yáñez, Alejandro; Enríquez, Ricardo; Figueroa, Jaime

2012-06-30

Prolactin (PRL)-releasing peptide (PrRP) is a strong candidate stimulator of pituitary PRL transcription and secretion in teleosts. However, the role in control of extrapituitary PRL expression or its effects on innate immunity are unclear even in mammals. To study the possible presence of PrRP in peripheral organs, PrRP expression patterns and their effect on innate immunity were characterised in SHK-1 cells and head kidney (HK) leukocytes purified from the salmonid, Salmo salar. We detected immunoreactive cells in leukocytes from blood and HK of S. salar and found that PrRP mRNA was abundantly expressed in these cells. We have recently reported that physiological concentrations of native PRL, downstream of neuropeptide PrRP were able to induce expression of pro-inflammatory cytokines and the production of reactive oxygen species (ROS) in HK leukocytes and macrophages from S. salar and Sparus aurata. It is of interest to note that in this work we have revealed that synthetic PrRP was able to induce expression of pro-inflammatory cytokines (interleukins) IL-1β, IL-6, IL-8, IL-12 and PRL. We also show here that PrRP increased both (ROS) production and phagocytosis. Taken together, our results demonstrate for the first time that PrRP may be a local modulator of innate immune responses in leukocytes from S. salar. Copyright © 2012 Elsevier B.V. All rights reserved.

Mediating role of activity level in the depressive realism effect.

PubMed

Blanco, Fernando; Matute, Helena; A Vadillo, Miguel

2012-01-01

Several classic studies have concluded that the accuracy of identifying uncontrollable situations depends heavily on depressive mood. Nondepressed participants tend to exhibit an optimistic illusion of control, whereas depressed participants tend to better detect a lack of control. Recently, we suggested that the different activity levels (measured as the probability of responding during a contingency learning task) exhibited by depressed and nondepressed individuals is partly responsible for this effect. The two studies presented in this paper provide further support for this mediational hypothesis, in which mood is the distal cause of the illusion of control operating through activity level, the proximal cause. In Study 1, the probability of responding, P(R), was found to be a mediator variable between the depressive symptoms and the judgments of control. In Study 2, we intervened directly on the mediator variable: The P(R) for both depressed and nondepressed participants was manipulated through instructions. Our results confirm that P(R) manipulation produced differences in the participants' perceptions of uncontrollability. Importantly, the intervention on the mediator variable cancelled the effect of the distal cause; the participants' judgments of control were no longer mood dependent when the P(R) was manipulated. This result supports the hypothesis that the so-called depressive realism effect is actually mediated by the probability of responding.

Laser action of Pr3+ in LiYF4 and spectroscopy of Eu2+-sensitized Pr in BaY2F8

NASA Astrophysics Data System (ADS)

Knowles, David S.; Gabbe, David; Jenssen, H. P.; Zhang, Z.

1988-06-01

Laser action in flashlamp-pumped Pr:LiYF4 at room temperature is observed at 640 nm with a 15-J threshold, but only about 0.01 percent slope efficiency. Increased efficiency from sensitizing the Pr with Eu2+ is explored in the system Eu,Pr:BaY2F8. Codoped samples have been grown by the Czochralski growth method, and energy transfer between 2+ and Pr3+ is observed to be very weak. This is probably due to the poor overlap of the Eu2+ emission with the Pr3+ absorption lines, leading to the conclusion that hosts with a stronger crystal field at the Eu2+ site need to be identified.

Smectite clays in Mars soil: evidence for their presence and role in Viking biology experimental results.

PubMed

Banin, A; Rishpon, J

1979-12-01

Various chemical, physical and geological observations indicate that smectite clays are probably the major components of the Martian soil. Satisfactory ground-based chemical simulation of the Viking biology experimental results was obtained with the smectite clays nontronite and montmorillonite when they contained iron and hydrogen as adsorbed ions. Radioactive gas was released from the medium solution used in the Viking Labeled Release (LR) experiment when interacted with the clays, at rates and quantities similar to those measured by Viking on Mars. Heating of the active clay (mixed with soluble salts) to 160 degrees C in CO2 atmosphere reduced the decomposition activity considerably, again, as was observed on Mars. The decomposition reaction in LR experiment is postulated to be iron-catalyzed formate decomposition on the clay surface. The main features of the Viking Pyrolytic Release (PR) experiment were also simulated recently (Hubbard, 1979) which the iron clays, including a relatively low '1st peak' and significant '2nd peak'. The accumulated observations on various Martian soil properties and the results of simulation experiments, thus indicate that smectite clays are major and active components of the Martian soil. It now appears that many of the results of the Viking biology experiments can be explained on the basis of their surface activity in catalysis and adsorption.

Probability of detection evaluation results for railroad tank car nondestructive testing : final report.

DOT National Transportation Integrated Search

2016-08-01

The Federal Railroad Administration (FRA), Transportation Technology Center, Inc. (TTCI), and rail industry participants have : performed probability of detection (POD) assessments to evaluate nondestructive testing (NDT) technologies, which are : pr...

Mapping the biological condition of USA rivers and streams

EPA Science Inventory

We predicted the probable (pr) biological condition (BC) of ~5.4 million km of stream within the conterminous USA (CONUS). National maps of prBC could provide an important tool for prioritizing monitoring and restoration of streams. The USEPA uses a spatially balanced survey desi...

Evaluation of critical distances for energy transfer between Pr{sup 3+} and Ce{sup 3+} in yttrium aluminium garnet

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

Zeng, Peng; Wei, Xiantao; Yin, Min

A series of Pr{sup 3+}/Ce{sup 3+} doped yttrium aluminium garnet (Y{sub 3}Al{sub 5}O{sub 12} or simply YAG) phosphors were synthesized to investigate the energy transfer between Pr{sup 3+} and Ce{sup 3+} for their potential application in a white light-emitting diode and quantum information storage and processing. The excitation and emission spectra of YAG:Pr{sup 3+}/Ce{sup 3+} were measured and analyzed, and it revealed that the reabsorption between Pr{sup 3+} and Ce{sup 3+} was so weak that it can be ignored, and the energy transfer from Pr{sup 3+} (5d) to Ce{sup 3+} (5d) and Ce{sup 3+} (5d) to Pr{sup 3+} ({sup 1}D{submore » 2}) did occur. By analyzing the excitation and the emission spectra, the energy transfer from Pr{sup 3+} (5d) to Ce{sup 3+} (5d) and Ce{sup 3+} (5d) to Pr{sup 3+} ({sup 1}D{sub 2}) was examined in detail with an original strategy deduced from fluorescence dynamics and the Dexter energy transfer theory, and the critical distances of energy transfer were derived to be 7.9 Å and 4.0 Å for Pr{sup 3+} (5d) to Ce{sup 3+} (5d) and Ce{sup 3+} (5d) to Pr{sup 3+} ({sup 1}D{sub 2}), respectively. The energy transfer rates of the two processes of various concentrations were discussed and evaluated. Furthermore, for the purpose of sensing a single Pr{sup 3+} state with a Ce{sup 3+} ion, the optimal distance of Ce{sup 3+} from Pr{sup 3+} was evaluated as 5.60 Å, where the probability of success reaches its maximum value of 78.66%, and meanwhile the probabilities were evaluated for a series of Y{sup 3+} sites in a YAG lattice. These results will be of valuable reference for achievement of the optimal energy transfer efficiency in Pr{sup 3+}/Ce{sup 3+} doped YAG and other similar systems.« less

New insights into flavivirus biology: the influence of pH over interactions between prM and E proteins

NASA Astrophysics Data System (ADS)

Oliveira, Edson R. A.; de Alencastro, Ricardo B.; Horta, Bruno A. C.

2017-11-01

Diseases caused by flaviviruses, such as dengue and zika, are globally recognized as major threats. During infection, a critical point in their replicative cycle is the maturation step, which occurs throughout the cellular exocytic pathway. This step is a pH-dependent process that involves the modification of the viral envelope by converting prM (pre-membrane) into M (membrane) proteins with the release of a "pr peptide". After this reaction, the pr peptides remain bound to the viral envelope while the virions cross the acidic trans-Golgi network, and are released only at neutral pH after secretion of the virus particles. Despite this current knowledge, the molecular basis of the flavivirus maturation step is largely unknown. Here, based on the crystal structure of the dengue pr-E complex ("pr peptide" bound to virus envelope protein) and using molecular dynamics simulations, we found that the pH shift from acidic to neutral yields considerable structural changes in the system. Dynamic cross correlation maps and root mean square deviation analyses revealed that the pr-E junction is clearly unstable under neutral pH. Secondary structure analysis also revealed that the fusion loop region, present in the E protein, is sensitive to pH and tends to unstructure at a neutral environment. Moreover, we found that five residues present in the E protein, Gly102, His244, Thr70, Thr68 and Asn67 are critical to confer stability to the pr-E complex while inside the Golgi apparatus. This work brings details about the dynamical behavior of the pr-E system, helps to better understand the flavivirus biology and may also be of use in the development of novel antiviral strategies.

Deoxycholic Acid-Mediated Sphingosine-1-Phosphate Receptor 2 Signaling Exacerbates DSS-Induced Colitis through Promoting Cathepsin B Release.

PubMed

Zhao, Shengnan; Gong, Zizhen; Du, Xixi; Tian, Chunyan; Wang, Lingyu; Zhou, Jiefei; Xu, Congfeng; Chen, Yingwei; Cai, Wei; Wu, Jin

2018-01-01

We recently have proved that excessive fecal DCA caused by high-fat diet may serve as an endogenous danger-associated molecular pattern to activate NLRP3 inflammasome and thus contributes to the development of inflammatory bowel disease (IBD). Moreover, the effect of DCA on inflammasome activation is mainly mediated through bile acid receptor sphingosine-1-phosphate receptor 2 (S1PR2); however, the intermediate process remains unclear. Here, we sought to explore the detailed molecular mechanism involved and examine the effect of S1PR2 blockage in a colitis mouse model. In this study, we found that DCA could dose dependently upregulate S1PR2 expression. Meanwhile, DCA-induced NLRP3 inflammasome activation is at least partially achieved through stimulating extracellular regulated protein kinases (ERK) signaling pathway downstream of S1PR2 followed by promoting of lysosomal cathepsin B release. DCA enema significantly aggravated DSS-induced colitis in mice and S1PR2 inhibitor as well as inflammasome inhibition by cathepsin B antagonist substantially reducing the mature IL-1 β production and alleviated colonic inflammation superimposed by DCA. Therefore, our findings suggest that S1PR2/ERK1/2/cathepsin B signaling plays a critical role in triggering inflammasome activation by DCA and S1PR2 may represent a new potential therapeutic target for the management of intestinal inflammation in individuals on a high-fat diet.

Targeted drug delivery and enhanced intracellular release using functionalized liposomes

NASA Astrophysics Data System (ADS)

Garg, Ashish

The ability to target cancer cells using an appropriate drug delivery system can significantly reduce the associated side effects from cancer therapies and can help in improving the overall quality of life, post cancer survival. Integrin alpha5beta1 is expressed on several types of cancer cells, including colon cancer and plays an important role in tumor growth and metastasis. Thus, the ability to target the integrin alpha 5beta1 using an appropriate drug delivery nano-vector can significantly help in inhibiting tumor growth and reducing tumor metastasis. The work in this thesis focuses on designing and optimizing, functionalized stealth liposomes (liposomes covered with polyethylene glycol (PEG)) that specifically target the integrin alpha5beta1. The PEG provides a steric barrier allowing the liposomes to circulate in the blood for longer duration and the functionalizing moiety, PR_b peptide specifically recognizes and binds to integrin alpha5beta1 expressing cells. The work demonstrates that by optimizing the amount of PEG and PR_b on the liposomal interface, nano-vectors can be engineered that bind to CT26.WT colon cancer cells in a specific manner and internalize through alpha 5beta1-mediated endocytosis. To further improve the efficacy of the system, PR_b functionalized pH-sensitive stealth liposomes that exhibit triggered release under mild acidic conditions present in endocytotic vesicles were designed. The study showed that PR_b functionalized pH-sensitive stealth liposomes, undergo destabilization under mildly acidic conditions and incorporation of the PR_b peptide does not significantly affect the pH-sensitivity of the liposomes. PR_b functionalized pH-sensitive stealth liposomes bind to CT26.WT colon carcinoma cells that express integrin alpha5beta 1, undergo cellular internalization, and release their load intracellularly in a short period of time as compared to other formulations. PR_b-targeted pH-sensitive stealth liposomes encapsulating 5-fluorouracil (5-FU) show significantly higher cytotoxicity than the PR_b-targeted inert stealth liposomes and the non-targeted stealth liposomes (both pH-sensitive and inert). The studies demonstrated that optimized PR_b functionalized pH sensitive liposomes have the potential to deliver a payload, such as chemotherapeutic agents, directly to colon cancer cells in an efficient and specific manner.

Effect of Pr Valence State on Interfacial Structure and Electrical Properties of Pr Oxide/PrON/Ge Gate Stack Structure

NASA Astrophysics Data System (ADS)

Kato, Kimihiko; Sakashita, Mitsuo; Takeuchi, Wakana; Kondo, Hiroki; Nakatsuka, Osamu; Zaima, Shigeaki

2011-04-01

In this study, we investigated the valence state and chemical bonding state of Pr in a Pr oxide/PrON/Ge structure. We clarified the relationship between the valence state of Pr and the Pr oxide/Ge interfacial reaction using Pr oxide/Ge and Pr oxide/PrON/Ge samples. We found the formation of three Pr oxide phases in Pr oxide films; hexagonal Pr2O3 (h-Pr2O3) (Pr3+), cubic Pr2O3 (c-Pr2O3) (Pr3+), and c-PrO2 (Pr4+). We also investigated the effect of a nitride interlayer on the interfacial reaction in Pr oxide/Ge gate stacks. In a sample with a nitride interlayer (Pr oxide/PrON/Ge), metallic Pr-Pr bonds are also formed in the c-Pr2O3 film. After annealing in H2 ambient, the diffusion of Ge into Pr oxide is not observed in this sample. Pr-Pr bonds probably prevent the interfacial reaction and Ge oxide formation, considering that the oxygen chemical potential of this film is lower than that of a GeO2/Ge system. On the other hand, the rapid thermal oxidation (RTO) treatment terminates the O vacancies and defects in c-Pr2O3. As a result, c-PrO2 with tetravalent Pr is formed in the Pr oxide/PrON/Ge sample with RTO. In this sample, the leakage current density is effectively decreased in comparison with the sample without RTO. Hydrogen termination works effectively in Pr oxide/PrON/Ge samples with and without RTO, and we can achieve an interface state density of as low as 4 ×1011 eV-1·cm-2.

Upregulation of transmitter release probability improves a conversion of synaptic analogue signals into neuronal digital spikes

PubMed Central

2012-01-01

Action potentials at the neurons and graded signals at the synapses are primary codes in the brain. In terms of their functional interaction, the studies were focused on the influence of presynaptic spike patterns on synaptic activities. How the synapse dynamics quantitatively regulates the encoding of postsynaptic digital spikes remains unclear. We investigated this question at unitary glutamatergic synapses on cortical GABAergic neurons, especially the quantitative influences of release probability on synapse dynamics and neuronal encoding. Glutamate release probability and synaptic strength are proportionally upregulated by presynaptic sequential spikes. The upregulation of release probability and the efficiency of probability-driven synaptic facilitation are strengthened by elevating presynaptic spike frequency and Ca2+. The upregulation of release probability improves spike capacity and timing precision at postsynaptic neuron. These results suggest that the upregulation of presynaptic glutamate release facilitates a conversion of synaptic analogue signals into digital spikes in postsynaptic neurons, i.e., a functional compatibility between presynaptic and postsynaptic partners. PMID:22852823

Humic substances interfere with detection of pathogenic prion protein

USGS Publications Warehouse

Smith, Christen B.; Booth, Clarissa J.; Wadzinski, Tyler J.; Legname, Giuseppe; Chappell, Rick; Johnson, Christopher J.; Pedersen, Joel A.

2014-01-01

Studies examining the persistence of prions (the etiological agent of transmissible spongiform encephalopathies) in soil require accurate quantification of pathogenic prion protein (PrPTSE) extracted from or in the presence of soil particles. Here, we demonstrate that natural organic matter (NOM) in soil impacts PrPTSE detection by immunoblotting. Methods commonly used to extract PrPTSE from soils release substantial amounts of NOM, and NOM inhibited PrPTSE immunoblot signal. The degree of immunoblot interference increased with increasing NOM concentration and decreasing NOM polarity. Humic substances affected immunoblot detection of prion protein from both deer and hamsters. We also establish that after interaction with humic acid, PrPTSE remains infectious to hamsters inoculated intracerebrally, and humic acid appeared to slow disease progression. These results provide evidence for interactions between PrPTSE and humic substances that influence both accurate measurement of PrPTSE in soil and disease transmission.

Acceptability of Daily Use of Free Oral Pre-exposure Prophylaxis (PrEP) Among Transgender Women Sex Workers in Shenyang, China.

PubMed

Wang, Zixin; Lau, Joseph T F; Yang, Xueying; Cai, Yong; Gross, Danielle L; Ma, Tiecheng; Liu, Yan

2017-12-01

This study investigated the acceptability of daily use of free oral pre-exposure prophylaxis (PrEP) and associated factors among transgender women sex workers in Shenyang, China, following a briefing on PrEP. A total of 183 HIV negative or sero-status unknown participants completed the cross-sectional survey. The prevalence of acceptability of daily use of free oral PrEP was 61.2%. Adjusting for education level and monthly income, variables on negative attitudes toward PrEP (i.e., having concerns about the side-effects of PrEP) [Adjusted odds ratios (AOR): 0.26], perceived subjective norms (i.e., perceiving support from male partners to take PrEP) (AOR: 2.08), and perceived behavioral control (e.g., perceiving complete control over using PrEP) (AOR: 2.10-16.72) were significantly associated with acceptability of daily use of free oral PrEP. In addition, experiencing violence during sex work, perceived risk of contracting HIV from clients and probable anxiety were also significant. Future PrEP promotion campaigns should consider these factors.

Perceived risk of diabetes seriously underestimates actual diabetes risk: The KORA FF4 study

PubMed Central

Stang, Andreas; Bongaerts, Brenda; Kuss, Oliver; Herder, Christian; Roden, Michael; Quante, Anne; Holle, Rolf; Huth, Cornelia; Peters, Annette; Meisinger, Christa

2017-01-01

Objective Early detection of diabetes and prediabetic states is beneficial for patients, but may be delayed by patients´ being overly optimistic about their own health. Therefore, we assessed how persons without known diabetes perceive their risk of having or developing diabetes, and we identified factors associated with perception of diabetes risk. Research design and methods 1,953 participants without previously known diabetes from the population-based, German KORA FF4 Study (59.1 years, 47.8% men) had an oral glucose tolerance test. They estimated their probability of having undiagnosed diabetes mellitus (UDM) on a six category scale, and assessed whether they were at risk of developing diabetes in the future. We cross-tabulated glycemic status with risk perception, and fitted robust Poisson regression models to identify determinants of diabetes risk perception. Results 74% (95% CI: 65–82) of persons with UDM believed that their probability of having undetected diabetes was low or very low. 72% (95% CI: 69–75) of persons with prediabetes believed that they were not at risk of developing diabetes. In people with prediabetes, seeing oneself at risk of diabetes was associated with self-rated poor general health (prevalence ratio (PR) = 3.1 (95% CI: 1.4–6.8), parental diabetes (PR = 2.6, 1.9–3.4), high educational level (PR = 1.9 (1.4–2.5)), lower age (PR = 0.7, 0.6–0.8, per 1 standard deviation increase), female sex (PR = 1.2, 0.9–1.5) and obesity (PR = 1.5, 1.2–2.0). Conclusions People with undiagnosed diabetes or prediabetes considerably underestimate their probability of having or developing diabetes. Contrary to associations with actual diabetes risk, perceived diabetes risk was lower in men, lower educated and older persons. PMID:28141837

Assessment of the probability of contaminating Mars

NASA Technical Reports Server (NTRS)

Judd, B. R.; North, D. W.; Pezier, J. P.

1974-01-01

New methodology is proposed to assess the probability that the planet Mars will by biologically contaminated by terrestrial microorganisms aboard a spacecraft. Present NASA methods are based on the Sagan-Coleman formula, which states that the probability of contamination is the product of the expected microbial release and a probability of growth. The proposed new methodology extends the Sagan-Coleman approach to permit utilization of detailed information on microbial characteristics, the lethality of release and transport mechanisms, and of other information about the Martian environment. Three different types of microbial release are distinguished in the model for assessing the probability of contamination. The number of viable microbes released by each mechanism depends on the bio-burden in various locations on the spacecraft and on whether the spacecraft landing is accomplished according to plan. For each of the three release mechanisms a probability of growth is computed, using a model for transport into an environment suited to microbial growth.

Prolonged-release fampridine treatment improved subject-reported impact of multiple sclerosis: Item-level analysis of the MSIS-29.

PubMed

Gasperini, Claudio; Hupperts, Raymond; Lycke, Jan; Short, Christine; McNeill, Manjit; Zhong, John; Mehta, Lahar R

2016-11-15

Prolonged-release (PR) fampridine is approved to treat walking impairment in persons with multiple sclerosis (MS); however, treatment benefits may extend beyond walking. MOBILE was a phase 2, 24-week, double-blind, placebo-controlled exploratory study to assess the impact of 10mg PR-fampridine twice daily versus placebo on several subject-assessed measures. This analysis evaluated the physical and psychological health outcomes of subjects with progressing or relapsing MS from individual items of the Multiple Sclerosis Impact Scale (MSIS-29). PR-fampridine treatment (n=68) resulted in greater improvements from baseline in the MSIS-29 physical (PHYS) and psychological (PSYCH) impact subscales, with differences of 89% and 148% in mean score reduction from baseline (n=64) at week 24 versus placebo, respectively. MSIS-29 item analysis showed that a higher percentage of PR-fampridine subjects had mean improvements in 16/20 PHYS and 6/9 PSYCH items versus placebo after 24weeks. Post hoc analysis of the 12-item Multiple Sclerosis Walking Scale (MSWS-12) improver population (≥8-point mean improvement) demonstrated differences in mean reductions from baseline of 97% and 111% in PR-fampridine MSIS-29 PHYS and PSYCH subscales versus the overall placebo group over 24weeks. A higher percentage of MSWS-12 improvers treated with PR-fampridine showed mean improvements in 20/20 PHYS and 8/9 PSYCH items versus placebo at 24weeks. In conclusion, PR-fampridine resulted in physical and psychological benefits versus placebo, sustained over 24weeks. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Different Molecular Mechanisms Mediate Direct or Glia-Dependent Prion Protein Fragment 90-231 Neurotoxic Effects in Cerebellar Granule Neurons.

PubMed

Thellung, Stefano; Gatta, Elena; Pellistri, Francesca; Villa, Valentina; Corsaro, Alessandro; Nizzari, Mario; Robello, Mauro; Florio, Tullio

2017-10-01

Glia over-stimulation associates with amyloid deposition contributing to the progression of central nervous system neurodegenerative disorders. Here we analyze the molecular mechanisms mediating microglia-dependent neurotoxicity induced by prion protein (PrP)90-231, an amyloidogenic polypeptide corresponding to the protease-resistant portion of the pathological prion protein scrapie (PrP Sc ). PrP90-231 neurotoxicity is enhanced by the presence of microglia within neuronal culture, and associated to a rapid neuronal [Ca ++ ] i increase. Indeed, while in "pure" cerebellar granule neuron cultures, PrP90-231 causes a delayed intracellular Ca ++ entry mediated by the activation of NMDA receptors; when neuron and glia are co-cultured, a transient increase of [Ca ++ ] i occurs within seconds after treatment in both granule neurons and glial cells, then followed by a delayed and sustained [Ca ++ ] i raise, associated with the induction of the expression of inducible nitric oxide synthase and phagocytic NADPH oxidase. [Ca ++ ] i fast increase in neurons is dependent on the activation of multiple pathways since it is not only inhibited by the blockade of voltage-gated channel activity and NMDA receptors but also prevented by the inhibition of nitric oxide and PGE 2 release from glial cells. Thus, Ca ++ homeostasis alteration, directly induced by PrP90-231 in cerebellar granule cells, requires the activation of NMDA receptors, but is greatly enhanced by soluble molecules released by activated glia. In glia-enriched cerebellar granule cultures, the activation of inducible nitric oxide (iNOS) and NADPH oxidase represents the main mechanism of toxicity since their pharmacological inhibition prevented PrP90-231 neurotoxicity, whereas NMDA blockade by D(-)-2-amino-5-phosphonopentanoic acid is ineffective; conversely, in pure cerebellar granule cultures, NMDA blockade but not iNOS inhibition strongly reduced PrP90-231 neurotoxicity. These data indicate that amyloidogenic peptides induce neurotoxic signals via both direct neuron interaction and glia activation through different mechanisms responsible of calcium homeostasis disruption in neurons and potentiating each other: the activation of excitotoxic pathways via NMDA receptors and the release of radical species that establish an oxidative milieu.

LOPP: A Location Privacy Protected Anonymous Routing Protocol for Disruption Tolerant Network

NASA Astrophysics Data System (ADS)

Lu, Xiaofeng; Hui, Pan; Towsley, Don; Pu, Juhua; Xiong, Zhang

In this paper, we propose an anonymous routing protocol, LOPP, to protect the originator's location privacy in Delay/Disruption Tolerant Network (DTN). The goals of our study are to minimize the originator's probability of being localized (Pl) and maximize the destination's probability of receiving the message (Pr). The idea of LOPP is to divide a sensitive message into k segments and send each of them to n different neighbors. Although message fragmentation could reduce the destination's probability to receive a complete message, LOPP can decrease the originator's Pl. We validate LOPP on a real-world human mobility dataset. The simulation results show that LOPP can decrease the originator's Pl by over 54% with only 5.7% decrease in destination's Pr. We address the physical localization issue of DTN, which was not studied in the literature.

Celecoxib Inhibits Prion Protein 90-231-Mediated Pro-inflammatory Responses in Microglial Cells.

PubMed

Villa, Valentina; Thellung, Stefano; Corsaro, Alessandro; Novelli, Federica; Tasso, Bruno; Colucci-D'Amato, Luca; Gatta, Elena; Tonelli, Michele; Florio, Tullio

2016-01-01

Activation of microglia is a central event in the atypical inflammatory response occurring during prion encephalopathies. We report that the prion protein fragment encompassing amino acids 90-231 (PrP90-231), a model of the neurotoxic activity of the pathogenic prion protein (PrP(Sc)), causes activation of both primary microglia cultures and N9 microglial cells in vitro. This effect was characterized by cell proliferation arrest and induction of a secretory phenotype, releasing prostaglandin E2 (PGE2) and nitric oxide (NO). Conditioned medium from PrP90-231-treated microglia induced in vitro cytotoxicity of A1 mesencephalic neurons, supporting the notion that soluble mediators released by activated microglia contributes to the neurodegeneration during prion diseases. The neuroinflammatory role of COX activity, and its potential targeting for anti-prion therapies, was tested measuring the effects of ketoprofen and celecoxib (preferential inhibitors of COX1 and COX2, respectively) on PrP90-231-induced microglial activation. Celecoxib, but not ketoprofen significantly reverted the growth arrest as well as NO and PGE2 secretion induced by PrP90-231, indicating that PrP90-231 pro-inflammatory response in microglia is mainly dependent on COX2 activation. Taken together, these data outline the importance of microglia in the neurotoxicity occurring during prion diseases and highlight the potentiality of COX2-selective inhibitors to revert microglia as adjunctive pharmacological approach to contrast the neuroinflammation-dependent neurotoxicity.

Announcement of the Public Release of Airborne Multiangle SpectroPolarimetric Imager (AirMSPI) Level 1B2 V006

Atmospheric Science Data Center

2018-05-21

... Radar Definition Experiment (RADEX) SPEX engineering flights + Porter Ranch gas leak overflights (SPEX-PR) ... The SPEX engineering flights + Porter Ranch gas leak overflights (SPEX-PR) flight ... Armstrong Flight Research Center in Palmdale, CA. The SPEX engineering flights conducted on February 2 through February 5, 2016 focused on ...

Kepler Planet Reliability Metrics: Astrophysical Positional Probabilities for Data Release 25

NASA Technical Reports Server (NTRS)

Bryson, Stephen T.; Morton, Timothy D.

2017-01-01

This document is very similar to KSCI-19092-003, Planet Reliability Metrics: Astrophysical Positional Probabilities, which describes the previous release of the astrophysical positional probabilities for Data Release 24. The important changes for Data Release 25 are:1. The computation of the astrophysical positional probabilities uses the Data Release 25 processed pixel data for all Kepler Objects of Interest.2. Computed probabilities now have associated uncertainties, whose computation is described in x4.1.3.3. The scene modeling described in x4.1.2 uses background stars detected via ground-based high-resolution imaging, described in x5.1, that are not in the Kepler Input Catalog or UKIRT catalog. These newly detected stars are presented in Appendix B. Otherwise the text describing the algorithms and examples is largely unchanged from KSCI-19092-003.

Autoantibodies developing to myeloperoxidase and proteinase 3 in systemic vasculitis stimulate neutrophil cytotoxicity toward cultured endothelial cells.

PubMed Central

Savage, C. O.; Pottinger, B. E.; Gaskin, G.; Pusey, C. D.; Pearson, J. D.

1992-01-01

The ability of vasculitis-associated anti-neutrophil cytoplasm antibodies (ANCA) to activate neutrophils and mediate release of radiolabel from 111Indium-labeled cultured human umbilical vein endothelial cells (HUVEC) was determined as a measure of the potential cytotoxicity of ANCA-activated neutrophils against vascular endothelium. Priming of neutrophils with low doses of phorbol 12-myristate 13-acetate (PMA) (1 ng/ml) and ionomycin (0.1 mumol/1) was required, together with pretreatment of endothelial cells with BCNU (1,3-bis-[2-chloroethyl]-1-nitrosourea; 0.26 mmol/l). Under these conditions and using a 4-hour serum-free assay system, mouse monoclonal antibodies (MAb) to the target autoantigens proteinase-3 (Pr-3) and myeloperoxidase (MPO) mediated enhanced release of 111Indium from HUVEC compared with control MAb. Human IgG Fab2 C-ANCA (recognizing Pr-3) and P-ANCA (recognizing MPO) did likewise. Preactivation of HUVEC with TNF (50 U/ml, 4 hr) enhanced the release of 111Indium from HUVEC generated by neutrophils activated with anti-Pr-3 and anti-MPO MAb. These data support the suggestion that activation of neutrophils by ANCA within the vascular lumen may contribute to endothelial cell injury. PMID:1323218

Severe post-renal acute kidney injury, post-obstructive diuresis and renal recovery.

PubMed

Hamdi, Aïcha; Hajage, David; Van Glabeke, Emmanuel; Belenfant, Xavier; Vincent, François; Gonzalez, Frédéric; Ciroldi, Magali; Obadia, Edouard; Chelha, Riad; Pallot, Jean-Louis; Das, Vincent

2012-12-01

Study Type--Therapy (case series) Level of Evidence 4. What's known on the subject? and What does the study add? The pathophysiology of post-renal acute kidney injury (PR-AKI), i.e. caused by urinary tract obstruction, has been extensively studied in animal models but clinical studies on this subject are outdated, and/or have focused on the mechanisms of 'post-obstructive diuresis' (POD), a potentially life-threatening polyuria that can develop after the release of obstruction. In severe PR-AKI, the risk of occurrence of POD is high. POD occurrence predicts renal recovery without the persistence of severe chronic kidney failure. In the present study, the occurrence of POD and the persistence of chronic renal sequelae could be predicted early from clinical variables at admission before the release of obstruction. • To identify predictors of post-obstructive diuresis (POD) occurrence or severe chronic renal failure (CRF) persistence after the release of urinary tract obstruction in the setting of post-renal acute kidney injury (PR-AKI). • Bi-centre retrospective observational study of all patients with PR-AKI treated in two intensive care units (ICUs) from 1998 to 2010. • Clinical, biological and imaging characteristics on admission and after the release of obstruction were analysed with univariate and, if possible, multivariate analysis to search for predictors of (i) occurrence of POD (diuresis >4 L/day) after the release of obstruction; (ii) persistence of severe CRF (estimated glomerular filtration rate <30 mL/min/1.73 m(2), including end-stage CRF) at 3 months. • On admission, median (range) serum creatinine was 866 (247-3119) µmol/L. • POD occurred in 34 (63%) of the 54 analysable patients. On admission, higher serum creatinine (Odds ratio [OR] 1.002 per 1 µmol/L, 95% confidence interval [CI] 1.000-1.004, P = 0.004), higher serum bicarbonate (OR 1.36 per 1 mmol/L, 95% CI 1.13-1.65, P < 0.001), and urinary retention (OR 6.96, 95% CI 1.34-36.23, P = 0.01) independently predicted POD occurrence. • Severe CRF persisted in seven (21%) of the 34 analysable patients, including two (6%) cases of end-stage CRF. Predictors of severe CRF persistence after univariate analysis were: lower blood haemoglobin (P < 0.001) and lower serum bicarbonate (P = 0.03) on admission, longer time from admission to the release of obstruction (P = 0.01) and absence of POD (P = 0.04) after the release of obstruction. • In severe PR-AKI treated in ICU, POD occurrence was a frequent event that predicted renal recovery without severe CRF. • POD occurrence or severe CRF persistence could be predicted early from clinical and biological variables at admission before the release of obstruction. © 2012 THE AUTHORS. BJU INTERNATIONAL © 2012 BJU INTERNATIONAL.

The prenyl-binding protein PrBP/δ: a chaperone participating in intracellular trafficking

PubMed Central

Zhang, Houbin; Constantine, Ryan; Frederick, Jeanne M.; Baehr, Wolfgang

2012-01-01

Expressed ubiquitously, PrBP/δ functions as chaperone/co-factor in the transport of a subset of prenylated proteins. PrBP/δ features an immunoglobulin-like β-sandwich fold for lipid binding, and interacts with diverse partners. PrBP/δ binds both C-terminal C15 and C20 prenyl side chains of phototransduction polypeptides and small GTP-binding (G) proteins of the Ras superfamily. PrBP/δ also interacts with the small GTPases, ARL2 and ARL3, which act as release factors (GDFs) for prenylated cargo. Targeted deletion of the mouse Pde6d gene encoding PrBP/δ resulted in impeded trafficking to the outer segments of GRK1 and cone PDE6 which are predicted to be farnesylated and geranylgeranylated, respectively. Rod and cone transducin trafficking was largely unaffected. These trafficking defects produce progressive cone-rod dystrophy in the Pde6d−/− mouse. PMID:22960045

The role of birthplace and educational attainment on induced abortion inequalities.

PubMed

González-Rábago, Yolanda; Rodriguez-Alvarez, Elena; Borrell, Luisa N; Martín, Unai

2017-01-13

Induced abortion (IA) has shown social inequality related to birthplace and education with higher rates of IAs in immigrant and in less educated women relative to their native and highly educated counterparts. This study examined the independent and joint effects of birthplace and education on IA, repeated and IA performed during the 2nd trimester of pregnancy among women residing in the Basque Country, Spain. We conducted a cross-sectional population-based study of IA among women aged 25-49 years residing in the Basque Country, Spain, between 2011 and 2013. Log-binomial regression was used to quantify the independent and joint effects of birthplace and education attainment on all outcomes. Immigrant women exhibited higher probability of having an IAs (PR: 5.31), a repeated (PR: 7.23) or a 2nd trimester IAs (PR: 4.07) than women born in Spain. We observed higher probabilities for all outcomes among women with a primary or less education relative to those with a graduate education (All IAs PR: 2.51; repeated PR: 6.00; 2nd trimester PR: 3.08). However, no significant heterogeneity was observed for the effect of education on the association of birthplace with IAs, repeated or 2nd trimester IAs. Birthplace and education are key factors to explain not only an IA decision but also having a repeated or a 2nd trimester IA. However, the effects of birthplace and education may be independent from each other on these outcomes. A better understanding of these factors on IAs is needed when designing programs for sexual and reproductive health aimed to reduce inequalities among women.

A deletion mutation in the 5' part of the pol gene of Moloney murine leukemia virus blocks proteolytic processing of the gag and pol polyproteins.

PubMed Central

Crawford, S; Goff, S P

1985-01-01

Deletion mutations in the 5' part of the pol gene of Moloney murine leukemia virus were generated by restriction enzyme site-directed mutagenesis of cloned proviral DNA. DNA sequence analysis indicated that one such deletion was localized entirely within the 5' part of the pol gene, did not affect the region encoding reverse transcriptase, and preserved the translational reading frame downstream of the mutation. The major viral precursor polyproteins (Pr65gag, Pr200gag-pol, and gPr80env) were synthesized at wild-type levels in cell lines carrying the mutant genome. These cell lines assembled and released wild-type levels of virion particles into the medium. Cleavage of both Pr65gag and Pr200gag-pol precursors to the mature proteins was completely blocked in the mutant virions. Surprisingly, these virions contained high levels of active reverse transcriptase; examination of the endogenous reverse transcription products synthesized by the mutant virions revealed normal amounts of minus-strand strong-stop DNA, indicating that the RNA genome was packaged and that reverse transcription in detergent-permeabilized virions was not significantly impaired. Processing of gPr80env to gP70env and P15E was not affected by the mutation, but cleavage of P15E to P12E was not observed. The mutant particles were poorly infectious; analysis indicated that infection was blocked at an early stage. The data are consistent with the idea that the 5' part of the pol gene encodes a protease directly responsible for processing Pr65gag, and possibly Pr200gag-pol, to the structural virion proteins. It appears that cleavage of the gag gene product is not required for budding and release of virions and that complete processing of the pol gene product to the mature form of reverse transcriptase is not required for its functional activation. Images PMID:3882995

Factors affecting publication in peer-reviewed journals of abstracts presented from 2008 to 2012 ACVO meetings.

PubMed

Bentley, Ellison; Koester, Megan; Bdolah-Abram, Tali; Yair, Nadav; Ofri, Ron

2018-04-14

To examine variables that affect publication of ACVO meeting abstracts in peer-reviewed journals and compare results to ECVO publication rate (PR). Published papers were identified via online searches for abstracts from 2008 to 2012 ACVO/ECVO meetings. Variables analyzed (via Pearson's chi-Squared test) included the following: oral presentation/poster, type of abstract (clinical/basic science/case report), species, ocular tissue, nationality, funding, first/last/any author a diplomate, resident as first author, and author affiliation (private practice/university). One hundred and eighty-six of 577 ACVO abstracts were published within 608 ± 479 days, with 103 published in Veterinary Ophthalmology. Significant factors included the following: nationality of first/last authors (P = .005); English as first language (P < .001); presentation type (P < .001, oral 40% PR, poster 22% PR); type of study (P = .037, clinical study 35% PR, basic science 30% PR, case report 16% PR); resident as first author (P < .001); diplomate as any author except first/last (P < .001); first author affiliation (P = .001, university 37% PR, practice 21% PR); last author affiliation (P = .003, university 36% PR, practice 22% PR); and species (P < .001, horses 53% PR, multiple species 50% PR, cats 35% PR, food animals 31% PR, exotics/wildlife 31% PR, dogs 27% PR, laboratory animals/in vitro 24%). Nonsignificant factors were as follows: diplomate as first/last author, funding, and ocular tissue. Presentation type, resident as first author, university affiliation of first author, and species had the greatest effect on publication probability. For the same period, ECVO PR was 87 of 299, which was not significantly different from ACVO PR (P = .342). At 32%, ACVO PR for the study years is similar to ECVO PR of 29%. © 2018 American College of Veterinary Ophthalmologists.

Analysis of nucleic acid chaperoning by the prion protein and its inhibition by oligonucleotides.

PubMed

Guichard, Cécile; Ivanyi-Nagy, Roland; Sharma, Kamal Kant; Gabus, Caroline; Marc, Daniel; Mély, Yves; Darlix, Jean-Luc

2011-10-01

Prion diseases are unique neurodegenerative illnesses associated with the conversion of the cellular prion protein (PrP(C)) into the aggregated misfolded scrapie isoform, named PrP(Sc). Recent studies on the physiological role of PrP(C) revealed that this protein has probably multiple functions, notably in cell-cell adhesion and signal transduction, and in assisting nucleic acid folding. In fact, in vitro findings indicated that the human PrP (huPrP) possesses nucleic acid binding and annealing activities, similarly to nucleic acid chaperone proteins that play essential roles in cellular DNA and RNA metabolism. Here, we show that a peptide, representing the N-terminal domain of huPrP, facilitates nucleic acid annealing by two parallel pathways nucleated through the stem termini. We also show that PrP of human or ovine origin facilitates DNA strand exchange, ribozyme-directed cleavage of an RNA template and RNA trans-splicing in a manner similar to the nucleocapsid protein of HIV-1. In an attempt to characterize inhibitors of PrP-chaperoning in vitro we discovered that the thioaptamer 5'-GACACAAGCCGA-3' was extensively inhibiting the PrP chaperoning activities. At the same time a recently characterized methylated oligoribonucleotide inhibiting the chaperoning activity of the HIV-1 nucleocapsid protein was poorly impairing the PrP chaperoning activities.

Search Path Evaluation Incorporating Object Placement Structure

DTIC Science & Technology

2007-12-20

the probability of the set complement of this event: Pr(Ed) = 1 - kP PC (83) (k,t)I iIG Equation (83) provides the probability that if there is an...Networks," to appear in IEEE Transactions on Aerospace and Electronic Systems. 3. B. G. Koopman, Search and Screening: General Principles and Historical

Efficacy of a new filler-containing root coating material for dentin remineralization.

PubMed

Okuyama, Katsushi; Kadowaki, Yoshitaka; Matsuda, Yasuhiro; Hashimoto, Naoki; Oki, Saiko; Yamamoto, Hiroko; Tamaki, Yukimichi; Sano, Hidehiko

2016-08-01

To evaluate a new root coating material containing surface pre-reacted glass-ionomer (S-PRG) filler for remineralization of demineralized dentin. The dentin was exposed on root surfaces of human third molars and demineralized by immersion in demineralization solution for 4 days. The demineralized dentin surface was divided into three areas. The center area was left untreated. The area on one side of the center area was coated with protective wax. The area on the other side was coated with one of four test materials: fluoride-containing S-PRG filler (PRG Barrier Coat: PR), fluoride-containing bonding agent (Bond Force: BF), fluoride-containing glass-ionomer cement as a positive control (Fuji IX EXTRA: EX), or non-fluoride-containing bonding agent as a negative control (Clearfil MegaBond: MB). The samples were stored in remineralization solution for 7 days, and then cut into two slices. The mineral changes, defined as variation in mineral loss between wax-coated area and the central untreated area, were measured in one slice by transversal microradiography. The fluoride concentration was measured in the other slice by µ-particle-induced gamma/X-ray emission. Seven thin specimens (0.25-mm thickness) of each test material were used to determine fluoride ion release from the materials over 21 days. The mineral changes were greatest for EX, followed by PR, with no difference between BF and MB (P> 0.05). Regarding the fluoride concentrations in dentin, there was no difference between EX and PR (P> 0.05). MB had the lowest value (P< 0.01). Fluoride release from EX was largest, followed by PR, with BF showing low fluoride release (P< 0.05). MB had no fluoride release. A new coating material with S-PRG filler can be applied in a thin layer on root dentin, which could be especially useful for hard-to-access lesions. This material remineralized demineralized root dentin and had fluoride diffusion characteristics similar to those of glass-ionomer cement in vitro.

Progesterone receptor knockout mice have an improved glucose homeostasis secondary to -cell proliferation

NASA Astrophysics Data System (ADS)

Picard, Frédéric; Wanatabe, Mitsuhiro; Schoonjans, Kristina; Lydon, John; O'Malley, Bert W.; Auwerx, Johan

2002-11-01

Gestational diabetes coincides with elevated circulating progesterone levels. We show that progesterone accelerates the progression of diabetes in female db/db mice. In contrast, RU486, an antagonist of the progesterone receptor (PR), reduces blood glucose levels in both female WT and db/db mice. Furthermore, female, but not male, PR-/- mice had lower fasting glycemia than PR+/+ mice and showed higher insulin levels on glucose injection. Pancreatic islets from female PR-/- mice were larger and secreted more insulin consequent to an increase in -cell mass due to an increase in -cell proliferation. These findings demonstrate an important role of progesterone signaling in insulin release and pancreatic function and suggest that it affects the susceptibility to diabetes.

Role of the Cellular Prion Protein in Oligodendrocyte Precursor Cell Proliferation and Differentiation in the Developing and Adult Mouse CNS

PubMed Central

Bribián, Ana; Gavín, Rosalina; Reina, Manuel; García-Verdugo, José Manuel; Torres, Juan María; de Castro, Fernando; del Río, José Antonio

2012-01-01

There are numerous studies describing the signaling mechanisms that mediate oligodendrocyte precursor cell (OPC) proliferation and differentiation, although the contribution of the cellular prion protein (PrPc) to this process remains unclear. PrPc is a glycosyl-phosphatidylinositol (GPI)-anchored glycoprotein involved in diverse cellular processes during the development and maturation of the mammalian central nervous system (CNS). Here we describe how PrPc influences oligodendrocyte proliferation in the developing and adult CNS. OPCs that lack PrPc proliferate more vigorously at the expense of a delay in differentiation, which correlates with changes in the expression of oligodendrocyte lineage markers. In addition, numerous NG2-positive cells were observed in cortical regions of adult PrPc knockout mice, although no significant changes in myelination can be seen, probably due to the death of surplus cells. PMID:22529900

The prenyl-binding protein PrBP/δ: a chaperone participating in intracellular trafficking.

PubMed

Zhang, Houbin; Constantine, Ryan; Frederick, Jeanne M; Baehr, Wolfgang

2012-12-15

Expressed ubiquitously, PrBP/δ functions as chaperone/co-factor in the transport of a subset of prenylated proteins. PrBP/δ features an immunoglobulin-like β-sandwich fold for lipid binding, and interacts with diverse partners. PrBP/δ binds both C-terminal C15 and C20 prenyl side chains of phototransduction polypeptides and small GTP-binding (G) proteins of the Ras superfamily. PrBP/δ also interacts with the small GTPases, ARL2 and ARL3, which act as release factors (GDFs) for prenylated cargo. Targeted deletion of the mouse Pde6d gene encoding PrBP/δ resulted in impeded trafficking to the outer segments of GRK1 and cone PDE6 which are predicted to be farnesylated and geranylgeranylated, respectively. Rod and cone transducin trafficking was largely unaffected. These trafficking defects produce progressive cone-rod dystrophy in the Pde6d(-/-) mouse. Copyright © 2012 Elsevier Ltd. All rights reserved.

Cellular mechanisms responsible for cell-to-cell spreading of prions.

PubMed

Vilette, Didier; Courte, Josquin; Peyrin, Jean Michel; Coudert, Laurent; Schaeffer, Laurent; Andréoletti, Olivier; Leblanc, Pascal

2018-05-14

Prions are infectious agents that cause fatal neurodegenerative diseases. Current evidence indicates that they are essentially composed of an abnormally folded protein (PrP Sc ). These abnormal aggregated PrP Sc species multiply in infected cells by recruiting and converting the host PrP C protein into new PrP Sc . How prions move from cell to cell and progressively spread across the infected tissue is of crucial importance and may provide experimental opportunity to delay the progression of the disease. In infected cells, different mechanisms have been identified, including release of infectious extracellular vesicles and intercellular transfer of PrP Sc -containing organelles through tunneling nanotubes. These findings should allow manipulation of the intracellular trafficking events targeting PrP Sc in these particular subcellular compartments to experimentally address the relative contribution of these mechanisms to in vivo prion pathogenesis. In addition, such information may prompt further experimental strategies to decipher the causal roles of protein misfolding and aggregation in other human neurodegenerative diseases.

The Pearson walk with shrinking steps in two dimensions

NASA Astrophysics Data System (ADS)

Serino, C. A.; Redner, S.

2010-01-01

We study the shrinking Pearson random walk in two dimensions and greater, in which the direction of the Nth step is random and its length equals λN-1, with λ<1. As λ increases past a critical value λc, the endpoint distribution in two dimensions, P(r), changes from having a global maximum away from the origin to being peaked at the origin. The probability distribution for a single coordinate, P(x), undergoes a similar transition, but exhibits multiple maxima on a fine length scale for λ close to λc. We numerically determine P(r) and P(x) by applying a known algorithm that accurately inverts the exact Bessel function product form of the Fourier transform for the probability distributions.

PrP(C) homodimerization stimulates the production of PrPC cleaved fragments PrPN1 and PrPC1.

PubMed

Béland, Maxime; Motard, Julie; Barbarin, Alice; Roucou, Xavier

2012-09-19

An endoproteolytic cleavage termed α-cleavage between residues 111/112 is a characteristic feature of the cellular prion protein (PrP(C)). This cleavage generates a soluble N-terminal fragment (PrPN1) and a glycosylphosphatidylinositol-anchored C-terminal fragment (PrPC1). Independent studies demonstrate that modulating PrP(C) α-cleavage represents a potential therapeutic strategy in prion diseases. The regulation of PrP(C) α-cleavage is unclear. The only known domain that is essential for the α-cleavage to occur is a hydrophobic domain (HD). Importantly, the HD is also essential for the formation of PrP(C) homodimers. To explore the role of PrP(C) homodimerization on the α-cleavage, we used a well described inducible dimerization strategy whereby a chimeric PrP(C) composed of a modified FK506-binding protein (Fv) fused with PrP(C) and termed Fv-PrP is incubated in the presence of a dimerizer AP20187 ligand. We show that homodimerization leads to a considerable increase of PrP(C) α-cleavage in cultured cells and release of PrPN1 and PrPC1. Interestingly, enforced homodimerization increased PrP(C) levels at the plasma membrane, and preventing PrP(C) trafficking to the cell surface inhibited dimerization-induced α-cleavage. These observations were confirmed in primary hippocampal neurons from transgenic mice expressing Fv-PrP. The proteases responsible for the α-cleavage are still elusive, and in contrast to initial studies we confirm more recent investigations that neither ADAM10 nor ADAM17 are involved. Importantly, PrPN1 produced after PrP(C) homodimerization protects against toxic amyloid-β (Aβ) oligomers. Thus, our results show that PrP(C) homodimerization is an important regulator of PrP(C) α-cleavage and may represent a potential therapeutic avenue against Aβ toxicity in Alzheimer's disease.

Enhanced stabilization of Pb, Zn, and Cd in contaminated soils using oxalic acid-activated phosphate rocks.

PubMed

Zhang, Zhuo; Guo, Guanlin; Wang, Mei; Zhang, Jia; Wang, Zhixin; Li, Fasheng; Chen, Honghan

2018-01-01

Phosphate amendments, especially phosphate rock (PR), are one of the most commonly used materials to stabilize heavy metals in contaminated soils. However, most of PR reserve consists of low-grade ore, which limits the efficiency of PR for stabilizing heavy metals. This study was to enhance the stabilization of heavy metals through improving the available phosphorous (P) release of PR by oxalic acid activation. Raw PR and activated PR (APR) were characterized by scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDS), X-ray powder diffraction (XRD), Brunauer-Emmett-Teller (BET) surface analysis, and laser diffraction to determine the changes of structure and composition of APR. The stabilization effectiveness of lead (Pb), zinc (Zn), and cadmium (Cd) in soils by APR was investigated through toxicity leaching test and speciation analysis. The results indicated that after treatment by oxalic acid, (1) the crystallinity of the fluorapatite phase of PR transformed into the weddellite phase; (2) the surface area of PR increased by 37%; (3) the particle size of PR became homogenized (20-70 μm); and (4) the available P content in PR increased by 22 times. These changes of physicochemical characteristics of PR induced that APR was more effective to transform soil heavy metals from the non-residual fraction to the residual fraction and enhance the stabilization efficiency of Pb, Zn, and Cd than PR. These results are significant for the future use of low-grade PR to stabilize heavy metals.

[Mass media influence and risk of developing eating disorders in female students from Lima, Peru].

PubMed

Lazo Montoya, Yessenia; Quenaya, Alejandra; Mayta-Tristán, Percy

2015-12-01

Eating disorders (EDs) are a public health problem, and their relationship to mass media is still controversial. To assess whether there is an association between models of body image shown in mass media and the risk of developing EDs among female adolescent students from Lima, Peru. Cross-sectional study conducted in three schools located in the district of La Victoria, Lima, Peru. The risk of developing EDs was measured using the Eating Attitudes Test-26 (EAT-26), while mass media influence was measured using the Sociocultural Attitudes Towards Appearance Questionnaire-3 (SATAQ-3), which was categorized into tertiles both in the overall score and its subscales (information, pressure, general internalization, and athletic internalization). Adjusted prevalence ratios (aPR) for EDs were estimated. Four hundred and eighty-three students were included, their median age was 14 ? 3 years old. A risk of developing an ED was observed in 13.9% of them. Students who are more influenced by mass media (upper tertile of the SATAQ-3) have a higher probability of having a risk of developing an ED (aPR: 4.24; 95% confidence interval |-CI-|: 2.10-8.56), as well as those who have a greater access to information (PR: 1.89; 95% CI: 1.09-3.25), suffer more pressure (PR: 4.97; 95% CI: 2.31-10.69), show a greater general internalization (PR: 5.00; 95% CI: 2.39-10.43), and show a greater level of athletic internalization (PR: 4.35; 95% CI: 2.19-8-66). The greater the influence of mass media, the greater the probability of having a risk of developing an ED among female students from Lima, Peru.

Towards valid 'serious non-fatal injury' indicators for international comparisons based on probability of admission estimates.

PubMed

Cryer, Colin; Miller, Ted R; Lyons, Ronan A; Macpherson, Alison K; Pérez, Katherine; Petridou, Eleni Th; Dessypris, Nick; Davie, Gabrielle S; Gulliver, Pauline J; Lauritsen, Jens; Boufous, Soufiane; Lawrence, Bruce; de Graaf, Brandon; Steiner, Claudia A

2017-02-01

Governments wish to compare their performance in preventing serious injury. International comparisons based on hospital inpatient records are typically contaminated by variations in health services utilisation. To reduce these effects, a serious injury case definition has been proposed based on diagnoses with a high probability of inpatient admission (PrA). The aim of this paper was to identify diagnoses with estimated high PrA for selected developed countries. The study population was injured persons of all ages who attended emergency department (ED) for their injury in regions of Canada, Denmark, Greece, Spain and the USA. International Classification of Diseases (ICD)-9 or ICD-10 4-digit/character injury diagnosis-specific ED attendance and inpatient admission counts were provided, based on a common protocol. Diagnosis-specific and region-specific PrAs with 95% CIs were calculated. The results confirmed that femoral fractures have high PrA across all countries studied. Strong evidence for high PrA also exists for fracture of base of skull with cerebral laceration and contusion; intracranial haemorrhage; open fracture of radius, ulna, tibia and fibula; pneumohaemothorax and injury to the liver and spleen. Slightly weaker evidence exists for cerebellar or brain stem laceration; closed fracture of the tibia and fibula; open and closed fracture of the ankle; haemothorax and injury to the heart and lung. Using a large study size, we identified injury diagnoses with high estimated PrAs. These diagnoses can be used as the basis for more valid international comparisons of life-threatening injury, based on hospital discharge data, for countries with well-developed healthcare and data collection systems. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

The Flavivirus Precursor Membrane-Envelope Protein Complex: Structure and Maturation

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

Li, Long; Lok, Shee-Mei; Yu, I-Mei

2008-09-17

Many viruses go through a maturation step in the final stages of assembly before being transmitted to another host. The maturation process of flaviviruses is directed by the proteolytic cleavage of the precursor membrane protein (prM), turning inert virus into infectious particles. We have determined the 2.2 angstrom resolution crystal structure of a recombinant protein in which the dengue virus prM is linked to the envelope glycoprotein E. The structure represents the prM-E heterodimer and fits well into the cryo-electron microscopy density of immature virus at neutral pH. The pr peptide {beta}-barrel structure covers the fusion loop in E, preventingmore » fusion with host cell membranes. The structure provides a basis for identifying the stages of its pH-directed conformational metamorphosis during maturation, ending with release of pr when budding from the host.« less

MAÑANA: U.S. EPA, National Econ Corporation demostrarán prácticas seguras de trabajo con plomo para contratistas, se anunciará compromiso para reducir la exposición al plomo en la región

EPA Pesticide Factsheets

EPA News Release: MAÑANA: U.S. EPA, National Econ Corporation demostrarán prácticas seguras de trabajo con plomo para contratistas, se anunciará compromiso para reducir la exposición al plomo en la región

Transforming Growth Factor-β1 Attenuates Expression of Both the Progesterone Receptor and Dickkopf in Differentiated Human Endometrial Stromal Cells

PubMed Central

Kane, Nicole; Jones, Marius; Brosens, Jan J.; Saunders, Philippa T. K.; Kelly, Rodney W.; Critchley, Hilary O. D.

2008-01-01

TGFβ1 is thought to be intimately involved in cyclic tissue remodeling and inflammatory events associated with menstruation. Menstruation is initiated by progesterone withdrawal; however, the underlying mechanisms are not well understood. In the present study, we have tested the hypothesis that locally produced TGFβ1 may influence expression of progesterone receptor (PR) or the Wnt antagonist Dickkopf-1 (DKK) with consequential impact on regulation of menstruation. Endometrial stromal cells (ESC) were isolated from endometrial biopsy samples collected from patients undergoing gynecological procedures for benign indications. Treatment of differentiated ESC with TGFβ1 (10 ng/ml) significantly inhibited the expression of mRNAs encoding PR and DKK. TGFβ1 also attenuated the protein expression of PR and secretion of DKK proteins in culture supernatants. Neutralization of endogenous TGFβ1 signaling abolished the TGFβ1-induced effects, significantly increased expression of PR, and increased DKK protein release levels to that of differentiated ESCs, confirming the specificity of the TGFβ1 effect. Additionally, in vitro decidualization of ESCs significantly augmented DKK protein release. Moreover, although TGFβ1 was capable of signaling via the Sma- and mothers against decapentaplegic (MAD)-related protein (SMAD) pathway, the inhibitory effect on DKK was SMAD independent. Conversely, the inhibitory effect of TGFβ1 on PR was dependent on SMAD signal transduction. In conclusion, these results suggest that local TGFβ1 signaling can potentiate progesterone withdrawal by suppressing expression of PR and may coordinate tissue remodeling associated with menstruation by inducing Wnt-signaling via inhibition of DKK, which we found to be up-regulated as a consequence of decidualization of ESCs. PMID:18032694

Enhanced astroglial Ca2+ signaling increases excitatory synaptic strength in the epileptic brain.

PubMed

Álvarez-Ferradas, Carla; Morales, Juan Carlos; Wellmann, Mario; Nualart, Francisco; Roncagliolo, Manuel; Fuenzalida, Marco; Bonansco, Christian

2015-09-01

The fine-tuning of synaptic transmission by astrocyte signaling is crucial to CNS physiology. However, how exactly astroglial excitability and gliotransmission are affected in several neuropathologies, including epilepsy, remains unclear. Here, using a chronic model of temporal lobe epilepsy (TLE) in rats, we found that astrocytes from astrogliotic hippocampal slices displayed an augmented incidence of TTX-insensitive spontaneous slow Ca(2+) transients (STs), suggesting a hyperexcitable pattern of astroglial activity. As a consequence, elevated glutamate-mediated gliotransmission, observed as increased slow inward current (SICs) frequency, up-regulates the probability of neurotransmitter release in CA3-CA1 synapses. Selective blockade of spontaneous astroglial Ca(2+) elevations as well as the inhibition of purinergic P2Y1 or mGluR5 receptors relieves the abnormal enhancement of synaptic strength. Moreover, mGluR5 blockade eliminates any synaptic effects induced by P2Y1R inhibition alone, suggesting that the Pr modulation via mGluR occurs downstream of P2Y1R-mediated Ca(2+)-dependent glutamate release from astrocyte. Our findings show that elevated Ca(2+)-dependent glutamate gliotransmission from hyperexcitable astrocytes up-regulates excitatory neurotransmission in epileptic hippocampus, suggesting that gliotransmission should be considered as a novel functional key in a broad spectrum of neuropathological conditions. © 2015 Wiley Periodicals, Inc.

Modulation of the formation and release of bovine SRS-A in vitro by several anti-anaphylactic drugs.

PubMed

Burka, J F; Eyre, P

1975-01-01

Slow-reacting substance of anaphylaxis (SRS-A) is released immunologically from bovine lung in vitro. Various drugs known to protect calves and other animals during anaphylaxis were tested to investigate their modulation of the formation and release of SRS-A. The anti-inflammatory drugs, meclofenamate and aspirin, potentiated SRS-A release. Chlorphenesin and diethylcarbamazine citrate at high concentrations both inhibited SRS-A release. Two new anti-anaphylactic drugs, PR-D-92-EA and M&B 22,948, were particularly effective in inhibiting SRS-A release at low concentrations. The possible modes of actions of these drugs are discussed.

Modeling and measurement of vesicle pools at the cone ribbon synapse: changes in release probability are solely responsible for voltage-dependent changes in release

PubMed Central

Thoreson, Wallace B.; Van Hook, Matthew J.; Parmelee, Caitlyn; Curto, Carina

2015-01-01

Post-synaptic responses are a product of quantal amplitude (Q), size of the releasable vesicle pool (N), and release probability (P). Voltage-dependent changes in presynaptic Ca2+ entry alter post-synaptic responses primarily by changing P but have also been shown to influence N. With simultaneous whole cell recordings from cone photoreceptors and horizontal cells in tiger salamander retinal slices, we measured N and P at cone ribbon synapses by using a train of depolarizing pulses to stimulate release and deplete the pool. We developed an analytical model that calculates the total pool size contributing to release under different stimulus conditions by taking into account the prior history of release and empirically-determined properties of replenishment. The model provided a formula that calculates vesicle pool size from measurements of the initial post-synaptic response and limiting rate of release evoked by a train of pulses, the fraction of release sites available for replenishment, and the time constant for replenishment. Results of the model showed that weak and strong depolarizing stimuli evoked release with differing probabilities but the same size vesicle pool. Enhancing intraterminal Ca2+ spread by lowering Ca2+ buffering or applying BayK8644 did not increase PSCs evoked with strong test steps showing there is a fixed upper limit to pool size. Together, these results suggest that light-evoked changes in cone membrane potential alter synaptic release solely by changing release probability. PMID:26541100

Intermittent high-dose ethanol exposures increase motivation for operant ethanol self-administration: possible neurochemical mechanism.

PubMed

Li, Zhimin; Zharikova, Alevtina; Vaughan, Cheryl H; Bastian, Jaime; Zandy, Shannon; Esperon, Leonardo; Axman, Elyssia; Rowland, Neil E; Peris, Joanna

2010-01-15

We investigated the neurochemical mechanism of how high-dose ethanol exposure may increase motivation for ethanol consumption. First, we developed an animal model of increased motivation for ethanol using a progressive ratio (PR) schedule. Sprague-Dawley rats were trained to administer 10% ethanol-containing gelatin or plain gelatin (on alternate weeks) in daily 30-min sessions under different fixed ratio (FR) and PR schedules. During FR schedules, rats self-administered about 1 g/kg ethanol, which was decreased to 0.4+/-0.03 g/kg under PR10. Rats then received four pairs of either 3 g/kg ethanol or saline injections during the weeks when the reinforcer was plain gelatin. During subsequent ethanol gel sessions, breakpoints and ethanol consumption rose 40% in the high-dose ethanol group by the fourth set of injections with no change in plain gel responding. Alterations in amino acids in the ventral striatum (VS) during PR10 responding for 10% ethanol gelatin and plain gelatin were measured using microdialysis sampling coupled with capillary electrophoresis and laser-induced fluorescence detection. There was greater release of taurine, glycine and glutamate in the NAC of the high-dose ethanol rats during 10% ethanol-containing gelatin responding, compared to the control rats or during plain gel responding. An increase in the release of glycine in this same brain region has recently been shown to be involved with anticipation of a reward. Thus, it appears that intermittent high-dose ethanol exposure not only increases motivation for ethanol responding but may also change neurotransmitter release that mediates anticipation of reinforcement, which may play a key role in the development of alcoholism. Copyright 2009 Elsevier B.V. All rights reserved.

Specific heat of new perovskite-type cobaltates Pr{sub 1-x}Nd{sub x}CoO{sub 3}

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

Thakur, Rasna, E-mail: rasnarishu@gmail.com; Thakur, Rajesh K.; Gaur, N. K.

2016-05-23

Specific heat and Bulk modulus (B) of new perovskite-type cobaltates Pr{sub 1-x}Nd{sub x}CoO{sub 3} has been studied by means of a Modified Rigid Ion Model (MRIM) and Atoms in Molecules (AIM) theory in a wide temperature range (1 K ≤ T ≤1000 K). The effect of Nd doping on the elastic, cohesive and thermal properties of PrCoO{sub 3} have been studied probably for the first time by an atomistic approach. The computed results are in good agreement with the available experimental data.

Some New Approaches to Multivariate Probability Distributions.

DTIC Science & Technology

1986-12-01

Krishnaiah (1977). The following example may serve as an illustration of this point. EXAMPLE 2. (Fre^*chet’s bivariate continuous distribution...the error in the theorem of "" Prakasa Rao (1974) and to Dr. P.R. Krishnaiah for his valuable comments on the initial draft, his monumental patience and...M. and Proschan, F. (1984). Nonparametric Concepts and Methods in Reliability, Handbook of Statistics, 4, 613-655, (eds. P.R. Krishnaiah and P.K

Analysis of nucleic acid chaperoning by the prion protein and its inhibition by oligonucleotides

PubMed Central

Guichard, Cécile; Ivanyi-Nagy, Roland; Sharma, Kamal Kant; Gabus, Caroline; Marc, Daniel; Mély, Yves; Darlix, Jean-Luc

2011-01-01

Prion diseases are unique neurodegenerative illnesses associated with the conversion of the cellular prion protein (PrPC) into the aggregated misfolded scrapie isoform, named PrPSc. Recent studies on the physiological role of PrPC revealed that this protein has probably multiple functions, notably in cell–cell adhesion and signal transduction, and in assisting nucleic acid folding. In fact, in vitro findings indicated that the human PrP (huPrP) possesses nucleic acid binding and annealing activities, similarly to nucleic acid chaperone proteins that play essential roles in cellular DNA and RNA metabolism. Here, we show that a peptide, representing the N-terminal domain of huPrP, facilitates nucleic acid annealing by two parallel pathways nucleated through the stem termini. We also show that PrP of human or ovine origin facilitates DNA strand exchange, ribozyme-directed cleavage of an RNA template and RNA trans-splicing in a manner similar to the nucleocapsid protein of HIV-1. In an attempt to characterize inhibitors of PrP-chaperoning in vitro we discovered that the thioaptamer 5′-GACACAAGCCGA-3′ was extensively inhibiting the PrP chaperoning activities. At the same time a recently characterized methylated oligoribonucleotide inhibiting the chaperoning activity of the HIV-1 nucleocapsid protein was poorly impairing the PrP chaperoning activities. PMID:21737432

The thermodynamics of Pr55Gag-RNA interaction regulate the assembly of HIV

PubMed Central

Waddington, Lynne; Hijnen, Marcel; Velkov, Tony; McKinstry, William J.

2017-01-01

The interactions that occur during HIV Pr55Gag oligomerization and genomic RNA packaging are essential elements that facilitate HIV assembly. However, mechanistic details of these interactions are not clearly defined. Here, we overcome previous limitations in producing large quantities of full-length recombinant Pr55Gag that is required for isothermal titration calorimetry (ITC) studies, and we have revealed the thermodynamic properties of HIV assembly for the first time. Thermodynamic analysis showed that the binding between RNA and HIV Pr55Gag is an energetically favourable reaction (ΔG<0) that is further enhanced by the oligomerization of Pr55Gag. The change in enthalpy (ΔH) widens sequentially from: (1) Pr55Gag-Psi RNA binding during HIV genome selection; to (2) Pr55Gag-Guanosine Uridine (GU)-containing RNA binding in cytoplasm/plasma membrane; and then to (3) Pr55Gag-Adenosine(A)-containing RNA binding in immature HIV. These data imply the stepwise increments of heat being released during HIV biogenesis may help to facilitate the process of viral assembly. By mimicking the interactions between A-containing RNA and oligomeric Pr55Gag in immature HIV, it was noted that a p6 domain truncated Pr50Gag Δp6 is less efficient than full-length Pr55Gag in this thermodynamic process. These data suggest a potential unknown role of p6 in Pr55Gag-Pr55Gag oligomerization and/or Pr55Gag-RNA interaction during HIV assembly. Our data provide direct evidence on how nucleic acid sequences and the oligomeric state of Pr55Gag regulate HIV assembly. PMID:28222188

Poly-L-arginine synergizes with oligodeoxynucleotides containing CpG-motifs (CpG-ODN) for enhanced and prolonged immune responses and prevents the CpG-ODN-induced systemic release of pro-inflammatory cytokines.

PubMed

Lingnau, Karen; Egyed, Alena; Schellack, Carola; Mattner, Frank; Buschle, Michael; Schmidt, Walter

2002-10-04

This study describes an entirely synthetic vaccine composed of antigenic peptides (T cell epitopes), oligodeoxynucleotides containing CpG-motifs (CpG-ODN) and poly-L-arginine (pR). CpG-ODN are known to be potent inducers of predominantly type 1-like immune responses, while polycationic amino acids, like pR, facilitate the uptake of antigens into antigen presenting cells (APCs). We demonstrate that the application of peptides and pR/CpG-ODN results in strongly enhanced peptide-specific immune responses as compared to the application of peptides with either of the immunomodulators alone. High numbers of antigen-specific T cells can be observed even after only one injection of the vaccine for a remarkably long period of time (at least 372 days). Furthermore, the potentially harmful systemic release of pro-inflammatory cytokines induced upon injection of CpG-ODN is inhibited. Thus, the combined application of CpG-ODN and pR may represent a novel vaccine strategy in humans.

Interactions between inflammatory signals and the progesterone receptor in regulating gene expression in pregnant human uterine myocytes

PubMed Central

Lee, Yun; Sooranna, Suren R; Terzidou, Vasso; Christian, Mark; Brosens, Jan; Huhtinen, Kaisa; Poutanen, Matti; Barton, Geraint; Johnson, Mark R; Bennett, Phillip R

2012-01-01

The absence of a fall in circulating progesterone levels has led to the concept that human labour is associated with ‘functional progesterone withdrawal’ caused through changes in the expression or function of progesterone receptor (PR). At the time of labour, the human uterus is heavily infiltrated with inflammatory cells, which release cytokines to create a ‘myometrial inflammation’ via NF-κB activation. The negative interaction between NF-κB and PR, may represent a mechanism to account for ‘functional progesterone withdrawal’ at term. Conversely, PR may act to inhibit NF-κB function and so play a role in inhibition of myometrial inflammation during pregnancy. To model this inter-relationship, we have used small interfering (si) RNA-mediated knock-down of PR in human pregnant myocytes and whole genome microarray analysis to identify genes regulated through PR. We then activated myometrial inflammation using IL-1β stimulation to determine the role of PR in myometrial inflammation regulation. Through PR-knock-down, we found that PR regulates gene networks involved in myometrial quiescence and extracellular matrix integrity. Activation of myometrial inflammation was found to antagonize PR-induced gene expression, of genes normally upregulated via PR. We found that PR does not play a role in repression of pro-inflammatory gene networks induced by IL-1β and that only MMP10 was significantly regulated in opposite directions by IL-1β and PR. We conclude that progesterone acting through PR does not generally inhibit myometrial inflammation. Activation of myometrial inflammation does cause ‘functional progesterone withdrawal’ but only in the context of genes normally upregulated via PR. PMID:22435466

Prions Adhere to Soil Minerals and Remain Infectious

PubMed Central

Johnson, Christopher J; Phillips, Kristen E; Schramm, Peter T; McKenzie, Debbie; Aiken, Judd M; Pedersen, Joel A

2006-01-01

An unidentified environmental reservoir of infectivity contributes to the natural transmission of prion diseases (transmissible spongiform encephalopathies [TSEs]) in sheep, deer, and elk. Prion infectivity may enter soil environments via shedding from diseased animals and decomposition of infected carcasses. Burial of TSE-infected cattle, sheep, and deer as a means of disposal has resulted in unintentional introduction of prions into subsurface environments. We examined the potential for soil to serve as a TSE reservoir by studying the interaction of the disease-associated prion protein (PrPSc) with common soil minerals. In this study, we demonstrated substantial PrPSc adsorption to two clay minerals, quartz, and four whole soil samples. We quantified the PrPSc-binding capacities of each mineral. Furthermore, we observed that PrPSc desorbed from montmorillonite clay was cleaved at an N-terminal site and the interaction between PrPSc and Mte was strong, making desorption of the protein difficult. Despite cleavage and avid binding, PrPSc bound to Mte remained infectious. Results from our study suggest that PrPSc released into soil environments may be preserved in a bioavailable form, perpetuating prion disease epizootics and exposing other species to the infectious agent. PMID:16617377

PrEP implementation in the Asia-Pacific region: opportunities, implementation and barriers

PubMed Central

Zablotska, Iryna; Grulich, Andrew E; Phanuphak, Nittaya; Anand, Tarandeep; Janyam, Surang; Poonkasetwattana, Midnight; Baggaley, Rachel; van Griensven, Frits; Lo, Ying-Ru

2016-01-01

Introduction HIV epidemics in the Asia-Pacific region are concentrated among men who have sex with men (MSM) and other key populations. Pre-exposure prophylaxis (PrEP) is an effective HIV prevention intervention and could be a potential game changer in the region. We discuss the progress towards PrEP implementation in the Asia-Pacific region, including opportunities and barriers. Discussion Awareness about PrEP in the Asia-Pacific is still low and so are its levels of use. A high proportion of MSM who are aware of PrEP are willing to use it. Key PrEP implementation barriers include poor knowledge about PrEP, limited access to PrEP, weak or non-existent HIV prevention programmes for MSM and other key populations, high cost of PrEP, stigma and discrimination against key populations and restrictive laws in some countries. Only several clinical trials, demonstration projects and a few larger-scale implementation studies have been implemented so far in Thailand and Australia. However, novel approaches to PrEP implementation have emerged: researcher-, facility- and community-led models of care, with PrEP services for fee and for free. The WHO consolidated guidelines on HIV testing, treatment and prevention call for an expanded access to PrEP worldwide and have provided guidance on PrEP implementation in the region. Some countries like Australia have released national PrEP guidelines. There are growing community leadership and consultation processes to initiate PrEP implementation in Asia and the Pacific. Conclusions Countries of the Asia-Pacific region will benefit from adding PrEP to their HIV prevention packages, but for many this is a critical step that requires resourcing. Having an impact on the HIV epidemic requires investment. The next years should see the region transitioning from limited PrEP implementation projects to growing access to PrEP and expansion of HIV prevention programmes. PMID:27760688

PrEP implementation in the Asia-Pacific region: opportunities, implementation and barriers.

PubMed

Zablotska, Iryna; Grulich, Andrew E; Phanuphak, Nittaya; Anand, Tarandeep; Janyam, Surang; Poonkasetwattana, Midnight; Baggaley, Rachel; van Griensven, Frits; Lo, Ying-Ru

2016-01-01

HIV epidemics in the Asia-Pacific region are concentrated among men who have sex with men (MSM) and other key populations. Pre-exposure prophylaxis (PrEP) is an effective HIV prevention intervention and could be a potential game changer in the region. We discuss the progress towards PrEP implementation in the Asia-Pacific region, including opportunities and barriers. Awareness about PrEP in the Asia-Pacific is still low and so are its levels of use. A high proportion of MSM who are aware of PrEP are willing to use it. Key PrEP implementation barriers include poor knowledge about PrEP, limited access to PrEP, weak or non-existent HIV prevention programmes for MSM and other key populations, high cost of PrEP, stigma and discrimination against key populations and restrictive laws in some countries. Only several clinical trials, demonstration projects and a few larger-scale implementation studies have been implemented so far in Thailand and Australia. However, novel approaches to PrEP implementation have emerged: researcher-, facility- and community-led models of care, with PrEP services for fee and for free. The WHO consolidated guidelines on HIV testing, treatment and prevention call for an expanded access to PrEP worldwide and have provided guidance on PrEP implementation in the region. Some countries like Australia have released national PrEP guidelines. There are growing community leadership and consultation processes to initiate PrEP implementation in Asia and the Pacific. Countries of the Asia-Pacific region will benefit from adding PrEP to their HIV prevention packages, but for many this is a critical step that requires resourcing. Having an impact on the HIV epidemic requires investment. The next years should see the region transitioning from limited PrEP implementation projects to growing access to PrEP and expansion of HIV prevention programmes.

Evaluating release alternatives for a long-lived bird species under uncertainty about long-term demographic rates

USGS Publications Warehouse

Moore, Clinton T.; Converse, Sarah J.; Folk, Martin J.; Runge, Michael C.; Nesbitt, Stephen A.

2012-01-01

The release of animals to reestablish an extirpated population is a decision problem that is often attended by considerable uncertainty about the probability of success. Annual releases of captive-reared juvenile Whooping Cranes (Grus americana) were begun in 1993 in central Florida, USA, to establish a breeding, non-migratory population. Over a 12-year period, 286 birds were released, but by 2004, the introduced flock had produced only four wild-fledged birds. Consequently, releases were halted over managers' concerns about the performance of the released flock and uncertainty about the efficacy of further releases. We used data on marked, released birds to develop predictive models for addressing whether releases should be resumed, and if so, under what schedule. To examine the outcome of different release scenarios, we simulated the survival and productivity of individual female birds under a baseline model that recognized age and breeding-class structure and which incorporated empirically estimated stochastic elements. As data on wild-fledged birds from captive-reared parents were sparse, a key uncertainty that confronts release decision-making is whether captive-reared birds and their offspring share the same vital rates. Therefore, we used data on the only population of wild Whooping Cranes in existence to construct two alternatives to the baseline model. The probability of population persistence was highly sensitive to the choice of these three models. Under the baseline model, extirpation of the population was nearly certain under any scenario of resumed releases. In contrast, the model based on estimates from wild birds projected a high probability of persistence under any release scenario, including cessation of releases. Therefore, belief in either of these models suggests that further releases are an ineffective use of resources. In the third model, which simulated a population Allee effect, population persistence was sensitive to the release decision: high persistence probability was achieved only through the release of more birds, whereas extirpation was highly probable with cessation of releases. Despite substantial investment of time and effort in the release program, evidence collected to date does not favor one model over another; therefore, any decision about further releases must be made under considerable biological uncertainty. However, given an assignment of credibility weight to each model, a best, informed decision about releases can be made under uncertainty. Furthermore, if managers can periodically revisit the release decision and collect monitoring data to further inform the models, then managers have a basis for confronting uncertainty and adaptively managing releases through time.

[Compliancy of pre-exposure prophylaxis for HIV infection in men who have sex with men in Chengdu].

PubMed

Xu, J Y; Mou, Y C; Ma, Y L; Zhang, J Y

2017-05-10

Objective: To evaluate the compliancy of HIV pre-exposure prophylaxis (PrEP) in men who have sex with men (MSM) in Chengdu, Sichuan province, and explore the influencing factors. Methods: From 1 July 2013 to 30 September 2015, a random, open, multi-center and parallel control intervention study was conducted in 328 MSM enrolled by non-probability sampling in Chengdu. The MSM were divided into 3 groups randomly, i.e. daily group, intermittent group (before and after exposure) and control group. Clinical follow-up and questionnaire survey were carried out every 3 months. Their PrEP compliances were evaluated respectively and multivariate logistic regression analysis was conducted to identify the related factors. Results: A total of 141 MSM were surveyed, in whom 59(41.8 % ) had good PrEP compliancy. The PrEP compliancy rate was 69.0 % in daily group, higher than that in intermittent group (14.3 % ), the difference had significance ( χ (2)=45.29, P <0.001). Multivariate logistic analysis indicated that type of PrEP was the influencing factors of PrEP compliancy. Compared with daily group, the intermittent group had worse PrEP compliancy ( OR =0.07, 95 %CI : 0.03-0.16). Conclusion: The PrEP compliance of the MSM in this study was poor, the compliancy would be influenced by the type of PrEP.

Enhanced susceptibility of Prnp-deficient mice to kainate-induced seizures, neuronal apoptosis, and death: Role of AMPA/kainate receptors.

PubMed

Rangel, Alejandra; Burgaya, Ferran; Gavín, Rosalina; Soriano, Eduardo; Aguzzi, Adriano; Del Río, José A

2007-09-01

Normal physiologic functions of the cellular prion protein (PrPc) are still elusive. This GPI-anchored protein exerts many functions, including roles in neuron proliferation, neuroprotection or redox homeostasis. There are, however, conflicting data concerning its role in synaptic transmission. Although several studies report that PrPc participates in NMDA-mediated neurotransmission, parallel studies describe normal behavior of PrPc-mutant mice. Abnormal axon connections have been described in the dentate gyrus of the hippocampi of PrPc-deficient mice similar to those observed in epilepsy. A study indicates increased susceptibility to kainate (KA) in these mutant mice. We extend the observation of these studies by means of several histologic and biochemical analyses of KA-treated mice. PrPc-deficient mice showed increased sensitivity to KA-induced seizures in vivo and in vitro in organotypic slices. In addition, we show that this sensitivity is cell-specific because interference experiments to abolish PrPc expression increased susceptibility to KA in PrPc-expressing cells. We indicate a correlation of susceptibility to KA in cells lacking PrPc with the differential expression of GluR6 and GluR7 KA receptor subunits using real-time RT-PCR methods. These results indicate that PrPc exerts a neuroprotective role against KA-induced neurotoxicity, probably by regulating the expression of KA receptor subunits. (c) 2007 Wiley-Liss, Inc.

Transport of the Pathogenic Prion Protein through Landfill Materials

PubMed Central

Jacobson, Kurt H.; Lee, Seunghak; McKenzie, Debbie; Benson, Craig H.; Pedersen, Joel A.

2009-01-01

Transmissible spongiform encephalopathies (TSEs, prion diseases) are a class of fatal neurodegenerative diseases affecting a variety of mammalian species including humans. A misfolded form of the prion protein (PrPTSE) is the major, if not sole, component of the infectious agent. Recent TSE outbreaks in domesticated and wild animal populations has created the need for safe and effective disposal of large quantities of potentially infected materials. Here, we report the results of a study to evaluate the potential for transport of PrPTSE derived from carcasses and associated wastes in a municipal solid waste (MSW) landfill. Column experiments were conducted to evaluate PrPTSE transport in quartz sand, two fine-textured burial soils currently used in landfill practice, a green waste residual material (a potential burial material), and fresh and aged MSW. PrPTSE was retained by quartz sand and the fine-textured burial soils, with no detectable PrPTSE eluted over more than 40 pore volumes. In contrast, PrPTSE was more mobile in MSW and green waste residual. Transport parameters were estimated from the experimental data and used to model PrPTSE migration in a MSW landfill. To the extent that the PrPTSE used mimics that released from decomposing carcasses, burial of CWD-infected materials at MSW landfills could provide secure containment of PrPTSE provided reasonable burial strategies (e.g., encasement in soil) are used. PMID:19368208

Empirical estimation of the conditional probability of natech events within the United States.

PubMed

Santella, Nicholas; Steinberg, Laura J; Aguirra, Gloria Andrea

2011-06-01

Natural disasters are the cause of a sizeable number of hazmat releases, referred to as "natechs." An enhanced understanding of natech probability, allowing for predictions of natech occurrence, is an important step in determining how industry and government should mitigate natech risk. This study quantifies the conditional probabilities of natechs at TRI/RMP and SICS 1311 facilities given the occurrence of hurricanes, earthquakes, tornadoes, and floods. During hurricanes, a higher probability of releases was observed due to storm surge (7.3 releases per 100 TRI/RMP facilities exposed vs. 6.2 for SIC 1311) compared to category 1-2 hurricane winds (5.6 TRI, 2.6 SIC 1311). Logistic regression confirms the statistical significance of the greater propensity for releases at RMP/TRI facilities, and during some hurricanes, when controlling for hazard zone. The probability of natechs at TRI/RMP facilities during earthquakes increased from 0.1 releases per 100 facilities at MMI V to 21.4 at MMI IX. The probability of a natech at TRI/RMP facilities within 25 miles of a tornado was small (∼0.025 per 100 facilities), reflecting the limited area directly affected by tornadoes. Areas inundated during flood events had a probability of 1.1 releases per 100 facilities but demonstrated widely varying natech occurrence during individual events, indicating that factors not quantified in this study such as flood depth and speed are important for predicting flood natechs. These results can inform natech risk analysis, aid government agencies responsible for planning response and remediation after natural disasters, and should be useful in raising awareness of natech risk within industry. © 2011 Society for Risk Analysis.

[The concept of risk and its estimation].

PubMed

Zocchetti, C; Della Foglia, M; Colombi, A

1996-01-01

The concept of risk, in relation to human health, is a topic of primary interest for occupational health professionals. A new legislation recently established in Italy (626/94) according to European Community directives in the field of Preventive Medicine, called attention to this topic, and in particular to risk assessment and evaluation. Motivated by this context and by the impression that the concept of risk is frequently misunderstood, the present paper has two aims: the identification of the different meanings of the term "risk" in the new Italian legislation and the critical discussion of some commonly used definitions; and the proposal of a general definition, with the specification of a mathematical expression for quantitative risk estimation. The term risk (and risk estimation, assessment, or evaluation) has mainly referred to three different contexts: hazard identification, exposure assessment, and adverse health effects occurrence. Unfortunately, there are contexts in the legislation in which it is difficult to identify the true meaning of the term. This might cause equivocal interpretations and erroneous applications of the law because hazard evaluation, exposure assessment, and adverse health effects identification are completely different topics that require integrated but distinct approaches to risk management. As far as a quantitative definition of risk is of concern, we suggest an algorithm which connects the three basic risk elements (hazard, exposure, adverse health effects) by means of their probabilities of occurrence: the probability of being exposed (to a definite dose) given that a specific hazard is present (Pr(e[symbol: see text]p)), and the probability of occurrence of an adverse health effect as a consequence of that exposure (Pr(d[symbol: see text]e)). Using these quantitative components, risk can be defined as a sequence of measurable events that starts with hazard identification and terminates with disease occurrence; therefore, the following formal definition of risk is proposed: the probability of occurrence, in a given period of time, of an adverse health effect as a consequence of the existence of an hazard. In formula: R(d[symbol: see text]p) = Pr(e[symbol: see text]p) x Pr(d[symbol: see text]e). While Pr(e[symbol: see text]p) (exposure given hazard) must be evaluated in the situation under study, two alternatives exist for the estimation of the occurrence of adverse health effects (Pr(d[symbol: see text]e)): a "direct" estimation of the damage (Pr(d[symbol: see text]e) through formal epidemiologic studies conducted in the situation under observation; and an "indirect" estimation of Pr(d[symbol: see text]e) using information taken from the scientific literature (epidemiologic evaluations, dose-response relationships, extrapolations, ...). Both conditions are presented along with their respective advantages, disadvantages, and uncertainties. The usefulness of the proposed algorithm is discussed with respect to commonly used applications of risk assessment in occupational medicine; the relevance of time for risk estimation (both in the term of duration of observation, duration of exposure, and latency of effect) is briefly explained; and how the proposed algorithm takes into account (in terms of prevention and public health) both the etiologic relevance of the exposure and the consequences of exposure removal is highlighted. As a last comment, it is suggested that the diffuse application of good work practices (technical, behavioral, organizational, ...), or the exhaustive use of check lists, can be relevant in terms of improvement of prevention efficacy, but does not represent any quantitative procedure of risk assessment which, in any circumstance, must be considered the elective approach to adverse health effect prevention.

Signal transduction in neurons: effects of cellular prion protein on fyn kinase and ERK1/2 kinase.

PubMed

Tomasi, Vittorio

2010-12-16

It has been reported that cellular prion protein (PrPc) co-localizes with caveolin-1 and participates to signal transduction events by recruiting Fyn kinase. As PrPc is a secreted protein anchored to the outer surface membrane through a glycosylphosphatidylinositol (GPI) anchor (secPrP) and caveolin-1 is located in the inner leaflet of plasma membrane, there is a problem of how the two proteins can physically interact each other and transduce signals. By using the GST-fusion proteins system we observed that PrPc strongly interacts with caveolin-1 scaffolding domain and with a caveolin-1 hydrophilic C-terminal region, but not with the caveolin-1 N-terminal region. In vitro binding experiments were also performed to define the site(s) of PrPc interacting with cav-1. The results are consistent with a participation of PrPc octapeptide repeats motif in the binding to caveolin-1 scaffolding domain. The caveolar localization of PrPc was ascertained by co-immunoprecipitation, by co-localization after flotation in density gradients and by confocal microscopy analysis of PrPc and caveolin-1 distributions in a neuronal cell line (GN11) expressing caveolin-1 at high levels. We observed that, after antibody-mediated cross-linking or copper treatment, PrPc was internalized probably into caveolae. We propose that following translocation from rafts to caveolae or caveolae-like domains, secPrP could interact with caveolin-1 and induce signal transduction events.

Sodium molybdate prevents hypertension and vascular prostanoid imbalance in fructose-overloaded rats.

PubMed

Peredo, H A; Andrade, V; Donoso, A S; Lee, H J; Puyó, A M

2013-10-01

(1) Fructose (F) overload produces elevated blood pressure (BP), hyperglycaemia, hypertriglyceridemia and insulin resistance, resembling human metabolic syndrome. Previously, we found altered vascular prostanoid (PR) production in this model. (2) Sodium molybdate (Mo), as well as sodium tungstate, causes insulin-like effects and normalizes plasma glucose levels in streptozotocin-treated diabetic rats. We studied the effects of Mo on BP, metabolic parameters and release of PR from the mesenteric vascular bed (MVB) in F-overloaded rats. (3) Four groups of male Sprague-Dawley rats were analysed: Control, tap water to drink; F, F solution 10% W/V to drink; CMo, Mo 100 mg kg day(-1) and FMo, both treatments. After 9 weeks, the animals were killed and MVBs removed and the released PRs measured. (4) F increased BP, glycemia, triglyceridemia and insulinemia. Mo treatment prevented the increases in BP and glycemia, but did not modify triglyceridemia or insulinemia. In addition, Mo decreased BP in controls. (5) Prostaglandins (PG) F2 alpha and E2, PG 6-ketoF1 alpha and thromboxane (TX) B2 , as well as inactive metabolites of prostacyclin (PGI2 ) and TXA2 were detected. F decreased the production of vasodilator PRs PGI2 and PGE2 in MVB. Mo prevented these alterations and increased PGE2 in controls. Vasoconstrict or PRs PGF2 alpha and TXA2 release was not modified. (6) Mo treatment, beyond its known lowering effect on glycemia, prevents the reduction in the vascular release of vasodilator PR observed in this model. This could be one of the mechanisms by which Mo avoids the increase in BP caused by F overload in the rat. © 2013 John Wiley & Sons Ltd.

HIV providers' likelihood to prescribe pre-exposure prophylaxis (PrEP) for HIV prevention differs by patient type: a short report.

PubMed

Adams, Leah M; Balderson, Benjamin H

2016-09-01

Pre-exposure prophylaxis (PrEP), the antiretroviral treatment regimen for HIV-negative people at high risk of acquiring HIV, has demonstrated efficacy across clinical trials in several patient populations. The Centers for Disease Control (CDC) have released detailed guidelines to aid providers in prescribing PrEP for their high-risk patients, including men who have sex with men (MSM), high-risk heterosexuals, and injection drug users (IDUs). Given that much attention in PrEP has focused on MSM patients, the present study used an online survey to assess factors involved in HIV care providers' (n = 363) decisions about prescribing PrEP, along with their willingness to prescribe PrEP to patients from various risk populations (e.g., MSM, heterosexuals, IDUs). The efficacy of PrEP was an important factor in providers' decisions about prescribing PrEP, as were considerations about patients' adherence to the regimen, regular follow-up for care, and medication costs. This survey's findings also suggest that providers' willingness to prescribe PrEP varies by patient group, with providers most willing to initiate the regimen with MSM who have an HIV-positive partner, and least willing to prescribe to high-risk heterosexuals or IDUs. In the context of the current CDC recommendations for PrEP that include MSM, heterosexuals, and IDUs, examining providers' rationales for and barriers against supporting this HIV prevention strategy across patient groups merits further attention.

Generation of Infectious Prions and Detection with the Prion-Infected Cell Assay.

PubMed

Vella, Laura J; Coleman, Bradley; Hill, Andrew F

2017-01-01

Cell lines propagating prions are an efficient and useful means for studying the cellular and molecular mechanisms implicated in prion disease. Utilization of cell-based models has led to the finding that PrP C and PrP Sc are released from cells in association with extracellular vesicles known as exosomes. Exosomes have been shown to act as vehicles for infectivity, transferring infectivity between cell lines and providing a mechanism for prion spread between tissues. Here, we describe the methods for generating a prion-propagating cell line with prion-infected brain homogenate, cell lysate, conditioned media, and exosomes and also detection of protease-resistant PrP with the prion-infected cell assay.

Activity-dependent regulation of release probability at excitatory hippocampal synapses: a crucial role of FMRP in neurotransmission

PubMed Central

Wang, Xiao-Sheng; Peng, Chun-Zi; Cai, Wei-Jun; Xia, Jian; Jin, Daozhong; Dai, Yuqiao; Luo, Xue-Gang; Klyachko, Vitaly A.; Deng, Pan-Yue

2014-01-01

Transcriptional silencing of the Fmr1 gene encoding fragile X mental retardation protein (FMRP) causes Fragile X Syndrome (FXS), the most common form of inherited intellectual disability and the leading genetic cause of autism. FMRP has been suggested to play important roles in regulating neurotransmission and short-term synaptic plasticity at excitatory hippocampal and cortical synapses. However, the origins and the mechanisms of these FMRP actions remain incompletely understood, and the role of FMRP in regulating synaptic release probability and presynaptic function remains debated. Here we used variance-mean analysis and peak scaled nonstationary variance analysis to examine changes in both pre- and postsynaptic parameters during repetitive activity at excitatory CA3-CA1 hippocampal synapses in a mouse model of FXS. Our analyses revealed that loss of FMRP did not affect the basal release probability or basal synaptic transmission, but caused an abnormally elevated release probability specifically during repetitive activity. These abnormalities were not accompanied by changes in EPSC kinetics, quantal size or postsynaptic AMPA receptor conductance. Our results thus indicate that FMRP regulates neurotransmission at excitatory hippocampal synapses specifically during repetitive activity via modulation of release probability in a presynaptic manner. Our study suggests that FMRP function in regulating neurotransmitter release is an activity-dependent phenomenon that may contribute to the pathophysiology of FXS. PMID:24646437

When maths trumps logic: probabilistic judgements in chimpanzees.

PubMed

Hanus, Daniel; Call, Josep

2014-12-01

When searching for hidden food, do chimpanzees take into account both the number of hidden items and the number of potential hiding locations? We presented chimpanzees with two trays, each of them containing a different food/cup ratio and therefore a different likelihood of finding a baited cup among empty alternatives. Subjects' performance was directly influenced by the relative difference (probability ratio (PR)) between the two given probabilities. Interestingly, however, they did not appreciate the special value of a truly safe option (with P = 1.0). Instead, they seemed to 'blindly' rely on the PR between the two options, systematically preferring the more likely one once a certain threshold had been reached. A control condition ruled out the possibility of low-level learning explanations for the observed performance. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Formation of M-Like Intermediates in Proteorhodopsin in Alkali Solutions (pH ≥ ∼8.5) Where the Proton Release Occurs First in Contrast to the Sequence at Lower pH.

PubMed

Tamogami, Jun; Sato, Keitaro; Kurokawa, Sukuna; Yamada, Takumi; Nara, Toshifumi; Demura, Makoto; Miyauchi, Seiji; Kikukawa, Takashi; Muneyuki, Eiro; Kamo, Naoki

2016-02-23

Proteorhodopsin (PR) is an outward light-driven proton pump observed in marine eubacteria. Despite many structural and functional similarities to bacteriorhodopsin (BR) in archaea, which also acts as an outward proton pump, the mechanism of the photoinduced proton release and uptake is different between two H(+)-pumps. In this study, we investigated the pH dependence of the photocycle and proton transfer in PR reconstituted with the phospholipid membrane under alkaline conditions. Under these conditions, as the medium pH increased, a blue-shifted photoproduct (defined as Ma), which is different from M, with a pKa of ca. 9.2 was produced. The sequence of the photoinduced proton uptake and release during the photocycle was inverted with the increase in pH. A pKa value of ca. 9.5 was estimated for this inversion and was in good agreement with the pKa value of the formation of Ma (∼ 9.2). In addition, we measured the photoelectric current generated by PRs attached to a thin polymer film at varying pH. Interestingly, increases in the medium pH evoked bidirectional photocurrents, which may imply a possible reversal of the direction of the proton movement at alkaline pH. On the basis of these findings, a putative photocycle and proton transfer scheme in PR under alkaline pH conditions was proposed.

Highly potent metallopeptide analogues of luteinizing hormone-releasing hormone.

PubMed Central

Bajusz, S; Janaky, T; Csernus, V J; Bokser, L; Fekete, M; Srkalovic, G; Redding, T W; Schally, A V

1989-01-01

Metal complexes related to the cytotoxic complexes cisplatin [cis-diamminedichloroplatinum(II)] and transbis(salicylaldoximato)copper(II) were incorporated into suitably modified luteinizing hormone-releasing hormone (LH-RH) analogues containing D-lysine at position 6. Some of the metallopeptides thus obtained proved to be highly active LH-RH agonists or antagonists. For instance, SB-40, a PtCl2-containing metallopeptide in which platinum is coordinated to an N epsilon-(DL-2,3-diaminopropionyl)-D-lysine residue [D-Lys(DL-A2pr] at position 6, showed 50 times higher LH-releasing potency than the native hormone. SB-95, [Ac-D-Nal(2)1,D-Phe(pCl)2, D-Pal(3)2, Arg5,D-Lys[DL-A2pr(Sal2Cu)]6,D-Ala10]LH-RH, where Nal(2) is 3-(2-naphthyl)alanine, Pal(3) is 3-(3-pyridyl)alanine, and copper(II) is coordinated to the salicylideneimino moieties resulting from condensation of salicylaldehyde with D-Lys(DL-A2pr)6, caused 100% inhibition of ovulation at a dose of 3 micrograms in rats. Most metallopeptide analogues of LH-RH showed high affinities for the membrane receptors of rat pituitary and human breast cancer cells. Some of these metallopeptides had cytotoxic activity against human breast cancer and prostate cancer cell lines in vitro (this will be the subject of a separate paper on cytotoxicity evaluation). Such cytostatic metallopeptides could be envisioned as targeted chemotherapeutic agents in cancers that contain receptors for LH-RH-like peptides. PMID:2548206

Highly potent metallopeptide analogues of luteinizing hormone-releasing hormone.

PubMed

Bajusz, S; Janaky, T; Csernus, V J; Bokser, L; Fekete, M; Srkalovic, G; Redding, T W; Schally, A V

1989-08-01

Metal complexes related to the cytotoxic complexes cisplatin [cis-diamminedichloroplatinum(II)] and transbis(salicylaldoximato)copper(II) were incorporated into suitably modified luteinizing hormone-releasing hormone (LH-RH) analogues containing D-lysine at position 6. Some of the metallopeptides thus obtained proved to be highly active LH-RH agonists or antagonists. For instance, SB-40, a PtCl2-containing metallopeptide in which platinum is coordinated to an N epsilon-(DL-2,3-diaminopropionyl)-D-lysine residue [D-Lys(DL-A2pr] at position 6, showed 50 times higher LH-releasing potency than the native hormone. SB-95, [Ac-D-Nal(2)1,D-Phe(pCl)2, D-Pal(3)2, Arg5,D-Lys[DL-A2pr(Sal2Cu)]6,D-Ala10]LH-RH, where Nal(2) is 3-(2-naphthyl)alanine, Pal(3) is 3-(3-pyridyl)alanine, and copper(II) is coordinated to the salicylideneimino moieties resulting from condensation of salicylaldehyde with D-Lys(DL-A2pr)6, caused 100% inhibition of ovulation at a dose of 3 micrograms in rats. Most metallopeptide analogues of LH-RH showed high affinities for the membrane receptors of rat pituitary and human breast cancer cells. Some of these metallopeptides had cytotoxic activity against human breast cancer and prostate cancer cell lines in vitro (this will be the subject of a separate paper on cytotoxicity evaluation). Such cytostatic metallopeptides could be envisioned as targeted chemotherapeutic agents in cancers that contain receptors for LH-RH-like peptides.

Triggering HIV polyprotein processing by light using rapid photodegradation of a tight-binding protease inhibitor.

PubMed

Schimer, Jiří; Pávová, Marcela; Anders, Maria; Pachl, Petr; Šácha, Pavel; Cígler, Petr; Weber, Jan; Majer, Pavel; Řezáčová, Pavlína; Kräusslich, Hans-Georg; Müller, Barbara; Konvalinka, Jan

2015-03-09

HIV protease (PR) is required for proteolytic maturation in the late phase of HIV replication and represents a prime therapeutic target. The regulation and kinetics of viral polyprotein processing and maturation are currently not understood in detail. Here we design, synthesize, validate and apply a potent, photodegradable HIV PR inhibitor to achieve synchronized induction of proteolysis. The compound exhibits subnanomolar inhibition in vitro. Its photolabile moiety is released on light irradiation, reducing the inhibitory potential by 4 orders of magnitude. We determine the structure of the PR-inhibitor complex, analyze its photolytic products, and show that the enzymatic activity of inhibited PR can be fully restored on inhibitor photolysis. We also demonstrate that proteolysis of immature HIV particles produced in the presence of the inhibitor can be rapidly triggered by light enabling thus to analyze the timing, regulation and spatial requirements of viral processing in real time.

Triggering HIV polyprotein processing by light using rapid photodegradation of a tight-binding protease inhibitor

PubMed Central

Schimer, Jiří; Pávová, Marcela; Anders, Maria; Pachl, Petr; Šácha, Pavel; Cígler, Petr; Weber, Jan; Majer, Pavel; Řezáčová, Pavlína; Kräusslich, Hans-Georg; Müller, Barbara; Konvalinka, Jan

2015-01-01

HIV protease (PR) is required for proteolytic maturation in the late phase of HIV replication and represents a prime therapeutic target. The regulation and kinetics of viral polyprotein processing and maturation are currently not understood in detail. Here we design, synthesize, validate and apply a potent, photodegradable HIV PR inhibitor to achieve synchronized induction of proteolysis. The compound exhibits subnanomolar inhibition in vitro. Its photolabile moiety is released on light irradiation, reducing the inhibitory potential by 4 orders of magnitude. We determine the structure of the PR-inhibitor complex, analyze its photolytic products, and show that the enzymatic activity of inhibited PR can be fully restored on inhibitor photolysis. We also demonstrate that proteolysis of immature HIV particles produced in the presence of the inhibitor can be rapidly triggered by light enabling thus to analyze the timing, regulation and spatial requirements of viral processing in real time. PMID:25751579

Protease inhibitors-based therapy induces acquired spherocytic-like anaemia and ineffective erythropoiesis in chronic hepatitis C virus patients.

PubMed

Lupo, Francesca; Russo, Roberta; Iolascon, Achille; Ieluzzi, Donatella; Siciliano, Angela; Toniutto, Pierluigi; Matté, Alessandro; Piovesan, Sara; Raffetti, Elena; Turrini, Francesco; Dissegna, Denis; Donato, Francesco; Alberti, Alfredo; Zuliani, Valeria; Fattovich, Giovanna; De Franceschi, Lucia

2016-01-01

The addition of protease inhibitors, boceprevir (BOC) or telaprevir (TRV), to peg-interferon and ribavirin (PR) increases the incidence of anaemia in patients with chronic hepatitis C virus (HCV) infection. Although genetic variants in inosine triphosphatase (ITPA) gene have been linked to the haemolytic anaemia induced by PR, the mechanism sustaining severe anaemia during triple therapy is still unknown. This study aims to elucidate the molecular mechanisms underlying anaemia in chronic HCV patients with combined therapy. We studied 59 patients with chronic HCV genotype-1: 29 treated with TRV/PR and 30 with BOC/PR. We evaluated biochemical and haematological parameters, red cell index at baseline, 4, 12, 16 and 24 weeks of treatment; in a subgroup, we performed functional studies: osmotic fragility, red cell membrane protein separation, mass spectrometry analysis, quantification of erythroid microparticles release. IL28B and ITPA polymorphisms were also evaluated. We found early acute normochromic normocytic haemolytic anaemia (4-8 weeks) followed by a late macrocytic hypo-regenerative anaemia with inappropriate low reticulocyte count (12-24 weeks). Studies on red cells revealed: (i) presence of spherocytes; (ii) increased osmotic fragility; (iii) abnormalities in red cell membrane protein composition; (iv) reduced membrane-cytoskeleton stability; (v) increased release of erythroid microparticles. ITPA polymorphisms impacted only the early phase of anaemia. The bimodal pattern of anaemia in chronic HCV patients on triple therapy might be because of acquired spherocytic-like anaemia in the early phase, followed by hyporegenerative anaemia, most likely related to the combined effects of PR and TRV or BOC on erythropoiesis. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Impact of novel palmitoylated prolactin-releasing peptide analogs on metabolic changes in mice with diet-induced obesity

PubMed Central

Pelantová, Helena; Bugáňová, Martina; Pirník, Zdenko; Mikulášková, Barbora; Popelová, Andrea; Blechová, Miroslava; Haluzík, Martin; Železná, Blanka; Kuzma, Marek; Kuneš, Jaroslav; Maletínská, Lenka

2017-01-01

Analogs of anorexigenic neuropeptides, such as prolactin-releasing peptide (PrRP), have a potential as new anti-obesity drugs. In our previous study, palmitic acid attached to the N-terminus of PrRP enabled its central anorexigenic effects after peripheral administration. In this study, two linkers, γ-glutamic acid at Lys11 and a short, modified polyethylene glycol at the N-terminal Ser and/or Lys11, were applied for the palmitoylation of PrRP31 to improve its bioavailability. These analogs had a high affinity and activation ability to the PrRP receptor GPR10 and the neuropeptide FF2 receptor, as well as short-term anorexigenic effect similar to PrRP palmitoylated at the N-terminus. Two-week treatment with analogs that were palmitoylated through linkers to Lys11 (analogs 1 and 2), but not with analog modified both at the N-terminus and Lys11 (analog 3) decreased body and liver weights, insulin, leptin, triglyceride, cholesterol and free fatty acid plasma levels in a mouse model of diet-induced obesity. Moreover, the expression of uncoupling protein-1 was increased in brown fat suggesting an increase in energy expenditure. In addition, treatment with analogs 1 and 2 but not analog 3 significantly decreased urinary concentrations of 1-methylnicotinamide and its oxidation products N-methyl-2-pyridone-5-carboxamide and N-methyl-4-pyridone-3-carboxamide, as shown by NMR-based metabolomics. This observation confirmed the previously reported increase in nicotinamide derivatives in obesity and type 2 diabetes mellitus and the effectiveness of analogs 1 and 2 in the treatment of these disorders. PMID:28820912

Physiological stress and post-release mortality of white marlin (Kajikia albida) caught in the United States recreational fishery

PubMed Central

Schlenker, Lela S.; Latour, Robert J.; Brill, Richard W.; Graves, John E.

2016-01-01

White marlin, a highly migratory pelagic marine fish, support important commercial and recreational fisheries throughout their range in the tropical and subtropical Atlantic Ocean. More than 10 000 individuals can be caught annually in the United States recreational fishery, of which the vast majority are captured on circle hooks and released alive. The probability of post-release mortality of white marlin released from circle hooks has been documented to be <0.02, but the associated physiological stress resulting from capture and handling techniques has not been characterized despite its importance for understanding the health of released fish. We examined the physiological response of 68 white marlin caught on circle hooks in the recreational fishery and followed the fate of 22 of these fish with pop-up satellite archival tags programmed to release after 30 days. Measures of plasma sodium, chloride, glucose and lactate concentrations taken from fish that were briefly and consistently (mean = 120 s, standard deviation = 40 s) removed from the water increased with angling time, but post-release mortality was inversely related to angling time. The probability of post-release mortality was predicted by elevated plasma potassium concentrations and was more than 10 times greater than has been previously reported for white marlin caught on circle hooks that were not removed from the water. This disparity in estimates of post-release mortality suggests that removal of fish from the water for physiological sampling greatly heightens stress, disrupts homeostasis and thus increases the probability of post-release mortality. Our results demonstrate that elevated concentrations of plasma potassium predict mortality in white marlin and that the probability of post-release mortality is highly dependent on post-capture handling procedures. PMID:27293745

Physiological stress and post-release mortality of white marlin (Kajikia albida) caught in the United States recreational fishery.

PubMed

Schlenker, Lela S; Latour, Robert J; Brill, Richard W; Graves, John E

2016-01-01

White marlin, a highly migratory pelagic marine fish, support important commercial and recreational fisheries throughout their range in the tropical and subtropical Atlantic Ocean. More than 10 000 individuals can be caught annually in the United States recreational fishery, of which the vast majority are captured on circle hooks and released alive. The probability of post-release mortality of white marlin released from circle hooks has been documented to be <0.02, but the associated physiological stress resulting from capture and handling techniques has not been characterized despite its importance for understanding the health of released fish. We examined the physiological response of 68 white marlin caught on circle hooks in the recreational fishery and followed the fate of 22 of these fish with pop-up satellite archival tags programmed to release after 30 days. Measures of plasma sodium, chloride, glucose and lactate concentrations taken from fish that were briefly and consistently (mean = 120 s, standard deviation = 40 s) removed from the water increased with angling time, but post-release mortality was inversely related to angling time. The probability of post-release mortality was predicted by elevated plasma potassium concentrations and was more than 10 times greater than has been previously reported for white marlin caught on circle hooks that were not removed from the water. This disparity in estimates of post-release mortality suggests that removal of fish from the water for physiological sampling greatly heightens stress, disrupts homeostasis and thus increases the probability of post-release mortality. Our results demonstrate that elevated concentrations of plasma potassium predict mortality in white marlin and that the probability of post-release mortality is highly dependent on post-capture handling procedures.

pH-Sensitive PEGylated liposomes functionalized with a fibronectin-mimetic peptide show enhanced intracellular delivery to colon cancer cell.

PubMed

Garg, Ashish; Kokkoli, Efrosini

2011-08-01

pH-sensitive liposomes undergo rapid destabilization under mildly acidic conditions such as those found in endocytotic vesicles. Though this makes them promising drug carriers, their application is limited due to their rapid clearance from circulation by the reticulo-endothelial system. Researchers have therefore used pH-sensitive liposomes that are sterically stabilized by polyethylene glycol (PEG) molecules (stealth liposomes) on the liposome surface. The goal of this study is to bring bio-functionality to pH-sensitive PEGylated liposomes in order to facilitate their potential use as a targeted drug delivery agent. To improve the selectivity of these nanoparticles, we included a targeting moiety, PR_b which specifically recognizes and binds to integrin α(5)β(1) expressing cells. PR_b (KSSPHSRN(SG)(5)RGDSP) is a novel fibronectin-mimetic peptide sequence that mimics the cell adhesion domain of fibronectin. Integrin α(5)β(1) is expressed on several types of cancer cells, including colon cancer, and plays an important role in tumor growth and metastasis. We have thoroughly studied the release of calcein from pH-sensitive PEGylated liposomes by varying the lipid composition of the liposomes in the absence and presence of the targeting peptide, PR_b, and accounting for the first time for the effect of both pH and time (photo-bleaching effect) on the fluorescence signal of calcein. We have demonstrated that we can design PR_b-targeted pH-sensitive PEGylated liposomes, which can undergo destabilization under mildly acidic conditions and have shown that incorporating the PR_b peptide does not significantly affect the pH-sensitivity of the liposomes. PR_b-targeted pH-sensitive PEGylated liposomes bind to CT26.WT colon carcinoma cells that express integrin α(5)β(1), undergo cellular internalization, and release their load intracellularly in a short period of time as compared to other formulations. Our studies demonstrate that PR_b-functionalized pH-sensitive targeted delivery systems have the potential to deliver a payload directly to cancer cells in an efficient and specific manner.

Induction of salicylic acid-mediated defense response in perennial ryegrass against infection by Magnaporthe oryzae.

PubMed

Rahman, Alamgir; Kuldau, Gretchen A; Uddin, Wakar

2014-06-01

Incorporation of plant defense activators is an innovative approach to development of an integrated strategy for the management of turfgrass diseases. The effects of salicylic acid (SA), benzothiadiazole (BTH, chemical analog of SA), jasmonic acid (JA), and ethephon (ET, an ethylene-releasing compound) on development of gray leaf spot in perennial ryegrass (Lolium perenne L.) caused by Magnaporthe oryzae were evaluated. Gray leaf spot disease incidence and severity were significantly decreased when plants were treated prior to inoculation with SA, BTH, and partially by ET but not by JA. Accumulation of endogenous SA and elevated expression of pathogenesis-related (PR)-1, PR-3.1, and PR-5 genes were associated with inoculation of plants by M. oryzae. Treatment of plants with SA enhanced expression levels of PR-3.1 and PR-5 but did not affect the PR-1 level, whereas BTH treatment enhanced relative expression levels of all three PR genes. Microscopic observations of leaves inoculated with M. oryzae revealed higher frequencies of callose deposition at the penetration sites in SA- and BTH-treated plants compared with the control plants (treated with water). These results suggest that early and higher induction of these genes by systemic resistance inducers may provide perennial ryegrass with a substantial advantage to defend against infection by M. oryzae.

Effect of Baseline Anxiety and Depression Symptoms on Selected Outcomes Following Pulmonary Rehabilitation.

PubMed

Cullen, Kate; Talbot, Daniel; Gillmor, Julie; McGrath, Colin; OʼDonnell, Rory; Baily-Scanlan, Maria; Broderick, Julie

2017-07-01

Anxiety and depression are prevalent comorbidities in people with chronic respiratory diseases (CRDs). This study sought to quantify the influence of varying degrees of anxiety and depression on functional performance and disease impact in a population with CRDs following pulmonary rehabilitation (PR) intervention. The Hospital Anxiety and Depression Scale (HADS), the 6-Minute Walk Test (6MWT), and the Chronic Obstructive Pulmonary Disease Assessment Test (CAT) were assessed pre- and post-PR. Participants were categorized into 3 groups (None, Probable, and Present) based on their level of anxiety and depression. Functional performance and disease impact outcomes were compared pre- and post-PR. Patients consisted of a total of 134 program completers (72 males, 62 females; mean age = 67.8 years). Significant improvements in functional performance with regard to 6MWT scores were observed across all groups postintervention (P < .05). The Present group, in both the anxiety and depression domains, failed to reach a minimally clinically important difference postintervention. The Probable and Present groups achieved a significant improvement in CAT scores postintervention (P < .05). This study showed that symptoms of anxiety and depression in people with CRDs were significantly related to lower exercise tolerance levels and higher levels of disease impact. People with increased levels of anxiety and depression have the potential to significantly improve disease impact outcomes post-PR. The results demonstrated that the detection and treatment of anxiety and depression symptoms in people with CRDs are likely to be clinically important.

Cyanide detoxification in an insect herbivore: Molecular identification of β-cyanoalanine synthases from Pieris rapae.

PubMed

van Ohlen, Maike; Herfurth, Anna-Maria; Kerbstadt, Henrike; Wittstock, Ute

2016-03-01

Cyanogenic compounds occur widely in the plant kingdom. Therefore, many herbivores are adapted to the presence of these compounds in their diet by either avoiding cyanide release or by efficient cyanide detoxification mechanisms. The mechanisms of adaptation are not fully understood. Larvae of Pieris rapae (Lepidoptera: Pieridae) are specialist herbivores on glucosinolate-containing plants. They are exposed to cyanide during metabolism of phenylacetonitrile, a product of benzylglucosinolate breakdown catalyzed by plant myrosinases and larval nitrile-specifier protein (NSP) in the gut. Cyanide is metabolized to β-cyanoalanine and thiocyanate in the larvae. Here, we demonstrate that larvae of P. rapae possess β-cyanoalanine activity in their gut. We have identified three gut-expressed cDNAs designated PrBSAS1-PrBSAS3 which encode proteins with similarity to β-substituted alanine synthases (BSAS). Characterization of recombinant PrBSAS1-PrBSAS3 shows that they possess β-cyanoalanine activity. In phylogenetic trees, PrBSAS1-PrBSAS3, the first characterized insect BSAS, group together with a characterized mite β-cyanoalanine synthase and bacterial enzymes indicating a similar evolutionary history. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Comprehensive Study of Pr-Doped GdBa2Cu3O7 - y System

NASA Astrophysics Data System (ADS)

Yamani, Z.; Akhavan, M.

1997-09-01

An extensive study of the magnetic, electrical transport, and structural properties of the normal and superconducting states of Gd1 - xPrxBa2Cu3O7 - y (GdPr-123) is presented. Ceramic compounds have been synthesized by the solid state reaction technique, and characterized by XRD, SEM, TGA, and DT techniques. The parent compound GdBa2Cu3O7 - y (Gd-123) is a high-Tc superconductor and the endpoint compound, PrBa2Cu3O7 - y (Pr-123) is a magnetic insulator, both having the crystal structures isomorphic to the 123 phase structure. The superconducting transition temperature is reduced with increasing Pr content in a non-linear manner, in contrast to the Abrikosov-Gorkov pair breaking theory. A metal-insulator transition is observed at the critical Pr content, xcr 0.45, at which superconductivity completely disappears. Magnetic susceptibility measurements show that the nominal Pr valence is 3.86+, independent of the Pr content. The metal-insulator transition in this system is similar to that in the oxygen-deficient RBa2Cu3O7 - y (R-123) system. Based on this resemblance, we suggest that Pr doping reduces the carrier concentration (either by hole filling/localization or changes in the band structure) similar to the deoxygenated case. Hence, the environment surrounding the Cu-O layers is important to high-Tc superconductivity (HTSC). In this sense, HTSC cannot completely be two dimensional feature. A chain-plane correlation (CPC) effect is plausible. The normal state conduction mechanism has been interpreted by the quantum percolation theory based on localized states. Localization is probably caused by the Pr valence fluctuations in the GdPr-123 system.

Values and Preferences on the Use of Oral Pre-exposure Prophylaxis (PrEP) for HIV Prevention Among Multiple Populations: A Systematic Review of the Literature.

PubMed

Koechlin, Florence M; Fonner, Virginia A; Dalglish, Sarah L; O'Reilly, Kevin R; Baggaley, Rachel; Grant, Robert M; Rodolph, Michelle; Hodges-Mameletzis, Ioannis; Kennedy, Caitlin E

2017-05-01

Daily oral pre-exposure prophylaxis (PrEP) is the use of antiretroviral drugs by HIV-negative people to prevent HIV infection. WHO released new guidelines in 2015 recommending PrEP for all populations at substantial risk of HIV infection. To prepare these guidelines, we conducted a systematic review of values and preferences among populations that might benefit from PrEP, women, heterosexual men, young women and adolescent girls, female sex workers, serodiscordant couples, transgender people and people who inject drugs, and among healthcare providers who may prescribe PrEP. A comprehensive search strategy reviewed three electronic databases of articles and HIV-related conference abstracts (January 1990-April 2015). Data abstraction used standardised forms to categorise by population groups and relevant themes. Of 3068 citations screened, 76 peer-reviewed articles and 28 conference abstracts were included. Geographic coverage was global. Most studies (N = 78) evaluated hypothetical use of PrEP, while 26 studies included individuals who actually took PrEP or placebo. Awareness of PrEP was low, but once participants were presented with information about PrEP, the majority said they would consider using it. Concerns about safety, side effects, cost and effectiveness were the most frequently cited barriers to use. There was little indication of risk compensation. Healthcare providers would consider prescribing PrEP, but need more information before doing so. Findings from a rapidly expanding evidence base suggest that the majority of populations most likely to benefit from PrEP feel positively towards it. These same populations would benefit from overcoming current implementation challenges with the shortest possible delay.

Probabilistic Approach to Conditional Probability of Release of Hazardous Materials from Railroad Tank Cars during Accidents

DOT National Transportation Integrated Search

2009-10-13

This paper describes a probabilistic approach to estimate the conditional probability of release of hazardous materials from railroad tank cars during train accidents. Monte Carlo methods are used in developing a probabilistic model to simulate head ...

Polymyalgia rheumatica and giant cell arteritis: a 5-year epidemiologic and clinical study in Reggio Emilia, Italy.

PubMed

Salvarani, C; Macchioni, P L; Tartoni, P L; Rossi, F; Baricchi, R; Castri, C; Chiaravalloti, F; Portioli, I

1987-01-01

Among the population of Reggio Emilia, Italy, 56 patients with polymyalgia rheumatica (PR) and giant cell arteritis (GCA) were identified during the 5-year period 1981-85. The average annual incidence rates of PR and GCA were 12.8 and 8.8 respectively per 100,000 population aged 50 years or older. Forty-nine patients were followed up and the mean duration of follow-up was 32 months. All the patients received steroid therapy. We have evaluated the cumulative probability of requiring continued steroid therapy between patients with PR only, GCA only, and PR associated with GCA using life-table methods with permanent discontinuation of therapy as an end point. The different duration of steroid therapy between these 3 groups did not achieve statistical significance by the method of Lee and Desu. We identified a 5 variable discriminant function that correctly predicted whether the duration of therapy would be longer or shorter than 16 months (median duration of therapy) in 80% of our patients followed up for at least 24 months. The presence of synovitis in PR is also discussed.

The thermogenic effect of leptin is dependent on a distinct population of prolactin-releasing peptide neurons in the dorsomedial hypothalamus.

PubMed

Dodd, Garron T; Worth, Amy A; Nunn, Nicolas; Korpal, Aaron K; Bechtold, David A; Allison, Margaret B; Myers, Martin G; Statnick, Michael A; Luckman, Simon M

2014-10-07

Leptin is a critical regulator of metabolism, which acts on brain receptors (Lepr) to reduce energy intake and increase energy expenditure. Some of the cellular pathways mediating leptin's anorectic actions are identified, but those mediating the thermogenic effects have proven more difficult to decipher. We define a population of neurons in the dorsomedial hypothalamic nucleus (DMH) containing the RFamide PrRP, which is activated by leptin. Disruption of Lepr selectively in these cells blocks thermogenic responses to leptin and causes obesity. A separate population of leptin-insensitive PrRP neurons in the brainstem is required, instead, for the satiating actions of the gut-derived hormone cholecystokinin (CCK). Global deletion of PrRP (in a loxSTOPlox-PrRP mouse) results in obesity and attenuated responses to leptin and CCK. Cre-recombinase-mediated reactivation of PrRP in brainstem rescues the anorectic actions of CCK, but reactivation in the hypothalamus is required to re-establish the thermogenic effect of leptin. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Forecasting of future earthquakes in the northeast region of India considering energy released concept

NASA Astrophysics Data System (ADS)

Zarola, Amit; Sil, Arjun

2018-04-01

This study presents the forecasting of time and magnitude size of the next earthquake in the northeast India, using four probability distribution models (Gamma, Lognormal, Weibull and Log-logistic) considering updated earthquake catalog of magnitude Mw ≥ 6.0 that occurred from year 1737-2015 in the study area. On the basis of past seismicity of the region, two types of conditional probabilities have been estimated using their best fit model and respective model parameters. The first conditional probability is the probability of seismic energy (e × 1020 ergs), which is expected to release in the future earthquake, exceeding a certain level of seismic energy (E × 1020 ergs). And the second conditional probability is the probability of seismic energy (a × 1020 ergs/year), which is expected to release per year, exceeding a certain level of seismic energy per year (A × 1020 ergs/year). The logarithm likelihood functions (ln L) were also estimated for all four probability distribution models. A higher value of ln L suggests a better model and a lower value shows a worse model. The time of the future earthquake is forecasted by dividing the total seismic energy expected to release in the future earthquake with the total seismic energy expected to release per year. The epicentre of recently occurred 4 January 2016 Manipur earthquake (M 6.7), 13 April 2016 Myanmar earthquake (M 6.9) and the 24 August 2016 Myanmar earthquake (M 6.8) are located in zone Z.12, zone Z.16 and zone Z.15, respectively and that are the identified seismic source zones in the study area which show that the proposed techniques and models yield good forecasting accuracy.

Qualitative Release Assessment to Estimate the Likelihood of Henipavirus Entering the United Kingdom

PubMed Central

Snary, Emma L.; Ramnial, Vick; Breed, Andrew C.; Stephenson, Ben; Field, Hume E.; Fooks, Anthony R.

2012-01-01

The genus Henipavirus includes Hendra virus (HeV) and Nipah virus (NiV), for which fruit bats (particularly those of the genus Pteropus) are considered to be the wildlife reservoir. The recognition of henipaviruses occurring across a wider geographic and host range suggests the possibility of the virus entering the United Kingdom (UK). To estimate the likelihood of henipaviruses entering the UK, a qualitative release assessment was undertaken. To facilitate the release assessment, the world was divided into four zones according to location of outbreaks of henipaviruses, isolation of henipaviruses, proximity to other countries where incidents of henipaviruses have occurred and the distribution of Pteropus spp. fruit bats. From this release assessment, the key findings are that the importation of fruit from Zone 1 and 2 and bat bushmeat from Zone 1 each have a Low annual probability of release of henipaviruses into the UK. Similarly, the importation of bat meat from Zone 2, horses and companion animals from Zone 1 and people travelling from Zone 1 and entering the UK was estimated to pose a Very Low probability of release. The annual probability of release for all other release routes was assessed to be Negligible. It is recommended that the release assessment be periodically re-assessed to reflect changes in knowledge and circumstances over time. PMID:22328916

Ca2+-induced Ca2+ Release Phenomena in Mammalian Sympathetic Neurons Are Critically Dependent on the Rate of Rise of Trigger Ca2+

PubMed Central

Hernández-Cruz, Arturo; Escobar, Ariel L.; Jiménez, Nicolás

1997-01-01

The role of ryanodine-sensitive intracellular Ca2+ stores present in nonmuscular cells is not yet completely understood. Here we examine the physiological parameters determining the dynamics of caffeine-induced Ca2+ release in individual fura-2–loaded sympathetic neurons. Two ryanodine-sensitive release components were distinguished: an early, transient release (TR) and a delayed, persistent release (PR). The TR component shows refractoriness, depends on the filling status of the store, and requires caffeine concentrations ≥10 mM. Furthermore, it is selectively suppressed by tetracaine and intracellular BAPTA, which interfere with Ca2+-mediated feedback loops, suggesting that it constitutes a Ca2+-induced Ca2+-release phenomenon. The dynamics of release is markedly affected when Sr2+ substitutes for Ca2+, indicating that Sr2+ release may operate with lower feedback gain than Ca2+ release. Our data indicate that when the initial release occurs at an adequately fast rate, Ca2+ triggers further release, producing a regenerative response, which is interrupted by depletion of releasable Ca2+ and Ca2+-dependent inactivation. A compartmentalized linear diffusion model can reproduce caffeine responses: When the Ca2+ reservoir is full, the rapid initial Ca2+ rise determines a faster occupation of the ryanodine receptor Ca2+ activation site giving rise to a regenerative release. With the store only partially loaded, the slower initial Ca2+ rise allows the inactivating site of the release channel to become occupied nearly as quickly as the activating site, thereby suppressing the initial fast release. The PR component is less dependent on the store's Ca2+ content. This study suggests that transmembrane Ca2+ influx in rat sympathetic neurons does not evoke widespread amplification by CICR because of its inability to raise [Ca2+] near the Ca2+ release channels sufficiently fast to overcome their Ca2+-dependent inactivation. Conversely, caffeine-induced Ca2+ release can undergo considerable amplification especially when Ca2+ stores are full. We propose that the primary function of ryanodine-sensitive stores in neurons and perhaps in other nonmuscular cells, is to emphasize subcellular Ca2+ gradients resulting from agonist-induced intracellular release. The amplification gain is dependent both on the agonist concentration and on the filling status of intracellular Ca2+ stores. PMID:9041445

Prolactin-releasing peptide affects gastric motor function in rat by modulating synaptic transmission in the dorsal vagal complex.

PubMed

Grabauskas, Gintautas; Zhou, Shi-Yi; Das, Sudipto; Lu, Yuanxu; Owyang, Chung; Moises, Hylan C

2004-12-15

Prolactin-releasing peptide (PrRP) is a recently discovered neuropeptide implicated in the central control of feeding behaviour and autonomic homeostasis. PrRP-containing neurones and PrRP receptor mRNA are found in abundance in the caudal portion of the nucleus tractus solitarius (NTS), an area which together with the dorsal motor nucleus of the vagus (DMV) comprises an integrated structure, the dorsal vagal complex (DVC) that processes visceral afferent signals from and provides parasympathetic motor innervation to the gastrointestinal tract. In this study, microinjection experiments were conducted in vivo in combination with whole-cell recording from neurones in rat medullary slices to test the hypothesis that PrRP plays a role in the central control of gastric motor function, acting within the DVC to modulate the activity of preganglionic vagal motor neurones that supply the stomach. Microinjection of PrRP (0.2 pmol (20 nl)(-1)) into the DMV at the level of the area postrema (+0.2 to +0.6 mm from the calamus scriptorius, CS) markedly stimulated gastric contractions and increased intragastric pressure (IGP). Conversely, administration of peptide into the DMV at sites caudal to the obex (0.0 to -0.3 mm from the CS) decreased IGP and reduced phasic contractions. These effects occurred without change in mean arterial pressure and were abolished by ipsilateral vagotomy, indicating mediation via a vagal-dependent mechanism(s). The pattern of gastric motor responses evoked by PrRP mimicked that produced by administration of L-glutamate at the same sites, and both the effects of L-glutamate and PrRP were abolished following local administration of NMDA and non-NMDA-type glutamate receptor antagonists. On the other hand, microinjection of PrRP into the medial or comissural nucleus of the solitary tract (mNTS and comNTS, respectively) resulted in less robust changes in IGP in a smaller percentage of animals, accompanied by marked alterations in arterial pressure. Superfusion of brain slices with PrRP (100-300 nm) produced a small depolarization and increased spontaneous firing in 10 of 30 retrogradely labelled gastric-projecting DMV neurones. The excitatory effects were blocked by administration of TTX (2 mum) or specific glutamate receptor antagonists, indicating that they resulted from interactions of PrRP at a presynaptic site. Congruent with this, PrRP increased the amplitude of excitatory postsynaptic currents (EPSCs, 154 +/- 33%, 12 of 25 neurones) evoked by electrical stimulation in mNTS or comNTS. In addition, administration of PrRP decreased the paired-pulse ratio of EPSCs evoked by two identical stimuli delivered 100 ms apart (from 0.95 +/- 0.08 to 0.71 +/- 0.11, P < 0.05), whereas it did not affect the amplitude of inward currents evoked by exogenous application of L-glutamate to the slice. The frequency, but not amplitude of spontaneous EPSCs and action potential-independent miniature EPSCs was also increased by administration of PrRP, suggesting that the peptide was acting at least in part at receptors on presynaptic nerve terminals to enhance glutamatergic transmission. In recordings obtained from a separate group of slices, we did not observe any direct effects of PrRP on spontaneous discharge or postsynaptic excitability in either mNTS or comNTS neurones (n = 31). These data indicate that PrRP may act within the DVC to regulate gastric motor function by modulating the efficacy of conventional excitatory synaptic inputs from the NTS onto gastric-projecting vagal motor neurones.

Prolactin-releasing peptide affects gastric motor function in rat by modulating synaptic transmission in the dorsal vagal complex

PubMed Central

Grabauskas, Gintautas; Zhou, Shi-Yi; Das, Sudipto; Lu, Yuanxu; Owyang, Chung; Moises, Hylan C

2004-01-01

Prolactin-releasing peptide (PrRP) is a recently discovered neuropeptide implicated in the central control of feeding behaviour and autonomic homeostasis. PrRP-containing neurones and PrRP receptor mRNA are found in abundance in the caudal portion of the nucleus tractus solitarius (NTS), an area which together with the dorsal motor nucleus of the vagus (DMV) comprises an integrated structure, the dorsal vagal complex (DVC) that processes visceral afferent signals from and provides parasympathetic motor innervation to the gastrointestinal tract. In this study, microinjection experiments were conducted in vivo in combination with whole-cell recording from neurones in rat medullary slices to test the hypothesis that PrRP plays a role in the central control of gastric motor function, acting within the DVC to modulate the activity of preganglionic vagal motor neurones that supply the stomach. Microinjection of PrRP (0.2 pmol (20 nl)−1) into the DMV at the level of the area postrema (+0.2 to +0.6 mm from the calamus scriptorius, CS) markedly stimulated gastric contractions and increased intragastric pressure (IGP). Conversely, administration of peptide into the DMV at sites caudal to the obex (0.0 to −0.3 mm from the CS) decreased IGP and reduced phasic contractions. These effects occurred without change in mean arterial pressure and were abolished by ipsilateral vagotomy, indicating mediation via a vagal-dependent mechanism(s). The pattern of gastric motor responses evoked by PrRP mimicked that produced by administration of l-glutamate at the same sites, and both the effects of l-glutamate and PrRP were abolished following local administration of NMDA and non-NMDA-type glutamate receptor antagonists. On the other hand, microinjection of PrRP into the medial or comissural nucleus of the solitary tract (mNTS and comNTS, respectively) resulted in less robust changes in IGP in a smaller percentage of animals, accompanied by marked alterations in arterial pressure. Superfusion of brain slices with PrRP (100–300 nm) produced a small depolarization and increased spontaneous firing in 10 of 30 retrogradely labelled gastric-projecting DMV neurones. The excitatory effects were blocked by administration of TTX (2 μm) or specific glutamate receptor antagonists, indicating that they resulted from interactions of PrRP at a presynaptic site. Congruent with this, PrRP increased the amplitude of excitatory postsynaptic currents (EPSCs, 154 ± 33%, 12 of 25 neurones) evoked by electrical stimulation in mNTS or comNTS. In addition, administration of PrRP decreased the paired-pulse ratio of EPSCs evoked by two identical stimuli delivered 100 ms apart (from 0.95 ± 0.08 to 0.71 ± 0.11, P < 0.05), whereas it did not affect the amplitude of inward currents evoked by exogenous application of l-glutamate to the slice. The frequency, but not amplitude of spontaneous EPSCs and action potential-independent miniature EPSCs was also increased by administration of PrRP, suggesting that the peptide was acting at least in part at receptors on presynaptic nerve terminals to enhance glutamatergic transmission. In recordings obtained from a separate group of slices, we did not observe any direct effects of PrRP on spontaneous discharge or postsynaptic excitability in either mNTS or comNTS neurones (n = 31). These data indicate that PrRP may act within the DVC to regulate gastric motor function by modulating the efficacy of conventional excitatory synaptic inputs from the NTS onto gastric-projecting vagal motor neurones. PMID:15486017

Degradation of the disease-associated prion protein by a serine protease from lichens.

USGS Publications Warehouse

Johnson, C.J.; Bennett, J.P.; Biro, S.M.; Duque-Velasquez, J. C.; Rodriguez, C.M.; Bessen, R.A.; Rocke, T.E.

2011-01-01

The disease-associated prion protein (PrPTSE), the probable etiological agent of the transmissible spongiform encephalopathies (TSEs), is resistant to degradation and can persist in the environment. Lichens, mutualistic symbioses containing fungi, algae, bacteria and occasionally cyanobacteria, are ubiquitous in the environment and have evolved unique biological activities allowing their survival in challenging ecological niches. We investigated PrPTSE inactivation by lichens and found acetone extracts of three lichen species (Parmelia sulcata, Cladonia rangiferina and Lobaria pulmonaria) have the ability to degrade prion protein (PrP) from TSE-infected hamsters, mice and deer. Immunoblots measuring PrP levels and protein misfolding cyclic amplification indicated at least two logs of reductions in PrPTSE. Degradative activity was not found in closely related lichen species or in algae or a cyanobacterium that inhabit lichens. Degradation was blocked by Pefabloc SC, a serine protease inhibitor, but not inhibitors of other proteases or enzymes. Additionally, we found that PrP levels in PrPTSE-enriched preps or infected brain homogenates are also reduced following exposure to freshly-collected P. sulcata or an aqueous extract of the lichen. Our findings indicate that these lichen extracts efficiently degrade PrPTSE and suggest that some lichens could have potential to inactivate TSE infectivity on the landscape or be a source for agents to degrade prions. Further work to clone and characterize the protease, assess its effect on TSE infectivity and determine which organism or organisms present in lichens produce or influence the protease activity is warranted.

Degradation of the disease-associated prion protein by a serine protease from lichens

USGS Publications Warehouse

Johnson, Christopher J.; Bennett, James P.; Biro, S.M.; Duque-Velasquez, J. C.; Rodriguez, Cynthia M.; Bessen, R.A.; Rocke, Tonie E.

2011-01-01

The disease-associated prion protein (PrPTSE), the probable etiological agent of the transmissible spongiform encephalopathies (TSEs), is resistant to degradation and can persist in the environment. Lichens, mutualistic symbioses containing fungi, algae, bacteria and occasionally cyanobacteria, are ubiquitous in the environment and have evolved unique biological activities allowing their survival in challenging ecological niches. We investigated PrPTSE inactivation by lichens and found acetone extracts of three lichen species (Parmelia sulcata, Cladonia rangiferina and Lobaria pulmonaria) have the ability to degrade prion protein (PrP) from TSE-infected hamsters, mice and deer. Immunoblots measuring PrP levels and protein misfolding cyclic amplification indicated at least two logs of reductions in PrPTSE. Degradative activity was not found in closely related lichen species or in algae or a cyanobacterium that inhabit lichens. Degradation was blocked by Pefabloc SC, a serine protease inhibitor, but not inhibitors of other proteases or enzymes. Additionally, we found that PrP levels in PrPTSE-enriched preps or infected brain homogenates are also reduced following exposure to freshly-collected P. sulcata or an aqueous extract of the lichen. Our findings indicate that these lichen extracts efficiently degrade PrPTSE and suggest that some lichens could have potential to inactivate TSE infectivity on the landscape or be a source for agents to degrade prions. Further work to clone and characterize the protease, assess its effect on TSE infectivity and determine which organism or organisms present in lichens produce or influence the protease activity is warranted.

Risk Indicators for Periodontitis in US Adults: NHANES 2009 to 2012.

PubMed

Eke, Paul I; Wei, Liang; Thornton-Evans, Gina O; Borrell, Luisa N; Borgnakke, Wenche S; Dye, Bruce; Genco, Robert J

2016-10-01

Through the use of optimal surveillance measures and standard case definitions, it is now possible to more accurately determine population-average risk profiles for severe (SP) and non-severe periodontitis (NSP) in adults (aged 30 years and older) in the United States. Data from the 2009 to 2012 National Health and Nutrition Examination Survey were used, which, for the first time, used the "gold standard" full-mouth periodontitis surveillance protocol to classify severity of periodontitis following suggested Centers for Disease Control/American Academy of Periodontology case definitions. Probabilities of periodontitis by: 1) sociodemographics, 2) behavioral factors, and 3) comorbid conditions were assessed using prevalence ratios (PRs) estimated by predicted marginal probability from multivariable generalized logistic regression models. Analyses were further stratified by sex for each classification of periodontitis. Likelihood of total periodontitis (TP) increased with age for overall and NSP relative to non-periodontitis. Compared with non-Hispanic whites, TP was more likely in Hispanics (adjusted [a]PR = 1.38; 95% confidence interval 95% CI: 1.26 to 1.52) and non-Hispanic blacks (aPR = 1.35; 95% CI: 1.22 to 1.50), whereas SP was most likely in non-Hispanic blacks (aPR = 1.82; 95% CI: 1.44 to 2.31). There was at least a 50% greater likelihood of TP in current smokers compared with non-smokers. In males, likelihood of TP in adults aged 65 years and older was greater (aPR = 2.07; 95% CI: 1.76 to 2.43) than adults aged 30 to 44 years. This probability was even greater in women (aPR = 3.15; 95% CI: 2.63 to 3.77). Likelihood of TP was higher in current smokers relative to non-smokers regardless of sex and periodontitis classification. TP was more likely in men with uncontrolled diabetes mellitus (DM) compared with adults without DM. Assessment of risk profiles for periodontitis in adults in the United States based on gold standard periodontal measures show important differences by severity of disease and sex. Cigarette smoking, specifically current smoking, remains an important modifiable risk for all levels of periodontitis severity. Higher likelihood of TP in older adults and in males with uncontrolled DM is noteworthy. These findings could improve identification of target populations for effective public health interventions to improve periodontal health of adults in the United States.

Evaluation of test-strategies for estimating probability of low prevalence of paratuberculosis in Danish dairy herds.

PubMed

Sergeant, E S G; Nielsen, S S; Toft, N

2008-06-15

Paratuberculosis is a chronic infection affecting cattle and other ruminants. In the dairy industry, losses due to paratuberculosis can be substantial in infected herds and several countries have implemented national programmes based on herd-classification to manage the disease. The aim of this study was to develop a method to estimate the probability of low within-herd prevalence of paratuberculosis for Danish dairy herds. A stochastic simulation model was developed using the R programming environment. Features of this model included: use of age-specific estimates of test-sensitivity and specificity; use of a distribution of observed values (rather than a fixed, low value) for design prevalence; and estimates of the probability of low prevalence (PrLow) based on a specific number of test-positive animals, rather than for a result less than or equal to a specified cut-point number of reactors. Using this model, five herd-testing strategies were evaluated: (1) milk-ELISA on all lactating cows; (2) milk-ELISA on lactating cows4 years old; (4) faecal culture on all lactating cows; and (5) milk-ELISA plus faecal culture in series on all lactating cows. The five testing strategies were evaluated using observed milk-ELISA results from 19 Danish dairy herds as well as for simulated results from the same herds assuming that they were uninfected. Whole-herd milk-ELISA was the preferred strategy, and considered the most cost-effective strategy of the five alternatives. The five strategies were all efficient in detecting infection, i.e. estimating a low PrLow in infected herds, however, PrLow estimates for milk-ELISA on age-cohorts were too low in simulated uninfected herds and the strategies involving faecal culture were too expensive to be of practical interest. For simulated uninfected herds, whole-herd milk-ELISA resulted in median PrLow values>0.9 for most herds, depending on herd size and age-structure. None of the strategies provided enough power to establish a high PrLow in smaller herds, or herds with a younger age-structure. Despite this, it appears as if the method is a useful approach for herd-classification for most herds in the Danish dairy industry.

Characterization of the gag/fusion protein encoded by the defective Duplan retrovirus inducing murine acquired immunodeficiency syndrome.

PubMed Central

Huang, M; Jolicoeur, P

1990-01-01

Murine acquired immunodeficiency syndrome is induced by a defective retrovirus. Sequencing of this defective viral genome revealed a long open reading frame which encodes a putative gag/fusion protein, N-MA-p12-CA-NC-COOH, (D. C. Aziz, Z. Hanna, and P. Jolicoeur, Nature (London) 338:505-508, 1989). We raised a specific antibody to the unique p12 domain of this gag fusion precursor, Pr60gag. We found that Pr60gag was indeed encoded by the defective viral genome both in cell-free translation reticulocyte extracts and in infected mouse fibroblasts. Pr60gag was found to be myristylated, phosphorylated, and attached to the cell membrane, like other helper murine leukemia virus (MuLV) gag precursors. Pr60gag was not substantially cleaved within the nonproducer cells and was not released from these cells. However, in the presence of helper MuLV proteins, it formed phenotypically mixed particles. In these particles, Pr60gag was only partially cleaved. In helper MuLV-producing cells harboring the defective virus, a gag-related p40 intermediate was generated both intracellularly and extracellularly. In these cells, Pr60gag appeared to behave as a dominant negative mutant, interfering with proper cleavage of helper Pr65gag. Our data indicate that Pr60gag is a major (and possibly the only) gene product of the defective murine acquired immunodeficiency syndrome virus and is likely to harbor some determinants of pathogenicity of this virus. Images PMID:2243376

Influence of the PDE5 inhibitor tadalafil on redox status and antioxidant defense system in C2C12 skeletal muscle cells.

PubMed

Duranti, Guglielmo; Ceci, Roberta; Sgrò, Paolo; Sabatini, Stefania; Di Luigi, Luigi

2017-05-01

Phosphodiesterase type 5 inhibitors (PDE5Is), widely known for their beneficial effects onto male erectile dysfunction, seem to exert favorable effects onto metabolism as well. Tadalafil exposure increases oxidative metabolism of C2C12 skeletal muscle cells. A rise in fatty acid (FA) metabolism, requiring more oxygen, could induce a larger reactive oxygen species (ROS) release as a byproduct thus leading to a redox imbalance. The aim of this study was to determine how PDE5I tadalafil influences redox status in skeletal muscle cells to match the increasing oxidative metabolism. To this purpose, differentiated C2C12 skeletal muscle cells were treated with tadalafil and analyzed for total antioxidant capacity (TAC) and glutathione levels as marker of redox status; enzyme activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) engaged in antioxidant defense; and lipid peroxidation (TBARS) and protein carbonyls (PrCar) as markers of oxidative damage. Tadalafil increased total intracellular glutathione (tGSH), CAT, SOD, and GPx enzymatic activities while no changes were found in TAC. A perturbation of redox status, as showed by the decrease in the ratio between reduced/oxidized glutathione (GSH/GSSG), was observed. Nevertheless, it did not cause any change in TBARS and PrCar levels probably due to the enhancement in the antioxidant enzymatic network. Taken together, these data indicate that tadalafil, besides improving oxidative metabolism, may be beneficial to skeletal muscle cells by enhancing the enzymatic antioxidant system capacity.

RIM-binding protein 2 regulates release probability by fine-tuning calcium channel localization at murine hippocampal synapses

PubMed Central

Grauel, M. Katharina; Reddy-Alla, Suneel; Willmes, Claudia G.; Brockmann, Marisa M.; Trimbuch, Thorsten; Rosenmund, Tanja; Pangalos, Maria; Vardar, Gülçin; Stumpf, Alexander; Walter, Alexander M.; Rost, Benjamin R.; Eickholt, Britta J.; Haucke, Volker; Schmitz, Dietmar; Sigrist, Stephan J.; Rosenmund, Christian

2016-01-01

The tight spatial coupling of synaptic vesicles and voltage-gated Ca2+ channels (CaVs) ensures efficient action potential-triggered neurotransmitter release from presynaptic active zones (AZs). Rab-interacting molecule-binding proteins (RIM-BPs) interact with Ca2+ channels and via RIM with other components of the release machinery. Although human RIM-BPs have been implicated in autism spectrum disorders, little is known about the role of mammalian RIM-BPs in synaptic transmission. We investigated RIM-BP2–deficient murine hippocampal neurons in cultures and slices. Short-term facilitation is significantly enhanced in both model systems. Detailed analysis in culture revealed a reduction in initial release probability, which presumably underlies the increased short-term facilitation. Superresolution microscopy revealed an impairment in CaV2.1 clustering at AZs, which likely alters Ca2+ nanodomains at release sites and thereby affects release probability. Additional deletion of RIM-BP1 does not exacerbate the phenotype, indicating that RIM-BP2 is the dominating RIM-BP isoform at these synapses. PMID:27671655

Two-dimensional fuzzy fault tree analysis for chlorine release from a chlor-alkali industry using expert elicitation.

PubMed

Renjith, V R; Madhu, G; Nayagam, V Lakshmana Gomathi; Bhasi, A B

2010-11-15

The hazards associated with major accident hazard (MAH) industries are fire, explosion and toxic gas releases. Of these, toxic gas release is the worst as it has the potential to cause extensive fatalities. Qualitative and quantitative hazard analyses are essential for the identification and quantification of these hazards related to chemical industries. Fault tree analysis (FTA) is an established technique in hazard identification. This technique has the advantage of being both qualitative and quantitative, if the probabilities and frequencies of the basic events are known. This paper outlines the estimation of the probability of release of chlorine from storage and filling facility of chlor-alkali industry using FTA. An attempt has also been made to arrive at the probability of chlorine release using expert elicitation and proven fuzzy logic technique for Indian conditions. Sensitivity analysis has been done to evaluate the percentage contribution of each basic event that could lead to chlorine release. Two-dimensional fuzzy fault tree analysis (TDFFTA) has been proposed for balancing the hesitation factor involved in expert elicitation. Copyright © 2010 Elsevier B.V. All rights reserved.

Humpback whales feed on hatchery-released juvenile salmon

PubMed Central

Straley, Janice M.; McPhee, Megan V.; Atkinson, Shannon; Reifenstuhl, Steve

2017-01-01

Humpback whales are remarkable for the behavioural plasticity of their feeding tactics and the diversity of their diets. Within the last decade at hatchery release sites in Southeast Alaska, humpback whales have begun exploiting juvenile salmon, a previously undocumented prey. The anthropogenic source of these salmon and their important contribution to local fisheries makes the emergence of humpback whale predation a concern for the Southeast Alaska economy. Here, we describe the frequency of observing humpback whales, examine the role of temporal and spatial variables affecting the probability of sighting humpback whales and describe prey capture behaviours at five hatchery release sites. We coordinated twice-daily 15 min observations during the spring release seasons 2010–2015. Using logistic regression, we determined that the probability of occurrence of humpback whales increased after releases began and decreased after releases concluded. The probability of whale occurrence varied among release sites but did not increase significantly over the 6 year study period. Whales were reported to be feeding on juvenile chum, Chinook and coho salmon, with photographic and video records of whales feeding on coho salmon. The ability to adapt to new prey sources may be key to sustaining their population in a changing ocean. PMID:28791145

Humpback whales feed on hatchery-released juvenile salmon.

PubMed

Chenoweth, Ellen M; Straley, Janice M; McPhee, Megan V; Atkinson, Shannon; Reifenstuhl, Steve

2017-07-01

Humpback whales are remarkable for the behavioural plasticity of their feeding tactics and the diversity of their diets. Within the last decade at hatchery release sites in Southeast Alaska, humpback whales have begun exploiting juvenile salmon, a previously undocumented prey. The anthropogenic source of these salmon and their important contribution to local fisheries makes the emergence of humpback whale predation a concern for the Southeast Alaska economy. Here, we describe the frequency of observing humpback whales, examine the role of temporal and spatial variables affecting the probability of sighting humpback whales and describe prey capture behaviours at five hatchery release sites. We coordinated twice-daily 15 min observations during the spring release seasons 2010-2015. Using logistic regression, we determined that the probability of occurrence of humpback whales increased after releases began and decreased after releases concluded. The probability of whale occurrence varied among release sites but did not increase significantly over the 6 year study period. Whales were reported to be feeding on juvenile chum, Chinook and coho salmon, with photographic and video records of whales feeding on coho salmon. The ability to adapt to new prey sources may be key to sustaining their population in a changing ocean.

C-Terminal HIV-1 Transframe p6* Tetrapeptide Blocks Enhanced Gag Cleavage Incurred by Leucine Zipper Replacement of a Deleted p6* Domain.

PubMed

Yu, Fu-Hsien; Huang, Kuo-Jung; Wang, Chin-Tien

2017-05-15

HIV-1 protease (PR) functions as a homodimer mediating virus maturation following virus budding. Gag-Pol dimerization is believed to trigger embedded PR activation by promoting PR dimer formation. Early PR activation can lead to markedly reduced virus yields due to premature Gag cleavage. The p6* peptide, located between Gag and PR, is believed to ensure virus production by preventing early PR maturation. Studies aimed at finding supporting evidence for this proposal are limited due to a reading frame overlap between p6* and the p6gag budding domain. To determine if p6* affects virus production via the modulation of PR activation, we engineered multiple constructs derived from Dp6*PR (an assembly- and processing-competent construct with Pol fused at the inactivated PR C terminus). The data indicated that a p6* deletion adjacent to active PR significantly impaired virus processing. We also observed that the insertion of a leucine zipper (LZ) dimerization motif in the deleted region eliminated virus production in a PR activity-dependent manner, suggesting that the LZ insertion triggered premature PR activation by facilitating PR dimer formation. As few as four C-terminal p6* residues remaining at the p6*/PR junction were sufficient to restore virus yields, with a Gag processing profile similar to that of the wild type. Our study provides supporting evidence in a virus assembly context that the C-terminal p6* tetrapeptide plays a role in preventing premature PR maturation. IMPORTANCE Supporting evidence for the assumption that p6* retards PR maturation in the context of virus assembly is lacking. We found that replacing p6* with a leucine zipper peptide abolished virus assembly due to the significant enhancement of Gag cleavage. However, as few as four C-terminal p6* residues remaining in the deleted region were sufficient for significant PR release, as well as for counteracting leucine zipper-incurred premature Gag cleavage. Our data provide evidence that (i) p6* ensures virus assembly by preventing early PR activation and (ii) four C-terminal p6* residues are critical for modulating PR activation. Current PR inhibitor development efforts are aimed largely at mature PR, but there is a tendency for HIV-1 variants that are resistant to multiple protease inhibitors to emerge. Our data support the idea of modulating PR activation by targeting PR precursors as an alternative approach to controlling HIV-1/AIDS. Copyright © 2017 American Society for Microbiology.

Arsenic-induced plant growth of arsenic-hyperaccumulator Pteris vittata: Impact of arsenic and phosphate rock.

PubMed

Han, Yong-He; Yang, Guang-Mei; Fu, Jing-Wei; Guan, Dong-Xing; Chen, Yanshan; Ma, Lena Q

2016-04-01

Phosphate rock (PR) has been shown to promote plant growth and arsenic (As) uptake by As-hyperaccumulator Pteris vittata (PV). However, little is known about its behaviors in agricultural soils. In this study, impact of 50 mg kg(-1) As and/or 1.5% PR amendment on plant As accumulation and growth was investigated by growing PV for 90 d in three agricultural soils. While As amendment significantly increased plant As uptake and substantially promoted PV growth, the opposite was observed with PR amendment. Arsenic amendment increased plant frond As from 16.9-265 to 961-6017 mg kg(-1),whereas PR amendment lowered frond As to 10.2-216 mg kg(-1). The As-induced plant growth stimulation was 69-71%. While PR amendment increased plant Ca and P uptake, As amendment showed opposite results. The PV biomass was highly correlated with plant As at r = 0.82, but with weak correlations with plant Ca or P at r < 0.30. This study confirmed that 1) As significantly promoted PV growth, probably independent of Ca or P uptake, 2) PR amendment didn't enhance plant growth or As uptake by PV in agricultural soils with adequate available P, and 3) PV effluxed arsenite (AsIII) growing in agricultural soils. Published by Elsevier Ltd.

Photoelectric polarization-sensitive broadband photoresponse from interface junction states in graphene

DOE PAGES

Kalugin, Nikolai G.; Jing, Lei; Morell, Eric Suarez; ...

2016-10-24

Graphene has established itself as a promising optoelectronic material. Many details of the photoresponse (PR) mechanisms in graphene in the THz-to-visible range have been revealed, however, new intricacies continue to emerge. Interface junctions, formed at the boundaries between parts of graphene with different number of layers or different stacking orders, and making connection between electrical contacts, provide another peculiar setup to establish PR. Here, we experimentally demonstrate an enhanced polarization sensitive photoelectric PR in graphene sheets containing interface junctions as compared to homogenous graphene sheets in the visible, infrared, and THz spectral regions. Our numerical simulations show that highly localizedmore » electronic states are created at the interface junctions, and these states exhibit a unique energy spectrum and enhanced probabilities for optical transitions. Here, the interaction of electrons from interface junction states with electromagnetic fields generates a polarization-sensitive PR that is maximal for the polarization direction perpendicular to the junction interface.« less

Photoelectric polarization-sensitive broadband photoresponse from interface junction states in graphene

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

Kalugin, Nikolai G.; Jing, Lei; Morell, Eric Suarez

Graphene has established itself as a promising optoelectronic material. Many details of the photoresponse (PR) mechanisms in graphene in the THz-to-visible range have been revealed, however, new intricacies continue to emerge. Interface junctions, formed at the boundaries between parts of graphene with different number of layers or different stacking orders, and making connection between electrical contacts, provide another peculiar setup to establish PR. Here, we experimentally demonstrate an enhanced polarization sensitive photoelectric PR in graphene sheets containing interface junctions as compared to homogenous graphene sheets in the visible, infrared, and THz spectral regions. Our numerical simulations show that highly localizedmore » electronic states are created at the interface junctions, and these states exhibit a unique energy spectrum and enhanced probabilities for optical transitions. Here, the interaction of electrons from interface junction states with electromagnetic fields generates a polarization-sensitive PR that is maximal for the polarization direction perpendicular to the junction interface.« less

Systematic evaluation of NASA precipitation radar estimates using NOAA/NSSL National Mosaic QPE products

NASA Astrophysics Data System (ADS)

Kirstetter, P.; Hong, Y.; Gourley, J. J.; Chen, S.; Flamig, Z.; Zhang, J.; Howard, K.; Petersen, W. A.

2011-12-01

Proper characterization of the error structure of TRMM Precipitation Radar (PR) quantitative precipitation estimation (QPE) is needed for their use in TRMM combined products, water budget studies and hydrological modeling applications. Due to the variety of sources of error in spaceborne radar QPE (attenuation of the radar signal, influence of land surface, impact of off-nadir viewing angle, etc.) and the impact of correction algorithms, the problem is addressed by comparison of PR QPEs with reference values derived from ground-based measurements (GV) using NOAA/NSSL's National Mosaic QPE (NMQ) system. An investigation of this subject has been carried out at the PR estimation scale (instantaneous and 5 km) on the basis of a 3-month-long data sample. A significant effort has been carried out to derive a bias-corrected, robust reference rainfall source from NMQ. The GV processing details will be presented along with preliminary results of PR's error characteristics using contingency table statistics, probability distribution comparisons, scatter plots, semi-variograms, and systematic biases and random errors.

The sources of Antarctic bottom water in a global ice ocean model

NASA Astrophysics Data System (ADS)

Goosse, Hugues; Campin, Jean-Michel; Tartinville, Benoı̂t

Two mechanisms contribute to the formation of Antarctic bottom water (AABW). The first, and probably the most important, is initiated by the brine released on the Antarctic continental shelf during ice formation which is responsible for an increase in salinity. After mixing with ambient water at the shelf break, this salty and dense water sinks along the shelf slope and invades the deepest part of the global ocean. For the second one, the increase of surface water density is due to strong cooling at the ocean-atmosphere interface, together with a contribution from brine release. This induces deep convection and the renewal of deep waters. The relative importance of these two mechanisms is investigated in a global coupled ice-ocean model. Chlorofluorocarbon (CFC) concentrations simulated by the model compare favourably with observations, suggesting a reasonable deep water ventilation in the Southern Ocean, except close to Antarctica where concentrations are too high. Two artificial passive tracers released at surface on the Antarctic continental shelf and in the open-ocean allow to show clearly that the two mechanisms contribute significantly to the renewal of AABW in the model. This indicates that open-ocean convection is overestimated in our simulation. Additional experiments show that the amount of AABW production due to the export of dense shelf waters is quite sensitive to the parameterisation of the effect of downsloping and meso-scale eddies. Nevertheless, shelf waters always contribute significantly to deep water renewal. Besides, increasing the P.R. Gent, J.C. McWilliams [Journal of Physical Oceanography 20 (1990) 150-155] thickness diffusion can nearly suppress the AABW formation by open-ocean convection.

A protocol for searching the most probable phase-retrieved maps in coherent X-ray diffraction imaging by exploiting the relationship between convergence of the retrieved phase and success of calculation.

PubMed

Sekiguchi, Yuki; Hashimoto, Saki; Kobayashi, Amane; Oroguchi, Tomotaka; Nakasako, Masayoshi

2017-09-01

Coherent X-ray diffraction imaging (CXDI) is a technique for visualizing the structures of non-crystalline particles with size in the submicrometer to micrometer range in material sciences and biology. In the structural analysis of CXDI, the electron density map of a specimen particle projected along the direction of the incident X-rays can be reconstructed only from the diffraction pattern by using phase-retrieval (PR) algorithms. However, in practice, the reconstruction, relying entirely on the computational procedure, sometimes fails because diffraction patterns miss the data in small-angle regions owing to the beam stop and saturation of the detector pixels, and are modified by Poisson noise in X-ray detection. To date, X-ray free-electron lasers have allowed us to collect a large number of diffraction patterns within a short period of time. Therefore, the reconstruction of correct electron density maps is the bottleneck for efficiently conducting structure analyses of non-crystalline particles. To automatically address the correctness of retrieved electron density maps, a data analysis protocol to extract the most probable electron density maps from a set of maps retrieved from 1000 different random seeds for a single diffraction pattern is proposed. Through monitoring the variations of the phase values during PR calculations, the tendency for the PR calculations to succeed when the retrieved phase sets converged on a certain value was found. On the other hand, if the phase set was in persistent variation, the PR calculation tended to fail to yield the correct electron density map. To quantify this tendency, here a figure of merit for the variation of the phase values during PR calculation is introduced. In addition, a PR protocol to evaluate the similarity between a map of the highest figure of merit and other independently reconstructed maps is proposed. The protocol is implemented and practically examined in the structure analyses for diffraction patterns from aggregates of gold colloidal particles. Furthermore, the feasibility of the protocol in the structure analysis of organelles from biological cells is examined.

Reliable evaluation of the quantal determinants of synaptic efficacy using Bayesian analysis

PubMed Central

Beato, M.

2013-01-01

Communication between neurones in the central nervous system depends on synaptic transmission. The efficacy of synapses is determined by pre- and postsynaptic factors that can be characterized using quantal parameters such as the probability of neurotransmitter release, number of release sites, and quantal size. Existing methods of estimating the quantal parameters based on multiple probability fluctuation analysis (MPFA) are limited by their requirement for long recordings to acquire substantial data sets. We therefore devised an algorithm, termed Bayesian Quantal Analysis (BQA), that can yield accurate estimates of the quantal parameters from data sets of as small a size as 60 observations for each of only 2 conditions of release probability. Computer simulations are used to compare its performance in accuracy with that of MPFA, while varying the number of observations and the simulated range in release probability. We challenge BQA with realistic complexities characteristic of complex synapses, such as increases in the intra- or intersite variances, and heterogeneity in release probabilities. Finally, we validate the method using experimental data obtained from electrophysiological recordings to show that the effect of an antagonist on postsynaptic receptors is correctly characterized by BQA by a specific reduction in the estimates of quantal size. Since BQA routinely yields reliable estimates of the quantal parameters from small data sets, it is ideally suited to identify the locus of synaptic plasticity for experiments in which repeated manipulations of the recording environment are unfeasible. PMID:23076101

A novel application of multi-event modeling to estimate class segregation in a highly migratory oceanic vertebrate.

PubMed

Chapple, T K; Chambert, T; Kanive, P E; Jorgensen, S J; Rotella, J J; Anderson, S D; Carlisle, A B; Block, B A

2016-12-01

Spatial segregation of animals by class (i.e., maturity or sex) within a population due to differential rates of temporary emigration (TE) from study sites can be an important life history feature to consider in population assessment and management. However, such rates are poorly known; new quantitative approaches to address these knowledge gaps are needed. We present a novel application of multi-event models that takes advantage of two sources of detections to differentiate temporary emigration from apparent absence to quantify class segregation within a study population of double-marked (photo-identified and tagged with coded acoustic transmitters) white sharks (Carcharodon carcharias) in central California. We use this model to test if sex-specific patterns in TE result in disparate apparent capture probabilities (p o ) between male and female white sharks, which can affect the observed sex ratio. The best-supported model showed a contrasting pattern of Pr(TE) from coastal aggregation sites between sexes (for males Pr[TE] = 0.015 [95% CI = 0.00, 0.31] and Pr[TE]= 0.57 [0.40, 0.72] for females), but not maturity classes. Additionally, by accounting for Pr(TE) and imperfect detection, we were able to estimate class-specific values of true capture probability (p * ) for tagged and untagged sharks. The best-supported model identified differences between maturity classes but no difference between sexes or tagging impacts (tagged mature sharks p *  = 0.55 (0.46-0.63) and sub-adult sharks p*   = 0.36 (0.25, 0.50); and untagged mature sharks p *  = 0.50 (0.39-0.61) and sub-adults p *  = 0.18 (0.10, 0.31). Estimated sex-based differences in p o were linked to sex-specific differences in Pr(TE) but not in p * ; once the Pr(TE) is accounted for, the p * between sexes was not different. These results indicate that the observed sex ratio is not a consequence of unequal detectability and sex-specific values of Pr(TE) are important drivers of the observed male-dominated sex ratio. Our modeling approach reveals complex class-specific patterns in Pr(TE) and p * in a mark-recapture data set, and highlights challenges for the population modeling and conservation of white sharks in central California. The model we develop here can be used to estimate rates of temporary emigration and class segregation when two detection methods are used. © 2016 by the Ecological Society of America.

Acceptability of PrEP among HIV negative Portuguese men who have sex with men that attended 2014 Lisbon pride fair.

PubMed

Rocha, Luís Miguel; Campos, Maria José; Brito, João; Fuertes, Ricardo; Rojas, Jesus; Pinto, Nuno; Mendão, Luís; Esteves, Julio

2014-01-01

Consistent use of PrEP reduces HIV transmission from sexual practices amongst men who have sex with men (MSM) up to 92% [1]. Lisbon MSM cohort study estimates point that 59.3% of their participants at entrance (1593 HIV negative MSM enrolled between April 2011 and May 2013) were eligible for PrEP [2], according to the 2014 USA PrEP guidelines [3]. Studies about PrEP acceptability and implementation support policies aimed at increasing and rolling out its use. Hence, the exploratory study about PrEP acceptability in MSM at Lisbon. A street-based intercept survey, adapted from Mantell et al. study [4], was the one used on MSM attending the 2014 Lisbon pride fair. The survey included socio-demographic data, PrEP awareness and readiness to use it, probability of MSM's social network to also use it, promptness to join PrEP-related studies, type of PrEP warranted and condomless anal sex practice in the last six months. A total of 110 HIV negative Portuguese MSM responded, with a median age of 33% and 84% of them identified themselves as gay. A majority of MSM were unaware of PrEP (59%); those that were aware, had heard of it trough CheckpointLx (31%), internet (22%) or health professionals (20%). 66% were likely or very likely to participate in PrEP-related studies. 57% of MSM were likely or very likely to use PrEP if available and reported that some, if not almost all of their social network, will do it too (70%). Type of PrEP preferred was oral, a pill a day (43%), followed by oral, intermittent intake (32%). Overall 41% of MSM had condomless anal sex practice in the last six months. In this MSM Portuguese sample, a general willingness to adopt PrEP was predominant, specially the oral daily intake. Forty-one percent of participants had had condomless anal sex practice in the last six months and therefore fitted within the criteria to be on Pre-Exposure Prophylaxis (PrEP), according to MSM Risk Index in 2014 USA PrEP guidelines. PrEP, when available in Portugal, should be a powerful tool for HIV prevention in this key population.

Survival and growth of American alligator (Alligator mississippiensis) hatchlings after artificial incubation and repatriation

USGS Publications Warehouse

Temsiripong, Y.; Woodward, A.R.; Ross, J.P.; Kubilis, P.S.; Percival, H.F.

2006-01-01

Hatchling American Alligators (Alligator mississippiensis) produced from artificially incubated wild eggs were returned to their natal areas (repatriated). We compared artificially incubated and repatriated hatchlings released within and outside the maternal alligator's home range with naturally incubated hatchlings captured and released within the maternal alligator's home range on Lake Apopka, Lake Griffin, and Orange Lake in Florida. We used probability of recapture and total length at approximately nine months after hatching as indices of survival and growth rates. Artificially incubated hatchlings released outside of the maternal alligator's home range had lower recapture probabilities than either naturally incubated hatchlings or artificially incubated hatchlings released near the original nest site. Recapture probabilities of other treatments did not differ significantly. Artificially incubated hatchlings were approximately 6% shorter than naturally incubated hatchlings at approximately nine months after hatching. We concluded that repatriation of hatchlings probably would not have long-term effects on populations because of the resiliency of alligator populations to alterations of early age-class survival and growth rates of the magnitude that we observed. Repatriation of hatchlings may be an economical alternative to repatriation of older juveniles for population restoration. However, the location of release may affect subsequent survival and growth. Copyright 2006 Society for the Study of Amphibians and Reptiles.

Degradation of the Disease-Associated Prion Protein by a Serine Protease from Lichens

PubMed Central

Johnson, Christopher J.; Bennett, James P.; Biro, Steven M.; Duque-Velasquez, Juan Camilo; Rodriguez, Cynthia M.; Bessen, Richard A.; Rocke, Tonie E.

2011-01-01

The disease-associated prion protein (PrPTSE), the probable etiological agent of the transmissible spongiform encephalopathies (TSEs), is resistant to degradation and can persist in the environment. Lichens, mutualistic symbioses containing fungi, algae, bacteria and occasionally cyanobacteria, are ubiquitous in the environment and have evolved unique biological activities allowing their survival in challenging ecological niches. We investigated PrPTSE inactivation by lichens and found acetone extracts of three lichen species (Parmelia sulcata, Cladonia rangiferina and Lobaria pulmonaria) have the ability to degrade prion protein (PrP) from TSE-infected hamsters, mice and deer. Immunoblots measuring PrP levels and protein misfolding cyclic amplification indicated at least two logs of reductions in PrPTSE. Degradative activity was not found in closely related lichen species or in algae or a cyanobacterium that inhabit lichens. Degradation was blocked by Pefabloc SC, a serine protease inhibitor, but not inhibitors of other proteases or enzymes. Additionally, we found that PrP levels in PrPTSE-enriched preps or infected brain homogenates are also reduced following exposure to freshly-collected P. sulcata or an aqueous extract of the lichen. Our findings indicate that these lichen extracts efficiently degrade PrPTSE and suggest that some lichens could have potential to inactivate TSE infectivity on the landscape or be a source for agents to degrade prions. Further work to clone and characterize the protease, assess its effect on TSE infectivity and determine which organism or organisms present in lichens produce or influence the protease activity is warranted. PMID:21589935

Dynamics of Preferential Substrate Recognition in HIV-1 Protease: Redefining the Substrate Envelope

PubMed Central

Özen, Ayşegül; Haliloğlu, Türkan; Schiffer, Celia A.

2011-01-01

HIV-1 protease (PR) permits viral maturation by processing the Gag and Gag-Pro-Pol polyproteins. Though HIV-1 PR inhibitors (PIs) are used in combination antiviral therapy, the emergence of drug resistance has limited their efficacy. The rapid evolution of HIV-1 necessitates the consideration of drug resistance in novel drug-design strategies. Drug-resistant HIV-1 PR variants, while no longer efficiently inhibited, continue to efficiently hydrolyze the natural viral substrates. Though highly diverse in sequence, the HIV-1 PR substrates bind in a conserved three-dimensional shape we defined as the “substrate envelope”. We previously showed that resistance mutations arise where PIs protrude beyond the substrate envelope, as these regions are crucial for drug binding but not for substrate recognition. Here, we extend this model by considering the role of protein dynamics in the interaction of HIV-1 PR with its substrates. Seven molecular dynamics simulations of PR-substrate complexes were performed to estimate the conformational flexibility of substrates in their complexes. Interdependency of the substrate-protease interactions may compensate for the variations in cleavage-site sequences, and explain how a diverse set of sequences can be recognized as substrates by the same enzyme. This diversity may be essential for regulating sequential processing of substrates. We also define a dynamic substrate envelope as a more accurate representation of PR-substrate interactions. This dynamic substrate envelope, described by a probability distribution function, is a powerful tool for drug design efforts targeting ensembles of resistant HIV-1 PR variants with the aim of developing drugs that are less susceptible to resistance. PMID:21762811

Degradation of the disease-associated prion protein by a serine protease from lichens

USGS Publications Warehouse

Johnson, C.J.; Bennett, J.P.; Biro, S.M.; Duque-Velasquez, J.C.; Rodriguez, C.M.; Bessen, R.A.; Rocke, T.E.; Bartz, Jason C.

2011-01-01

The disease-associated prion protein (PrP(TSE)), the probable etiological agent of the transmissible spongiform encephalopathies (TSEs), is resistant to degradation and can persist in the environment. Lichens, mutualistic symbioses containing fungi, algae, bacteria and occasionally cyanobacteria, are ubiquitous in the environment and have evolved unique biological activities allowing their survival in challenging ecological niches. We investigated PrP(TSE) inactivation by lichens and found acetone extracts of three lichen species (Parmelia sulcata, Cladonia rangiferina and Lobaria pulmonaria) have the ability to degrade prion protein (PrP) from TSE-infected hamsters, mice and deer. Immunoblots measuring PrP levels and protein misfolding cyclic amplification indicated at least two logs of reductions in PrP(TSE). Degradative activity was not found in closely related lichen species or in algae or a cyanobacterium that inhabit lichens. Degradation was blocked by Pefabloc SC, a serine protease inhibitor, but not inhibitors of other proteases or enzymes. Additionally, we found that PrP levels in PrP(TSE)-enriched preps or infected brain homogenates are also reduced following exposure to freshly-collected P. sulcata or an aqueous extract of the lichen. Our findings indicate that these lichen extracts efficiently degrade PrP(TSE) and suggest that some lichens could have potential to inactivate TSE infectivity on the landscape or be a source for agents to degrade prions. Further work to clone and characterize the protease, assess its effect on TSE infectivity and determine which organism or organisms present in lichens produce or influence the protease activity is warranted.

qPR: An adaptive partial-report procedure based on Bayesian inference.

PubMed

Baek, Jongsoo; Lesmes, Luis Andres; Lu, Zhong-Lin

2016-08-01

Iconic memory is best assessed with the partial report procedure in which an array of letters appears briefly on the screen and a poststimulus cue directs the observer to report the identity of the cued letter(s). Typically, 6-8 cue delays or 600-800 trials are tested to measure the iconic memory decay function. Here we develop a quick partial report, or qPR, procedure based on a Bayesian adaptive framework to estimate the iconic memory decay function with much reduced testing time. The iconic memory decay function is characterized by an exponential function and a joint probability distribution of its three parameters. Starting with a prior of the parameters, the method selects the stimulus to maximize the expected information gain in the next test trial. It then updates the posterior probability distribution of the parameters based on the observer's response using Bayesian inference. The procedure is reiterated until either the total number of trials or the precision of the parameter estimates reaches a certain criterion. Simulation studies showed that only 100 trials were necessary to reach an average absolute bias of 0.026 and a precision of 0.070 (both in terms of probability correct). A psychophysical validation experiment showed that estimates of the iconic memory decay function obtained with 100 qPR trials exhibited good precision (the half width of the 68.2% credible interval = 0.055) and excellent agreement with those obtained with 1,600 trials of the conventional method of constant stimuli procedure (RMSE = 0.063). Quick partial-report relieves the data collection burden in characterizing iconic memory and makes it possible to assess iconic memory in clinical populations.

Guidelines for Use of the Approximate Beta-Poisson Dose-Response Model.

PubMed

Xie, Gang; Roiko, Anne; Stratton, Helen; Lemckert, Charles; Dunn, Peter K; Mengersen, Kerrie

2017-07-01

For dose-response analysis in quantitative microbial risk assessment (QMRA), the exact beta-Poisson model is a two-parameter mechanistic dose-response model with parameters α>0 and β>0, which involves the Kummer confluent hypergeometric function. Evaluation of a hypergeometric function is a computational challenge. Denoting PI(d) as the probability of infection at a given mean dose d, the widely used dose-response model PI(d)=1-(1+dβ)-α is an approximate formula for the exact beta-Poisson model. Notwithstanding the required conditions α<β and β>1, issues related to the validity and approximation accuracy of this approximate formula have remained largely ignored in practice, partly because these conditions are too general to provide clear guidance. Consequently, this study proposes a probability measure Pr(0 < r < 1 | α̂, β̂) as a validity measure (r is a random variable that follows a gamma distribution; α̂ and β̂ are the maximum likelihood estimates of α and β in the approximate model); and the constraint conditions β̂>(22α̂)0.50 for 0.02<α̂<2 as a rule of thumb to ensure an accurate approximation (e.g., Pr(0 < r < 1 | α̂, β̂) >0.99) . This validity measure and rule of thumb were validated by application to all the completed beta-Poisson models (related to 85 data sets) from the QMRA community portal (QMRA Wiki). The results showed that the higher the probability Pr(0 < r < 1 | α̂, β̂), the better the approximation. The results further showed that, among the total 85 models examined, 68 models were identified as valid approximate model applications, which all had a near perfect match to the corresponding exact beta-Poisson model dose-response curve. © 2016 Society for Risk Analysis.

qPR: An adaptive partial-report procedure based on Bayesian inference

PubMed Central

Baek, Jongsoo; Lesmes, Luis Andres; Lu, Zhong-Lin

2016-01-01

Iconic memory is best assessed with the partial report procedure in which an array of letters appears briefly on the screen and a poststimulus cue directs the observer to report the identity of the cued letter(s). Typically, 6–8 cue delays or 600–800 trials are tested to measure the iconic memory decay function. Here we develop a quick partial report, or qPR, procedure based on a Bayesian adaptive framework to estimate the iconic memory decay function with much reduced testing time. The iconic memory decay function is characterized by an exponential function and a joint probability distribution of its three parameters. Starting with a prior of the parameters, the method selects the stimulus to maximize the expected information gain in the next test trial. It then updates the posterior probability distribution of the parameters based on the observer's response using Bayesian inference. The procedure is reiterated until either the total number of trials or the precision of the parameter estimates reaches a certain criterion. Simulation studies showed that only 100 trials were necessary to reach an average absolute bias of 0.026 and a precision of 0.070 (both in terms of probability correct). A psychophysical validation experiment showed that estimates of the iconic memory decay function obtained with 100 qPR trials exhibited good precision (the half width of the 68.2% credible interval = 0.055) and excellent agreement with those obtained with 1,600 trials of the conventional method of constant stimuli procedure (RMSE = 0.063). Quick partial-report relieves the data collection burden in characterizing iconic memory and makes it possible to assess iconic memory in clinical populations. PMID:27580045

Melatonin-mediated β-catenin activation protects neuron cells against prion protein-induced neurotoxicity.

PubMed

Jeong, Jae-Kyo; Lee, Ju-Hee; Moon, Ji-Hong; Lee, You-Jin; Park, Sang-Youel

2014-11-01

Activation of β-catenin in neurons regulates mitochondrial function and protects against protein misfolding disorders, including Alzheimer's disease and Huntington's disease. Melatonin, a natural secretory product of the pineal gland, exerts neuroprotective effects through the activation of β-catenin. In this study, melatonin increased β-catenin protein expression and activation in human neuroblastoma cell lines SH-SY5Y cells. Melatonin also inhibited PrP (106-126)-induced neurotoxicity and the inhibition attenuated by treatment of β-catenin inhibitor ICG-001. Activation of β-catenin blocked PrP (106-126)-mediated downregulation of anti-apoptotic protein survivin and Bcl-2. Reduction of mitochondrial membrane potential, translocation of Bax, and cytochrome c release which induced by PrP (106-126) treatment were inhibited by β-catenin activation, which contributed to prevented PrP (106-126)-induced neuronal cell death. In conclusion, β-catenin activation by melatonin prevented PrP (106-126)-induced neuronal cell death through regulating anti-apoptotic proteins and mitochondrial pathways. These results also suggest the therapeutic value of Wnt/β-catenin signaling in prion-related disorders as influenced by melatonin. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

IRIS Toxicological Review of Trimethylbenzenes (Interagency Science Discussion Draft)

EPA Science Inventory

In September 2016, EPA finalized the IRIS assessment of Trimethylbenzenes. The Toxicological Review was reviewed internally by EPA and by other federal agencies and White House Offices before public release in June 2016. Consistent with the May 2009 IRIS assessment development pr...

Risk analysis for dry snow slab avalanche release by skier triggering

NASA Astrophysics Data System (ADS)

McClung, David

2013-04-01

Risk analysis is of primary importance for skier triggering of avalanches since human triggering is responsible for about 90% of deaths from slab avalanches in Europe and North America. Two key measureable quantities about dry slab avalanche release prior to initiation are the depth to the weak layer and the slope angle. Both are important in risk analysis. As the slope angle increases, the probability of avalanche release increases dramatically. As the slab depth increases, the consequences increase if an avalanche releases. Among the simplest risk definitions is (Vick, 2002): Risk = (Probability of failure) x (Consequences of failure). Here, these two components of risk are the probability or chance of avalanche release and the consequences given avalanche release. In this paper, for the first time, skier triggered avalanches were analyzed from probability theory and its relation to risk for both the D and . The data consisted of two quantities : (,D) taken from avalanche fracture line profiles after an avalanche has taken place. Two data sets from accidentally skier triggered avalanches were considered: (1) 718 for and (2) a set of 1242 values of D which represent average values along the fracture line. The values of D were both estimated (about 2/3) and measured (about 1/3) by ski guides from Canadian Mountain Holidays CMH). I also analyzed 1231 accidentally skier triggered avalanches reported by CMH ski guides for avalanche size (representing destructive potential) on the Canadian scale. The size analysis provided a second analysis of consequences to verify that using D. The results showed that there is an intermediate range of both D and with highest risk. ForD, the risk (product of consequences and probability of occurrence) is highest for D in the approximate range 0.6 m - 1.0 m. The consequences are low for lower values of D and the chance of release is low for higher values of D. Thus, the highest product is in the intermediate range. For slope angles, the risk analysis showed there are two ranges: ˜ 320; × 460for which risk is lowest. In this case, both the range of and the consequences vary by about a factor of two so the probability of release dominates the risk analysis to yield low risk at the tails of the distribution of with highest risk in the middle (330 - 450) of the expected range (250 - 550).

Electrophysiological properties of prion-positive cardiac progenitors derived from murine embryonic stem cells.

PubMed

Fujii, Hiroshi; Ikeuchi, Yu; Kurata, Yasutaka; Ikeda, Nobuhito; Bahrudin, Udin; Li, Peili; Nakayama, Yuji; Endo, Ryo; Hasegawa, Akira; Morikawa, Kumi; Miake, Junichiro; Yoshida, Akio; Hidaka, Kyoko; Morisaki, Takayuki; Ninomiya, Haruaki; Shirayoshi, Yasuaki; Yamamoto, Kazuhiro; Hisatome, Ichiro

2012-01-01

The prion protein (PrP) has been reported to serve as a surface maker for isolation of cardiomyogenic progenitors from murine embryonic stem (ES) cells. Although PrP-positive cells exhibited automaticity, their electrophysiological characteristics remain unresolved. The aim of the present study was therefore to investigate the electrophysiological properties of PrP-positive cells in comparison with those of HCN4p-or Nkx2.5-positive cells. Differentiation of AB1, HCN5p-EGFP and hcgp7 ES cells into cardiac progenitors was induced by embryoid body (EB) formation. EBs were dissociated and cells expressing PrP, HCN4-EGFP and/or Nkx2.5-GFP were collected via flow cytometry. Sorted cells were subjected to reverse transcriptase-polymerase chain reaction, immunostaining and patch-clamp experiments. PrP-positive cells expressed mRNA of undifferentiation markers, first and second heart field markers, and cardiac-specific genes and ion channels, indicating their commitment to cardiomyogenic progenitors. PrP-positive cells with automaticity showed positive and negative chronotropic responses to isoproterenol and carbamylcholine, respectively. Hyperpolarization-activated cation current (I(f)) was barely detectable, whereas Na(+) and L-type Ca(2+) channel currents were frequently observed. Their spontaneous activity was slowed by inhibition of sarcoplasmic reticulum Ca(2+) uptake and release but not by blocking I(f). The maximum diastolic potential of their spontaneous firings was more depolarized than that of Nkx2.5-GFP-positive cells. PrP-positive cells contained cardiac progenitors that separated from the lineage of sinoatrial node cells. PrP can be used as a marker to enrich nascent cardiac progenitors.

40 CFR 280.40 - General requirements for all UST systems.

Code of Federal Regulations, 2012 CFR

2012-07-01

... release detection that: (1) Can detect a release from any portion of the tank and the connected... shown in the table) with a probability of detection (Pd) of 0.95 and a probability of false alarm (Pfa) of 0.05. Method Section Date after which Pd/Pfa must be demonstrated Manual Tank Gauging 280.43(b...

40 CFR 280.40 - General requirements for all UST systems.

Code of Federal Regulations, 2013 CFR

2013-07-01

... release detection that: (1) Can detect a release from any portion of the tank and the connected... shown in the table) with a probability of detection (Pd) of 0.95 and a probability of false alarm (Pfa) of 0.05. Method Section Date after which Pd/Pfa must be demonstrated Manual Tank Gauging 280.43(b...

40 CFR 280.40 - General requirements for all UST systems.

Code of Federal Regulations, 2010 CFR

2010-07-01

... release detection that: (1) Can detect a release from any portion of the tank and the connected... shown in the table) with a probability of detection (Pd) of 0.95 and a probability of false alarm (Pfa) of 0.05. Method Section Date after which Pd/Pfa must be demonstrated Manual Tank Gauging 280.43(b...

40 CFR 280.40 - General requirements for all UST systems.

Code of Federal Regulations, 2011 CFR

2011-07-01

... release detection that: (1) Can detect a release from any portion of the tank and the connected... shown in the table) with a probability of detection (Pd) of 0.95 and a probability of false alarm (Pfa) of 0.05. Method Section Date after which Pd/Pfa must be demonstrated Manual Tank Gauging 280.43(b...

40 CFR 280.40 - General requirements for all UST systems.

Code of Federal Regulations, 2014 CFR

2014-07-01

... release detection that: (1) Can detect a release from any portion of the tank and the connected... shown in the table) with a probability of detection (Pd) of 0.95 and a probability of false alarm (Pfa) of 0.05. Method Section Date after which Pd/Pfa must be demonstrated Manual Tank Gauging 280.43(b...

[Perception of risk factors for cancer in the Spanish population].

PubMed

Sanz-Barbero, Belén; Prieto-Flores, María Eugenia; Otero-García, Laura; Abt-Sacks, Analía; Bernal, Mariola; Cambas, Naiara

2014-01-01

To analyze the perception of the Spanish population of risk factors for cancer. Data were extracted from the OncoBarometro 2010 survey. Multivariate logistic models were applied to analyze the perception of the population on the importance of various risk factors: smoking, alcohol, sun, food, weight, sexually transmitted diseases, family history, radiation exposure, exposure to toxic substances and air pollution. The answers were rated on a 0 to 10 scale and were converted to low (0-6) and high (7-10) categories. The measure of association used was the prevalence ratio (PR). The greatest importance was assigned to smoking (high importance: 83.1%), whereas the least importance was assigned to weight (26.5%). In general, the probability of perceiving risk factors as important was lower among men (PR sun: 0.87; PR sexually transmitted diseases: 0.78) and increased among people who received professional advice on cancer prevention (PR alcohol: 1.11; PR sun: 1.18; PR food; 1.31; PR weight: 1.92). In particular, knowledge of symptoms and extreme fear of cancer were associated with perceiving smoking as an important risk factor, whereas a high perceived vulnerability to cancer was associated with perceiving exposure to toxic substances, pollution and smoking as important risk factors. Greater awareness is required of the association of cancer with overweight and sexually transmitted diseases. The recommendations given by health professionals on cancer prevention are key to increasing the population's awareness of risk factors for cancer. Copyright © 2013 SESPAS. Published by Elsevier Espana. All rights reserved.

Hard choices in assessing survival past dams — a comparison of single- and paired-release strategies

USGS Publications Warehouse

Zydlewski, Joseph D.; Stich, Daniel S.; Sigourney, Douglas B.

2017-01-01

Mark–recapture models are widely used to estimate survival of salmon smolts migrating past dams. Paired releases have been used to improve estimate accuracy by removing components of mortality not attributable to the dam. This method is accompanied by reduced precision because (i) sample size is reduced relative to a single, large release; and (ii) variance calculations inflate error. We modeled an idealized system with a single dam to assess trade-offs between accuracy and precision and compared methods using root mean squared error (RMSE). Simulations were run under predefined conditions (dam mortality, background mortality, detection probability, and sample size) to determine scenarios when the paired release was preferable to a single release. We demonstrate that a paired-release design provides a theoretical advantage over a single-release design only at large sample sizes and high probabilities of detection. At release numbers typical of many survival studies, paired release can result in overestimation of dam survival. Failures to meet model assumptions of a paired release may result in further overestimation of dam-related survival. Under most conditions, a single-release strategy was preferable.

Southern African guidelines on the safe use of pre-exposure prophylaxis in persons at risk of acquiring HIV-1 infection

PubMed Central

Rebe, Kevin; Venter, Francois; Maartens, Gary; Moorhouse, Michelle; Conradie, Francesca; Wallis, Carole; Black, Vivian; Harley, Beth; Eakles, Robyn

2016-01-01

The Southern African HIV Clinicians Society published its first set of oral pre-exposure prophylaxis (PrEP) guidelines in June 2012 for men who have sex with men (MSM) who are at risk of HIV infection. With the flurry of data that has been generated in PrEP clinical research since the first guideline, it became evident that there was a need to revise and expand the PrEP guidelines with new evidence of safety and efficacy of PrEP in several populations, including MSM, transgender persons, heterosexual men and women, HIV-serodiscordant couples and people who inject drugs. This need is particularly relevant following the World Health Organization (WHO) Consolidated Treatment Guidelines released in September 2015. These guidelines advise that PrEP is a highly effective, safe, biomedical option for HIV prevention that can be incorporated with other combination prevention strategies in Southern Africa, given the high prevalence of HIV in the region. PrEP should be tailored to populations at highest risk of HIV acquisition, whilst further data from studies in the region accrue to guide optimal deployment to realise the greatest impact regionally. PrEP may be used intermittently during periods of perceived HIV acquisition risk, rather than continually and lifelong, as is the case with antiretroviral treatment. Recognition and accurate measurement of potential risk in individuals and populations also warrants discussion, but are not extensively covered in these guidelines. PMID:29568613

Behavioral profiles of the captive juvenile whooping crane (Grus americana) as an indicator of reintroduction behavior and survival

USGS Publications Warehouse

Kreger, M.D.

2003-01-01

Predation by bobcats (Lynx rufus) has been the greatest cause of mortality of whooping cranes (Grus americana) in the reintroduced population in Florida. This study investigated whether the behavior of juvenile cranes during captive rearing and shortly after release can be used to predict their chances of survival once released in the wild. This study also examined differences in behavior based on rearing treatments and whether differences observed during rearing continued at the release site. Experimental rearing treatments were parent reared (PR), hand reared (RR), and hand reared with exercise (HRE). Two annual cycles of cranes were observed from hatch to 20 weeks of age in captivity (n=56 birds). Post-release bebavioral data were collected at the release site for a minimum of two weeks (n=34 birds), with mortality data collected up to one year post release (n=38 birds). Behavioral time budgets were compared using repeated measures ANOVA. Logistic regression was used to build a model to identify behaviors that were associated with first-year survival. During rearing, PR birds were the most vigilant. There were no behavioral differences between HR and HRE birds. Generally, rearing treatments had few long-term effects on the post-release behavior of the birds. The main behavioral differences during rearing and after release were the frequency of bouts and the percentage of time spent performing different behaviors. This may be attributed to foraging strategies and adaptation from captive conditions to the wild. Survival was not related to rearing treatment. Fifty-five percent of the birds survived the first year post-release based upon data pooled over two years. During rearing, the frequency of foraging bouts was positively correlated to survival. Survival was negatively correlated to the frequency of walking bouts during rearing, and release weight of the birds. These correlations accounted for 32 percent of the variability in survival. At the release site, 20 percent of post-release survival was negatively correlated with the frequency of non vigilant bouts. This study suggests that none of the rearing treatments confer a survival advantage during the first year post release, however, survival may be improved by encouraging additional foraging opportunities during rearing.

Alternative Asbestos Control Method and the Asbestos Releasability Research

EPA Science Inventory

Alternative Asbestos Control Method shows promise in speed, cost, and efficiency if equally protective. ORD conducted side by side test of AACM vs NESHAP on identical asbestos-containing buildings at Fort Chaffee. This abstract and presentation are based, at least in part, on pr...

IRIS Toxicological Review of Pentachlorophenol (Interagency Science Discussion Draft)

EPA Science Inventory

EPA is releasing the draft report, Toxicological Review of Pentachlorophenol, that was distributed to Federal agencies and White House Offices for comment during the Science Discussion step of the IRIS Assessment Development Pr...

Incorporation of thorium in the rhabdophane structure: Synthesis and characterization of Pr1-2xCaxThxPO4·nH2O solid solutions

NASA Astrophysics Data System (ADS)

Qin, Danwen; Mesbah, Adel; Gausse, Clémence; Szenknect, Stéphanie; Dacheux, Nicolas; Clavier, Nicolas

2017-08-01

Thorium incorporation in the rhabdophane structure as Pr1-2xCaxThxPO4·nH2O solid solutions was successfully achieved and resulted in the preparation of a low temperature precursor of the monazite-cheralite type Pr1-2xCaxThxPO4. The rhabdophane compounds are considered as potential neoformed phases in case of release of actinides from the phosphate-based ceramic wasteforms envisaged to host radionuclides in the back-end of the nuclear fuel cycle. A multiparametric study was thus undertaken to specify the wet chemistry conditions (starting stoichiometry, temperature, heating time) leading to single phase Pr1-2xCaxThxPO4·nH2O powdered samples. The excess of calcium appeared to be a prevailing factor with a suggested initial Ca:Th ratio being equal to 10. Similarly, the recommended heating time should exceed 4 days while the optimal temperature of synthesis is 110 °C. Under these conditions, the stability domain of Pr1-2xCaxThxPO4·nH2O ranged from x = 0.00 to x = 0.15. After heating at 1100 °C under air during 6 h, rhabdophane-type samples were fully converted into the highly durable Pr1-2xCaxThxPO4 cheralite ceramic wasteform.

Vernonia cinerea Less. supplementation and strenuous exercise reduce smoking rate: relation to oxidative stress status and beta-endorphin release in active smokers.

PubMed

Leelarungrayub, Donrawee; Pratanaphon, Sainatee; Pothongsunun, Prapas; Sriboonreung, Thanyaluck; Yankai, Araya; Bloomer, Richard J

2010-05-26

The aim of this study was to evaluate the effects of Vernonia cinerea Less. (VC) supplementation and exercise on oxidative stress biomarkers, beta-endorphin release, and the rate of cigarette smoking. Volunteer smokers were randomly divided into four groups: group 1: VC supplement; group 2: exercise with VC supplement; group 3: exercise; and group 4: control. VC was prepared by wash and dry techniques and taken orally before smoking, matching the frequency of strenuous exercise (three times weekly). Before and after a two month period, exhaled carbon monoxide (CO), blood oxidative stress (malondialdehyde [MDA], nitric oxide [NOx], protein hydroperoxide [PrOOH] and total antioxidant capacity [TAC]), beta-endorphin and smoking rate were measured, and statistically analyzed. In Group 1, MDA, PrOOH, and NOx significantly decreased, whereas TAC increased (p < 0.05). In Group 2, MDA and PrOOH decreased (p < 0.05), with no other changes noted (p > 0.05). In Group 3, MDA, PrOOH, NOx, TAC, and beta-endorphin levels increased significantly (p < 0.05). Group 4 showed no change in oxidative stress variables or beta-endorphine levels (p > 0.05). All groups had lower levels of CO after the intervention. The smoking rate for light cigarette decreased in group 2(62.7%), 1(59.52%), 3 (53.57%) and 4(14.04%), whereas in self-rolled cigarettes it decreased in group 1 (54.47%), 3 (42.30%), 2 (40%) and 4 (9.2%). Supplementation with Vernonia cinerea Less and exercise provided benefit related to reduced smoking rate, which may be related to oxidaive stress and beta-endorphine levels.

Vernonia cinerea Less. supplementation and strenuous exercise reduce smoking rate: relation to oxidative stress status and beta-endorphin release in active smokers

PubMed Central

2010-01-01

Purpose The aim of this study was to evaluate the effects of Vernonia cinerea Less. (VC) supplementation and exercise on oxidative stress biomarkers, beta-endorphin release, and the rate of cigarette smoking. Methods Volunteer smokers were randomly divided into four groups: group 1: VC supplement; group 2: exercise with VC supplement; group 3: exercise; and group 4: control. VC was prepared by wash and dry techniques and taken orally before smoking, matching the frequency of strenuous exercise (three times weekly). Before and after a two month period, exhaled carbon monoxide (CO), blood oxidative stress (malondialdehyde [MDA], nitric oxide [NOx], protein hydroperoxide [PrOOH] and total antioxidant capacity [TAC]), beta-endorphin and smoking rate were measured, and statistically analyzed. Results In Group 1, MDA, PrOOH, and NOx significantly decreased, whereas TAC increased (p < 0.05). In Group 2, MDA and PrOOH decreased (p < 0.05), with no other changes noted (p > 0.05). In Group 3, MDA, PrOOH, NOx, TAC, and beta-endorphin levels increased significantly (p < 0.05). Group 4 showed no change in oxidative stress variables or beta-endorphine levels (p > 0.05). All groups had lower levels of CO after the intervention. The smoking rate for light cigarette decreased in group 2(62.7%), 1(59.52%), 3 (53.57%) and 4(14.04%), whereas in self-rolled cigarettes it decreased in group 1 (54.47%), 3 (42.30%), 2 (40%) and 4 (9.2%). Conclusion Supplementation with Vernonia cinerea Less and exercise provided benefit related to reduced smoking rate, which may be related to oxidaive stress and beta-endorphine levels. PMID:20500899

A guide to treating gait impairment with prolonged-release fampridine (Fampyra®) in patients with multiple sclerosis.

PubMed

Ramió-Torrentà, L; Álvarez-Cermeño, J C; Arroyo, R; Casanova-Estruch, B; Fernández, O; García-Merino, J A; Hernández, M A; Izquierdo, G; Martínez-Yélamos, S; Meca, J; Moral, E; Olascoaga, J; Prieto, J M; Saiz, A

2018-06-01

Gait impairment, a frequent sign in multiple sclerosis (MS), places a major burden on patients since it results in progressive loss of personal and social autonomy, along with work productivity. This guide aims to provide recommendations on how to evaluate gait impairment and use prolonged-release fampridine (PR-fampridine) as treatment for MS patients with gait impairment in Spain. PR-fampridine dosed at 10mg every 12hours is currently the only drug approved to treat gait impairment in adults with MS. Additionally, PR-fampridine has been shown in clinical practice to significantly improve quality of life (QoL) in patients who respond to treatment. Treatment response can be assessed with the Timed 25-Foot Walk (T25FW) or the 12-item MS Walking Scale (MSWS-12); tests should be completed before and after starting treatment. The minimum time recommended for evaluating treatment response is 2 weeks after treatment onset. Patients are considered responders and permitted to continue the treatment when they demonstrate a decrease in their T25FW time or an increase in MSWS-12 scores. A re-evaluation is recommended at least every 6 months. The SF-36 (Short Form-36) and the MSIS-29 (MS Impact Scale-29) tests are recommended for clinicians interested in performing a detailed QoL assessment. This drug is generally well-tolerated and has a good safety profile. It should be taken on an empty stomach and renal function must be monitored regularly. These recommendations will help ensure safer and more efficient prescription practices and easier management of PR-fampridine as treatment for gait impairment in Spanish adults with MS. Copyright © 2015 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

The impact of new partial AUC parameters for evaluating the bioequivalence of prolonged-release formulations.

PubMed

Boily, Michaël; Dussault, Catherine; Massicotte, Julie; Guibord, Pascal; Lefebvre, Marc

2015-01-23

To demonstrate bioequivalence (BE) between two prolonged-release (PR) drug formulations, single dose studies under fasting and fed state as well as at least one steady-state study are currently required by the European Medicines Agency (EMA). Recently, however, there have been debates regarding the relevance of steady-state studies. New requirements in single-dose investigations have also been suggested by the EMA to address the absence of a parameter that can adequately assess the equivalence of the shape of the curves. In the draft guideline issued in 2013, new partial area under the curve (pAUC) pharmacokinetic (PK) parameters were introduced to that effect. In light of these potential changes, there is a need of supportive clinical evidence to evaluate the impact of pAUCs on the evaluation of BE between PR formulations. In this retrospective analysis, it was investigated whether the newly defined parameters were associated with an increase in discriminatory ability or a change in variability compared to the conventional PK parameters. Among the single dose studies that met the requirements already in place, 20% were found unable to meet the EMA's new requirements in regards to the pAUC PK parameters. When pairing fasting and fed studies for a same formulation, the failure rate increased to 40%. In some cases, due to the high variability of these parameters, an increase of the sample size would be required to prove BE. In other cases however, the pAUC parameters demonstrated a robust ability to detect differences between the shapes of the curves of PR formulations. The present analysis should help to better understand the impact of the upcoming changes in European regulations on PR formulations and in the design of future BE studies. Copyright © 2014 Elsevier B.V. All rights reserved.

Contribution of prolonged-release melatonin and anti-benzodiazepine campaigns to the reduction of benzodiazepine and Z-drugs consumption in nine European countries.

PubMed

Clay, Emilie; Falissard, Bruno; Moore, Nicholas; Toumi, Mondher

2013-04-01

Benzodiazepines (BZD) and benzodiazepine receptor agonists (zolpidem, zaleplon, zopiclone, altogether Z-drugs) are most commonly prescribed for the treatment of insomnia. However, long-term use of BZD/Z-drugs is associated with major adverse events including, but not limited to, falls and fractures, domestic and traffic accidents, confusion, cognitive impairment, Alzheimer's disease and cancer. The prolonged use of these drugs is thought to be related to severe withdrawal symptoms and potential dependency. The chronic and extensive use of BZD/Z drugs has become a public health issue and has led to multiple campaigns to reduce both prescription and consumption of BZD/Z-drugs. Prolonged-release (PR) melatonin is the first of a new class of melatonin receptor agonist drugs that has demonstrated clinically relevant efficacy on improving quality of sleep and morning alertness, with a good safety profile. This study aimed to analyze and evaluate the impact of anti-BZD/Z-drugs campaigns and the availability of alternative pharmacotherapy (PR-melatonin) on the consumption of BZD and Z-drugs in several European countries. Annual sales data from nine European countries were extracted from the IMS sales database and analyzed to determine whether trends in use of these treatment options were attributed to campaigns and/or availability and affordability of safer alternatives on the market. Campaigns aiming to reduce the use of BZD/Z-drugs failed when they were not associated with the availability and market uptake of PR-melatonin. The reimbursement of PR-melatonin supports better penetration rates and a higher reduction in sales for BZD/Z-drugs.

Population pharmacokinetic modelling of tramadol using inverse Gaussian function for the assessment of drug absorption from prolonged and immediate release formulations.

PubMed

Brvar, Nina; Mateović-Rojnik, Tatjana; Grabnar, Iztok

2014-10-01

This study aimed to develop a population pharmacokinetic model for tramadol that combines different input rates with disposition characteristics. Data used for the analysis were pooled from two phase I bioavailability studies with immediate (IR) and prolonged release (PR) formulations in healthy volunteers. Tramadol plasma concentration-time data were described by an inverse Gaussian function to model the complete input process linked to a two-compartment disposition model with first-order elimination. Although polymorphic CYP2D6 appears to be a major enzyme involved in the metabolism of tramadol, application of a mixture model to test the assumption of two and three subpopulations did not reveal any improvement of the model. The final model estimated parameters with reasonable precision and was able to estimate the interindividual variability of all parameters except for the relative bioavailability of PR vs. IR formulation. Validity of the model was further tested using the nonparametric bootstrap approach. Finally, the model was applied to assess absorption kinetics of tramadol and predict steady-state pharmacokinetics following administration of both types of formulations. For both formulations, the final model yielded a stable estimate of the absorption time profiles. Steady-state simulation supports switching of patients from IR to PR formulation. Copyright © 2014 Elsevier B.V. All rights reserved.

Proteolytic Processing and Assembly of gag and gag-pol Proteins of TED, a Baculovirus-Associated Retrotransposon of the Gypsy Family

PubMed Central

Hajek, Kathryn L.; Friesen, Paul D.

1998-01-01

TED (transposable element D) is an env-containing member of the gypsy family of retrotransposons that represents a possible retrovirus of invertebrates. This lepidopteran (moth) retroelement contains gag and pol genes that encode proteins capable of forming viruslike particles (VLP) with reverse transcriptase. Since VLP are likely intermediates in TED transposition, we investigated the roles of gag and pol in TED capsid assembly and maturation. By using constructed baculovirus vectors and TED Gag-specific antiserum, we show that the principal translation product of gag (Pr55gag) is cleaved to produce a single VLP structural protein, p37gag. Replacement of Asp436 within the retrovirus-like active site of the pol-encoded protease (PR) abolished Pr55gag cleavage and demonstrated the requirement for PR in capsid processing. As shown by expression of an in-frame fusion of TED gag and pol, PR is derived from the Gag-Pol polyprotein Pr195gag-pol. The PR cleavage site within Pr55gag was mapped to a position near the junction of a basic, nucleocapsid-like domain and a C-terminal acidic domain. Once released by cleavage, the C-terminal fragment was not detected. This acidic fragment was dispensable for VLP assembly, as demonstrated by the formation of VLP by C-terminal Pr55gag truncation proteins and replacement of the acidic domain with a heterologous protein. In contrast, C-terminal deletions that extended into the adjacent nucleocapsid-like domain of Pr55gag abolished VLP recovery and demonstrated that this central region contributes to VLP assembly or stability, or both. Collectively, these data suggest that the single TED protein p37gag provides both capsid and nucleocapsid functions. TED may therefore use a simple processing strategy for VLP assembly and genome packaging. PMID:9765414

Proteolytic processing and assembly of gag and gag-pol proteins of TED, a baculovirus-associated retrotransposon of the gypsy family.

PubMed

Hajek, K L; Friesen, P D

1998-11-01

TED (transposable element D) is an env-containing member of the gypsy family of retrotransposons that represents a possible retrovirus of invertebrates. This lepidopteran (moth) retroelement contains gag and pol genes that encode proteins capable of forming viruslike particles (VLP) with reverse transcriptase. Since VLP are likely intermediates in TED transposition, we investigated the roles of gag and pol in TED capsid assembly and maturation. By using constructed baculovirus vectors and TED Gag-specific antiserum, we show that the principal translation product of gag (Pr55(gag)) is cleaved to produce a single VLP structural protein, p37(gag). Replacement of Asp436 within the retrovirus-like active site of the pol-encoded protease (PR) abolished Pr55(gag) cleavage and demonstrated the requirement for PR in capsid processing. As shown by expression of an in-frame fusion of TED gag and pol, PR is derived from the Gag-Pol polyprotein Pr195(gag-pol). The PR cleavage site within Pr55(gag) was mapped to a position near the junction of a basic, nucleocapsid-like domain and a C-terminal acidic domain. Once released by cleavage, the C-terminal fragment was not detected. This acidic fragment was dispensable for VLP assembly, as demonstrated by the formation of VLP by C-terminal Pr55(gag) truncation proteins and replacement of the acidic domain with a heterologous protein. In contrast, C-terminal deletions that extended into the adjacent nucleocapsid-like domain of Pr55(gag) abolished VLP recovery and demonstrated that this central region contributes to VLP assembly or stability, or both. Collectively, these data suggest that the single TED protein p37(gag) provides both capsid and nucleocapsid functions. TED may therefore use a simple processing strategy for VLP assembly and genome packaging.

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.

The promises and challenges of pre-exposure prophylaxis as part of the emerging paradigm of combination HIV prevention.

PubMed

Cáceres, Carlos F; Koechlin, Florence; Goicochea, Pedro; Sow, Papa-Salif; O'Reilly, Kevin R; Mayer, Kenneth H; Godfrey-Faussett, Peter

2015-01-01

Towards the end of the twentieth century, significant success was achieved in reducing incidence in several global HIV epidemics through ongoing prevention strategies. However, further progress in risk reduction was uncertain. For one thing, it was clear that social vulnerability had to be addressed, through research on interventions addressing health systems and other structural barriers. As soon as antiretroviral treatment became available, researchers started to conceive that antiretrovirals might play a role in decreasing either susceptibility in uninfected people or infectiousness among people living with HIV. In this paper we focus on the origin, present status, and potential contribution of pre-exposure prophylaxis (PrEP) within the combination HIV prevention framework. After a phase of controversy, PrEP efficacy trials took off. By 2015, daily oral PrEP, using tenofovir alone or in combination with emtricitabine, has been proven efficacious, though efficacy seems heavily contingent upon adherence to pill uptake. Initial demonstration projects after release of efficacy results have shown that PrEP can be implemented in real settings and adherence can be high, leading to high effectiveness. Despite its substantial potential, beliefs persist about unfeasibility in real-life settings due to stigma, cost, adherence, and potential risk compensation barriers. The strategic synergy of behavioural change communication, biomedical strategies (including PrEP), and structural programmes is providing the basis for the combination HIV prevention framework. If PrEP is to ever become a key component of that framework, several negative beliefs must be confronted based on emerging evidence; moreover, research gaps regarding PrEP implementation must be filled, and appropriate prioritization strategies must be set up. Those challenges are significant, proportional to the impact that PrEP implementation may have in the global response to HIV.

The promises and challenges of pre-exposure prophylaxis as part of the emerging paradigm of combination HIV prevention

PubMed Central

Cáceres, Carlos F; Koechlin, Florence; Goicochea, Pedro; Sow, Papa-Salif; O'Reilly, Kevin R; Mayer, Kenneth H; Godfrey-Faussett, Peter

2015-01-01

Introduction Towards the end of the twentieth century, significant success was achieved in reducing incidence in several global HIV epidemics through ongoing prevention strategies. However, further progress in risk reduction was uncertain. For one thing, it was clear that social vulnerability had to be addressed, through research on interventions addressing health systems and other structural barriers. As soon as antiretroviral treatment became available, researchers started to conceive that antiretrovirals might play a role in decreasing either susceptibility in uninfected people or infectiousness among people living with HIV. In this paper we focus on the origin, present status, and potential contribution of pre-exposure prophylaxis (PrEP) within the combination HIV prevention framework. Discussion After a phase of controversy, PrEP efficacy trials took off. By 2015, daily oral PrEP, using tenofovir alone or in combination with emtricitabine, has been proven efficacious, though efficacy seems heavily contingent upon adherence to pill uptake. Initial demonstration projects after release of efficacy results have shown that PrEP can be implemented in real settings and adherence can be high, leading to high effectiveness. Despite its substantial potential, beliefs persist about unfeasibility in real-life settings due to stigma, cost, adherence, and potential risk compensation barriers. Conclusions The strategic synergy of behavioural change communication, biomedical strategies (including PrEP), and structural programmes is providing the basis for the combination HIV prevention framework. If PrEP is to ever become a key component of that framework, several negative beliefs must be confronted based on emerging evidence; moreover, research gaps regarding PrEP implementation must be filled, and appropriate prioritization strategies must be set up. Those challenges are significant, proportional to the impact that PrEP implementation may have in the global response to HIV. PMID:26198341

Effect of hyperthyroidism on circulating prolactin and hypothalamic expression of tyrosine hydroxylase, prolactin signaling cascade members and estrogen and progesterone receptors during late pregnancy and lactation in the rat.

PubMed

Pennacchio, Gisela E; Neira, Flavia J; Soaje, Marta; Jahn, Graciela A; Valdez, Susana R

2017-02-15

Hyperthyroidism (HyperT) compromises pregnancy and lactation, hindering suckling-induced PRL release. We studied the effect of HyperT on hypothalamic mRNA (RT-qPCR) and protein (Western blot) expression of tyrosine hydroxylase (TH), PRL receptor (PRLR) and signaling pathway members, estrogen-α (ERα) and progesterone (PR) receptors on late pregnancy (days G19, 20 and 21) and early lactation (L2) in rats. HyperT advanced pre-partum PRL release, reduced circulating PRL on L2 and increased TH mRNA (G21 and L2), p-TH, PRLR mRNA, STAT5 protein (G19 and L2), PRLR protein (G21) and CIS protein (G19). PRs mRNAs and protein decreased on G19 but afterwards PRA mRNA (G20), PRB mRNA (G21) and PRA mRNA and protein (L2) increased. ERα protein increased on G19 and decreased on G20. Thus, the altered hypothalamic PRLR, STAT5, PR and ERα expression in hyperthyroid rats may induce elevated TH expression and activation, that consequently, elevate dopaminergic tone during lactation, blunting suckling-induced PRL release and litter growth. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Estimating the population size and colony boundary of subterranean termites by using the density functions of directionally averaged capture probability.

PubMed

Su, Nan-Yao; Lee, Sang-Hee

2008-04-01

Marked termites were released in a linear-connected foraging arena, and the spatial heterogeneity of their capture probabilities was averaged for both directions at distance r from release point to obtain a symmetrical distribution, from which the density function of directionally averaged capture probability P(x) was derived. We hypothesized that as marked termites move into the population and given sufficient time, the directionally averaged capture probability may reach an equilibrium P(e) over the distance r and thus satisfy the equal mixing assumption of the mark-recapture protocol. The equilibrium capture probability P(e) was used to estimate the population size N. The hypothesis was tested in a 50-m extended foraging arena to simulate the distance factor of field colonies of subterranean termites. Over the 42-d test period, the density functions of directionally averaged capture probability P(x) exhibited four phases: exponential decline phase, linear decline phase, equilibrium phase, and postequilibrium phase. The equilibrium capture probability P(e), derived as the intercept of the linear regression during the equilibrium phase, correctly projected N estimates that were not significantly different from the known number of workers in the arena. Because the area beneath the probability density function is a constant (50% in this study), preequilibrium regression parameters and P(e) were used to estimate the population boundary distance 1, which is the distance between the release point and the boundary beyond which the population is absent.

Angiotensin Receptor Blockers and Risk of Prostate Cancer among United States Veterans

PubMed Central

Rao, Gowtham A; Mann, Joshua R.; Bottai, Matteo; Uemura, Hiroji; Burch, James B; Bennett, Charles Lee; Haddock, Kathlyn Sue; Hébert, James R

2013-01-01

Objectives To address concerns regarding increased risk of prostate cancer (PrCA) among Angiotensin Receptor Blocker users, we used national retrospective data from the Department of Veterans Affairs (VA) through the Veterans Affairs Informatics and Computing Infrastructure (VINCI). Methods We identified a total of 543,824 unique Veterans who were classified into either ARB treated or not-treated in 1:15 ratio. The two groups were balanced using inverse probability of treatment weights. A double-robust cox-proportional hazards model was used to estimate the hazard ratio for PrCA incidence. To evaluate for a potential Gleason score stage migration we conducted weighted Cochrane-Armitage test. Results Post weighting, the rates of PrCA in treated and not-treated groups were 506 (1.5%) and 8,269 (1.6%), respectively; representing a hazard ratio of (0.91, p-value 0.049). There was no significant difference in Gleason scores between the two groups. Conclusions We found a small, but statistically significant, reduction in the incidence of clinically detected PrCA among patients assigned to receive ARB with no countervailing effect on degree of differentiation (as indicated by Gleason score). Findings from this study support FDA’s recent conclusion that ARB use does not increase risk of incident PrCA. PMID:23686462

Factors associated with recurrence of alcohol-related traffic violations in southern Brazil.

PubMed

Schmitz, Aurinez R; Goldim, José R; Guimarães, Luciano S P; Lopes, Fernanda M; Kessler, Felix; Sousa, Tanara; Gonçalves, Veralice M; Pechansky, Flavio

2014-09-01

To analyze variables associated with recurrence of blood alcohol content (BAC)-related traffic violations among drivers in southern Brazil. This cross-sectional study included 12,204 driving-under-the-influence (DUI) offenders according to data provided by the Rio Grande do Sul state Transportation Department. Sociodemographic characteristics, license duration, license category, and psychological assessment results were analyzed. Drivers convicted of DUI more than once in 2009/2010 were considered recidivists. Variables were evaluated using descriptive statistical analysis and Poisson regression, adjusted by sex, age, and education level. A total of 538 (4.41%) drivers were considered recidivists. The following variables showed the strongest associations with recidivism: being aged 41-50 years (prevalence ratio [PR] = 3.41), being licensed for ≥ 12 years (PR = 1.86), being licensed for motorcycles, cars and trucks (PR = 1.36), having a license with psychological restrictions (PR = 1.33), and driving a truck or a similar vehicle at the moment of notification (PR = 1.08). In the age group with the highest risk for recurrence, drivers showed a higher probability of having a diagnosis of alcohol dependence and other psychiatric comorbidities that hinder the control of alcohol use. Psychological assessments seem to be important in predicting repeat offenses, especially when limited aptitudes are suspected, and should therefore be better investigated.

Promoter/repressor system of Lactobacillus plantarum phage og1e: characterization of the promoters pR49-pR-pL and overproduction of the cro-like protein cng in Escherichia coli.

PubMed

Kakikawa, M; Watanabe, N; Funawatashi, T; Oki, M; Yasukawa, H; Taketo, A; Kodaira, K I

1998-07-30

The Lactobacillus plantarum phage og1e (42259bp) has two repressor-like genes cng and cpg oriented oppositely, accompanied by three potential promoters pR, pL and pR49, and seven operator-like sequences (GATAC-boxes) (Kodaira et al., 1997). In this study, the og1e putative promoters were introduced into the Escherichia coli promoter-detecting plasmid pKK232-8. In E. coli CK111, pR (pKPR1), pL (pKPL1) and pR49 (pKPR49) exhibited distinct CAT activities. When pKPR1 or pKPL1 was coexistent with a compatible plasmid pACYC184 carrying pR-cng (pA4PRCN1), the CAT activity was decreased significantly. On the other hand, cng directed a protein (Cng) of 10.1 kDa in E. coli under the control of T7 promoter. Gel mobility-shift assays demonstrated that Cng binds specifically to a DNA region containing the GATAC-boxes. In addition, primer extension analyses demonstrated that the two sequences pR and pL act as a promoter in L. plantarum as well as in E. coli. These results suggested that the potential promoters pR and pL probably function for the lytic and lysogenic pathways, respectively, and Cng may act as a repressor presumably through the GATAC-boxes as operators.

Estimation of sensitivity and specificity of pregnancy diagnosis using transrectal ultrasonography and ELISA for pregnancy-associated glycoprotein in dairy cows using a Bayesian latent class model.

PubMed

Shephard, R W; Morton, J M

2018-01-01

To determine the sensitivity (Se) and specificity (Sp) of pregnancy diagnosis using transrectal ultrasonography and an ELISA for pregnancy-associated glycoprotein (PAG) in milk, in lactating dairy cows in seasonally calving herds approximately 85-100 days after the start of the herd's breeding period. Paired results were used from pregnancy diagnosis using transrectal ultrasonography and ELISA for PAG in milk carried out approximately 85 and 100 days after the start of the breeding period, respectively, from 879 cows from four herds in Victoria, Australia. A Bayesian latent class model was used to estimate the proportion of cows pregnant, the Se and Sp of each test, and covariances between test results in pregnant and non-pregnant cows. Prior probability estimates were defined using beta distributions for the expected proportion of cows pregnant, Se and Sp for each test, and covariances between tests. Markov Chain Monte Carlo iterations identified posterior distributions for each of the unknown variables. Posterior distributions for each parameter were described using medians and 95% probability (i.e. credible) intervals (PrI). The posterior median estimates for Se and Sp for each test were used to estimate positive predictive and negative predictive values across a range of pregnancy proportions. The estimate for proportion pregnant was 0.524 (95% PrI = 0.485-0.562). For pregnancy diagnosis using transrectal ultrasonography, Se and Sp were 0.939 (95% PrI = 0.890-0.974) and 0.943 (95% PrI = 0.885-0.984), respectively; for ELISA, Se and Sp were 0.963 (95% PrI = 0.919-0.990) and 0.870 (95% PrI = 0.806-0.931), respectively. The estimated covariance between test results was 0.033 (95% PrI = 0.008-0.046) and 0.035 (95% PrI = 0.018-0.078) for pregnant and non-pregnant cows, respectively. Pregnancy diagnosis results using transrectal ultrasonography had a higher positive predictive value but lower negative predictive value than results from the ELISA across the range of pregnancy proportions assessed. Pregnancy diagnosis using transrectal ultrasonography and ELISA for PAG in milk had similar Se but differed in predictive values. Pregnancy diagnosis in seasonally calving herds around 85-100 days after the start of the breeding period using the ELISA is expected to result in a higher negative predictive value but lower positive predictive value than pregnancy diagnosis using transrectal ultrasonography. Thus, with the ELISA, a higher proportion of the cows with negative results will be non-pregnant, relative to results from transrectal ultrasonography, but a lower proportion of cows with positive results will be pregnant.

Stent-based delivery of adeno-associated viral vectors with sustained vascular transduction and iNOS-mediated inhibition of in-stent restenosis

PubMed Central

Fishbein, Ilia; Guerrero, David T.; Alferiev, Ivan S.; Foster, Jonathan B.; Minutolo, Nicholas G.; Chorny, Michael; Mas Monteys, Alejandro; Driesbaugh, Kathryn H.; Nagaswami, Chandrasekaran; Levy, Robert J.

2017-01-01

In-stent restenosis remains an important clinical problem in the era of drug eluting stents. Development of clinical gene therapy protocols for the prevention and treatment of in-stent restenosis is hampered by the lack of adequate local delivery systems. Herein we describe a novel stent-based gene delivery platform capable of providing local arterial gene transfer with adeno-associated viral (AAV) vectors. This system exploits the natural affinity of protein G (PrG) to bind to the Fc region of mammalian IgG, making PrG a universal adaptor for surface immobilization of vector-capturing antibodies (Ab). Our results: 1) demonstrate the feasibility of reversible immobilization of AAV2 vectors using vector tethering by AAV2-specific Ab appended to the stent surface through covalently attached PrG, 2) show sustained release kinetics of PrG/Ab-immobilized AAV2 vector particles into simulated physiological medium in vitro and site-specific transduction of cultured cells, 3) provide evidence of long-term (12 weeks) arterial expression of luciferase with PrG/Ab-tethered AAV2Luc, and 4) show anti-proliferative activity and anti-restenotic efficacy of stent-immobilized AAV2iNOS in the rat carotid artery model of stent angioplasty. PMID:28832561

Parkin Overexpression Ameliorates PrP106-126-Induced Neurotoxicity via Enhanced Autophagy in N2a Cells.

PubMed

Khan, Sher Hayat; Zhao, Deming; Shah, Syed Zahid Ali; Hassan, Mohammad Farooque; Zhu, Ting; Song, Zhiqi; Zhou, Xiangmei; Yang, Lifeng

2017-05-01

Transmissible spongiform encephalopathies (TSEs) are caused by the accumulation of the abnormal prion protein scrapie (PrP Sc ). Prion protein aggregation, misfolding, and cytotoxicity in the brain are the major causes of neuronal dysfunction and ultimate neurodegeneration in all TSEs. Parkin, an E3 ubiquitin ligase, has been studied extensively in all major protein misfolding aggregating diseases, especially Parkinson's disease and Alzheimer's disease, but the role of parkin in TSEs remains unknown. Here we investigated the role of parkin in a prion disease cell model in which neuroblastoma2a (N2a) cells were treated with prion peptide PrP106-126. We observed a gradual decrease in the soluble parkin level upon treatment with PrP106-126 in a time-dependent manner. Furthermore, endogenous parkin colocalized with FITC-tagged prion fragment106-126. Overexpression of parkin in N2a cells via transfection repressed apoptosis by enhancing autophagy. Parkin-overexpressing cells also showed reductions in apoptotic BAX translocation to the mitochondria and cytochrome c release to the cytosol, which ultimately inhibited activation of proapoptotic caspases. Taken together, our findings reveal a parkin-mediated cytoprotective mechanism against PrP106-126 toxicity, which is a novel potential therapeutic target for treating prion diseases.

Fife organizes synaptic vesicles and calcium channels for high-probability neurotransmitter release

PubMed Central

Rao, Monica; Ukken, Fiona

2017-01-01

The strength of synaptic connections varies significantly and is a key determinant of communication within neural circuits. Mechanistic insight into presynaptic factors that establish and modulate neurotransmitter release properties is crucial to understanding synapse strength, circuit function, and neural plasticity. We previously identified Drosophila Piccolo-RIM-related Fife, which regulates neurotransmission and motor behavior through an unknown mechanism. Here, we demonstrate that Fife localizes and interacts with RIM at the active zone cytomatrix to promote neurotransmitter release. Loss of Fife results in the severe disruption of active zone cytomatrix architecture and molecular organization. Through electron tomographic and electrophysiological studies, we find a decrease in the accumulation of release-ready synaptic vesicles and their release probability caused by impaired coupling to Ca2+ channels. Finally, we find that Fife is essential for the homeostatic modulation of neurotransmission. We propose that Fife organizes active zones to create synaptic vesicle release sites within nanometer distance of Ca2+ channel clusters for reliable and modifiable neurotransmitter release. PMID:27998991

7 CFR 1493.20 - Definition of terms.

Code of Federal Regulations, 2013 CFR

2013-01-01

... Secretary of Agriculture. (c) Contacts P/R. A notice issued by FAS/USDA by public press release which contains specific names, addresses, and telephone and facsimile numbers of contacts within FAS/USDA and CCC... appropriate FOB, FAS, CFR or CIF basis. Discounts and allowances include, but are not limited to, the...

7 CFR 1493.410 - Definition of terms.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Secretary of Agriculture. (c) Contacts P/R. A notice issued by FAS/USDA by public press release which contains specific names, addresses, and telephone and facsimile numbers of contacts within FAS/USDA and CCC... agricultural commodity, above and beyond the commodity's value, stated on the appropriate FOB, FAS, CFR or CIF...

7 CFR 1493.410 - Definition of terms.

Code of Federal Regulations, 2013 CFR

2013-01-01

... Secretary of Agriculture. (c) Contacts P/R. A notice issued by FAS/USDA by public press release which contains specific names, addresses, and telephone and facsimile numbers of contacts within FAS/USDA and CCC... agricultural commodity, above and beyond the commodity's value, stated on the appropriate FOB, FAS, CFR or CIF...

7 CFR 1493.410 - Definition of terms.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Secretary of Agriculture. (c) Contacts P/R. A notice issued by FAS/USDA by public press release which contains specific names, addresses, and telephone and facsimile numbers of contacts within FAS/USDA and CCC... agricultural commodity, above and beyond the commodity's value, stated on the appropriate FOB, FAS, CFR or CIF...

7 CFR 1493.20 - Definition of terms.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Secretary of Agriculture. (c) Contacts P/R. A notice issued by FAS/USDA by public press release which contains specific names, addresses, and telephone and facsimile numbers of contacts within FAS/USDA and CCC... appropriate FOB, FAS, CFR or CIF basis. Discounts and allowances include, but are not limited to, the...

7 CFR 1493.20 - Definition of terms.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Secretary of Agriculture. (c) Contacts P/R. A notice issued by FAS/USDA by public press release which contains specific names, addresses, and telephone and facsimile numbers of contacts within FAS/USDA and CCC... appropriate FOB, FAS, CFR or CIF basis. Discounts and allowances include, but are not limited to, the...

TRACE-LEVEL MEASUREMENT OF COMPLEX COMBUSTION EFFLUENTS AND RESIDUES USING MULTIDIMENSIONAL GAS CHROMATOGRAPHY-MASS SPECTROMETRY (MDGC-MS). (R828190)

EPA Science Inventory

The identification and quantitation of non-method-specific target analytes have greater importance with respect to EPA's current combustion strategy. The risk associated with combustion process emissions must now be characterized. EPA has recently released draft guidance on pr...

Inhibiting Inosine Hydrolase and Alanine Racemase to Enhance the Germination of Bacillus anthracis Sterne Spores: Potential Spore Decontamination Strategies

DTIC Science & Technology

2015-06-19

animal waste an~ decompositiOn DISTRIBUTION STATEMENT A: Approved for public release; distribution is unlimited. UNCLASSIFIED PR-15-306 Anthrax...influx of water. Ungerminated spore Germination Germinated spore Spore hydratation ~ Non-refractile spore Refractile spore • Fluorescence

Enhanced host immune recognition of E.coli causing mastitis in CD-14 transgenic mice.

USDA-ARS?s Scientific Manuscript database

Escherchia coli causes mastitis, an economically significant disease in dairy animals. E. coli endotoxin (lipopolysaccharide, LPS) when bound by host membrane proteins such as CD-14, causes release of pro-inflammatory cytokines recruiting neutrophils as a early innate immune response. Excessive pr...

Application du processus de Markov sur les occurrences des précipitations journalières au Congo-Brazzaville

NASA Astrophysics Data System (ADS)

Samba, Gaston; Mpounza, Marcel

2005-11-01

This study deals with the daily precipitation occurrence during the rainy season in different locations in Congo-Brazzaville. The Markov-chain probability model has been used for defining probable dry and wet rainy sequences at each station, and transition probabilities between daily precipitations of two successive days. The main results are: in Congo, the dependence on the preceding day of the daily precipitations occurrence; the confirmation of two main climatic region (equatorial climate to the north and tropical wet to the south); the lack of coherence in the distribution of precipitations. To cite this article: G. Samba, M. Mpounza, C. R. Geoscience 337 (2005).

An Exclusion Zone for Ca2+ Channels around Docked Vesicles Explains Release Control by Multiple Channels at a CNS Synapse

PubMed Central

Keller, Daniel; Babai, Norbert; Kochubey, Olexiy; Han, Yunyun; Markram, Henry; Schürmann, Felix; Schneggenburger, Ralf

2015-01-01

The spatial arrangement of Ca2+ channels and vesicles remains unknown for most CNS synapses, despite of the crucial importance of this geometrical parameter for the Ca2+ control of transmitter release. At a large model synapse, the calyx of Held, transmitter release is controlled by several Ca2+ channels in a "domain overlap" mode, at least in young animals. To study the geometrical constraints of Ca2+ channel placement in domain overlap control of release, we used stochastic MCell modelling, at active zones for which the position of docked vesicles was derived from electron microscopy (EM). We found that random placement of Ca2+ channels was unable to produce high slope values between release and presynaptic Ca2+ entry, a hallmark of domain overlap, and yielded excessively large release probabilities. The simple assumption that Ca2+ channels can be located anywhere at active zones, except below a critical distance of ~ 30 nm away from docked vesicles ("exclusion zone"), rescued high slope values and low release probabilities. Alternatively, high slope values can also be obtained by placing all Ca2+ channels into a single supercluster, which however results in significantly higher heterogeneity of release probabilities. We also show experimentally that high slope values, and the sensitivity to the slow Ca2+ chelator EGTA-AM, are maintained with developmental maturation of the calyx synapse. Taken together, domain overlap control of release represents a highly organized active zone architecture in which Ca2+ channels must obey a certain distance to docked vesicles. Furthermore, domain overlap can be employed by near-mature, fast-releasing synapses. PMID:25951120

Enhanced broadband near-infrared luminescence from Pr3+-doped tellurite glass with silver nanoparticles

NASA Astrophysics Data System (ADS)

Cheng, Pan; Zhou, Yaxun; Zhou, Minghan; Su, Xiue; Zhou, Zizhong; Yang, Gaobo

2017-11-01

Pr3+-doped tellurite glasses containing metallic silver NPs were synthesized by the conventional melt-quenching technique. Structural, thermal and optical properties of the synthesized glass samples were characterized by X-Ray diffraction (XRD) curves, Raman spectra, differential scanning calorimeter (DSC) curves, transmission electron microscopy (TEM) images, UV/Vis/NIR absorption and near-infrared fluorescence emission spectra. The XRD curves confirmed the amorphous structural nature of the synthesized glasses, the Raman spectra identified the presence of different vibrational groups, the DSC curves verified the good thermal stability, and the TEM images revealed the nucleated silver NPs with average diameter about 10 nm dispersed in the glass matrix and its surface Plasmon resonance (SPR) absorption band was located at around 510 nm. Besides, Judd-Ofelt intensity parameters Ωt (t = 2, 4, 6) and other important spectroscopic parameters like transition probability, radiative lifetime, branching ratio were calculated to evaluate the radiative properties of Pr3+ levels from the measured optical absorption spectra. It was found that Pr3+-doped tellurite glasses could emit an ultra-broadband fluorescence extending from 1250 to 1650 nm under the 488 nm excitation, and this fluorescence emission increased further with the introduction of silver NPs. The enhanced fluorescence was mainly attributed to the increased local electric field around Pr3+ induced by silver NPs. The present results demonstrate that Pr3+-Ag codoped tellurite glass is a promising candidate for the near-infrared band ultra-broadband fiber amplifiers covering the expanded low-loss communication window.

Cost-effectiveness Analysis of Nutritional Support for the Prevention of Pressure Ulcers in High-Risk Hospitalized Patients.

PubMed

Tuffaha, Haitham W; Roberts, Shelley; Chaboyer, Wendy; Gordon, Louisa G; Scuffham, Paul A

2016-06-01

To evaluate the cost-effectiveness of nutritional support compared with standard care in preventing pressure ulcers (PrUs) in high-risk hospitalized patients. An economic model using data from a systematic literature review. A meta-analysis of randomized controlled trials on the efficacy of nutritional support in reducing the incidence of PrUs was conducted. Modeled cohort of hospitalized patients at high risk of developing PrUs and malnutrition simulated during their hospital stay and up to 1 year. Standard care included PrU prevention strategies, such as redistribution surfaces, repositioning, and skin protection strategies, along with standard hospital diet. In addition to the standard care, the intervention group received nutritional support comprising patient education, nutrition goal setting, and the consumption of high-protein supplements. The analysis was from a healthcare payer perspective. Key outcomes of the model included the average costs and quality-adjusted life years. Model results were tested in univariate sensitivity analyses, and decision uncertainty was characterized using a probabilistic sensitivity analysis. Compared with standard care, nutritional support was cost saving at AU $425 per patient and marginally more effective with an average 0.005 quality-adjusted life years gained. The probability of nutritional support being cost-effective was 87%. Nutritional support to prevent PrUs in high-risk hospitalized patients is cost-effective with substantial cost savings predicted. Hospitals should implement the recommendations from the current PrU practice guidelines and offer nutritional support to high-risk patients.

A Single Glycine-Alanine Exchange Directs Ligand Specificity of the Elephant Progestin Receptor

PubMed Central

Wierer, Michael; Schrey, Anna K.; Kühne, Ronald; Ulbrich, Susanne E.

2012-01-01

The primary gestagen of elephants is 5α-dihydroprogesterone (DHP), which is unlike all other mammals studied until now. The level of DHP in elephants equals that of progesterone in other mammals, and elephants are able to bind DHP with similar affinity to progesterone indicating a unique ligand-binding specificity of the elephant progestin receptor (PR). Using site-directed mutagenesis in combination with in vitro binding studies we here report that this change in specificity is due to a single glycine to alanine exchange at position 722 (G722A) of PR, which specifically increases DHP affinity while not affecting binding of progesterone. By conducting molecular dynamics simulations comparing human and elephant PR ligand-binding domains (LBD), we observed that the alanine methyl group at position 722 is able to push the DHP A-ring into a position similar to progesterone. In the human PR, the DHP A-ring position is twisted towards helix 3 of PR thereby disturbing the hydrogen bond pattern around the C3-keto group, resulting in a lower binding affinity. Furthermore, we observed that the elephant PR ligand-binding pocket is more rigid than the human analogue, which probably explains the higher affinity towards both progesterone and DHP. Interestingly, the G722A substitution is not elephant-specific, rather it is also present in five independent lineages of mammalian evolution, suggesting a special role of the substitution for the development of distinct mammalian gestagen systems. PMID:23209719

Poverty, gender and incarceration in sixteenth-century Paris.

PubMed

Broomhall, Susan

2004-01-01

The experience of prison remains a relatively little-studied aspect of late-medieval and early-modern criminalization of the activities of the poor. This study examines how poverty and gender influenced incarceration practices, treatment and release in sixteenth-century Paris. A study of the archives of the ecclesiastical gaol at Saint-Germain-des-Prés from 1537 to 1579 suggests that both poverty and gender affected the crimes for which women and men were imprisoned, the length of time they remained in detention and the reasons for their release.

The Production of Printed Circuit Boards, Photo-Anodised and Screen Printed Instrument Panels.

DTIC Science & Technology

1981-01-01

Laboratories, Melbourne 12. RELEASE LIMITATIONS (of the document): Approved for Public Release. 12.0. OVERSEAS: N.0.1 I P.R. 1 A I I B I I C I D EI 13...solutions. 5.1 baths Required (N.B. Tanks shoula be of rigid P.V.C.) 1. Amonium persulphate solution 100 gm/L. 2. Sulphuric acid 10% (A.R. GRADE...120 degrees C for at least 10 mins. Etchant 1: 55% weight/volume solution of ferric nitrate used at 49 degrees C. This solution is made by adding

A cost utility analysis of simeprevir used with peginterferon + ribavirin in the management of genotype 1 hepatitis C virus infection, from the perspective of the UK National Health Service.

PubMed

Westerhout, Kirsten; Treur, Maarten; Mehnert, Angelika; Pascoe, Katie; Ladha, Imran; Belsey, Jonathan

2015-01-01

Triple therapy using a protease inhibitor (PI) with peginterferon and ribavirin (PR) is increasingly used in patients with chronic hepatitis C virus (HCV) infection. The most recently introduced PI, simeprevir (SMV), offers high levels of viral eradication combined with a reduced overall duration of therapy. The objective of this study was to compare the cost-effectiveness of SMV + PR vs PR alone or in combination with telaprevir (TVR) or boceprevir (BOC) in patients infected with genotype 1 HCV Method: A cost-utility model was constructed, incorporating two phases, capturing the efficacy of therapy in an initial treatment phase, followed by a long-term post-treatment Markov phase, capturing lifetime outcomes according to whether a sustained viral response (SVR) had been achieved on treatment. Dosage regimens were based on the EMA approved label for each treatment. SVR estimates and adverse event rates were derived from a mixed treatment comparison. Baseline characteristics were drawn from an analysis of a UK HCV data-set and clinician opinion. Health state transition probabilities, utilities, and health state costs were drawn from previously published economic analyses. The model considered direct health costs only, and the perspective was that of the UK National Health Service. The model yielded an ICER for SMV + PR vs PR alone of £9725/QALY for treatment-naïve and £7819/QALY for treatment-experienced. Benefit was driven by increased likelihood of achieving SVR, with consequent long-term utility gains. SMV + PR dominated TVR + PR and BOC + PR in both patient groups. This principally reflected the QALY benefit of an increased likelihood of SVR with SMV, combined with lower overall drug costs, due to reduced mean treatment duration. Compared to other currently licensed treatment options, SMV + PR represents a cost effective treatment option for patients with chronic genotype 1 HCV infection.

Experimental approaches to the interaction of the prion protein with nucleic acids and glycosaminoglycans: Modulators of the pathogenic conversion.

PubMed

Silva, Jerson L; Vieira, Tuane C R G; Gomes, Mariana P B; Rangel, Luciana P; Scapin, Sandra M N; Cordeiro, Yraima

2011-03-01

The concept that transmissible spongiform encephalopathies (TSEs) are caused only by proteins has changed the traditional paradigm that disease transmission is due solely to an agent that carries genetic information. The central hypothesis for prion diseases proposes that the conversion of a cellular prion protein (PrP(C)) into a misfolded, β-sheet-rich isoform (PrP(Sc)) accounts for the development of (TSE). There is substantial evidence that the infectious material consists chiefly of a protein, PrP(Sc), with no genomic coding material, unlike a virus particle, which has both. However, prions seem to have other partners that chaperone their activities in converting the PrP(C) into the disease-causing isoform. Nucleic acids (NAs) and glycosaminoglycans (GAGs) are the most probable accomplices of prion conversion. Here, we review the recent experimental approaches that have been employed to characterize the interaction of prion proteins with nucleic acids and glycosaminoglycans. A PrP recognizes many nucleic acids and GAGs with high affinities, and this seems to be related to a pathophysiological role for this interaction. A PrP binds nucleic acids and GAGs with structural selectivity, and some PrP:NA complexes can become proteinase K-resistant, undergoing amyloid oligomerization and conversion to a β-sheet-rich structure. These results are consistent with the hypothesis that endogenous polyanions (such as NAs and GAGs) may accelerate the rate of prion disease progression by acting as scaffolds or lattices that mediate the interaction between PrP(C) and PrP(Sc) molecules. In addition to a still-possible hypothesis that nucleic acids and GAGs, especially those from the host, may modulate the conversion, the recent structural characterization of the complexes has raised the possibility of developing new diagnostic and therapeutic strategies. Copyright © 2010 Elsevier Inc. All rights reserved.

PREVENTION REFERENCE MANUAL: CONTROL TECHNOLOGIES, VOL. 2. POST-RELEASE MITIGATION MEASURES FOR CONTROLLING ACCIDENTAL RELEASES OF AIR TOXICS

EPA Science Inventory

The volume discusses prevention and protection measures for controlling accidental releases of air toxics. The probability of accidental releases depends on the extent to which deviations (in magnitude and duration) in the process can be tolerated before a loss of chemical contai...

CD36 Participates in PrP106–126-Induced Activation of Microglia

PubMed Central

Tan, Rongrong; Shi, Fushan; Lu, Yun; Zhang, Siming; Yin, Xiaomin; Zhou, Xiangmei; Zhao, Deming

2012-01-01

Microglial activation is a characteristic feature of the pathogenesis of prion diseases. The molecular mechanisms that underlie prion-induced microglial activation are not very well understood. In the present study, we investigated the role of the class B scavenger receptor CD36 in microglial activation induced by neurotoxic prion protein (PrP) fragment 106–126 (PrP106–126). We first examined the time course of CD36 mRNA expression upon exposure to PrP106–126 in BV2 microglia. We then analyzed different parameters of microglial activation in PrP106–126-treated cells in the presence or not of anti-CD36 monoclonal antibody (mAb). The cells were first incubated for 1 h with CD36 monoclonal antibody to block the CD36 receptor, and were then treated with neurotoxic prion peptides PrP106–126. The results showed that PrP106–126 treatment led to a rapid yet transitory increase in the mRNA expression of CD36, upregulated mRNA and protein levels of proinflammatory cytokines (IL-1β, IL-6 and TNF-α), increased iNOS expression and nitric oxide (NO) production, stimulated the activation of NF-κB and caspase-1, and elevated Fyn activity. The blockade of CD36 had no effect on PrP106–126-stimulated NF-κB activation and TNF-α protein release, abrogated the PrP106–126-induced iNOS stimulation, downregulated IL-1β and IL-6 expression at both mRNA and protein levels as well as TNF-α mRNA expression, decreased NO production and Fyn phosphorylation, reduced caspase-1 cleavage induced by moderate PrP106–126 –treatment, but had no effect on caspase-1 activation after treatment with a high concentration of PrP106–126. Together, these results suggest that CD36 is involved in PrP106–126-induced microglial activation and that the participation of CD36 in the interaction between PrP106–126 and microglia may be mediated by Src tyrosine kinases. Our findings provide new insights into the mechanisms underlying the activation of microglia by neurotoxic prion peptides and open perspectives for new therapeutic strategies for prion diseases by modulation of CD36 signaling. PMID:22292032

Spontaneous and evoked release are independently regulated at individual active zones.

PubMed

Melom, Jan E; Akbergenova, Yulia; Gavornik, Jeffrey P; Littleton, J Troy

2013-10-30

Neurotransmitter release from synaptic vesicle fusion is the fundamental mechanism for neuronal communication at synapses. Evoked release following an action potential has been well characterized for its function in activating the postsynaptic cell, but the significance of spontaneous release is less clear. Using transgenic tools to image single synaptic vesicle fusion events at individual release sites (active zones) in Drosophila, we characterized the spatial and temporal dynamics of exocytotic events that occur spontaneously or in response to an action potential. We also analyzed the relationship between these two modes of fusion at single release sites. A majority of active zones participate in both modes of fusion, although release probability is not correlated between the two modes of release and is highly variable across the population. A subset of active zones is specifically dedicated to spontaneous release, indicating a population of postsynaptic receptors is uniquely activated by this mode of vesicle fusion. Imaging synaptic transmission at individual release sites also revealed general rules for spontaneous and evoked release, and indicate that active zones with similar release probability can cluster spatially within individual synaptic boutons. These findings suggest neuronal connections contain two information channels that can be spatially segregated and independently regulated to transmit evoked or spontaneous fusion signals.

HiRISE observations of gas sublimation-driven activity in Mars' southern polar regions: III. Models of processes involving translucent ice

USGS Publications Warehouse

Portyankina, G.; Markiewicz, W.J.; Thomas, N.; Hansen, C.J.; Milazzo, M.

2010-01-01

Enigmatic surface features, known as 'spiders', found at high southern martian latitudes, are probably caused by sublimation-driven erosion under the seasonal carbon dioxide ice cap. The Mars Reconnaissance Orbiter (MRO) High Resolution Imaging Science Experiment (HiRISE) has imaged this terrain in unprecedented details throughout southern spring. It has been postulated [Kieffer, H.H., Titus, T.N., Mullins, K.F., Christensen, P.R., 2000. J. Geophys. Res. 105, 9653-9700] that translucent CO2 slab ice traps gas sublimating at the ice surface boundary. Wherever the pressure is released the escaping gas jet entrains loose surface material and carries it to the top of the ice where it is carried downslope and/or downwind and deposited in a fan shape. Here we model two stages of this scenario: first, the cleaning of CO2 slab ice from dust, and then, the breaking of the slab ice plate under the pressure built below it by subliming ice. Our modeling results and analysis of HiRISE images support the gas jet hypothesis and show that outbursts happen very early in spring. ?? 2009 Elsevier Inc. All rights reserved.

[Conversion to tapentadol PR improves analgesia and quality of life in patients with severe and chronic pain despite using tramadol > 300 mg/d].

PubMed

Richter, Uwe; Waldmann-Rex, Susanne; Lehmann, Ute

2015-06-01

This subgroup analysis of a non-interventional study involving general practitioners and internists investigated the administration of tapentadol PR (prolonged release) in patients with widely-utilized tramadol pretreatment in routine clinical practice in Germany. Data of all patients in the study cohort who had tramadol as the only opioid in their previous therapy were included in the analysis (n = 685); among them especially the 99 patients with tramadol dosages exceeding 300 mg/d were focused. Data collection during the 3-month observation period included previous and concomitant analgesic treatment, tapentadol PR dosage, pain intensity, sleep and quality of life parameters, and tolerability of tapentadol PR. Back pain was the most common cause of pain (n = 86/99), other pain diagnoses were (partly additionally) recorded in 68 cases. A mixed type of pain dominated. The previous tramadol therapy was usually combined with non-opioids (n = 74), co-analgesics (n = 44) and analgesic rescue medication (n = 35). Tapentadol PR therapy reduced the mean initial pain intensity of 7.3 ± 1.5 to 3.1 ± 1.8 points (NRS-11, 11-point pain scale, n = 96) at the end of observation, using an average dosage of 218.7 mg/d. Tapentadol PR was finally applied as the sole analgesic in 32/95 patients. 69/96 patients achieved a clinically meaningful pain relief of at least 50 %, while 63 patients gained a pain reduction of ≥ 4 NRS-points. 89/95 patients reached or exceeded their additional individual treatment goal. This was accompanied by a significant decrease in pain-related impairments of daily activities and an improvement in quality of life with an overall good tolerability of tapentadol PR. Treatment with tapentadol PR was assessed positively by physicians and patients. Data analysis shows a clinically relevant benefit in patients unsuccessfully pretreated with tramadol by consecutive conversion to the potent analgesic tapentadol PR.

A Functional Interplay between Human Immunodeficiency Virus Type 1 Protease Residues 77 and 93 Involved in Differential Regulation of Precursor Autoprocessing and Mature Protease Activity

PubMed Central

Counts, Christopher J.; Ho, P. Shing; Donlin, Maureen J.; Tavis, John E.; Chen, Chaoping

2015-01-01

HIV-1 protease (PR) is a viral enzyme vital to the production of infectious virions. It is initially synthesized as part of the Gag-Pol polyprotein precursor in the infected cell. The free mature PR is liberated as a result of precursor autoprocessing upon virion release. We previously described a model system to examine autoprocessing in transfected mammalian cells. Here, we report that a covariance analysis of miniprecursor (p6*-PR) sequences derived from drug naïve patients identified a series of amino acid pairs that vary together across independent viral isolates. These covariance pairs were used to build the first topology map of the miniprecursor that suggests high levels of interaction between the p6* peptide and the mature PR. Additionally, several PR-PR covariance pairs are located far from each other (>12 Å Cα to Cα) relative to their positions in the mature PR structure. Biochemical characterization of one such covariance pair (77–93) revealed that each residue shows distinct preference for one of three alkyl amino acids (V, I, and L) and that a polar or charged amino acid at either of these two positions abolishes precursor autoprocessing. The most commonly observed 77V is preferred by the most commonly observed 93I, but the 77I variant is preferred by other 93 variances (L, V, or M) in supporting precursor autoprocessing. Furthermore, the 77I93V covariant enhanced precursor autoprocessing and Gag polyprotein processing but decreased the mature PR activity. Therefore, both covariance and biochemical analyses support a functional association between residues 77 and 93, which are spatially distant from each other in the mature PR structure. Our data also suggests that these covariance pairs differentially regulate precursor autoprocessing and the mature protease activity. PMID:25893662

Notes on Search, Detection and Localization Modeling. Revision 4

DTIC Science & Technology

1990-10-01

2, --- , k where the subregions are relabeled so that the following order relation holds: pi/6 1 > p 2!6 2 > ... > pr65 and where k is chosen so... Interfaces ," Operations Research, Vol. 19, No.3, pp 559-586, 1971. 15. Coggins, P.B., "Detection Probability Computations for Random Search of an

[Access by hearing-disabled individuals to health services in a southern Brazilian city].

PubMed

Freire, Daniela Buchrieser; Gigante, Luciana Petrucci; Béria, Jorge Umberto; Palazzo, Lílian dos Santos; Figueiredo, Andréia Cristina Leal; Raymann, Beatriz Carmen Warth

2009-04-01

This cross-sectional study aimed to compare access to health services and preventive measures by persons with hearing disability and those with normal hearing in Canoas, Rio Grande do Sul State, Brazil. The sample included 1,842 individuals 15 years or older (52.9% of whom were females). The most frequent income bracket was twice the minimum wage or more, or approximately U$360/month (42.7%). Individuals with hearing disability were more likely to have visited a physician in the previous two months (PR = 1.3, 95%CI: 1.10-1.51) and to have been hospitalized in the previous 12 months (PR = 2.1, 95%CI: 1.42-3.14). Regarding mental health, individuals with hearing disability showed 1.5 times greater probability of health care due to mental disorders and 4.2 times greater probability of psychiatric hospitalization as compared to those with normal hearing. Consistent with other studies, women with hearing disability performed less breast self-examination and had fewer Pap smears. The data indicate the need to invest in specific campaigns for this group of individuals with special needs.

Recent revisions of phosphate rock reserves and resources: a critique

NASA Astrophysics Data System (ADS)

Edixhoven, J. D.; Gupta, J.; Savenije, H. H. G.

2014-12-01

Phosphate rock (PR) is a finite mineral indispensable for fertilizer production, while P (phosphorus) is a major pollutant if applied or discharged in excess, causing widespread eutrophication (Carpenter and Bennet, 2011). High-grade PR is obtained from deposits which took millions of years to form and which are gradually being depleted. Recently, global PR reserves as reported by the US Geological Survey (USGS) have increased from 16 000 Mt PR in 2010 to 65 000 Mt PR in 2011 and further to 67 000 Mt PR in 2014. The majority of this 4-fold increase is based on a 2010 report by the International Fertilizer Development Center (IFDC), which increased Moroccan reserves from 5700 Mt PR as reported by USGS, to 51 000 Mt PR, reported as upgraded ("beneficiated") concentrate. The report also increased global resources from 163 000 Mt PR reported in the literature in 1989 to 290 000 Mt PR. IFDC used a simplified resource terminology which does not use the underlying thresholds for reserves and resources used in the USGS classification. IFDC proposed that agreement should be reached on PR resource terminology which should be as simple as possible. The report has profoundly influenced the PR scarcity debate, shifting the emphasis from resource scarcity to the pollution angle of the phosphate problem. In view of the high dependence of food production on PR and the importance of data on PR reserves and resources for scientific analysis and policy making, data on PR deposits should be transparent, comparable, reliable, and credible. We analyze (i) how IFDC's simplified terminology compares to international best practice in resource classification and whether it is likely to yield data that meet these requirements, (ii) whether the difference in volume between raw PR ore and upgraded PR concentrate is sufficiently noted in the literature, and (iii) whether the IFDC report presents an accurate picture of PR reserves and resources. We conclude that, while there is a global development toward common criteria in resource reporting, IFDC's lack of clear thresholds for reserves and resources contravenes this and that the vagueness of its definitions for reserves and resources may allow deposits to be termed reserves or resources which could not be recognized as such under leading mineral resource classifications. The difference between PR ore and PR concentrate is barely noted in the literature, causing pervasive confusion and a significant degree of error in many assessments. Finally, we find that the report most likely presents an inflated picture of global reserves, in particular those of Morocco, where the aggregate resources of three of the four Moroccan/Western Saharan major PR deposits appear to have been simply converted to "reserves". Following the release of the IFDC report, various analysts have concluded or suggested that the available PR deposits or even the currently reported resources would likely last several thousands of years at current consumption rates. However, the data on which these statements were based do not appear to warrant such a conclusion. Further research is required as to the quantity of PR deposits and their viability for future extraction, using uniform and transparent classification terminology.

Fusion competent synaptic vesicles persist upon active zone disruption and loss of vesicle docking

PubMed Central

Wang, Shan Shan H.; Held, Richard G.; Wong, Man Yan; Liu, Changliang; Karakhanyan, Aziz; Kaeser, Pascal S.

2016-01-01

In a nerve terminal, synaptic vesicle docking and release are restricted to an active zone. The active zone is a protein scaffold that is attached to the presynaptic plasma membrane and opposed to postsynaptic receptors. Here, we generated conditional knockout mice removing the active zone proteins RIM and ELKS, which additionally led to loss of Munc13, Bassoon, Piccolo, and RIM-BP, indicating disassembly of the active zone. We observed a near complete lack of synaptic vesicle docking and a strong reduction in vesicular release probability and the speed of exocytosis, but total vesicle numbers, SNARE protein levels, and postsynaptic densities remained unaffected. Despite loss of the priming proteins Munc13 and RIM and of docked vesicles, a pool of releasable vesicles remained. Thus, the active zone is necessary for synaptic vesicle docking and to enhance release probability, but releasable vesicles can be localized distant from the presynaptic plasma membrane. PMID:27537483

Cost-effectiveness of raising HDL cholesterol by adding prolonged-release nicotinic acid to statin therapy in the secondary prevention setting: a French perspective.

PubMed

Roze, S; Ferrières, J; Bruckert, E; Van Ganse, E; Chapman, M J; Liens, D; Renaudin, C

2007-11-01

To evaluate the cost-effectiveness of raising high-density lipoprotein cholesterol (HDL-C) with add-on nicotinic acid in statin-treated patients with coronary heart disease (CHD) and low HDL-C, from the French healthcare system perspective. Computer simulation economic modelling incorporating two decision analytic submodels was used. The first submodel generated a cohort of 2000 patients and simulated lipid changes using baseline characteristics and treatment effects from the ARterial Biology for the Investigation of the Treatment Effects of Reducing cholesterol (ARBITER 2) study. Prolonged-release (PR) nicotinic acid (1 g/day) was added in patients with HDL-C < 40 mg/dl (1.03 mmol/l) on statin alone. The second submodel used standard Markov techniques to evaluate long-term clinical and economic outcomes based on Framingham risk estimates. Direct medical costs were accounted from a third party payer perspective [2004 Euros (euro)] and discounted by 3%. Addition of PR nicotinic acid to statin therapy resulted in substantial health gain and increased life expectancy, at a cost well within the threshold (< 50,000 euros per life year gained) considered good value for money in Western Europe. Raising HDL-C by adding PR nicotinic acid to statin therapy in CHD patients was cost-effective in France at a level considered to represent good value for money by reimbursement authorities in Europe. This strategy was highly cost-effective in CHD patients with type 2 diabetes.

Nicotine modulates multiple regions in the limbic stress network regulating activation of hypophysiotrophic neurons in hypothalamic paraventricular nucleus.

PubMed

Yu, Guoliang; Sharp, Burt M

2012-08-01

Nicotine intake affects CNS responses to stressors. We reported that nicotine self-administration (SA) augmented the hypothalamo-pituitary-adrenal (HPA) stress response, in part because of the altered neurotransmission and neuropeptide expression within hypothalamic paraventricular nucleus (PVN). Limbic-PVN interactions involving medial prefrontal cortex, amygdala, and bed nucleus of the stria terminalis (BST) greatly impact the HPA stress response. Therefore, we investigated the effects of nicotine SA on stress-induced neuronal activation in limbic-PVN network, using c-Fos protein immunohistochemistry and retrograde tracing. Nicotine decreased stress-induced c-Fos in prelimbic cortex (PrL), anteroventral BST (avBST), and peri-PVN, but increased c-Fos induction in medial amygdala (MeA), locus coeruleus, and PVN. Fluoro-gold (FG) was injected into avBST or PVN, as GABAergic neurons in avBST projecting to PVN corticotrophin-releasing factor neurons relay information from both PrL glutamatergic and MeA GABAergic neurons. The stress-induced c-Fos expression in retrograde-labeled FG+ neurons was decreased in PrL by nicotine, but increased in MeA, and also reduced in avBST. Therefore, within limbic-PVN network, nicotine SA exerts selective regional effects on neuronal activation by stress. These findings expand the mechanistic framework by demonstrating altered limbic-BST-PVN interactions underlying the disinhibition of PVN corticotrophin-releasing factor neurons, an essential component of the amplified HPA response to stress by nicotine. © 2012 The Authors. Journal of Neurochemistry © 2012 International Society for Neurochemistry.

Performance of Male Psychopaths Following Conditional Release from Prison.

ERIC Educational Resources Information Center

Hart, Stephen D.; And Others

1988-01-01

Administered Psychopathy Checklist (PCL) to criminals being released from prison on parole or mandatory supervision, then examined official parole supervision files for postrelease behavior. Violation of release conditions, suspensions, and presentation of supervisory problems were directly proportional, and the probability of subjects remaining…

Gastrin-releasing peptide in human nasal mucosa.

PubMed

Baraniuk, J N; Lundgren, J D; Goff, J; Peden, D; Merida, M; Shelhamer, J; Kaliner, M

1990-04-01

Gastrin-releasing peptide (GRP), the 27 amino acid mammalian form of bombesin, was studied in human inferior turbinate nasal mucosa. The GRP content of the mucosa measured by radioimmunoassay was 0.60 +/- 0.25 pmol/g tissue (n = 9 patients; mean +/- SEM). GRP-immunoreactive nerves detected by the immunogold method of indirect immunohistochemistry were found predominantly in small muscular arteries, arterioles, venous sinusoids, and between submucosal gland acini. 125I-GRP binding sites determined by autoradiography were exclusively and specifically localized to nasal epithelium and submucosal glands. There was no binding to vessels. The effects of GRP on submucosal gland product release were studied in short-term explant culture. GRP (10 microM) significantly stimulated the release of the serous cell-specific product lactoferrin, and [3H]glucosamine-labeled glycoconjugates which are products of epithelial goblet cells and submucosal gland cells. These observations indicate that GRP released from nerve fibers probably acts on glandular GRP receptors to induce glycoconjugate release from submucosal glands and epithelium and lactoferrin release from serous cells, but that GRP would probably not affect vascular permeability.

Grape polyphenols and propolis mixture inhibits inflammatory mediator release from human leukocytes and reduces clinical scores in experimental arthritis.

PubMed

Mossalayi, M D; Rambert, J; Renouf, E; Micouleau, M; Mérillon, J M

2014-02-15

Polyphenols from red fruits and bee-derived propolis (PR) are bioactive natural products in various in vitro and in vivo models. The present study shows that hematotoxicity-free doses of grape polyphenols (GPE) and PR differentially decreased the secretion of pro-inflammatory cytokines from activated human peripheral blood leucocytes. While GPE inhibited the monocytes/macrophage response, propolis decreased both monokines and interferon γ (IFNγ) production. When used together, their distinct effects lead to the attenuation of all inflammatory mediators, as supported by a significant modulation of the transcriptomic profile of pro-inflammatory genes in human leukocytes. To enforce in vitro data, GPE+PR were tested for their ability to improve clinical scores and cachexia in chronic rat adjuvant-induced arthritis (AA). Extracts significantly reduced arthritis scores and cachexia, and this effect was more significant in animals receiving continuous low doses compared to those receiving five different high doses. Animals treated daily had significantly better clinical scores than corticoid-treated rats. Together, these findings indicate that the GPE+PR combination induces potent anti-inflammatory activity due to their complementary immune cell modulation. Copyright © 2013 Elsevier GmbH. All rights reserved.

Terminal Maturation of Orthochromatic Erythroblasts Is Impaired in Burn Patients.

PubMed

Hasan, Shirin; Mosier, Michael J; Conrad, Peggie; Szilagyi, Andrea; Gamelli, Richard L; Muthumalaiappan, Kuzhali

2018-02-20

Mechanisms of erythropoietin (Epo)-resistant anemia in burn patients are poorly understood. We have recently found that administering a nonselective beta 1,2-adrenergic blocker propranolol (PR) was effective in reversing myelo-erythroid commitment through MafB regulation and increase megakaryocyte erythrocyte progenitors in burn patients' peripheral blood mononuclear cell (PBMC)-derived ex vivo culture system. Having known that Epo-dependent proliferation of early erythroblasts is intact after burn injury, here we inquired whether or not Epo-independent maturation stage of erythropoiesis is affected by burn injury and the relative role of PR on late-stage erythropoiesis. While majority of erythropoiesis occurs in the bone marrow, maturation into reticulocytes is crucial for their release into sinusoids to occupy the peripheral circulation for which enucleation is vital. peripheral blood mononuclear cells (PBMCs) from burn patients were extended beyond commitment and proliferation stages to late maturation stage in ex vivo culture to understand the role of PR in burn patients. Burn impedes late maturation of orthochromatic erythroblasts into reticulocytes by restricting the enucleation step. Late-stage erythropoiesis is impaired in burn patients irrespective of PR treatment. Further, substituting the microenvironment with control plasma (homologous) in place of autologous plasma rescues the conversion of orthochromatic erythroblasts to reticulocytes. Results show promise in formulating interventions to regulate late-stage erythropoiesis, which can be used in combination with PR to reduce the number of transfusions.

Cellular automata model for drug release from binary matrix and reservoir polymeric devices.

PubMed

Johannes Laaksonen, Timo; Mikael Laaksonen, Hannu; Tapio Hirvonen, Jouni; Murtomäki, Lasse

2009-04-01

Kinetics of drug release from polymeric tablets, inserts and implants is an important and widely studied area. Here we present a new and widely applicable cellular automata model for diffusion and erosion processes occurring during drug release from polymeric drug release devices. The model divides a 2D representation of the release device into an array of cells. Each cell contains information about the material, drug, polymer or solvent that the domain contains. Cells are then allowed to rearrange according to statistical rules designed to match realistic drug release. Diffusion is modeled by a random walk of mobile cells and kinetics of chemical or physical processes by probabilities of conversion from one state to another. This is according to the basis of diffusion coefficients and kinetic rate constants, which are on fundamental level just probabilities for certain occurrences. The model is applied to three kinds of devices with different release mechanisms: erodable matrices, diffusion through channels or pores and membrane controlled release. The dissolution curves obtained are compared to analytical models from literature and the validity of the model is considered. The model is shown to be compatible with all three release devices, highlighting easy adaptability of the model to virtually any release system and geometry. Further extension and applications of the model are envisioned.

Propagation Effects and Circuit Performance of Modern Military Radio Systems with Particular Emphasis on those Employing Bandspreading Held in Arcueil (Paris) France 17-21 October 1988

DTIC Science & Technology

1989-12-01

probabilit6 de fausse alarme ( Pfa ) lorsque le signal nest pas pr~sent. Le coupiePnd, Pfa perrnet de comparer entre elles les diff6rentes hypoth~ses de...detection of initial sync is required to qualify possible bit slips. The frame acceptance probability PFA , frame rejection probability PFR, frame...a bit slip and those not, represented by PFBS and PFA respectively in Figure 3a. With a frame represented by two halves, the possible outcome may be

Previous tubal ectopic pregnancy raises the incidence of repeated ectopic pregnancies in in vitro fertilization-embryo transfer patients.

PubMed

Weigert, Monika; Gruber, Diego; Pernicka, Elisabeth; Bauer, Peter; Feichtinger, Wilfried

2009-01-01

To investigate the incidence of Tubal Ectopic Pregnancies (TEP) in IVF-ET patients with respect to the status of the fallopian tubes after a previous TEP. This retrospective study compares patients undergoing 481 IVF-ET cycles after conservatively or surgically treated TEP(s) with a Control Group (idiopathic or male factor for IVF-ET indication). Medical reports of surgery and/or hysterosalpingograms prior to the IVF cycles classified the status of the fallopian tubes. 12 TEPs (8.95%/Pregnancies (PR)) occurred in the Study Group. In the Control Group one TEP (0.75%/PR; p < 0.001) was found. Smoking increased the probability of TEPs (p = 0.0028) and of pathological pregnancies (abortion, biochemical and ectopic PR; (p = 0.0411)). For statistic evolution logistic regression (PROC GENMOD) and a repeated measure model were applied. Women with a previous TEP should be informed about the significantly increased risk for a further TEP in IVF-ET treatment, especially if they are smoking.

Evolutionary landscape of the Mycobacterium tuberculosis complex from the viewpoint of PhoPR: implications for virulence regulation and application to vaccine development.

PubMed

Broset, Esther; Martín, Carlos; Gonzalo-Asensio, Jesús

2015-10-20

Different members of the Mycobacterium genus have evolved to cause tuberculosis in diverse human populations and in a variety of animal species. Our cumulative knowledge of mycobacterial genomes indicates that mutations in the PhoPR two-component virulence system were acquired not only during the natural evolution of mycobacterial species but also during in vitro subculture, which has given rise to the attenuated reference strain H37Ra or to different daughter strains of Mycobacterium bovis BCG. PhoPR is a well-known regulator of pathogenic phenotypes, including secretion of the virulence factor ESAT-6, biosynthesis of acyltrehalose-based lipids, and modulation of antigen export, in members of the Mycobacterium tuberculosis complex (MTBC). Evolutionarily conserved polymorphisms in PhoPR from Mycobacterium africanum, M. bovis, or M. tuberculosis H37Ra result in loss of functional phenotypes. Interestingly, some members of the MTBC have acquired compensatory mutations to counteract these polymorphisms and, probably, to maintain their pathogenic potential. Some of these compensatory mutations include the insertion of the IS6110 element upstream from phoPR in a particular M. bovis strain that is able to transmit between humans or polymorphisms in M. africanum and M. bovis that affect the regulatory region of the espACD operon, allowing PhoPR-independent ESAT-6 secretion. This review highlights the increasing knowledge of the significance of PhoPR in the evolution of the MTBC and its potential application in the construction of new attenuated vaccines based on phoPR inactivation. In this context, the live attenuated vaccine MTBVAC, based on a phoP fadD26 deletion mutant of M. tuberculosis, is the first vaccine of this kind to successfully enter into clinical development, representing a historic milestone in the field of human vaccinology. Copyright © 2015 Broset et al.

Evolutionary Landscape of the Mycobacterium tuberculosis Complex from the Viewpoint of PhoPR: Implications for Virulence Regulation and Application to Vaccine Development

PubMed Central

Broset, Esther

2015-01-01

ABSTRACT Different members of the Mycobacterium genus have evolved to cause tuberculosis in diverse human populations and in a variety of animal species. Our cumulative knowledge of mycobacterial genomes indicates that mutations in the PhoPR two-component virulence system were acquired not only during the natural evolution of mycobacterial species but also during in vitro subculture, which has given rise to the attenuated reference strain H37Ra or to different daughter strains of Mycobacterium bovis BCG. PhoPR is a well-known regulator of pathogenic phenotypes, including secretion of the virulence factor ESAT-6, biosynthesis of acyltrehalose-based lipids, and modulation of antigen export, in members of the Mycobacterium tuberculosis complex (MTBC). Evolutionarily conserved polymorphisms in PhoPR from Mycobacterium africanum, M. bovis, or M. tuberculosis H37Ra result in loss of functional phenotypes. Interestingly, some members of the MTBC have acquired compensatory mutations to counteract these polymorphisms and, probably, to maintain their pathogenic potential. Some of these compensatory mutations include the insertion of the IS6110 element upstream from phoPR in a particular M. bovis strain that is able to transmit between humans or polymorphisms in M. africanum and M. bovis that affect the regulatory region of the espACD operon, allowing PhoPR-independent ESAT-6 secretion. This review highlights the increasing knowledge of the significance of PhoPR in the evolution of the MTBC and its potential application in the construction of new attenuated vaccines based on phoPR inactivation. In this context, the live attenuated vaccine MTBVAC, based on a phoP fadD26 deletion mutant of M. tuberculosis, is the first vaccine of this kind to successfully enter into clinical development, representing a historic milestone in the field of human vaccinology. PMID:26489860

Costs and cost-efficacy analysis of the 2017 GESIDA/Spanish National AIDS Plan recommended guidelines for initial antiretroviral therapy in HIV-infected adults.

PubMed

Rivero, Antonio; Pérez-Molina, José Antonio; Blasco, Antonio Javier; Arribas, José Ramón; Asensi, Víctor; Crespo, Manuel; Domingo, Pere; Iribarren, José Antonio; Lázaro, Pablo; López-Aldeguer, José; Lozano, Fernando; Martínez, Esteban; Moreno, Santiago; Palacios, Rosario; Pineda, Juan Antonio; Pulido, Federico; Rubio, Rafael; Santos, Jesús; de la Torre, Javier; Tuset, Montserrat; Gatell, Josep M

2018-05-01

GESIDA and the Spanish National AIDS Plan panel of experts have recommended preferred (PR), alternative (AR) and other regimens (OR) for antiretroviral therapy (ART) as initial therapy in HIV-infected patients for 2017. The objective of this study was to evaluate the costs and the efficiency of initiating treatment with PR and AR. Economic assessment of costs and efficiency (cost-efficacy) based on decision tree analyses. Efficacy was defined as the probability of reporting a viral load <50copies/mL at week 48, in an intention-to-treat analysis. Cost of initiating treatment with an ART regimen was defined as the costs of ART and its consequences (adverse effects, changes of ART regimen and drug resistance studies) during the first 48 weeks. The payer perspective (National Health System) was applied considering only differential direct costs: ART (official prices), management of adverse effects, resistance studies and HLA B*5701 screening. The setting was Spain and the costs correspond to those of 2017. A deterministic sensitivity analysis was conducted, building three scenarios for each regimen: base case, most favourable and least favourable. In the base case scenario, the cost of initiating treatment ranged from 6882 euro for TFV/FTC/RPV (AR) to 10,904 euros for TFV/FTC+RAL (PR). The efficacy varied from 0.82 for TFV/FTC+DRV/p (AR) to 0.92 for TAF/FTC/EVG/COBI (PR). The efficiency, in terms of cost-efficacy, ranged from 7923 to 12,765 euros per responder at 48 weeks, for ABC/3TC/DTG (PR) and TFV/FTC+RAL (PR), respectively. Considering ART official prices, the most efficient regimen was ABC/3TC/DTG (PR), followed by TFV/FTC/RPV (AR) and TAF/FTC/EVG/COBI (PR). Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Head-on crashes on two-way interurban roads: a public health concern in road safety.

PubMed

Olabarria, Marta; Santamariña-Rubio, Elena; Marí-Dell'Olmo, Marc; Gotsens, Mercè; Novoa, Ana M; Borrell, Carme; Pérez, Katherine

2015-09-01

To describe the magnitude and characteristics of crashes and drivers involved in head-on crashes on two-way interurban roads in Spain between 2007 and 2012, and to identify the factors associated with the likelihood of head-on crashes on these roads compared with other types of crash. A cross-sectional study was conducted using the National Crash Register. The dependent variables were head-on crashes with injury (yes/no) and drivers involved in head-on crashes (yes/no). Factors associated with head-on crashes and with being a driver involved in a head-on crash versus other types of crash were studied using a multivariate robust Poisson regression model to estimate proportion ratios (PR) and confidence intervals (95% CI). There were 9,192 head-on crashes on two-way Spanish interurban roads. A total of 15,412 men and 3,862 women drivers were involved. Compared with other types of crash, head-on collisions were more likely on roads 7 m or more wide, on road sections with curves, narrowings or drop changes, on wet or snowy surfaces, and in twilight conditions. Transgressions committed by drivers involved in head-on crashes were driving in the opposite direction and incorrectly overtaking another vehicle. Factors associated with a lower probability of head-on crashes were the existence of medians (PR=0.57; 95%CI: 0.48-0.68) and a paved shoulder of less than 1.5 meters (PR=0.81; 95%CI: 0.77-0.86) or from 1.5 to 2.45 meters (PR=0.90; 95%CI: 0.84-0.96). This study allowed the characterization of crashes and drivers involved in head-on crashes on two-way interurban roads. The lower probability observed on roads with median strips point to these measures as an effective way to reduce these collisions. Copyright © 2014 SESPAS. Published by Elsevier Espana. All rights reserved.

Augmented sphingosine 1 phosphate receptor-1 signaling in cardiac fibroblasts induces cardiac hypertrophy and fibrosis through angiotensin II and interleukin-6

PubMed Central

Ohkura, Sei-ichiro; Takashima, Shin-ichiro; Yoshioka, Kazuaki; Okamoto, Yasuo; Inagaki, Yutaka; Sugimoto, Naotoshi; Kitano, Teppei; Takamura, Masayuki; Wada, Takashi; Kaneko, Shuichi; Takuwa, Yoh

2017-01-01

Background: Cardiac fibroblasts, together with cardiomyocytes, occupy the majority of cells in the myocardium and are involved in myocardial remodeling. The lysophospholipid mediator sphigosine-1-phosphate (S1P) regulates functions of cardiovascular cells through multiple receptors including S1PR1–S1PR3. S1PR1 but not other S1P receptors was upregulated in angiotensin II-induced hypertrophic hearts. Therefore, we investigated a role of S1PR1 in fibroblasts for cardiac remodeling by employing transgenic mice that overexpressed S1PR1 under the control of α-smooth muscle actin promoter. In S1PR1-transgenic mouse heart, fibroblasts and/or myofibroblasts were hyperplastic, and those cells as well as vascular smooth muscle cells overexpressed S1PR1. Transgenic mice developed bi-ventricular hypertrophy by 12-week-old and diffuse interstitial fibrosis by 24-week-old without hemodynamic stress. Cardiac remodeling in transgenic mice was associated with greater ERK phosphorylation, upregulation of fetal genes, and systolic dysfunction. Transgenic mouse heart showed increased mRNA expression of angiotensin-converting enzyme and interleukin-6 (IL-6). Isolated fibroblasts from transgenic mice exhibited enhanced generation of angiotensin II, which in turn stimulated IL-6 release. Either an AT1 blocker or angiotensin-converting enzyme inhibitor prevented development of cardiac hypertrophy and fibrosis, systolic dysfunction and increased IL-6 expression in transgenic mice. Finally, administration of anti-IL-6 antibody abolished an increase in tyrosine phosphorylation of STAT3, a major signaling molecule downstream of IL-6, in the transgenic mouse heart and prevented development of cardiac hypertrophy in transgenic mice. These results demonstrate a promoting role of S1PR1 in cardiac fibroblasts for cardiac remodeling, in which angiotensin II—AT1 and IL-6 are involved. PMID:28771545

Implementation of pre-exposure prophylaxis for human immunodeficiency virus infection: progress and emerging issues in research and policy.

PubMed

Cáceres, Carlos F; Borquez, Annick; Klausner, Jeffrey D; Baggaley, Rachel; Beyrer, Chris

2016-01-01

In this article, we present recent evidence from studies focused on the implementation, effectiveness and cost-effectiveness of pre-exposure prophylaxis (PrEP) for HIV infection; discuss PrEP scale-up to date, including the observed levels of access and policy development; and elaborate on key emerging policy and research issues to consider for further scale-up, with a special focus on lower-middle income countries. The 2015 WHO Early Release Guidelines for HIV Treatment and Prevention reflect both scientific evidence and new policy perspectives. Those guidelines present a timely challenge to health systems for the scaling up of not only treatment for every person living with HIV infection but also the offer of PrEP to those at substantial risk. Delivery and uptake of both universal antiretroviral therapy (ART) and PrEP will require nation-wide commitment and could reinvigorate health systems to develop more comprehensive "combination prevention" programmes and support wider testing linked to both treatments and other prevention options for populations at highest risk who are currently not accessing services. Various gaps in current health systems will need to be addressed to achieve strategic scale-up of PrEP, including developing prioritization strategies, strengthening drug regulations, determining cost and funding sources, training health providers, supporting user adherence and creating demand. The initial steps in the scale-up of PrEP globally suggest feasibility, acceptability and likely impact. However, to prevent setbacks in less well-resourced settings, countries will need to anticipate and address challenges such as operational and health systems barriers, drug cost and regulatory policies, health providers' openness to prescribing PrEP to populations at substantial risk, demand and legal and human rights issues. Emerging problems will require creative solutions and will continue to illustrate the complexity of PrEP implementation.

Implementation of pre-exposure prophylaxis for human immunodeficiency virus infection: progress and emerging issues in research and policy

PubMed Central

Cáceres, Carlos F; Borquez, Annick; Klausner, Jeffrey D; Baggaley, Rachel; Beyrer, Chris

2016-01-01

Background In this article, we present recent evidence from studies focused on the implementation, effectiveness and cost-effectiveness of pre-exposure prophylaxis (PrEP) for HIV infection; discuss PrEP scale-up to date, including the observed levels of access and policy development; and elaborate on key emerging policy and research issues to consider for further scale-up, with a special focus on lower-middle income countries. Discussion The 2015 WHO Early Release Guidelines for HIV Treatment and Prevention reflect both scientific evidence and new policy perspectives. Those guidelines present a timely challenge to health systems for the scaling up of not only treatment for every person living with HIV infection but also the offer of PrEP to those at substantial risk. Delivery and uptake of both universal antiretroviral therapy (ART) and PrEP will require nation-wide commitment and could reinvigorate health systems to develop more comprehensive “combination prevention” programmes and support wider testing linked to both treatments and other prevention options for populations at highest risk who are currently not accessing services. Various gaps in current health systems will need to be addressed to achieve strategic scale-up of PrEP, including developing prioritization strategies, strengthening drug regulations, determining cost and funding sources, training health providers, supporting user adherence and creating demand. Conclusions The initial steps in the scale-up of PrEP globally suggest feasibility, acceptability and likely impact. However, to prevent setbacks in less well-resourced settings, countries will need to anticipate and address challenges such as operational and health systems barriers, drug cost and regulatory policies, health providers’ openness to prescribing PrEP to populations at substantial risk, demand and legal and human rights issues. Emerging problems will require creative solutions and will continue to illustrate the complexity of PrEP implementation. PMID:27760685

Identification of petroleum hydrocarbons using a reduced number of PAHs selected by Procrustes rotation.

PubMed

Fernández-Varela, R; Andrade, J M; Muniategui, S; Prada, D; Ramírez-Villalobos, F

2010-04-01

Identifying petroleum-related products released into the environment is a complex and difficult task. To achieve this, polycyclic aromatic hydrocarbons (PAHs) are of outstanding importance nowadays. Despite traditional quantitative fingerprinting uses straightforward univariate statistical analyses to differentiate among oils and to assess their sources, a multivariate strategy based on Procrustes rotation (PR) was applied in this paper. The aim of PR is to select a reduced subset of PAHs still capable of performing a satisfactory identification of petroleum-related hydrocarbons. PR selected two subsets of three (C(2)-naphthalene, C(2)-dibenzothiophene and C(2)-phenanthrene) and five (C(1)-decahidronaphthalene, naphthalene, C(2)-phenanthrene, C(3)-phenanthrene and C(2)-fluoranthene) PAHs for each of the two datasets studied here. The classification abilities of each subset of PAHs were tested using principal components analysis, hierarchical cluster analysis and Kohonen neural networks and it was demonstrated that they unraveled the same patterns as the overall set of PAHs. (c) 2009 Elsevier Ltd. All rights reserved.

Muon spin relaxation and rotation studies of the filled skutterudite alloys praseodymium osmium ruthenium antimonide and praseodymium lanthanum osmium antimonide

NASA Astrophysics Data System (ADS)

Shu, Lei

Some filled skutterudite compounds have recently been found to exhibit very interesting properties. The first Pr-based heavy-fermion superconductor, PrOs4Sb12, is an intriguing material due to the unusual properties of both its normal and superconducting states. Comprehensive muon spin rotation and relaxation studies and magnetic susceptibility measurements, described in this dissertation, have been performed to investigate the microscopic properties of PrOs4Sb12 and its Ru and La doped alloys. The temperature dependence of penetration depth measured in the vortex state of PrOs4Sb12 using transverse-field muon spin rotation (TF-muSR) is weaker than those measured by radiofrequency measurements. A scenario based on two-band superconductivity in PrOs4Sb 12, is proposed to resolve this difference. TF-muSR experiments also suggest the suppression of superfluid density with Ru doping, probably due to impurity scattering. In addition, magnetic susceptibility data as well as analysis of the muSR data in PrOs4Sb12 reveal a nearly linear relation of mu+ Knight shift vs. magnetic susceptibility. This suggests that the muon charge does not affect the crystalline electric field splitting of Pr3+ near neighbors. Additional evidence comes from the fact that the superconducting transition temperature Tc measured from muSR is consistent with the bulk superconducting values. Zero-field muon spin relaxation (ZF-muSR) experiments have been carried out in the Pr(Os1-xRux) 4Sb12 and Pr1-yLayOs 4Sb12 alloy systems to investigate the time-reversal symmetry (TRS) breaking found in an earlier ZF-muSR study of the end compound PrOs 4Sb12. The results from measurements at KEK, Japan, suggest that Ru doping is considerably more efficient than La doping in suppressing TRS breaking superconducting in PrOs4Sb12. However, we think that the spontaneous local field that indicates TRS breaking detected by ZF-muSR may depend on sample quality if those fields are from inhomogeneity in the superconducting order parameter, since our ZF-muSR experiment detects nonzero spontaneous fields for Pr(Os0.9Ru0.1)4 Sb12 from measurement at ISIS, United Kingdom in different samples. Longitudinal-field muon spin relaxation experiments also have been carried out to elucidate the anomalous dynamic muon spin relaxation detected by ZF-muSR in those alloys. The dynamic muon relaxation found in the alloys appears to be due to 141Pr nuclear spin fluctuations, where the 141Pr moments are enhanced by hyperfine coupling to the Pr 3+ Van Vleck susceptibility.

TEMPORAL TRENDS OF AROCLOR 1268 IN THE TAUNTON RIVER ESTUARY: EVIDENCE OF EARLY PRODUCTION, USE AND RELEASE TO THE ENVIRONMENT

EPA Science Inventory

Sediment cores were collected at three sites from the Lower Taunton River in Narragansett Bay, MA, dated and examined for PCBs. At each site, PCBs first appear in the sediment cores at depths corresponding to 1929 based on a combination of radiometric and anthropogenic dating pr...

POP-pincer osmium-polyhydrides: head-to-head (Z)-dimerization of terminal alkynes.

PubMed

Alós, Joaquín; Bolaño, Tamara; Esteruelas, Miguel A; Oliván, Montserrat; Oñate, Enrique; Valencia, Marta

2013-05-20

A wide range of osmium-polyhydride complexes stabilized by the POP-pincer ligand xant(P(i)Pr2)2 (9,9-dimethyl-4,5-bis(diisopropylphosphino)xanthene) have been synthesized through cis-OsCl2{κ-S-(DMSO)4} (1, DMSO = dimethyl sulfoxide). Treatment of toluene solutions of this adduct with the diphosphine, under reflux, leads to OsCl2{xant(P(i)Pr2)2}(κ-S-DMSO) (2). The reaction of 2 with H2 in the presence of Et3N affords OsH3Cl{xant(P(i)Pr2)2} (3), which can be also prepared by addition of xant(P(i)Pr2)2 to toluene solutions of the unsaturated d(4)-trihydride OsH3Cl(P(i)Pr3)2 (5). Complex 3 reductively eliminates H2 in toluene at 90 °C. In the presence of dimethyl sulfoxide, the resulting monohydride is trapped by the S-donor molecule to give OsHCl{xant(P(i)Pr2)2}(κ-S-DMSO) (6). The reaction of 2 with H2 is sensible to the Brønsted base. Thus, in contrast to Et3N, NaH removes both chloride ligands and the hexahydride OsH6{xant(P(i)Pr2)2} (7), containing a κ(2)-P-binding diphosphine, is formed under 3 atm of hydrogen at 50 °C. Complex 7 releases a H2 molecule to yield the tetrahydride OsH4{xant(P(i)Pr2)2} (8), which can be also prepared by reaction of OsH6(P(i)Pr3)2 (9) with xant(P(i)Pr2)2. Complex 8 reduces H(+) to give, in addition to H2, the oxidized OsH4-species [OsH4(OTf){xant(P(i)Pr2)2}](+) (10, OTf = trifluoromethanesulfonate). The redox process occurs in two stages via the OsH5-cation [OsH5{xant(P(i)Pr2)2}](+) (11). The metal oxidation state four can be recovered. The addition of acetonitrile to 10 leads to [OsH2(η(2)-H2)(CH3CN){xant(P(i)Pr2)2}](2+) (12). The deprotonation of 12 yields the osmium(IV) trihydride [OsH3(CH3CN){xant(P(i)Pr2)2}](+) (13), which is also formed by addition of HOTf to the acetonitrile solutions of 8. The latter is further an efficient catalyst precursor for the head-to-head (Z)-dimerization of phenylacetylene and tert-butylacetylene. During the activation process of the tetrahydride, the bis(alkynyl)vinylidene derivatives Os(C≡CR)2(=C═CHR){xant(P(i)Pr2)2} (R = Ph (14), (t)Bu (15)) are formed.

mer, fac, and Bidentate Coordination of an Alkyl-POP Ligand in the Chemistry of Nonclassical Osmium Hydrides.

PubMed

Esteruelas, Miguel A; García-Yebra, Cristina; Martín, Jaime; Oñate, Enrique

2017-01-03

Nonclassical and classical osmium polyhydrides containing the diphosphine 9,9-dimethyl-4,5-bis(diisopropylphosphino)xanthene (xant(P i Pr 2 ) 2 ), coordinated in κ 3 -mer, κ 3 -fac, and κ 2 -P,P fashions, have been isolated during the cyclic formation of H 2 by means of the sequential addition of H + and H - or H - and H + to the classical trihydride OsH 3 Cl{xant(P i Pr 2 ) 2 } (1). This complex adds H + to form the compressed dihydride dihydrogen complex [OsCl(H···H)(η 2 -H 2 ){xant(P i Pr 2 ) 2 }] + (2). Under argon, cation 2 loses H 2 and the resulting unsaturated fragment dimerizes to give [(Os(H···H){xant(P i Pr 2 ) 2 }) 2 (μ-Cl) 2 ] 2+ (3). During the transformation the phosphine changes its coordination mode from mer to fac. The benzofuran counterpart of 1, OsH 3 Cl{dbf(P i Pr 2 ) 2 } (4; dbf(P i Pr 2 ) 2 = 4,6-bis(diisopropylphosphino)dibenzofuran), also adds H + to afford the benzofuran counterpart of 2, [OsCl(H···H)(η 2 -H 2 ){xant(P i Pr 2 ) 2 }] + (5), which in contrast to the latter is stable and does not dimerize. Acetonitrile breaks the chloride bridge of 3 to form the dihydrogen [OsCl(η 2 -H 2 )(CH 3 CN){xant(P i Pr 2 ) 2 }] + (6), regenerating the mer coordination of the diphosphine. The hydride ion also breaks the chloride bridge of 3. The addition of KH to 3 leads to 1, closing a cycle for the formation of H 2 . Complex 1 reacts with a second hydride ion to give OsH 4 {xant(P i Pr 2 ) 2 } (7) as consequence of the displacement of the chloride. Similarly to the latter, the oxygen atom of the mer-coordinated diphosphine of 7 has a tendency to be displaced by the hydride ion. Thus, the addition of KH to 7 yields [OsH 5 {xant(P i Pr 2 ) 2 }] - (8), containing a κ 2 -P,P-diphosphine. Complex 8 is easily protonated to afford OsH 6 {xant(P i Pr 2 ) 2 } (9), which releases H 2 to regenerate 7, closing a second cycle for the formation of molecular hydrogen.

Assessing survival of Mid-Columbia River released juvenile salmonids at McNary Dam, Washington, 2008-09

USGS Publications Warehouse

Evans, Scott D.; Walker, Christopher E.; Brewer, Scott J.; Adams, Noah S.

2010-01-01

Few studies have evaluated survival of juvenile salmon over long river reaches in the Columbia River and information regarding the survival of sockeye salmon at lower Columbia River dams is lacking. To address these information gaps, the U.S. Geological Survey was contracted by the U.S. Army Corps of Engineers to evaluate the possibility of using tagged fish released in the Mid-Columbia River to assess passage and survival at and downstream of McNary Dam. Using the acoustic telemetry systems already in place for a passage and survival study at McNary Dam, fish released from the tailraces of Wells, Rocky Reach, Rock Island, Wanapum, and Priest Rapids Dams were detected at McNary Dam and at the subsequent downstream arrays. These data were used to generate route-specific survival probabilities using single-release models from fish released in the Mid-Columbia River. We document trends in passage and survival probabilities at McNary Dam for yearling Chinook and sockeye salmon and juvenile steelhead released during studies in the Mid-Columbia River. Trends in the survival and passage of these juvenile salmonid species are presented and discussed. However, comparisons made across years and between study groups are not possible because of differences in the source of the test fish, the type of acoustic tags used, the absence of the use of passive integrated transponder tags in some of the release groups, differences in tagging and release protocols, annual differences in dam operations and configurations, differences in how the survival models were constructed (that is, number of routes that could be estimated given the number of fish detected), and the number and length of reaches included in the analysis (downstream reach length and arrays). Despite these differences, the data we present offer a unique opportunity to examine the migration behavior and survival of a group of fish that otherwise would not be studied. This is particularly true for sockeye salmon because little information is available about their survival as they pass hydroelectric dams in the lower Columbia River. Collecting information on fish released in the Mid-Columbia River, as well as on fish released 8 kilometers upstream of McNary Dam, allowed us to evaluate similarities and differences in passage and survival probabilities. In general, juvenile salmonids released in the Mid-Columbia River and detected at and downstream of McNary Dam showed trends in passage and survival probabilities that were similar to fish released 8 kilometers upstream of McNary Dam. This suggests that increased migration time or length of migration had little effect on behavior and survival of Mid-Columbia River released juvenile salmonids detected at McNary Dam.

Systems Approach to Defeating Maritime Improvised Explosive Devices in U.S. Ports

DTIC Science & Technology

2008-12-01

DETECTION Pfi PROBABILITY OF FALSE IDENTIFICATION PHPK PROBABILITY OF HIT/PROBABILITY OF KILL PMA POST MISSION ANALYSIS PNNL PACIFIC...16 Naval Warfare Publication 27-2(Rev. B), Section 1.8.4.1(unclassified) 42 detection analysis is conducted...NAVAL POSTGRADUATE SCHOOL MONTEREY, CALIFORNIA Approved for public release; distribution is unlimited Prepared

Modeling Precipitation Dependent Forest Resilience in India

NASA Astrophysics Data System (ADS)

Das, P.; Behera, M. D.; Roy, P. S.

2018-04-01

The impact of long term climate change that imparts stress on forest could be perceived by studying the regime shift of forest ecosystem. With the change of significant precipitation, forest may go through density change around globe at different spatial and temporal scale. The 100 class high resolution (60 meter spatial resolution) Indian vegetation type map was used in this study recoded into four broad categories depending on phrenology as (i) forest, (ii) scrubland, (iii) grassland and (iv) treeless area. The percentage occupancy of forest, scrub, grass and treeless were observed as 19.9 %, 5.05 %, 1.89 % and 7.79 % respectively. Rest of the 65.37 % land area was occupied by the cropland, built-up, water body and snow covers. The majority forest cover were appended into a 5 km × 5 km grid, along with the mean annual precipitation taken from Bioclim data. The binary presence and absence of different vegetation categories in relates to the annual precipitation was analyzed to calculate their resilience expressed in probability values ranging from 0 to 1. Forest cover observed having resilience probability (Pr) < 0.3 in only 0.3 % (200 km2) of total forest cover in India, which was 4.3 % < 0.5 Pr. Majority of the scrubs and grass (64.92 % Pr < 0.5) from North East India which were the shifting cultivation lands showing low resilience, having their high tendency to be transform to forest. These results have spatial explicitness to highlight the resilient and non-resilient distribution of forest, scrub and grass, and treeless areas in India.

Slow-release fertilizers 101

Treesearch

Robin Rose

2002-01-01

Slow release fertilizers have been in common use within the horticultural industry for decades. Probably the mostly commonly heard of product is Scott's Osmocote which has been around for a quite a long time. However, some time ago slow release fertilizers moved out of the potted greenhouse environment and onto golf courses, suburban lawns and bushes, and orchards...

Hybrid stochastic framework predicts efficacy of prophylaxis against HIV: An example with different dolutegravir prophylaxis schemes.

PubMed

Duwal, Sulav; Dickinson, Laura; Khoo, Saye; von Kleist, Max

2018-06-01

To achieve the 90-90-90 goals set by UNAIDS, the number of new HIV infections needs to decrease to approximately 500,000 by 2020. One of the 'five pillars' to achieve this goal is pre-exposure prophylaxis (PrEP). Truvada (emtricitabine-tenofovir) is currently the only medication approved for PrEP. Despite its advantages, Truvada is costly and requires individuals to adhere to the once-daily regimen. To improve PrEP, many next-generation regimen, including long-acting formulations, are currently investigated. However, pre-clinical testing may not guide candidate selection, since it often fails to translate into clinical efficacy. On the other hand, quantifying prophylactic efficacy in the clinic is ethically problematic and requires to conduct long (years) and large (N>1000 individuals) trials, precluding systematic evaluation of candidates and deployment strategies. To prioritize- and help design PrEP regimen, tools are urgently needed that integrate pharmacological-, viral- and host factors determining prophylactic efficacy. Integrating the aforementioned factors, we developed an efficient and exact stochastic simulation approach to predict prophylactic efficacy, as an example for dolutegravir (DTG). Combining the population pharmacokinetics of DTG with the stochastic framework, we predicted that plasma concentrations of 145.18 and 722.23nM prevent 50- and 90% sexual transmissions respectively. We then predicted the reduction in HIV infection when DTG was used in PrEP, PrEP 'on demand' and post-exposure prophylaxis (PEP) before/after virus exposure. Once daily PrEP with 50mg oral DTG prevented 99-100% infections, and 85% of infections when 50% of dosing events were missed. PrEP 'on demand' prevented 79-84% infections and PEP >80% when initiated within 6 hours after virus exposure and continued for as long as possible. While the simulation framework can easily be adapted to other PrEP candidates, our simulations indicated that oral 50mg DTG is non-inferior to Truvada. Moreover, the predicted 90% preventive concentrations can guide release kinetics of currently developed DTG nano-formulations.

A 30-year history of earthquake crisis communication in California and lessons for the future

NASA Astrophysics Data System (ADS)

Jones, L.

2015-12-01

The first statement from the US Geological Survey to the California Office of Emergency Services quantifying the probability of a possible future earthquake was made in October 1985 about the probability (approximately 5%) that a M4.7 earthquake located directly beneath the Coronado Bay Bridge in San Diego would be a foreshock to a larger earthquake. In the next 30 years, publication of aftershock advisories have become routine and formal statements about the probability of a larger event have been developed in collaboration with the California Earthquake Prediction Evaluation Council (CEPEC) and sent to CalOES more than a dozen times. Most of these were subsequently released to the public. These communications have spanned a variety of approaches, with and without quantification of the probabilities, and using different ways to express the spatial extent and the magnitude distribution of possible future events. The USGS is re-examining its approach to aftershock probability statements and to operational earthquake forecasting with the goal of creating pre-vetted automated statements that can be released quickly after significant earthquakes. All of the previous formal advisories were written during the earthquake crisis. The time to create and release a statement became shorter with experience from the first public advisory (to the 1988 Lake Elsman earthquake) that was released 18 hours after the triggering event, but was never completed in less than 2 hours. As was done for the Parkfield experiment, the process will be reviewed by CEPEC and NEPEC (National Earthquake Prediction Evaluation Council) so the statements can be sent to the public automatically. This talk will review the advisories, the variations in wording and the public response and compare this with social science research about successful crisis communication, to create recommendations for future advisories

A Preliminary Trial: Double-Blind Comparison of Nefazodone, Bupropion-SR and Placebo in the Treatment of Cannabis Dependence

PubMed Central

Carpenter, Kenneth M.; McDowell, David; Brooks, Daniel J.; Cheng, Wendy; Levin, Frances R.

2009-01-01

The present study investigated the efficacy of nefazodone and bupropion-sustained release for treating cannabis dependence. A double blind, placebo controlled, piggy back design was employed to assess if nefazodone and bupropion-sustained release increased the probability of abstinence from cannabis and reduced the severity of cannabis dependence and cannabis withdrawal symptoms during a 13-week outpatient treatment program. One-hundred and six participants (M=32 years; Females n=25) were randomized to one of three medication conditions (nefazodone, bupropion-sustained release, or placebo) and participated in a weekly individually based coping skills therapy program. Results indicated a an increased probability of achieving abstinence over the course of treatment and a decrease in the severity of cannabis dependence and the withdrawal symptom of irritability. There were no significant effects demonstrated for nefazodone and bupropion-sustained release on cannabis use or cannabis withdrawal symptoms. The results indicate nefazodone and bupropion-sustained release may have limited efficacy in treating cannabis dependence. PMID:19219666

Errors in the estimation of the variance: implications for multiple-probability fluctuation analysis.

PubMed

Saviane, Chiara; Silver, R Angus

2006-06-15

Synapses play a crucial role in information processing in the brain. Amplitude fluctuations of synaptic responses can be used to extract information about the mechanisms underlying synaptic transmission and its modulation. In particular, multiple-probability fluctuation analysis can be used to estimate the number of functional release sites, the mean probability of release and the amplitude of the mean quantal response from fits of the relationship between the variance and mean amplitude of postsynaptic responses, recorded at different probabilities. To determine these quantal parameters, calculate their uncertainties and the goodness-of-fit of the model, it is important to weight the contribution of each data point in the fitting procedure. We therefore investigated the errors associated with measuring the variance by determining the best estimators of the variance of the variance and have used simulations of synaptic transmission to test their accuracy and reliability under different experimental conditions. For central synapses, which generally have a low number of release sites, the amplitude distribution of synaptic responses is not normal, thus the use of a theoretical variance of the variance based on the normal assumption is not a good approximation. However, appropriate estimators can be derived for the population and for limited sample sizes using a more general expression that involves higher moments and introducing unbiased estimators based on the h-statistics. Our results are likely to be relevant for various applications of fluctuation analysis when few channels or release sites are present.

ESO PR Highlights in 2000

NASA Astrophysics Data System (ADS)

2001-01-01

At the beginning of the new millennium, ESO and its staff are facing the future with confidence. The four 8.2-m Unit Telescopes of the Very Large Telescope (VLT) are in great shape and the VLT Interferometer (VLTI) will soon have "first fringes". The intercontinental ALMA project is progressing well and concepts for extremely large optical/infrared telescopes are being studied. They can also look back at a fruitful and rewarding past year. Perhaps the most important, single development has been the rapid transition of the Very Large Telescope (VLT). From being a "high-tech project under construction" it has now become a highly proficient, world-class astronomical observatory. This trend is clearly reflected in ESO's Press Releases , as more and more front-line scientific results emerge from rich data obtained at this very efficient facility. There were also exciting news from several of the instruments at La Silla. At the same time, the ESO community may soon grow, as steps towards membership are being taken by various European countries. Throughout 2000, a total of 54 PR communications were made, with a large number of Press Photos and Video Clips, cf. the 2000 PR Index. Some of the ESO PR highlights may be accessed directly via the clickable image on the present page. ESO PR Photo 01/01 is also available in a larger (non-clickable) version [ JPEG: 566 x 566 pix - 112k]. It may be reproduced, if credit is given to the European Southern Observatory.

Central and peripheral effects of chronic food restriction and weight restoration in the rat.

PubMed

Kinzig, Kimberly P; Hargrave, Sara L; Tao, Erin E

2009-02-01

Previous studies have demonstrated that some endocrine consequences of long-term caloric restriction persist after weight restoration in human subjects. Here we evaluate effects of chronic food restriction in rats that were restricted to 70% of control kcal for 4 wk and subsequently weight restored. Measures were taken from rats at 80% (chronically restricted; CR), 90% (partially weight restored; PR), 100% (fully weight restored; FR), and after 4 wk at 100% body weight of controls (extended weight restored; ER). Plasma insulin and leptin were decreased, and ghrelin was increased in CR compared with controls. Leptin and ghrelin normalized with weight restoration at PR, FR, and ER; however, baseline insulin was not normalized until the ER state. Hypothalamic mRNA expression levels for proopiomelanocortin (POMC), agouti-related protein (AgRP), and neuropeptide Y (NPY) revealed significantly less POMC mRNA expression in CR and PR rats, and significantly less arcuate NPY mRNA in PR and FR. In the dorsomedial hypothalamus, CR, PR, and FR rats had significantly increased NPY expression that was not normalized until the ER state. In response to a test meal, insulin and ghrelin release patterns were altered through the FR stage, and ghrelin remained affected at ER. Collectively, these data demonstrate that mere weight restoration is not sufficient to normalize hypothalamic gene expression levels and endocrine responses to a meal, and that meal-related ghrelin responses persist despite weight restoration for up to 4 wk.

The Volumetric Diversity of Misfolded Prion Protein Oligomers Revealed by Pressure Dissociation*

PubMed Central

Torrent, Joan; Lange, Reinhard; Rezaei, Human

2015-01-01

Protein oligomerization has been associated with a wide range of diseases. High pressure approaches offer a powerful tool for deciphering the underlying molecular mechanisms by revealing volume changes associated with the misfolding and assembly reactions. We applied high pressure to induce conformational changes in three distinct β-sheet-rich oligomers of the prion protein PrP, a protein characterized by a variety of infectious quaternary structures that can propagate stably and faithfully and cause diseases with specific phenotypic traits. We show that pressure induces dissociation of the oligomers and leads to a lower volume monomeric PrP state that refolds into the native conformation after pressure release. By measuring the different pressure and temperature sensitivity of the tested PrP oligomers, we demonstrate significantly different void volumes in their quaternary structure. In addition, by focusing on the kinetic and energetic behavior of the pressure-induced dissociation of one specific PrP oligomer, we reveal a large negative activation volume and an increase in both apparent activation enthalpy and entropy. This suggests a transition state ensemble that is less structured and significantly more hydrated than the oligomeric state. Finally, we found that site-specific fluorescent labeling allows monitoring of the transient population of a kinetic intermediate in the dissociation reaction. Our results indicate that defects in atomic packing may deserve consideration as a new factor that influences differences between PrP assemblies and that could be relevant also for explaining the origin of prion strains. PMID:26126829

GABA from reactive astrocytes impairs memory in mouse models of Alzheimer's disease.

PubMed

Jo, Seonmi; Yarishkin, Oleg; Hwang, Yu Jin; Chun, Ye Eun; Park, Mijeong; Woo, Dong Ho; Bae, Jin Young; Kim, Taekeun; Lee, Jaekwang; Chun, Heejung; Park, Hyun Jung; Lee, Da Yong; Hong, Jinpyo; Kim, Hye Yun; Oh, Soo-Jin; Park, Seung Ju; Lee, Hyo; Yoon, Bo-Eun; Kim, YoungSoo; Jeong, Yong; Shim, Insop; Bae, Yong Chul; Cho, Jeiwon; Kowall, Neil W; Ryu, Hoon; Hwang, Eunmi; Kim, Daesoo; Lee, C Justin

2014-08-01

In Alzheimer's disease (AD), memory impairment is the most prominent feature that afflicts patients and their families. Although reactive astrocytes have been observed around amyloid plaques since the disease was first described, their role in memory impairment has been poorly understood. Here, we show that reactive astrocytes aberrantly and abundantly produce the inhibitory gliotransmitter GABA by monoamine oxidase-B (Maob) and abnormally release GABA through the bestrophin 1 channel. In the dentate gyrus of mouse models of AD, the released GABA reduces spike probability of granule cells by acting on presynaptic GABA receptors. Suppressing GABA production or release from reactive astrocytes fully restores the impaired spike probability, synaptic plasticity, and learning and memory in the mice. In the postmortem brain of individuals with AD, astrocytic GABA and MAOB are significantly upregulated. We propose that selective inhibition of astrocytic GABA synthesis or release may serve as an effective therapeutic strategy for treating memory impairment in AD.

Integrity of Helix 2-Helix 3 Domain of the PrP Protein Is Not Mandatory for Prion Replication*

PubMed Central

Salamat, Khalid; Moudjou, Mohammed; Chapuis, Jérôme; Herzog, Laetitia; Jaumain, Emilie; Béringue, Vincent; Rezaei, Human; Pastore, Annalisa; Laude, Hubert; Dron, Michel

2012-01-01

The process of prion conversion is not yet well understood at the molecular level. The regions critical for the conformational change of PrP remain mostly debated and the extent of sequence change acceptable for prion conversion is poorly documented. To achieve progress on these issues, we applied a reverse genetic approach using the Rov cell system. This allowed us to test the susceptibility of a number of insertion mutants to conversion into prion in the absence of wild-type PrP molecules. We were able to propagate several prions with 8 to 16 extra amino acids, including a polyglycine stretch and His or FLAG tags, inserted in the middle of the protease-resistant fragment. These results demonstrate the possibility to increase the length of the loop between helices H2 and H3 up to 4-fold, without preventing prion replication. They also indicate that this loop probably remains unstructured in PrPSc. We also showed that bona fide prions can be produced following insertion of octapeptides in the two C-terminal turns of H2. These insertions do not interfere with the overall fold of the H2-H3 domain indicating that the highly conserved sequence of the terminal part of H2 is not critical for the conversion. Altogether these data showed that the amplitude of modifications acceptable for prion conversion in the core of the globular domain of PrP is much greater than one might have assumed. These observations should help to refine structural models of PrPSc and elucidate the conformational changes underlying prions generation. PMID:22511770

Integrity of helix 2-helix 3 domain of the PrP protein is not mandatory for prion replication.

PubMed

Salamat, Khalid; Moudjou, Mohammed; Chapuis, Jérôme; Herzog, Laetitia; Jaumain, Emilie; Béringue, Vincent; Rezaei, Human; Pastore, Annalisa; Laude, Hubert; Dron, Michel

2012-06-01

The process of prion conversion is not yet well understood at the molecular level. The regions critical for the conformational change of PrP remain mostly debated and the extent of sequence change acceptable for prion conversion is poorly documented. To achieve progress on these issues, we applied a reverse genetic approach using the Rov cell system. This allowed us to test the susceptibility of a number of insertion mutants to conversion into prion in the absence of wild-type PrP molecules. We were able to propagate several prions with 8 to 16 extra amino acids, including a polyglycine stretch and His or FLAG tags, inserted in the middle of the protease-resistant fragment. These results demonstrate the possibility to increase the length of the loop between helices H2 and H3 up to 4-fold, without preventing prion replication. They also indicate that this loop probably remains unstructured in PrP(Sc). We also showed that bona fide prions can be produced following insertion of octapeptides in the two C-terminal turns of H2. These insertions do not interfere with the overall fold of the H2-H3 domain indicating that the highly conserved sequence of the terminal part of H2 is not critical for the conversion. Altogether these data showed that the amplitude of modifications acceptable for prion conversion in the core of the globular domain of PrP is much greater than one might have assumed. These observations should help to refine structural models of PrP(Sc) and elucidate the conformational changes underlying prions generation.

A Venom Serpin Splicing Isoform of the Endoparasitoid Wasp Pteromalus puparum Suppresses Host Prophenoloxidase Cascade by Forming Complexes with Host Hemolymph Proteinases*

PubMed Central

Yan, Zhichao; Fang, Qi; Liu, Yang; Xiao, Shan; Yang, Lei; Wang, Fei; An, Chunju; Werren, John H.; Ye, Gongyin

2017-01-01

To ensure successful parasitism, parasitoid wasps inject venom along with their eggs into their hosts. The venom serves to suppress host immune responses, including melanization. Venom from Pteromalus puparum, a pupal endoparasitoid, inhibits melanization of host hemolymph in vitro in a dose-dependent manner. Using assay-guided fractionation, a serpin splicing isoform with phenoloxidase inhibitory activity was identified as P. puparum serpin-1, venom isoform (PpS1V). This serpin gene has 16 predicted splicing isoforms that differ only in the C-terminal region. RT-PCR results show that the specific serpin isoform is differentially expressed in the venom gland. Recombinant PpS1V (rPpS1V) suppresses host prophenoloxidase (PPO) activation rather than inhibiting the phenoloxidase directly. Pulldown assays show that PpS1V forms complexes with two host hemolymph proteins, here named Pieris rapae hemolymph proteinase 8 (PrHP8) and P. rapae prophenoloxidase-activating proteinase 1 (PrPAP1), based on gene sequence blasting and phylogenetic analysis. The role of rPrPAP1 in the PPO activation cascade and its interaction with rPpS1V were confirmed. The stoichiometry of inhibition of PrPAP1 by PpS1V is 2.3. PpS1V also inhibits PPO activation in a non-natural host, Ostrinia furnacalis, through forming a complex with O. furnacalis serine protease 13 (OfSP13), an ortholog to PrPAP1. Our results identify a venom-enriched serpin isoform in P. puparum that inhibits host PPO activation, probably by forming a complex with host hemolymph proteinase PrPAP1. PMID:27913622

The Use of Command and Control to Enhance Agility and Achieve Synchronization on the AirLand Battlefield,

DTIC Science & Technology

1986-05-15

for public release; distribution is unlimited. APPROVED FOJ Pr~rrLT~c FTAS 86-3641 86 11 18 134 UNCLASSIFIED SECURITY CLASSIFICATION OF THIS -PAGE 7! J...Military Staff, Its HistorY and Devlopment. Harrisburg, PA: The Stackpole Company, 1961. Home, Alistair. To Lose a Battle. New York: Penguin Books, 1979

Lichens: Unexpected anti-prion agents?

USGS Publications Warehouse

Rodriguez, Cynthia M.; Bennett, James P.; Johnson, Christopher J.

2012-01-01

The prion diseases sheep scrapie and cervid chronic wasting disease are transmitted, in part, via an environmental reservoir of infectivity; prions released from infected animals persist in the environment and can cause disease years later. Central to controlling disease transmission is the identification of methods capable of inactivating these agents on the landscape. We have found that certain lichens, common, ubiquitous, symbiotic organisms, possess a serine protease capable of degrading prion protein (PrP) from prion-infected animals. The protease functions against a range of prion strains from various hosts and reduces levels of abnormal PrP by at least two logs. We have now tested more than 20 lichen species from several geographical locations and from various taxa and found that approximately half of these species degrade PrP. Critical next steps include examining the effect of lichens on prion infectivity and cloning the protease responsible for PrP degradation. The impact of lichens on prions in the environment remains unknown. We speculate that lichens could have the potential to degrade prions when they are shed from infected animals onto lichens or into environments where lichens are abundant. In addition, lichens are frequently consumed by cervids and many other animals and the effect of dietary lichens on prion disease transmission should also be considered.

Monte Carlo simulation of single accident airport risk profile

NASA Technical Reports Server (NTRS)

1979-01-01

A computer simulation model was developed for estimating the potential economic impacts of a carbon fiber release upon facilities within an 80 kilometer radius of a major airport. The model simulated the possible range of release conditions and the resulting dispersion of the carbon fibers. Each iteration of the model generated a specific release scenario, which would cause a specific amount of dollar loss to the surrounding community. By repeated iterations, a risk profile was generated, showing the probability distribution of losses from one accident. Using accident probability estimates, the risks profile for annual losses was derived. The mechanics are described of the simulation model, the required input data, and the risk profiles generated for the 26 large hub airports.

Synthesis, structure and properties of bimetallic sodium rare-earth (RE) borohydrides, NaRE(BH4)4, RE = Ce, Pr, Er or Gd.

PubMed

Payandeh GharibDoust, SeyedHosein; Ravnsbæk, Dorthe B; Černý, Radovan; Jensen, Torben R

2017-10-10

Formation, stability and properties of new metal borohydrides within RE(BH 4 ) 3 -NaBH 4 , RE = Ce, Pr, Er or Gd is investigated. Three new bimetallic sodium rare-earth borohydrides, NaCe(BH 4 ) 4 , NaPr(BH 4 ) 4 and NaEr(BH 4 ) 4 are formed based on an addition reaction between NaBH 4 and halide free rare-earth metal borohydrides RE(BH 4 ) 3 , RE = Ce, Pr, Er. All the new compounds crystallize in the orthorhombic crystal system. NaCe(BH 4 ) 4 has unit cell parameters of a = 6.8028(5), b = 17.5181(13), c = 7.2841(5) Å and space group Pbcn. NaPr(BH 4 ) 4 is isostructural to NaCe(BH 4 ) 4 with unit cell parameters of a = 6.7617(2), b = 17.4678(7), c = 7.2522(3) Å. NaEr(BH 4 ) 4 crystallizes in space group Cmcm with unit cell parameters of a = 8.5379(2), b = 12.1570(4), c = 9.1652(3) Å. The structural relationships, also to the known RE(BH 4 ) 3 , are discussed in detail and related to the stability and synthesis conditions. Heat treatment of NaBH 4 -Gd(BH 4 ) 3 mixture forms an unstable amorphous phase, which decomposes after one day at RT. NaCe(BH 4 ) 4 and NaPr(BH 4 ) 4 show reversible hydrogen storage capacity of 1.65 and 1.04 wt% in the fourth H 2 release, whereas that of NaEr(BH 4 ) 4 continuously decreases. This is mainly assigned to formation of metal hydrides and possibly slower formation of sodium borohydride. The dehydrogenated state clearly contains rare-earth metal borides, which stabilize boron in the dehydrogenated state.

Novel celecoxib analogues inhibit glial production of prostaglandin E2, nitric oxide, and oxygen radicals reverting the neuroinflammatory responses induced by misfolded prion protein fragment 90-231 or lipopolysaccharide.

PubMed

Villa, Valentina; Thellung, Stefano; Bajetto, Adriana; Gatta, Elena; Robello, Mauro; Novelli, Federica; Tasso, Bruno; Tonelli, Michele; Florio, Tullio

2016-11-01

We tested the efficacy of novel cyclooxygenase 2 (COX-2) inhibitors in counteracting glia-driven neuroinflammation induced by the amyloidogenic prion protein fragment PrP90-231 or lipopolysaccharide (LPS). In search for molecules with higher efficacy than celecoxib, we focused our study on its 2,3-diaryl-1,3-thiazolidin-4-one analogues. As experimental models, we used the immortalized microglial cell line N9, rat purified microglial primary cultures, and mixed cultures of astrocytes and microglia. Microglia activation in response to PrP90-231 or LPS was characterized by growth arrest, morphology changes and the production of reactive oxygen species (ROS). Moreover, PrP90-231 treatment caused the overexpression of the inducible nitric oxide synthase (iNOS) and COX-2, with the consequent nitric oxide (NO), and prostaglandin E 2 (PGE 2 ) accumulation. These effects were challenged by different celecoxib analogues, among which Q22 (3-[4-(sulfamoyl)phenyl]-2-(4-tolyl)thiazolidin-4-one) inhibited microglia activation more efficiently than celecoxib, lowering both iNOS and COX-2 activity and reducing ROS release. During neurodegenerative diseases, neuroinflammation induced by amyloidogenic peptides causes the activation of both astrocytes and microglia with these cell populations mutually regulating each other. Thus the effects of PrP90-231 and LPS were also studied on mixed glial cultures containing astrocytes and microglia. PrP90-231 treatment elicited different responses in the co-cultures induced astrocyte proliferation and microglia growth arrest, resulting in a differential ability to release proinflammatory molecules with the production of NO and ROS mainly attributable on microglia, while COX-2 expression was induced also in astrocytes. Q22 effects on both NO and PGE 2 secretion were more significant in the mixed glial cultures than in purified microglia, demonstrating Q22 ability to revert the functional interaction between astrocytes and microglia. These results demonstrate that Q22 is a powerful drug able to revert glial neuroinflammatory responses and might represent a lead to explore the chemical space around celecoxib frameworks to design even more effective agents, paving the way to novel approaches to contrast the neuroinflammation-dependent toxicity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Impact of chemotherapy relative dose intensity on cause-specific and overall survival for stage I-III breast cancer: ER+/PR+, HER2- vs. triple-negative.

PubMed

Zhang, Lu; Yu, Qingzhao; Wu, Xiao-Cheng; Hsieh, Mei-Chin; Loch, Michelle; Chen, Vivien W; Fontham, Elizabeth; Ferguson, Tekeda

2018-05-01

To investigate the impact of chemotherapy relative dose intensity (RDI) on cause-specific and overall survival for stage I-III breast cancer: estrogen receptor or progesterone receptor positive, human epidermal-growth factor receptor negative (ER+/PR+ and HER2-) vs. triple-negative (TNBC) and to identify the optimal RDI cut-off points in these two patient populations. Data were collected by the Louisiana Tumor Registry for two CDC-funded projects. Women diagnosed with stage I-III ER+/PR+, HER2- breast cancer, or TNBC in 2011 with complete information on RDI were included. Five RDI cut-off points (95, 90, 85, 80, and 75%) were evaluated on cause-specific and overall survival, adjusting for multiple demographic variables, tumor characteristics, comorbidity, use of granulocyte-growth factor/cytokines, chemotherapy delay, chemotherapy regimens, and use of hormone therapy. Cox proportional hazards models and Kaplan-Meier survival curves were estimated and adjusted by stabilized inverse probability treatment weighting (IPTW) of propensity score. Of 494 ER+/PR+, HER2- patients and 180 TNBC patients, RDI < 85% accounted for 30.4 and 27.8%, respectively. Among ER+/PR+, HER2- patients, 85% was the only cut-off point at which the low RDI was significantly associated with worse overall survival (HR = 1.93; 95% CI 1.09-3.40). Among TNBC patients, 75% was the cut-off point at which the high RDI was associated with better cause-specific (HR = 2.64; 95% CI 1.09, 6.38) and overall survival (HR = 2.39; 95% CI 1.04-5.51). Higher RDI of chemotherapy is associated with better survival for ER+/PR+, HER2- patients and TNBC patients. To optimize survival benefits, RDI should be maintained ≥ 85% in ER+/PR+, HER2- patients, and ≥ 75% in TNBC patients.

LPS-induced systemic inflammation reveals an immunomodulatory role for the prion protein at the blood-brain interface.

PubMed

Salvesen, Ø; Reiten, M R; Espenes, A; Bakkebø, M K; Tranulis, M A; Ersdal, C

2017-05-22

The cellular prion protein (PrP C ) is an evolutionary conserved protein abundantly expressed not only in the central nervous system but also peripherally including the immune system. A line of Norwegian dairy goats naturally devoid of PrP C (PRNP Ter/Ter ) provides a novel model for studying PrP C physiology. In order to explore putative roles for PrP C in acute inflammatory responses, we performed a lipopolysaccharide (LPS, Escherichia coli O26:B6) challenge of 16 goats (8 PRNP +/+ and 8 PRNP Ter/Ter ) and included 10 saline-treated controls (5 of each PRNP genotype). Clinical examinations were performed continuously, and blood samples were collected throughout the trial. Genome-wide transcription profiles of the choroid plexus, which is at the blood-brain interface, and the hippocampus were analyzed by RNA sequencing, and the same tissues were histologically evaluated. All LPS-treated goats displayed clinical signs of sickness behavior, which were of significantly (p < 0.01) longer duration in animals without PrP C . In the choroid plexus, a substantial alteration of the transcriptome and activation of Iba1-positive cells were observed. This response included genotype-dependent differential expression of several genes associated with the immune response, such as ISG15, CXCL12, CXCL14, and acute phase proteins, among others. Activation of cytokine-responsive genes was skewed towards a more profound type I interferon response, and a less obvious type II response, in PrP C -deficient goats. The magnitude of gene expression in response to LPS was smaller in the hippocampus than in the choroid plexus. Resting state expression profiles revealed a few differences between the PRNP genotypes. Our data suggest that PrP C acts as a modulator of certain pathways of innate immunity signaling, particularly downstream of interferons, and probably contributes to protection of vulnerable tissues against inflammatory damage.

Induction of SA-signaling pathway and ethylene biosynthesis in Trichoderma harzianum-treated tomato plants after infection of the root-knot nematode Meloidogyne incognita.

PubMed

Leonetti, Paola; Zonno, Maria Chiara; Molinari, Sergio; Altomare, Claudio

2017-04-01

Salicylic acid-signaling pathway and ethylene biosynthesis were induced in tomato treated with Trichoderma harzianum when infected by root-knot nematodes and limited the infection by activation of SAR and ethylene production. Soil pre-treatment with Trichoderma harzianum (Th) strains ITEM 908 (T908) and T908-5 decreased susceptibility of tomato to Meloidogyne incognita, as assessed by restriction in nematode reproduction and development. The effect of T. harzianum treatments on plant defense was detected by monitoring the expression of the genes PR-1/PR-5 and JERF3/ACO, markers of the SA- and JA/ET-dependent signaling pathways, respectively. The compatible nematode-plant interaction in absence of fungi caused a marked suppression of PR-1, PR-5, and ACO gene expressions, either locally or systemically, whilst expression of JERF3 gene resulted unaffected. Conversely, when plants were pre-treated with Th-strains, over-expression of PR-1, PR-5, and ACO genes was observed in roots 5 days after nematode inoculation. JERF3 gene expression did not change in Th-colonized plants challenged with nematodes. In the absence of nematodes, Trichoderma-root interaction was characterized by the inhibition of both SA-dependent signaling pathway and ET biosynthesis, and, in the case of PR-1 and ACO genes, this inhibition was systemic. JERF3 gene expression was systemically restricted only at the very early stages of plant-fungi interaction. Data presented indicate that Th-colonization primed roots for Systemic Acquired Resistance (SAR) against root-knot nematodes and reacted to nematode infection more efficiently than untreated plants. Such a response probably involves also activation of ET production, through an augmented transcription of the ACO gene, which encodes for the enzyme catalyzing the last step of ET biosynthesis. JA signaling and Induced Systemic Resistance (ISR) do not seem to be involved in the biocontrol action of the tested Th-strains against RKNs.

Analysis of the costs and cost-effectiveness of the guidelines recommended by the 2018 GESIDA/Spanish National AIDS Plan for initial antiretroviral therapy in HIV-infected adults.

PubMed

Pérez-Molina, José Antonio; Martínez, Esteban; Blasco, Antonio Javier; Arribas, José Ramón; Domingo, Pere; Iribarren, José Antonio; Knobel, Hernando; Lázaro, Pablo; López-Aldeguer, José; Lozano, Fernando; Mariño, Ana; Miró, José M; Moreno, Santiago; Negredo, Eugenia; Pulido, Federico; Rubio, Rafael; Santos, Jesús; de la Torre, Javier; Tuset, Montserrat; von Wichmann, Miguel A; Gatell, Josep M

2018-06-05

The GESIDA/National AIDS Plan expert panel recommended preferred regimens (PR), alternative regimens (AR) and other regimens (OR) for antiretroviral treatment (ART) as initial therapy in HIV-infected patients for 2018. The objective of this study was to evaluate the costs and the efficiency of initiating treatment with PR and AR. Economic assessment of costs and efficiency (cost-effectiveness) based on decision tree analyses. Effectiveness was defined as the probability of reporting a viral load <50copies/mL at week 48, in an intention-to-treat analysis. Cost of initiating treatment with an ART regimen was defined as the costs of ART and its consequences (adverse effects, changes of ART regimen, and drug-resistance studies) over the first 48 weeks. The payer perspective (National Health System) was applied considering only differential direct costs: ART (official prices), management of adverse effects, studies of resistance, and HLA B*5701 testing. The setting was Spain and the costs correspond to those of 2018. A deterministic sensitivity analysis was conducted, building three scenarios for each regimen: base case, most favourable and least favourable. In the base-case scenario, the cost of initiating treatment ranges from 6788 euros for TAF/FTC/RPV (AR) to 10,649 euros for TAF/FTC+RAL (PR). The effectiveness varies from 0.82 for TAF/FTC+DRV/r (AR) to 0.91 for TAF/FTC+DTG (PR). The efficiency, in terms of cost-effectiveness, ranges from 7814 to 12,412 euros per responder at 48 weeks, for ABC/3TC/DTG (PR) and TAF/FTC+RAL (PR), respectively. Considering ART official prices, the most efficient regimen was ABC/3TC/DTG (PR), followed by TAF/FTC/RPV (AR) and TAF/FTC/EVG/COBI (AR). Copyright © 2018 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Induced maturation of human immunodeficiency virus.

PubMed

Mattei, Simone; Anders, Maria; Konvalinka, Jan; Kräusslich, Hans-Georg; Briggs, John A G; Müller, Barbara

2014-12-01

HIV-1 assembles at the plasma membrane of virus-producing cells as an immature, noninfectious particle. Processing of the Gag and Gag-Pol polyproteins by the viral protease (PR) activates the viral enzymes and results in dramatic structural rearrangements within the virion--termed maturation--that are a prerequisite for infectivity. Despite its fundamental importance for viral replication, little is currently known about the regulation of proteolysis and about the dynamics and structural intermediates of maturation. This is due mainly to the fact that HIV-1 release and maturation occur asynchronously both at the level of individual cells and at the level of particle release from a single cell. Here, we report a method to synchronize HIV-1 proteolysis in vitro based on protease inhibitor (PI) washout from purified immature virions, thereby temporally uncoupling virus assembly and maturation. Drug washout resulted in the induction of proteolysis with cleavage efficiencies correlating with the off-rate of the respective PR-PI complex. Proteolysis of Gag was nearly complete and yielded the correct products with an optimal half-life (t(1/2)) of ~5 h, but viral infectivity was not recovered. Failure to gain infectivity following PI washout may be explained by the observed formation of aberrant viral capsids and/or by pronounced defects in processing of the reverse transcriptase (RT) heterodimer associated with a lack of RT activity. Based on our results, we hypothesize that both the polyprotein processing dynamics and the tight temporal coupling of immature particle assembly and PR activation are essential for correct polyprotein processing and morphological maturation and thus for HIV-1 infectivity. Cleavage of the Gag and Gag-Pol HIV-1 polyproteins into their functional subunits by the viral protease activates the viral enzymes and causes major structural rearrangements essential for HIV-1 infectivity. This proteolytic maturation occurs concomitant with virus release, and investigation of its dynamics is hampered by the fact that virus populations in tissue culture contain particles at all stages of assembly and maturation. Here, we developed an inhibitor washout strategy to synchronize activation of protease in wild-type virus. We demonstrated that nearly complete Gag processing and resolution of the immature virus architecture are accomplished under optimized conditions. Nevertheless, most of the resulting particles displayed irregular morphologies, Gag-Pol processing was not faithfully reconstituted, and infectivity was not recovered. These data show that HIV-1 maturation is sensitive to the dynamics of processing and also that a tight temporal link between virus assembly and PR activation is required for correct polyprotein processing. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Negative Energy Balance Blocks Neural and Behavioral Responses to Acute Stress by "Silencing" Central Glucagon-Like Peptide 1 Signaling in Rats.

PubMed

Maniscalco, James W; Zheng, Huiyuan; Gordon, Patrick J; Rinaman, Linda

2015-07-29

Previous reports indicate that caloric restriction attenuates anxiety and other behavioral responses to acute stress, and blunts the ability of stress to increase anterior pituitary release of adrenocorticotropic hormone. Since hindbrain glucagon-like peptide-1 (GLP-1) neurons and noradrenergic prolactin-releasing peptide (PrRP) neurons participate in behavioral and endocrine stress responses, and are sensitive to the metabolic state, we examined whether overnight food deprivation blunts stress-induced recruitment of these neurons and their downstream hypothalamic and limbic forebrain targets. A single overnight fast reduced anxiety-like behavior assessed in the elevated-plus maze and acoustic startle test, including marked attenuation of light-enhanced startle. Acute stress [i.e., 30 min restraint (RES) or 5 min elevated platform exposure] robustly activated c-Fos in GLP-1 and PrRP neurons in fed rats, but not in fasted rats. Fasting also significantly blunted the ability of acute stress to activate c-Fos expression within the anterior ventrolateral bed nucleus of the stria terminalis (vlBST). Acute RES stress suppressed dark-onset food intake in rats that were fed ad libitum, whereas central infusion of a GLP-1 receptor antagonist blocked RES-induced hypophagia, and reduced the ability of RES to activate PrRP and anterior vlBST neurons in ad libitum-fed rats. Thus, an overnight fast "silences" GLP-1 and PrRP neurons, and reduces both anxiety-like and hypophagic responses to acute stress. The partial mimicking of these fasting-induced effects in ad libitum-fed rats after GLP-1 receptor antagonism suggests a potential mechanism by which short-term negative energy balance attenuates neuroendocrine and behavioral responses to acute stress. The results from this study reveal a potential central mechanism for the "metabolic tuning" of stress responsiveness. A single overnight fast, which markedly reduces anxiety-like behavior in rats, reduces or blocks the ability of acute stress to activate hindbrain neurons that are immunoreactive for either prolactin-releasing peptide or glucagon-like peptide 1, and attenuates the activation of their stress-sensitive projection targets in the limbic forebrain. In nonfasted rats, central antagonism of glucagon-like peptide 1 receptors partially mimics the effect of an overnight fast by blocking the ability of acute stress to inhibit food intake, and by attenuating stress-induced activation of hindbrain and limbic forebrain neurons. We propose that caloric restriction attenuates behavioral and physiological responses to acute stress by "silencing" central glucagon-like peptide 1 signaling pathways. Copyright © 2015 the authors 0270-6474/15/3510701-14$15.00/0.

Negative Energy Balance Blocks Neural and Behavioral Responses to Acute Stress by “Silencing” Central Glucagon-Like Peptide 1 Signaling in Rats

PubMed Central

Maniscalco, James W.; Zheng, Huiyuan; Gordon, Patrick J.

2015-01-01

Previous reports indicate that caloric restriction attenuates anxiety and other behavioral responses to acute stress, and blunts the ability of stress to increase anterior pituitary release of adrenocorticotropic hormone. Since hindbrain glucagon-like peptide-1 (GLP-1) neurons and noradrenergic prolactin-releasing peptide (PrRP) neurons participate in behavioral and endocrine stress responses, and are sensitive to the metabolic state, we examined whether overnight food deprivation blunts stress-induced recruitment of these neurons and their downstream hypothalamic and limbic forebrain targets. A single overnight fast reduced anxiety-like behavior assessed in the elevated-plus maze and acoustic startle test, including marked attenuation of light-enhanced startle. Acute stress [i.e., 30 min restraint (RES) or 5 min elevated platform exposure] robustly activated c-Fos in GLP-1 and PrRP neurons in fed rats, but not in fasted rats. Fasting also significantly blunted the ability of acute stress to activate c-Fos expression within the anterior ventrolateral bed nucleus of the stria terminalis (vlBST). Acute RES stress suppressed dark-onset food intake in rats that were fed ad libitum, whereas central infusion of a GLP-1 receptor antagonist blocked RES-induced hypophagia, and reduced the ability of RES to activate PrRP and anterior vlBST neurons in ad libitum-fed rats. Thus, an overnight fast “silences” GLP-1 and PrRP neurons, and reduces both anxiety-like and hypophagic responses to acute stress. The partial mimicking of these fasting-induced effects in ad libitum-fed rats after GLP-1 receptor antagonism suggests a potential mechanism by which short-term negative energy balance attenuates neuroendocrine and behavioral responses to acute stress. SIGNIFICANCE STATEMENT The results from this study reveal a potential central mechanism for the “metabolic tuning” of stress responsiveness. A single overnight fast, which markedly reduces anxiety-like behavior in rats, reduces or blocks the ability of acute stress to activate hindbrain neurons that are immunoreactive for either prolactin-releasing peptide or glucagon-like peptide 1, and attenuates the activation of their stress-sensitive projection targets in the limbic forebrain. In nonfasted rats, central antagonism of glucagon-like peptide 1 receptors partially mimics the effect of an overnight fast by blocking the ability of acute stress to inhibit food intake, and by attenuating stress-induced activation of hindbrain and limbic forebrain neurons. We propose that caloric restriction attenuates behavioral and physiological responses to acute stress by “silencing” central glucagon-like peptide 1 signaling pathways. PMID:26224855

Molecular Features of the Copper Binding Sites in the Octarepeat Domain of the Prion Protein†

PubMed Central

Burns, Colin S.; Aronoff-Spencer, Eliah; Dunham, Christine M.; Lario, Paula; Avdievich, Nikolai I.; Antholine, William E.; Olmstead, Marilyn M.; Vrielink, Alice; Gerfen, Gary J.; Peisach, Jack; Scott, William G.; Millhauser, Glenn L.

2010-01-01

Recent evidence suggests that the prion protein (PrP) is a copper binding protein. The N-terminal region of human PrP contains four sequential copies of the highly conserved octarepeat sequence PHGGGWGQ spanning residues 60–91. This region selectively binds Cu2+ in vivo. In a previous study using peptide design, EPR, and CD spectroscopy, we showed that the HGGGW segment within each octarepeat comprises the fundamental Cu2+ binding unit [Aronoff-Spencer et al. (2000) Biochemistry 40, 13760–13771]. Here we present the first atomic resolution view of the copper binding site within an octarepeat. The crystal structure of HGGGW in a complex with Cu2+ reveals equatorial coordination by the histidine imidazole, two deprotonated glycine amides, and a glycine carbonyl, along with an axial water bridging to the Trp indole. Companion S-band EPR, X-band ESEEM, and HYSCORE experiments performed on a library of 15N-labeled peptides indicate that the structure of the copper binding site in HGGGW and PHGGGWGQ in solution is consistent with that of the crystal structure. Moreover, EPR performed on PrP(23–28, 57–91) and an 15N-labeled analogue demonstrates that the identified structure is maintained in the full PrP octarepeat domain. It has been shown that copper stimulates PrP endocytosis. The identified Gly–Cu linkage is unstable below pH ≈6.5 and thus suggests a pH-dependent molecular mechanism by which PrP detects Cu2+ in the extracellular matrix or releases PrP-bound Cu2+ within the endosome. The structure also reveals an unusual complementary interaction between copper-structured HGGGW units that may facilitate molecular recognition between prion proteins, thereby suggesting a mechanism for transmembrane signaling and perhaps conversion to the pathogenic form. PMID:11900542

Transport and processing of the Rous sarcoma virus Gag protein in the endoplasmic reticulum.

PubMed Central

Krishna, N K; Weldon, R A; Wills, J W

1996-01-01

The Gag proteins of replication-competent retroviruses direct budding at the plasma membrane and are cleaved by the viral protease (PR) just before or very soon after particle release. In contrast, defective retroviruses that bud into the endoplasmic reticulum (ER) have been found, and morphologically these appear to contain uncleaved Gag proteins. From this, it has been proposed that activation of PR may depend upon a host factor found only at the plasma membrane. However, if Gag proteins were cleaved by PR before the particle could pinch off the ER membrane, then the only particles that would remain visible are those that packaged smaller-than-normal amounts of PR, and these would have an immature morphology. To distinguish between these two hypotheses, we made use of the Rous sarcoma virus (RSV) Gag protein, the PR of RSV IS included on each Gag molecule. To target Gag to the ER, a signal peptide was installed at its amino terminus in place of the plasma membrane-binding domain. An intervening, hydrophobic, transmembrane anchor was included to keep Gag extended into the cytoplasm. We found that PR-mediated processing occurred, although the cleavage products were rapidly degraded. When the anchor was removed, allowing the entire protein to be inserted into the lumen of the ER, Gag processing occurred with a high level of efficiency, and the cleavage products were quite stable. Thus, PR activation does not require targeting of Gag molecules to the plasma membrane. Unexpectedly, molecules lacking the transmembrane anchor were rapidly secreted from the cell in a nonmembrane-enclosed form and in a manner that was very sensitive to brefeldin A and monensin. In contrast, the wild-type RSV and Moloney murine leukemia virus Gag proteins were completely insensitive to these inhibitors, suggesting that the normal mechanism of transport to the plasma membrane does not require interactions with the secretory pathway. PMID:8627676

Release of colicin E2 from Escherichia coli.

PubMed

Pugsley, A P; Rosenbusch, J P

1981-07-01

Treatment of Escherichia coli K-12(ColE2.P9) with 500 ng of mitomycin C per ml resulted in rapid and almost synchronous colicin E2 production. Colicin accumulated outside the cytoplasmic membrane, most probably in the periplasmic space. Colicin release occurred during a period in which the turbidity of the culture declined markedly. Periplasmic alkaline phosphatase was released during the same period, but cytoplasmic beta-galactosidase release was delayed.

Verb deficits in Alzheimer’s disease and agrammatism: Implications for lexical organization☆

PubMed Central

Kim, Mikyong; Thompson, Cynthia K.

2011-01-01

This study examined the nature of verb deficits in 14 individuals with probable Alzheimer’s Disease (PrAD) and nine with agrammatic aphasia. Production was tested, controlling both semantic and syntactic features of verbs, using noun and verb naming, sentence completion, and narrative tasks. Noun and verb comprehension and a grammaticality judgment task also were administered. Results showed that while both PrAD and agrammatic subjects showed impaired verb naming, the syntactic features of verbs (i.e., argument structure) influenced agrammatic, but not Alzheimer’s disease patients’ verb production ability. That is, agrammatic patients showed progressively greater difficulty with verbs associated with more arguments, as has been shown in previous studies (e.g., Kim & Thompson, 2000; Thompson, 2003; Thompson, Lange, Schneider, & Shapiro, 1997), and suggest a syntactic basis for verb production deficits in agrammatism. Conversely, the semantic complexity of verbs affected PrAD, but not agrammatic, patients’ performance, suggesting “bottom-up” breakdown in their verb lexicon, paralleling that of nouns, resulting from the degradation or loss of semantic features of verbs. PMID:14698726

[Analysis of SOX10 gene mutation in a family affected with Waardenburg syndrome type II].

PubMed

Zheng, Lei; Yan, Yousheng; Chen, Xue; Zhang, Chuan; Zhang, Qinghua; Feng, Xuan; Hao, Shen

2018-02-10

OBJECTIVE To detect potential mutation of SOX10 gene in a pedigree affected with Warrdenburg syndrome type II. METHODS Genomic DNA was extracted from peripheral blood samples of the proband and his family members. Exons and flanking sequences of MITF, PAX3, SOX10, SNAI2, END3 and ENDRB genes were analyzed by chip capturing and high throughput sequencing. Suspected mutations were verified with Sanger sequencing. RESULTS A c.127C>T (p.R43X) mutation of the SOX10 gene was detected in the proband, for which both parents showed a wild-type genotype. CONCLUSION The c.127C>T (p.R43X) mutation of SOX10 gene probably underlies the ocular symptoms and hearing loss of the proband.

Trio of Neptunes and their Belt

NASA Astrophysics Data System (ADS)

2006-05-01

Using the ultra-precise HARPS spectrograph on ESO's 3.6-m telescope at La Silla (Chile), a team of European astronomers have discovered that a nearby star is host to three Neptune-mass planets. The innermost planet is most probably rocky, while the outermost is the first known Neptune-mass planet to reside in the habitable zone. This unique system is likely further enriched by an asteroid belt. ESO PR Photo 18a/06 ESO PR Photo 18a/06 Planetary System Around HD 69830 (Artist's Impression) "For the first time, we have discovered a planetary system composed of several Neptune-mass planets", said Christophe Lovis, from the Geneva Observatory and lead-author of the paper presenting the results [1]. During more than two years, the astronomers carefully studied HD 69830, a rather inconspicuous nearby star slightly less massive than the Sun. Located 41 light-years away towards the constellation of Puppis (the Stern), it is, with a visual magnitude of 5.95, just visible with the unaided eye. The astronomers' precise radial-velocity measurements [2] allowed them to discover the presence of three tiny companions orbiting their parent star in 8.67, 31.6 and 197 days. "Only ESO's HARPS instrument installed at the La Silla Observatory, Chile, made it possible to uncover these planets", said Michel Mayor, also from Geneva Observatory, and HARPS Principal Investigator. "Without any doubt, it is presently the world's most precise planet-hunting machine" [3]. ESO PR Photo 18d/06 ESO PR Photo 18d/06 Phase Folded Measurements of HD 69830 The detected velocity variations are between 2 and 3 metres per second, corresponding to about 9 km/h! That's the speed of a person walking briskly. Such tiny signals could not have been distinguished from 'simple noise' by most of today's available spectrographs. The newly found planets have minimum masses between 10 and 18 times the mass of the Earth. Extensive theoretical simulations favour an essentially rocky composition for the inner planet, and a rocky/gas structure for the middle one. The outer planet has probably accreted some ice during its formation, and is likely to be made of a rocky/icy core surrounded by a quite massive envelope. Further calculations have also shown that the system is in a dynamically stable configuration. ESO PR Photo 18e/06 ESO PR Photo 18e/06 Formation Process of the Planetary System The outer planet also appears to be located near the inner edge of the habitable zone, where liquid water can exist at the surface of rocky/icy bodies. Although this planet is probably not Earth-like due to its heavy mass, its discovery opens the way to exciting perspectives. "This alone makes this system already exceptional", said Willy Benz, from Bern University, and co-author. "But the recent discovery by the Spitzer Space Telescope that the star most likely hosts an asteroid belt is adding the cherry to the cake." With three roughly equal-mass planets, one being in the habitable zone, and an asteroid belt, this planetary system shares many properties with our own solar system. "The planetary system around HD 69830 clearly represents a Rosetta stone in our understanding of how planets form", said Michel Mayor. "No doubt it will help us better understand the huge diversity we have observed since the first extra-solar planet was found 11 years ago." High resolution images and their captions are available on this page. Video footage and animations are also available on this page.

Folded or Not? Tracking Bet v 1 Conformation in Recombinant Allergen Preparations

PubMed Central

Seutter von Loetzen, Christian; Schweimer, Kristian; Bellinghausen, Iris; Treudler, Regina; Simon, Jan C.; Vogel, Lothar; Völker, Elke; Randow, Stefanie; Reuter, Andreas; Rösch, Paul; Vieths, Stefan; Holzhauser, Thomas; Schiller, Dirk

2015-01-01

Background Recombinant Bet v 1a (rBet v 1a) has been used in allergy research for more than three decades, including clinical application of so-called hypoallergens. Quantitative IgE binding to rBet v 1a depends on its native protein conformation, which might be compromised upon heterologous expression, purification, or mutational engineering of rBet v 1a. Objective To correlate experimental/theoretical comparisons of IgE binding of defined molar ratios of folded/misfolded recombinant Bet v 1a variants and to determine accuracy and precision of immuno- and physicochemical assays routinely used to assess the quality of recombinant allergen preparations. Methods rBet v 1a and its misfolded variant rBet v 1aS112P/R145P were heterologously expressed and purified from Escherichia coli. Structural integrities and oligomerisation of the recombinant allergens were evaluated by 1H-nuclear magnetic resonance (1H-NMR), circular dichroism (CD) spectroscopy, and dynamic light scattering (DLS). IgE binding of defined combinations of rBet v 1a and rBet v 1aS112P/R145P was assessed using immunoblotting (IB), enzyme-linked immunosorbent assay (ELISA) and mediator release (MR) of humanized rat basophilic leukemia cells sensitized with serum IgE of subjects allergic to birch pollen. Experimental and theoretically expected results of the analyses were compared. Results 1H-NMR spectra of rBet v 1a and rBet v 1aS112P/R145P demonstrate a native and highly disordered protein conformations, respectively. The CD spectra suggested typical alpha-helical and beta-sheet secondary structure content of rBet v 1a and random coil for rBet v 1aS112P/R145P. The hydrodynamic radii (RH) of 2.49 ± 0.39 nm (rBet v 1a) and 3.1 ± 0.56 nm (rBet v 1aS112P/R145P) showed monomeric dispersion of both allergens in solution. Serum IgE of birch pollen allergic subjects bound to 0.1% rBet v 1a in the presence of 99.9% of non-IgE binding rBet v 1aS112P/R145P. Immunoblot analysis overestimated, whereas ELISA and mediator release assay underestimated the actual quantity of IgE-reactive rBet v 1a in mixtures of rBet v 1a/rBet v 1aS112P/R145P with a molar ratio of rBet v 1a ≤ 10%. Conclusion Valid conclusions on quantitative IgE binding of recombinant Bet v 1a preparations depend on the accuracy and precision of physico- and immunochemical assays with which natively folded allergen is detected. PMID:26186356

Dynamics and Thermochemistry of Oxygen Uptake by a Mixed Ce-Pr Oxide

NASA Astrophysics Data System (ADS)

Sinev, M. Yu.; Fattakhova, Z. T.; Bychkov, V. Yu.; Lomonosov, V. I.; Gordienko, Yu. A.

2018-03-01

The dynamics of oxygen uptake by mixed Ce0.55Pr0.45O2-x oxide is studied in a pulsed oxygen supply mode using in situ high-temperature heat flow differential scanning calorimetry. It is stated that the oxidation proceeds in two regimes: a fast one at the beginning of the oxidation process, and a slow one, which is controlled by the diffusion of oxygen through the bulk of the solid at the later stages of the process. Analysis of the shape of calorimetric profiles reveals some processes, accompanied by heat release, that occur in the sample in the absence of oxygen in the gas phase. These could be due to both the redistribution of consumed oxygen in the oxide lattice and the lattice relaxation associated with the transformation of phases with different arrangements of oxygen vacancies in them. The heat effect (which diminishes from 60 to 40 kJ/mol in the course of oxygen uptake) associated with the oxidation of the reduced form of mixed Ce-Pr oxide, corresponds to the oxidation of praseodymium ions from (3+) to (4+).

Anemia and hemoglobin levels among Indigenous Xavante children, Central Brazil.

PubMed

Ferreira, Aline Alves; Santos, Ricardo Ventura; Souza, July Anne Mendonça de; Welch, James R; Coimbra, Carlos E A

2017-01-01

To evaluate the prevalence of anemia, mean hemoglobin levels, and the main nutritional, demographic, and socioeconomic factors among Xavante children in Mato Grosso State, Brazil. A survey was conducted with children under 10 years of age in two indigenous Xavante communities within the Pimentel Barbosa Indigenous Reserve. Hemoglobin concentration levels, anthropometric measurements, and socioeconomic/demographic data were collected by means of clinical measurements and structured interviews. The cut-off points recommended by the World Health Organization were used for anemia classification. Linear regression analyses with hemoglobin as the outcome and Poisson regression with robust variance and with the presence or absence of anemia as outcomes were performed (95%CI). Lower mean hemoglobin values were observed in children under 2 years of age, without a significant difference between sexes. Anemia was observed among 50.8% of children overall, with the highest prevalence among children under 2 years of age (77.8%). Age of the child was inversely associated with the occurrence of anemia (adjusted PR = 0.60; 95%CI 0.38-0.95) and mean hemoglobin values increased significantly with age. Greater height-for-age z-score values reduced the probability of having anemia by 1.8 times (adjusted PR = 0.59; 95%CI 0.34-1.00). Presence of another child with anemia within the household increased the probability of the occurrence of anemia by 52.9% (adjusted PR = 1.89; 95%CI 1.16-3.09). Elevated levels of anemia among Xavante children reveal a disparity between this Indigenous population and the national Brazilian population. Results suggest that anemia is determined by complex and variable relationships between socioeconomic, sociodemographic, and biological factors.

Relation of plasma tryptophan concentrations during pregnancy to maternal sleep and mental well-being: The GUSTO cohort.

PubMed

van Lee, Linde; Cai, Shirong; Loy, See Ling; Tham, Elaine K H; Yap, Fabian K P; Godfrey, Keith M; Gluckman, Peter D; Shek, Lynette P C; Teoh, Oon Hoe; Goh, Daniel Y T; Tan, Kok Hian; Chong, Yap Seng; Meaney, Michael J; Chen, Helen; Broekman, Birit F P; Chong, Mary F F

2018-01-01

Evidence suggests a relation between plasma tryptophan concentrations and sleep and mental well-being. As no studies have been performed in pregnant women, we studied the relation of plasma tryptophan concentrations during pregnancy with sleep quality, and mood during and after pregnancy. Pregnant women (n = 572) from the Growing Up in Singapore Towards healthy Outcomes study completed the Pittsburgh Sleep Quality Index (PSQI), the Edinburgh Postnatal Depression Scale (EPDS) and the State-Trait Anxiety Inventory (STAI) at 26-28 weeks gestation and three months post-delivery. Plasma tryptophan concentrations were measured at 26-28 weeks gestation. Poisson regressions estimated prevalence ratios (PR) for the association between tryptophan and poor sleep quality (PSQI global score > 5), probable antenatal depression (EPDS ≥ 15) and probable anxiety (STAI-state ≥ 41) were calculated adjusting for covariates. Mean plasma tryptophan concentrations was 48.0µmol/L (SD: 8.09). Higher plasma tryptophan concentrations were associated with a lower prevalence of antenatal poor sleep quality adjusting for covariates [PR: 0.88 (95% CI 0.80, 0.97) per 10µmol/L], especially in those participants who also suffered from anxiety symptoms [PR: 0.80 (95% CI 0.67, 0.95)]. No associations were observed between tryptophan concentrations during pregnancy and postnatal sleep quality or mental well-being. Subjective measures were used to assess sleep and mental well-being. We observed that higher plasma tryptophan concentrations were associated with a 12% lower prevalence of poor sleep quality during pregnancy, in particular among those with anxiety symptoms. These findings suggest the importance of having adequate tryptophan concentrations during pregnancy. Copyright © 2017 Elsevier B.V. All rights reserved.

Air Sea Rescue

DTIC Science & Technology

1942-01-01

ES) 10. SPONSOR/MONITOR’S ACRONYM(S) 11. SPONSOR/MONITOR’S REPORT NUMBER(S) 12. DISTRIBUTION/AVAILABILITY STATEMENT Approved for public release ...1. Dinglf Drill. ............. 67 2. DiBfhy Equipment. ............ 57 S. Aboard tlie life»Raft. ......... 68 4. Rationing of Food aart Water...fl 4. PUats ................ f4 5. Pood front Pr«»fc V«t«r. ........ 7* 8. Food Alonf Shore ........... 76 f. Skcll Pith .............. fi 8. Birds

Improving Future Construction Project Quality Through Analysis of Completed Contract Documentation

DTIC Science & Technology

1992-06-01

S lO\\\\ei taicit~y opciai~tIion and( mnaintenanice costs. and(In i sonic Cases lo\\\\ Ceill al conistmictmoii Colst. 6.2 H IItR F uSIA1Wl( - Sminilam...scotut limil Inlspect(ilonlhi inc l,st I eniult .i3 it ems concem lng, patching glass Customler Pr esent tlnal Ins111lwpectinn1 Yes Release (4

Diagnostic and Predictive Values of Thirst, Angiotensin II, and Vasopressin During Trauma Resuscitation

DTIC Science & Technology

2010-09-01

and plasma AVP and AT2 levels across a broader spectrum of hemorrhagic shock severity may be warranted. The authors wish to thank the medical, nursing ...301. 2. Olsson K. Central control of vasopressin release and thirst. Acta Paediatr Scand Suppl. 1983;305:36–9. Pr eh os p E m er g C ar e D ow nl oa

Association between preovulatory concentrations of estradiol and expression of uterine milk protein precursor, inhibin beta A, Period 1, proenkephalin-A, and receptors for oxytocin, progesterone, and estradiol

USDA-ARS?s Scientific Manuscript database

Cows that did not exhibit standing estrus around the time of gonadotropin-releasing hormone (GnRH)-induced ovulation had decreased pregnancy success compared to cows that exhibited estrus. Therefore, the objective of the present experiment was to characterize changes in expression of uterine milk pr...

pH-Responsive Hydrogel With an Anti-Glycation Agent for Modulating Experimental Periodontitis.

PubMed

Yu, Min-Chen; Chang, Chih-Yeun; Chao, Yi-Chi; Jheng, Yi-Han; Yang, Connie; Lee, Ning; Yu, Shan-Huey; Yu, Xin-Hong; Liu, Dean-Mo; Chang, Po-Chun

2016-06-01

Stimulus-responsive devices have emerged as a novel approach for local drug delivery. This study investigates the feasibility of a novel chitosan-based, pH-responsive hydrogel loaded with N-phenacylthiazolium bromide (PTB), which cleaves the crosslinks of advanced glycation end products on the extracellular matrix. A chitosan-based hydrogel loaded with PTB was fabricated, and the in vitro release profile was evaluated within pH 5.5 to 7.4. BALB/cJ mice and Sprague-Dawley rats were used to evaluate the effects during the induction and recovery phases of periodontitis, respectively, and animals in each phase were divided into four groups: 1) no periodontitis induction; 2) ligature-induced experimental periodontitis (group PR); 3) experimental periodontitis plus hydrogel without PTB (group PH); and 4) experimental periodontitis plus hydrogel with PTB (group PP). The therapeutic effects were evaluated by microcomputed tomographic imaging of periodontal bone level (PBL) loss and histomorphometry for inflammatory cell infiltration and collagen density. PTB was released faster at pH 5.5 to 6.5 and consistently slower at pH 7.4. In the induction phase, PBL and inflammatory cell infiltration were significantly reduced in group PP relative to group PR, and the loss of collagen matrix was significantly reduced relative to that observed in group PH. In the recovery phase, PBL and inflammatory cell infiltration were significantly reduced, and significantly greater collagen deposition was noted in group PP relative to groups PR and PH at 4 and 14 days after silk removal. Chitosan-based, pH-responsive hydrogels loaded with PTB can retard the initiation of and facilitate the recovery from experimental periodontitis.

Quasar probabilities and redshifts from WISE mid-IR through GALEX UV photometry

NASA Astrophysics Data System (ADS)

DiPompeo, M. A.; Bovy, J.; Myers, A. D.; Lang, D.

2015-09-01

Extreme deconvolution (XD) of broad-band photometric data can both separate stars from quasars and generate probability density functions for quasar redshifts, while incorporating flux uncertainties and missing data. Mid-infrared photometric colours are now widely used to identify hot dust intrinsic to quasars, and the release of all-sky WISE data has led to a dramatic increase in the number of IR-selected quasars. Using forced photometry on public WISE data at the locations of Sloan Digital Sky Survey (SDSS) point sources, we incorporate this all-sky data into the training of the XDQSOz models originally developed to select quasars from optical photometry. The combination of WISE and SDSS information is far more powerful than SDSS alone, particularly at z > 2. The use of SDSS+WISE photometry is comparable to the use of SDSS+ultraviolet+near-IR data. We release a new public catalogue of 5537 436 (total; 3874 639 weighted by probability) potential quasars with probability PQSO > 0.2. The catalogue includes redshift probabilities for all objects. We also release an updated version of the publicly available set of codes to calculate quasar and redshift probabilities for various combinations of data. Finally, we demonstrate that this method of selecting quasars using WISE data is both more complete and efficient than simple WISE colour-cuts, especially at high redshift. Our fits verify that above z ˜ 3 WISE colours become bluer than the standard cuts applied to select quasars. Currently, the analysis is limited to quasars with optical counterparts, and thus cannot be used to find highly obscured quasars that WISE colour-cuts identify in significant numbers.

The pool of fast releasing vesicles is augmented by myosin light chain kinase inhibition at the calyx of Held synapse.

PubMed

Srinivasan, Geetha; Kim, Jun Hee; von Gersdorff, Henrique

2008-04-01

Synaptic strength is determined by release probability and the size of the readily releasable pool of docked vesicles. Here we describe the effects of blocking myosin light chain kinase (MLCK), a cytoskeletal regulatory protein thought to be involved in myosin-mediated vesicle transport, on synaptic transmission at the mouse calyx of Held synapse. Application of three different MLCK inhibitors increased the amplitude of the early excitatory postsynaptic currents (EPSCs) in a stimulus train, without affecting the late steady-state EPSCs. A presynaptic locus of action for MLCK inhibitors was confirmed by an increase in the frequency of miniature EPSCs that left their average amplitude unchanged. MLCK inhibition did not affect presynaptic Ca(2+) currents or action potential waveform. Moreover, Ca(2+) imaging experiments showed that [Ca(2+)](i) transients elicited by 100-Hz stimulus trains were not altered by MLCK inhibition. Studies using high-frequency stimulus trains indicated that MLCK inhibitors increase vesicle pool size, but do not significantly alter release probability. Accordingly, when AMPA-receptor desensitization was minimized, EPSC paired-pulse ratios were unaltered by MLCK inhibition, suggesting that release probability remains unaltered. MLCK inhibition potentiated EPSCs even when presynaptic Ca(2+) buffering was greatly enhanced by treating slices with EGTA-AM. In addition, MLCK inhibition did not affect the rate of recovery from short-term depression. Finally, developmental studies revealed that EPSC potentiation by MLCK inhibition starts at postnatal day 5 (P5) and remains strong during synaptic maturation up to P18. Overall, our data suggest that MLCK plays a crucial role in determining the size of the pool of synaptic vesicles that undergo fast release at a CNS synapse.

Prion Replication Elicits Cytopathic Changes in Differentiated Neurosphere Cultures

PubMed Central

Iwamaru, Yoshifumi; Takenouchi, Takato; Imamura, Morikazu; Shimizu, Yoshihisa; Miyazawa, Kohtaro; Mohri, Shirou; Yokoyama, Takashi

2013-01-01

The molecular mechanisms of prion-induced cytotoxicity remain largely obscure. Currently, only a few cell culture models have exhibited the cytopathic changes associated with prion infection. In this study, we introduced a cell culture model based on differentiated neurosphere cultures isolated from the brains of neonatal prion protein (PrP)-null mice and transgenic mice expressing murine PrP (dNP0 and dNP20 cultures). Upon exposure to mouse Chandler prions, dNP20 cultures supported the de novo formation of abnormal PrP and the resulting infectivity, as assessed by bioassays. Furthermore, this culture was susceptible to various prion strains, including mouse-adapted scrapie, bovine spongiform encephalopathy, and Gerstmann-Sträussler-Scheinker syndrome prions. Importantly, a subset of the cells in the infected culture that was mainly composed of astrocyte lineage cells consistently displayed late-occurring, progressive signs of cytotoxicity as evidenced by morphological alterations, decreased cell viability, and increased lactate dehydrogenase release. These signs of cytotoxicity were not observed in infected dNP0 cultures, suggesting the requirement of endogenous PrP expression for prion-induced cytotoxicity. Degenerated cells positive for glial fibrillary acidic protein accumulated abnormal PrP and exhibited features of apoptotic death as assessed by active caspase-3 and terminal deoxynucleotidyltransferase nick-end staining. Furthermore, caspase inhibition provided partial protection from prion-mediated cell death. These results suggest that differentiated neurosphere cultures can provide an in vitro bioassay for mouse prions and permit the study of the molecular basis for prion-induced cytotoxicity at the cellular level. PMID:23740992

The Medial Amygdala-Medullary PrRP-Synthesizing Neuron Pathway Mediates Neuroendocrine Responses to Contextual Conditioned Fear in Male Rodents

PubMed Central

Yoshida, Masahide; Takayanagi, Yuki

2014-01-01

Fear responses play evolutionarily beneficial roles, although excessive fear memory can induce inappropriate fear expression observed in posttraumatic stress disorder, panic disorder, and phobia. To understand the neural machineries that underlie these disorders, it is important to clarify the neural pathways of fear responses. Contextual conditioned fear induces freezing behavior and neuroendocrine responses. Considerable evidence indicates that the central amygdala plays an essential role in expression of freezing behavior after contextual conditioned fear. On the other hand, mechanisms of neuroendocrine responses remain to be clarified. The medial amygdala (MeA), which is activated after contextual conditioned fear, was lesioned bilaterally by infusion of N-methyl-d-aspartate after training of fear conditioning. Plasma oxytocin, ACTH, and prolactin concentrations were significantly increased after contextual conditioned fear in sham-lesioned rats. In MeA-lesioned rats, these neuroendocrine responses but not freezing behavior were significantly impaired compared with those in sham-lesioned rats. In contrast, the magnitudes of neuroendocrine responses after exposure to novel environmental stimuli were not significantly different in MeA-lesioned rats and sham-lesioned rats. Contextual conditioned fear activated prolactin-releasing peptide (PrRP)-synthesizing neurons in the medulla oblongata. In MeA-lesioned rats, the percentage of PrRP-synthesizing neurons activated after contextual conditioned fear was significantly decreased. Furthermore, neuroendocrine responses after contextual conditioned fear disappeared in PrRP-deficient mice. Our findings suggest that the MeA-medullary PrRP-synthesizing neuron pathway plays an important role in neuroendocrine responses to contextual conditioned fear. PMID:24877622

The medial amygdala-medullary PrRP-synthesizing neuron pathway mediates neuroendocrine responses to contextual conditioned fear in male rodents.

PubMed

Yoshida, Masahide; Takayanagi, Yuki; Onaka, Tatsushi

2014-08-01

Fear responses play evolutionarily beneficial roles, although excessive fear memory can induce inappropriate fear expression observed in posttraumatic stress disorder, panic disorder, and phobia. To understand the neural machineries that underlie these disorders, it is important to clarify the neural pathways of fear responses. Contextual conditioned fear induces freezing behavior and neuroendocrine responses. Considerable evidence indicates that the central amygdala plays an essential role in expression of freezing behavior after contextual conditioned fear. On the other hand, mechanisms of neuroendocrine responses remain to be clarified. The medial amygdala (MeA), which is activated after contextual conditioned fear, was lesioned bilaterally by infusion of N-methyl-d-aspartate after training of fear conditioning. Plasma oxytocin, ACTH, and prolactin concentrations were significantly increased after contextual conditioned fear in sham-lesioned rats. In MeA-lesioned rats, these neuroendocrine responses but not freezing behavior were significantly impaired compared with those in sham-lesioned rats. In contrast, the magnitudes of neuroendocrine responses after exposure to novel environmental stimuli were not significantly different in MeA-lesioned rats and sham-lesioned rats. Contextual conditioned fear activated prolactin-releasing peptide (PrRP)-synthesizing neurons in the medulla oblongata. In MeA-lesioned rats, the percentage of PrRP-synthesizing neurons activated after contextual conditioned fear was significantly decreased. Furthermore, neuroendocrine responses after contextual conditioned fear disappeared in PrRP-deficient mice. Our findings suggest that the MeA-medullary PrRP-synthesizing neuron pathway plays an important role in neuroendocrine responses to contextual conditioned fear.

Survival Estimates for the Passage of Juvenile Chinook Salmon through Snake River Dams and Reservoirs, 1993 Annual Report.

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

Iwamoto, Robert N.; Sandford, Benjamin P.; McIntyre, Kenneth W.

1994-04-01

A pilot study was conducted to estimate survival of hatchery-reared yearling chinook salmon through dams and reservoirs on the Snake River. The goals of the study were to: (1) field test and evaluate the Single-Release, Modified-Single-Release, and Paired-Release Models for the estimation of survival probabilities through sections of a river and hydroelectric projects; (2) identify operational and logistical constraints to the execution of these models; and (3) determine the usefulness of the models in providing estimates of survival probabilities. Field testing indicated that the numbers of hatchery-reared yearling chinook salmon needed for accurate survival estimates could be collected at differentmore » areas with available gear and methods. For the primary evaluation, seven replicates of 830 to 1,442 hatchery-reared yearling chinook salmon were purse-seined from Lower Granite Reservoir, PIT tagged, and released near Nisqually John boat landing (River Kilometer 726). Secondary releases of PIT-tagged smolts were made at Lower Granite Dam to estimate survival of fish passing through turbines and after detection in the bypass system. Similar secondary releases were made at Little Goose Dam, but with additional releases through the spillway. Based on the success of the 1993 pilot study, the authors believe that the Single-Release and Paired-Release Models will provide accurate estimates of juvenile salmonid passage survival for individual river sections, reservoirs, and hydroelectric projects in the Columbia and Snake Rivers.« less

Kidnapping model: an extension of Selten's game.

PubMed

Iqbal, Azhar; Masson, Virginie; Abbott, Derek

2017-12-01

Selten's game is a kidnapping model where the probability of capturing the kidnapper is independent of whether the hostage has been released or executed. Most often, in view of the elevated sensitivities involved, authorities put greater effort and resources into capturing the kidnapper if the hostage has been executed, in contrast with the case when a ransom is paid to secure the hostage's release. In this paper, we study the asymmetric game when the probability of capturing the kidnapper depends on whether the hostage has been executed or not and find a new uniquely determined perfect equilibrium point in Selten's game.

Using Multiple and Logistic Regression to Estimate the Median WillCost and Probability of Cost and Schedule Overrun for Program Managers

DTIC Science & Technology

2017-03-23

PUBLIC RELEASE; DISTRIBUTION UNLIMITED Using Multiple and Logistic Regression to Estimate the Median Will- Cost and Probability of Cost and... Cost and Probability of Cost and Schedule Overrun for Program Managers Ryan C. Trudelle Follow this and additional works at: https://scholar.afit.edu...afit.edu. Recommended Citation Trudelle, Ryan C., "Using Multiple and Logistic Regression to Estimate the Median Will- Cost and Probability of Cost and

Release of ( sup 14 C)5-hydroxytryptamine from human platelets by red wine

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

Jarman, J.; Glover, V.; Sandler, M.

1991-01-01

Red wine, at a final dilution of 1/50, caused released of ({sup 14}C)5-hydroxytryptamine (5-HT) from preloaded platelets, an effect which was not observed with any white wines or beers tested. Since 5-HT, is probably released from body stores during migraine attacks and red wine is known to provoke migraine episodes in susceptible individuals, release of 5-HT, possibly from central stores, could represent a plausible mechanism for its mode of action.

An optimized expression vector for improving the yield of dengue virus-like particles from transfected insect cells.

PubMed

Charoensri, Nicha; Suphatrakul, Amporn; Sriburi, Rungtawan; Yasanga, Thippawan; Junjhon, Jiraphan; Keelapang, Poonsook; Utaipat, Utaiwan; Puttikhunt, Chunya; Kasinrerk, Watchara; Malasit, Prida; Sittisombut, Nopporn

2014-09-01

Recombinant virus-like particles (rVLPs) of flaviviruses are non-infectious particles released from cells expressing the envelope glycoproteins prM and E. Dengue virus rVLPs are recognized as a potential vaccine candidate, but large scale production of these particles is hindered by low yields and the occurrence of cytopathic effects. In an approach to improve the yield of rVLPs from transfected insect cells, several components of a dengue serotype 2 virus prM+E expression cassette were modified and the effect of these modifications was assessed during transient expression. Enhancement of extracellular rVLP levels by simultaneous substitutions of the prM signal peptide and the stem-anchor region of E with homologous cellular and viral counterparts, respectively, was further augmented by codon optimization. Extensive formation of multinucleated cells following transfection with the codon-optimized expression cassette was abrogated by introducing an E fusion loop mutation. This mutation also helped restore the extracellular E levels affected negatively by alteration of a charged residue at the pr-M junction, which was intended to promote maturation of rVLPs during export. Optimized expression cassettes generated in this multiple add-on modification approach should be useful in the generation of stably expressing clones and production of dengue virus rVLPs for immunogenicity studies. Copyright © 2014 Elsevier B.V. All rights reserved.

Pheromone-Induced Morphogenesis Improves Osmoadaptation Capacity by Activating the HOG MAPK Pathway**

PubMed Central

Baltanás, Rodrigo; Bush, Alan; Couto, Alicia; Durrieu, Lucía; Hohmann, Stefan; Colman-Lerner, Alejandro

2013-01-01

Environmental and internal conditions expose cells to a multiplicity of stimuli whose consequences are difficult to predict. Here, we investigate the response to mating pheromone of yeast cells adapted to high osmolarity. Events downstream of pheromone binding involve two mitogen-activated protein kinase (MAPK) cascades: the pheromone response (PR) and the cell-wall integrity response (CWI). Although these MAPK pathways share components with each and a third MAPK pathway, the high osmolarity response (HOG), they are normally only activated by distinct stimuli, a phenomenon called insulation. We found that in cells adapted to high osmolarity, PR activated the HOG pathway in a pheromone- and osmolarity- dependent manner. Activation of HOG by the PR was not due to loss of insulation, but rather a response to a reduction in internal osmolarity, which resulted from an increase in glycerol release caused by the PR. By analyzing single-cell time courses, we found that stimulation of HOG occurred in discrete bursts that coincided with the “shmooing” morphogenetic process. Activation required the polarisome, the cell wall integrity MAPK Slt2, and the aquaglyceroporin Fps1. HOG activation resulted in high glycerol turnover that improved adaptability to rapid changes in osmolarity. Our work shows how a differentiation signal can recruit a second, unrelated sensory pathway to enable responses to yeast to multiple stimuli. PMID:23612707

Influence of Dexamethasone on Some Reproductive Hormones and Uterine Progesterone Receptor Localization in Pregnant Yankasa Sheep in Semiarid Zones of Nigeria.

PubMed

Yahi, Dauda; Ojo, Nicholas Adetayo; Mshelia, Gideon Dauda

2017-01-01

Dexamethasone is widely used in both veterinary and human medical practices. However, it seems to cause some deleterious effects on pregnancy probably by causing changes in the reproductive hormone levels and their corresponding receptor concentrations. This study investigated the effects of dexamethasone on these parameters. Twenty healthy adult Yankasa sheep comprising 18 ewes and 2 rams were used for this study. Pregnancies were achieved by natural mating after estrus synchronization. Dexamethasone was administered at 0.25 mg/kg body weight on days 1, 3, and 5 during first trimester; days 51, 53, and 55 during second trimester; and days 101, 103, and 105 during the third trimester. Blood samples were collected biweekly for hormonal assay. Uterine biopsies were harvested through caesarean section for immunohistochemical analysis. Results showed that dexamethasone significantly ( p < 0.05) decreased progesterone concentrations and caused abortion in Yankasa sheep but had no significant ( p > 0.05) effect on estrogen, while progesterone receptors (PR) were upregulated. The abortion could probably be due to decreased progesterone concentrations as a consequence of the adverse effects on placenta. The PR upregulation may be a compensatory mechanism to increase progesterone sensitivity. It was concluded that dexamethasone should not be used in advanced pregnancy in Yankasa sheep.

Influence of Dexamethasone on Some Reproductive Hormones and Uterine Progesterone Receptor Localization in Pregnant Yankasa Sheep in Semiarid Zones of Nigeria

PubMed Central

Ojo, Nicholas Adetayo; Mshelia, Gideon Dauda

2017-01-01

Dexamethasone is widely used in both veterinary and human medical practices. However, it seems to cause some deleterious effects on pregnancy probably by causing changes in the reproductive hormone levels and their corresponding receptor concentrations. This study investigated the effects of dexamethasone on these parameters. Twenty healthy adult Yankasa sheep comprising 18 ewes and 2 rams were used for this study. Pregnancies were achieved by natural mating after estrus synchronization. Dexamethasone was administered at 0.25 mg/kg body weight on days 1, 3, and 5 during first trimester; days 51, 53, and 55 during second trimester; and days 101, 103, and 105 during the third trimester. Blood samples were collected biweekly for hormonal assay. Uterine biopsies were harvested through caesarean section for immunohistochemical analysis. Results showed that dexamethasone significantly (p < 0.05) decreased progesterone concentrations and caused abortion in Yankasa sheep but had no significant (p > 0.05) effect on estrogen, while progesterone receptors (PR) were upregulated. The abortion could probably be due to decreased progesterone concentrations as a consequence of the adverse effects on placenta. The PR upregulation may be a compensatory mechanism to increase progesterone sensitivity. It was concluded that dexamethasone should not be used in advanced pregnancy in Yankasa sheep. PMID:29181440

"An estimate of the probability of vesicle exocytosis in a Monte Carlo model of buffered diffusion of calcium channel currents"

NASA Astrophysics Data System (ADS)

Dimcovic, Z. M.; Eagan, T. P.; Kidane, T. K.; Brown, R. W.; Petschek, R. G.; McEnery, M. W.

2001-10-01

The opening of voltage-dependent calcium channels results in an influx of calcium ions promoting the fusion of synaptic vesicles. The fusion leads to release of neurotransmitters, which in turn allow the propagation of nerve impulses. A Monte Carlo model of the diffusion of calcium following its surge into the cell is used to estimate the probability for exocytosis. Besides the calcium absorption by fixed and mobile buffers, key ingredients are the physical size and position of the tethered vesicle and a sensing model for the interaction of the vesicle and calcium. The release probability is compared to previously published studies where the finite vesicle size was not considered. (Supported by NIH MH55747, AHA 96001250, NSF0086643, and a CWRU Presidential Research Initiative grant.)

Methodology of Calculation the Terminal Settling Velocity Distribution of Spherical Particles for High Values of the Reynold's Number

NASA Astrophysics Data System (ADS)

Surowiak, Agnieszka; Brożek, Marian

2014-03-01

The particle settling velocity is the feature of separation in such processes as flowing classification and jigging. It characterizes material forwarded to the separation process and belongs to the so-called complex features because it is the function of particle density and size. i.e. the function of two simple features. The affiliation to a given subset is determined by the values of two properties and the distribution of such feature in a sample is the function of distributions of particle density and size. The knowledge about distribution of particle settling velocity in jigging process is as much important factor as knowledge about particle size distribution in screening or particle density distribution in dense media beneficiation. The paper will present a method of determining the distribution of settling velocity in the sample of spherical particles for the turbulent particle motion in which the settling velocity is expressed by the Newton formula. Because it depends on density and size of particle which are random variable of certain distributions, the settling velocity is a random variable. Applying theorems of probability, concerning distributions function of random variables, the authors present general formula of probability density function of settling velocity for the turbulent motion and particularly calculate probability density function for Weibull's forms of frequency functions of particle size and density. Distribution of settling velocity will calculate numerically and perform in graphical form. The paper presents the simulation of calculation of settling velocity distribution on the basis of real distributions of density and projective diameter of particles assuming that particles are spherical. Prędkość opadania ziarna jest cechą rozdziału w takich procesach przeróbki surowców jak klasyfikacja czy wzbogacanie w osadzarce. Cecha ta opisuje materiał kierowany do procesu rozdziału i należy do tzw. cech złożonych, ze względu na to, że jest funkcją dwóch cech prostych, którymi są: wielkość ziarna i gęstość ziarna. Przynależność do określonego podzbioru ziaren jest określona przez wartość dwóch cech, a rozkład tych cech w próbce jest funkcją rozkładów gęstości i wielkości ziarna. Znajomość rozkładu prędkości opadania ziaren w osadzarce jest istotnym parametrem jak znajomość rozkładu wielkości ziarna w procesie przesiewania czy znajomość rozkładu gęstości w procesie wzbogacania w cieczach ciężkich. W artykule przedstawiono metodykę wyliczania rozkładu prędkości opadania ziaren sferycznych w warunkach ruchu turbulentnego wyrażonego przy pomocy równania Newtona. Zarówno gęstość jak i wielkość ziarna są zmiennymi losowymi o określonych rozkładach. W związku z tym prędkość opadania ziarna jako funkcja cech prostych tj. gęstości i wielkości ziarna będzie również zmienną losową o rozkładzie, który jest funkcją rozkładów argumentów prostych. Wykorzystując twierdzenia rachunku prawdopodobieństwa odnoszące się do rozkładów funkcji zmiennych losowych przedstawiono ogólny wzór na funkcję gęstości rozkładu prędkości opadania w warunkach ruchu turbulentnego. Empiryczne rozkłady wielkości i gęstości ziaren aproksymowano rozkładem Weibulla. Rozkład prędkości opadania wyliczono numerycznie i przedstawiono w postaci graficznej. W artykule przedstawiono symulację wyliczania rozkładu prędkości opadania w oparciu o rzeczywiste rozkłady gęstości i średnicy projekcyjnej ziaren zakładając, że ziarna mają kształt sferyczny.

Cloning of the prepro C-RFa gene and brain localization of the active peptide in Salmo salar.

PubMed

Montefusco-Siegmund, R A; Romero, A; Kausel, G; Muller, M; Fujimoto, M; Figueroa, J

2006-08-01

In all vertebrates, the synthesis and release of prolactin (Prl) from pituitary lactotroph cells is tightly controlled by hypothalamic factors. We have cloned and characterized a hypothalamic cDNA from Atlantic salmon (Salmo salar) encoding C-RFa, a peptide structurally related to mammalian Prl-releasing peptide (PrRP). The deduced preprohormone precursor is composed of 155 amino acid residues presenting a 87.1% similarity to chum salmon C-RFa and a 100% similarity to all fish C-RFa in the bioactive precursor motifs. C-RFa-immunoreactive perikarya and fibres were located in the brain of S. salar, especially in the hypothalamus, olfactory tract, optic tectum and cerebellum. In contrast, immunolabelled fibres were not observed in the pituitary stalk or in the hypophysis. However, interestingly, we detected immunolabelled cells in the rostral pars distalis of the pituitary in the basolateral region in which Prl is synthesized. These results were confirmed by obtaining a strong signal by using reverse transcription/polymerase chain reaction (RT-PCR) on mRNA from both hypothalamus and pituitary. These data show, for the first time, by immunohistochemistry and RT-PCR, that C-RFa is produced in pituitary cells. Finally, based on these results, a possible function for C-RFa as a locally produced PrRP in this teleost is discussed.

Disordered cellular automaton traffic flow model: phase separated state, density waves and self organized criticality

NASA Astrophysics Data System (ADS)

Fourrate, K.; Loulidi, M.

2006-01-01

We suggest a disordered traffic flow model that captures many features of traffic flow. It is an extension of the Nagel-Schreckenberg (NaSch) stochastic cellular automata for single line vehicular traffic model. It incorporates random acceleration and deceleration terms that may be greater than one unit. Our model leads under its intrinsic dynamics, for high values of braking probability pr, to a constant flow at intermediate densities without introducing any spatial inhomogeneities. For a system of fast drivers pr→0, the model exhibits a density wave behavior that was observed in car following models with optimal velocity. The gap of the disordered model we present exhibits, for high values of pr and random deceleration, at a critical density, a power law distribution which is a hall mark of a self organized criticality phenomena.

Erythropoietin plus granulocyte colony-stimulating factor in the treatment of myelodysplastic syndromes. Identification of a subgroup of responders. The Spanish Erythropathology Group.

PubMed

Remacha, A F; Arrizabalaga, B; Villegas, A; Manteiga, R; Calvo, T; Julià, A; Fernández Fuertes, I; González, F A; Font, L; Juncà, J; del Arco, A; Malcorra, J J; Equiza, E P; de Mendiguren, B P; Romero, M

1999-12-01

Anemia leading to transfusion is probably the most important problem in patients with myelodysplastic syndromes (MDS). Human recombinant erythropoietin (rHuEpo) and granulocyte colony-stimulating factor (G-CSF) have been used to treat patients with anemia of MDS, but fewer than 50% respond. The aim of this work was to evaluate the benefit of rHuEpo +/- G-CSF treatment and to isolate the response predictive variables in a group of selected patients with MDS. A non-randomized multicenter trial was carried out in 32 patients with MDS. The inclusion criteria were age >= 18 years, refractory anemia (RA) or refractory anemia with ringed sideroblasts, Hb <= 100 g/L or receiving transfusions and serum erythropoietin <= 250 U/L. These patients were treated with subcutaneous rHuEpo (300 U/kg) three times a week for 8 weeks. In the case of partial response (PR) or no response (NR) subcutaneosly administered G-CSF (1 microg/kg) three times a week was added to the rHuEpo for 8 more weeks. If the patient achieved complete response (CR) or PR in the second phase, he was included in a follow-up phase of 24 weeks in which the dose of growth factors was tapered down. Several variables, including the score published by the Scandinavian-American group, were used as possible predictive variables. An erythroid response was observed in 16 patients (50%); in 12 it was a CR and in 4 it was a PR. During the period of rHuEpo administration, 7 CR and 4 PR (34.4%) were documented. Of the 14 patients in whom G-CSF was added to rHuEpo, 7 (50%) responded (3 CR and 4 PR). No major side-effects associated with growth factors were observed. The multivariate analysis showed that of the different variables evaluated only the Scandinavian-American response score was significant with a relative probability of response of 11.8 (95% confident intervals: 2.5-53) when this score was > +1 (77% of cases responded). In contrast, when this score was <= 1 only 15 % of the cases responded. Use of the Scandinavian-American response score is to be recommended in a patient-oriented approach to treating MDS cases with the Epo and G-CSF. Treatment with rHuEpo and G-CSF is safe, its main drawback being its cost. However, a long-term study evaluating the regimen's cost-benefit ratio is warranted.

ESO Delegation to Visit Chile: the Chile-Eso Treaty and Paranal

NASA Astrophysics Data System (ADS)

1994-05-01

The ESO Council, in its extraordinary session on 28 April 1994, among other matters discussed the relations with the Republic of Chile and the situation around Paranal mountain [1], the designated site for the ESO Very Large Telescope (VLT). Council decided to send a high ranking delegation to Santiago de Chile to discuss with Chilean authorities the pending problems, including the finalisation of the new Treaty between the Republic of Chile and ESO and the legal aspects of the Paranal location. The ESO delegation will consist of Dr. Peter Creola (President of ESO Council), Dr. Catherine Cesarsky (Vice-President of ESO Council), Dr. Henrik Grage (Former Vice-President of ESO Council) and Professor Riccardo Giacconi (ESO Director General), the latter accompanied by his advisers. The delegation will arrive in Chile during the second half of May 1994. The ESO delegation will meet with the Chilean Minister of Foreign Affairs, Mr. Carlos Figueroa, and the Secretary of State in the Ministry of Foreign Affairs, Mr. Jose Miguel Insulza. Other meetings at high level are being planned. The delegation will report about these discussions to the ESO Council during its ordinary session on 7 - 8 June 1994. FOUR PARANAL PHOTOS AVAILABLE A series of four photos which show the current status of the work at Paranal has been prepared. Photographic colour prints for use by the media can be requested from the ESO Information and Photographic Service (please remember to indicate the identification numbers). [1] See ESO Press Release 07/94 of 21 April 1994. PHOTO CAPTIONS ESO PR PHOTO 08/94-1: CERRO PARANAL This aerial photo of the Paranal mountain, the designated site for the ESO Very Large Telescope (VLT), was obtained on 22 March 1994. Paranal is situated in the driest part of the Chilean Atacama desert, approx. 130 km south of the city of Antofagasta, and about 12 km from the Pacific Ocean. In this view towards the West, the ocean is seen in the background. The altitude is 2650 metres. The top of the mountain has been levelled to make place for the extensive VLT installations. ESO has constructed a road from the main road in the area (the ``Old Panamericana'') to the summit. It passes by the ESO base camp (in the foreground, left of the road). The constructors' camp is located on the other side of the road. This photo (ESO PR Photo 08/94-1) accompanies ESO Press Release 08/94 of 6 May 1994 and may be reproduced, if credit is given to the European Southern Observatory. ESO PR PHOTO 08/94-2: CERRO PARANAL This aerial photo of the Paranal mountain, the designated site for the ESO Very Large Telescope (VLT), was obtained on 22 March 1994. Paranal is located in the driest part of the Chilean Atacama desert, approx. 130 km south of the city of Antofagasta, and about 12 km from the Pacific Ocean. The altitude is 2650 metres. In this view towards the East, the high mountains of the Andean Cordillera are in the background. The top of the mountain has been levelled to make place for the extensive VLT installations. The four excavations for the buildings that will house the four 8.2 metre VLT unit telescopes are clearly seen. There are some dust clouds from the construction activity at the site. There are several other peaks in this area which may possibly be used for astronomical installations. The one to the left on which some site testing equipment can be seen, is known as the ``NTT Peak''. This photo (ESO PR Photo 08/94-2) accompanies ESO Press Release 08/94 of 6 May 1994 and may be reproduced, if credit is given to the European Southern Observatory. ESO PR PHOTO 08/94-3: CERRO PARANAL This aerial photo of the Paranal mountain, the designated site for the ESO Very Large Telescope (VLT), was obtained on 22 March 1994. Paranal is located in the driest part of the Chilean Atacama desert, approx. 130 km south of the city of Antofagasta, and about 12 km from the Pacific Ocean. The altitude is 2650 metres. The top of the mountain has been levelled to make place for the extensive VLT installations. The four excavations for the buildings that will house the four 8.2 metre VLT unit telescopes are clearly seen. The positions of some of the future structures have been marked. The control building will be located on the platform at the rightmost edge of the mountain. This photo (ESO PR Photo 08/94-3) accompanies ESO Press Release 08/94 of 6 May 1994 and may be reproduced, if credit is given to the European Southern Observatory. ESO PR PHOTO 08/94-4: CERRO PARANAL This photo of the ESO Base Camp at the foot of the Paranal mountain, the designated site for the ESO Very Large Telescope (VLT), was obtained in late March 1994. Paranal is located in the driest part of the Chilean Atacama desert, approx. 130 km south of the city of Antofagasta, and about 12 km from the Pacific Ocean. The altitude is 2650 metres. The top of the mountain has been levelled to make place for the extensive VLT installations. This photo (ESO PR Photo 08/94-4) accompanies ESO Press Release 08/94 of 6 May 1994 and may be reproduced, if credit is given to the European Southern Observatory.

Analysis of multiple tank car releases in train accidents.

PubMed

Liu, Xiang; Liu, Chang; Hong, Yili

2017-10-01

There are annually over two million carloads of hazardous materials transported by rail in the United States. The American railroads use large blocks of tank cars to transport petroleum crude oil and other flammable liquids from production to consumption sites. Being different from roadway transport of hazardous materials, a train accident can potentially result in the derailment and release of multiple tank cars, which may result in significant consequences. The prior literature predominantly assumes that the occurrence of multiple tank car releases in a train accident is a series of independent Bernoulli processes, and thus uses the binomial distribution to estimate the total number of tank car releases given the number of tank cars derailing or damaged. This paper shows that the traditional binomial model can incorrectly estimate multiple tank car release probability by magnitudes in certain circumstances, thereby significantly affecting railroad safety and risk analysis. To bridge this knowledge gap, this paper proposes a novel, alternative Correlated Binomial (CB) model that accounts for the possible correlations of multiple tank car releases in the same train. We test three distinct correlation structures in the CB model, and find that they all outperform the conventional binomial model based on empirical tank car accident data. The analysis shows that considering tank car release correlations would result in a significantly improved fit of the empirical data than otherwise. Consequently, it is prudent to consider alternative modeling techniques when analyzing the probability of multiple tank car releases in railroad accidents. Copyright © 2017 Elsevier Ltd. All rights reserved.

40 CFR Appendix C to Part 191 - Guidance for Implementation of Subpart B

Code of Federal Regulations, 2014 CFR

2014-07-01

... that the remaining probability distribution of cumulative releases would not be significantly changed... with § 191.13 into a “complementary cumulative distribution function” that indicates the probability of... distribution function for each disposal system considered. The Agency assumes that a disposal system can be...

40 CFR Appendix C to Part 191 - Guidance for Implementation of Subpart B

Code of Federal Regulations, 2011 CFR

2011-07-01

... that the remaining probability distribution of cumulative releases would not be significantly changed... with § 191.13 into a “complementary cumulative distribution function” that indicates the probability of... distribution function for each disposal system considered. The Agency assumes that a disposal system can be...

Release the Prisoners Game

ERIC Educational Resources Information Center

Van Hecke, Tanja

2011-01-01

This article presents the mathematical approach of the optimal strategy to win the "Release the prisoners" game and the integration of this analysis in a math class. Outline lesson plans at three different levels are given, where simulations are suggested as well as theoretical findings about the probability distribution function and its mean…

Validity of the Test of Infant Motor Performance for prediction of 6-, 9- and 12-month scores on the Alberta Infant Motor Scale.

PubMed

Campbell, Suzann K; Kolobe, Thubi H A; Wright, Benjamin D; Linacre, John Michael

2002-04-01

The Test of Infant Motor Performance (TIMP) is a test of functional movement in infants from 32 weeks' post-conceptional age to 4 months postterm. The purpose of this study was to assess in 96 infants (44 females, 52 males) with varying risk, the relation between measures on the TIMP at 7, 30, 60, and 90 days after term age and percentile ranks (PR) on the Alberta Infant Motor Scale (AIMS). Correlation between scores on the TIMP and the AIMS was highest for TIMP tests at 90 days and AIMS testing at 6 months (r=0.67, p=0.0001), but all comparisons were statistically significant except those between the TIMP at 7 days and AIMS PR at 9 months. In a multiple regression analysis combining a perinatal risk score and 7-day TIMP measures to predict 12-month AIMS PR, risk, but not TIMP, predicted outcome (21% of variance explained). At older ages TIMP measures made increasing contributions to prediction of 12-month AIMS PR (30% of variance explained by 90-day TIMP). The best TIMP score to maximize specificity and correctly identify 84% of the infants above versus below the 10th PR at 6 months was a cut-off point of 1 SD below the mean. The same cut-off point correctly identified 88% of the infants at 12 months. A cut-off of -0.5 SD, however, maximized sensitivity at 92%. A negative test result, i.e. score above -0.5 SD at 3 months, carried only a 2% probability of a poor 12-month outcome. We conclude that TIMP scores significantly predict AIMS PR 6 to 12 months later, but the TIMP at 3 months of age has the greatest degree of validity for predicting motor performance on the AIMS at 12 months and can be used clinically to identify infants likely to benefit from intervention.

The Epiphytic Fungus Pseudozyma aphidis Induces Jasmonic Acid- and Salicylic Acid/Nonexpressor of PR1-Independent Local and Systemic Resistance1[C][W

PubMed Central

Buxdorf, Kobi; Rahat, Ido; Gafni, Aviva; Levy, Maggie

2013-01-01

Pseudozyma spp. are yeast-like fungi, classified in the Ustilaginales, which are mostly epiphytic or saprophytic and are not pathogenic to plants. Several Pseudozyma species have been reported to exhibit biological activity against powdery mildews. However, previous studies have reported that Pseudozyma aphidis, which can colonize plant surfaces, is not associated with the ‎‎collapse of powdery ‎mildew colonies. In this report, we describe a novel P. aphidis strain and study its interactions with its plant host and the plant pathogen Botrytis cinerea. This isolate was found to secrete extracellular metabolites that inhibit various fungal pathogens in vitro and significantly reduce B. cinerea infection in vivo. Moreover, P. aphidis sensitized Arabidopsis (Arabidopsis thaliana) plants’ defense machinery via local and systemic induction of PATHOGENESIS-RELATED1 (PR1) and PLANT DEFENSIN1.2 (PDF1.2) expression. P. aphidis also reduced B. cinerea infection, locally and systemically, in Arabidopsis mutants impaired in jasmonic acid (JA) or salicylic acid (SA) signaling. Thus, in addition to direct inhibition, P. aphidis may inhibit B. cinerea infection via induced resistance in a manner independent of SA, JA, and Nonexpressor of PR1 (NPR1). P. aphidis primed the plant defense machinery and induced stronger activation of PDF1.2 after B. cinerea infection. Finally, P. aphidis fully or partially reconstituted PR1 and PDF1.2 expression in npr1-1 mutant and in plants with the SA hydroxylase NahG transgene, but not in a jasmonate resistant1-1 mutant, after B. cinerea infection, suggesting that P. aphidis can bypass the SA/NPR1, but not JA, pathway to activate PR genes. Thus, either partial gene activation is sufficient to induce resistance, or the resistance is not directed solely through PR1 and PDF1.2 but probably through other pathogen-resistance genes or pathways as well. PMID:23388119

The epiphytic fungus Pseudozyma aphidis induces jasmonic acid- and salicylic acid/nonexpressor of PR1-independent local and systemic resistance.

PubMed

Buxdorf, Kobi; Rahat, Ido; Gafni, Aviva; Levy, Maggie

2013-04-01

Pseudozyma spp. are yeast-like fungi, classified in the Ustilaginales, which are mostly epiphytic or saprophytic and are not pathogenic to plants. Several Pseudozyma species have been reported to exhibit biological activity against powdery mildews. However, previous studies have reported that Pseudozyma aphidis, which can colonize plant surfaces, is not associated with the collapse of powdery mildew colonies. In this report, we describe a novel P. aphidis strain and study its interactions with its plant host and the plant pathogen Botrytis cinerea. This isolate was found to secrete extracellular metabolites that inhibit various fungal pathogens in vitro and significantly reduce B. cinerea infection in vivo. Moreover, P. aphidis sensitized Arabidopsis (Arabidopsis thaliana) plants' defense machinery via local and systemic induction of pathogenesis-related1 (PR1) and plant defensin1.2 (PDF1.2) expression. P. aphidis also reduced B. cinerea infection, locally and systemically, in Arabidopsis mutants impaired in jasmonic acid (JA) or salicylic acid (SA) signaling. Thus, in addition to direct inhibition, P. aphidis may inhibit B. cinerea infection via induced resistance in a manner independent of SA, JA, and Nonexpressor of PR1 (NPR1). P. aphidis primed the plant defense machinery and induced stronger activation of PDF1.2 after B. cinerea infection. Finally, P. aphidis fully or partially reconstituted PR1 and PDF1.2 expression in npr1-1 mutant and in plants with the SA hydroxylase NahG transgene, but not in a jasmonate resistant1-1 mutant, after B. cinerea infection, suggesting that P. aphidis can bypass the SA/NPR1, but not JA, pathway to activate PR genes. Thus, either partial gene activation is sufficient to induce resistance, or the resistance is not directed solely through PR1 and PDF1.2 but probably through other pathogen-resistance genes or pathways as well.

Unaltered Angiogenesis-Regulating Activities of Platelets in Mild Type 2 Diabetes Mellitus despite a Marked Platelet Hyperreactivity.

PubMed

Miao, Xinyan; Zhang, Wei; Huang, Zhangsen; Li, Nailin

2016-01-01

Type 2 diabetes mellitus (T2DM) is associated with platelet dysfunction and impaired angiogenesis. Aim of the study is to investigate if platelet dysfunction might hamper platelet angiogenic activities in T2DM patients. Sixteen T2DM patients and gender/age-matched non-diabetic controls were studied. Flow cytometry and endothelial colony forming cell (ECFC) tube formation on matrigel were used to assess platelet reactivity and angiogenic activity, respectively. Thrombin receptor PAR1-activating peptide (PAR1-AP) induced higher platelet P-selectin expression, and evoked more rapid and intense platelet annexin V binding in T2DM patients, seen as a more rapid increase of annexin V+ platelets (24.3±6.4% vs 12.6±3.8% in control at 2 min) and a higher elevation (30.9±5.1% vs 24.3±3.0% at 8 min). However, PAR1-AP and PAR4-AP induced similar releases of angiogenic regulators from platelets, and both stimuli evoked platelet release of platelet angiogenic regulators to similar extents in T2DM and control subjects. Thus, PAR1-stimulated platelet releasate (PAR1-PR) and PAR4-PR similarly enhanced capillary-like network/tube formation of ECFCs, and the enhancements did not differ between T2DM and control subjects. Direct supplementation of platelets to ECFCs at the ratio of 1:200 enhanced ECFC tube formation even more markedly, leading to approximately 100% increases of the total branch points of ECFC tube formation, for which the enhancements were also similar between patients and controls. In conclusion, platelets from T2DM subjects are hyperreactive. Platelet activation induced by high doses of PAR1-AP, however, results in similar releases of angiogenic regulators in mild T2DM and control subjects. Platelets from T2DM and control subjects also demonstrate similar enhancements on ECFC angiogenic activities.

Trends in Glyburide Compared With Insulin Use for Gestational Diabetes Treatment in the United States, 2000–2011

PubMed Central

Castillo, Wendy Camelo; Boggess, Kim; Stürmer, Til; Brookhart, M. Alan; Benjamin, Daniel K.; Funk, Michele Jonsson

2014-01-01

Objective To describe trends and identify factors associated with choice of pharmacotherapy for gestational diabetes (GDM) from 2000–2011 using a healthcare claims database. Methods This was a retrospective cohort study of a large nationwide population of commercially insured women with GDM and pharmacy claims for glyburide or insulin prior to delivery, 2000–2011. We excluded women younger than 15 years or older than 50 years, those with prior type 2 diabetes, or those who had multiple gestations. We estimated trends over time in the use of glyburide compared with insulin and prevalence ratios (PR) and 95% confidence intervals (CI) for the association between covariates of interest and treatment with glyburide compared with insulin. Results We identified 10,778 women with GDM treated with glyburide (n=5,873) or insulin (n=4,905). From 2000–2011, glyburide use increased from 7.4% to 64.5%, becoming the more common treatment in 2007. Women less likely to be treated with glyburide were those with metabolic syndrome (PR=0.71, 95%CI: 0.50– 0.99), hyperandrogenism (PR=0.77, 95%CI: 0.62–0.97), polycystic ovarian syndrome (PR=0.88, 95%CI: 0.78–0.99), hypothyroidism (PR=0.89, 95%CI: 0.83–0.96) or undergoing infertility treatment (PR=0.93, 95%CI: 0.86–1.02). The probability of receiving glyburide decreased by 5% for every 10-year increase in maternal age (PR=0.95, 95%CI: 0.91–0.99). Among women prescribed with glyburide, 7.8% switched or augmented to a different drug class compared with 1.1% of insulin initiators. Conclusion Glyburide has replaced insulin as the more common pharmacotherapy for GDM over the last decade among those privately insured. Given its rapid uptake and the potential implications of suboptimal glucose control on maternal and neonatal health, robust evaluation of glyburide’s relative effectiveness is warranted to inform treatment decisions for women with gestational diabetes. PMID:24807336

Tandem High-Dose Chemotherapy and Autologous Stem Cell Transplantation for High-Grade Gliomas in Children and Adolescents

PubMed Central

2017-01-01

With the aim to investigate the outcome of tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT) for high-grade gliomas (HGGs), we retrospectively reviewed the medical records of 30 patients with HGGs (16 glioblastomas, 7 anaplastic astrocytomas, and 7 other HGGs) between 2006 and 2015. Gross or near total resection was possible in 11 patients. Front-line treatment after surgery was radiotherapy (RT) in 14 patients and chemotherapy in the remaining 16 patients including 3 patients less than 3 years of age. Eight of 12 patients who remained progression free and 5 of the remaining 18 patients who experienced progression during induction treatment underwent the first HDCT/auto-SCT with carboplatin + thiotepa + etoposide (CTE) regimen and 11 of them proceeded to the second HDCT/auto-SCT with cyclophosphamide + melphalan (CyM) regimen. One patient died from hepatic veno-occlusive disease (VOD) during the second HDCT/auto-SCT; otherwise, toxicities were manageable. Four patients in complete response (CR) and 3 of 7 patients in partial response (PR) or second PR at the first HDCT/auto-SCT remained event free: however, 2 patients with progressive tumor experienced progression again. The probabilities of 3-year overall survival (OS) after the first HDCT/auto-SCT in 11 patients in CR, PR, or second PR was 58.2% ± 16.9%. Tumor status at the first HDCT/auto-SCT was the only significant factor for outcome after HDCT/auto-SCT. There was no difference in survival between glioblastoma and other HGGs. This study suggests that the outcome of HGGs in children and adolescents after HDCT/auto-SCT is encouraging if the patient could achieve CR or PR before HDCT/auto-SCT. PMID:28049229

Mechanism of the photochemical ligand substitution reactions of fac-[Re(bpy)(CO)(3)(PR(3))](+) complexes and the properties of their triplet ligand-field excited states.

PubMed

Koike, Kazuhide; Okoshi, Nobuaki; Hori, Hisao; Takeuchi, Koji; Ishitani, Osamu; Tsubaki, Hideaki; Clark, Ian P; George, Michael W; Johnson, Frank P A; Turner, James J

2002-09-25

We report herein the mechanism of the photochemical ligand substitution reactions of a series of fac-[Re(X(2)bpy)(CO)(3)(PR(3))](+) complexes (1) and the properties of their triplet ligand-field ((3)LF) excited states. The reason for the photostability of the rhenium complexes [Re(X(2)bpy)(CO)(3)(py)](+) (3) and [Re(X(2)bpy)(CO)(3)Cl] (4) was also investigated. Irradiation of an acetonitrile solution of 1 selectively gave the biscarbonyl complexes cis,trans-[Re(X(2)bpy)(CO)(2)(PR(3))(CH(3)CN)](+) (2). Isotope experiments clearly showed that the CO ligand trans to the PR(3) ligand was selectively substituted. The photochemical reactions proceeded via a dissociative mechanism from the (3)LF excited state. The thermodynamical data for the (3)LF excited states of complexes 1 and the corrective nonradiative decay rate constants for the triplet metal-to-ligand charge-transfer ((3)MLCT) states were obtained from temperature-dependence data for the emission lifetimes and for the quantum yields of the photochemical reactions and the emission. Comparison of 1 with [Re(X(2)bpy)(CO)(3)(py)](+) (3) and [Re(X(2)bpy)(CO)(3)Cl] (4) indicated that the (3)LF states of some 3- and 4-type complexes are probably accessible from the (3)MLCT state even at ambient temperature, but these complexes were stable to irradiation at 365 nm. The photostability of 3 and 4, in contrast to 1, can be explained by differences in the trans effects of the PR(3), py, and Cl(-) ligands.

Metabolic syndrome in fixed-shift workers.

PubMed

Canuto, Raquel; Pattussi, Marcos Pascoal; Macagnan, Jamile Block Araldi; Henn, Ruth Liane; Olinto, Maria Teresa Anselmo

2015-01-01

OBJECTIVE To analyze if metabolic syndrome and its altered components are associated with demographic, socioeconomic and behavioral factors in fixed-shift workers. METHODS A cross-sectional study was conducted on a sample of 902 shift workers of both sexes in a poultry processing plant in Southern Brazil in 2010. The diagnosis of metabolic syndrome was determined according to the recommendations from Harmonizing the Metabolic Syndrome. Its frequency was evaluated according to the demographic (sex, skin color, age and marital status), socioeconomic (educational level, income and work shift), and behavioral characteristics (smoking, alcohol intake, leisure time physical activity, number of meals and sleep duration) of the sample. The multivariate analysis followed a theoretical framework for identifying metabolic syndrome in fixed-shift workers. RESULTS The prevalence of metabolic syndrome in the sample was 9.3% (95%CI 7.4;11.2). The most frequently altered component was waist circumference (PR 48.4%; 95%CI 45.5;51.2), followed by high-density lipoprotein. Work shift was not associated with metabolic syndrome and its altered components. After adjustment, the prevalence of metabolic syndrome was positively associated with women (PR 2.16; 95%CI 1.28;3.64), workers aged over 40 years (PR 3.90; 95%CI 1.78;8.93) and those who reported sleeping five hours or less per day (PR 1.70; 95%CI 1.09;2.24). On the other hand, metabolic syndrome was inversely associated with educational level and having more than three meals per day (PR 0.43; 95%CI 0.26;0.73). CONCLUSIONS Being female, older and deprived of sleep are probable risk factors for metabolic syndrome, whereas higher educational level and higher number of meals per day are protective factors for metabolic syndrome in fixed-shift workers.

Immediate clinical and haemodynamic benefits of restoration of pulmonary valvar competence in patients with pulmonary hypertension.

PubMed

Lurz, P; Nordmeyer, J; Coats, L; Taylor, A M; Bonhoeffer, P; Schulze-Neick, I

2009-04-01

To analyse the potential benefit of restoration of pulmonary valvar competence in patients with severe pulmonary regurgitation (PR) and pulmonary hypertension (PH) associated with congenital heart disease. Retrospective study. Tertiary paediatric and adult congenital heart cardiac centre. Percutaneous pulmonary valve implantation (PPVI). All patients who underwent PPVI for treatment of PR in the presence of PH (mean PAP >25 mm Hg). Seven patients with severe PH as a result of congenital heart disease and severe PR underwent PPVI. The valve implantation procedure was feasible and uncomplicated in all seven cases, successfully abolishing PR. There was a significant increase in diastolic (15.4 (7.3) to 34.0 (8.5) mm Hg; p = 0.007) and mean (29.7 (8.1) to 41.3 (12.9) mm Hg; p = 0.034) pulmonary artery pressures, and an improvement in NYHA functional class (from median IV to median III; p<0.008). Peripheral oxygen saturations rose from 85.9% (11.0%) to 91.7% (8.3%) (p = 0.036). Right ventricular (RV) volumes decreased (from 157.0 (44.7) to 140.3 (53.3) ml/m(2)), while effective RV stroke volume increased (from 23.4 (9.3) to 41.0 (11.6) ml/m(2)). During a median follow-up of 20.3 months (range 1.3-47.5), valvar competence was well maintained despite near systemic pulmonary pressures. None of the valved stents were explanted during follow-up. Trans-catheter treatment of PR in patients with PH is well tolerated and leads to clinical and haemodynamic improvement, most probably caused by a combination of increased pulmonary perfusion pressures and RV efficiency.

SERUM THYROTROPIN CONCENTRATIONS ARE NOT PREDICTIVE OF AGGRESSIVE BREAST CANCER BIOLOGY IN EUTHYROID INDIVIDUALS

PubMed Central

Villa, Natalie M.; Li, Ning; Yeh, Michael W.; Hurvitz, Sara A.; Dawson, Nicole A.; Leung, Angela M.

2015-01-01

Objective The potential influence of hypothyroidism on breast cancer remains incompletely understood. The objective of this study was to investigate the relationship between serum thyrotropin [thyroid-stimulating hormone (TSH)] concentration and markers of aggressive breast cancer biology, as defined by receptor expression profile, tumor grade, and American Joint Committee on Cancer (AJCC) stage characteristics. Methods This was a retrospective cohort study of patients from 2002–2014. All breast cancer patients who had complete receptor (estrogen receptor, ER; progesterone receptor, PR; and Her2/neu) and pre-diagnosis serum TSH data (n=437) were included. All patients had one of six receptor profiles: ER+ PR+ Her2/neu −, ER+ PR− Her2/neu−, ER+ PR+ Her2/neu+, ER+ PRHer2/ neu+, ER− PR− Her2/neu+, ER− PR− Her2/neu−. Log-transformed serum TSH concentrations were analyzed using multinomial and logistic regressions for a potential relationship with markers of breast cancer aggressiveness. Results Increasing serum TSH concentration was associated with a lower probability of having the receptor expression profile ER+ PR+ Her2/neu+ compared to patients with the ER+ PR+ Her2/neu− profile (OR=0.52, p=0.0045). No significant associations between other receptor expression profiles and serum TSH concentration were found. All time-weighted and unweighted median serum TSH concentrations were within normal limits. No significant associations between serum TSH concentration and tumor grade, overall AJCC stage, or tumor size (T), lymph node positivity (N), or presence of metastasis (M) were observed. Conclusions Serum TSH was not associated with markers of breast cancer aggressiveness in our cohort. PMID:26121443

Radiolysis of lignin: Prospective mechanism of high-temperature decomposition

NASA Astrophysics Data System (ADS)

Ponomarev, A. V.

2017-12-01

The range of the radiation-thermal processes resulting in conversion of lignin into monomeric phenols is considered. Statistically the most probable places of macromolecule ionization are aromatic units. Release of phenolic products from a lignin macromolecule is the multistage process beginning via fragmentation of primary cation-radicals. Reactions of electrons and small radicals with macromolecules, also as degradation of cation-radicals, result in formation of phenoxyl radicals. Macroradicals possess lower heat stability in comparison with macromolecules. Thermal decomposition of macroradicals leads to release of monohydric and dihydric phenols. The probability of benzenediols formation increases in the presence of alkanes. As noted, partial transformation of lignin into charcoal is inevitable.

Projected Shell Model Description of Positive Parity Band of 130Pr Nucleus

NASA Astrophysics Data System (ADS)

Singh, Suram; Kumar, Amit; Singh, Dhanvir; Sharma, Chetan; Bharti, Arun; Bhat, G. H.; Sheikh, J. A.

2018-02-01

Theoretical investigation of positive parity yrast band of odd-odd 130Pr nucleus is performed by applying the projected shell model. The present study is undertaken to investigate and verify the very recently observed side band in 130Pr theoretically in terms of quasi-particle (qp) configuration. From the analysis of band diagram, the yrast as well as side band are found to arise from two-qp configuration πh 11/2 ⊗ νh 11/2. The present calculations are viewed to have qualitatively reproduced the known experimental data for yrast states, transition energies, and B( M1) / B( E2) ratios of this nucleus. The recently observed positive parity side band is also reproduced by the present calculations. The energy states of the side band are predicted up to spin 25+, which is far above the known experimental spin of 18+ and this could serve as a motivational factor for future experiments. In addition, the reduced transition probability B( E2) for interband transitions has also been calculated for the first time in projected shell model, which would serve as an encouragement for other research groups in the future.

Flap Conformations in HIV-1 Protease are Altered by Mutations

NASA Astrophysics Data System (ADS)

Fanucci, Gail; Blackburn, Mandy; Veloro, Angelo; Galiano, Luis; Fangu, Ding; Simmerling, Carlos

2009-03-01

HIV-1 protease (PR) is an enzyme that is a major drug target in the treatment of AIDS. Although the structure and function of HIV-1 PR have been studied for over 20 years, questions remain regarding the conformations and dynamics of the β-hairpin turns (flaps) that cover the active site cavity. Distance measurements with pulsed EPR spectroscopy of spin labeled constructs of HIV-1 PR have been used to characterize the flap conformations in the apo and inhibitor bound states. From the most probably distances and the breadth of the distance distribution profiles from analysis of the EPR data, insights regarding the flap conformations and flexibility are gained. The EPR results clearly show how drug pressure selected mutations alter the average conformation of the flaps and the degree of opening of the flaps. Molecular dynamics simulations successfully regenerate the experimentally determined distance distribution profiles, and more importantly, provide structural models for full interpretation of the EPR results. By combining experiment and theory to understand the role that altered flap flexibility/conformations play in the mechanism of drug resistance, key insights are gained toward the rational development of new inhibitors of this important enzyme.

Protease-Mediated Maturation of HIV: Inhibitors of Protease and the Maturation Process.

PubMed

Adamson, Catherine S

2012-01-01

Protease-mediated maturation of HIV-1 virus particles is essential for virus infectivity. Maturation occurs concomitant with immature virus particle release and is mediated by the viral protease (PR), which sequentially cleaves the Gag and Gag-Pol polyproteins into mature protein domains. Maturation triggers a second assembly event that generates a condensed conical capsid core. The capsid core organizes the viral RNA genome and viral proteins to facilitate viral replication in the next round of infection. The fundamental role of proteolytic maturation in the generation of mature infectious particles has made it an attractive target for therapeutic intervention. Development of small molecules that target the PR active site has been highly successful and nine protease inhibitors (PIs) have been approved for clinical use. This paper provides an overview of their development and clinical use together with a discussion of problems associated with drug resistance. The second-half of the paper discusses a novel class of antiretroviral drug termed maturation inhibitors, which target cleavage sites in Gag not PR itself. The paper focuses on bevirimat (BVM) the first-in-class maturation inhibitor: its mechanism of action and the implications of naturally occurring polymorphisms that confer reduced susceptibility to BVM in phase II clinical trials.

Smart Fluid System Dually Responsive to Light and Electric Fields: An Electrophotorheological Fluid.

PubMed

Yoon, Chang-Min; Jang, Yoonsun; Noh, Jungchul; Kim, Jungwon; Jang, Jyongsik

2017-10-24

Electrophotorheological (EPR) fluids, whose rheological activity is dually responsive to light and electric fields (E fields), is formulated by mixing photosensitive spiropyran-decorated silica (SP-sSiO 2 ) nanoparticles with zwitterionic lecithin and mineral oil. A reversible photorheological (PR) activity of the EPR fluid is developed via the binding and releasing mechanism of lecithin and merocyanine (MC, a photoisomerized form of SP) under ultraviolet (UV) and visible (VIS) light applications. Moreover, the EPR fluid exhibits an 8-fold higher electrorheological (ER) performance compared to the SP-sSiO 2 nanoparticle-based ER fluid (without lecithin) under an E field, which is attributed to the enhanced dielectric properties facilitated by the binding of the lecithin and SP molecules. Upon dual application of UV light and an E field, the EPR fluid exhibits high EPR performance (ca. 115.3 Pa) that far exceeds its separate PR (ca. 0.8 Pa) and ER (ca. 57.5 Pa) activities, because of the synergistic contributions of the PR and ER effects through rigid and fully connected fibril-like structures. Consequently, this study offers a strategy on formulation of dual-stimuli responsive smart fluid systems.

Nuclear energy release from fragmentation

NASA Astrophysics Data System (ADS)

Li, Cheng; Souza, S. R.; Tsang, M. B.; Zhang, Feng-Shou

2016-08-01

It is well known that binary fission occurs with positive energy gain. In this article we examine the energetics of splitting uranium and thorium isotopes into various numbers of fragments (from two to eight) with nearly equal size. We find that the energy released by splitting 230,232Th and 235,238U into three equal size fragments is largest. The statistical multifragmentation model (SMM) is applied to calculate the probability of different breakup channels for excited nuclei. By weighing the probability distributions of fragment multiplicity at different excitation energies, we find the peaks of energy release for 230,232Th and 235,238U are around 0.7-0.75 MeV/u at excitation energy between 1.2 and 2 MeV/u in the primary breakup process. Taking into account the secondary de-excitation processes of primary fragments with the GEMINI code, these energy peaks fall to about 0.45 MeV/u.

Physical Characterization of a Highly Infectious Monodisperse Preparation of TSE Infectivity as a Substrate for Diagnostic Development

DTIC Science & Technology

2005-09-01

brain homogenate from normal mice and mice infected with bovine spongiform encephalopathy (BSE) and the assay correctly identified the three positive...brains of mice infected with bovine spongiform encephalopathy contain PrP that is resistant to proteolytic digestion and can be detected by western blot...Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Rational development of diagnostics and therapies for the transmissible spongiform

Zero Calcium Score as a Filter for Further Testing in Patients Admitted to the Coronary Care Unit with Chest Pain.

PubMed

Correia, Luis Cláudio Lemos; Esteves, Fábio P; Carvalhal, Manuela; Souza, Thiago Menezes Barbosa de; Sá, Nicole de; Correia, Vitor Calixto de Almeida; Alexandre, Felipe Kalil Beirão; Lopes, Fernanda; Ferreira, Felipe; Noya-Rabelo, Márcia

2017-06-12

The accuracy of zero coronary calcium score as a filter in patients with chest pain has been demonstrated at the emergency room and outpatient clinics, populations with low prevalence of coronary artery disease (CAD). To test the gatekeeping role of zero calcium score in patients with chest pain admitted to the coronary care unit (CCU), where the pretest probability of CAD is higher than that of other populations. Patients underwent computed tomography for calcium scoring, and obstructive CAD was defined by a minimum 70% stenosis on invasive angiography. In 146 patients studied, the prevalence of CAD was 41%. A zero calcium score was present in 35% of the patients. The sensitivity and specificity of zero calcium score yielded a negative likelihood ratio of 0.16. After logistic regression adjustment for pretest probability, zero calcium score was independently associated with lower odds of CAD (OR = 0.12, 95%CI = 0.04-0.36), increasing the area under the ROC curve of the clinical model from 0.76 to 0.82 (p = 0.006). Zero calcium score provided a net reclassification improvement of 0.20 (p = 0.0018) over the clinical model when using a pretest probability threshold of 10% for discharging without further testing. In patients with pretest probability < 50%, zero calcium score had a negative predictive value of 95% (95%CI = 83%-99%), with a number needed to test of 2.1 for obtaining one additional discharge. Zero calcium score substantially reduces the pretest probability of obstructive CAD in patients admitted to the CCU with acute chest pain. (Arq Bras Cardiol. 2017; [online].ahead print, PP.0-0). A acurácia do escore de cálcio coronário zero como um filtro nos pacientes com dor torácica aguda tem sido demonstrada na sala de emergência e nos ambulatórios, populações com baixa prevalência de doença arterial coronariana (DAC). Testar o papel do escore de cálcio zero como filtro nos pacientes com dor torácica admitidos numa unidade coronariana intensiva (UCI), na qual a probabilidade pré-teste de DAC é maior do que em outras populações. Pacientes foram submetidos a tomografia computadorizada para quantificar o escore de cálcio, DAC obstrutiva foi definida por uma estenose mínima de 70% na cineangiocoronariografia invasiva. Um escore clínico para estimar a probabilidade pré-teste de DAC obstrutiva foi criado em amostra de 370 pacientes, usado para definir subgrupos na definição de valores preditivos negativos do escore zero. Em 146 pacientes estudados, a prevalência de DAC foi 41% e o escore de cálcio zero foi demonstrado em 35% deles. A sensibilidade e a especificidade para escore de cálcio zero resultaram numa razão de verossimilhança negativa de 0,16. Após ajuste com um escore clínico com a regressão logística para a probabilidade pré-teste, o escore de cálcio zero foi preditor independente associado a baixa probabilidade de DAC (OR = 0,12, IC95% = 0,04-0,36), aumentando a área abaixo da curva ROC do modelo clínico de 0,76 para 0,82 (p = 0,006). Considerando a probabilidade de DAC < 10% como ponto de corte para alta precoce, o escore de cálcio aumentou a proporção de pacientes para alta precoce de 8,2% para 25% (NRI = 0,20; p = 0,0018). O escore de cálcio zero apresentou valor preditivo negativo de 90%. Em pacientes com probabilidade pré-teste < 50%, o valor preditivo negativo foi 95% (IC95% = 83%-99%). O escore de cálcio zero reduz substancialmente a probabilidade pré-teste de DAC obstrutiva em pacientes internados em UCI com dor torácica aguda. (Arq Bras Cardiol. 2017; [online].ahead print, PP.0-0).

The Detection of Signals in Impulsive Noise.

DTIC Science & Technology

1983-06-01

ASSI FICATION/ DOWN GRADING SCHEOUL1E * I1S. DISTRIBUTION STATEMENT (of th0i0 Rhport) Approved for Public Release; Distribucion Unlimited * 17...has a symmetric distribution, sgn(x i) will be -1 with probability 1/2 and +1 with probability 1/2. Considering the sum of observations as 0 binomial

Estimating inbreeding rates in natural populations: Addressing the problem of incomplete pedigrees

USGS Publications Warehouse

Miller, Mark P.; Haig, Susan M.; Ballou, Jonathan D.; Steel, E. Ashley

2017-01-01

Understanding and estimating inbreeding is essential for managing threatened and endangered wildlife populations. However, determination of inbreeding rates in natural populations is confounded by incomplete parentage information. We present an approach for quantifying inbreeding rates for populations with incomplete parentage information. The approach exploits knowledge of pedigree configurations that lead to inbreeding coefficients of F = 0.25 and F = 0.125, allowing for quantification of Pr(I|k): the probability of observing pedigree I given the fraction of known parents (k). We developed analytical expressions under simplifying assumptions that define properties and behavior of inbreeding rate estimators for varying values of k. We demonstrated that inbreeding is overestimated if Pr(I|k) is not taken into consideration and that bias is primarily influenced by k. By contrast, our new estimator, incorporating Pr(I|k), is unbiased over a wide range of values of kthat may be observed in empirical studies. Stochastic computer simulations that allowed complex inter- and intragenerational inbreeding produced similar results. We illustrate the effects that accounting for Pr(I|k) can have in empirical data by revisiting published analyses of Arabian oryx (Oryx leucoryx) and Red deer (Cervus elaphus). Our results demonstrate that incomplete pedigrees are not barriers for quantifying inbreeding in wild populations. Application of our approach will permit a better understanding of the role that inbreeding plays in the dynamics of populations of threatened and endangered species and may help refine our understanding of inbreeding avoidance mechanisms in the wild.

76 FR 800 - Ameren Missouri, Combined License Application for Callaway Plant Unit 2; Environmental Assessment...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-06

... significantly increase the probability or consequences of accidents. No changes are being made in the types of effluents that may be released offsite. There is no significant increase in the amount of any effluent released offsite. There is no significant increase in occupational or public radiation exposure. Therefore...

42 CFR 90.4 - Contents of requests for health assessments.

Code of Federal Regulations, 2012 CFR

2012-10-01

... number of the requestor; (2) The organization or group the requestor represents, if any; (3) The name... individuals have been exposed to a hazardous substance and that the probable source is a release, or... of concern or the identities of parties believed to be potentially responsible for the release; (2...

42 CFR 90.4 - Contents of requests for health assessments.

Code of Federal Regulations, 2014 CFR

2014-10-01

... number of the requestor; (2) The organization or group the requestor represents, if any; (3) The name... individuals have been exposed to a hazardous substance and that the probable source is a release, or... of concern or the identities of parties believed to be potentially responsible for the release; (2...

42 CFR 90.4 - Contents of requests for health assessments.

Code of Federal Regulations, 2013 CFR

2013-10-01

... number of the requestor; (2) The organization or group the requestor represents, if any; (3) The name... individuals have been exposed to a hazardous substance and that the probable source is a release, or... of concern or the identities of parties believed to be potentially responsible for the release; (2...

42 CFR 90.4 - Contents of requests for health assessments.

Code of Federal Regulations, 2011 CFR

2011-10-01

... number of the requestor; (2) The organization or group the requestor represents, if any; (3) The name... individuals have been exposed to a hazardous substance and that the probable source is a release, or... of concern or the identities of parties believed to be potentially responsible for the release; (2...

Enclosure fire hazard analysis using relative energy release criteria. [burning rate and combustion control

NASA Technical Reports Server (NTRS)

Coulbert, C. D.

1978-01-01

A method for predicting the probable course of fire development in an enclosure is presented. This fire modeling approach uses a graphic plot of five fire development constraints, the relative energy release criteria (RERC), to bound the heat release rates in an enclosure as a function of time. The five RERC are flame spread rate, fuel surface area, ventilation, enclosure volume, and total fuel load. They may be calculated versus time based on the specified or empirical conditions describing the specific enclosure, the fuel type and load, and the ventilation. The calculation of these five criteria, using the common basis of energy release rates versus time, provides a unifying framework for the utilization of available experimental data from all phases of fire development. The plot of these criteria reveals the probable fire development envelope and indicates which fire constraint will be controlling during a criteria time period. Examples of RERC application to fire characterization and control and to hazard analysis are presented along with recommendations for the further development of the concept.

Splanchnic preganglionic neurons in man. III. Morphometry of myelinated fibers of rami communicantes.

PubMed

Low, P A; Dyck, P J

1978-01-01

The myelinated fiber (MF) composition of T6-T8 Rami Communicantes were obtained in 9 healthy persons of various ages. The textbook picture that distal rami (DR) contain all of the myelinated fibers and therefore are white, while proximal rami (PR) contain none of them and therefore are grey must be modified. We found that DR usually contained abundant MFs and that PR concordance was found between segmental numbers of intermediolateral nuclei cytons, ventral root small myelinated fibers (SMFs), and rami total small MFs to suggest that both rami probably contain the distal myelinated axons of preganglionic autonomic fibers. Finally, there was an attrition of total MFs of rami with age, similar to what we had previously found for ILC cytons and for root SMFs. The decrease in number of pre-ganglionic autonomic neurons with age is thought to be of sufficient magnitude to account for the dysautonomia of the elderly.

Development of a probiotic delivery system from agrowastes, soy protein isolate, and microbial transglutaminase.

PubMed

Yew, Sok-Eng; Lim, Ting-Jin; Lew, Lee-Ching; Bhat, Rajeev; Mat-Easa, Azhar; Liong, Min-Tze

2011-04-01

Probiotic delivery system was developed via the use of microbial transglutaminase (MTG) cross-linked soy protein isolate (SPI) incorporated with agrowastes such as banana peel (BE), banana pulp (BU), and pomelo rind (PR). Inoculums of Lactobacillus bulgaricus FTDC 1511 were added to the cross-linked protein matrix. The incorporation of agrowastes had significantly (P<0.05) reduced the strength, pH value, and the lightness of the SPI gel carriers, while sodium dodecyl sulfate-polyacrylamide gel electrophoresis profiles revealed that the occurring cross-links within the SPI gel carriers were attributed to the addition of MTG. Scanning electron microscope micrographs illustrated that SPI carriers containing agrowastes have exhibited a less-dense protein matrix. All the SPI carriers possessed maximum swelling ratio at 4 to 4.5 within 15 min in simulated gastric fluid (SGF), whereas the maximum swelling ratios of SPI/BE, SPI/BU, and SPI/PR were higher compared to that of control in simulated intestinal fluid (SIF). Additionally, SPI carriers in SGF medium did not show degradation of structure, whereas a major collapse of network was observed in SIF medium, indicating controlled-release in the intestines. The addition of agrowastes into SPI carriers led to a significantly (P<0.0001) lower release of L. bulgaricus FTDC 1511 in SGF medium and a higher release in SIF medium, compared to that of the control. SPI carriers containing agrowastes may be useful transports for living probiotic cells through the stomach prior to delivery in the lower intestines.   Agrowastes could be utilized as a new probiotic carrier for enhanced gastrointestinal transit and during storage. This also reduces the amount of agrowastes accumulated.

Pharmacokinetics of Long-Acting Tenofovir Alafenamide (GS-7340) Subdermal Implant for HIV Prophylaxis

PubMed Central

Gunawardana, Manjula; Remedios-Chan, Mariana; Miller, Christine S.; Fanter, Rob; Yang, Flora; Marzinke, Mark A.; Hendrix, Craig W.; Beliveau, Martin; Moss, John A.; Smith, Thomas J.

2015-01-01

Oral or topical daily administration of antiretroviral (ARV) drugs to HIV-1-negative individuals in vulnerable populations is a promising strategy for HIV-1 prevention. Adherence to the dosing regimen has emerged as a critical factor determining efficacy outcomes of clinical trials. Because adherence to therapy is inversely related to the dosing period, sustained release or long-acting ARV formulations hold significant promise for increasing the effectiveness of HIV-1 preexposure prophylaxis (PrEP) by reducing dosing frequency. A novel, subdermal implant delivering the potent prodrug tenofovir alafenamide (TAF) with controlled, sustained, zero-order (linear) release characteristics is described. A candidate device delivering TAF at 0.92 mg day−1 in vitro was evaluated in beagle dogs over 40 days for pharmacokinetics and preliminary safety. No adverse events related to treatment with the test article were noted during the course of the study, and no significant, unusual abnormalities were observed. The implant maintained a low systemic exposure to TAF (median, 0.85 ng ml−1; interquartile range [IQR], 0.60 to 1.50 ng ml−1) and tenofovir (TFV; median, 15.0 ng ml−1; IQR, 8.8 to 23.3 ng ml−1), the product of in vivo TAF hydrolysis. High concentrations (median, 512 fmol/106 cells over the first 35 days) of the pharmacologically active metabolite, TFV diphosphate, were observed in peripheral blood mononuclear cells at levels over 30 times higher than those associated with HIV-1 PrEP efficacy in humans. Our report on the first sustained-release nucleoside reverse transcriptase inhibitor (NRTI) for systemic delivery demonstrates a successful proof of principle and holds significant promise as a candidate for HIV-1 prophylaxis in vulnerable populations. PMID:25896688

Final safety analysis report for the Galileo mission: Volume 3 (Book 2), Nuclear risk analysis document: Appendices: Revision 1

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

Not Available

1989-01-25

It is the purpose of the NRAD to provide an analysis of the range of potential consequences of accidents which have been identified that are associated with the launching and deployment of the Galileo mission spacecraft. The specific consequences analyzed are those associated with the possible release of radioactive material (fuel) of the Radioisotope Thermoelectric Generators (RTGs). They are in terms of radiation doses to people and areas of deposition of radioactive material. These consequence analyses can be used in several ways. One way is to identify the potential range of consequences which might have to be dealt with ifmore » there were to be an accident with a release of fuel, so as to assure that, given such an accident, the health and safety of the public will be reasonably protected. Another use of the information, in conjunction with accident and release probabilities, is to estimate the risks associated with the mission. That is, most space launches occur without incident. Given an accident, the most probable result relative to the RTGs is complete containment of the radioactive material. Only a small fraction of accidents might result in a release of fuel and subsequent radiological consequences. The combination of probability with consequence is risk, which can be compared to other human and societal risks to assure that no undue risks are implied by undertaking the mission. Book 2 contains eight appendices.« less

Safety analysis report for the Galileo Mission. Volume 3, book 2: Nuclear risk analysis document. Appendices, revision 1

NASA Astrophysics Data System (ADS)

1989-01-01

It is the purpose of the NRAD to provide an analysis of the range of potential consequences of accidents which have been identified that are associated with the launching and deployment of the Galileo mission spacecraft. The specific consequences analyzed are those associated with the possible release of radioactive material (fuel) of the Radioisotope Thermoelectric Generators (RTGs). They are in terms of radiation doses to people and areas of deposition of radioactive material. These consequence analyses can be used in several ways. One way is to identify the potential range of consequences which might have to be dealt with if there were to be an accident with a release of fuel, so as to assure that, given such an accident, the health and safety of the public will be reasonably protected. Another use of the information, in conjunction with accident and release probabilities, is to estimate the risks associated with the mission. That is, most space launches occur without incident. Given an accident, the most probable result relative to the RTGs is complete containment of the radioactive material. Only a small fraction of accidents might result in a release of fuel and subsequent radiological consequences. The combination of probability with consequence is risk, which can be compared to other human and societal risks to assure that no undue risks are implied by undertaking the mission. Book 2 contains eight appendices.

Coordination Polymers of 5-Alkoxy Isophthalic Acids

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

McCormick, Laura J.; Morris, Samuel A.; Slawin, Alexandra M. Z.

The topology of coordination polymers containing 5-alkoxy isophthalic acids and first row transition metals was found to be dependent on the combination of solvent system used and length of the alkyl chain. Four different framework types were thus identified: Phase A, M 6(ROip) 5(OH) 2(H 2O) 4·xH 2O (M = Co and R = Et, Pr, or nBu, or M = Zn and R = Et); Phase B,M 2(ROip) 2(H 2O) (M = Co or Zn and R = Et, Pr, nBu, or iBu, or M = Mn and R = nBu or iBu); Phase C, Zn 3(EtOip) 2(OH) 2;more » and Phase D, Zn 2(EtOip) 2(H 2O) 3. Preliminary screening of the NO storage and release capabilities of the Co-containing materials is also reported.« less

Coordination Polymers of 5-Alkoxy Isophthalic Acids

DOE PAGES

McCormick, Laura J.; Morris, Samuel A.; Slawin, Alexandra M. Z.; ...

2016-08-23

The topology of coordination polymers containing 5-alkoxy isophthalic acids and first row transition metals was found to be dependent on the combination of solvent system used and length of the alkyl chain. Four different framework types were thus identified: Phase A, M 6(ROip) 5(OH) 2(H 2O) 4·xH 2O (M = Co and R = Et, Pr, or nBu, or M = Zn and R = Et); Phase B,M 2(ROip) 2(H 2O) (M = Co or Zn and R = Et, Pr, nBu, or iBu, or M = Mn and R = nBu or iBu); Phase C, Zn 3(EtOip) 2(OH) 2;more » and Phase D, Zn 2(EtOip) 2(H 2O) 3. Preliminary screening of the NO storage and release capabilities of the Co-containing materials is also reported.« less

Study of sea-surface slope distribution and its effect on radar backscatter based on Global Precipitation Measurement Ku-band precipitation radar measurements

NASA Astrophysics Data System (ADS)

Yan, Qiushuang; Zhang, Jie; Fan, Chenqing; Wang, Jing; Meng, Junmin

2018-01-01

The collocated normalized radar backscattering cross-section measurements from the Global Precipitation Measurement (GPM) Ku-band precipitation radar (KuPR) and the winds from the moored buoys are used to study the effect of different sea-surface slope probability density functions (PDFs), including the Gaussian PDF, the Gram-Charlier PDF, and the Liu PDF, on the geometrical optics (GO) model predictions of the radar backscatter at low incidence angles (0 deg to 18 deg) at different sea states. First, the peakedness coefficient in the Liu distribution is determined using the collocations at the normal incidence angle, and the results indicate that the peakedness coefficient is a nonlinear function of the wind speed. Then, the performance of the modified Liu distribution, i.e., Liu distribution using the obtained peakedness coefficient estimate; the Gaussian distribution; and the Gram-Charlier distribution is analyzed. The results show that the GO model predictions with the modified Liu distribution agree best with the KuPR measurements, followed by the predictions with the Gaussian distribution, while the predictions with the Gram-Charlier distribution have larger differences as the total or the slick filtered, not the radar filtered, probability density is included in the distribution. The best-performing distribution changes with incidence angle and changes with wind speed.

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

Hosseinizadeh, Ahmad; Mashayekhi, Ghoncheh; Copperman, Jeremy

Using a manifold-based analysis of experimental diffraction snapshots from an X-ray free electron laser, we determine the three-dimensional structure and conformational landscape of the PR772 virus to a detector-limited resolution of 9 nm. Our results indicate that a single conformational coordinate controls reorganization of the genome, growth of a tubular structure from a portal vertex and release of the genome. Furthermore, these results demonstrate that single-particle X-ray scattering has the potential to shed light on key biological processes.

Discovery of Host Factors and Pathways Utilized in Hantaviral Infection

DTIC Science & Technology

2015-09-01

STATEMENT: Approved for Public Release; Distribution Unlimited The views, opinions and/or findings contained in this report are those of the author ...NUMBER 5b. GRANT NUMBER W81XWH-14-1-0204 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR (S) Paul Bates 5d. PROJECT NUMBER PR130590 5e. TASK NUMBER E-Mail...Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Hantaviruses are negative-sense RNA enveloped viruses that are transmitted to humans in aerosols of rodent

Probability analysis of multiple-tank-car release incidents in railway hazardous materials transportation.

PubMed

Liu, Xiang; Saat, Mohd Rapik; Barkan, Christopher P L

2014-07-15

Railroads play a key role in the transportation of hazardous materials in North America. Rail transport differs from highway transport in several aspects, an important one being that rail transport involves trains in which many railcars carrying hazardous materials travel together. By contrast to truck accidents, it is possible that a train accident may involve multiple hazardous materials cars derailing and releasing contents with consequently greater potential impact on human health, property and the environment. In this paper, a probabilistic model is developed to estimate the probability distribution of the number of tank cars releasing contents in a train derailment. Principal operational characteristics considered include train length, derailment speed, accident cause, position of the first car derailed, number and placement of tank cars in a train and tank car safety design. The effect of train speed, tank car safety design and tank car positions in a train were evaluated regarding the number of cars that release their contents in a derailment. This research provides insights regarding the circumstances affecting multiple-tank-car release incidents and potential strategies to reduce their occurrences. The model can be incorporated into a larger risk management framework to enable better local, regional and national safety management of hazardous materials transportation by rail. Copyright © 2014 Elsevier B.V. All rights reserved.

The potential for damage from the accidental release of conductive carbon fibers from burning composites

NASA Technical Reports Server (NTRS)

Bell, V. L.

1980-01-01

The potential damage to electrical equipment caused by the release of carbon fibers from burning commercial airliners is assessed in terms of annual expected costs and maximum losses at low probabilities of occurrence. A materials research program to provide alternate or modified composite materials for aircraft structures is reviewed.

Cardiac electrical conduction, autonomic activity and biomarker release during recovery from prolonged strenuous exercise in trained male cyclists.

PubMed

Stewart, Glenn M; Kavanagh, Justin J; Koerbin, Gus; Simmonds, Michael J; Sabapathy, Surendran

2014-01-01

Although markers of myocyte injury, electrolyte disturbances and an autonomic imbalance have been reported following exercise, the effect of prolonged strenuous activity on cardiac electrical conduction is not well understood. This study examined atrial and ventricular conduction dynamics during recovery from exercise. Electrocardiographic intervals were obtained from eight highly-trained males before, during recovery (15, 30, 45 and 60 min post-exercise) and 24 h after a prolonged bout of strenuous exercise. Time-domain, frequency-domain and non-linear analyses of the RR, PR and QT intervals were analysed to investigate the effect of exercise on autonomic modulation and cardiac electrical conduction. Serum electrolyte and high-sensitivity cardiac troponin T (hs-cTnT) concentrations were measured before exercise, and after 60 min and 24 h of recovery. The root mean square of the successive differences of RR, PR and QT intervals was significantly reduced during recovery (p < 0.05). Normalised low- and high-frequency power of RR intervals significantly increased and decreased, respectively, during recovery. Approximate entropy of PR and QT intervals, and the QT-variability index significantly increased during recovery. All measures except mean QT interval (pre 422 ± 10 ms vs 24 h post 442 ± 11 ms, p = 0.013) returned to pre-exercise values after 24 h. Serum hs-cTnT was significantly elevated 60 min after exercise (pre 5.2 ± 0.7 ng L(-1) vs 60 min post 27.4 ± 6.2 ng L(-1), p = 0.01) and correlated with exercising heart rate (R(2) = 0.89, p < 0.001). Serum electrolyte concentrations were unchanged (p > 0.05). The results suggest suppressed parasympathetic and/or sustained sympathetic modulation of heart rate during recovery, concomitant with perturbations in atrial and ventricular conduction dynamics. Exercise-induced hs-cTnT release was heart rate dependent.

A field investigation of a modified intravaginal progesterone releasing device and oestradiol benzoate based ovulation synchronisation protocol designed for fixed-time artificial insemination of Brahman heifers.

PubMed

Edwards, S A A; Boe-Hansen, G B; Satake, N; Chandra, K; McGowan, M R

2015-09-01

Pregnancy rates (PR) to fixed-time AI (FTAI) in Brahman heifers were compared after treatment with a traditional oestradiol-based protocol (OPO-8) or a modified protocol (OPO-6) where the duration of intravaginal progesterone releasing device (IPRD) was reduced from 8 to 6 days, and the interval from IPRD removal to oestradiol benzoate (ODB) was increased from 24 to 36 h. Rising 2 yo heifers on Farm A: (n = 238 and n = 215; two consecutive days AI); B (n = 271); and C (n = 393) were allocated to OPO-8 or OPO-6. An IPRD was inserted and 1mg ODB i.m. on Day 0 for OPO-8 heifers and Day 2 for OPO-6 heifers. On Day 8, the IPRD was removed and 500 μg cloprostenol i.m. At 24h, for OPO-8 heifers, and 36 h, for OPO-6 heifers, post IPRD removal all heifers received 1mg ODB i.m. FTAI was conducted at 54 and 72 h post IPRD removal for OPO-8 and OPO-6 heifers. At Farm A, OPO-6 heifers, AI on the second day, the PR was 52.4% to FTAI (P = 0.024) compared to 36.8% for OPO-8 heifers. However, no differences were found between OPO-8 and OPO-6 protocols at Farm A (first day of AI) (39.9 vs. 35.7%), or Farms B (26.2 vs. 35.4%) and C (43.2% vs. 40.3%). Presence of a corpus luteum at IPRD insertion affected PR to FTAI (43.9% vs. 28.8%; P < 0.001). This study has shown that the modified ovulation synchronisation protocol OPO-6 may be a viable alternative to the OPO-8 protocol for FTAI in B. indicus heifers. Copyright © 2015 Elsevier B.V. All rights reserved.

Effect of formulation and processing variables on the characteristics of microspheres for water-soluble drugs prepared by w/o/o double emulsion solvent diffusion method.

PubMed

Lee, J; Park, T G; Choi, H

2000-02-25

80% except for acetaminophen, due to its lower solubility in water and higher solubility in corn oil. The release profile of the drug was pH dependent. In acidic medium, the release rate was much slower, however, the drug was released quickly at pH 7.4. Tacrine showed unexpected release profiles, probably due to ionic interaction with polymer matrix and the shell structure and the highest release rate was obtained at pH 2.0. The prepared microspheres had a sponge-like inner structure with or without central hollow core and the surface was dense with no apparent pores.

Efficacy of Second Generation Direct-Acting Antiviral Agents for Treatment Naïve Hepatitis C Genotype 1: A Systematic Review and Network Meta-Analysis

PubMed Central

Sobhonslidsuk, Abhasnee; Thakkinstian, Ammarin; Teerawattananon, Yot

2015-01-01

Background The treatment of hepatitis C (HCV) infections has significantly changed in the past few years due to the introduction of direct-acting antiviral agents (DAAs). DAAs could improve the sustained virological response compared to pegylated interferon with ribavirin (PR). However, there has been no evidence from randomized controlled trials (RCTs) that directly compare the efficacy among the different regimens of DAAs. Aim Therefore, we performed a systematic review and network meta-analysis aiming to compare the treatment efficacy between different DAA regimens for treatment naïve HCV genotype 1. Methods Medline and Scopus were searched up to 25th May 2015. RCTs investigating the efficacy of second generation DAA regimens for treatment naïve HCV genotype 1 were eligible for the review. Due to the lower efficacy and more side effects of first generation DAAs, this review included only second generation DAAs approved by the US or EU Food and Drug Administration, that comprised of simeprevir (SMV), sofosbuvir (SOF), daclatasvir (DCV), ledipasvir (LDV), and paritaprevir/ritonavir/ombitasvir plus dasabuvir (PrOD). Primary outcomes were sustained virological response at weeks 12 (SVR12) and 24 (SVR24) after the end of treatment and adverse drug events (i.e. serious adverse events, anemia, and fatigue). Efficacy of all treatment regimens were compared by applying a multivariate random effect meta-analysis. Incidence rates of SVR12 and SVR24, and adverse drug events of each treatment regimen were pooled using ‘pmeta’ command in STATA program. Results Overall, 869 studies were reviewed and 16 studies were eligible for this study. Compared with the PR regimen, SOF plus PR, SMV plus PR, and DVC plus PR regimens yielded significantly higher probability of having SVR24 with pooled risk ratios (RR) of 1.98 (95% CI 1.24, 3.14), 1.46 (95% CI: 1.22, 1.75), and 1.68 (95% CI: 1.14, 2.46), respectively. Pooled incidence rates of SVR12 and SVR24 in all treatment regimens without PR, i.e. SOF plus LDV with/without ribavirin, SOF plus SMV with/without ribavirin, SOF plus DCV with/without ribavirin, and PrOD with/without ribavirin, (pooled incidence of SVR12 ranging from 93% to 100%, and pooled incidence of SVR24 ranging from 89% to 96%) were much higher than the pooled incidence rates of SVR12 (51%) and SVR24 (48%) in PR alone. In comparing SOF plus LDV with ribavirin and SOF plus LDV without ribavirin, the chance of having SVR12 was not significantly different between these two regimens, with the pooled RR of 0.99 (95% CI: 0.97, 1.01). Regarding adverse drug events, risk of serious adverse drug events, anemia and fatigue were relatively higher in treatment regimens with PR than the treatment regimens without PR. The main limitation of our study is that a subgroup analysis according to dosages and duration of treatment could not be performed. Therefore, the dose and duration of recommended treatment have been suggested in range and not in definite value. Conclusions Both DAA plus PR and dual DAA regimens should be included in the first line drug for treatment naïve HCV genotype 1 because of the significant clinical benefits over PR alone. However, due to high drug costs, an economic evaluation should be conducted in order to assess the value of the investment when making coverage decisions. PMID:26720298

Titanic Weather Forecasting

NASA Astrophysics Data System (ADS)

2004-04-01

New Detailed VLT Images of Saturn's Largest Moon Optimizing space missions Titan, the largest moon of Saturn was discovered by Dutch astronomer Christian Huygens in 1655 and certainly deserves its name. With a diameter of no less than 5,150 km, it is larger than Mercury and twice as large as Pluto. It is unique in having a hazy atmosphere of nitrogen, methane and oily hydrocarbons. Although it was explored in some detail by the NASA Voyager missions, many aspects of the atmosphere and surface still remain unknown. Thus, the existence of seasonal or diurnal phenomena, the presence of clouds, the surface composition and topography are still under debate. There have even been speculations that some kind of primitive life (now possibly extinct) may be found on Titan. Titan is the main target of the NASA/ESA Cassini/Huygens mission, launched in 1997 and scheduled to arrive at Saturn on July 1, 2004. The ESA Huygens probe is designed to enter the atmosphere of Titan, and to descend by parachute to the surface. Ground-based observations are essential to optimize the return of this space mission, because they will complement the information gained from space and add confidence to the interpretation of the data. Hence, the advent of the adaptive optics system NAOS-CONICA (NACO) [1] in combination with ESO's Very Large Telescope (VLT) at the Paranal Observatory in Chile now offers a unique opportunity to study the resolved disc of Titan with high sensitivity and increased spatial resolution. Adaptive Optics (AO) systems work by means of a computer-controlled deformable mirror that counteracts the image distortion induced by atmospheric turbulence. It is based on real-time optical corrections computed from image data obtained by a special camera at very high speed, many hundreds of times each second (see e.g. ESO Press Release 25/01 , ESO PR Photos 04a-c/02, ESO PR Photos 19a-c/02, ESO PR Photos 21a-c/02, ESO Press Release 17/02, and ESO Press Release 26/03 for earlier NACO images, and ESO Press Release 11/03 for MACAO-VLTI results.) The southern smile ESO PR Photo 08a/04 ESO PR Photo 08a/04 Images of Titan on November 20, 25 and 26, 2002 Through Five Filters (VLT YEPUN + NACO) [Preview - JPEG: 522 x 400 pix - 40k] [Normal - JPEG: 1043 x 800 pix - 340k] [Hires - JPEG: 2875 x 2205 pix - 1.2M] Caption: ESO PR Photo 08a/04 shows Titan (apparent visual magnitude 8.05, apparent diameter 0.87 arcsec) as observed with the NAOS/CONICA instrument at VLT Yepun (Paranal Observatory, Chile) on November 20, 25 and 26, 2003, between 6.00 UT and 9.00 UT. The median seeing values were 1.1 arcsec and 1.5 arcsec respectively for the 20th and 25th. Deconvoluted ("sharpened") images of Titan are shown through 5 different narrow-band filters - they allow to probe in some detail structures at different altitudes and on the surface. Depending on the filter, the integration time varies from 10 to 100 seconds. While Titan shows its leading hemisphere (i.e. the one observed when Titan moves towards us) on Nov. 20, the trailing side (i.e the one we see when Titan moves away from us in its course around Saturn) - which displays less bright surface features - is observed on the last two dates. ESO PR Photo 08b/04 ESO PR Photo 08b/04 Titan Observed Through Nine Different Filters on November 26, 2002 [Preview - JPEG: 480 x 400 pix - 36k] [Normal - JPEG: 960 x 800 pix - 284k] Caption: ESO PR Photo 08b/04: Images of Titan taken on November 26, 2002 through nine different filters to probe different altitudes, ranging from the stratosphere to the surface. On this night, a stable "seeing" (image quality before adaptive optics correction) of 0.9 arcsec allowed the astronomers to attain the diffraction limit of the telescope (0.032 arcsec resolution). Due to these good observing conditions, Titan's trailing hemisphere was observed with contrasts of about 40%, allowing the detection of several bright features on this surface region, once thought to be quite dark and featureless. ESO PR Photo 08c/04 ESO PR Photo 08c/04 Titan Surface Projections [Preview - JPEG: 601 x 400 pix - 64k] [Normal - JPEG: 1201 x 800 pix - 544k] Caption: ESO PR Photo 08c/04 : Titan images obtained with NACO on November 26th, 2002. Left: Titan's surface projection on the trailing hemisphere as observed at 1.3 μm, revealing a complex brightness structure thanks to the high image contrast of about 40%. Right: a new, possibly meteorological, phenomenon observed at 2.12 μm in Titan's atmosphere, in the form of a bright feature revolving around the South Pole. A team of French astronomers [2] have recently used the NACO state-of-the-art adaptive optics system on the fourth 8.2-m VLT unit telescope, Yepun, to map the surface of Titan by means of near-infrared images and to search for changes in the dense atmosphere. These extraordinary images have a nominal resolution of 1/30th arcsec and show details of the order of 200 km on the surface of Titan. To provide the best possible views, the raw data from the instrument were subjected to deconvolution (image sharpening). Images of Titan were obtained through 9 narrow-band filters, sampling near-infrared wavelengths with large variations in methane opacity. This permits sounding of different altitudes ranging from the stratosphere to the surface. Titan harbours at 1.24 and 2.12 μm a "southern smile", that is a north-south asymmetry, while the opposite situation is observed with filters probing higher altitudes, such as 1.64, 1.75 and 2.17 μm. A high-contrast bright feature is observed at the South Pole and is apparently caused by a phenomenon in the atmosphere, at an altitude below 140 km or so. This feature was found to change its location on the images from one side of the south polar axis to the other during the week of observations. Outlook An additional series of NACO observations of Titan is foreseen later this month (April 2004). These will be a great asset in helping optimize the return of the Cassini/Huygens mission. Several of the instruments aboard the spacecraft depend on such ground-based data to better infer the properties of Titan's surface and lower atmosphere. Although the astronomers have yet to model and interpret the physical and geophysical phenomena now observed and to produce a full cartography of the surface, this first analysis provides a clear demonstration of the marvellous capabilities of the NACO imaging system. More examples of the exciting science possible with this facility will be found in a series of five papers published today in the European research journal Astronomy & Astrophysics (Vol. 47, L1 to L24).

Automated Weather Observing System (AWOS) Demonstration Program.

DTIC Science & Technology

1984-09-01

month "bur:-in" r "debugging" period and a 10-month ’usefu I life " period. Fhe butrn- in pr i ,J was i sed to establish the Data Acquisition System...Histograms. Histograms provide a graphical means of showing how well the probability distribution of residu : , approaches a normal or Gaussian distribution...Organization Report No. 7- Author’s) Paul .J. O t Brien et al. DOT/FAA/CT-84/20 9. Performing Organlzation Name and Address 10. Work Unit No. (TRAIS

SoC: Une Nouvelle Approche de l’Amelioration des Performances des Systemes pour Combattre les Problemes de Disponibilite a Long Terme (SoC: A New Approach to Enhance System Performances and to Combat the Long-Term Availability Issue)

DTIC Science & Technology

2001-01-01

cin~tique Properties»> ou o IP »>. En fait, ces IP ne sont rien (exemple : un missile en vol libre ). Meme si on peut d’autres que des composants sur...probablement pas radicalement le problkme peuvent soit achet~s soit &tre issus de conceptions au niveau des composants 6lectroniques. pr&c~dentes. Les

A statistical analysis of the daily streamflow hydrograph

NASA Astrophysics Data System (ADS)

Kavvas, M. L.; Delleur, J. W.

1984-03-01

In this study a periodic statistical analysis of daily streamflow data in Indiana, U.S.A., was performed to gain some new insight into the stochastic structure which describes the daily streamflow process. This analysis was performed by the periodic mean and covariance functions of the daily streamflows, by the time and peak discharge -dependent recession limb of the daily streamflow hydrograph, by the time and discharge exceedance level (DEL) -dependent probability distribution of the hydrograph peak interarrival time, and by the time-dependent probability distribution of the time to peak discharge. Some new statistical estimators were developed and used in this study. In general features, this study has shown that: (a) the persistence properties of daily flows depend on the storage state of the basin at the specified time origin of the flow process; (b) the daily streamflow process is time irreversible; (c) the probability distribution of the daily hydrograph peak interarrival time depends both on the occurrence time of the peak from which the inter-arrival time originates and on the discharge exceedance level; and (d) if the daily streamflow process is modeled as the release from a linear watershed storage, this release should depend on the state of the storage and on the time of the release as the persistence properties and the recession limb decay rates were observed to change with the state of the watershed storage and time. Therefore, a time-varying reservoir system needs to be considered if the daily streamflow process is to be modeled as the release from a linear watershed storage.

Association between the level of education and knowledge, attitudes and practices regarding dengue in the Caribbean region of Colombia.

PubMed

Diaz-Quijano, Fredi Alexander; Martínez-Vega, Ruth Aralí; Rodriguez-Morales, Alfonso J; Rojas-Calero, Ronald Alexander; Luna-González, María Lucrecia; Díaz-Quijano, Ronald Giovanny

2018-01-16

Community integration in dengue control requires assessments of knowledge, attitudes and practices (KAPs), which can vary widely according to demographic and educational factors. We aimed to describe and compare the KAPs according to level of education in municipalities in the Caribbean region of Colombia. A survey was administered from October to December 2015, including families selected through probabilistic sampling in eleven municipalities. The analysis focused on the comparative description of the responses according to level of education. The KAP prevalence ratios (PR) according to education were estimated using Poisson regression (robust), including age and sex as adjustment variables. Out of 1057 participants, 1054 (99.7%) surveys were available for analysis, including 614 (58.3%) who had a high school level of education or higher and 440 (41.7%) who had a lower level of education (not high school graduates). The high school graduates showed a higher frequency of correct answers in relation to knowledge about dengue symptoms and transmission. On the other hand, graduates showed a higher probability of practices and attitudes that favor dengue control, including not storing water in containers (PR: 2.2; 95% Confidence Interval [CI]: 1.42-3.43), attend community meetings (PR: 1.33; 95% CI: 1.07-1.65), educate family members and neighbors in prevention measures (PR: 1.35; 95% CI: 1.15-1.59). Level of education could be a key determinant of knowledge of the disease and its transmission, as well as attitudes and practices, especially those that involve the integration of community efforts for dengue control.

Variation of photoluminescence features in Pr{sup 3+} doped lithium-fluoro-borate glass by changing different modifier oxides (MgO, CaO, CdO and PbO)-Judd-Ofelt theory application

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

Balakrishna, A.; Rajesh, D.; Babu, S.

2015-06-24

Pr{sup 3+} (1.0 mol%) doped different modifier oxide based six lithium-fluoro-borate glasses with chemical composition of 49Li{sub 2}B{sub 4}O{sub 7}-20BaF{sub 2}-10NaF-20MO (where M= Mg, Ca, Cd and Pb), 49Li{sub 2}B{sub 4}O{sub 7}-20BaF{sub 2}-10NaF-10MgO-10CaO and 49Li{sub 2}B{sub 4}O{sub 7}-20BaF{sub 2}-10NaF-10CdO-10PbO were prepared by conventional melt quenching technique. Judd-Ofelt theory has been applied for evaluating the Judd-Ofelt intensity parameters for Pr{sup 3+} ion in these glass compositions and are in turn to used to predict radiative properties such as radiative transition probabilities (A{sub T}), branching ratios (β) and stimulated emission cross-section (σ{sub P}). Stimulated emission cross-section (σ{sub p}) of prominent emission transitions,more » {sup 3}P{sub 0}→{sup 3}H{sub 4} and {sup 1}D{sub 2}→{sup 3}H{sub 4} of Pr{sup 3+} ion in all lithium-fluoro-borate glasses were calculated. Among all the emission transitions, {sup 3}P{sub 0}→{sup 3}H{sub 4} posseses higher branching ratio and stimulated emission cross-section in Mg-Ca glass, which leads to the best laser excitation at 487 nm wavelength.« less

Availability of High Quality TRMM Ground Validation Data from Kwajalein, RMI: A Practical Application of the Relative Calibration Adjustment Technique

NASA Technical Reports Server (NTRS)

Marks, David A.; Wolff, David B.; Silberstein, David S.; Tokay, Ali; Pippitt, Jason L.; Wang, Jianxin

2008-01-01

Since the Tropical Rainfall Measuring Mission (TRMM) satellite launch in November 1997, the TRMM Satellite Validation Office (TSVO) at NASA Goddard Space Flight Center (GSFC) has been performing quality control and estimating rainfall from the KPOL S-band radar at Kwajalein, Republic of the Marshall Islands. Over this period, KPOL has incurred many episodes of calibration and antenna pointing angle uncertainty. To address these issues, the TSVO has applied the Relative Calibration Adjustment (RCA) technique to eight years of KPOL radar data to produce Ground Validation (GV) Version 7 products. This application has significantly improved stability in KPOL reflectivity distributions needed for Probability Matching Method (PMM) rain rate estimation and for comparisons to the TRMM Precipitation Radar (PR). In years with significant calibration and angle corrections, the statistical improvement in PMM distributions is dramatic. The intent of this paper is to show improved stability in corrected KPOL reflectivity distributions by using the PR as a stable reference. Inter-month fluctuations in mean reflectivity differences between the PR and corrected KPOL are on the order of 1-2 dB, and inter-year mean reflectivity differences fluctuate by approximately 1 dB. This represents a marked improvement in stability with confidence comparable to the established calibration and uncertainty boundaries of the PR. The practical application of the RCA method has salvaged eight years of radar data that would have otherwise been unusable, and has made possible a high-quality database of tropical ocean-based reflectivity measurements and precipitation estimates for the research community.

Continental-scale simulation of burn probabilities, flame lengths, and fire size distribution for the United States

Treesearch

Mark A. Finney; Charles W. McHugh; Isaac Grenfell; Karin L. Riley

2010-01-01

Components of a quantitative risk assessment were produced by simulation of burn probabilities and fire behavior variation for 134 fire planning units (FPUs) across the continental U.S. The system uses fire growth simulation of ignitions modeled from relationships between large fire occurrence and the fire danger index Energy Release Component (ERC). Simulations of 10,...

Interactions of phosphate solubilising microorganisms with natural rare-earth phosphate minerals: a study utilizing Western Australian monazite.

PubMed

Corbett, Melissa K; Eksteen, Jacques J; Niu, Xi-Zhi; Croue, Jean-Philippe; Watkin, Elizabeth L J

2017-06-01

Many microbial species are capable of solubilising insoluble forms of phosphate and are used in agriculture to improve plant growth. In this study, we apply the use of known phosphate solubilising microbes (PSM) to the release of rare-earth elements (REE) from the rare-earth phosphate mineral, monazite. Two sources of monazite were used, a weathered monazite and mineral sand monazite, both from Western Australia. When incubated with PSM, the REE were preferentially released into the leachate. Penicillum sp. released a total concentration of 12.32 mg L -1 rare-earth elements (Ce, La, Nd, and Pr) from the weathered monazite after 192 h with little release of thorium and iron into solution. However, cultivation on the mineral sands monazite resulted in the preferential release of Fe and Th. Analysis of the leachate detected the production of numerous low-molecular weight organic acids. Gluconic acid was produced by all microorganisms; however, other organic acids produced differed between microbes and the monazite source provided. Abiotic leaching with equivalent combinations of organic acids resulted in the lower release of REE implying that other microbial processes are playing a role in solubilisation of the monazite ore. This study demonstrates that microbial solubilisation of monazite is promising; however, the extent of the reaction is highly dependent on the monazite matrix structure and elemental composition.

Activation of human gingival epithelial cells by cell-surface components of black-pigmented bacteria: augmentation of production of interleukin-8, granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor and expression of intercellular adhesion molecule 1.

PubMed

Sugiyama, A; Uehara, A; Iki, K; Matsushita, K; Nakamura, R; Ogawa, T; Sugawara, S; Takada, H

2002-01-01

Black-pigmented anaerobic bacteria, such as Porphyromonas gingivalis and Prevotella intermedia, are amongst the predominant bacteria in periodontal pockets and have been implicated in periodontal diseases. To elucidate the roles of gingival keratinocytes, which are the first cells encountered by oral bacteria in periodontal diseases, human gingival keratinocytes in primary culture were stimulated with cell-surface components of P gingivalis and Pr. intermedia. A glycoprotein fraction from Pr. intermedia (PGP) clearly augmented the release of interleukin-8, granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor, as determined by enzyme-linked immunosorbent assay. This PGP also induced expression of intercellular adhesion molecule-1 (ICAM-1), as determined by flow cytometry. The augmentation of mRNA expression for these molecules was also confirmed by reverse transcription PCR. In contrast, lipopolysaccharide (LPS) from Pr. intermedia and Escherichia coli was completely inactive in these assays. LPS fraction and purified fimbriae from P gingivalis exhibited weak activities. Cytokine production and ICAM-1 expression by gingival keratinocytes might cause accumulation and activation of neutrophils in the epithelium and, therefore, may be involved in the initiation and development of inflammation in periodontal tissues.

User Guide to the Aircraft Cumulative Probability Chart Template

DTIC Science & Technology

2009-07-01

Technology Organisation *AeroStructures Technologies DSTO-TR-2332 ABSTRACT To ensure aircraft structural integrity is maintained to an acceptable level...cracking (or failure) which may be used to assess the life of aircraft structures . RELEASE LIMITATION Approved for public release Report...ADDRESS(ES) DSTO Defence Science and Technology Organisation ,506 Lorimer St,Fishermans Bend Victoria 3207 Australia, , , 8. PERFORMING ORGANIZATION

Pathways of acetylcholine synthesis, transport and release as targets for treatment of adult-onset cognitive dysfunction.

PubMed

Amenta, F; Tayebati, S K

2008-01-01

Acetylcholine (ACh) is a neurotransmitter widely diffused in central, peripheral, autonomic and enteric nervous system. This paper has reviewed the main mechanisms of ACh synthesis, storage, and release. Presynaptic choline transport supports ACh production and release, and cholinergic terminals express a unique transporter critical for neurotransmitter release. Neurons cannot synthesize choline, which is ultimately derived from the diet and is delivered through the blood stream. ACh released from cholinergic synapses is hydrolyzed by acetylcholinesterase into choline and acetyl coenzyme A and almost 50% of choline derived from ACh hydrolysis is recovered by a high-affinity choline transporter. Parallel with the development of cholinergic hypothesis of geriatric memory dysfunction, cholinergic precursor loading strategy was tried for treating cognitive impairment occurring in Alzheimer's disease. Controlled clinical studies denied clinical usefulness of choline and lecithin (phosphatidylcholine), whereas for other phospholipids involved in choline biosynthetic pathways such as cytidine 5'-diphosphocholine (CDP-choline) or alpha-glyceryl-phosphorylcholine (choline alphoscerate) a modest improvement of cognitive dysfunction in adult-onset dementia disorders is documented. These inconsistencies have probably a metabolic explanation. Free choline administration increases brain choline availability but it does not increase ACh synthesis/or release. Cholinergic precursors to serve for ACh biosynthesis should be incorporate and stored into phospholipids in brain. It is probable that appropriate ACh precursors and other correlated molecules (natural or synthesized) could represent a tool for developing therapeutic strategies by revisiting and updating treatments/supplementations coming out from this therapeutic stalemate.

Paired-pulse facilitation and depression at unitary synapses in rat hippocampus: quantal fluctuation affects subsequent release.

PubMed Central

Debanne, D; Guérineau, N C; Gähwiler, B H; Thompson, S M

1996-01-01

1. Excitatory synaptic transmission between pairs of monosynaptically coupled pyramidal cells was examined in rat hippocampal slice cultures. Action potentials were elicited in single CA3 pyramidal cells impaled with microelectrodes and unitary excitatory postsynaptic currents (EPSCs) were recorded in whole-cell voltage-clamped CA1 or CA3 cells. 2. The amplitude of successive unitary EPSCs in response to single action potentials varied. The amplitude of EPSCs was altered by adenosine or changes in the [Mg2+]/[CA2+] ratio. We conclude that single action potentials triggered the release of multiple quanta of glutamate. 3. When two action potentials were elicited in the presynaptic cell, the amplitude of the second EPSC was inversely related to the amplitude of the first. Paired-pulse facilitation (PPF) was observed when the first EPSC was small, i.e. the second EPSC was larger than the first, whereas paired-pulse depression (PPD) was observed when the first EPSC was large. 4. The number of trials displaying PPD was greater when release probability was increased, and smaller when release probability was decreased. 5. PPD was not postsynaptically mediated because it was unaffected by decreasing ionic flux with 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) or receptor desensitization with aniracetam. 6. PPF was maximal at an interstimulus interval of 70 ms and recovered within 500 ms. Recovery from PPD occurred within 5 s. 7. We propose that multiple release sites are formed by the axon of a CA3 pyramidal cell and a single postsynaptic CA1 or CA3 cell. PPF is observed if the first action potential fails to release transmitter at most release sites. PPD is observed if the first action potential successfully triggers release at most release sites. 8. Our observations of PPF are consistent with the residual calcium hypothesis. We conclude that PPD results from a decrease in quantal content, perhaps due to short-term depletion of readily releasable vesicles. PMID:9011608

A reconnaissance geochemical study of La Primavera geothermal area, Jalisco, Mexico

USGS Publications Warehouse

Mahood, G.A.; Truesdell, A.H.; Templos, M.L.A.

1983-01-01

The Sierra La Primavera, a late Pleistocene rhyolitic caldera complex in Jalisco, Me??xico, contains fumaroles and large-discharge 65??C hot springs that are associated with faults related to caldera collapse and to later magma insurgence. The nearly-neutral, sodium bicarbonate, hot springs occur at low elevations at the margins of the complex, whereas the water-rich fumaroles are high and central. The Comisio??n Federal de Electricidad de Me??xico (CFE) has recently drilled two deep holes at the center of the Sierra (PR-1 and Pr-2) and one deep hole at the western margin. Temperatures as high as 285??C were encountered at 1160 m in PR-1, which produced fluids with 820 to 865 mg/kg chloride after flashing to one atmosphere. Nearby, PR-2 encountered temperatures to 307??C at 2000 m and yielded fluids with chloride contents fluctuating between 1100 and 1560 mg/kg after flashing. Neither of the high-temperature wells produced steam in commercial quantities. The well at the western margin of the Sierra produced fluids similar to those from the hot springs. The temperature reached a maximum of 100??C near the surface and decreased to 80??C at 2000 m. Various geothermometers (quartz conductive, Na/K, Na-K-Ca, ??18O(SO4-H2O) and D/H (steam-water) all yield temperatures of 170 ?? 20??C when applied to the hot spring waters, suggesting that these spring waters flow from a large shallow reservoir at this temperature. Because the hot springs are much less saline than the fluids recovered in PR-1 and PR-2, the mixed fluid in the shallow reservoir can contain no more than 10-20% deep fluid. This requires that most of the heat is transferred by steam. There is probably a thin vapor-dominated zone in the central part of the Sierra, through which steam and gases are transferred to the overlying shallow reservoir. Fluids from this reservoir cool from ???170??C to 65??C by conduction during the 5-7 km of lateral flow to the hot springs. ?? 1983.

Flame-ion chemistry of the lanthanide metals Ce, Pr and Nd

NASA Astrophysics Data System (ADS)

Patterson, Patricia M.; Goodings, John M.

1996-01-01

A pair of premixed, H2---O2---Ar flames of fuel-rich (FR) and fuel-lean (FL) composition, both at atmospheric pressure and 2425 K, were doped with about 10-6 mol fraction of the lanthanide metals La, Ce, Pr and Nd; from a previous study, La was used as a benchmark. The metals produce solid particles in the flames and gaseous metallic species. The latter include metallic atoms A near the flame reaction zone, but only the monoxide AO, the oxide hydroxide OAOH and, in some cases, the dioxide AO2 further downstream at equilibrium. Metallic ions (< 1% of the total metal) were observed by sampling the flames through a nozzle into a mass spectrometer. All of the observed ions can be represented by four hydrate series: (a) major signals of AO+·nH2O (n = 0-3) for La, Ce, Pr and Nd; (b) small signals of AO2H+·nH2O (n = 0-2) for Ce, Pr and Nd; (c) still smaller signals of AO2+·nH2O (n = 0, 1) for Ce, Pr and Nd in the FL flame only; and (d) tiny signals of AOH+·nH2O (n = 0, 1) for Pr and Nd in the FR flame only. The actual structures of some of these ions may not correspond to simple hydrates: e.g. AO+·H2O = A(OH)2+ = protonated OAOH; AO2H+·H2O = A(OH)3+, etc. Since hydrogen flames contain essentially no natural ionization, a major objective was to consider probable ionization mechanisms for the metals. The primary reactions include both chemi-ionization, and thermal (collisional) ionization of AO whose ionization energy is low (about 5 eV). Some of the ions are formed by secondary ion/molecule reactions including three-body hydration, proton transfer, electron (charge) transfer, H atom abstraction by radicals and oxidation. In addition, the chemical ionization of the metallic species by H3O+ was investigated. The flame-ion chemistry of these metals is discussed in detail.

Production of Insulated Footwear Using Liquid Injection Molding Equipment. 2. Instruction Manual

DTIC Science & Technology

1980-09-01

Viscosity 0 70 0 C 20 Poise Speci fic Gravity 1.04 Nonstickenstoffe release agent and Stapler Wax are commercial preparations with no typical...soluble in most organic solvents. It decomposes in acidic solvents. 2. HANDLING LUCEL-4 is intended for industrial use only. It should be handled with...SENSITIVE GLUED 3" wide (7.6 cm), 60 lb, TAPE (27 kilograms), 3" pr. SOURCE: Industrial Paper Co., Waterbury, CT 47 11. CASE Plain Kraft, Printed

Attaining Stability: A Case for Accepting a Nuclearized Iran

DTIC Science & Technology

2009-02-11

St ra te gy Re se ar ch Pr oj ec t ATTAINING STABILITY: A CASE FOR ACCEPTING A NUCLEARIZED IRAN BY BRIGADIER NAUSHAD KAYANI Pakistan Army...DISTRIBUTION STATEMENT A : Approved for Public Release. Distribution is Unlimited. Only a work of the United States Government is not subject to copyright. Based...upon the nature of a particular student-author’s employment, a paper may not be a work of the United States Government and may, in fact, be protected

All Prime Contract Awards by State or Country, Place, and Contractor, FY 87. Part 2. Agoura Hills, California-Lafayette, California.

DTIC Science & Technology

1987-01-01

OWNGRADING SCHEDULE Approved for public release 4. PERFORMING ORGANIZATION REPORT NUMBER(S) 5. MONITORING ORGANIZATION REPORT NUMBER(S) DIOR/ST11-87...Pr- 2 6a. NAME OF PERFORMING ORGANIZATION 6b. OFFICE SYMBOL 7a. NAME OF MONITORING ORGANIZATION WHS, Directorate for (if applicable) nformation...SPONSORING 1Sb. OFFICE SYMBOL 9. PROCUREMENT INSTRUMENT IDENTIFICATION NUMBER ORGANIZATION (if applicable) Sc. ADDRESS (City, State, and ZIP Code) 10. SOURCE

Passage and survival probabilities of juvenile Chinook salmon at Cougar Dam, Oregon, 2012

USGS Publications Warehouse

Beeman, John W.; Evans, Scott D.; Haner, Philip V.; Hansel, Hal C.; Hansen, Amy C.; Smith, Collin D.; Sprando, Jamie M.

2014-01-01

This report describes studies of juvenile-salmon dam passage and apparent survival at Cougar Dam, Oregon, during two operating conditions in 2012. Cougar Dam is a 158-meter tall rock-fill dam used primarily for flood control, and passes water through a temperature control tower to either a powerhouse penstock or to a regulating outlet (RO). The temperature control tower has moveable weir gates to enable water of different elevations and temperatures to be drawn through the dam to control water temperatures downstream. A series of studies of downstream dam passage of juvenile salmonids were begun after the National Oceanic and Atmospheric Administration determined that Cougar Dam was impacting the viability of anadromous fish stocks. The primary objectives of the studies described in this report were to estimate the route-specific fish passage probabilities at the dam and to estimate the survival probabilities of fish passing through the RO. The first set of dam operating conditions, studied in November, consisted of (1) a mean reservoir elevation of 1,589 feet, (2) water entering the temperature control tower through the weir gates, (3) most water routed through the turbines during the day and through the RO during the night, and (4) mean RO gate openings of 1.2 feet during the day and 3.2 feet during the night. The second set of dam operating conditions, studied in December, consisted of (1) a mean reservoir elevation of 1,507 ft, (2) water entering the temperature control tower through the RO bypass, (3) all water passing through the RO, and (4) mean RO gate openings of 7.3 feet during the day and 7.5 feet during the night. The studies were based on juvenile Chinook salmon (Oncorhynchus tshawytscha) surgically implanted with radio transmitters and passive integrated transponder (PIT) tags. Inferences about general dam passage percentage and timing of volitional migrants were based on surface-acclimated fish released in the reservoir. Dam passage and apparent survival probabilities were estimated using the Route-Specific-Survival Model with data from surface-acclimated fish released near the water surface directly upstream of the temperature control tower (treatment group) and slightly downstream of the dam (control group). In this study, apparent survival is the joint probability of surviving and migrating through the study area during the life of the transmitters. Two rearing groups were used to enable sufficient sample sizes for the studies. The groups differed in feed type, and for the December study only, the rearing location. Fish from each group were divided nearly equally among all combinations of release sites, release times, and surgeons. The sizes, travel times, and survivals of the two rearing groups were similar. There were statistical differences in fish lengths and travel times of the two groups, but they were small and likely were not biologically meaningful. There also was evidence of a difference in single-release estimates of survival between the rearing groups during the December study, but the differences had little effect on the relative survival estimates so the analyses of passage and survival were based on data from the rearing groups pooled. Conditions during the December study were more conducive to passing volitionally migrating fish than conditions during the November study. The passage percentage of the fish released in the reservoir was similar between studies (about 70 percent), but the passage occurred in a median of 1.0 day during the December study and a median of 9.3 days during the November study. More than 93 percent of the dam passage of volitionally migrating fish occurred at night during each study. This finding corroborates results of previous studies at Cougar Dam and suggests that the operating conditions at night are most important to volitionally migrating fish, given the current configuration of the dam. Most fish released near the temperature control tower passed through the RO. A total of 92.2 percent of the treatment group passed through the RO during the November study and the RO was the only route open during the December study. The assumptions of the survival model were either met or adjusted for during each study. There was little evidence that tagger skill or premature failure of radio transmitters had an effect on survival estimates. There were statistically significant differences in travel times between treatment and control groups through several of the river reaches they had in common, but the differences were typically only a few hours, and the two groups likely experienced the same in-river conditions. There was direct evidence of bias due to detection of euthanized fish with live transmitters released as part of the study design. The bias was ameliorated by adjusting the survival estimates for the probability of detecting dead fish with live transmitters, which reduced the estimated survival probabilities by about 0.02. The data and models indicated that the treatment effect was not fully expressed until the study reach terminating with Marshall Island Park on the Willamette River, a distance of 105.8 kilometers downstream of Cougar Dam. This was the first reach in which the 95-percent confidence interval of the estimated reach-specific relative survival overlapped 1.0, indicating similar survival of treatment and control groups. The median travel time of the treatment group from release to Marshall Island Park was 1.64 days during the November study and 1.36 days during the December study. The survival probability of fish that passed into the RO was greater during the December study than during the November study. The relative survival probability of fish passing through the RO was 0.4594 (standard error [SE] 0.0543) during the November study and 0.7389 (SE 0.1160) during the December study. These estimates represent relative survival probabilities from release near Cougar Dam to the Marshall Island site. The estimated survival probability of RO passage was lower than previous studies based on balloon and PIT tags, but higher than a similar study based on radio transmitters. We suggest that, apart from dam operations, the differences in survival primarily are due to the release location. We hypothesize that the balloon- and PIT-tagged fish released through a hose at a point near the RO gate opening experienced more benign conditions than the radio-tagged fish passing the RO volitionally. This hypothesis could be tested with further study. An alternative hypothesis is that some live fish remained within the study area beyond the life of their radio transmitter. The results from these and previous studies indicate that entrainment and survival of juvenile salmonids passing Cougar Dam varies with dam operating conditions. The condition most conducive to dam passage has been the discharge and low pool elevation condition tested during December 2012. That condition included large RO gate openings and was the condition with the highest dam passage survival.

Dengue Surveillance in Veterans Affairs Healthcare Facilities, 2007–2010

PubMed Central

Schirmer, Patricia L.; Lucero-Obusan, Cynthia A.; Benoit, Stephen R.; Santiago, Luis M.; Stanek, Danielle; Dey, Achintya; Martinez, Mirsonia; Oda, Gina; Holodniy, Mark

2013-01-01

Background Although dengue is endemic in Puerto Rico (PR), 2007 and 2010 were recognized as epidemic years. In the continental United States (US), outside of the Texas-Mexico border, there had not been a dengue outbreak since 1946 until dengue re-emerged in Key West, Florida (FL), in 2009–2010. The objective of this study was to use electronic and manual surveillance systems to identify dengue cases in Veterans Affairs (VA) healthcare facilities and then to clinically compare dengue cases in Veterans presenting for care in PR and in FL. Methodology Outpatient encounters from 1/2007–12/2010 and inpatient admissions (only available from 10/2009–12/2010) with dengue diagnostic codes at all VA facilities were identified using VA's Electronic Surveillance System for Early Notification of Community-based Epidemics (ESSENCE). Additional case sources included VA data from Centers for Disease Control and Prevention BioSense and VA infection preventionists. Case reviews were performed. Categorical data was compared using Mantel-Haenszel or Fisher Exact tests and continuous variables using t-tests. Dengue case residence was mapped. Findings Two hundred eighty-eight and 21 PR and FL dengue cases respectively were identified. Of 21 FL cases, 12 were exposed in Key West and 9 were imported. During epidemic years, FL cases had significantly increased dengue testing and intensive care admissions, but lower hospitalization rates and headache or eye pain symptoms compared to PR cases. There were no significant differences in clinical symptoms, laboratory abnormalities or outcomes between epidemic and non-epidemic year cases in FL and PR. Confirmed/probable cases were significantly more likely to be hospitalized and have thrombocytopenia or leukopenia compared to suspected cases. Conclusions Dengue re-introduction in the continental US warrants increased dengue surveillance and education in VA. Throughout VA, under-testing of suspected cases highlights the need to emphasize use of diagnostic testing to better understand the magnitude of dengue among Veterans. PMID:23516642

A single-phase white light emitting Pr3+ doped Ba2CaWO6 phosphor: synthesis, photoluminescence and optical properties

NASA Astrophysics Data System (ADS)

Sreeja, E.; Vidyadharan, Viji; Jose, Saritha K.; George, Anns; Joseph, Cyriac; Unnikrishnan, N. V.; Biju, P. R.

2018-04-01

Pr3+ doped Ba2CaWO6 phosphor were prepared by traditional high-temperature solid-state reaction technique. The structure evolution was systematically investigated by X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy (EDS), Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and transmission electron microscopy (TEM) analysis. The X-ray powder diffraction patterns indicate that the prepared phosphors crystallized in the cubic double-perovskite structure. The functional groups were identified using FTIR spectra and the elements present in the composition were confirmed by the EDS profile. The morphology of the phosphor was identified using SEM and TEM analysis. The PL spectra illustrated that these phosphors could be efficiently excited by charge transfer band of host and the maximum luminescence intensity was observed at 0.06 wt% of Pr3+ ion. Upon the charge transfer band excitation, emission spectra showed peaks at 489, 532, 647, 685 and 737 nm corresponding to 3P0→3H4, 3P1→3H5, 3P0→3F2, 3P0→3F3 and 3P0→3F4 transitions respectively. The concentration quenching of Ba2CaWO6:Pr3+ phosphor can be mainly attributed to dipole-dipole interaction. The CIE coordinates were estimated to be close to the white region. The decay curves are well fitted with double exponential decay models. The standard and modified Judd-Ofelt (JO) theories were used to determine the Judd-Ofelt intensity parameters, radiative transition probabilities and branching ratios. The optical properties indicate that Ba2CaWO6:Pr3+ phosphors can produce white light emission from a single phase host and its potential application for solid-state lighting and display devices.

A Prediction Model to Help with the Assessment of Adenopathy in Lung Cancer: HAL.

PubMed

O'Connell, Oisin J; Almeida, Francisco A; Simoff, Michael J; Yarmus, Lonny; Lazarus, Ray; Young, Benjamin; Chen, Yu; Semaan, Roy; Saettele, Timothy M; Cicenia, Joseph; Bedi, Harmeet; Kliment, Corrine; Li, Liang; Sethi, Sonali; Diaz-Mendoza, Javier; Feller-Kopman, David; Song, Juhee; Gildea, Thomas; Lee, Hans; Grosu, Horiana B; Machuzak, Michael; Rodriguez-Vial, Macarena; Eapen, George A; Jimenez, Carlos A; Casal, Roberto F; Ost, David E

2017-06-15

Estimating the probability of finding N2 or N3 (prN2/3) malignant nodal disease on endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in patients with non-small cell lung cancer (NSCLC) can facilitate the selection of subsequent management strategies. To develop a clinical prediction model for estimating the prN2/3. We used the AQuIRE (American College of Chest Physicians Quality Improvement Registry, Evaluation, and Education) registry to identify patients with NSCLC with clinical radiographic stage T1-3, N0-3, M0 disease that had EBUS-TBNA for staging. The dependent variable was the presence of N2 or N3 disease (vs. N0 or N1) as assessed by EBUS-TBNA. Univariate followed by multivariable logistic regression analysis was used to develop a parsimonious clinical prediction model to estimate prN2/3. External validation was performed using data from three other hospitals. The model derivation cohort (n = 633) had a 25% prevalence of malignant N2 or N3 disease. Younger age, central location, adenocarcinoma histology, and higher positron emission tomography-computed tomography N stage were associated with a higher prN2/3. Area under the receiver operating characteristic curve was 0.85 (95% confidence interval, 0.82-0.89), model fit was acceptable (Hosmer-Lemeshow, P = 0.62; Brier score, 0.125). We externally validated the model in 722 patients. Area under the receiver operating characteristic curve was 0.88 (95% confidence interval, 0.85-0.90). Calibration using the general calibration model method resulted in acceptable goodness of fit (Hosmer-Lemeshow test, P = 0.54; Brier score, 0.132). Our prediction rule can be used to estimate prN2/3 in patients with NSCLC. The model has the potential to facilitate clinical decision making in the staging of NSCLC.

Effects of the η(5)-C5H4(i)Pr Ligand on the Properties Exhibited by Its Tungsten Nitrosyl Complexes.

PubMed

Fabulyak, Diana; Baillie, Rhett A; Patrick, Brian O; Legzdins, Peter; Rosenfeld, Devon C

2016-02-15

Reaction of Na[η(5)-C5H4(i)Pr] with W(CO)6 in refluxing THF for 4 days generates a solution of Na[(η(5)-C5H4(i)Pr)W(CO)3] that when treated with N-methyl-N-nitroso-p-toluenesulfonamide at ambient temperatures affords (η(5)-C5H4(i)Pr)W(NO)(CO)2 (1) that is isolable in good yield as an analytically pure orange oil. Treatment of 1 with an equimolar amount of I2 in Et2O at ambient temperatures affords (η(5)-C5H4(i)Pr)W(NO)I2 (2) as a dark brown solid in excellent yield. Sequential treatment at low temperatures of 2 with 0.5 equiv of Mg(CH2CMe3)2 and Mg(CH2CH═CMe2)2 in Et2O produces the alkyl allyl complex, (η(5)-C5H4(i)Pr)W(NO)(CH2CMe3)(η(3)-CH2CHCMe2) (3), as a thermally sensitive yellow liquid. Complex 3 may also be synthesized, albeit in low yield, in one vessel at low temperatures by reacting 1 first with 1 equiv of PCl5 and then with the binary magnesium reagents specified above. Interestingly, similar treatment of 1 in Et2O with PCl5 and only 0.5 equiv of Mg(CH2CH═CMe2)2 results in the formation of the unusual complex (η(5)-C5H4(i)Pr)W(NO)(PCl2CMe2CH═CH2)Cl2 (4), which probably is formed via a metathesis reaction of the binary magnesium reagent with (η(5)-C5H4(i)Pr)W(NO)(PCl3)Cl2. The C-D activation of C6D6 by complex 3 has been investigated and compared to that exhibited by its η(5)-C5Me5, η(5)-C5Me4H, and η(5)-C5Me4(n)Pr analogues. Kinetic analyses of the various activations have established that the presence of the η(5)-C5H4(i)Pr ligand significantly increases the rate of the reaction, an outcome that can be attributed to a combination of steric and electronic factors. In addition, mechanistic studies have established that in solution 3 loses neopentane under ambient conditions to generate exclusively the 16e η(2)-diene intermediate complex (η(5)-C5H4(i)Pr)W(NO)(η(2)-CH2═CMeCH═CH2), which then effects the subsequent C-D activations. This behavior contrasts with that exhibited by the η(5)-C5Me5 analogue of 3 which forms both η(2)-diene and η(2)-allene intermediates upon thermolysis. Sixteen-electron (η(5)-C5H4(i)Pr)W(NO)(η(2)-CH2═CMeCH═CH2) has been isolated as its 18e PMe3 adduct. All new organometallic complexes have been characterized by conventional spectroscopic and analytical methods, and the solid-state molecular structures of two of them have been established by single-crystal X-ray crystallographic analyses.

Assessment of risk to Boeing commerical transport aircraft from carbon fibers. [fiber release from graphite/epxoy materials

NASA Technical Reports Server (NTRS)

Clarke, C. A.; Brown, E. L.

1980-01-01

The possible effects of free carbon fibers on aircraft avionic equipment operation, removal costs, and safety were investigated. Possible carbon fiber flow paths, flow rates, and transfer functions into the Boeing 707, 727, 737, 747 aircraft and potentially vulnerable equipment were identified. Probabilities of equipment removal and probabilities of aircraft exposure to carbon fiber were derived.

Natural and technologic hazardous material releases during and after natural disasters: a review.

PubMed

Young, Stacy; Balluz, Lina; Malilay, Josephine

2004-04-25

Natural disasters may be powerful and prominent mechanisms of direct and indirect hazardous material (hazmat) releases. Hazardous materials that are released as the result of a technologic malfunction precipitated by a natural event are referred to as natural-technologic or na-tech events. Na-tech events pose unique environmental and human hazards. Disaster-associated hazardous material releases are of concern, given increases in population density and accelerating industrial development in areas subject to natural disasters. These trends increase the probability of catastrophic future disasters and the potential for mass human exposure to hazardous materials released during disasters. This systematic review summarizes direct and indirect disaster-associated releases, as well as environmental contamination and adverse human health effects that have resulted from natural disaster-related hazmat incidents. Thorough examination of historic disaster-related hazmat releases can be used to identify future threats and improve mitigation and prevention efforts.

The Binomial Model in Fluctuation Analysis of Quantal Neurotransmitter Release

PubMed Central

Quastel, D. M. J.

1997-01-01

The mathematics of the binomial model for quantal neurotransmitter release is considered in general terms, to explore what information might be extractable from statistical aspects of data. For an array of N statistically independent release sites, each with a release probability p, the compound binomial always pertains, with = N

, p′ ≡ 1 - var(m)/ =

(1 + cvp2) and n′ ≡ /p′ = N/(1 + cvp2), where m is the output/stimulus and cvp2 is var(p)/

2. Unless n′ is invariant with ambient conditions or stimulation paradigms, the simple binomial (cvp = 0) is untenable and n′ is neither N nor the number of “active” sites or sites with a quantum available. At each site p = popA, where po is the output probability if a site is “eligible” or “filled” despite previous quantal discharge, and pA (eligibility probability) depends at least on the replenishment rate, po, and interstimulus time. Assuming stochastic replenishment, a simple algorithm allows calculation of the full statistical composition of outputs for any hypothetical combinations of po's and refill rates, for any stimulation paradigm and spontaneous release. A rise in n′ (reduced cvp) tends to occur whenever po varies widely between sites, with a raised stimulation frequency or factors tending to increase po's. Unlike and var(m) at equilibrium, output changes early in trains of stimuli, and covariances, potentially provide information about whether changes in reflect change in or in . Formulae are derived for variance and third moments of postsynaptic responses, which depend on the quantal mix in the signals. A new, easily computed function, the area product, gives noise-unbiased variance of a series of synaptic signals and its peristimulus time distribution, which is modified by the unit channel composition of quantal responses and if the signals reflect mixed responses from synapses with different quantal time course. PMID:9017200

Self-Awareness and Self-Monitoring of Cognitive and Behavioral Deficits in Behavioral Variant Frontotemporal Dementia, Primary Progressive Aphasia and Probable Alzheimer’s Disease

PubMed Central

Banks, Sarah; Weintraub, Sandra

2008-01-01

Lack of insight is a core diagnostic criterion for behavioral variant frontotemporal dementia (bvFTD), and is believed to be intact in the early stages of primary progressive aphasia (PPA). In other neurological conditions, symptom-specific insight has been noted, with behavioral symptoms appearing especially vulnerable to reduced insight. Different components of insight, self-awareness and self-monitoring, are also often considered separate phenomena. The current study compared insight in patients with PPA, bvFTD, and probable Alzheimer’s disease (PrAD) and a group of cognitively intact control subjects. Additionally, differences in insight for the domains primarily affected by the three types of dementia, namely, Behavior, Naming, and Memory, were assessed, and self-awareness and self-monitoring were compared. A total of 55 participants were enrolled. Participants were asked to complete self-estimate scales demonstrating their perceived ability immediately prior to, and immediately following a test in each domain of interest. Results indicated that PPA and normal control groups performed very similarly on control (Weight and Eyesight) and cognitive domains, whereas bvFTD and PrAD patients were unable to accurately assess Memory. All three diagnostic groups failed to accurately assess their behavioral symptoms, suggesting that this domain is vulnerable to loss of insight across diagnoses. Naming ability, in contrast, was either accurately assessed or underestimated in all groups. Finally, there were no notable differences between self-awareness and self-monitoring, potential explanations for this are examined. PMID:18194832

Ca2+ release by inositol-trisphosphorothioate in isolated triads of rabbit skeletal muscle.

PubMed Central

Valdivia, C; Valdivia, H H; Potter, B V; Coronado, R

1990-01-01

The effectiveness of the nonmetabolizable second messenger analogue DL-myo-inositol 1,4,5-trisphosphorothioate (IPS3) described by Cooke, A. M., R. Gigg, and B. V. L. Potter, (1987b. Jour. Chem. Soc. Chem. Commun. 1525-1526.) was examined in triads purified from rabbit skeletal muscle. A Ca2+ electrode uptake-release assay was used to determine the size and sensitivity of the IPS3-releasable pool of Ca2+ in isolated triads. Uptake was initiated by 1 mM MgATP, pCa 5.8, pH 7.5 Release was initiated when the free Ca2+ had lowered to pCa approximately 7. We found that 5-25 microM myo-inositol 1,4,5-trisphosphate (IP3), and separately IPS3, consistently released 5-20% of the Ca2+ pool actively loaded into triads. Single channel recording was used to determine if ryanodine receptor Ca2+ release channels were affected by IPS3 at the same myoplasmic Ca2+ and IPS3 concentrations. Open probability of ryanodine receptor Ca2+ release channels was monitored in triads fused to bilayers over long periods (200 s) in the absence and following addition of 30 microM IPS3 to the same channel. At myoplasmic pCa approximately 7, IPS3 had no effect in the absence of MgATP (Po = 0.0094 +/- 0.001 in control and Po = 0.01 +/- 0.006 after IPS3) and slightly increased activity in the presence of 1 mM MgATP (Po = 0.024 +/- 0.03 in control and Po = 0.05 +/- 0.03 after IPS3). Equally small effects were observed at higher myoplasmic Ca2+. The onset of channel activation by IPS3 or IP3 was slow, on the time scale 20-60 s. We suggest that in isolated triads of rabbit skeletal muscle, IP3-induced release of stored Ca2+ is probably not mediated by the opening of Ca2+ release channels. PMID:2168221

Drug interactions with neuromuscular blockers.

PubMed

Feldman, S; Karalliedde, L

1996-10-01

Drugs administered to patients undergoing anaesthesia may complicate the use of the neuromuscular blockers that are given to provide good surgical conditions. The various sites of interaction include actions on motor nerve conduction and spinal reflexes, acetylcholine (ACh) synthesis, mobilisation and release, sensitivity of the motor end plate to ACh and the ease of propagation of the motor action potential. In addition, many drugs affect the pharmacokinetics of neuromuscular blockers, especially as most drugs depend to a greater or lesser extent upon renal excretion. The clinically significant interaction between nondepolarisers and depolarisers may be due to blockade of the pre-synaptic nicotinic receptors by the depolarisers, leading to decreased ACh mobilisation and release. Synergism between nondepolarisers probably results from post-synaptic receptor mechanisms. Volatile anaesthetic agents affect the sensitivity of the motor end-plate (post-synaptic receptor blockade) in addition to having effects on pre-synaptic nicotinic function. The effects of nondepolarisers are likely to be potentiated and their action prolonged by large doses of local anaesthetics due to depression of nerve conduction, depression of ACh formation, mobilisation and release, decreases in post-synaptic receptor channel opening times and reductions in muscular contraction. Most antibacterials have effects on pre-synaptic mechanisms. Procainamide and quinidine principally block nicotinic receptor channels. Magnesium has a marked inhibitory effect on ACh release. Calcium antagonists could theoretically interfere with neurotransmitter release and muscle contractility. Phenytoin and lithium decrease ACh release, whilst corticosteroids and furosemide (frusemide) tend to increase the release of the transmitter. Ecothiopate, tacrine, organophosphates, propanidid, metoclopramide and bambuterol depress cholinesterase activity and prolong the duration of the neuromuscular block. The probability of clinically significant interactions increases in patients receiving several drugs with possible effects on neuromuscular transmission and muscle contraction.

Autonomous learning in gesture recognition by using lobe component analysis

NASA Astrophysics Data System (ADS)

Lu, Jian; Weng, Juyang

2007-02-01

Gesture recognition is a new human-machine interface method implemented by pattern recognition(PR).In order to assure robot safety when gesture is used in robot control, it is required to implement the interface reliably and accurately. Similar with other PR applications, 1) feature selection (or model establishment) and 2) training from samples, affect the performance of gesture recognition largely. For 1), a simple model with 6 feature points at shoulders, elbows, and hands, is established. The gestures to be recognized are restricted to still arm gestures, and the movement of arms is not considered. These restrictions are to reduce the misrecognition, but are not so unreasonable. For 2), a new biological network method, called lobe component analysis(LCA), is used in unsupervised learning. Lobe components, corresponding to high-concentrations in probability of the neuronal input, are orientation selective cells follow Hebbian rule and lateral inhibition. Due to the advantage of LCA method for balanced learning between global and local features, large amount of samples can be used in learning efficiently.

A maximum entropy thermodynamics of small systems.

PubMed

Dixit, Purushottam D

2013-05-14

We present a maximum entropy approach to analyze the state space of a small system in contact with a large bath, e.g., a solvated macromolecular system. For the solute, the fluctuations around the mean values of observables are not negligible and the probability distribution P(r) of the state space depends on the intricate details of the interaction of the solute with the solvent. Here, we employ a superstatistical approach: P(r) is expressed as a marginal distribution summed over the variation in β, the inverse temperature of the solute. The joint distribution P(β, r) is estimated by maximizing its entropy. We also calculate the first order system-size corrections to the canonical ensemble description of the state space. We test the development on a simple harmonic oscillator interacting with two baths with very different chemical identities, viz., (a) Lennard-Jones particles and (b) water molecules. In both cases, our method captures the state space of the oscillator sufficiently well. Future directions and connections with traditional statistical mechanics are discussed.

Fear Potentiated Startle Increases Phospholipase D (PLD) Expression/Activity and PLD-Linked Metabotropic Glutamate Receptor Mediated Post-Tetanic Potentiation in Rat Amygdala

PubMed Central

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

2016-01-01

Long-term memory (LTM) of fear stores activity dependent modifications that include changes in amygdala signaling. Previously, we identified an enhanced probability of release of glutamate mediated signaling to be important in rat fear potentiated startle (FPS), a well-established translational behavioral measure of fear. Here, we investigated short- and long-term synaptic plasticity in FPS involving metabotropic glutamate receptors (mGluRs) and associated downstream proteomic changes in the thalamic-lateral amygdala pathway (Th-LA). Aldolase A, an inhibitor of phospholipase D (PLD), expression was reduced, concurrent with significantly elevated PLD protein expression. Blocking the PLD-mGluR signaling significantly reduced PLD activity. While transmitter release probability increased in FPS, PLD-mGluR agonist and antagonist actions were occluded. In the unpaired group (UNP), blocking the PLD-mGluR increased while activating the receptor decreased transmitter release probability, consistent with decreased synaptic potentials during tetanic stimulation. FPS Post-tetanic potentiation (PTP) immediately following long-term potentiation (LTP) induction was significantly increased. Blocking PLD-mGluR signaling prevented PTP and reduced cumulative PTP probability but not LTP maintenance in both groups. These effects are similar to those mediated through mGluR7, which is co-immunoprecipitated with PLD in FPS. Lastly, blocking mGluR-PLD in the rat amygdala was sufficient to prevent behavioral expression of fear memory. Thus, our study in the Th-LA pathway provides the first evidence for PLD as an important target of mGluR signaling in amygdala fear-associated memory. Importantly, the PLD-mGluR provides a novel therapeutic target for treating maladaptive fear memories in posttraumatic stress and anxiety disorders. PMID:26748024

Vertical Profiles of Latent Heat Release Over the Global Tropics using TRMM Rainfall Products from December 1997 to November 2001

NASA Technical Reports Server (NTRS)

Tao, W.-K.; Lang, S.; Simpson, J.; Meneghini, R.; Halverson, J.; Johnson, R.; Adler, R.; Starr, David (Technical Monitor)

2002-01-01

NASA Tropical Rainfall Measuring Mission (TRMM) precipitation radar (PR) derived rainfall information will be used to estimate the four-dimensional structure of global monthly latent heating and rainfall profiles over the global tropics from December 1997 to November 2000. Rainfall, latent heating and radar reflectivity structures between El Nino (DJF 1997-98) and La Nina (DJF 1998-99) will be examined and compared. The seasonal variation of heating over various geographic locations (i.e., oceanic vs continental, Indian ocean vs west Pacific, Africa vs S. America) will also be analyzed. In addition, the relationship between rainfall, latent heating (maximum heating level), radar reflectivity and SST is examined and will be presented in the meeting. The impact of random error and bias in stratiform percentage estimates from PR on latent heating profiles is studied and will also be presented in the meeting. Additional information is included in the original extended abstract.

Pathways of fish invasions in the Mid-Atlantic region of the United States

USGS Publications Warehouse

Lapointe, Nicolas W. R.; Fuller, Pam; Neilson, Matthew; Murphy, Brian R.; Angermeier, Paul

2016-01-01

Non-native fish introductions are a major threat to biodiversity and fisheries, and occur through numerous pathways that vary regionally in importance. A key strategy for managing invasions is to focus prevention efforts on pathways posing the greatest risk of future introductions. We identified high-risk pathways for fish establishment in the Mid-Atlantic region of the United States based on estimates of probability of establishment and records of previous introductions, which were considered in the context of emerging socioeconomic trends. We used estimates of propagule pressure, species’ environmental tolerance, and size of species pool to assess the risk of establishment by pathway. Pathways varied considerably in historic importance and species composition, with the majority of species introduced intentionally via stocking (primarily for sport, forage, or biocontrol) or bait release. Bait release, private stocking, illegal introductions intended to establish reproducing populations (e.g., of sport fish), aquaculture, and the sale of live organisms all create risks for future invasions in the Mid-Atlantic region. Of these pathways, bait release probably poses the greatest risk of introductions for the Mid-Atlantic region because propagule pressure is moderate, most released species are tolerant of local environmental conditions, and the pool of species available for transplantation is large. Our findings differ considerably from studies in other regions (e.g., bait release is a dominant pathway in the Mid-Atlantic region, whereas illegal introduction of sport fish is dominant in the western US and aquarium releases are dominant in Florida), demonstrating the need for regional-scale assessments of, and management strategies for, introduction pathways.

Regular use of dental services among adults and older adults in a vulnerable region in Southern Brazil.

PubMed

Machado, Luciene Petcov; Camargo, Maria Beatriz Junqueira; Jeronymo, José Carlos Milanez; Bastos, Gisele Alsina Nader

2012-06-01

To estimate the prevalence of regular use of dental care services by adults and older adults residing in vulnerable community and to identify associated factors. A population-based cross-sectional study was carried out with 3,391 adults and older adults residing in areas of social vulnerability in Porto Alegre, Southern Brazil, from July to December of 2009. A systematic sampling method was used the selection probability proportional to the population of each of the the 121 census sectors. The outcome for regular use of dental care services was defined as regular use of dental services, regardless of the presence of dental problems. A standardized questionnaire was administered, which included demographic, socioeconomic, type of dental care services, self-perception of dental health and self-perceived needs variables. A chi-square test for heterogeneity was used for bivariate analyses, and a Poisson regression with a robust variance and Wald tests were performed for the adjusted analysis. The prevalence of regular use of dental services was 25.7%. The prevalence was higher among people with >12 years schooling (PR 2.48 [95%CI:1.96;3.15]), higher income (PR 1.95[95%CI: 1.03;1.53]), use of private health services (PR 1.43 [95%CI: 1.20;1.71]),excellent self-perceived oral health (PR 4.44 [95%CI: 3.07;6.42]) and a self-perceived need for consultation related to routine checkup (RP 2.13 [95%CI: 1.54;2.96]). Inequalities were found in the regular use of dental services. Integrated approaches that raise awareness of oral health, improve self-care and expand access to dental services, may contribute to increase the use of dental services on a regular basis.

Food Insecurity and the Negative Impact on Brazilian Children's Health-Why Does Food Security Matter for Our Future Prosperity? Brazilian National Survey (PNDS 2006/07).

PubMed

Poblacion, Ana Paula; Cook, John T; Marín-León, Leticia; Segall-Corrêa, Ana Maria; Silveira, Jonas A C; Konstantyner, Tulio; Taddei, José Augusto A C

2016-12-01

Food insecurity (FI) refers to limited or uncertain access to food resulting from financial constraints. Numerous studies have shown association between FI and adverse health outcomes among adults and children around the world, but in Brazil, such information is scarce, especially if referring to nationally representative information. To test for an independent association between FI and health outcomes. Most recent Brazilian Demographic and Health Survey using nationally representative complex probability sampling. Participants were 3923 children <5 years of age, each representing a household. Data from the validated Brazilian Food Insecurity Scale were dichotomized as food secure (food security/mild FI) or food insecure (moderate FI/severe FI). Poisson regression was used to test for associations between FI and various health indicators. Models adjusted for socioeconomic and demographic variables showed that children hospitalized for pneumonia or diarrhea were 30% more prevalent in FI households (adjusted prevalence ratio [aPR]: 1.3; 1.1-1.6). Underweight children were 40% more prevalent in FI households (aPR: 1.4; 1.1-1.7). Children who didn't eat meat and fruits and vegetables every day were 20% and 70% more prevalent in FI households (aPR: 1.2; 1.1-1.4 and aPR: 1.7; 1.3-2.3), respectively. Children who grow up in food-insecure households have been shown to have worse health conditions than those in food-secure households. Consequently, their human capital accumulation and work-life productivity are likely to be reduced in the future, leading them into adulthood less capable of generating sufficient income, resulting in a cycle of intergenerational poverty and FI. © The Author(s) 2016.

Incident and long-term HIV-1 infection among pregnant women in Brazil: Transmitted drug resistance and mother-to-child transmission.

PubMed

Lima, Yanna Andressa Ramos; Cardoso, Ludimila Paula Vaz; Reis, Mônica Nogueira da Guarda; Stefani, Mariane Martins Araújo

2016-11-01

Primary infection, seroconversion, and transmitted drug resistance (TDR) during pregnancy may influence the risk of mother-to-child-transmission (MTCT) of HIV-1 infection. This study estimated recent seroconversion, TDR rates, HIV-1 subtypes and pregnancy outcomes among 95 recently diagnosed, antiretroviral (ARV)-naïve pregnant women recruited during antenatal care in central western Brazil. Recent seroconversion was defined by BED-capture enzyme immunoassay (<155 days) and ambiguous nucleotides base calls (<1 year) in pol sequences (protease-PR and reverse transcriptase-RT regions). TDR was evaluated by the Calibrated Population Resistance tool. HIV-1 subtypes were defined by REGA and phylogenetic analyses. The median age of participants was 25 years; the median gestational age at diagnosis was 20.5 weeks. Based on serology and sequence polymorphism, recent infection was identified in 11.6% (11/95) and, 9 of them (82%), probably seroconverted during pregnancy; one MTCT case was observed among them. Three cases of stillbirth were observed among chronic infected patients (3.6%; 3/84). Moderate rate of TDR was observed (9/90, 10%, CI95% 4.7-18.1%). Subtype B was 60% (54/90), 13.3% (12/90) was subtype C, 6.7% (6/90) was subtype F1. Recombinant B(PR) /F1(RT) and F1(PR) /B(RT) viruses comprised 15.5% (14/90); B(PR) /C(RT) mosaics represented 4.4% (4/90). Seroconversion during pregnancy, late presentation to antenatal care and moderate TDR identified in this study represent significant challenges for the MTCT elimination. J. Med. Virol. 88:1936-1943, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

DNA commission of the International Society of Forensic Genetics: Recommendations on the evaluation of STR typing results that may include drop-out and/or drop-in using probabilistic methods

PubMed Central

Gill, P.; Gusmão, L.; Haned, H.; Mayr, W.R.; Morling, N.; Parson, W.; Prieto, L.; Prinz, M.; Schneider, H.; Schneider, P.M.; Weir, B.S.

2015-01-01

DNA profiling of biological material from scenes of crimes is often complicated because the amount of DNA is limited and the quality of the DNA may be compromised. Furthermore, the sensitivity of STR typing kits has been continuously improved to detect low level DNA traces. This may lead to (1) partial DNA profiles and (2) detection of additional alleles. There are two key phenomena to consider: allelic or locus ‘drop-out’, i.e. ‘missing’ alleles at one or more genetic loci, while ‘drop-in’ may explain alleles in the DNA profile that are additional to the assumed main contributor(s). The drop-in phenomenon is restricted to 1 or 2 alleles per profile. If multiple alleles are observed at more than two loci then these are considered as alleles from an extra contributor and analysis can proceed as a mixture of two or more contributors. Here, we give recommendations on how to estimate probabilities considering drop-out, Pr(D), and drop-in, Pr(C). For reasons of clarity, we have deliberately restricted the current recommendations considering drop-out and/or drop-in at only one locus. Furthermore, we offer recommendations on how to use Pr(D) and Pr(C) with the likelihood ratio principles that are generally recommended by the International Society of Forensic Genetics (ISFG) as measure of the weight of the evidence in forensic genetics. Examples of calculations are included. An Excel spreadsheet is provided so that scientists and laboratories may explore the models and input their own data. PMID:22864188

Oligomers of Amyloid β Prevent Physiological Activation of the Cellular Prion Protein-Metabotropic Glutamate Receptor 5 Complex by Glutamate in Alzheimer Disease.

PubMed

Haas, Laura T; Strittmatter, Stephen M

2016-08-12

The dysfunction and loss of synapses in Alzheimer disease are central to dementia symptoms. We have recently demonstrated that pathological Amyloid β oligomer (Aβo) regulates the association between intracellular protein mediators and the synaptic receptor complex composed of cellular prion protein (PrP(C)) and metabotropic glutamate receptor 5 (mGluR5). Here we sought to determine whether Aβo alters the physiological signaling of the PrP(C)-mGluR5 complex upon glutamate activation. We provide evidence that acute exposure to Aβo as well as chronic expression of familial Alzheimer disease mutant transgenes in model mice prevents protein-protein interaction changes of the complex induced by the glutamate analog 3,5-dihydroxyphenylglycine. We further show that 3,5-dihydroxyphenylglycine triggers the phosphorylation and activation of protein-tyrosine kinase 2-β (PTK2B, also referred to as Pyk2) and of calcium/calmodulin-dependent protein kinase II in wild-type brain slices but not in Alzheimer disease transgenic brain slices or wild-type slices incubated with Aβo. This study further distinguishes two separate Aβo-dependent signaling cascades, one dependent on extracellular Ca(2+) and Fyn kinase activation and the other dependent on the release of Ca(2+) from intracellular stores. Thus, Aβo triggers multiple distinct PrP(C)-mGluR5-dependent events implicated in neurodegeneration and dementia. We propose that targeting the PrP(C)-mGluR5 complex will reverse aberrant Aβo-triggered states of the complex to allow physiological fluctuations of glutamate signaling. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Effects of 4-aminopyridine on cardiac repolarization, PR interval, and heart rate in patients with spinal cord injury.

PubMed

Isoda, Wakana C; Segal, Jack L

2003-02-01

To determine the effects of 4-aminopyridine (4-AP) on heart rate and PR, QT, and QTc intervals in patients with longstanding spinal cord injury (SCI). Randomized, active-treatment-controlled, dose level-blinded study, with allocation concealed. University-affiliated, tertiary care medical center. Sixty otherwise healthy male and female outpatients with traumatic SCI of more than 1 year's duration. Intervention. Oral administration and dose titration to tolerance of an immediate-release formulation of 4-AP. The PR interval, heart rate, QT interval, and QTc interval obtained from standard 12-lead electrocardiograms (ECGs) at baseline (before administration of 4-AP) and after 1 month of treatment were compared. The QTc intervals were derived by using Bazett's formula (equation) incorporated into standard computerized analyses of 12-lead ECG printouts. The paired t test was performed to test for the significance of differences between means and variances. No statistically significant differences were noted in heart rate or between ECG time intervals measured at baseline and after 1 month of treatment with 4-AP among all patients with SCI or between subgroups stratified by injury level (tetraplegia, paraplegia) or sex. During the 1-month period that 4-AP was administered, the heart rate and PR, QT, and QTc intervals all remained unchanged and stayed well within normal range in comparison to literature-derived control values. 4-Aminopyridine does not appear to influence the length of cardiac time intervals or heart rate and, hence, is unlikely to cause potentially life-threatening ventricular dysrrhythmias when administered long-term and taken orally in dosages of up to 30 mg/day. Specifically, cardiac repolarization (QTc interval) is unaffected in patients with SCI who continuously receive 4-AP for up to 1 month.

Critical spreading dynamics of parity conserving annihilating random walks with power-law branching

NASA Astrophysics Data System (ADS)

Laise, T.; dos Anjos, F. C.; Argolo, C.; Lyra, M. L.

2018-09-01

We investigate the critical spreading of the parity conserving annihilating random walks model with Lévy-like branching. The random walks are considered to perform normal diffusion with probability p on the sites of a one-dimensional lattice, annihilating in pairs by contact. With probability 1 - p, each particle can also produce two offspring which are placed at a distance r from the original site following a power-law Lévy-like distribution P(r) ∝ 1 /rα. We perform numerical simulations starting from a single particle. A finite-time scaling analysis is employed to locate the critical diffusion probability pc below which a finite density of particles is developed in the long-time limit. Further, we estimate the spreading dynamical exponents related to the increase of the average number of particles at the critical point and its respective fluctuations. The critical exponents deviate from those of the counterpart model with short-range branching for small values of α. The numerical data suggest that continuously varying spreading exponents sets up while the branching process still results in a diffusive-like spreading.

Making the cut: Depression screening in urban general hospital clinics for culturally diverse Latino populations.

PubMed

Gutnick, Damara; Siegel, Carole; Laska, Eugene; Wanderling, Joseph; Wagner, Ellen Cogen; Haugland, Gary; Conlon, Mary K

We examined whether the cut-point 10 for the Patient Health Questionnaire-9 (PHQ9) depression screen used in primary care populations is equally valid for Mexicans (M), Ecuadorians (E), Puerto Ricans (PR) and non-Hispanic whites (W) from inner-city hospital-based primary care clinics; and whether stressful life events elevate scores and the probability of major depressive disorder (MDD). Over 18-months, a sample of persons from hospital clinics with a positive initial PHQ2 and a subsequent PHQ9 were administered a stressful life event questionnaire and a Structured Clinical Interview to establish an MDD diagnosis, with oversampling of those between 8 and 12: (n=261: 75 E, 71 M, 51 PR, 64 W). For analysis, the sample was weighted using chart review (n=368) to represent a typical clinic population. Receiver Operating Characteristics analysis selected cut-points maximizing sensitivity (Sn) plus specificity (Sp). The optimal cut-point for all groups was 13 with the corresponding Sn and Sp estimates for E=(Sn 73%, Sp 71%), M=(76%, 81%), PR=(81%, 63%) and W=(80%, 74%). Stressful life events impacted screen scores and MDD diagnosis. Elevating the PHQ9 cut-point for inner-city Latinos as well as whites is suggested to avoid high false positive rates leading to improper treatment with clinical and economic consequences. Copyright © 2016 Elsevier Inc. All rights reserved.

Attenuation of cocaine self-administration by chronic oral phendimetrazine in rhesus monkeys.

PubMed

Czoty, P W; Blough, B E; Fennell, T R; Snyder, R W; Nader, M A

2016-06-02

Chronic treatment with the monoamine releaser d-amphetamine has been consistently shown to decrease cocaine self-administration in laboratory studies and clinical trials. However, the abuse potential of d-amphetamine is an obstacle to widespread clinical use. Approaches are needed that exploit the efficacy of the agonist approach but avoid the abuse potential associated with dopamine releasers. The present study assessed the effectiveness of chronic oral administration of phendimetrazine (PDM), a pro-drug for the monoamine releaser phenmetrazine (PM), to decrease cocaine self-administration in four rhesus monkeys. Each day, monkeys pressed a lever to receive food pellets under a 50-response fixed-ratio (FR) schedule of reinforcement and self-administered cocaine (0.003-0.56 mg/kg per injection, i.v.) under a progressive-ratio (PR) schedule in the evening. After completing a cocaine self-administration dose-response curve, sessions were suspended and PDM was administered (1.0-9.0 mg/kg, p.o., b.i.d.). Cocaine self-administration was assessed using the PR schedule once every 7 days while food-maintained responding was studied daily. When a persistent decrease in self-administration was observed, the cocaine dose-effect curve was re-determined. Daily PDM treatment decreased cocaine self-administration by 30-90% across monkeys for at least 4 weeks. In two monkeys, effects were completely selective for cocaine. Tolerance developed to initial decreases in food-maintained responding in the third monkey and in the fourth subject, fluctuations were observed that were lower in magnitude than effects on cocaine self-administration. Cocaine dose-effect curves were shifted down and/or rightward in three monkeys. These data provide further support for the use of agonist medications for cocaine abuse, and indicate that the promising effects of d-amphetamine extend to a more clinically viable pharmacotherapy. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Uncertainty Models for Knowledge-Based Systems

DTIC Science & Technology

1991-08-01

sists of the subsets of a constituting the a-algebra A such that = Pr Note that the sum of (A over A in general exceeds unity or is divergent . (Of...f is a g.d.f. Hence, again PCf = -Pf I - Pf = Cf Now, analogous to Sklar’s Theroem mentioned previously, define ior any n a 1 C n U (SBVq n ((sBVq [0...then extends the following basic theroem in a natural way to the above example: The entropy of a joint probability function which has independent

Erosional Equivalences of Levees: Steady and Intermittent Wave Overtopping

DTIC Science & Technology

2010-01-01

represents the proportion of the individual wave period for which the runup exceeds the levee crest. We require that the average Still Water Level1 tan α zc R... Levee Fig. 5. Definition sketch for potential wave runup. Runu p , R Centroids of Equal Runup Probabilities R m in = z c Pr ob ab ili ty D en si...Erosional equivalences of levees : Steady and intermittent wave overtopping R.G. Dean a, J.D. Rosati b, T.L. Walton c, B.L. Edge d , a Department of

Understanding Information Uncertainty within the Context of a Net-Centric Data Model: A Mine Warfare Example

DTIC Science & Technology

2008-06-01

key assumption in the calculation of the primary MIW MOEs of the estimated risk to a transitor and the expected time required to clear all of the mines...primary MOE of Risk, or Probability of Damage to a Ship Transitor , is calculated by using information in the highlighted circle on the left, to include...percent clearance achieved. 0 E( ) Pr( | , ) r R r r m p ∞ = = ∗∑ (0.2) Risk can be calculated for each transitor given the expected number of

C-H activations at iridium(I) square-planar complexes promoted by a fifth ligand.

PubMed

Martín, Marta; Torres, Olga; Oñate, Enrique; Sola, Eduardo; Oro, Luis A

2005-12-28

In the presence of ligands such as acetonitrile, ethylene, or propylene, the Ir(I) complex [Ir(1,2,5,6-eta-C8H12)(NCMe)(PMe3)]BF4 (1) transforms into the Ir(III) derivatives [Ir(1-kappa-4,5,6-eta-C8H12)(NCMe)(L)(PMe3)]BF4 (L = NCMe, 2; eta2-C2H4, 3; eta2-C3H6, 4), respectively, through a sequence of C-H oxidative addition and insertion elementary steps. The rate of this transformation depends on the nature of L and, in the case of NCMe, the pseudo-first-order rate constants display a dependence upon ligand concentration suggesting the formation of five-coordinate reaction intermediates. A similar reaction between 1 and vinyl acetate affords the Ir(III) complex [Ir(1-kappa-4,5,6-eta-C8H12){kappa-O-eta2-OC(Me)OC2H3}(PMe3)]BF4 (7) via the isolable five-coordinate Ir(I) compound [Ir(1,2,5,6-eta-C8H12){kappa-O-eta2-OC(Me)OC2H3}(PMe3)]BF4 (6). DFT (B3LYP) calculations in model complexes show that reactions initiated by acetonitrile or ethylene five-coordinate adducts involve C-H oxidative addition transition states of lower energy than that found in the absence of these ligands. Key species in these ligand-assisted transformations are the distorted (nonsquare-planar) intermediates preceding the intramolecular C-H oxidative addition step, which are generated after release of one cyclooctadiene double bond from the five-coordinate species. The feasibility of this mechanism is also investigated for complexes [IrCl(L)(PiPr3)2] (L = eta2-C2H4, 27; eta2-C3H6, 28). In the presence of NCMe, these complexes afford the C-H activation products [IrClH(CH=CHR)(NCMe)(PiPr3)2] (R = H, 29; Me, 30) via the common cyclometalated intermediate [IrClH{kappa-P,C-P(iPr)2CH(CH3)CH2}(NCMe)(PiPr3)] (31). The most effective C-H oxidative addition mechanism seems to involve three-coordinate intermediates generated by photochemical release of the alkene ligand. However, in the absence of light, the reaction rates display dependences upon NCMe concentration again indicating the intermediacy of five-coordinate acetonitrile adducts.

Evaluation of a mark-recapture method for estimating mortality and migration rates of stratified populations

USGS Publications Warehouse

Dorazio, R.M.; Rago, P.J.

1991-01-01

We simulated mark–recapture experiments to evaluate a method for estimating fishing mortality and migration rates of populations stratified at release and recovery. When fish released in two or more strata were recovered from different recapture strata in nearly the same proportions, conditional recapture probabilities were estimated outside the [0, 1] interval. The maximum likelihood estimates tended to be biased and imprecise when the patterns of recaptures produced extremely "flat" likelihood surfaces. Absence of bias was not guaranteed, however, in experiments where recapture rates could be estimated within the [0, 1] interval. Inadequate numbers of tag releases and recoveries also produced biased estimates, although the bias was easily detected by the high sampling variability of the estimates. A stratified tag–recapture experiment with sockeye salmon (Oncorhynchus nerka) was used to demonstrate procedures for analyzing data that produce biased estimates of recapture probabilities. An estimator was derived to examine the sensitivity of recapture rate estimates to assumed differences in natural and tagging mortality, tag loss, and incomplete reporting of tag recoveries.

Fall Chinook Salmon Survival and Supplementation Studies in the Snake River and Lower Snake River Reservoirs, 1995 Annual Report.

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

Williams, John G.; Bjomn

1997-03-01

In 1994, the National Marine Fisheries Service and the US Fish and Wildlife Service began a cooperative study to investigate migrational characteristics of subyearling fall chinook salmon in the Snake River. The primary study objectives were to (1) determine the feasibility of estimating detection and passage survival probabilities of natural and hatchery subyearling fall chinook salmon released in the Snake River (Chapter 1), (2) investigate relationships between detection and passage survival probabilities and travel time of subyearling fall chinook salmon and environmental influences such as flow volume and water temperature (Chapter 1), (3) monitor and evaluate dispersal of hatchery subyearlingmore » chinook salmon into nearshore rearing areas used by natural fish (Chapter 2), and (4) monitor and evaluate travel time to Lower Granite Dam, growth from release in the Snake River to recapture at Lower Granite Dam, ATPase levels of fish recaptured at Lower Granite Dam, and survival from release in the free-flowing Snake River to the tailrace of Lower Granite Dam (Chapter 2).« less

Volatile element chemistry of selected lunar, meteoritic, and terrestrial samples

NASA Technical Reports Server (NTRS)

Simoneit, B. R.; Christiansen, P. C.; Burlingame, A. L.

1973-01-01

Using vacuum pyrolysis and high resolution mass spectrometry, a study is made of the gas release patterns of representative lunar samples, meteorites, terrestrial samples, and synthetic samples doped with various sources of carbon and nitrogen. The pyrolytic gas evolution patterns were intercorrelated, allowing an assessment of the possible sources of the volatilizable material in the lunar samples to be made. Lightly surface adsorbed species and more strongly chemisorbed species are released from ambient to 300 C and from 300 to 500 C, respectively. The low-temperature volatiles (less than 500 C) derived from various chondrites correlate well with the gas evolution patterns of volatile-rich samples, as for example 74220 and 61221. Solar wind entrapped species and molecules derived from reactions probably in the grain surfaces are evolved from about 500 to 700 C, respectively. Solar wind implanted C, N, and S species are generated from 750 to 1150 C, probably by reaction with the mineral matrix during the annealing process. Possible indigenous and/or refractory carbide, nitride, and sulfide C, N, and S are released in the region from 1200 C to fusion.

An operational system of fire danger rating over Mediterranean Europe

NASA Astrophysics Data System (ADS)

Pinto, Miguel M.; DaCamara, Carlos C.; Trigo, Isabel F.; Trigo, Ricardo M.

2017-04-01

A methodology is presented to assess fire danger based on the probability of exceedance of prescribed thresholds of daily released energy. The procedure is developed and tested over Mediterranean Europe, defined by latitude circles of 35 and 45°N and meridians of 10°W and 27.5°E, for the period 2010-2016. The procedure involves estimating the so-called static and daily probabilities of exceedance. For a given point, the static probability is estimated by the ratio of the number of daily fire occurrences releasing energy above a given threshold to the total number of occurrences inside a cell centred at the point. The daily probability of exceedance which takes into account meteorological factors by means of the Canadian Fire Weather Index (FWI) is in turn estimated based on a Generalized Pareto distribution with static probability and FWI as covariates of the scale parameter. The rationale of the procedure is that small fires, assessed by the static probability, have a weak dependence on weather, whereas the larger fires strongly depend on concurrent meteorological conditions. It is shown that observed frequencies of exceedance over the study area for the period 2010-2016 match with the estimated values of probability based on the developed models for static and daily probabilities of exceedance. Some (small) variability is however found between different years suggesting that refinements can be made in future works by using a larger sample to further increase the robustness of the method. The developed methodology presents the advantage of evaluating fire danger with the same criteria for all the study area, making it a good parameter to harmonize fire danger forecasts and forest management studies. Research was performed within the framework of EUMETSAT Satellite Application Facility for Land Surface Analysis (LSA SAF). Part of methods developed and results obtained are on the basis of the platform supported by The Navigator Company that is currently providing information about fire meteorological danger for Portugal for a wide range of users.

Critical Role of Airway Macrophages in Modulating Disease Severity during Influenza Virus Infection of Mice ▿

PubMed Central

Tate, Michelle D.; Pickett, Danielle L.; van Rooijen, Nico; Brooks, Andrew G.; Reading, Patrick C.

2010-01-01

Airway macrophages provide a first line of host defense against a range of airborne pathogens, including influenza virus. In this study, we show that influenza viruses differ markedly in their abilities to infect murine macrophages in vitro and that infection of macrophages is nonproductive and no infectious virus is released. Virus strain BJx109 (H3N2) infected macrophages with high efficiency and was associated with mild disease following intranasal infection of mice. In contrast, virus strain PR8 (H1N1) was poor in its ability to infect macrophages and highly virulent for mice. Depletion of airway macrophages by clodronate-loaded liposomes led to the development of severe viral pneumonia in BJx109-infected mice but did not modulate disease severity in PR8-infected mice. The severe disease observed in macrophage-depleted mice infected with BJx109 was associated with exacerbated virus replication in the airways, leading to severe airway inflammation, pulmonary edema, and vascular leakage, indicative of lung injury. Thymic atrophy, lymphopenia, and dysregulated cytokine and chemokine production were additional systemic manifestations associated with severe disease. Thus, airway macrophages play a critical role in limiting lung injury and associated disease caused by BJx109. Furthermore, the inability of PR8 to infect airway macrophages may be a critical factor contributing to its virulence for mice. PMID:20504924

Nicotine Modulates Multiple Regions in the Limbic Stress Network Regulating Activation of Hypophysiotrophic Neurons in Hypothalamic Paraventricular Nucleus

PubMed Central

Yu, Guoliang; Sharp, Burt M.

2012-01-01

Nicotine intake affects CNS responses to stressors. We reported that nicotine self-administration (SA) augmented the hypothalamo-pituitary-adrenal (HPA) stress response, in part due to altered neurotransmission and neuropeptide expression within hypothalamic paraventricular nucleus (PVN). Limbic-PVN interactions involving medial prefrontal cortex, amygdala, bed nucleus of the stria terminalis (BST) greatly impact the HPA stress response. Therefore, we investigated the effects of nicotine SA on stress-induced neuronal activation in limbic-PVN network, using c-Fos protein immunohistochemistry and retrograde tracing. Nicotine decreased stress-induced c-Fos in prelimbic cortex (PrL), anteroventral BST (avBST), and peri-PVN; but increased c-Fos induction in medial amygdala (MeA), locus coeruleus, and PVN. Fluoro-gold (FG) was injected into avBST or PVN, since GABAergic neurons in avBST projecting to PVN corticotrophin-releasing factor (CRF) neurons relay information from both PrL glutamatergic and MeA GABAergic neurons. The stress-induced c-Fos expression in retrograde-labeled FG+ neurons was decreased in PrL by nicotine, but increased in MeA, and also reduced in avBST. Therefore, within limbic-PVN network, nicotine SA exerts selective regional effects on neuronal activation by stress. These findings expand the mechanistic framework by demonstrating altered limbic-BST-PVN interactions underlying the disinhibition of PVN CRF neurons, an essential component of the amplified HPA response to stress by nicotine. PMID:22578217

Effects of pathogen reduction systems on platelet microRNAs, mRNAs, activation, and function

PubMed Central

Osman, Abdimajid; Hitzler, Walter E.; Meyer, Claudius U.; Landry, Patricia; Corduan, Aurélie; Laffont, Benoit; Boilard, Eric; Hellstern, Peter; Vamvakas, Eleftherios C.

2015-01-01

Pathogen reduction (PR) systems for platelets, based on chemically induced cross-linking and inactivation of nucleic acids, potentially prevent transfusion transmission of infectious agents, but can increase clinically significant bleeding in some clinical studies. Here, we documented the effects of PR systems on microRNA and mRNA levels of platelets stored in the blood bank, and assessed their impact on platelet activation and function. Unlike platelets subjected to gamma irradiation or stored in additive solution, platelets treated with Intercept (amotosalen + ultraviolet-A [UVA] light) exhibited significantly reduced levels of 6 of the 11 microRNAs, and 2 of the 3 anti-apoptotic mRNAs (Bcl-xl and Clusterin) that we monitored, compared with platelets stored in plasma. Mirasol (riboflavin + UVB light) treatment of platelets did not produce these effects. PR neither affected platelet microRNA synthesis or function nor induced cross-linking of microRNA-sized endogenous platelet RNA species. However, the reduction in the platelet microRNA levels induced by Intercept correlated with the platelet activation (p < 0.05) and an impaired platelet aggregation response to ADP (p < 0.05). These results suggest that Intercept treatment may induce platelet activation, resulting in the release of microRNAs and mRNAs from platelets. The clinical implications of this reduction in platelet nucleic acids secondary to Intercept remain to be established. PMID:24749844

The relationship of body size to survivorship of hatchling snapping turtles (Chelydra serpentina): an evaluation of the "bigger is better" hypothesis.

PubMed

Congdon, Justin D; Nagle, Roy D; Dunham, Arthur E; Beck, Chirstopher W; Kinney, Owen M; Yeomans, S Rebecca

1999-11-01

In many organisms, body size is positively correlated with traits that are presumably related to fitness. If directional selection frequently favors larger offspring (the "bigger is better" hypothesis), the results of such selection should be detectable with field experiments. We tested the "bigger is better" hypothesis in hatchling snapping turtles (Chelydra serpentina) by conducting one long-term and three short-term experiments on the University of Michigan E.S. George Reserve in southeastern Michigan. In the fall of 1995 and 1996, we released hatchlings at artificial nests separated from the nearest wetland by fences. We recorded the proportion of hatchlings recaptured, the time it took hatchlings to move to fences from artificial nests 45, 55, and 80 m away, and dispersion along the fence. We determined whether the response variables and probability of recapture at fences were associated with hatchling body size. During 1995, average travel times of hatchlings from the experimental nests were not related to distance from the fence; however, time to recapture was positively correlated with dispersion from the zero point on the fence, and the maximum time to reach the fence was almost twice as long for hatchlings from the 80-m nest compared to those from the 45-m nest. Sixty-seven percent of the hatchlings reached the fence and the proportions doing so from each nest were not different. Body size was not significantly related to probability of recapture in either of the 1995 experiments. In 1996, 59% of released hatchlings were recaptured. Time to recapture was not related to dispersion from the zero point or to body size. Cubic spline analysis suggested stabilizing selection on body size. We also conducted a set of long-term hatchling release experiments between 1980-1993 to compare the survival of hatchlings released at nest sites to that of hatchlings released directly into marshes, and we looked for relationships between survivorship and hatchling body size. During 7 years in which more than 30 hatchlings were released, 413 hatchlings were released directly into the marsh and 262 were released at nests: their probability of survival did not differ. Over all years, for both release groups combined and for each group separately, survival was not related to body size. In 1983 alone, survival was also not related to body size for either group or for both groups combined. In our three short-term experiments and one long-term experiment, we found no evidence to support the "bigger is better" hypothesis. When selection on body size did occur, selection was stabilizing, not directional for larger size.

Release of salicylic acid, diclofenac acid and diclofenac acid salts from isotropic and anisotropic nonionic surfactant systems across rat skin.

PubMed

Gabboun, N H; Najib, N M; Ibrahim, H G; Assaf, S

2001-01-05

Release of salicylic acid, diclofenac acid, diclofenac diethylamine and diclofenac sodium, from lyotropic structured systems, namely; neat and middle liquid crystalline phases, across mid-dorsal hairless rat skin into aqueous buffer were studied. Release results were compared with those from the isotropic systems. The donor systems composed of the surfactant polyoxyethylene (20) isohexadecyl ether, HCl buffer of pH 1 or distilled water and the specific drug. High performance liquid chromatography (HPLC) methods were used to monitor the transfer of the drugs across the skin barrier. Results indicated that the rate-determining step in the transport process was the release of the drug from the specified donor system. Further, apparent zero order release was demonstrated with all systems. Except for diclofenac sodium, drug fluxes decreased as the donor medium changed from isotropic to anisotropic. The decrease in fluxes was probably due to the added constrains on the movement of drug molecules. By changing the anisotropic donor medium from neat to middle phase, drug flux decreased in case of salicylic acid and diclofenac sodium. In the mean time, flux increased in case of the diethylamine salt and appeared nearly similar in case of diclofenac acid. Rates of drug transfer across the skin from the anisotropic donors seemed to be largely controlled by the entropy contribution to the transport process. The type and extent of drug-liquid crystal interactions probably influenced the latter.

New approach for point pollution source identification in rivers based on the backward probability method.

PubMed

Wang, Jiabiao; Zhao, Jianshi; Lei, Xiaohui; Wang, Hao

2018-06-13

Pollution risk from the discharge of industrial waste or accidental spills during transportation poses a considerable threat to the security of rivers. The ability to quickly identify the pollution source is extremely important to enable emergency disposal of pollutants. This study proposes a new approach for point source identification of sudden water pollution in rivers, which aims to determine where (source location), when (release time) and how much pollutant (released mass) was introduced into the river. Based on the backward probability method (BPM) and the linear regression model (LR), the proposed LR-BPM converts the ill-posed problem of source identification into an optimization model, which is solved using a Differential Evolution Algorithm (DEA). The decoupled parameters of released mass are not dependent on prior information, which improves the identification efficiency. A hypothetical case study with a different number of pollution sources was conducted to test the proposed approach, and the largest relative errors for identified location, release time, and released mass in all tests were not greater than 10%. Uncertainty in the LR-BPM is mainly due to a problem with model equifinality, but averaging the results of repeated tests greatly reduces errors. Furthermore, increasing the gauging sections further improves identification results. A real-world case study examines the applicability of the LR-BPM in practice, where it is demonstrated to be more accurate and time-saving than two existing approaches, Bayesian-MCMC and basic DEA. Copyright © 2018 Elsevier Ltd. All rights reserved.

Conformational landscape of a virus by single-particle X-ray scattering

DOE PAGES

Hosseinizadeh, Ahmad; Mashayekhi, Ghoncheh; Copperman, Jeremy; ...

2017-08-14

Using a manifold-based analysis of experimental diffraction snapshots from an X-ray free electron laser, we determine the three-dimensional structure and conformational landscape of the PR772 virus to a detector-limited resolution of 9 nm. Our results indicate that a single conformational coordinate controls reorganization of the genome, growth of a tubular structure from a portal vertex and release of the genome. Furthermore, these results demonstrate that single-particle X-ray scattering has the potential to shed light on key biological processes.

Reactions of the linear tetranuclear complex Ru sub 4 (CO) sub 10 (CH sub 3 C double bond C(H)C(H) double bond N-i-Pr) sub 2 with oxidizing reagents. Syntheses of halide-bridged (Ru(CO) sub 2 X(CH sub 3 C double bond C(H)C(H) double bond N-i-Pr)) sub 2 and fac-Ru(CO) sub 3 X(CH sub 3 C double bond C(H)C(H) double bond N-i-Pr)

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

Mul, W.P.; Elsevier, C.J.; van Leijen, M.

1991-01-01

The linear tetranuclear complex Ru{sub 4}(CO){sub 10}(CH{sub 3}C{double bond}C(H)C(H){double bond}N-i-Pr){sub 2} (1), containing two {eta}{sup 5}-azaruthenacyclopentadienyl systems, reacts with oxidizing reagents (I{sub 2}, Br{sub 2}, NBS, CCl{sub 4}) at elevated temperatures (40-90C) in heptane or benzene to give the new dimeric halide-bridged organoruthenium(II) complexes (Ru(CO){sub 2}X(CH{sub 3}C{double bond}C(H)C(H){double bond}N-i-Pr)){sub 2} (X = I (3a), X = Br (3b), Cl (3c); yield 30-80%) together with (Ru(CO){sub 3}X{sub 2}){sub 2}. The reactions of 1 with CX{sub 4} (X = I, Br, Cl) are accelerated by CO, probably because Ru{sub 4}(CO){sub 12}(CH{sub 3}C{double bond}C(H)C(H){double bond}N-i-Pr){sub 2} (5), which contains two unbridged metal-metal bonds,more » is formed prior to oxidation. The halide-bridged dimers 3a-c are obtained as mixtures of four isomers, the configurations of which are discussed. Splitting of the halide bridges takes place when a solution of 3a-c is saturated with CO, whereby mononuclear fac-Ru(CO){sub 3}X(CH{sub 3}C{double bond}C(H)C(H){double bond}N-i-Pr) (4a-c) is obtained. This process is reversible; ie., passing a stream of nitrogen through a solution of 4a-c or removal of the solvent under vacuum causes the reverse reaction with reformation of 3a-c. Compounds 3a-c and 4a-c have been characterized by IR (3, 4), FD mass (3), {sup 1}H (3, 4), and {sup 13}C{l brace}H{r brace} NMR (4) spectroscopy and satisfactory elemental analyses have been obtained for 3a-c. Compounds 3 and 4 are suitable precursors for the preparation of new homo- and heteronuclear transition-metal complexes.« less

From the Cover: 7,8-Dihydroxyflavone Rescues Lead-Induced Impairment of Vesicular Release: A Novel Therapeutic Approach for Lead Intoxicated Children.

PubMed

Zhang, Xiao-Lei; McGlothan, Jennifer L; Miry, Omid; Stansfield, Kirstie H; Loth, Meredith K; Stanton, Patric K; Guilarte, Tomás R

2018-01-01

Childhood lead (Pb2+) intoxication is a public health problem of global proportion. Lead exposure during development produces multiple effects on the central nervous system including impaired synapse formation, altered synaptic plasticity, and learning deficits. In primary hippocampal neurons in culture and hippocampal slices, Pb2+ exposure inhibits vesicular release and reduces the number of fast-releasing sites, an effect associated with Pb2+ inhibition of NMDA receptor-mediated trans-synaptic Brain-Derived Neurotrophic Factor (BDNF) signaling. The objective of this study was to determine if activation of TrkB, the cognate receptor for BDNF, would rescue Pb2+-induced impairments of vesicular release. Rats were chronically exposed to Pb2+ prenatally and postnatally until 50 days of age. This chronic Pb2+ exposure paradigm enhanced paired-pulse facilitation of synaptic potentials in Schaffer collateral-CA1 synapses in the hippocampus, a phenomenon indicative of reduced vesicular release probability. Decreased vesicular release probability was confirmed by both mean-variance analysis and direct 2-photon imaging of vesicular release from hippocampal slices of rats exposed to Pb2+in vivo. We also found a Pb2+-induced impairment of calcium influx in Schaffer collateral-CA1 synaptic terminals. Intraperitoneal injections of Pb2+ rats with the TrkB receptor agonist 7,8-dihydroxyflavone (5 mg/kg) for 14-15 days starting at postnatal day 35, reversed all Pb2+-induced impairments of presynaptic transmitter release at Schaffer collateral-CA1 synapses. This study demonstrates for the first time that in vivo pharmacological activation of TrkB receptors by small molecules such as 7,8-dihydroxyflavone can reverse long-term effects of chronic Pb2+ exposure on presynaptic terminals, pointing to TrkB receptor activation as a promising therapeutic intervention in Pb2+-intoxicated children. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Classification and assessment of retrieved electron density maps in coherent X-ray diffraction imaging using multivariate analysis.

PubMed

Sekiguchi, Yuki; Oroguchi, Tomotaka; Nakasako, Masayoshi

2016-01-01

Coherent X-ray diffraction imaging (CXDI) is one of the techniques used to visualize structures of non-crystalline particles of micrometer to submicrometer size from materials and biological science. In the structural analysis of CXDI, the electron density map of a sample particle can theoretically be reconstructed from a diffraction pattern by using phase-retrieval (PR) algorithms. However, in practice, the reconstruction is difficult because diffraction patterns are affected by Poisson noise and miss data in small-angle regions due to the beam stop and the saturation of detector pixels. In contrast to X-ray protein crystallography, in which the phases of diffracted waves are experimentally estimated, phase retrieval in CXDI relies entirely on the computational procedure driven by the PR algorithms. Thus, objective criteria and methods to assess the accuracy of retrieved electron density maps are necessary in addition to conventional parameters monitoring the convergence of PR calculations. Here, a data analysis scheme, named ASURA, is proposed which selects the most probable electron density maps from a set of maps retrieved from 1000 different random seeds for a diffraction pattern. Each electron density map composed of J pixels is expressed as a point in a J-dimensional space. Principal component analysis is applied to describe characteristics in the distribution of the maps in the J-dimensional space. When the distribution is characterized by a small number of principal components, the distribution is classified using the k-means clustering method. The classified maps are evaluated by several parameters to assess the quality of the maps. Using the proposed scheme, structure analysis of a diffraction pattern from a non-crystalline particle is conducted in two stages: estimation of the overall shape and determination of the fine structure inside the support shape. In each stage, the most accurate and probable density maps are objectively selected. The validity of the proposed scheme is examined by application to diffraction data that were obtained from an aggregate of metal particles and a biological specimen at the XFEL facility SACLA using custom-made diffraction apparatus.

ESO PR Highlights in 2005

NASA Astrophysics Data System (ADS)

2006-01-01

2005 was the year of Physics. It was thus also in part the year of astronomy and this is clearly illustrated by the numerous breakthroughs that were achieved, in particular using ESO's telescopes. One of the highlights was without any doubt the confirmation of the first image of an exoplanet , around the star 2M1207 (see ESO PR 12/05). ESO's telescopes also found a Neptune-mass exoplanet around a small star ( PR 30/05) - a discovery that proves crucial in the census of other planetary systems, and imaged a tiny companion in the close vicinity of the star GQ Lupi, a very young object still surrounded by a disc, with an age between 100,000 and 2 million years ( PR 09/05). Moreover, using a new high-contrast adaptive optics camera on the VLT, the NACO Simultaneous Differential Imager, or NACO SDI, astronomers were able for the first time to image a companion 120 times fainter than its star , very near the star AB Doradus A. This companion appears to be almost twice as heavy as theory predicts it to be ( PR 02/05). ESO's telescopes proved very useful in helping to solve a 30-year old puzzle . Astronomers have for the first time observed the visible light from a short gamma-ray burst (GRB). Using the 1.5m Danish telescope at La Silla (Chile), they showed that these short, intense bursts of gamma-ray emission most likely originate from the violent collision of two merging neutron stars ( PR 26/05). Additional evidence came from witnessing another event with the VLT ( PR 32/05). Also in this field, astronomers found the farthest known gamma-ray burst with ESO's VLT, observing an object with a redshift 6.3, i.e. that is seen when the Universe was less than 900 million years old ( PR 22/05). On July 4, NASA's Deep Impact spacecraft plunged onto Comet 9P/Tempel 1 with the aim to create a crater and expose pristine material from beneath the surface. For two days before and six days after, all major ESO telescopes have been observing the comet, in a coordinated fashion and in very close collaboration with the space mission' scientific team, in what was perhaps the most comprehensive ground-observing campaign of a celestial object. On this occasion, a dedicated Deep Impact at ESO web site was created, reporting on all the developments. This was not the sole contribution of ESO to the study of the solar system . The NACO SDI instrument was used to obtain outstanding images of Titan, the satellite of Saturn ( PHOT 04/05) and NACO also allowed astronomers to discover the first triple asteroid - two small asteroids orbiting a larger one known since 1866 as 87 Sylvia ( PR 21/05). 2005 was also a very important year for sub-millimetric astronomy at ESO. In July, APEX , the 12-m Atacama Pathfinder Experiment's telescope had first light ( PR 18/05) and since then, has been performing regular science observations ( PR 25/05). Moreover, two major contracts have been signed for ALMA , the Atacama Large Millimeter Array project, among which the largest-ever European industrial contract for a ground-based astronomy project ( PR 31/05 and 34/05). ESO's Very Large Telescope (VLT) proves to be a very efficient science machine that reached in April 2005, the count of more than 1000 scientific papers (see ESO PR 11/05) and the trend does not seem to change, as about 350 papers were published in 2005 based on data collected with the VLT. This efficiency was also recognised worldwide as ESO received the ComputerWorld Honors Program 21st Century Achievement Award in the Science Category ( PR 16/05). The interferometric mode of the VLT (VLTI) was able to observe with unprecedented detail the environment of two stars ( PR 29/05). The VLTI has also seen another extension of its already impressive capabilities by combining interferometrically the light from two relocatable 1.8-m Auxiliary Telescopes ( PR 06/05). ESO PR Highlights 2005 In 2005 again, many nice, amazing astronomical images have been obtained with ESO's telescopes: the super star cluster Westerlund 1 ( PR 08/05), the blob in the LMC ( PHOT 12/05), dream galaxies ( PHOT 24/05), a colossal cosmic eye ( PHOT 31/05), a monster being fed (PHOT 33/05), a perturbed family ( PHOT 34/05), and a cosmic Christmas ghost ( PHOT 42/05). All this, in addition to some images of the observatories ( PR 33/05 and PHOT 43/05). These developments are described in ESO's Press Releases, most with Press Photos, cf. the 2005 PR Index. Some of last year's ESO PR highlights may be accessed directly via the first clickable image above while some of the Press Photos are available via the second clickable image.

Radiological criteria for underground nuclear tests

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

Malik, J.S.; Brownlee, R.R.; Costa, C.F.

1981-04-01

The radiological criteria for the conduct of nuclear tests have undergone many revisions with the current criteria being 0.17 rad for uncontrolled populations and 0.5 rad for controllable populations. Their effect upon operations at the Nevada Test Site and the current off-site protective plans are reviewed for areas surrounding the Site. The few accidental releases that have occurred are used to establish estimates of probability of release and of hazard to the population. These are then put into context by comparing statistical data on other accidents and cataclysms. The guidelines established by DOE Manual Chapter MC-0524 have never been exceededmore » during the entire underground nuclear test program. The probability of real hazard to off-site populations appears to be sufficiently low as not to cause undue concern to the citizenry.« less

Fire danger rating over Mediterranean Europe based on fire radiative power derived from Meteosat

NASA Astrophysics Data System (ADS)

Pinto, Miguel M.; DaCamara, Carlos C.; Trigo, Isabel F.; Trigo, Ricardo M.; Feridun Turkman, K.

2018-02-01

We present a procedure that allows the operational generation of daily forecasts of fire danger over Mediterranean Europe. The procedure combines historical information about radiative energy released by fire events with daily meteorological forecasts, as provided by the Satellite Application Facility for Land Surface Analysis (LSA SAF) and the European Centre for Medium-Range Weather Forecasts (ECMWF). Fire danger is estimated based on daily probabilities of exceedance of daily energy released by fires occurring at the pixel level. Daily probability considers meteorological factors by means of the Canadian Fire Weather Index (FWI) and is estimated using a daily model based on a generalized Pareto distribution. Five classes of fire danger are then associated with daily probability estimated by the daily model. The model is calibrated using 13 years of data (2004-2016) and validated against the period of January-September 2017. Results obtained show that about 72 % of events releasing daily energy above 10 000 GJ belong to the extreme class of fire danger, a considerably high fraction that is more than 1.5 times the values obtained when using the currently operational Fire Danger Forecast module of the European Forest Fire Information System (EFFIS) or the Fire Risk Map (FRM) product disseminated by the LSA SAF. Besides assisting in wildfire management, the procedure is expected to help in decision making on prescribed burning within the framework of agricultural and forest management practices.

Evidence for a global seismic-moment release sequence

USGS Publications Warehouse

Bufe, C.G.; Perkins, D.M.

2005-01-01

Temporal clustering of the larger earthquakes (foreshock-mainshock-aftershock) followed by relative quiescence (stress shadow) are characteristic of seismic cycles along plate boundaries. A global seismic-moment release history, based on a little more than 100 years of instrumental earthquake data in an extended version of the catalog of Pacheco and Sykes (1992), illustrates similar behavior for Earth as a whole. Although the largest earthquakes have occurred in the circum-Pacific region, an analysis of moment release in the hemisphere antipodal to the Pacific plate shows a very similar pattern. Monte Carlo simulations confirm that the global temporal clustering of great shallow earthquakes during 1952-1964 at M ??? 9.0 is highly significant (4% random probability) as is the clustering of the events of M ??? 8.6 (0.2% random probability) during 1950-1965. We have extended the Pacheco and Sykes (1992) catalog from 1989 through 2001 using Harvard moment centroid data. Immediately after the 1950-1965 cluster, significant quiescence at and above M 8.4 begins and continues until 2001 (0.5% random probability). In alternative catalogs derived by correcting for possible random errors in magnitude estimates in the extended Pacheco-Sykes catalog, the clustering of M ??? 9 persists at a significant level. These observations indicate that, for great earthquakes, Earth behaves as a coherent seismotectonic system. A very-large-scale mechanism for global earthquake triggering and/or stress transfer is implied. There are several candidates, but so far only viscoelastic relaxation has been modeled on a global scale.

TU-F-17A-08: The Relative Accuracy of 4D Dose Accumulation for Lung Radiotherapy Using Rigid Dose Projection Versus Dose Recalculation On Every Breathing Phase

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

Lamb, J; Lee, C; Tee, S

2014-06-15

Purpose: To investigate the accuracy of 4D dose accumulation using projection of dose calculated on the end-exhalation, mid-ventilation, or average intensity breathing phase CT scan, versus dose accumulation performed using full Monte Carlo dose recalculation on every breathing phase. Methods: Radiotherapy plans were analyzed for 10 patients with stage I-II lung cancer planned using 4D-CT. SBRT plans were optimized using the dose calculated by a commercially-available Monte Carlo algorithm on the end-exhalation 4D-CT phase. 4D dose accumulations using deformable registration were performed with a commercially available tool that projected the planned dose onto every breathing phase without recalculation, as wellmore » as with a Monte Carlo recalculation of the dose on all breathing phases. The 3D planned dose (3D-EX), the 3D dose calculated on the average intensity image (3D-AVE), and the 4D accumulations of the dose calculated on the end-exhalation phase CT (4D-PR-EX), the mid-ventilation phase CT (4D-PR-MID), and the average intensity image (4D-PR-AVE), respectively, were compared against the accumulation of the Monte Carlo dose recalculated on every phase. Plan evaluation metrics relating to target volumes and critical structures relevant for lung SBRT were analyzed. Results: Plan evaluation metrics tabulated using 4D-PR-EX, 4D-PR-MID, and 4D-PR-AVE differed from those tabulated using Monte Carlo recalculation on every phase by an average of 0.14±0.70 Gy, - 0.11±0.51 Gy, and 0.00±0.62 Gy, respectively. Deviations of between 8 and 13 Gy were observed between the 4D-MC calculations and both 3D methods for the proximal bronchial trees of 3 patients. Conclusions: 4D dose accumulation using projection without re-calculation may be sufficiently accurate compared to 4D dose accumulated from Monte Carlo recalculation on every phase, depending on institutional protocols. Use of 4D dose accumulation should be considered when evaluating normal tissue complication probabilities as well as in clinical situations where target volumes are directly inferior to mobile critical structures.« less

Establishment probability in newly founded populations.

PubMed

Gusset, Markus; Müller, Michael S; Grimm, Volker

2012-06-20

Establishment success in newly founded populations relies on reaching the established phase, which is defined by characteristic fluctuations of the population's state variables. Stochastic population models can be used to quantify the establishment probability of newly founded populations; however, so far no simple but robust method for doing so existed. To determine a critical initial number of individuals that need to be released to reach the established phase, we used a novel application of the "Wissel plot", where -ln(1 - P0(t)) is plotted against time t. This plot is based on the equation P(0)t=1-c(1)e(-ω(1t)), which relates the probability of extinction by time t, P(0)(t), to two constants: c(1) describes the probability of a newly founded population to reach the established phase, whereas ω(1) describes the population's probability of extinction per short time interval once established. For illustration, we applied the method to a previously developed stochastic population model of the endangered African wild dog (Lycaon pictus). A newly founded population reaches the established phase if the intercept of the (extrapolated) linear parts of the "Wissel plot" with the y-axis, which is -ln(c(1)), is negative. For wild dogs in our model, this is the case if a critical initial number of four packs, consisting of eight individuals each, are released. The method we present to quantify the establishment probability of newly founded populations is generic and inferences thus are transferable to other systems across the field of conservation biology. In contrast to other methods, our approach disaggregates the components of a population's viability by distinguishing establishment from persistence.

Simulation and analysis of chemical release in the ionosphere

NASA Astrophysics Data System (ADS)

Gao, Jing-Fan; Guo, Li-Xin; Xu, Zheng-Wen; Zhao, Hai-Sheng; Feng, Jie

2018-05-01

Ionospheric inhomogeneous plasma produced by single point chemical release has simple space-time structure, and cannot impact radio wave frequencies higher than Very High Frequency (VHF) band. In order to produce more complicated ionospheric plasma perturbation structure and trigger instabilities phenomena, multiple-point chemical release scheme is presented in this paper. The effects of chemical release on low latitude ionospheric plasma are estimated by linear instability growth rate theory that high growth rate represents high irregularities, ionospheric scintillation occurrence probability and high scintillation intension in scintillation duration. The amplitude scintillations and the phase scintillations of 150 MHz, 400 MHz, and 1000 MHz are calculated based on the theory of multiple phase screen (MPS), when they propagate through the disturbed area.

Using the Viking biology experimental results to obtain chemical information about Martian regolith

NASA Technical Reports Server (NTRS)

Plumb, Robert C.

1992-01-01

Although initially formulated as biology experiments, most of the results produced by the Viking Labeled Release (LR), Gas Exchange (GEX), and Pyrolytic Release (PR) experiments have been reproduced by chemical means. The experiments do not need more study as 'biological' phenomena, but they do deserve much more careful consideration from a chemical viewpoint. They are the only 'wet-chemical' experiments that scientists have performed on another planet, but they have not found very general use as sources of scientific information. There is a large set of potentially useful chemical observations, e.g., the three resolvable and precisely measured kinetic components of the release of C-14-labeled gases, the thermal sensitivity and magnitudes of the oxidation reaction(s) of the LR experiments, the kinetics and magnitude of the O2 and CO2 release of the GEX experiments, the thermal sensitivity of the GEX results, the differences between the thermal sensitivity of the GEX and the thermal sensitivity of the LR responses, and the kinetics and magnitudes of the LR successive injection reabsorption effect. It should be possible to test many chemical aspects of hypothetical martian phenomena in experiments using the biology experimental configurations and derive much valuable information by comparisons with the Viking observations.

Analysis of North Atlantic tropical cyclone intensify change using data mining

NASA Astrophysics Data System (ADS)

Tang, Jiang

Tropical cyclones (TC), especially when their intensity reaches hurricane scale, can become a costly natural hazard. Accurate prediction of tropical cyclone intensity is very difficult because of inadequate observations on TC structures, poor understanding of physical processes, coarse model resolution and inaccurate initial conditions, etc. This study aims to tackle two factors that account for the underperformance of current TC intensity forecasts: (1) inadequate observations of TC structures, and (2) deficient understanding of the underlying physical processes governing TC intensification. To tackle the problem of inadequate observations of TC structures, efforts have been made to extract vertical and horizontal structural parameters of latent heat release from Tropical Rainfall Measuring Mission (TRMM) Precipitation Radar (PR) data products. A case study of Hurricane Isabel (2003) was conducted first to explore the feasibility of using the 3D TC structure information in predicting TC intensification. Afterwards, several structural parameters were extracted from 53 TRMM PR 2A25 observations on 25 North Atlantic TCs during the period of 1998 to 2003. A new generation of multi-correlation data mining algorithm (Apriori and its variations) was applied to find roles of the latent heat release structure in TC intensification. The results showed that the buildup of TC energy is indicated by the height of the convective tower, and the relative low latent heat release at the core area and around the outer band. Adverse conditions which prevent TC intensification include the following: (1) TC entering a higher latitude area where the underlying sea is relative cold, (2) TC moving too fast to absorb the thermal energy from the underlying sea, or (3) strong energy loss at the outer band. When adverse conditions and amicable conditions reached equilibrium status, tropical cyclone intensity would remain stable. The dataset from Statistical Hurricane Intensity Prediction Scheme (SHIPS) covering the period of 1982-2003 and the Apriori-based association rule mining algorithm were used to study the associations of underlying geophysical characteristics with the intensity change of tropical cyclones. The data have been stratified into 6 TC categories from tropical depression to category 4 hurricanes based on their strength. The result showed that the persistence of intensity change in the past and the strength of vertical shear in the environment are the most prevalent factors for all of the 6 TC categories. Hyper-edge searching had found 3 sets of parameters which showed strong intramural binds. Most of the parameters used in SHIPS model have a consistent "I-W" relation over different TC categories, indicating a consistent function of those parameters in TC development. However, the "I-W" relations of the relative momentum flux and the meridional motion change from tropical storm stage to hurricane stage, indicating a change in the role of those two parameters in TC development. Because rapid intensification (RI) is a major source of errors when predicting hurricane intensity, the association rule mining algorithm was performed on RI versus non-RI tropical cyclone cases using the same SHIPS dataset. The results had been compared with those from the traditional statistical analysis conducted by Kaplan and DeMaria (2003). The rapid intensification rule with 5 RI conditions proposed by the traditional statistical analysis was found by the association rule mining in this study as well. However, further analysis showed that the 5 RI conditions can be replaced by another association rule using fewer conditions but with a higher RI probability (RIP). This means that the rule with all 5 constraints found by Kaplan and DeMaria is not optimal, and the association rule mining technique can find a rule with fewer constraints yet fits more RI cases. The further analysis with the highest RIPs over different numbers of conditions has demonstrated that the interactions among multiple factors are responsible for the RI process of TCs. However, the influence of factors saturates at certain numbers. This study has shown successful data mining examples in studying tropical cyclone intensification using association rules. The higher RI probability with fewer conditions found by association rule technique is significant. This work demonstrated that data mining techniques can be used as an efficient exploration method to generate hypotheses, and that statistical analysis should be performed to confirm the hypotheses, as is generally expected for data mining applications.

Controlled release of ibuprofen by meso-macroporous silica

NASA Astrophysics Data System (ADS)

Santamaría, E.; Maestro, A.; Porras, M.; Gutiérrez, J. M.; González, C.

2014-02-01

Structured meso-macroporous silica was successfully synthesized from an O/W emulsion using decane as a dispersed phase. Sodium silicate solution, which acts as a silica source and a poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (EO19PO39EO19) denoted as P84 was used in order to stabilize the emulsion and as a mesopore template. The materials obtained were characterized through transmission electron microscopy (TEM), scanning electron microscopy (SEM), small-angle X-ray diffraction scattering (SAXS) and nitrogen adsorption-desorption isotherms. Ibuprofen (IBU) was selected as the model drug and loaded into ordered meso-macroporous materials. The effect of the materials’ properties on IBU drug loading and release was studied. The results showed that the loading of IBU increases as the macropore presence in the material is increased. The IBU adsorption process followed the Langmuir adsorption isotherm. A two-step release process, consisting of an initial fast release and then a slower release was observed. Macropores enhanced the adsorption capacity of the material; this was probably due to the fact that they allowed the drug to access internal pores. When only mesopores were present, ibuprofen was probably adsorbed on the mesopores close to the surface. Moreover, the more macropore present in the material, the slower the release behaviour observed, as the ibuprofen adsorbed in the internal pores had to diffuse along the macropore channels up to the surface of the material. The material obtained from a highly concentrated emulsion was functionalized with amino groups using two methods, the post-grafting mechanism and the co-condensation mechanism. Both routes improve IBU adsorption in the material and show good behaviour as a controlled drug delivery system.

Inhibition of Anaerobic Phosphate Release by Nitric Oxide in Activated Sludge

PubMed Central

Van Niel, E. W. J.; Appeldoorn, K. J.; Zehnder, A. J. B.; Kortstee, G. J. J.

1998-01-01

Activated sludge not containing significant numbers of denitrifying, polyphosphate [poly(P)]-accumulating bacteria was grown in a fill-and-draw system and exposed to alternating anaerobic and aerobic periods. During the aerobic period, poly(P) accumulated up to 100 mg of P · g of (dry) weight. When portions of the sludge were incubated anaerobically in the presence of acetate, 80 to 90% of the intracellular poly(P) was degraded and released as orthophosphate. Degradation of poly(P) was mainly catalyzed by the concerted action of polyphosphate:AMP phosphotransferase and adenylate kinase, resulting in ATP formation. In the presence of 0.3 mM nitric oxide (NO) in the liquid-phase release of phosphate, uptake of acetate, formation of poly-β-hydroxybutyrate, utilization of glycogen, and formation of ATP were severely inhibited or completely abolished. In cell extracts of the sludge, adenylate kinase activity was completely inhibited by 0.15 mM NO. The nature of this inhibition was probably noncompetitive, similar to that with hog adenylate kinase. Activated sludge polyphosphate glucokinase was also completely inhibited by 0.15 mM NO. It is concluded that the inhibitory effect of NO on acetate-mediated phosphate release by the sludge used in this study is due to the inhibition of adenylate kinase in the phosphate-releasing organisms. The inhibitory effect of nitrate and nitrite on phosphate release is probably due to their conversion to NO. The lack of any inhibitory effect of NO on adenylate kinase of the poly(P)-accumulating Acinetobacter johnsonii 210A suggests that this type of organism is not involved in the enhanced biological phosphate removal by the sludges used. PMID:9687452

Calcium release and its voltage dependence in frog cut muscle fibers equilibrated with 20 mM EGTA

PubMed Central

1995-01-01

Sarcoplasmic reticulum (SR) Ca release was studied at 13-16 degrees C in cut fibers (sarcomere length, 3.4-3.9 microns) mounted in a double Vaseline-gap chamber. The amplitude and duration of the action- potential stimulated free [Ca] transient were reduced by equilibration with end-pool solutions that contained 20 mM EGTA with 1.76 mM Ca and 0.63 mM phenol red, a maneuver that appeared to markedly reduce the amount of Ca complexed by troponin. A theoretical analysis shows that, under these conditions, the increase in myoplasmic free [Ca] is expected to be restricted to within a few hundred nanometers of the SR Ca release sites and to have a time course that essentially matches that of release. Furthermore, almost all of the Ca that is released from the SR is expected to be rapidly bound by EGTA and exchanged for protons with a 1:2 stoichiometry. Consequently, the time course of SR Ca release can be estimated by scaling the delta pH signal measured with phenol red by -beta/2. The value of beta, the buffering power of myoplasm, was determined in fibers equilibrated with a combination of EGTA, phenol red, and fura-2; its mean value was 22 mM/pH unit. The Ca content of the SR (expressed as myoplasmic concentration) was estimated from the total amount of Ca released by either a train of action potentials or a depleting voltage step; its mean value was 2,685 microM in the action-potential experiments and 2,544 microM in the voltage- clamp experiments. An action potential released, on average, 0.14 of the SR Ca content with a peak rate of release of approximately 5%/ms. A second action potential, elicited 20 ms later, released only 0.6 times as much Ca (expressed as a fraction of the SR content), probably because Ca inactivation of Ca release was produced by the first action potential. During a depolarizing voltage step to 60 mV, the rate of Ca release rapidly increased to a peak value of approximately 3%/ms and then decreased to a quasi-steady level that was only 0.6 times as large; this decrease was also probably due to Ca inactivation of Ca release. SR Ca release was studied with small step depolarizations that open no more than one SR Ca channel in 7,000 and increase the value of spatially averaged myoplasmic free [Ca] by only 0.2 nM. PMID:8537818

Determination of barge impact probabilities for bridge design.

DOT National Transportation Integrated Search

2016-04-01

Waterway bridges in the United States are designed to resist vessel collision loads according to design provisions released by the American Association of State : Highway and Transportation Officials (AASHTO). These provisions provide detailed proced...

Cargo Fire Hazards and Hazard Control for the Offshore Bulk Fuel Systems (OBFS).

DTIC Science & Technology

1980-06-01

used to evaluate the probability of cargo fuel spills during different ship operational modes. An undesired hazardous event such as a spill of volume...occur. if a cargo release occurs due to either collision or hostile action the probability of ignition is very high . Ignition can be caused by the...Separate auxiliary burners independent from the ship propulsion system provide similar flue gas composition. However as noted previously, a low sulfur

A diffusion climatology for Cape Canaveral, Florida

NASA Technical Reports Server (NTRS)

Siler, R. K.

1980-01-01

The problem of toxic effluent released by a space shuttle launch on local plant and animal life is discussed. Based on several successive years of data, nine basic weather patterns were identified, and the probabilities of pattern occurrence, of onshore/alongshore cloud transport, of precipitation accompanying the latter, and of ground-level concentrations of hydrogen chloride were determined. Diurnal variations for the patterns were also investigated. Sketches showing probable movement of launch cloud exhaust and isobaric maps are presented.

Inverse modeling methods for indoor airborne pollutant tracking: literature review and fundamentals.

PubMed

Liu, X; Zhai, Z

2007-12-01

Reduction in indoor environment quality calls for effective control and improvement measures. Accurate and prompt identification of contaminant sources ensures that they can be quickly removed and contaminated spaces isolated and cleaned. This paper discusses the use of inverse modeling to identify potential indoor pollutant sources with limited pollutant sensor data. The study reviews various inverse modeling methods for advection-dispersion problems and summarizes the methods into three major categories: forward, backward, and probability inverse modeling methods. The adjoint probability inverse modeling method is indicated as an appropriate model for indoor air pollutant tracking because it can quickly find source location, strength and release time without prior information. The paper introduces the principles of the adjoint probability method and establishes the corresponding adjoint equations for both multi-zone airflow models and computational fluid dynamics (CFD) models. The study proposes a two-stage inverse modeling approach integrating both multi-zone and CFD models, which can provide a rapid estimate of indoor pollution status and history for a whole building. Preliminary case study results indicate that the adjoint probability method is feasible for indoor pollutant inverse modeling. The proposed method can help identify contaminant source characteristics (location and release time) with limited sensor outputs. This will ensure an effective and prompt execution of building management strategies and thus achieve a healthy and safe indoor environment. The method can also help design optimal sensor networks.

Comparisons of Instantaneous TRMM Ground Validation and Satellite Rain Rate Estimates at Different Spatial Scales

NASA Technical Reports Server (NTRS)

Wolff, David B.; Fisher, Brad L.

2007-01-01

This study provides a comprehensive inter-comparison of instantaneous rain estimates from the two rain sensors aboard the TRMM satellite with ground data from thee designated Ground Validation Sites: Kwajalein Atoll, Melbourne, Florida and Houston, Texas. The satellite rain retrievals utilize rain observations collected by the TRMM microwave imager (TMI) and the Precipitation Radar (PR) aboard the TRMM satellite. Three standard instantaneous rain products are the generated from the rain information retrieved from the satellite using the TMI, PR and Combined (COM) rain algorithms. The validation data set used in this study was obtained from instantaneous rain rates inferred from ground radars at each GV site. The first comparison used 0.5(sup 0) x 0.5(sup 0) gridded data obtained from the TRMM 3668 product, and similarly gridded GV data obtained from ground-based radars. The comparisons were made at the same spatial and temporal scales in order to eliminate sampling biases in our comparisons. An additional comparison was made by averaging rain rates for the PR, COM and GV estimates within each TMI footprint (approx. 150 square kilometers). For this analysis, unconditional mean rain rates from PR, COM and GV estimates were calculated within each TMI footprint that was observed within 100 km from the respective GV site (and also observed by the PR). This analysis used all the available matching data from the period 1999-2004, representing a sample size of over 50,000 footprints for each site. In the first analysis our results showed that all of the respective rain rate estimates agree well, with some exceptions. The more salient differences were associated with heavy rain events in which one or more of the algorithms failed to properly retrieve these extreme events. Also, it appears that there is a preferred mode of precipitation for TMI rain rates at or near 2 mm per hour over the ocean. This mode was noted over ocean areas of Melbourne, Florida and Kwajalein, Republic of the Marshall Islands, and is shown to exist in TRMM tropical-global ocean areas as well. Further research by algorithm developers is needed to explain or justify the seemingly errant observed probability distributions.

Costs and cost-effectiveness analysis of 2015 GESIDA/Spanish AIDS National Plan recommended guidelines for initial antiretroviral therapy in HIV-infected adults.

PubMed

Berenguer, Juan; Rivero, Antonio; Blasco, Antonio Javier; Arribas, José Ramón; Boix, Vicente; Clotet, Bonaventura; Domingo, Pere; González-García, Juan; Knobel, Hernando; Lázaro, Pablo; López, Juan Carlos; Llibre, Josep M; Lozano, Fernando; Miró, José M; Podzamczer, Daniel; Tuset, Montserrat; Gatell, Josep M

2016-01-01

GESIDA and the AIDS National Plan panel of experts suggest a preferred (PR), alternative (AR) and other regimens (OR) for antiretroviral treatment (ART) as initial therapy in HIV-infected patients for 2015. The objective of this study is to evaluate the costs and the effectiveness of initiating treatment with these regimens. Economic assessment of costs and effectiveness (cost/effectiveness) based on decision tree analyses. Effectiveness was defined as the probability of reporting a viral load <50 copies/mL at week 48, in an intention-to-treat analysis. Cost of initiating treatment with an ART regimen was defined as the costs of ART and its consequences (adverse effects, changes of ART regimen, and drug resistance studies) during the first 48 weeks. The payer perspective (National Health System) was applied, only taking into account differential direct costs: ART (official prices), management of adverse effects, studies of resistance, and HLA B*5701 testing. The setting is Spain and the costs correspond to those of 2015. A deterministic sensitivity analysis was conducted, building three scenarios for each regimen: base case, most favourable and least favourable. In the base case scenario, the cost of initiating treatment ranges from 4663 Euros for 3TC+LPV/r (OR) to 10,902 Euros for TDF/FTC+RAL (PR). The effectiveness varies from 0.66 for ABC/3TC+ATV/r (AR) and ABC/3TC+LPV/r (OR), to 0.89 for TDF/FTC+DTG (PR) and TDF/FTC/EVG/COBI (AR). The efficiency, in terms of cost/effectiveness, ranges from 5280 to 12,836 Euros per responder at 48 weeks, for 3TC+LPV/r (OR) and RAL+DRV/r (OR), respectively. The most efficient regimen was 3TC+LPV/r (OR). Among the PR and AR, the most efficient regimen was TDF/FTC/RPV (AR). Among the PR regimes, the most efficient was ABC/3TC+DTG. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Costs and cost-efficacy analysis of the 2016 GESIDA/Spanish AIDS National Plan recommended guidelines for initial antiretroviral therapy in HIV-infected adults.

PubMed

Rivero, Antonio; Pérez-Molina, José Antonio; Blasco, Antonio Javier; Arribas, José Ramón; Crespo, Manuel; Domingo, Pere; Estrada, Vicente; Iribarren, José Antonio; Knobel, Hernando; Lázaro, Pablo; López-Aldeguer, José; Lozano, Fernando; Moreno, Santiago; Palacios, Rosario; Pineda, Juan Antonio; Pulido, Federico; Rubio, Rafael; de la Torre, Javier; Tuset, Montserrat; Gatell, Josep M

2017-02-01

GESIDA and the AIDS National Plan panel of experts suggest preferred (PR), alternative (AR), and other regimens (OR) for antiretroviral treatment (ART) as initial therapy in HIV-infected patients for the year 2016. The objective of this study is to evaluate the costs and the efficacy of initiating treatment with these regimens. Economic assessment of costs and efficiency (cost/efficacy) based on decision tree analyses. Efficacy was defined as the probability of reporting a viral load <50copies/mL at week 48 in an intention-to-treat analysis. Cost of initiating treatment with an ART regimen was defined as the costs of ART and its consequences (adverse effects, changes of ART regimen, and drug resistance studies) during the first 48 weeks. The payer perspective (National Health System) was applied, only taking into account differential direct costs: ART (official prices), management of adverse effects, studies of resistance, and HLA B*5701 testing. The setting is Spain and the costs correspond to those of 2016. A sensitivity deterministic analysis was conducted, building three scenarios for each regimen: base case, most favourable, and least favourable. In the base case scenario, the cost of initiating treatment ranges from 4663 Euros for 3TC+LPV/r (OR) to 10,894 Euros for TDF/FTC+RAL (PR). The efficacy varies from 0.66 for ABC/3TC+ATV/r (AR) and ABC/3TC+LPV/r (OR), to 0.89 for TDF/FTC+DTG (PR) and TDF/FTC/EVG/COBI (AR). The efficiency, in terms of cost/efficacy, ranges from 5280 to 12,836 Euros per responder at 48 weeks, for 3TC+LPV/r (OR), and RAL+DRV/r (OR), respectively. Despite the overall most efficient regimen being 3TC+LPV/r (OR), among the PR and AR, the most efficient regimen was ABC/3TC/DTG (PR). Among the AR regimes, the most efficient was TDF/FTC/RPV. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Dispersal and oviposition of laboratory-reared gravid females of Toxorhynchites moctezuma in an arid urban area of Sonora, Mexico.

PubMed

Macías-Duarte, Alberto; Alvarado-Castro, J Andrés; Dórame-Navarro, María E; Félix-Torres, A Amalia

2009-12-01

Dengue is a serious public health problem worldwide. Biological control of its vector, Aedes aegypti, remains a feasible option in light of increasing urbanization and insecticide resistance. We studied the dispersal and oviposition activity of Toxorhynchites moctezuma in a dengue-endemic urban area in SSonora, Mexico, to provide information about the potential of Toxorhynchites as a control agent for Ae. aegypti in arid areas. We released 210 and 100 laboratory-reared gravid females of Tx. moctezuma in 2 city blocks during the summer and fall of 1993. We set 3 1-liter containers and 1 car tire as sentinel traps at each of 10 backyards within each city block. Spatial and temporal patterns of dispersal and oviposition activity differed between city blocks and between releases. However, a Cox regression analysis showed no significant difference in the per-day probability of Tx. moctezuma oviposition events in sentinel traps between summer and fall releases. Per-day oviposition probability was nearly 5 times greater for sentineltraps that contained larvae of Ae. aegypti, suggesting a high specificity of the predator for its prey. The proportion of sentinel traps positive for Tx. moctezuma eggs did not increase substantially after the 8th day piost-release, reaching 66% and 23% for sentinel traps with and without Ae. aegypti larvae, respectively.

New Concepts in the Evaluation of Biodegradation/Persistence of Chemical Substances Using a Microbial Inoculum

PubMed Central

Thouand, Gérald; Durand, Marie-José; Maul, Armand; Gancet, Christian; Blok, Han

2011-01-01

The European REACH Regulation (Registration, Evaluation, Authorization of CHemical substances) implies, among other things, the evaluation of the biodegradability of chemical substances produced by industry. A large set of test methods is available including detailed information on the appropriate conditions for testing. However, the inoculum used for these tests constitutes a “black box.” If biodegradation is achievable from the growth of a small group of specific microbial species with the substance as the only carbon source, the result of the test depends largely on the cell density of this group at “time zero.” If these species are relatively rare in an inoculum that is normally used, the likelihood of inoculating a test with sufficient specific cells becomes a matter of probability. Normally this probability increases with total cell density and with the diversity of species in the inoculum. Furthermore the history of the inoculum, e.g., a possible pre-exposure to the test substance or similar substances will have a significant influence on the probability. A high probability can be expected for substances that are widely used and regularly released into the environment, whereas a low probability can be expected for new xenobiotic substances that have not yet been released into the environment. Be that as it may, once the inoculum sample contains sufficient specific degraders, the performance of the biodegradation will follow a typical S shaped growth curve which depends on the specific growth rate under laboratory conditions, the so called F/M ratio (ratio between food and biomass) and the more or less toxic recalcitrant, but possible, metabolites. Normally regulators require the evaluation of the growth curve using a simple approach such as half-time. Unfortunately probability and biodegradation half-time are very often confused. As the half-time values reflect laboratory conditions which are quite different from environmental conditions (after a substance is released), these values should not be used to quantify and predict environmental behavior. The probability value could be of much greater benefit for predictions under realistic conditions. The main issue in the evaluation of probability is that the result is not based on a single inoculum from an environmental sample, but on a variety of samples. These samples can be representative of regional or local areas, climate regions, water types, and history, e.g., pristine or polluted. The above concept has provided us with a new approach, namely “Probabio.” With this approach, persistence is not only regarded as a simple intrinsic property of a substance, but also as the capability of various environmental samples to degrade a substance under realistic exposure conditions and F/M ratio. PMID:21863143

Occupational risk for Legionella infection among dental healthcare workers: meta-analysis in occupational epidemiology.

PubMed

Petti, Stefano; Vitali, Matteo

2017-07-13

The occupational risk for Legionella infection among dental healthcare workers (DHCWs) is conjectured because of the risk of routine inhalation of potentially contaminated aerosols produced by the dental instruments. Nevertheless, occupational epidemiology studies are contrasting. This meta-analysis assessed the level of scientific evidence regarding the relative occupational risk for Legionella infection among DHCWs. Literature search was performed without time and language restrictions, using broad data banks (PubMed, Scopus, Web of Science, GOOGLE Scholar) and generic keywords ('legionella' AND 'dent*'). Analytical cross-sectional studies comparing prevalence of high serum Legionella antibody levels in DHCWs and occupationally unexposed individuals were considered. The relative occupational risk was assessed through prevalence ratio (PR) with 95% CI. Between-study heterogeneity was assessed (Cochran's Q test) and was used to choose the meta-analytic method. Study quality (modified Newcastle-Ottawa Scale) and publication bias (Begg and Mazumdar's test, Egger and colleagues' test, trim and fill R 0 method) were assessed formally and considered for the sensitivity analysis. Sensitivity analysis to study inclusion, subgroup analyses (dental staff categories; publication year, before vs after 1998, ie, 5 years after the release by the Centers for Disease Control and Prevention of the infection control guidelines in dental healthcare setting) were performed. Seven studies were included (2232 DHCWs, 1172 occupationally unexposed individuals). No evidence of publication bias was detected. The pooled PR estimate was statistically non-significant at 95% level (1.7; 95% CI 0.8 to 3.2), study-quality adjustment did not change the PR considerably (PR, 1.5; 95% CI 0.5 to 4.1). PR was statistically significant before 1998 and no longer significant after 1998. Subgroup analysis according to DHCW categories was inconclusive. There is no scientific evidence that DHCWs are at high occupational risk. The differences between former and recent studies could be due to different characteristics of municipal water systems and the infection control guideline dissemination. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Prospective comparison of two models of integrating early infant male circumcision with maternal child health services in Kenya: The Mtoto Msafi Mbili Study

PubMed Central

Adera, Fredrick; Mackesy-Amiti, Mary Ellen; Adipo, Timothy; Nordstrom, Sherry K.; Mehta, Supriya D.; Jaoko, Walter; Langi, F. L. Fredrik G.; Obiero, Walter; Obat, Edmon; Otieno, Fredrick O.; Young, Marisa R.

2017-01-01

As countries scale up adult voluntary medical male circumcision (VMMC) for HIV prevention, they are looking ahead to long term sustainable strategies, including introduction of early infant male circumcision (EIMC). To address the lack of evidence regarding introduction of EIMC services in sub-Saharan African settings, we conducted a simultaneous, prospective comparison of two models of EIMC service delivery in Homa Bay County, Kenya. In one division a standard delivery package (SDP) was introduced and included health facility-based provision of EIMC services with community engagement for client referral versus in a different division a standard package plus (SDPplus) that included community-delivered EIMC services. Babies 1–60 days old were eligible for EIMC. A representative sample of mothers and fathers of baby boys at 16 health facilities was surveyed. We examined differences between mothers and fathers in the SDP and SDPplus divisions and identified factors associated with EIMC uptake. We report adjusted prevalence ratios (aPR). Of 1660 mothers interviewed, 1501 (89%) gave approval to contact the father, and 1259 fathers (84%) were interviewed. The proportion of babies circumcised was slightly greater in the SDPplus division than the SDP division (27.3% vs 23.7%), but the difference was not significant (p = 0.08). In adjusted analyses, however, the prevalence of babies being circumcised was greater in the SDPplus division (aPR = 1.23, 95% CI:1.04–1.45) and the factors associated with a baby being circumcised were the mother having received information about EIMC (during pregnancy, aPR = 4.81, 95% CI: 2.21–3.42), having discussed circumcision with the father if married or cohabiting (aPR = 5.39, 95% CI: 3.31–8.80) or being single (aPR = 5.67, 95% CI: 3.31–9.69), perceiving herself to be living with HIV (aPR = 1.39, 95% CI: 1.15–1.67), or having a post-secondary education (aPR = 1.33, 95% CI: 1.04–1.69), and the father being Muslim (aPR = 1.85, 95% CI: 1.29–2.65) or circumcised (aPR = 1.34, 95% CI: 1.13–1.59). The median age of 2117 babies circumcised was 8 days (IQR: 1–36), and the median weight was 3.6 kg (IQR: 3.2–4.4). There were 6 moderate adverse events (AEs) (0.28%); 5 severe AEs (0.24%), all involving an injury to the glans penis, requiring hospitalization and corrective surgery; and one death probably related to the procedure. There were no AEs among the 365 procedures performed outside health facilities. Information and education campaigns must reach members of the general population, especially men and fathers, who are influential to the EIMC decision. Serious AEs using the Mogen clamp are rare, but do occur and require efficient, reliable emergency back-up. Our results can assist countries considering scale-up of EIMC services for HIV prevention as their adult VMMC programs mature. PMID:28880904

Releases of whooping cranes to the Florida nonmigratory flock: a structured decision-making approach: report to the International Whooping Crane Recovery Team, September 22, 2008

USGS Publications Warehouse

Moore, Clinton T.; Converse, Sarah J.; Folk, Martin J.; Boughton, Robin; Brooks, Bill; French, John B.; O'Meara, Timothy; Putnam, Michael; Rodgers, James; Spalding, Marilyn

2008-01-01

We used a structured decision-making approach to inform the decision of whether the Florida Fish and Wildlife Conservation Commission should request of the International Whooping Crane Recovery Team that additional whooping crane chicks be released into the Florida Non-Migratory Population (FNMP). Structured decision-making is an application of decision science that strives to produce transparent, replicable, and defensible decisions that recognize the appropriate roles of management policy and science in decision-making. We present a multi-objective decision framework, where management objectives include successful establishment of a whooping crane population in Florida, minimization of costs, positive public relations, information gain, and providing a supply of captive-reared birds to alternative crane release projects, such as the Eastern Migratory Population. We developed models to predict the outcome relative to each of these objectives under 29 different scenarios of the release methodology used from 1993 to 2004, including options of no further releases and variable numbers of releases per year over the next 5-30 years. In particular, we developed a detailed set of population projection models, which make substantially different predictions about the probability of successful establishment of the FNMP. We used expert elicitation to develop prior model weights (measures of confidence in population model predictions); the results of the population model weighting and modelaveraging exercise indicated that the probability of successful establishment of the FNMP ranged from 9% if no additional releases are made, to as high as 41% with additional releases. We also used expert elicitation to develop weights (relative values) on the set of identified objectives, and we then used a formal optimization technique for identifying the optimal decision, which considers the tradeoffs between objectives. The optimal decision was identified as release of 3 cohorts (24 birds) per year over the next 10 years. However, any decision that involved release of 1-3 cohorts (8-24 birds) per year over the next 5 to 20 years, as well as decisions that involve skipping releases in every other year, performed better in our analysis than the alternative of no further releases. These results were driven by the relatively high objective weights that experts placed on the population objective (i.e., successful establishment of the FNMP) and the information gain objective (where releases are expected to accelerate learning on what was identified as a primary uncertainty: the demographic performance of wild-hatched birds). Additional considerations that were not formally integrated into the analysis are also discussed.

SURFACE CONTAINMENT FOR GEOTHERMAL BRINES

EPA Science Inventory

This report examines the probability of significant releases of geothermal brine to the surface environment through unplanned or accidental events. It then evaluates the containment measures that may be used to prevent environmental damage. The results indicate that major spills ...

[Socio-demographic and health conditions associated with paid work in adults (50-69 years) in Greater Metropolitan Belo Horizonte, Minas Gerais State, Brazil].

PubMed

Castro, Camila Menezes Sabino de; Mambrini, Juliana Vaz de Melo; Sampaio, Rosana Ferreira; Macinko, James; Lima-Costa, Maria Fernanda

2015-08-01

Factors associated with paid work were examined in a probabilistic sample of 3,320 adults (50-69 years) in Greater Metropolitan Belo Horizonte, Minas Gerais State, Brazil. Prevalence of paid work was 62.8% in men and 35.8% in women. For both men and women, paid work was positively associated with schooling and negatively associated with self-rated health. The probability of having paid work was higher for single women and those who knew someone that had suffered discrimination at the workplace. For men, prevalence of paid work varied from 67.2% in those with ≥ 8 years of schooling and better self-rated health, as compared to 37.8% in those with less schooling and poor self-rated health (PR = 0.56; 95%CI: 0.37-0.87). In women, the corresponding prevalence rates were 42.1% and 3.6% (PR = 0.09; 95%CI: 0.03-0.26). For women with little schooling and poor self-rated health, the likelihood of having paid work was ten times lower than for their male counterparts.

AGE AND REPEATED BIOPSY INFLUENCE ANTEMORTEM PRP(CWD) TESTING IN MULE DEER (ODOCOILEUS HEMIONUS) IN COLORADO, USA.

PubMed

Geremia, Chris; Hoeting, Jennifer A; Wolfe, Lisa L; Galloway, Nathan L; Antolin, Michael F; Spraker, Terry R; Miller, Michael W; Hobbs, N Thompson

2015-10-01

Biopsy of rectal mucosa-associated lymphoid tissue provides a useful, but imperfect, live-animal test for chronic wasting disease (CWD) in mule deer (Odocoileus hemionus). It is difficult and expensive to complete these tests on free-ranging animals, and wildlife health managers will benefit from methods that can accommodate test results of varying quality. To this end, we developed a hierarchical Bayesian model to estimate the probability that an individual is infected based on test results. Our model was estimated with the use of data on 210 adult female mule deer repeatedly tested during 2010-14. The ability to identify infected individuals correctly declined with age and may have been influenced by repeated biopsy. Fewer isolated lymphoid follicles (where PrP(CWD) accumulates) were obtained in biopsies of older deer and the proportion of follicles showing PrP(CWD) was reduced. A deer's genotype in the prion gene (PRNP) also influenced detection. At least five follicles were needed in a biopsy to assure a 95% accurate test in PRNP genotype 225SS deer.

Photoinduced dynamics to photoluminescence in Ln3+ (Ln = Ce, Pr) doped β-NaYF4 nanocrystals computed in basis of non-collinear spin DFT with spin-orbit coupling

NASA Astrophysics Data System (ADS)

Han, Yulun; Vogel, Dayton J.; Inerbaev, Talgat M.; May, P. Stanley; Berry, Mary T.; Kilin, Dmitri S.

2018-03-01

In this work, non-collinear spin DFT + U approaches with spin-orbit coupling (SOC) are applied to Ln3+ doped β-NaYF4 (Ln = Ce, Pr) nanocrystals in Vienna ab initio Simulation Package taking into account unpaired spin configurations using the Perdew-Burke-Ernzerhof functional in a plane wave basis set. The calculated absorption spectra from non-collinear spin DFT + U approaches are compared with that from spin-polarised DFT + U approaches. The spectral difference indicates the importance of spin-flip transitions of Ln3+ ions. Suite of codes for nonadiabatic dynamics has been developed for 2-component spinor orbitals. On-the-fly nonadiabatic coupling calculations provide transition probabilities facilitated by nuclear motion. Relaxation rates of electrons and holes are calculated using Redfield theory in the reduced density matrix formalism cast in the basis of non-collinear spin DFT + U with SOC. The emission spectra are calculated using the time-integrated method along the excited state trajectories based on nonadiabatic couplings.

Bipartite units of nonlocality

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

Forster, Manuel; Wolf, Stefan

Imagine a task in which a group of separated players aim to simulate a statistic that violates a Bell inequality. Given measurement choices the players shall announce an output based solely on the results of local operations--which they can discuss before the separation--on shared random data and shared copies of a so-called unit correlation. In the first part of this paper we show that in such a setting the simulation of any bipartite correlation, not containing the possibility of signaling, can be made arbitrarily accurate by increasing the number of shared Popescu-Rohrlich (PR) boxes. This establishes the PR box asmore » a simple asymptotic unit of bipartite nonlocality. In the second part we study whether this property extends to the multipartite case. More generally, we ask if it is possible for separated players to asymptotically reproduce any nonsignaling statistic by local operations on bipartite unit correlations. We find that nonadaptive strategies are limited by a constant accuracy and that arbitrary strategies on n resource correlations make a mistake with a probability greater or equal to c/n, for some constant c.« less

Prostaglandin action on transmitter release of adrenergic neuroeffector junctions.

PubMed

Hedqvist, P

1976-01-01

The results presented here indicate that 1. The inhibitory action of the endoperoxides on NE release can be at least partly explained in terms of formation of degradation products, presumably mainly PGE2. 2. PGA2 is less active and the PG analogue 16,16-dimethyl-PGE2 more active than PGEs on transmitter release from adrenergic nerves. 3. PGF2alpha seems to enhance vascular responses to renal nerve activity solely by a postjunctional action. 4. PG synthesis inhibition augments NE turnover in a number of rat organs, thereby increasing the probability of PGs being involved in the control of adrenergic neurotransmission in vivo. 5. Prolongation of the duration of the impulse and action potential counteracts the effect of PGE on NE release, thereby strengthening the view that PGs operate on NE release from adrenergic nerve terminals by interfering with Ca2+ influx.

PRRT2 Is a Key Component of the Ca2+-Dependent Neurotransmitter Release Machinery

PubMed Central

Valente, Pierluigi; Castroflorio, Enrico; Rossi, Pia; Fadda, Manuela; Sterlini, Bruno; Cervigni, Romina Ines; Prestigio, Cosimo; Giovedì, Silvia; Onofri, Franco; Mura, Elisa; Guarnieri, Fabrizia C.; Marte, Antonella; Orlando, Marta; Zara, Federico; Fassio, Anna; Valtorta, Flavia; Baldelli, Pietro; Corradi, Anna; Benfenati, Fabio

2016-01-01

Summary Heterozygous mutations in proline-rich transmembrane protein 2 (PRRT2) underlie a group of paroxysmal disorders, including epilepsy, kinesigenic dyskinesia, and migraine. Most of the mutations lead to impaired PRRT2 expression, suggesting that loss of PRRT2 function may contribute to pathogenesis. We show that PRRT2 is enriched in presynaptic terminals and that its silencing decreases the number of synapses and increases the number of docked synaptic vesicles at rest. PRRT2-silenced neurons exhibit a severe impairment of synchronous release, attributable to a sharp decrease in release probability and Ca2+ sensitivity and associated with a marked increase of the asynchronous/synchronous release ratio. PRRT2 interacts with the synaptic proteins SNAP-25 and synaptotagmin 1/2. The results indicate that PRRT2 is intimately connected with the Ca2+-sensing machinery and that it plays an important role in the final steps of neurotransmitter release. PMID:27052163

[Effect of S1PR2 inhibition on epithelial ovarian cancer SKOV3 cell proliferation in vitro and in vivo].

PubMed

Dai, L; Liu, Y X; Xie, L; Di, W

2018-02-25

Objective: To study the effect and mechanism of S1PR2 inhibition on epithelial ovarian cancer SKOV3 cell proliferation in vitro and in vivo. Methods: (1) A pair of S1PR2 gene small interference RNA (siRNA) , namely si-S1PR2, and a pair of negative control siRNA were designed. Western blot methods were used to detect the silence efficiency of the S1PR2 in the si-S1PR2 group, blank control group and negative control group. (2) Study in vitro: the experiment included three groups, namely si-S1PR2 group, blank control group and negative control group. Cell counting kit-8 (CCK-8) assay was used to detect the proliferation inhibition rates of the transfected cells. The cell cycles of the transfected cells were measured by flow cytometry. Western blot was used to detect the levels of phosph-extracellular regulated protein kinase 1/2 (p-ERK1/2) of the transfected cells. (3) Study in vivo:to establish intraperitoneal transplantation models, 8 mice in each group were intraperitoneally injected with 5×10(6) SKOV3 cells. Phosphate buffered saline (PBS) or JTE-013 were administered into mice twice per week starting on day 7 after the injection of the cancer cells. Twenty-eight days after nude mice intraperitoneal injection with JTE-013 or PBS, the mice were sacrificed and the number and the weight of visible tumors were calculated. Results: (1) The results of western blot showed that the relative S1PR2 protein expression levels were 0.24±0.04 in the si-S1PR2 group, which was lower than that in the blank control group (1.10±0.14, P< 0.01) and negative control group (1.07±0.13, P< 0.01) . (2) The results of CCK-8 assay indicated that after transfected for 24, 48 and 72 hours, the proliferation inhibition rate of si-S1PR2 group were respectively (26.6±3.3) %, (35.0±3.4) %, and (34.0±2.8) %, significantly lower than those in the blank control group (all 0; all P< 0.01) and negative control group [ (1.7±0.9) %, (2.5±0.5) %,and (2.4±1.1) % respectively; all P< 0.01]. The results of flow cytometry showed that the G(0)/G(1) ratio in the si-S1PR2 group [ (70.9±2.8) %] was significantly higher than those in the blank control group [ (61.7±2.4) %, P< 0.01] and negative control group [ (62.1±3.3) %, P< 0.01]. Western blot showed that the relative expression level of p-ERK1/2 in si-S1PR2 group (0.11±0.03) was significantly lower than those in the blank control group [ (0.62±0.09) , P< 0.01] and negative control group [ (0.68±0.09) , P< 0.01]. (3)Twenty-eight days after nude mice intraperitoneal injection with JTE-013 or PBS, the tumor number of the control group and JTE-013 group were respectively 15.4±4.3 and 8.2±3.7, the tumor weight were (0.45±0.12) and (0.21±0.07) g, respectively. The tumor number and weight in the JTE-013 group were significantly less than those in the control group (all P< 0.01) . Conclusions: The growth of ovarian cancer cells could be decreased by S1PR2 inhibition in vitro and in vivo. One of the mechanisms of the growth inhibitory effect is probably that S1PR2 inhibition lower the phosphorylation level of extracellular regulated protein kinase 1/2 (ERK1/2) pathway, which prevent the transformation of ovarian cancer cells from phase G(1) to S.

Genetic stability of a dengue vaccine based on chimeric yellow fever/dengue viruses.

PubMed

Mantel, N; Girerd, Y; Geny, C; Bernard, I; Pontvianne, J; Lang, J; Barban, V

2011-09-02

A tetravalent dengue vaccine based on four live, attenuated, chimeric viruses (CYD1-4), constructed by replacing the genes coding for premembrane (prM) and envelope (E) proteins of the yellow fever (YF)-17D vaccine strain with those of the four serotypes of dengue virus, is in clinical phase III evaluation. We assessed the vaccine's genetic stability by fully sequencing each vaccine virus throughout the development and manufacturing process. The four viruses displayed complete genetic stability, with no change from premaster seed lots to bulk lots. When pursuing the virus growth beyond bulk lots, a few genetic variations were observed. Usually both the initial nucleotide and the new one persisted, and mutations appeared after a relatively high number of virus duplication cycles (65-200, depending on position). Variations were concentrated in the prM-E and non-structural (NS)4B regions. PrM-E variations had no impact on lysis-plaque size or neurovirulence in mice. None of the variations located in the YF-17D-derived genes corresponded with reversion to the wild-type Yellow Fever sequence. Variations in NS4B likely reflect virus adaptation to Vero cells growth. A low to undetectable viremia has been reported previously [1-3] in vaccinated non-human and human primates. Combined with the data reported here about the genetic stability of the vaccine strains, the probability of in vivo emergence of mutant viruses appears very low. Copyright © 2011 Elsevier Ltd. All rights reserved.

Tilting-induced decrease in systolic blood pressure in bedridden hypertensive elderly inpatients: effects of azelnidipine.

PubMed

Morimoto, Shigeto; Takahashi, Takashi; Okaishi, Kohya; Nakahashi, Takeshi; Nomura, Kohji; Kanda, Tsugiyasu; Okuro, Masashi; Murai, Hiroshi; Nishino, Tomoichi; Matsumoto, Masayuki

2006-12-01

The object of this study was to examine blood pressure (BP) variability due to postural change in elderly hypertensive patients. The subjects studied were 154 elderly inpatients in a hospital for the elderly (48 male and 106 female; median age: 82 years), consisting of age- and sex-matched bedridden (n=39) and non-bedridden (n=39) normotensive controls and bedridden (n=38) and non-bedridden (n=38) hypertensive patients. BP and pulse rate (PR) were measured in the supine position, then again after a 2-min, 45 deg head-up tilt with the legs horizontal. The decrease in systolic BP (SBP) on tilting in the bedridden hypertensive group (median: -10 mmHg; range: -32 to 9 mmHg) was significantly (p<0.008) greater than those in the other three groups. Monotherapy with azeinidipine, a long-acting calcium channel blocker, for 3 months not only significantly reduced the basal BP and PR of hypertensive patients in the two groups, but also significantly (p<0.05) attenuated the tilt-induced decrease in the SBP to -3 mmHg (-19 to 25 mmHg) and enhanced the change in PR from -1 bpm (-10 to 7 bpm) to 1 bpm (-4 to 23 bpm) in the bedridden hypertensive group. Our findings indicate that tilt-induced decrease in SBP is a rather common phenomenon in bedridden elderly hypertensive patients, and that treatment with azelnidipine attenuates tilt-induced decrease in SBP, probably through an improvement of baroreceptor sensitivity.

Revival of ferromagnetic behavior in charge-ordered Pr0.75Na0.25MnO3 manganite by ruthenium doping at Mn site and its MR effect

NASA Astrophysics Data System (ADS)

Elyana, E.; Mohamed, Z.; Kamil, S. A.; Supardan, S. N.; Chen, S. K.; Yahya, A. K.

2018-02-01

Ru doping in charge-ordered Pr0.75Na0.25Mn1-xRuxO3 (x = 0-0.1) manganites was studied to investigate its effect on structure, electrical transport, magnetic properties, and magnetotransport properties. DC electrical resistivity (ρ), magnetic susceptibility, and χ' measurements showed that sample x = 0 exhibits insulating behavior within the entire temperature range and antiferromagnetic (AFM) behavior below the charge-ordering (CO) transition temperature TCO of 221 K. Ru4+ substitution (x>0.01) suppressed the CO state, which resulted in the revival of paramagnetic to ferromagnetic (FM) transition at the Curie temperature Tc, increasing from 120 K (x = 0.01) to 193 K (x = 0.1). Deviation from the Curie-Weiss law above Tc in the 1/χ' versus T plot for x = 0.01 doped samples indicated the existence of Griffiths phase with Griffith temperature at 169 K. Electrical resistivity measurements showed that Ru4+ substitution increased the metallic-to-insulating transition temperature TMI from 144 K (x = 0.01) to 192 K (x = 0.05) due to enhanced double-exchange mechanism, but TMI decreased to 176 K (x = 0.1) probably due to the existence of AFM clusters within the FM domain. The present work also discussed the possible theoretical models at the resistivity curve of Pr0.75Na0.25Mn1-xRuxO3 (x = 0-0.1) for the entire temperature range.

A systematic review of population based epidemiological studies in Myasthenia Gravis

PubMed Central

2010-01-01

Background The aim was to collate all myasthenia gravis (MG) epidemiological studies including AChR MG and MuSK MG specific studies. To synthesize data on incidence rate (IR), prevalence rate (PR) and mortality rate (MR) of the condition and investigate the influence of environmental and technical factors on any trends or variation observed. Methods Studies were identified using multiple sources and meta-analysis performed to calculate pooled estimates for IR, PR and MR. Results 55 studies performed between 1950 and 2007 were included, representing 1.7 billion population-years. For All MG estimated pooled IR (eIR): 5.3 per million person-years (C.I.:4.4, 6.1), range: 1.7 to 21.3; estimated pooled PR: 77.7 per million persons (C.I.:64.0, 94.3), range 15 to 179; MR range 0.1 to 0.9 per millions person-years. AChR MG eIR: 7.3 (C.I.:5.5, 7.8), range: 4.3 to 18.0; MuSK MG IR range: 0.1 to 0.32. However marked variation persisted between populations studied with similar methodology and in similar areas. Conclusions We report marked variation in observed frequencies of MG. We show evidence of increasing frequency of MG with year of study and improved study quality. This probably reflects improved case ascertainment. But other factors must also influence disease onset resulting in the observed variation in IR across geographically and genetically similar populations. PMID:20565885

Catalytical Photocyclization of Arylamines with a-Olefins in the Synthesis of 2-Alkylquinoline

ERIC Educational Resources Information Center

Makhmutov, Aynur; Usmanov, Salavat; Mustafin, Ahat

2016-01-01

The article deals with the results of investigation of the process of catalytical photocyclization of aniline and aniline hydrochloride with a-olefins (hexene-1, heptene-1 and octene-1). The following compounds of d- and f-metals are tested as probable catalysts: CuSO4•5H2O, EuCl3•6H2O, PrCl3•6H2O, TbCl3•6H2O, La2O3, MnO2, NiSO4•6H2O, NiCl2•6H2O,…

Effects of Random Shadings, Phasing Errors, and Element Failures on the Beam Patterns of Linear and Planar Arrays

DTIC Science & Technology

1980-03-14

failure Sigmar (Or) in line 50, the standard deviation of the relative error of the weights Sigmap (o) in line 60, the standard deviation of the phase...200, the weight structures in the x and y coordinates Q in line 210, the probability of element failure Sigmar (Or) in line 220, the standard...NUMBER OF ELEMENTS =u;2*H 120 PRINT "Pr’obability of elemenit failure al;O 130 PRINT "Standard dtvi&t ion’ oe r.1&tive ýrror of wl; Sigmar 14 0 PRINT

Load and Pi control flux through the branched kinetic cycle of myosin V.

PubMed

Kad, Neil M; Trybus, Kathleen M; Warshaw, David M

2008-06-20

Myosin V is a processive actin-based motor protein that takes multiple 36-nm steps to deliver intracellular cargo to its destination. In the laser trap, applied load slows myosin V heavy meromyosin stepping and increases the probability of backsteps. In the presence of 40 mm phosphate (P(i)), both forward and backward steps become less load-dependent. From these data, we infer that P(i) release commits myosin V to undergo a highly load-dependent transition from a state in which ADP is bound to both heads and its lead head trapped in a pre-powerstroke conformation. Increasing the residence time in this state by applying load increases the probability of backstepping or detachment. The kinetics of detachment indicate that myosin V can detach from actin at two distinct points in the cycle, one of which is turned off by the presence of P(i). We propose a branched kinetic model to explain these data. Our model includes P(i) release prior to the most load-dependent step in the cycle, implying that P(i) release and load both act as checkpoints that control the flux through two parallel pathways.

Fission Product Release and Survivability of UN-Kernel LWR TRISO Fuel

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

Besmann, Theodore M; Ferber, Mattison K; Lin, Hua-Tay

2014-01-01

A thermomechanical assessment of the LWR application of TRISO fuel with UN kernels was performed. Fission product release under operational and transient temperature conditions was determined by extrapolation from range calculations and limited data from irradiated UN pellets. Both fission recoil and diffusive release were considered and internal particle pressures computed for both 650 and 800 m diameter kernels as a function of buffer layer thickness. These pressures were used in conjunction with a finite element program to compute the radial and tangential stresses generated with a TRISO particle as a function of fluence. Creep and swelling of the innermore » and outer pyrolytic carbon layers were included in the analyses. A measure of reliability of the TRISO particle was obtained by measuring the probability of survival of the SiC barrier layer and the maximum tensile stress generated in the pyrolytic carbon layers as a function of fluence. These reliability estimates were obtained as functions of the kernel diameter, buffer layer thickness, and pyrolytic carbon layer thickness. The value of the probability of survival at the end of irradiation was inversely proportional to the maximum pressure.« less

Fission product release and survivability of UN-kernel LWR TRISO fuel

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

T. M. Besmann; M. K. Ferber; H.-T. Lin

2014-05-01

A thermomechanical assessment of the LWR application of TRISO fuel with UN kernels was performed. Fission product release under operational and transient temperature conditions was determined by extrapolation from fission product recoil calculations and limited data from irradiated UN pellets. Both fission recoil and diffusive release were considered and internal particle pressures computed for both 650 and 800 um diameter kernels as a function of buffer layer thickness. These pressures were used in conjunction with a finite element program to compute the radial and tangential stresses generated within a TRISO particle undergoing burnup. Creep and swelling of the inner andmore » outer pyrolytic carbon layers were included in the analyses. A measure of reliability of the TRISO particle was obtained by computing the probability of survival of the SiC barrier layer and the maximum tensile stress generated in the pyrolytic carbon layers from internal pressure and thermomechanics of the layers. These reliability estimates were obtained as functions of the kernel diameter, buffer layer thickness, and pyrolytic carbon layer thickness. The value of the probability of survival at the end of irradiation was inversely proportional to the maximum pressure.« less

Lipid biosensor interactions with wild type and matrix deletion HIV-1 Gag proteins.

PubMed

Barklis, Eric; Staubus, August O; Mack, Andrew; Harper, Logan; Barklis, Robin Lid; Alfadhli, Ayna

2018-05-01

The matrix (MA) domain of the HIV-1 precursor Gag protein (PrGag) has been shown interact with the HIV-1 envelope (Env) protein, and to direct PrGag proteins to plasma membrane (PM) assembly sites by virtue of its affinity to phosphatidylinositol-4,5-bisphosphate (PI[4,5]P2). Unexpectedly, HIV-1 viruses with large MA deletions (ΔMA) have been shown to be conditionally infectious as long as they are matched with Env truncation mutant proteins or alternative viral glycoproteins. To characterize the interactions of wild type (WT) and ΔMA Gag proteins with PI(4,5)P2 and other acidic phospholipids, we have employed a set of lipid biosensors as probes. Our investigations showed marked differences in WT and ΔMA Gag colocalization with biosensors, effects on biosensor release, and association of biosensors with virus-like particles. These results demonstrate an alternative approach to the analysis of viral protein-lipid associations, and provide new data as to the lipid compositions of HIV-1 assembly sites. Copyright © 2018 Elsevier Inc. All rights reserved.

Endogenous murine leukemia virus-encoded proteins in radiation leukemias of BALB/c mice

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

Tress, E.; Pierotti, M.; DeLeo, A.B.

1982-02-01

To explore the role of endogenous retroviruses in radiation-induced leukemogenesis in the mouse, we have examined virus-encoded proteins in nine BALB/c leukemias by pulsechase labeling procedures and serological typing with monospecific and monoclonal antibodies. The major gag precursor protein, Pr65/sup gag/, was observed in all cases, but only three leukemias expressed detectable amounts of the glycosylated gag species, gP95/sup gag/, or its precursor, Pr75/sup gag/. No evidence was found for synthesis of gag-host fusion proteins. None of the leukemias released infectious xenotropic or dualtropic virus, but all nine expressed at least one env protein with xenotropic properties. In two instancesmore » a monoclonal antibody, 35/56, which is specific for the NuLV G/sub IX/ antigen, displayed a distinctive reactivity with this class of env protein, although this antibody is unreactive with replicating xenotropic viruses. An ecotropic/xenotropic recombinant env protein with the same 35/56 phenotype was observed in a leukemia induced by a strongly leukemogenic virus isolated from a BALB/c radiation leukemia.« less

A Markov State-based Quantitative Kinetic Model of Sodium Release from the Dopamine Transporter

NASA Astrophysics Data System (ADS)

Razavi, Asghar M.; Khelashvili, George; Weinstein, Harel

2017-01-01

The dopamine transporter (DAT) belongs to the neurotransmitter:sodium symporter (NSS) family of membrane proteins that are responsible for reuptake of neurotransmitters from the synaptic cleft to terminate a neuronal signal and enable subsequent neurotransmitter release from the presynaptic neuron. The release of one sodium ion from the crystallographically determined sodium binding site Na2 had been identified as an initial step in the transport cycle which prepares the transporter for substrate translocation by stabilizing an inward-open conformation. We have constructed Markov State Models (MSMs) from extensive molecular dynamics simulations of human DAT (hDAT) to explore the mechanism of this sodium release. Our results quantify the release process triggered by hydration of the Na2 site that occurs concomitantly with a conformational transition from an outward-facing to an inward-facing state of the transporter. The kinetics of the release process are computed from the MSM, and transition path theory is used to identify the most probable sodium release pathways. An intermediate state is discovered on the sodium release pathway, and the results reveal the importance of various modes of interaction of the N-terminus of hDAT in controlling the pathways of release.

Messages from the Abyss

NASA Astrophysics Data System (ADS)

2003-10-01

VLT Observes Infrared Flares from Black Hole at Galactic Centre [1] Summary An international team of astronomers led by researchers at the Max-Planck Institute for Extraterrestrial Physics (MPE) in Garching (Germany) [2] has discovered powerful infrared flares from the supermassive black hole at the heart of the Milky Way . The signals, rapidly flickering on a scale of minutes, must come from hot gas falling into the black hole, just before it disappears below the "event horizon" of the monster. The new observations strongly suggest that the Galactic Centre black hole rotates rapidly . Never before have scientists been able to study phenomena in the immediate neighbourhood of a black hole in such a detail. The new result is based on observations obtained with the NACO Adaptive Optics instrument on the 8.2-m VLT YEPUN telescope and is published in this week's edition of the research journal Nature. PR Photo 29a/03 : A powerful flare from the black hole at the galactic centre. PR Photo 29b/03 : Light curve of the flare . PR Video 01/03 : A powerful flare from the black hole at the galactic centre . Flashes of light from disappearing matter ESO PR Photo 29a/03 ESO PR Photo 29a/03 [Preview - JPEG: 650 x 400 pix - 118k [Normal - JPEG: 1300 x 800 pix - 370k] ESO PR Video Clip 01/03 [MPEG] ESO PR Video Clip 01/03 [MPEG Video; 29X k] Captions : PR Photo 29a/03 and PR Video Clip 01/03 show the detection of a powerful flare from the centre of the Milky Way galaxy. These and other adaptive optics (AO) images (with resolution 0.040 arcsec in the near-infrared H-band at wavelength 1.65 µm) of the central region of the Milky Way were obtained with the NACO imager on the 8.2-m VLT YEPUN telescope at the ESO Paranal Observatory on May 9, 2003. The image covers a sky area of about 1 x 1 arcsec, corresponding to about 45 light-days at the distance of the Galactic Centre. The time (in minutes from the beginning of the data set at 6h59m24s (UT) on May 9, 2003) is shown at the upper right of each image. North is up and East to the left. The position of the 15-year orbiting star S2 (cf. ESO Press Release 17/02 ) is marked by a cross and the astrometric location of the black hole is indicated by a circle. The scene was the usual one in the VLT Control Room at the Paranal Observatory in the early morning of May 9, 2003. Groups of astronomers from different nations were sitting in front of the computer screens, pointing the four giant telescopes in different directions and recording the sparse photons from the remotest corners of the Universe. There were the usual brief exchanges of information, numbers, wavelengths, strange acronyms, but then suddenly something happened at the YEPUN desk.... " What is that star doing there? " exclaimed Rainer Schödel , one of the MPE scientists in the team working with the NACO Adaptive Optics instrument [3] that delivers razor-sharp images. He and Reinhard Genzel, leader of the team and MPE Director, were observing the Milky Way Centre, when they saw the "new" object on the screen in front of them. The astronomers were puzzled and then became excited - something unusual must be going on, there at the centre of our galaxy! And then, a few minutes later, the "star" disappeared from view. Now the scientists had little doubt - they had just witnessed, for the first time, a powerful near-infrared flare from exactly the direction of the supermassive black hole at the heart of the Milky Way , cf. PR Photo 29a/03 and PR Video Clip 01/03 . " We had been looking for infrared emission from that black hole for more than a decade " recalls another team member, Andreas Eckart of the Cologne University. " We were certain that the black hole must be accreting matter from time to time. As this matter falls towards the surface of the black hole, it gets hotter and hotter and starts emitting infrared radiation ". But no such infrared radiation had been seen until that night at the VLT. This was the wonderful moment of breakthrough. Never before had anybody witnessed the last "scream" from matter in the deadly grip of a black hole, about to pass the point of no return towards an unknown fate. At the border ESO PR Photo 29b/03 ESO PR Photo 29b/03 [Preview - JPEG: 400 x 516 pix - 87k [Normal - JPEG: 800 x 1032 pix - 219k] Captions : PR Photo 29b/03 displays the "light curve" of a light flare from the galactic centre, as observed in the K-band (wavelength 2.2 µm) on June 16, 2003. This and a second flare discovered about 24 hours earlier show variability on a time scale of a few minutes and appear to show larger variations (arrows) with a 17-minute periodicity. The rapid variability implies that the infrared emission comes from just outside (the event horizon of) the black hole. If the periodicity is a fundamental property of the motion of gas orbiting the black hole, the Galactic Centre black hole must rotate with about half the maximum spin rate allowed by General Relativity. The present observations thus probe the space-time structure in the immediate vicinity of that event horizon. A careful analysis of the new observational data, reported in this week's issue of the Nature magazine, has revealed that the infrared emission originates from within a few thousandths of an arcsecond [4] from the position of the black hole (corresponding to a distance of a few light-hours) and that it varies on time scales of minutes ( PR Photo 29b/03 ). This proves that the infrared signals must come from just outside the so-called "event horizon" of the black hole, that is the "surface of no return" from which even light cannot escape. The rapid variability seen in all data obtained by the VLT clearly indicates that the region around this horizon must have chaotic properties - very much like those seen in thunderstorms or solar flares [5]. " Our data give us unprecedented information about what happens just outside the event horizon and let us test the predictions of General Relativity " explains Daniel Rouan , a team member from Paris-Meudon Observatory. " The most striking result is an apparent 17-minute periodicity in the light curves of two of the detected flares. If this periodicity is caused by the motion of gas orbiting the black hole, the inevitable conclusion is that the black hole must be rotating rapidly ". Reinhard Genzel is very pleased: " This is a major breakthrough. We know from theory that a black hole can only have mass, spin and electrical charge. Last year we were able to unambiguously prove the existence and determine the mass of the Galactic Centre black hole ( ESO Press Release 17/02 ). If our assumption is correct that the periodicity is the fundamental orbital time of the accreting gas, we now have also measured its spin for the first time . And that turns out to be about half of the maximum spin that General Relativity allows ". He adds: " Now the era of observational black hole physics has truly begun !" More information The results described in this ESO press release are presented in a report published today in the research journal "Nature" ("Near-IR Flares from Accreting Gas around the Supermassive Black Hole in the Galactic Centre", by Reinhard Genzel and co-authors).

Coordination behavior of bis-phenolate saturated and unsaturated N-heterocyclic carbene ligands to zirconium: reactivity and activity in the copolymerization of cyclohexene oxide with CO2.

PubMed

Lalrempuia, Ralte; Breivik, Frida; Törnroos, Karl W; Le Roux, Erwan

2017-06-27

Tetravalent zirconium complexes supported by tridentate bis-phenolate imidazolidin-2-ylidene (L1), imidazol-2-ylidene (L2) and benzimidazol-2-ylidene (L3) NHC ligands were synthesized and evaluated as precursors for the copolymerization of cyclohexene oxide (CHO) with CO 2 . While the reactivity of the imidazolidinium [H 3 L1] chloride salt with Zr(OiPr) 4 (HOiPr), and subsequent ligand exchanges with either (CH 3 ) 3 SiCl or LiOiPr lead to a series of heteroleptic compounds (κ 3 -O,C,O-L1)Zr(X) 2 (THF) (X = Cl, OiPr), both imidazolium [H 3 L2] and benzimidazolium [H 3 L3] chloride salts give a mixture of homoleptic (κ 3 -O,C,O-NHC) 2 Zr and zwitterionic (κ 2 -O,O-HL)ZrCl 2 (OiPr) compounds along with traces or the absence of the heteroleptic intermediate (κ 3 -O,C,O-NHC)Zr(Cl)(OiPr)(THF). Such dissimilar reactivity between the unsaturated and saturated NHC ligands is predominantly ascribed to the increased acidity of azolium salts along with the π-donor strength of the C carbene in L2 and L3-Zr moieties. The reactivity with the more acidic azolium salts (H 3 L2/3) and the destabilized Zr-X trans to NHC carbene bond results in a significant increase in the amount of homoleptic compounds generating HCl. The released HCl reacts preferentially with the heteroleptic intermediates having non-planar NHC ligands (i.e. L2/3) promoting the formation of zwitterionic complexes. The in situ deprotonation of the isolated zwitterionic (κ 2 -O,O-HL3)ZrCl 2 (OiPr) compound by using Ag 2 O gives the homoleptic complex as the major component along with a bimetallic hydroxo-bridged [(κ 3 -O,C,O-L3)Zr(μ-OH)(OiPr)] 2 compound. Of particular interest is that only the heteroleptic NHC-Zr(iv) complexes were identified to be active and highly selective towards the copolymerization of CHO with CO 2 independently of the co-catalysts used (both anionic and neutral) under mild conditions (P CO 2 < 1 bar, T = 60 °C), and gave atactic and completely alternating copolymers in a controlled manner (M w /M n ≈ 1.3-1.8). In contrast, the isolated homoleptic, zwitterionic and bimetallic zirconium species were found to be inactive under similar reaction conditions. Although the activity found for NHC-Zr(iv) complexes is nearly of the same order of magnitude as that of the NHC-Ti(iv) analogues, these results are the first examples of tetravalent zirconium complexes achieving high selectivity (99% in PCHC) in the catalyzed copolymerization of CHO with CO 2 .

Optimization and production of curdlan gum using Bacillus cereus PR3 isolated from rhizosphere of leguminous plant.

PubMed

Prakash, S; Rajeswari, K; Divya, P; Ferlin, M; Rajeshwari, C T; Vanavil, B

2018-05-28

Curdlan gum is a neutral water-insoluble bacterial exopolysaccharide composed primarily of linear β-(1,3) glycosidic linkages. Recently, there has been increasing interest in the applications of curdlan and its derivatives. Curdlan is found to inhibit tumors and its sulfated derivative possess anti-HIV activity. Curdlan is biodegradable, non-toxic towards human, environment and edible which makes it suitable as drug-delivery vehicles for sustained drug release. The increasing demand for the growing applications of curdlan requires an efficient high yield fermentation production process so as to satisfy the industrial needs. In this perspective, the present work is aimed to screen and isolate an efficient curdlan gum producing bacteria from rhizosphere of ground nut plant using aniline-blue agar. High yielding isolate was selected based on curdlan yield and identified as Bacillus cereus using gas-chromatography fatty acid methyl ester analysis. B. cereus PR3 curdlan gum was characterized using FT-IR spectroscopy, SEM, XRD and TGA. Fermentation time for curdlan production using B. cereus PR3 was optimized. Media constituents like carbon, nitrogen and mineral sources were screened using Plackett-Burman design. Subsequent statistical analysis revealed that Starch, NH 4 NO 3 , K 2 HPO 4 , Na 2 SO 4 , KH 2 SO 4 and CaCl 2 were significant media constituents and these concentrations were optimized for enhancement of curdlan production up to 20.88 g/l.

Task 90-17: Decontaminability Study on the U.S. Army Resuscitation Device, Individual, Chemical (RDIC)

DTIC Science & Technology

1991-04-01

RESTRIC-iVE VARK;NGS Unclassified 2a. SECURITY CLASSIF’CAT.ON AuTrHORITr 3 DISTRIBUTION,’AVALA8ILTY OF REPORT Approved for public release; 2b t ... T ;•R7 UTiON, AVAILABILITY OF ABSTRACT 121 A8STRACT SEC:RITY CLASSIFICATION (n UNCý.ASSiFE01IJNL,MITFD C3 SAME AS 7Pr 0 D:)rc usicts Unc la-,qi f it...was used to wipe the RDIC for 3 .i,,. The second, which is impregnated with chloramine B and is wetted with hydroxyethane (45 ± 2 percent), zinc

Release of chemical permeation enhancers from drug-in-adhesive transdermal patches.

PubMed

Qvist, Michael H; Hoeck, Ulla; Kreilgaard, Bo; Madsen, Flemming; Frokjaer, Sven

2002-01-14

There is only limited knowledge of how chemical permeation enhancers release from transdermal drug delivery systems of the drug-in-adhesive type. In this study, the release of eight commonly known enhancers from eight types of polymer adhesives was evaluated using Franz diffusion cells. It was shown that all the enhancers released completely from the adhesives and followed a square root of time kinetic (Higuchi law). Using a statistical analysis it was shown that the release rate was more dependent on the type of enhancer than on the type of polymers. The mean release rates were in the range from 2.2 to 11.1%/ radical t for the slowest and fastest releasing enhancers, which correspond to a 50% release within 500 and 20 min, respectively. Furthermore, the release rates were inversely proportional to the cube root of the molal volumes of the enhancers and to their logarithmic partition coefficients between the polymer adhesive and the receptor fluid. It was found that the observed release rates were probably due to a high diffusion coefficient of the enhancers rather than due to an inhomogeneous embedment of the enhancers in the adhesives. The type of adhesive showed minor influence on the release rate, especially among the acrylic polymers no difference was seen. However, compared to the acrylic adhesives, the polyisobutylene adhesive showed slower release rates, while the silicone adhesive showed slightly faster release rates.

Induction of Maltose Release by Light in the Endosymbiont Chlorella variabilis of Paramecium bursaria.

PubMed

Shibata, Aika; Takahashi, Fumio; Kasahara, Masahiro; Imamura, Nobutaka

2016-11-01

The endosymbiotic green algae of Paramecium bursaria are known to release a photosynthate to the host cells. The endosymbiont Chlorella variabilis F36-ZK isolated in Japan releases maltose under acidic conditions, and such release requires both light and low pH. However, whether photosynthate release is due to light sensing by photoreceptors or is merely a consequence of active photosynthesis is unclear. Herein, we studied the effect of light on maltose release from C. variabilis F36-ZK; we measured maltose release using a combination of 1-phenyl-3-methyl-5-pyrazolone derivative and 14 C-tracer methods. Blue (450nm) or red (around 600nm) light was most effective to stimulate maltose release. This suggests that the photosynthetic pathway probably participates in maltose release, because the effective wavelength corresponds to the absorption spectrum of chlorophyll. Furthermore, maltose release was slightly affected by addition of a photosynthetic inhibitor, 3-(3,4-dichlorophenyl)-1,1-dimethylurea, but was abolished by another inhibitor of photosynthesis, 2,5-dibromo-6-isopropyl-3-methyl-1,4-benzoquinone, suggesting that electron flow through photosystem I may be more involved in maltose release. Interestingly, starving F36-ZK cells cultured under prolonged dark conditions did not release maltose but retained their photosynthetic capacity. Our results thus show that maltose release is regulated by light and cellular conditions in endosymbiotic Chlorella. Copyright © 2016. Published by Elsevier GmbH.

Effects of Aminoguanidine on Pre- and Post-Irradiation Regional Cerebral Blood Flow, Systemic Blood Pressure and Plasma Histamine Levels in the Primate,

DTIC Science & Technology

1991-01-01

released HA may not be the sole mediator of these effects. Because elevations in plasma HA are probably due to HA derived from degranulation of mast cells ...release of other bioactive substances from mast cells may also influence these cardiovascular effects. Surprisingly, in sham-irradiated monkeys. AG...histaminergic nificantly altered by the administration ofAG. Al- mechanisms may be misguided. Mast cells , the though the two irradiated groups were

Release of the Biological Control Agent Puccinia jaceae var. solstitialis for Management of Yellow Starthistle at Fort Hunter Liggett, CA

DTIC Science & Technology

2010-07-01

used to manipulate the environment by burning, grazing, or revegetation efforts. Five insect species and a fungus have been officially released as...satisfied, the fungus would probably do extremely well and stress the plant early in the growing season. Used in conjunction with seed- feeding insects , it...241 km) south of San Francisco. The fort is primarily used as a training facility, where activities such as field maneuvers and live fire

Nanoscale distribution of presynaptic Ca(2+) channels and its impact on vesicular release during development.

PubMed

Nakamura, Yukihiro; Harada, Harumi; Kamasawa, Naomi; Matsui, Ko; Rothman, Jason S; Shigemoto, Ryuichi; Silver, R Angus; DiGregorio, David A; Takahashi, Tomoyuki

2015-01-07

Synaptic efficacy and precision are influenced by the coupling of voltage-gated Ca(2+) channels (VGCCs) to vesicles. But because the topography of VGCCs and their proximity to vesicles is unknown, a quantitative understanding of the determinants of vesicular release at nanometer scale is lacking. To investigate this, we combined freeze-fracture replica immunogold labeling of Cav2.1 channels, local [Ca(2+)] imaging, and patch pipette perfusion of EGTA at the calyx of Held. Between postnatal day 7 and 21, VGCCs formed variable sized clusters and vesicular release became less sensitive to EGTA, whereas fixed Ca(2+) buffer properties remained constant. Experimentally constrained reaction-diffusion simulations suggest that Ca(2+) sensors for vesicular release are located at the perimeter of VGCC clusters (<30 nm) and predict that VGCC number per cluster determines vesicular release probability without altering release time course. This "perimeter release model" provides a unifying framework accounting for developmental changes in both synaptic efficacy and time course. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Release of elements to natural water from sediments of Lake Roosevelt, Washington, USA

USGS Publications Warehouse

Paulson, Anthony J.; Cox, Stephen E.

2007-01-01

Reservoir sediments from Lake Roosevelt (WA, USA) that were contaminated with smelter waste discharged into the Columbia River (BC, Canada) were examined using three measures of elemental release reflecting varying degrees of physical mixing and time scales. Aqueous concentrations of Cd, Cu, Pb, and Zn in the interstitial water of reservoir sediments, in the gently stirred overlying waters of incubated sediment cores, and in supernatants of aggressively tumbled slurries of reservoir sediments generally were higher than the concentrations from a reference site. When compared to chronic water-quality criteria, all three measures of release suggest that slag-contaminated sediments near the U.S.-Canadian border are potentially toxic as a result of Cu release and Pb release in two of the three measures. All three measures of Cd release suggest potential toxicity for one site farther down the reservoir, probably contaminated as a result of transport and adsorption of Cd from smelter liquid waste. Releases of Zn and As did not appear to be potentially toxic. Carbonate geochemistry indirectly affects the potential toxicity by increasing water hardness.

Patients Lacking a KIR-Ligand of HLA Group C1 or C2 Have a Better Outcome after Umbilical Cord Blood Transplantation.

PubMed

Martínez-Losada, Carmen; Martín, Carmen; Gonzalez, Rafael; Manzanares, Bárbara; García-Torres, Estefania; Herrera, Concha

2017-01-01

Donor natural killer (NK) cells can destroy residual leukemic cells after allogeneic hematopoietic stem cell transplantation. This effect is based on the interaction of killer-cell immunoglobulin-like receptors (KIR) of donor NK cells with ligands of the major histocompatibility complex found on the surface of the target cells. HLA-C1 subtypes provide the ligand for KIR2DL2 and KIR2DL3 and the HLA-C2 subtypes for KIR2DL1. We have studied the probability of relapse (PR) after single-unit unrelated cord blood transplantation (UCBT) in relation to the potential graft-vs.-leukemia effect mediated by NK cells present in the umbilical cord blood (UCB) by analyzing KIR-ligand and HLA-C typing of the receptor. Data from 33 consecutive patients given a single unit UCBT were included. We have considered two groups of patients based on the absence or the presence of one of the C-ligands for inhibitory KIR and the incompatibility HLA-C1/2 between UCB and patients. Group 1 ( n  = 21): the patient lacks a C-ligand for inhibitory KIR present in UCB NK cells, i.e., patients homozygous C1/C1 or C2/C2. Group 2 ( n  = 12): patients heterozygous C1/C2 in which KIR-mediated graft-vs.-leukemia effect is not expected (presence of both C ligands for inhibitory KIR in the receptor). With a median follow-up post-UCBT of 93 months, patients with absence of a C-ligand for inhibitory KIRs (Group 1) showed a lower actuarial PR than patients with both C-ligands (group 2): 21 ± 10 vs. 68 ± 18% at 2 year and 36 ± 13 vs. 84 ± 14% at 5 years ( p  = 0.025), respectively. In patients with acute lymphoblastic leukemia, the 2-year PR was 36 ± 21% for group 1 and 66 ± 26% for 2 ( p  = 0.038). Furthermore, group 1 had a lower incidence of grades II-IV acute graft-vs.-host disease ( p  = 0.04). In the setting of UCBT, the absence of a C-ligand (C1 or C2) of inhibitory KIR in the patient is associated with lower PR, which is probably due to the graft-vs.-host leukemia effect caused by UCB NK cells that lack a ligand for the inhibitory KIR 2DL1/2DL2/2DL3.

Precipitation Processes Derived from TRMM Satellite Data, Cloud Resolving Model and Field Campaigns

NASA Technical Reports Server (NTRS)

Tao, W.-K.; Lang, S.; Simpson, J.; Meneghini, R.; Halverson, J.; Johnson, R.; Adler, R.; Einaudi, Franco (Technical Monitor)

2001-01-01

Rainfall is a key link in the hydrologic cycle and is a primary heat source for the atmosphere. The vertical distribution of latent-heat release, which is accompanied by rainfall, modulates the large-scale circulations of the tropics and in turn can impact midlatitude weather. This latent heat release is a consequence of phase changes between vapor, liquid. and solid water. Present large-scale weather and climate models can simulate cloud latent heat release only crudely thus reducing their confidence in predictions on both global and regional scales. In this paper, NASA Tropical Rainfall Measuring (TRMM) precipitation radar (PR) derived rainfall information and the Goddard Convective and Stratiform Heating (CSH) algorithm used to estimate the four-dimensional structure of global monthly latent heating and rainfall profiles over the global tropics from December 1997 to October 2000. Rainfall latent heating and radar reflectively structure between ENSO (1997-1998 winter) and non-ENSO (1998-1999 winter) periods are examined and compared. The seasonal variation of heating over various geographic locations (i.e. Indian ocean vs west Pacific; Africa vs S. America) are also analyzed. In addition, the relationship between rainfall latent heating maximum heating level), radar reflectively and SST are examined.

Identification and characterisation of seventeen glutathione S-transferase genes from the cabbage white butterfly Pieris rapae.

PubMed

Liu, Su; Zhang, Yu-Xing; Wang, Wen-Long; Zhang, Bang-Xian; Li, Shi-Guang

2017-11-01

Insect glutathione S-transferases (GSTs) play essential roles in the detoxification of insecticides and other xenobiotic compounds. The cabbage white butterfly, Pieris rapae, is an economically important agricultural pest. In this study, 17 cDNA sequences encoding putative GSTs were identified in P. rapae. All cDNAs include a complete open reading frame and were designated PrGSTd1-PrGSTz2. Based on phylogenetic analysis, PrGSTs were divided into six classes (delta, epsilon, omega, sigma, theta and zeta). The exon-intron organizations of these PrGSTs were also analysed. Recombinant proteins of eight PrGSTs (PrGSTD1, PrGSTD2, PrGSTE1, PrGSTE2, PrGSTO1, PrGSTS1, PrGSTT1 and PrGSTZ1) were heterologously expressed in Escherichia coli, and all of these proteins displayed glutathione-conjugating activity towards 1-chloro-2,4-dinitrobenzene (CDNB). Expression patterns in various larval tissues, at different life stages, and following exposure to sublethal doses of abamectin, chlorantraniliprole or lambda-cyhalothrin were determined by reverse transcription-quantitative PCR. The results showed that PrGSTe3, PrGSTs1, PrGSTs2, and PrGSTs4 were mainly transcribed in the fat body, while PrGSTe2 was expressed predominantly in the Malpighian tubules. Four genes (PrGSTe2, PrGSTo4, PrGSTs4 and PrGSTt1) were mainly expressed in fourth-instar larvae, while others were ubiquitously expressed in egg, larval, pupa and/or adult stages. Abamectin treatment significantly upregulated ten genes (PrGSTd1, PrGSTd3, PrGSTe1, PrGSTe2, PrGSTo1, PrGSTo3, PrGSTs1, PrGSTs3, PrGSTs4 and PrGSTt1). Chlorantraniliprole and lambda-cyhalothrin treatment significantly upregulated nine genes (PrGSTd1, PrGSTd2, PrGSTe1, PrGSTe2, PrGSTe3, PrGSTs1, PrGSTs3, PrGSTs4 and PrGSTz1) and ten genes (PrGSTd1, PrGSTd3, PrGSTe1, PrGSTe2, PrGSTo1, PrGSTo2, PrGSTs1, PrGSTs2, PrGSTs3 and PrGSTz2), respectively. These GSTs are potentially involved in the detoxification of insecticides. Copyright © 2017 Elsevier Inc. All rights reserved.

Importance of vesicle release stochasticity in neuro-spike communication.

PubMed

Ramezani, Hamideh; Akan, Ozgur B

2017-07-01

Aim of this paper is proposing a stochastic model for vesicle release process, a part of neuro-spike communication. Hence, we study biological events occurring in this process and use microphysiological simulations to observe functionality of these events. Since the most important source of variability in vesicle release probability is opening of voltage dependent calcium channels (VDCCs) followed by influx of calcium ions through these channels, we propose a stochastic model for this event, while using a deterministic model for other variability sources. To capture the stochasticity of calcium influx to pre-synaptic neuron in our model, we study its statistics and find that it can be modeled by a distribution defined based on Normal and Logistic distributions.

Sodium lauryl sulfate impedes drug release from zinc-crosslinked alginate beads: switching from enteric coating release into biphasic profiles.

PubMed

Taha, Mutasem O; Nasser, Wissam; Ardakani, Adel; Alkhatib, Hatim S

2008-02-28

The aim of this research is to investigate the effects of sodium lauryl sulfate (SLS) on ionotropically cross-linked alginate beads. Different levels of SLS were mixed with sodium alginate and chlorpheniramine maleate (as loaded model drug). The resulting viscous solutions were dropped onto aqueous solutions of zinc or calcium ions for ionotropic curing. The generated beads were assessed by their drug releasing profiles, infrared and differential scanning colorimetery (DSC) traits. SLS was found to exert profound concentration-dependent impacts on the characteristics of zinc-crosslinked alginate beads such that moderate modifications in the levels of SLS switched drug release from enteric coating-like behavior to a biphasic release modifiable to sustained-release by the addition of minute amounts of xanthan gum. Calcium cross-linking failed to reproduce the same behavior, probably due to the mainly ionic nature of calcium-carboxylate bonds compared to the coordinate character of their zinc-carboxylate counterparts. Apparently, moderate levels of SLS repel water penetration into the beads, and therefore minimize chlorpheniramine release. However, higher SLS levels seem to discourage polymeric cross-linking and therefore allow biphasic drug release.

Changes in brain amino acid content induced by hyposmolar stress and energy deprivation.

PubMed

Haugstad, T S; Valø, E T; Langmoen, I A

1995-12-01

The changes in endogenous amino acids in brain extracellular and intracellular compartments evoked by hyposmotic stress and energy deprivation were compared. Tissue content and release of ten amino acids were measured simultaneously in rat hippocampal slices by means of high performance liquid chromatography. Hyposmotic stress induced a large release of taurine (25568 pmol mg-1 protein), and a smaller release of glutamate, accompanied by an inverse change in tissue content. Adding mannitol to correct osmolarity, blocked these changes. Energy deprivation caused an increase in the release of all amino acids except glutamine. The release was particularly large for glutamate and GABA (31141 and 13282 pmol mg-1, respectively). The intracellular concentrations were generally reduced, but the total amount of the released amino acids increased In contrast to the effect seen during hyposmolar stress, mannitol enhanced the changes due to energy deprivation. The results show that hyposmolar stress and energy deprivation cause different content and release profiles, suggesting that the mechanisms involved in the two situations are either different or modulated in different ways. The intracellular amino acid depletion seen during energy deprivation shows that increased outward transport is probably a primary event, and increased amino acid formation likely secondary to this release.

Relating Convective and Stratiform Rain to Latent Heating

NASA Technical Reports Server (NTRS)

Tao, Wei-Kuo; Lang, Stephen; Zeng, Xiping; Shige, Shoichi; Takayabu, Yukari

2010-01-01

The relationship among surface rainfall, its intensity, and its associated stratiform amount is established by examining observed precipitation data from the Tropical Rainfall Measuring Mission (TRMM) Precipitation Radar (PR). The results show that for moderate-high stratiform fractions, rain probabilities are strongly skewed toward light rain intensities. For convective-type rain, the peak probability of occurrence shifts to higher intensities but is still significantly skewed toward weaker rain rates. The main differences between the distributions for oceanic and continental rain are for heavily convective rain. The peak occurrence, as well as the tail of the distribution containing the extreme events, is shifted to higher intensities for continental rain. For rainy areas sampled at 0.58 horizontal resolution, the occurrence of conditional rain rates over 100 mm/day is significantly higher over land. Distributions of rain intensity versus stratiform fraction for simulated precipitation data obtained from cloud-resolving model (CRM) simulations are quite similar to those from the satellite, providing a basis for mapping simulated cloud quantities to the satellite observations. An improved convective-stratiform heating (CSH) algorithm is developed based on two sources of information: gridded rainfall quantities (i.e., the conditional intensity and the stratiform fraction) observed from the TRMM PR and synthetic cloud process data (i.e., latent heating, eddy heat flux convergence, and radiative heating/cooling) obtained from CRM simulations of convective cloud systems. The new CSH algorithm-derived heating has a noticeably different heating structure over both ocean and land regions compared to the previous CSH algorithm. Major differences between the new and old algorithms include a significant increase in the amount of low- and midlevel heating, a downward emphasis in the level of maximum cloud heating by about 1 km, and a larger variance between land and ocean in the new CSH algorithm.

Cost-effectiveness evaluation of clobetasol propionate shampoo (CPS) maintenance in patients with moderate scalp psoriasis: a Pan-European analysis.

PubMed

Papp, K; Poulin, Y; Barber, K; Lynde, C; Prinz, J C; Berg, M; Kerrouche, N; Rives, V P

2012-11-01

Scalp psoriasis is a difficult to treat and usually chronic manifestation of psoriasis. The CalePso study showed that CPS (Clobex(®) Shampoo) in maintenance therapy of scalp psoriasis (twice weekly) significantly increases the probability of keeping patient under remission during 6 months, compared with vehicle (40.3% relapses vs. 11.6% relapses, ITT). The objective of the study was to assess the cost-effectiveness of a maintenance therapy with CPS vs. its vehicle in nine European countries. A 24-week decision tree model was developed with 4-weekly time steps. The considered population has moderate scalp psoriasis successfully treated with a daily application of CPS up to 4 weeks. Data were taken from the CalePso study and from national experts' recommendations for alternative treatment choices, with their probabilities of success taken from literature to develop country-specific models. Health benefits are measured in disease-free days (DFD). The economic analysis includes drug and physician costs. A probabilistic sensitivity analysis (PrSA) assesses the uncertainty of the model. Depending on the country, the mean total number of DFDs per patient is 21-42% higher with CPS compared with vehicle, and the mean total cost is 11-31% lower. The mean costs per DFD are 30-46% lower with CPS compared with the vehicle. The PrSA showed in 1000 simulations that CPS is more effective vs. vehicle in 100% of the cases and less expensive than its vehicle in 80-99% of the cases. This model suggests that CPS is cost-effective in maintaining the success achieved in moderate scalp psoriasis patients. © 2011 The Authors. Journal of the European Academy of Dermatology and Venereology © 2011 European Academy of Dermatology and Venereology.

The Cost Effectiveness of Maintenance Schedules Following Pulmonary Rehabilitation in Patients with Chronic Obstructive Pulmonary Disease: An Economic Evaluation Alongside a Randomised Controlled Trial.

PubMed

Burns, Darren K; Wilson, Edward C F; Browne, Paula; Olive, Sandra; Clark, Allan; Galey, Penny; Dix, Emma; Woodhouse, Helene; Robinson, Sue; Wilson, Andrew

2016-02-01

Chronic obstructive pulmonary disease (COPD) affects approximately 3 million people in the UK. An 8-week pulmonary rehabilitation (PR) course is recommended under current guidelines. However, studies show that initial benefits diminish over time. We present here an economic evaluation conducted alongside a randomised controlled trial (RCT) of a low-intensity maintenance programme over a time horizon of 1 year delivered in UK primary and secondary care settings. Patients with COPD who completed at least 60 % of a standard 8-week PR programme were randomised to a 2-h maintenance session at 3, 6 and 9 months (n = 73) or treatment as usual (n = 75). Outcomes were change in Chronic Respiratory Questionnaire (CRQ) score, EQ-5D-based QALYs, cost (price year 2014) to the UK NHS and social services over the 12 months following initial PR, and incremental cost-effectiveness ratios (ICERs). At 12 months, incremental cost to the NHS and social services was -£204.04 (95 % CI -£1522 to £1114). Incremental CRQ and QALY gains were -0.007 (-0.461 to 0.447) and +0.015 (-0.050 to 0.079), respectively. Based on point estimates, PR maintenance therefore dominates treatment as usual from the perspective of the NHS and social services in terms of cost per QALY gained. Whether it is cost effective in terms of CRQ depends on whether the £204 per patient could be reinvested elsewhere to a CRQ gain of greater than 0.007. However, there is much decision uncertainty: 95 % CIs around increments did not exclude zero, and there is a 72.9 % (72.5 %) probability that the ICER is below £20,000 (£30,000) per QALY. Future research should explore whether more intensive maintenance regimens offer benefit to patients at reasonable cost.

Association of Clinical Response and Long-term Outcome Among Patients With Biopsied Orbital Pseudotumor Receiving Modern Radiation Therapy

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

Prabhu, Roshan S., E-mail: rprabhu@emory.edu; Kandula, Shravan; Liebman, Lang

2013-03-01

Purpose: To retrospectively evaluate institutional outcomes for patients treated with modern radiation therapy (RT) for biopsied orbital pseudotumor (OP). Methods and Materials: Twenty patients (26 affected orbits) with OP were treated with RT between January 2002 and December 2011. All patients underwent biopsy with histopathologic exclusion of other disease processes. Sixteen patients (80%) were treated with intensity modulated RT, 3 (15%) with opposed lateral beams, and 1 (5%) with electrons. Median RT dose was 27 Gy (range 25.2-30.6 Gy). Response to RT was evaluated at 4 months post-RT. Partial response (PR) was defined as improvement in orbital symptoms without anmore » increase in steroid dose. Complete response (CR) 1 and CR 2 were defined as complete resolution of orbital symptoms with reduction in steroid dose (CR 1) or complete tapering of steroids (CR 2). The median follow-up period was 18.6 months (range 4-81.6 months). Results: Seventeen patients (85%) demonstrated response to RT, with 7 (35%), 1 (5%), and 9 (45%) achieving a PR, CR 1, and CR 2, respectively. Of the 17 patients who had ≥PR at 4 months post-RT, 6 (35%) experienced recurrence of symptoms. Age (>46 years vs ≤46 years, P=.04) and clinical response to RT (CR 2 vs CR 1/PR, P=.05) were significantly associated with pseudotumor recurrence. Long-term complications were seen in 7 patients (35%), including 4 with cataract formation, 1 with chronic dry eye, 1 with enophthalmos, and 1 with keratopathy. Conclusions: RT is an effective treatment for improving symptoms and tapering steroids in patients with a biopsy supported diagnosis of OP. Older age and complete response to RT were associated with a significantly reduced probability of symptom recurrence. The observed late complications may be related to RT, chronic use of steroids/immunosuppressants, medical comorbidities, or combination of factors.« less

Male breast cancer according to tumor subtype and race: a population-based study.

PubMed

Chavez-Macgregor, Mariana; Clarke, Christina A; Lichtensztajn, Daphne; Hortobagyi, Gabriel N; Giordano, Sharon H

2013-05-01

Breast cancer occurs rarely in men. To the authors' knowledge, no population-based estimates of the incidence of human epidermal growth factor receptor 2 (HER2)-positive breast cancer or of the distribution of breast cancer subtypes among male breast cancer patients have been published to date. Therefore, the objective of the current study was to explore breast tumor subtype distribution by race/ethnicity among men in the large, ethnically diverse population of California. This study included men who were diagnosed with invasive breast cancer between 2005 and 2009 with known estrogen receptor (ER) and progesterone receptor (PR) (together, hormone receptor [HR]) status and HER2 status reported to the California Cancer Registry. Among the men with HR-positive tumors, survival probabilities between groups were compared using log-rank tests. Six hundred six patients were included. The median age at diagnosis was 68 years. Four hundred ninety-four men (81.5%) had HR-positive tumors (defined as ER-positive and/or PR-positive and HER2-negative). Ninety men (14.9%) had HER2-positive tumors, and 22 (3.6%) had triple receptor-negative (TN) tumors. Among the patients with HR-positive tumors, non-Hispanic black men and Hispanic men were more likely to have PR-negative tumors than non-Hispanic white men. No statistically significant differences in survival were observed according to tumor subtype (P = .08). Differences in survival according to race/ethnicity were observed among all patients (P = .087) and among those with HR-positive tumors (P = .0170), and non-Hispanic black men had poorer outcomes. In this large, representative cohort of men with breast cancer, the distribution of tumor subtypes was different from that reported for women and varied by patient race/ethnicity. Non-Hispanic black men were more likely to have TN tumors and ER-positive/PR-negative tumors than white men. Copyright © 2013 American Cancer Society.

Efficacy and mechanism of action of Proellex, an antiprogestin in aromatase overexpressing and Letrozole resistant T47D breast cancer cells.

PubMed

Gupta, Akash; Mehta, Rajeshwari; Alimirah, Fatouma; Peng, Xinjian; Murillo, Genoveva; Wiehle, Ronald; Mehta, Rajendra G

2013-01-01

Aromatase inhibitors (AI) are considered as a first line therapy for ER+PR+ breast cancers. However, many patients acquire resistance to AI. In this study, we determined the response of antiprogestin CDB-4124 (Proellex) on the aromatase overexpressing and Letrozole resistant cell lines and also studies its mechanism of action in inhibition of breast cancer cell proliferation. For these studies we generated aromatase overexpressing T47D (T47Darom) and respective control (T47Dcon) breast cancer cell lines by stable transfection with plasmid containing CYP19A1 gene, or empty vector respectively. Letrozole resistant cell line (T47DaromLR) was generated by incubating T47Darom for 75 weeks in the presence of 10 μM Letrozole. Cell proliferation was determined by MTT or crystal violet assays. Gene expressions were quantified by QRT-PCR whereas proteins were identified by western blot analyses, flow cytometry and immunofluorescence staining. Aromatase activity was determined by estradiol ELISA. The effects of Proellex on the anchorage independent growth were measured by soft agar colony formation. Statistical differences between the various groups were determined by Student's 't' test or ANOVA followed by Bonferroni's post hoc test. Results showed that T47Darom and T47DaromLR cell lines had significantly higher aromatase expression (mRNA; 80-90 fold and protein) and as a result exhibited increased aromatization of testosterone to estradiol as compared to T47Dcon. Both these cell lines showed enhanced growth in the presence of Testosterone (50-60%). In T47DaromLR cells increased PR-B and EGFR expression as compared to T47Dcon cells was observed. Proellex and other known aromatase inhibitors (Letrozole, Anastrozole, and Exemestane) inhibited testosterone induced cell proliferation and anchorage independent growth of T47Darom cells. Cell growth inhibition was significantly greater when cells were treated with Proellex alone or in combination with other AIs as compared to AIs alone. Proellex inhibited mRNA and protein levels of PR-B, reduced PRB/p300 complex formation in the nuclei and significantly reduced EGFR expression in T47Darom cells. Our results in the present study indicate that antiproliferative effect of Proellex is probably due to PR-B/EGFR modulation in ER+PR+, aromatase expressing cells. Overall these results suggest that antiprogestin, Proellex can be developed as a possible treatment strategy for aromatase overexpressing ER+/PR+ breast cancer patients as well as for aromatase inhibitor resistant breast cancer patients. Copyright © 2012 Elsevier Ltd. All rights reserved.

Sino-implant (II) - a levonorgestrel-releasing two-rod implant: systematic review of the randomized controlled trials

PubMed Central

Steiner, Markus J.; Lopez, Laureen M.; Grimes, David A.; Cheng, Linan; Shelton, Jim; Trussell, James; Farley, Timothy M.M.; Dorflinger, Laneta

2013-01-01

Background Sino-implant (II) is a subdermal contraceptive implant manufactured in China. This two-rod levonorgestrel-releasing implant has the same amount of active ingredient (150 mg levonorgestrel) and mechanism of action as the widely available contraceptive implant Jadelle. We examined randomized controlled trials of Sino-implant (II) for effectiveness and side effects. Study design We searched electronic databases for studies of Sino-implant (II), and then restricted our review to randomized controlled trials. The primary outcome of this review was pregnancy. Results Four randomized trials with a total of 15,943 women assigned to Sino-implant (II) had first-year probabilities of pregnancy ranging from 0.0% to 0.1%. Cumulative probabilities of pregnancy during the four years of the product's approved duration of use were 0.9% and 1.06% in the two trials that presented date for four-year use. Five-year cumulative probabilities of pregnancy ranged from 0.7% to 2.1%. In one trial, the cumulative probability of pregnancy more than doubled during the fifth year (from 0.9% to 2.1%), which may be why the implant is approved for four years of use in China. Five-year cumulative probabilities of discontinuation due to menstrual problems ranged from 12.5% to 15.5% for Sino-implant (II). Conclusions Sino-implant (II) is one of the most effective contraceptives available today. These available clinical data, combined with independent laboratory testing, and the knowledge that 7 million women have used this method since 1994, support the safety and effectiveness of Sino-implant (II). The lower cost of Sino-implant (II) compared with other subdermal implants could improve access to implants in resource-constrained settings. PMID:20159174

Self-imposed length limits in recreational fisheries

USGS Publications Warehouse

Chizinski, Christopher J.; Martin, Dustin R.; Hurley, Keith L.; Pope, Kevin L.

2014-01-01

A primary motivating factor on the decision to harvest a fish among consumptive-orientated anglers is the size of the fish. There is likely a cost-benefit trade-off for harvest of individual fish that is size and species dependent, which should produce a logistic-type response of fish fate (release or harvest) as a function of fish size and species. We define the self-imposed length limit as the length at which a captured fish had a 50% probability of being harvested, which was selected because it marks the length of the fish where the probability of harvest becomes greater than the probability of release. We assessed the influences of fish size, catch per unit effort, size distribution of caught fish, and creel limit on the self-imposed length limits for bluegill Lepomis macrochirus, channel catfish Ictalurus punctatus, black crappie Pomoxis nigromaculatus and white crappie Pomoxis annularis combined, white bass Morone chrysops, and yellow perch Perca flavescens at six lakes in Nebraska, USA. As we predicted, the probability of harvest increased with increasing size for all species harvested, which supported the concept of a size-dependent trade-off in costs and benefits of harvesting individual fish. It was also clear that probability of harvest was not simply defined by fish length, but rather was likely influenced to various degrees by interactions between species, catch rate, size distribution, creel-limit regulation and fish size. A greater understanding of harvest decisions within the context of perceived likelihood that a creel limit will be realized by a given angler party, which is a function of fish availability, harvest regulation and angler skill and orientation, is needed to predict the influence that anglers have on fish communities and to allow managers to sustainable manage exploited fish populations in recreational fisheries.

[Effect of slow-release aminophylline on pulmonary function in obstructive respiratory disease(author's transl)].

PubMed

Wiessmann, K J

1975-09-05

The effects on pulmonary function of a slow-release preparation of an oral broncholytic drug (containing 350 mg aminophylline, released over eight hours) was tested on 26 patients in a double-blind trial. There was a marked reduction of airway resistance and stimulation of breathing with decreased dynamic work of breathing. Distinctly improved alveolar function was demonstrated especially in a fall of arterial CO2 tension, but in some cases there was probably an increase in distribution abnormality. Central haemodynamic changes with a decreased in pulmonary artery pressure and changes in the other values lasted for more than ten hours on the first day of treatment, and were demonstrable on the fourth day even before the drug was taken that day. The criteria of an effective broncholytic slow-release drug with sustained effect were thus fulfilled.

Structure Based Discovery of Pan Active Botulinum Neurotoxin Inhibitors

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

Vieni, Casey; McGillick, Brian; Kumaran, Desigan

Clostridium botulinum neurotoxins (BoNTs) released by the bacterium Clostridium botulinum are the most potent toxins causing the fatal disease called botulism. There are seven distinct serotypes of BoNTs (A to G) released by various strains of botulinum. They all have high sequence homology and similar three-dimensional structure. The toxicity of BoNT follows a four-step process – binding, internalization, translocation, and cleavage of its target protein, one of the three components of the SNARE complex (Soluble N-ethylmaleimde-sensitive factor attachment protein receptor) required for membrane docking and neurotransmitter release. Cleavage of one of the three proteins causes blockage of neurotransmitter release leadingmore » to flaccid paralysis. Though anyone of the above four steps could be a target for developing antidotes for botulism, the catalytic domain is the most suitable target for post exposure treatment. Of the seven serotypes BoNT/A, B, E and probably F affect humans, with BoNT/A considered to be the most potent. Development of drugs for botulism is focused on serotype specific inhibitors, but a pan-active inhibitor acting on several serotypes is preferable since it is difficult to identify the serotype before the treatment, especially since there is at least a 36-hour window before botulism can be diagnosed. Using structure-based drug discovery, we have developed three heptapeptides based on the SNARE proteins which inhibit BoNT/A, B and E equally well. Probable reasons for pan-activity of these peptides are discussed.« less

Structure Based Discovery of Pan Active Botulinum Neurotoxin Inhibitors

DOE PAGES

Vieni, Casey; McGillick, Brian; Kumaran, Desigan; ...

2018-02-14

Clostridium botulinum neurotoxins (BoNTs) released by the bacterium Clostridium botulinum are the most potent toxins causing the fatal disease called botulism. There are seven distinct serotypes of BoNTs (A to G) released by various strains of botulinum. They all have high sequence homology and similar three-dimensional structure. The toxicity of BoNT follows a four-step process – binding, internalization, translocation, and cleavage of its target protein, one of the three components of the SNARE complex (Soluble N-ethylmaleimde-sensitive factor attachment protein receptor) required for membrane docking and neurotransmitter release. Cleavage of one of the three proteins causes blockage of neurotransmitter release leadingmore » to flaccid paralysis. Though anyone of the above four steps could be a target for developing antidotes for botulism, the catalytic domain is the most suitable target for post exposure treatment. Of the seven serotypes BoNT/A, B, E and probably F affect humans, with BoNT/A considered to be the most potent. Development of drugs for botulism is focused on serotype specific inhibitors, but a pan-active inhibitor acting on several serotypes is preferable since it is difficult to identify the serotype before the treatment, especially since there is at least a 36-hour window before botulism can be diagnosed. Using structure-based drug discovery, we have developed three heptapeptides based on the SNARE proteins which inhibit BoNT/A, B and E equally well. Probable reasons for pan-activity of these peptides are discussed.« less

Modelling the transport of oil after a proposed oil spill accident in Barents Sea and its environmental impact on Alke species

NASA Astrophysics Data System (ADS)

Lu, J.; Yuan, F.; Mikkelsen, J. D.; Ohm, C.; Stange, E.; Holand, M.

2017-08-01

Accidental oil spills can have significant effect on the coastal and marine environment. As the oil extraction and exploration activities increase in the Barents Sea, it is of increasingly importance to investigate the potential oil spill incidents associated with these activities. In this study, the transport and fate of oil after a proposed oil spill incident in Barents Sea was modelled by oil spill contingency and response model OSCAR. The possibility that the spilled oil reach the open sea and the strand area was calculated respectively. The influence area of the incident was calculated by combining the results from 200 simulations. The possibility that the spilled oil reach Alke species, a vulnerable species and on the National Red List of birds in Barents Sea, was analyzed by combining oil spill modelling results and the Alke species distribution data. The results showed that oil is dominated with a probability of 70-100% in the open sea to reach an area in a radius of 20km from the release location after 14 days of release. The probability reduces with the increasing distances from the release location. It is higher possibility that the spilled oil will reach the Alke species in the strand area than in the open sea in the summer. The total influence area of the release is 11 429 km2 for the surface water and 1528 km2 for the coastal area.

Gonadotropin-releasing hormone increased pregnancy risk in suckled beef cows not detected in estrus and subjected to a split-time artificial insemination program.

PubMed

Hill, S L; Grieger, D M; Olson, K C; Jaeger, J R; Dahlen, C R; Crosswhite, M R; Pereira, N Negrin; Underdahl, S R; Neville, B W; Ahola, J; Fischer, M C; Seidel, G E; Stevenson, J S

2016-09-01

We hypothesized that GnRH would increase pregnancy risk (PR) in a split-time AI program for cows in which estrus was not detected. A total of 1,236 suckled beef cows at 12 locations in 3 states (Colorado, Kansas, and North Dakota) were enrolled. Before applying the fixed-time AI program, BCS was assessed. Cows were treated on d -7 with a progesterone insert concurrent with 100 μg GnRH and on d 0 with 25 mg PGF plus removal of the insert. Estrus-detection patches were affixed to cows at insert removal. Estrus was defined to have occurred when an estrus-detection patch was >50% colored (activated). Cows in estrus by 65 h ( = 758; 61.3% of all cows) were randomly allocated to 2 treatments: 1) 100 μg GnRH and early + GnRH (E+G; = 373) or 2) AI only at 65 h (early - no GnRH [E-G]; = 385). The remaining cows were randomly allocated to 2 treatments: 1) 5(L+G; = 252) or 2) AI only at 84 h (late no GnRH [L-G]; = 226). Pregnancy was determined 35 d after AI via transrectal ultrasound. Pregnancy risk did not differ ( = 0.68) between E+G and E-G cows (61.9 vs. 60.4%, respectively). Conversely, for cows inseminated at 84 h, PR was greater ( = 0.01) in cows that received GnRH (L+G) compared with their herd mates not receiving GnRH (L- G; 41.7 vs. 30.8%, respectively). Of those cows not detected in estrus by 65 h, 42.1% were detected by 84 h, for a total expression of estrus by all cows of 77.6%. Administration of GnRH increased ( < 0.01) PR in cows not detected in estrus by 84 h (+GnRH = 33.4% [ = 146] vs. no GnRH = 15.0% [ = 128]) but had no effect in cows expressing estrus by 84 h (+GnRH = 65.3% [ = 103] vs. no GnRH = 61.7% [ = 97]). Neither estrus expression by 65 or 84 h nor PR was influenced by BCS, parity, or days postpartum at AI. Cows had greater PR when they had been detected in estrus before AI, and PR was improved by administration of GnRH at 65 h after insert removal in cows that were not detected in estrus and inseminated at 84 h.

Bevacizumab plus fotemustine as first-line treatment in metastatic melanoma patients: clinical activity and modulation of angiogenesis and lymphangiogenesis factors.

PubMed

Del Vecchio, Michele; Mortarini, Roberta; Canova, Stefania; Di Guardo, Lorenza; Pimpinelli, Nicola; Sertoli, Mario R; Bedognetti, Davide; Queirolo, Paola; Morosini, Paola; Perrone, Tania; Bajetta, Emilio; Anichini, Andrea

2010-12-01

To assess the clinical and biological activity of the association of bevacizumab and fotemustine as first-line treatment in advanced melanoma patients. Previously untreated, metastatic melanoma patients (n = 20) received bevacizumab (at 15 mg/kg every 3 weeks) and fotemustine (100 mg/m² by intravenous administration on days 1, 8, and 15, repeated after 4 weeks) in a multicenter, single-arm, open-label, phase II study. Primary endpoint was the best overall response rate; other endpoints were toxicity, time to progression (TTP), and overall survival (OS). Serum cytokines, angiogenesis, and lymphangiogenesis factors were monitored by multiplex arrays and by in vitro angiogenesis assays. Effects of fotemustine on melanoma cells, in vitro, on vascular endothelial growth factor (VEGF)-C release and apoptosis were assessed by ELISA and flow cytometry, respectively. One complete response, 2 partial responses (PR), and 10 patients with stable disease were observed. TTP and OS were 8.3 and 20.5 months, respectively. Fourteen patients experienced adverse events of toxicity grade 3-4. Serum VEGF-A levels in evaluated patients (n = 15) and overall serum proangiogenic activity were significantly inhibited. A significant reduction in VEGF-C levels was found in several post-versus pretherapy serum samples. In vitro, fotemustine inhibited VEGF-C release by melanoma cells without inducing significant cell death. Serum levels of interleukin (IL)-10 and IL-12p70 showed the highest levels in sera of PR patients, compared with patients with stable or progressive disease whereas IL-23 showed the opposite pattern. The combination of bevacizumab plus fotemustine has clinical activity in advanced melanoma and promotes systemic modulation of angiogenesis and lymphangiogenesis factors. ©2010 AACR.

Prime mission results of the dual-frequency precipitation radar on the global precipitation measurement core spacecraft and the version 5 GPM standard products

NASA Astrophysics Data System (ADS)

Furukawa, K.; Nio, T.; Oki, R.; Kubota, T.; Iguchi, T.

2017-09-01

The Dual-frequency Precipitation Radar (DPR) on the Global Precipitation Measurement (GPM) core satellite was developed by Japan Aerospace Exploration Agency (JAXA) and National Institute of Information and Communications Technology (NICT). The objective of the GPM mission is to observe global precipitation more frequently and accurately. The GPM core satellite is a joint product of National Aeronautics and Space Administration (NASA), JAXA and NICT. NASA developed the satellite bus and the GPM Microwave Imager (GMI), and JAXA and NICT developed the DPR. The inclination of the GPM core satellite is 65 degrees, and the nominal flight altitude is 407 km. The non-sunsynchronous circular orbit is necessary for measuring the diurnal change of rainfall. The DPR consists of two radars, which are Ku-band precipitation radar (KuPR) and Ka-band precipitation radar (KaPR). GPM core observatory was successfully launched by H2A launch vehicle on Feb. 28, 2014. DPR orbital check out was completed in May 2014. DPR products were released to the public on Sep. 2, 2014 and Normal Observation Operation period was started. JAXA is continuing DPR trend monitoring, calibration and validation operations to confirm that DPR keeps its function and performance on orbit. The results of DPR trend monitoring, calibration and validation show that DPR kept its function and performance on orbit during the 3 years and 2 months prime mission period. The DPR Prime mission period was completed in May 2017. The version 5 GPM products were released to the public in 2017. JAXA confirmed that GPM/DPR total system performance and the GPM version 5 products achieved the success criteria and the performance indicators that were defined for the JAXA GPM/DPR mission.

The action of neutrophil serine proteases on elastin and its precursor.

PubMed

Heinz, Andrea; Jung, Michael C; Jahreis, Günther; Rusciani, Anthony; Duca, Laurent; Debelle, Laurent; Weiss, Anthony S; Neubert, Reinhard H H; Schmelzer, Christian E H

2012-01-01

This study aimed to investigate the degradation of the natural substrates tropoelastin and elastin by the neutrophil-derived serine proteases human leukocyte elastase (HLE), proteinase 3 (PR3) and cathepsin G (CG). Focus was placed on determining their cleavage site specificities using mass spectrometric techniques. Moreover, the release of bioactive peptides from elastin by the three proteases was studied. Tropoelastin was comprehensively degraded by all three proteases, whereas less cleavage occurred in mature cross-linked elastin. An analysis of the cleavage site specificities of the three proteases in tropoelastin and elastin revealed that HLE and PR3 similarly tolerate hydrophobic and/or aliphatic amino acids such as Ala, Gly and Val at P(1), which are also preferred by CG. In addition, CG prefers the bulky hydrophobic amino acid Leu and accepts the bulky aromatic amino acids Phe and Tyr. CG shows a strong preference for the charged amino acid Lys at P(1) in tropoelastin, whereas Lys was not identified at P(1) in CG digests of elastin due to extensive cross-linking at Lys residues in mature elastin. All three serine proteases showed a clear preference for Pro at P(2) and P(4)'. With respect to the liberation of potentially bioactive peptides from elastin, the study revealed that all three serine proteases have a similar ability to release bioactive sequences, with CG producing the highest number of these peptides. In bioactivity studies, potentially bioactive peptides that have not been investigated on their bioactivity to date, were tested. Three new bioactive GxxPG motifs were identified; GVYPG, GFGPG and GVLPG. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Bayesian inverse modeling and source location of an unintended 131I release in Europe in the fall of 2011

NASA Astrophysics Data System (ADS)

Tichý, Ondřej; Šmídl, Václav; Hofman, Radek; Šindelářová, Kateřina; Hýža, Miroslav; Stohl, Andreas

2017-10-01

In the fall of 2011, iodine-131 (131I) was detected at several radionuclide monitoring stations in central Europe. After investigation, the International Atomic Energy Agency (IAEA) was informed by Hungarian authorities that 131I was released from the Institute of Isotopes Ltd. in Budapest, Hungary. It was reported that a total activity of 342 GBq of 131I was emitted between 8 September and 16 November 2011. In this study, we use the ambient concentration measurements of 131I to determine the location of the release as well as its magnitude and temporal variation. As the location of the release and an estimate of the source strength became eventually known, this accident represents a realistic test case for inversion models. For our source reconstruction, we use no prior knowledge. Instead, we estimate the source location and emission variation using only the available 131I measurements. Subsequently, we use the partial information about the source term available from the Hungarian authorities for validation of our results. For the source determination, we first perform backward runs of atmospheric transport models and obtain source-receptor sensitivity (SRS) matrices for each grid cell of our study domain. We use two dispersion models, FLEXPART and Hysplit, driven with meteorological analysis data from the global forecast system (GFS) and from European Centre for Medium-range Weather Forecasts (ECMWF) weather forecast models. Second, we use a recently developed inverse method, least-squares with adaptive prior covariance (LS-APC), to determine the 131I emissions and their temporal variation from the measurements and computed SRS matrices. For each grid cell of our simulation domain, we evaluate the probability that the release was generated in that cell using Bayesian model selection. The model selection procedure also provides information about the most suitable dispersion model for the source term reconstruction. Third, we select the most probable location of the release with its associated source term and perform a forward model simulation to study the consequences of the iodine release. Results of these procedures are compared with the known release location and reported information about its time variation. We find that our algorithm could successfully locate the actual release site. The estimated release period is also in agreement with the values reported by IAEA and the reported total released activity of 342 GBq is within the 99 % confidence interval of the posterior distribution of our most likely model.

The release of acetylcholine from post-ganglionic cell bodies in response to depolarization.

PubMed Central

Johnson, D A; Pilar, G

1980-01-01

1. Acetylcholine (Ach) release from parasympathetic ganglia cell somata was investigated in denervated avian ciliary ganglia. Three days after the input to the ganglion (the oculomotor nerve) was sectioned, all presynaptic nerve terminals had degenerated. 2. Denervated ganglia were shown to contain endogenous ACh and to be capable of synthesizing [3H]ACh from [3H]choline added to the incubation medium. 3. In response to depolarization induced by incubation in 50 mM-[K+]o, denervated ganglia released [3H]ACh into bath effluents in amounts approximately 15% of the non-denervated contralateral control. This release was shown to be Ca2+ dependent in both intact and denervated ganglia. 4. Antidromic electrical stimulation of ciliary nerves also elicited [3H]ACh release. Nicotine (1 microgram/microliter.) depolarized denervated ciliary ganglion cells and evoked release of the transmitter and this release was antagonized by curare. 5. It is concluded that the ganglionic cell bodies sysnthesized ACh and released the transmitter in response to K+ depolarization, antidromic stimulation and cholinergic agonists, despite the lack of morphological specializations usually associated with stimulus-induced release of neurotransmitter. The evidence suggests the existence of a mechanism of transmitter release which is Ca2+ dependent, probably from a cytoplasmic pool and therefore distinct from the usual vesicular release at the nerve terminal. Images Plate 1 Plate 2 PMID:6247485

Predator response to releases of American shad larvae in the Susquehanna River basin

USGS Publications Warehouse

Johnson, James H.; Ringler, N.H.

1998-01-01

Predation on American shad (Alosa sapidissima) larvae within the first two hours of release was examined from 1989 to 1992 on 31 occasions at stocking sites in the Susquehanna River basin. Twenty-two fish species consumed shad larvae; the dominant predators were spotfin shiner (Cyprinella spiloptera), mimic shiner (Notropis volucellus) and juvenile smallmouth bass (Micropterus dolomieu). The number of shad larvae found in predator stomachs ranged from 0 to 900. Mortality of shad larvae at the stocking site was usually less than 2%. The greatest mortality (9.6%) occurred at the highest stocking level (1.5 million larvae). Highly variable predation rates and release levels of shad insufficient to achieve predator satiation hindered the ability to determine a specific type of functional response of predators. Predator numbers increased with stocking density, indicating short-term aggregation at the release site. Because of practical problems associated with releasing the large numbers of larvae that would be required to satiate predators, routine stocking at these levels is probably unreasonable. Releases of 400,000 to 700,000 larvae may reduce predation by offsetting depensatory mechanisms that operate on small releases and the effects of increased predation due to predator aggregation on large releases. Night stocking may reduce predation on larval shad at the release site.

Altered neurotransmitter release, vesicle recycling and presynaptic structure in the pilocarpine model of temporal lobe epilepsy

PubMed Central

Upreti, Chirag; Otero, Rafael; Partida, Carlos; Skinner, Frank; Thakker, Ravi; Pacheco, Luis F.; Zhou, Zhen-yu; Maglakelidze, Giorgi; Velíšková, Jana; Velíšek, Libor; Romanovicz, Dwight; Jones, Theresa; Stanton, Patric K.

2012-01-01

In searching for persistent seizure-induced alterations in brain function that might be causally related to epilepsy, presynaptic transmitter release has relatively been neglected. To measure directly the long-term effects of pilocarpine-induced status epilepticus on vesicular release and recycling in hippocampal mossy fibre presynaptic boutons, we used (i) two-photon imaging of FM1-43 vesicular release in rat hippocampal slices; and (ii) transgenic mice expressing the genetically encoded pH-sensitive fluorescent reporter synaptopHluorin preferentially at glutamatergic synapses. In this study we found that, 1–2 months after pilocarpine-induced status epilepticus, there were significant increases in mossy fibre bouton size, faster rates of action potential-driven vesicular release and endocytosis. We also analysed the ultrastructure of rat mossy fibre boutons using transmission electron microscopy. Pilocarpine-induced status epilepticus led to a significant increase in the number of release sites, active zone length, postsynaptic density area and number of vesicles in the readily releasable and recycling pools, all correlated with increased release probability. Our data show that presynaptic release machinery is persistently altered in structure and function by status epilepticus, which could contribute to the development of the chronic epileptic state and may represent a potential new target for antiepileptic therapies. PMID:22344585

No evidence of enemy release in pathogen and microbial communities of common wasps (Vespula vulgaris) in their native and introduced range.

PubMed

Lester, Philip J; Bosch, Peter J; Gruber, Monica A M; Kapp, Eugene A; Peng, Lifeng; Brenton-Rule, Evan C; Buchanan, Joe; Stanislawek, Wlodek L; Archer, Michael; Corley, Juan C; Masciocchi, Maitè; Van Oystaeyen, Annette; Wenseleers, Tom

2015-01-01

When invasive species move to new environments they typically experience population bottlenecks that limit the probability that pathogens and parasites are also moved. The invasive species may thus be released from biotic interactions that can be a major source of density-dependent mortality, referred to as enemy release. We examined for evidence of enemy release in populations of the common wasp (Vespula vulgaris), which attains high densities and represents a major threat to biodiversity in its invaded range. Mass spectrometry proteomic methods were used to compare the microbial communities in wasp populations in the native (Belgium and England) and invaded range (Argentina and New Zealand). We found no evidence of enemy release, as the number of microbial taxa was similar in both the introduced and native range. However, some evidence of distinctiveness in the microbial communities was observed between countries. The pathogens observed were similar to a variety of taxa observed in honey bees. These taxa included Nosema, Paenibacillus, and Yersina spp. Genomic methods confirmed a diversity of Nosema spp., Actinobacteria, and the Deformed wing and Kashmir bee viruses. We also analysed published records of bacteria, viruses, nematodes and fungi from both V. vulgaris and the related invader V. germanica. Thirty-three different microorganism taxa have been associated with wasps including Kashmir bee virus and entomophagous fungi such as Aspergillus flavus. There was no evidence that the presence or absence of these microorganisms was dependent on region of wasp samples (i.e. their native or invaded range). Given the similarity of the wasp pathogen fauna to that from honey bees, the lack of enemy release in wasp populations is probably related to spill-over or spill-back from bees and other social insects. Social insects appear to form a reservoir of generalist parasites and pathogens, which makes the management of wasp and bee disease difficult.

No Evidence of Enemy Release in Pathogen and Microbial Communities of Common Wasps (Vespula vulgaris) in Their Native and Introduced Range

PubMed Central

Lester, Philip J.; Kapp, Eugene A.; Peng, Lifeng; Brenton-Rule, Evan C.; Buchanan, Joe; Stanislawek, Wlodek L.; Archer, Michael; Corley, Juan C.; Masciocchi, Maitè; Van Oystaeyen, Annette; Wenseleers, Tom

2015-01-01

When invasive species move to new environments they typically experience population bottlenecks that limit the probability that pathogens and parasites are also moved. The invasive species may thus be released from biotic interactions that can be a major source of density-dependent mortality, referred to as enemy release. We examined for evidence of enemy release in populations of the common wasp (Vespula vulgaris), which attains high densities and represents a major threat to biodiversity in its invaded range. Mass spectrometry proteomic methods were used to compare the microbial communities in wasp populations in the native (Belgium and England) and invaded range (Argentina and New Zealand). We found no evidence of enemy release, as the number of microbial taxa was similar in both the introduced and native range. However, some evidence of distinctiveness in the microbial communities was observed between countries. The pathogens observed were similar to a variety of taxa observed in honey bees. These taxa included Nosema, Paenibacillus, and Yersina spp. Genomic methods confirmed a diversity of Nosema spp., Actinobacteria, and the Deformed wing and Kashmir bee viruses. We also analysed published records of bacteria, viruses, nematodes and fungi from both V. vulgaris and the related invader V. germanica. Thirty-three different microorganism taxa have been associated with wasps including Kashmir bee virus and entomophagous fungi such as Aspergillus flavus. There was no evidence that the presence or absence of these microorganisms was dependent on region of wasp samples (i.e. their native or invaded range). Given the similarity of the wasp pathogen fauna to that from honey bees, the lack of enemy release in wasp populations is probably related to spill-over or spill-back from bees and other social insects. Social insects appear to form a reservoir of generalist parasites and pathogens, which makes the management of wasp and bee disease difficult. PMID:25798856

Public health risk management case concerning the city of Isfahan according to a hypothetical release of HF from a chemical plant.

PubMed

Azari, Mansour R; Sadighzadeh, Asghar; Bayatian, Majid

2018-06-19

Accidents have happened in the chemical industries all over the world with serious consequences for the adjacent heavily populated areas. In this study, the impact of the probable hypothetical event, releasing considerable amounts of hydrogen fluoride (HF) as a strong irritant into the atmosphere over the city of Isfahan from a strategic chemical plant, was simulated by computational fluid dynamics (CFD). In this model, the meteorological parameters were integrated into time and space, and dispersion of the pollutants was estimated based on a probable accidental release of HF. According to the hypothetical results of the simulation model in this study, HF clouds reached Isfahan in 20 min and exposed 80% of the general public to HF concentration in the range of 0-34 ppm. Then, they dissipated 240 min after the time of the incident. Supposing the uniform population density within the proximity of the city of Isfahan with the population of 1.75 million, 5% of the population (87,500 people) could be exposed for a few minutes to a HF concentration as high as 34 ppm. This concentration is higher than a very hazardous concentration described as the Immediate Danger to Life and Health (30 ppm). This hypothetical risk evaluation of environmental exposure to HF with the potential of health risks was very instrumental for the general public of Isfahan in terms of risk management. Similar studies based on probable accidental scenarios along with the application of a simulation model for computation of dispersed pollutants are recommended for risk evaluation and management of cities in the developing countries with a fast pace of urbanization around the industrial sites.

AGR-3/4 Irradiation Test Predictions using PARFUME

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

Skerjanc, William Frances; Collin, Blaise Paul

2016-03-01

PARFUME, a fuel performance modeling code used for high temperature gas reactors, was used to model the AGR-3/4 irradiation test using as-run physics and thermal hydraulics data. The AGR-3/4 test is the combined third and fourth planned irradiations of the Advanced Gas Reactor (AGR) Fuel Development and Qualification Program. The AGR-3/4 test train consists of twelve separate and independently controlled and monitored capsules. Each capsule contains four compacts filled with both uranium oxycarbide (UCO) unaltered “driver” fuel particles and UCO designed-to-fail (DTF) fuel particles. The DTF fraction was specified to be 1×10-2. This report documents the calculations performed to predictmore » failure probability of TRISO-coated fuel particles during the AGR-3/4 experiment. In addition, this report documents the calculated source term from both the driver fuel and DTF particles. The calculations include the modeling of the AGR-3/4 irradiation that occurred from December 2011 to April 2014 in the Advanced Test Reactor (ATR) over a total of ten ATR cycles including seven normal cycles, one low power cycle, one unplanned outage cycle, and one Power Axial Locator Mechanism cycle. Results show that failure probabilities are predicted to be low, resulting in zero fuel particle failures per capsule. The primary fuel particle failure mechanism occurred as a result of localized stresses induced by the calculated IPyC cracking. Assuming 1,872 driver fuel particles per compact, failure probability calculated by PARFUME leads to no predicted particle failure in the AGR-3/4 driver fuel. In addition, the release fraction of fission products Ag, Cs, and Sr were calculated to vary depending on capsule location and irradiation temperature. The maximum release fraction of Ag occurs in Capsule 7 reaching up to 56% for the driver fuel and 100% for the DTF fuel. The release fraction of the other two fission products, Cs and Sr, are much smaller and in most cases less than 1% for the driver fuel. The notable exception occurs in Capsule 7 where the release fraction for Cs and Sr reach up to 0.73% and 2.4%, respectively, for the driver fuel. For the DTF fuel in Capsule 7, the release fraction for Cs and Sr are estimated to be 100% and 5%, respectively.« less

Effects of exogenous salinity (NaCl) gradient on Cd release in acidified contaminated brown soil

NASA Astrophysics Data System (ADS)

Zhang, Lina; Rong, Yong; Mao, Li; Gao, Zhiyuan; Liu, Xiaoyu; Dong, Zhicheng

2018-02-01

Taking acidified Cd contaminated brown soil in Yantai as the research object, based on different exogenous salinity (NaCl) gradient (0%, 0.3%, 0.6%, 0.9%, 1.5%, 2% and 5%), indoor simulation experiments of Cd release were carried out after field investigation. Results showed that there was a significantly positive relation (r>0.90) between Cd release concentration/amount/ratio and exogenous salt (NaCl). Besides, the more exogenous salt (NaCl) was added; maximum release concentration/amount of Cd appeared the earlier. It was found that exogenous salt (NaCl) addition could obviously promote Cd release from acidified Cd contaminated brown soil. It was believed that this could be mainly due to the cation exchange between Cd2+ and Na+, together with the dissociation and/or complexation between Cl- and Cd2+. In addition, available adsorption sites reduction by exchange base in soil causing Cd changed from solid state to soil solution was also a probable reason.