Tetrahydrobenzo[h][1,6]naphthyridine-6-chlorotacrine hybrids as a new family of anti-Alzheimer agents targeting β-amyloid, tau, and cholinesterase pathologies.

PubMed

Di Pietro, Ornella; Pérez-Areales, F Javier; Juárez-Jiménez, Jordi; Espargaró, Alba; Clos, M Victòria; Pérez, Belén; Lavilla, Rodolfo; Sabaté, Raimon; Luque, F Javier; Muñoz-Torrero, Diego

2014-09-12

Optimization of an essentially inactive 3,4-dihydro-2H-pyrano[3,2-c]quinoline carboxylic ester derivative as acetylcholinesterase (AChE) peripheral anionic site (PAS)-binding motif by double O → NH bioisosteric replacement, combined with molecular hybridization with the AChE catalytic anionic site (CAS) inhibitor 6-chlorotacrine and molecular dynamics-driven optimization of the length of the linker has resulted in the development of the trimethylene-linked 1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridine-6-chlorotacrine hybrid 5a as a picomolar inhibitor of human AChE (hAChE). The tetra-, penta-, and octamethylene-linked homologues 5b-d have been also synthesized for comparison purposes, and found to retain the nanomolar hAChE inhibitory potency of the parent 6-chlorotacrine. Further biological profiling of hybrids 5a-d has shown that they are also potent inhibitors of human butyrylcholinesterase and moderately potent Aβ42 and tau anti-aggregating agents, with IC50 values in the submicromolar and low micromolar range, respectively. Also, in vitro studies using an artificial membrane model have predicted a good brain permeability for hybrids 5a-d, and hence, their ability to reach their targets in the central nervous system. The multitarget profile of the novel hybrids makes them promising leads for developing anti-Alzheimer drug candidates with more balanced biological activities. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Physician's assistants in primary care practices: delegation of tasks and physician supervision.

PubMed

Ekwo, E; Dusdieker, L B; Fethke, C; Daniels, M

1979-01-01

Little information is available on factors influencing physicians (MDs) to delegate health care tasks to physician's assistants (PAs). Information about assignment of tasks to PAs was sought from 19 MDs engaged in practice in primary care settings in Iowa. These MDs employed 28 PAs. Tasks assigned to PAs appeared to be those that MDs judged to require little or no supervision. Tasks that could be performed efficiently by other non-MD personnel were not asigned to PAs. However, PAs were observed at the practice sites to perform tasks which the MDs had indicated could be appropriately assigned to PAs, as well as some tasks that could be performed by other non-MD personnel. The MDs provided health care to 126 (13.6 percent) of the 925 patients seen by PAs for whom the sequences of patient-provider contact were recorded. In these settings, the PAs functioned with a high degree of autonomy in providing health care. These findings have implications for educators and potential employers of PAs.

2010 Annual Summary Report for the Area 3 and Area 5 Radioactive Management Sites at the Nevada National Security Site, Nye County, Nevada

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

NSTec Environmental Management

2011-03-01

The U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office performed an annual review of the Area 3 and Area 5 Radioactive Waste Management Site (RWMS) Performance Assessments (PAs) and Composite Analyses (CAs) in fiscal year (FY) 2010. This annual summary report presents data and conclusions from the FY 2010 review, and determines the adequacy of the PAs and CAs. Operational factors (e.g., waste forms and containers, facility design, and waste receipts), closure plans, monitoring results, and research and development (R&D) activities were reviewed to determine the adequacy of the PAs. Likewise, the environmental restoration activities at themore » Nevada National Security Site (NNSS) (formerly the Nevada Test Site) relevant to the sources of residual radioactive material that are considered in the CAs, the land-use planning, and the results of the environmental monitoring and R&D activities were reviewed to determine the adequacy of the CAs.« less

Field Calibration of XAD-Based Passive Air Sampler on the Tibetan Plateau: Wind Influence and Configuration Improvement.

PubMed

Gong, Ping; Wang, Xiaoping; Liu, Xiande; Wania, Frank

2017-05-16

The passive air sampler based on XAD-2 resin (XAD-PAS) has proven useful for collecting atmospheric persistent organic pollutants (POPs) in remote regions. Whereas laboratory studies have shown that, due to the open bottom of its housing, the passive sampling rate (PSR) of the XAD-PAS is susceptible to wind and other processes causing air turbulence, the sampler has not been calibrated in the field at sites experiencing high winds. In this study, the PSRs of the XAD-PAS were calibrated at three sites on the Tibetan Plateau, covering a wide range in temperature (T), pressure (P) and wind speed (v). At sites with low wind speeds (i.e., in a forest and an urban site), the PSRs are proportional to the ratio T 1.75 / P; at windy sites with an average wind speed above 3 m/s, the influence of v on PSRs cannot be ignored. Moreover, the open bottom of the XAD-PAS housing causes the PSRs to be influenced by wind angle and air turbulence caused by sloped terrain. Field calibration, wind speed measurements, and computational fluid dynamics (CFD) simulations indicate that a modified design incorporating an air spoiler consisting of 4 metal sheets dampens the turbulence caused by wind angle and sloped terrain and caps the PSR at ∼5 m 3 /day, irrespective of ambient wind. Therefore, the original XAD-PAS with an open bottom is suitable for deployment in urban areas and other less windy places, the modified design is preferable in mountain regions and other places where air circulation is complicated and strong.

Protecting Important Sites for Biodiversity Contributes to Meeting Global Conservation Targets

PubMed Central

Butchart, Stuart H. M.; Scharlemann, Jörn P. W.; Evans, Mike I.; Quader, Suhel; Aricò, Salvatore; Arinaitwe, Julius; Balman, Mark; Bennun, Leon A.; Bertzky, Bastian; Besançon, Charles; Boucher, Timothy M.; Brooks, Thomas M.; Burfield, Ian J.; Burgess, Neil D.; Chan, Simba; Clay, Rob P.; Crosby, Mike J.; Davidson, Nicholas C.; De Silva, Naamal; Devenish, Christian; Dutson, Guy C. L.; Fernández, David F. Día z; Fishpool, Lincoln D. C.; Fitzgerald, Claire; Foster, Matt; Heath, Melanie F.; Hockings, Marc; Hoffmann, Michael; Knox, David; Larsen, Frank W.; Lamoreux, John F.; Loucks, Colby; May, Ian; Millett, James; Molloy, Dominic; Morling, Paul; Parr, Mike; Ricketts, Taylor H.; Seddon, Nathalie; Skolnik, Benjamin; Stuart, Simon N.; Upgren, Amy; Woodley, Stephen

2012-01-01

Protected areas (PAs) are a cornerstone of conservation efforts and now cover nearly 13% of the world's land surface, with the world's governments committed to expand this to 17%. However, as biodiversity continues to decline, the effectiveness of PAs in reducing the extinction risk of species remains largely untested. We analyzed PA coverage and trends in species' extinction risk at globally significant sites for conserving birds (10,993 Important Bird Areas, IBAs) and highly threatened vertebrates and conifers (588 Alliance for Zero Extinction sites, AZEs) (referred to collectively hereafter as ‘important sites’). Species occurring in important sites with greater PA coverage experienced smaller increases in extinction risk over recent decades: the increase was half as large for bird species with>50% of the IBAs at which they occur completely covered by PAs, and a third lower for birds, mammals and amphibians restricted to protected AZEs (compared with unprotected or partially protected sites). Globally, half of the important sites for biodiversity conservation remain unprotected (49% of IBAs, 51% of AZEs). While PA coverage of important sites has increased over time, the proportion of PA area covering important sites, as opposed to less important land, has declined (by 0.45–1.14% annually since 1950 for IBAs and 0.79–1.49% annually for AZEs). Thus, while appropriately located PAs may slow the rate at which species are driven towards extinction, recent PA network expansion has under-represented important sites. We conclude that better targeted expansion of PA networks would help to improve biodiversity trends. PMID:22457717

Design, synthesis and biological activity of novel donepezil derivatives bearing N-benzyl pyridinium moiety as potent and dual binding site acetylcholinesterase inhibitors.

PubMed

Lan, Jin-Shuai; Zhang, Tong; Liu, Yun; Yang, Jing; Xie, Sai-Sai; Liu, Jing; Miao, Ze-Yang; Ding, Yue

2017-06-16

A series of new donepezil derivatives were designed synthesized and evaluated as multifunctional cholinesterase inhibitors against Alzheimer's disease (AD). In vitro studies showed that most of them exhibited significant potency to inhibit acetylcholinesterase and self-induced β-amyloid (Aβ) aggregation, and moderate antioxidant activity. Especially, compound 5b presented the greatest ability to inhibit cholinesterase (IC 50 , 1.9 nM for eeAChE and 0.8 nM for hAChE), good inhibition of Aβ aggregation (53.7% at 20 μM) and good antioxidant activity (0.54 trolox equivalents). Kinetic and molecular modeling studies indicated that compound 5b was a mixed-type inhibitor, binding simultaneously to the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. In addition, compound 5b could reduce PC12 cells death induced by oxidative stress and Aβ (1-42). Moreover, in vivo experiments showed that compound 5b was nontoxic and tolerated at doses up to 2000 mg/kg. These results suggested that compound 5b might be an excellent multifunctional agent for AD treatment. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Novel tacrine-1,2,3-triazole hybrids: In vitro, in vivo biological evaluation and docking study of cholinesterase inhibitors.

PubMed

Najafi, Zahra; Mahdavi, Mohammad; Saeedi, Mina; Karimpour-Razkenari, Elahe; Asatouri, Raymond; Vafadarnejad, Fahimeh; Moghadam, Farshad Homayouni; Khanavi, Mahnaz; Sharifzadeh, Mohammad; Akbarzadeh, Tahmineh

2017-01-05

A new series of tacrine-1,2,3-triazole hybrids were designed, synthesized, and evaluated as potent dual cholinesterase inhibitors. Most of synthesized compounds showed good in vitro inhibitory activities toward both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Among them, 7-chloro-N-((1-(4-methoxybenzyl)-1H-1,2,3-triazol-4-yl)methyl)-1,2,3,4-tetrahydroacridin-9-amine (5l) was found to be the most potent anti-AChE derivative (IC 50  = 0.521 μM) and N-((1-(4-methoxybenzyl)-1H-1,2,3-triazol-4-yl)methyl)-1,2,3,4-tetrahydroacridin-9-amine (5j) demonstrated the best anti-BChE activity (IC 50  = 0.055 μM). In vivo studies of compound 5l in Morris water maze task confirmed memory improvement in scopolamine-induced impairment. Also, molecular modeling and kinetic studies showed that compounds 5l and 5j bound simultaneously to the peripheral anionic site (PAS) and catalytic sites (CS) of the AChE and BChE. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Design, synthesis and evaluation of novel 7-aminoalkyl-substituted flavonoid derivatives with improved cholinesterase inhibitory activities.

PubMed

Luo, Wen; Chen, Ying; Wang, Ting; Hong, Chen; Chang, Li-Ping; Chang, Cong-Cong; Yang, Ya-Cheng; Xie, Song-Qiang; Wang, Chao-Jie

2016-02-15

A novel series of 7-aminoalkyl-substituted flavonoid derivatives 5a-5r were designed, synthesized and evaluated as potential cholinesterase inhibitors. The results showed that most of the synthesized compounds exhibited potent acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities at the micromolar range. Compound 2-(naphthalen-1-yl)-7-(8-(pyrrolidin-1-yl)octyloxy)-4H-chromen-4-one (5q) showed the best inhibitory activity (IC50, 0.64μM for AChE and 0.42μM for BChE) which were better than our previously reported compounds and the commercially available cholinergic agent Rivastigmine. The results from a Lineweaver-Burk plot indicated a mixed-type inhibition for compound 5q with AChE and BChE. Furthermore, molecular modeling study showed that 5q targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. Besides, these compounds (5a-5r) did not affect PC12 and HepG2 cell viability at the concentration of 10μM. Consequently, these flavonoid derivatives should be further investigated as multipotent agents for the treatment of Alzheimer's disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

Tertiary amine derivatives of chlorochalcone as acetylcholinesterase (AChE) and buthylcholinesterase (BuChE) inhibitors: the influence of chlorine, alkyl amine side chain and α,β-unsaturated ketone group.

PubMed

Gao, Xiao-Hui; Zhou, Chao; Liu, Hao-Ran; Liu, Lin-Bo; Tang, Jing-Jing; Xia, Xin-Hua

2017-12-01

A new series of tertiary amine derivatives of chlorochalcone (4a∼4l) were designed, synthesized and evaluated for the effect on acetylcholinesterase (AChE) and buthylcholinesterase (BuChE). The results indicated that all compounds revealed moderate or potent inhibitory activity against AChE, and some possessed high selectivity for AChE over BuChE. The structure-activity investigation showed that the substituted position of chlorine significantly influenced the activity and selectivity. The alteration of tertiary amine group also leads to obvious change in bioactivity. Among them, IC 50 of compound 4l against AChE was 0.17 ± 0.06 µmol/L, and the selectivity was 667.2 fold for AChE over BuChE. Molecular docking and enzyme kinetic study on compound 4l suggested that it simultaneously binds to the catalytic active site (CAS) and peripheral anionic site (PAS) of AChE. Further study showed that the pyrazoline derivatives synthesized from chlorochalcones had weaker activity and lower selectivity in inhibiting AChE compared to that of chlorochalcone derivatives.

A Tale of two Cities: Photoacoustic and Aethalometer Measurements Comparisons of Light Absorption in Mexico City and Las Vegas, NV, USA

NASA Astrophysics Data System (ADS)

Paredes-Miranda, G.; Arnott, W. P.; Marley, N. A.; Gaffney, J. S.

2007-05-01

As part of the Megacity Impacts on Regional and Global Environments, MIRAGE-Mex deployment to Mexico City in the period of 30 days, March 2006, a suite of photoacoustic spectrometers (PAS; W. Arnott & G. Paredes), nephelometer scattering, and aetholemeter absorption instruments (N. Marley & J.Gaffney) were installed to measure at ground level the light absorption and scattering by aerosols at the urban site at Instituto Mexicano del Petroleo (Mexican Oil Institute, denoted by IMP). This IMP site gave in-situ characterization of the Mexico City plume under favorable wind conditions. The PAS used at IMP operates at 532 nm, and conveniently allowed for characterization of gaseous absorption at this wavelength as well. Light scattering measurements are accomplished within the PAS by the reciprocal nephelometery method. In the urban site the aerosol absorption coefficient typically varies between 20 and 180 Mm-1 during the course of the day and significant diurnal variation of the aerosol single scattering albedo was observed. The Las Vegas, NV site was located at East Charleston Street on January-February, 2003. In east Las Vegas typical westerly winds carry the city plume across the site. Comparisons of PAS aerosol light absorption and aetholemeter absorption measurements at 521 nm at both Las Vegas NV and Mexico City sites will be presented. We will also present a broad overview of the diurnal variation of the scattering and absorption as well as the single scattering albedo and fraction of absorption due to gases at the sites in relation to secondary aerosol formation.

Inhibition and Larvicidal Activity of Phenylpropanoids from Piper sarmentosum on Acetylcholinesterase against Mosquito Vectors and Their Binding Mode of Interaction.

PubMed

Hematpoor, Arshia; Liew, Sook Yee; Chong, Wei Lim; Azirun, Mohd Sofian; Lee, Vannajan Sanghiran; Awang, Khalijah

2016-01-01

Aedes aegypti, Aedes albopictus and Culex quinquefasciatus are vectors of dengue fever and West Nile virus diseases. This study was conducted to determine the toxicity, mechanism of action and the binding interaction of three active phenylpropanoids from Piper sarmentosum (Piperaceae) toward late 3rd or early 4th larvae of above vectors. A bioassay guided-fractionation on the hexane extract from the roots of Piper sarmentosum led to the isolation and identification of three active phenylpropanoids; asaricin 1, isoasarone 2 and trans-asarone 3. The current study involved evaluation of the toxicity and acetylcholinesterase (AChE) inhibition of these compounds against Aedes aegypti, Aedes albopictus and Culex quinquefasciatus larvae. Asaricin 1 and isoasarone 2 were highly potent against Aedes aegypti, Aedes albopictus and Culex quinquefasciatus larvae causing up to 100% mortality at ≤ 15 μg/mL concentration. The ovicidal activity of asaricin 1, isoasarone 2 and trans-asarone 3 were evaluated through egg hatching. Asaricin 1 and isoasarone 2 showed potent ovicidal activity. Ovicidal activity for both compounds was up to 95% at 25μg/mL. Asaricin 1 and isoasarone 2 showed strong inhibition on acetylcholinesterase with relative IC50 values of 0.73 to 1.87 μg/mL respectively. These findings coupled with the high AChE inhibition may suggest that asaricin 1 and isoasarone 2 are neuron toxic compounds toward Aedes aegypti, Aedes albopictus and Culex quinquefasciatus. Further computational docking with Autodock Vina elaborates the possible interaction of asaricin 1 and isoasarone 2 with three possible binding sites of AChE which includes catalytic triads (CAS: S238, E367, H480), the peripheral sites (PAS: E72, W271) and anionic binding site (W83). The binding affinity of asaricin 1 and isoasarone 2 were relatively strong with asaricin 1 showed a higher binding affinity in the anionic pocket.

Complex and dynamic landscape of RNA polyadenylation revealed by PAS-Seq

PubMed Central

Shepard, Peter J.; Choi, Eun-A; Lu, Jente; Flanagan, Lisa A.; Hertel, Klemens J.; Shi, Yongsheng

2011-01-01

Alternative polyadenylation (APA) of mRNAs has emerged as an important mechanism for post-transcriptional gene regulation in higher eukaryotes. Although microarrays have recently been used to characterize APA globally, they have a number of serious limitations that prevents comprehensive and highly quantitative analysis. To better characterize APA and its regulation, we have developed a deep sequencing-based method called Poly(A) Site Sequencing (PAS-Seq) for quantitatively profiling RNA polyadenylation at the transcriptome level. PAS-Seq not only accurately and comprehensively identifies poly(A) junctions in mRNAs and noncoding RNAs, but also provides quantitative information on the relative abundance of polyadenylated RNAs. PAS-Seq analyses of human and mouse transcriptomes showed that 40%–50% of all expressed genes produce alternatively polyadenylated mRNAs. Furthermore, our study detected evolutionarily conserved polyadenylation of histone mRNAs and revealed novel features of mitochondrial RNA polyadenylation. Finally, PAS-Seq analyses of mouse embryonic stem (ES) cells, neural stem/progenitor (NSP) cells, and neurons not only identified more poly(A) sites than what was found in the entire mouse EST database, but also detected significant changes in the global APA profile that lead to lengthening of 3′ untranslated regions (UTR) in many mRNAs during stem cell differentiation. Together, our PAS-Seq analyses revealed a complex landscape of RNA polyadenylation in mammalian cells and the dynamic regulation of APA during stem cell differentiation. PMID:21343387

Protected area types, strategies and impacts in Brazil's Amazon: public protected area strategies do not yield a consistent ranking of protected area types by impact

PubMed Central

Pfaff, Alexander; Robalino, Juan; Sandoval, Catalina; Herrera, Diego

2015-01-01

The leading policy to conserve forest is protected areas (PAs). Yet, PAs are not a single tool: land users and uses vary by PA type; and public PA strategies vary in the extent of each type and in the determinants of impact for each type, i.e. siting and internal deforestation. Further, across regions and time, strategies respond to pressures (deforestation and political). We estimate deforestation impacts of PA types for a critical frontier, the Brazilian Amazon. We separate regions and time periods that differ in their deforestation and political pressures and document considerable variation in PA strategies across regions, time periods and types. The siting of PAs varies across regions. For example, all else being equal, PAs in the arc of deforestation are relatively far from non-forest, while in other states they are relatively near. Internal deforestation varies across time periods, e.g. it is more similar across the PA types for PAs after 2000. By contrast, after 2000, PA extent is less similar across PA types with little non-indigenous area created inside the arc. PA strategies generate a range of impacts for PA types—always far higher within the arc—but not a consistent ranking of PA types by impact. PMID:26460126

Ion exchange polymers for anion separations

DOEpatents

Jarvinen, Gordon D.; Marsh, S. Fredric; Bartsch, Richard A.

1997-01-01

Anion exchange resins including at least two positively charged sites and a ell-defined spacing between the positive sites are provided together with a process of removing anions or anionic metal complexes from aqueous solutions by use of such resins. The resins can be substituted poly(vinylpyridine) and substituted polystyrene.

Ion exchange polymers for anion separations

DOEpatents

Jarvinen, G.D.; Marsh, S.F.; Bartsch, R.A.

1997-09-23

Anion exchange resins including at least two positively charged sites and a well-defined spacing between the positive sites are provided together with a process of removing anions or anionic metal complexes from aqueous solutions by use of such resins. The resins can be substituted poly(vinylpyridine) and substituted polystyrene.

Systematic Profiling of Poly(A)+ Transcripts Modulated by Core 3’ End Processing and Splicing Factors Reveals Regulatory Rules of Alternative Cleavage and Polyadenylation

PubMed Central

Li, Wencheng; You, Bei; Hoque, Mainul; Zheng, Dinghai; Luo, Wenting; Ji, Zhe; Park, Ji Yeon; Gunderson, Samuel I.; Kalsotra, Auinash; Manley, James L.; Tian, Bin

2015-01-01

Alternative cleavage and polyadenylation (APA) results in mRNA isoforms containing different 3’ untranslated regions (3’UTRs) and/or coding sequences. How core cleavage/polyadenylation (C/P) factors regulate APA is not well understood. Using siRNA knockdown coupled with deep sequencing, we found that several C/P factors can play significant roles in 3’UTR-APA. Whereas Pcf11 and Fip1 enhance usage of proximal poly(A) sites (pAs), CFI-25/68, PABPN1 and PABPC1 promote usage of distal pAs. Strong cis element biases were found for pAs regulated by CFI-25/68 or Fip1, and the distance between pAs plays an important role in APA regulation. In addition, intronic pAs are substantially regulated by splicing factors, with U1 mostly inhibiting C/P events in introns near the 5’ end of gene and U2 suppressing those in introns with features for efficient splicing. Furthermore, PABPN1 inhibits expression of transcripts with pAs near the transcription start site (TSS), a property possibly related to its role in RNA degradation. Finally, we found that groups of APA events regulated by C/P factors are also modulated in cell differentiation and development with distinct trends. Together, our results support an APA code where an APA event in a given cellular context is regulated by a number of parameters, including relative location to the TSS, splicing context, distance between competing pAs, surrounding cis elements and concentrations of core C/P factors. PMID:25906188

Biological Synthesis of a Protein Analogue of Acetylcholinesterase: Monoclonal Anti-Idiotype Antibody Analogue of the Esteratic Site.

DTIC Science & Technology

1986-07-10

site- directed inhibitor DFP, the reversible site-directed inhibitors neostigmine, carbachol , edrophonium, and BW284c51; and the allosteric site...Esteratic 10-6 10 -7 - I0-2 Neostigmine Esteratic 10- 7 10- 6 - 10 5 Anionic PI Carbachol Esteratic 10- 4 10 3 10-1 Anionic PI Edrophonium Anionic 10

Location of Bromide Ions in Tetragonal Lysozyme Crystals

NASA Technical Reports Server (NTRS)

Lim, Kap; Nadarajah, Arunan; Forsythe, Elizabeth L.; Pusey, Marc L.

1998-01-01

Anions have been shown to play a dominant role in the crystallization of chicken egg white lysozyme from salt solutions. Previous studies employing X-ray crystallography had found one chloride ion binding site in the tetragonal crystal form of the protein and four nitrate ion binding sites in the monoclinic form. In this study the anion positions in the tetragonal form were determined from the difference Fourier map obtained from lysozyme crystal grown in bromide and chloride solutions. Five possible anion binding sites were found in this manner. Some of these sites were in pockets containing basic residues while others were near neutral, but polar, residues. The sole chloride ion binding site found in previous studies was confirmed, while four of these sites corresponded to four binding sites found for nitrate ions in monoclinic crystals. The study suggests that most of the anion binding sites in lysozyme remain unchanged, even when different anions and different crystal forms of lysozyme are employed.

Locations of Bromide Ions in Tetragonal Lysozyme Crystals

NASA Technical Reports Server (NTRS)

Lim, Kap; Nadarajah, Arunan; Forsythe, Elizabeth L.; Pusey, Marc L.

1998-01-01

Anions have been shown to play a dominant role in the crystallization of chicken egg-white lysozyme from salt solutions. Previous studies employing X-ray crystallography have found one chloride ion binding site in the tetragonal crystal form of the protein and four nitrate ion binding sites in the monoclinic form. In this study the anion positions in the tetragonal form were determined from the difference Fourier map obtained from lysozyme crystals grown in bromide and chloride solutions. Five possible anion-binding sites were found in this manner. Some of these sites were in pockets containing basic residues while others were near neutral, but polar, residues. The sole chloride ion binding site found in previous studies was confirmed, while four further sites were found which corresponded to the four binding sites found for nitrate ions in monoclinic crystals. The study suggests that most of the anion-binding sites in lysozyme remain unchanged even when different anions and different crystal forms of lysozyme are employed.

The effects of tramadol on postoperative shivering after sevoflurane and remifentanil anesthesia.

PubMed

Nakagawa, Taku; Hashimoto, Miki; Hashimoto, Yasunori; Shirozu, Kazuhiro; Hoka, Sumio

2017-01-03

Remifentanil has been reported to cause post-anesthetic shivering (PAS). Higher doses of remifentanil reportedly induce more intense PAS. Tramadol, a synthetic opioid that acts at multiple sites, is considered to be an effective treatment for PAS, but the evidence for its therapeutic benefit after remifentanil anesthesia is limited. We investigated the effect of tramadol on the incidence of PAS after remifentanil anesthesia. Sixty-three patients who had undergone upper abdominal surgery under general anesthesia were studied retrospectively. Tramadol was administered at induction of anesthesia. The patients were divided into four groups: HT(+), high dose remifentanil (1-1.5 μg/kg/min) with tramadol; HT(-), high dose remifentanil without tramadol; LT(+), low dose remifentanil (0.15-0.25 μg/kg/min) with tramadol; and LT(-), low dose remifentanil without tramadol. We recorded perioperative changes in nasopharyngeal temperature and episodes of PAS on emergence from anesthesia. The incidences of PAS in both tramadol treatment groups were significantly lower than the groups that did not receive tramadol. Nasopharyngeal temperature after surgery fell significantly more from baseline in the tramadol treatment groups compared with the non-treatment groups. Tramadol administered at induction of anesthesia appears to suppress PAS following remifentanil anesthesia.

Altered binding of thioflavin t to the peripheral anionic site of acetylcholinesterase after phosphorylation of the active site by chlorpyrifos oxon or dichlorvos

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

Sultatos, L.G.; Kaushik, R.

2008-08-01

The peripheral anionic site of acetylcholinesterase, when occupied by a ligand, is known to modulate reaction rates at the active site of this important enzyme. The current report utilized the peripheral anionic site specific fluorogenic probe thioflavin t to determine if the organophosphates chlorpyrifos oxon and dichlorvos bind to the peripheral anionic site of human recombinant acetylcholinesterase, since certain organophosphates display concentration-dependent kinetics when inhibiting this enzyme. Incubation of 3 nM acetylcholinesterase active sites with 50 nM or 2000 nM inhibitor altered both the B{sub max} and K{sub d} for thioflavin t binding to the peripheral anionic site. However, thesemore » changes resulted from phosphorylation of Ser203 since increasing either inhibitor from 50 nM to 2000 nM did not alter further thioflavin t binding kinetics. Moreover, the organophosphate-induced decrease in B{sub max} did not represent an actual reduction in binding sites, but instead likely resulted from conformational interactions between the acylation and peripheral anionic sites that led to a decrease in the rigidity of bound thioflavin t. A drop in fluorescence quantum yield, leading to an apparent decrease in B{sub max}, would accompany the decreased rigidity of bound thioflavin t molecules. The organophosphate-induced alterations in K{sub d} represented changes in binding affinity of thioflavin t, with diethylphosphorylation of Ser203 increasing K{sub d}, and dimethylphosphorylation of Ser203 decreasing K{sub d}. These results indicate that chlorpyrifos oxon and dichlorvos do not bind directly to the peripheral anionic site of acetylcholinesterase, but can affect binding to that site through phosphorylation of Ser203.« less

New multipotent tetracyclic tacrines with neuroprotective activity.

PubMed

Marco-Contelles, José; León, Rafael; de los Ríos, Cristóbal; García, Antonio G; López, Manuela G; Villarroya, Mercedes

2006-12-15

The synthesis and the biological evaluation (neuroprotection, voltage dependent calcium channel blockade, AChE/BuChE inhibitory activity and propidium binding) of new multipotent tetracyclic tacrine analogues (5-13) are described. Compounds 7, 8 and 11 showed a significant neuroprotective effect on neuroblastoma cells subjected to Ca(2+) overload or free radical induced toxicity. These compounds are modest AChE inhibitors [the best inhibitor (11) is 50-fold less potent than tacrine], but proved to be very selective, as for most of them no BuChE inhibition was observed. In addition, the propidium displacement experiments showed that these compounds bind AChE to the peripheral anionic site (PAS) of AChE and, consequently, are potential agents that can prevent the aggregation of beta-amyloid. Overall, compound 8 is a modest and selective AChE inhibitor, but an efficient neuroprotective agent against 70mM K(+) and 60microM H(2)O(2). Based on these results, some of these molecules can be considered as lead candidates for the further development of anti-Alzheimer drugs.

Analysis of alterative cleavage and polyadenylation by 3′ region extraction and deep sequencing

PubMed Central

Hoque, Mainul; Ji, Zhe; Zheng, Dinghai; Luo, Wenting; Li, Wencheng; You, Bei; Park, Ji Yeon; Yehia, Ghassan; Tian, Bin

2012-01-01

Alternative cleavage and polyadenylation (APA) leads to mRNA isoforms with different coding sequences (CDS) and/or 3′ untranslated regions (3′UTRs). Using 3′ Region Extraction And Deep Sequencing (3′READS), a method which addresses the internal priming and oligo(A) tail issues that commonly plague polyA site (pA) identification, we comprehensively mapped pAs in the mouse genome, thoroughly annotating 3′ ends of genes and revealing over five thousand pAs (~8% of total) flanked by A-rich sequences, which have hitherto been overlooked. About 79% of mRNA genes and 66% of long non-coding RNA (lncRNA) genes have APA; but these two gene types have distinct usage patterns for pAs in introns and upstream exons. Promoter-distal pAs become relatively more abundant during embryonic development and cell differentiation, a trend affecting pAs in both 3′-most exons and upstream regions. Upregulated isoforms generally have stronger pAs, suggesting global modulation of the 3′ end processing activity in development and differentiation. PMID:23241633

H passivation of Li on Zn-site in ZnO: Positron annihilation spectroscopy and secondary ion mass spectrometry

NASA Astrophysics Data System (ADS)

Johansen, K. M.; Zubiaga, A.; Tuomisto, F.; Monakhov, E. V.; Kuznetsov, A. Yu.; Svensson, B. G.

2011-09-01

The interaction of hydrogen (H) with lithium (Li) and zinc vacancies (VZn) in hydrothermally grown n-type zinc oxide (ZnO) has been investigated by positron annihilation spectroscopy (PAS) and secondary ion mass spectrometry. Li on Zn-site (LiZn) is found to be the dominant trap for migrating H atoms, while the trapping efficiency of VZn is considerably smaller. After hydrogenation, where the LiZn acceptor is passivated via formation of neutral LiZn-H pairs, VZn occurs as the prime PAS signature and with a concentration similar to that observed in nonhydrogenated Li-poor samples. Despite a low efficiency as an H trap, the apparent concentration of VZn in Li-poor samples decreases after hydrogenation, as detected by PAS, and evidence for formation of the neutral VZnH2 complex is presented.

Lead identification of acetylcholinesterase inhibitors-histamine H3 receptor antagonists from molecular modeling.

PubMed

Bembenek, Scott D; Keith, John M; Letavic, Michael A; Apodaca, Richard; Barbier, Ann J; Dvorak, Lisa; Aluisio, Leah; Miller, Kirsten L; Lovenberg, Timothy W; Carruthers, Nicholas I

2008-03-15

Currently, the only clinically effective treatment for Alzheimer's disease (AD) is the use of acetylcholinesterase (AChE) inhibitors. These inhibitors have limited efficacy in that they only treat the symptoms and not the disease itself. Additionally, they often have unpleasant side effects. Here we consider the viability of a single molecule having the actions of both an AChE inhibitor and histamine H(3) receptor antagonist. Both histamine H(3) receptor antagonists and AChE inhibitors improve and augment cholinergic neurotransmission in the cortex. However, whereas an AChE inhibitor will impart its effect everywhere, a histamine H(3) antagonist will raise acetylcholine levels mostly in the brain as its mode of action will primarily be on the central nervous system. Therefore, the combination of both activities in a single molecule could be advantageous. Indeed, studies suggest an appropriate dual-acting compound may offer the desired therapeutic effect with fewer unpleasant side effects [CNS Drugs2004, 18, 827]. Further, recent studies(2) indicate the peripheral anionic site (PAS) of AChE interacts with the beta-amyloid (betaA) peptide. Consequently, a molecule capable of disrupting this interaction may have a significant impact on the production of or the aggregation of betaA. This may result in slowing down the progression of the disease rather than only treating the symptoms as current therapies do. Here, we detail how the use of the available crystal structure information, pharmacophore modeling and docking (automated, manual, classical, and QM/MM) lead to the identification of an AChE inhibitor-histamine H(3) receptor antagonist. Further, based on our models we speculate that this dual-acting compound may interact with the PAS. Such a dual-acting compound may be able to affect the pathology of AD in addition to providing symptomatic relief.

Selective delivery of doxorubicin by novel stimuli-sensitive nano-ferritins overcomes tumor refractoriness.

PubMed

Fracasso, Giulio; Falvo, Elisabetta; Colotti, Gianni; Fazi, Francesco; Ingegnere, Tiziano; Amalfitano, Adriana; Doglietto, Giovanni Battista; Alfieri, Sergio; Boffi, Alberto; Morea, Veronica; Conti, Giamaica; Tremante, Elisa; Giacomini, Patrizio; Arcovito, Alessandro; Ceci, Pierpaolo

2016-10-10

Human ferritin heavy chain (HFt) has been demonstrated to possess considerable potential for targeted delivery of drugs and diagnostic agents to cancer cells. Here, we report the development of a novel HFt-based genetic construct (HFt-MP-PAS) containing a short peptide linker (MP) between each HFt subunit and an outer shielding polypeptide sequence rich in proline (P), serine (S) and alanine (A) residues (PAS). The peptide linker contains a matrix-metalloproteinases (MMPs) cleavage site that permits the protective PAS shield to be removed by tumor-driven proteolytic cleavage within the tumor microenvironment. For the first time HFt-MP-PAS ability to deliver doxorubicin to cancer cells, subcellular localization, and therapeutic efficacy on a xenogeneic mouse model of a highly refractory to conventional chemotherapeutics type of cancer were evaluated. HFt-MP-PAS-DOXO performance was compared with the novel albumin-based drug delivery system INNO-206, currently in phase III clinical trials. The results of this work provide solid evidence indicating that the stimuli-sensitive, long-circulating HFt-MP-PAS nanocarriers described herein have the potential to be exploited in cancer therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

fMRI and MRS measures of neuroplasticity in the pharyngeal motor cortex

PubMed Central

Michou, Emilia; Williams, Steve; Vidyasagar, Rishma; Downey, Darragh; Mistry, Satish; Edden, Richard A.E.; Hamdy, Shaheen

2016-01-01

Introduction Paired associative stimulation (PAS), is a novel non-invasive technique where two neural substrates are employed in a temporally coordinated manner in order to modulate cortico-motor excitability within the motor cortex (M1). In swallowing, combined pharyngeal electrical and transcranial-magnetic-stimulation induced beneficial neurophysiological and behavioural effects in healthy subjects and dysphagic stroke patients. Here, we aimed to investigate the whole-brain changes in neural activation during swallowing using functional magnetic resonance imaging (fMRI) following PAS application and in parallel assess associated GABA changes with magnetic resonance spectroscopy (MRS). Methods Healthy adults (n = 11, 38 ± 9 years old) were randomised to receive real and sham PAS to the ‘stronger’ motor cortex pharyngeal representation, on 2 separate visits. Following PAS, event-related fMRI was performed to assess changes in brain activation in response to water and saliva swallowing and during rest. Data were analysed (SPM8) at P < .001. MRS data were acquired using MEGA-PRESS before and after the fMRI acquisitions on both visits and GABA concentrations were measured (AMARES, jMRUI). Results Following real PAS, BOLD signal changes (group analyses) increased at the site of stimulation during water and saliva swallowing, compared to sham PAS. It is also evident that PAS induced significant increases in BOLD signal to contralateral (to stimulation) hemispheric areas that are of importance to the swallowing neural network. Following real PAS, GABA: creatine ratio showed a trend to increase contralateral to PAS. Conclusion Targeted PAS applied to the human pharyngeal motor cortex induces local and remote changes in both primary and non-primary areas for water and saliva tasks. There is a possibility that changes of the inhibitory neurotransmitter, GABA, may play a role in the changes in BOLD signal. These findings provide evidence for the mechanisms underlying the beneficial effects of PAS on the brain swallowing network. PMID:25976926

Molecular Control of Polyene Macrolide Biosynthesis

PubMed Central

Santos-Aberturas, Javier; Vicente, Cláudia M.; Guerra, Susana M.; Payero, Tamara D.; Martín, Juan F.; Aparicio, Jesús F.

2011-01-01

Control of polyene macrolide production in Streptomyces natalensis is mediated by the transcriptional activator PimM. This regulator, which combines an N-terminal PAS domain with a C-terminal helix-turn-helix motif, is highly conserved among polyene biosynthetic gene clusters. PimM, truncated forms of the protein without the PAS domain (PimMΔPAS), and forms containing just the DNA-binding domain (DBD) (PimMDBD) were overexpressed in Escherichia coli as GST-fused proteins. GST-PimM binds directly to eight promoters of the pimaricin cluster, as demonstrated by electrophoretic mobility shift assays. Assays with truncated forms of the protein revealed that the PAS domain does not mediate specificity or the distinct recognition of target genes, which rely on the DBD domain, but significantly reduces binding affinity up to 500-fold. Transcription start points were identified by 5′-rapid amplification of cDNA ends, and the binding regions of PimMDBD were investigated by DNase I protection studies. In all cases, binding took place covering the −35 hexamer box of each promoter, suggesting an interaction of PimM and RNA polymerase to cause transcription activation. Information content analysis of the 16 sequences protected in target promoters was used to deduce the structure of the PimM-binding site. This site displays dyad symmetry, spans 14 nucleotides, and adjusts to the consensus TVGGGAWWTCCCBA. Experimental validation of this binding site was performed by using synthetic DNA duplexes. Binding of PimM to the promoter region of one of the polyketide synthase genes from the Streptomyces nodosus amphotericin cluster containing the consensus binding site was also observed, thus proving the applicability of the findings reported here to other antifungal polyketides. PMID:21187288

Glomerular anionic site distribution in nonproteinuric rats. A computer-assisted morphometric analysis.

PubMed

Pilia, P A; Swain, R P; Williams, A V; Loadholt, C B; Ainsworth, S K

1985-12-01

The cationic ultrastructural tracer polyethyleneimine (PEI: pI approximately equal to 11.0), binds electrophysically to uniformly spaced discrete electron-dense anionic sites present in the laminae rarae of the rat glomerular basement membrane (GBM), mesangial reflections of the GBM, Bowman's capsule, and tubular basement membranes when administered intravenously. Computer-assisted morphometric analysis of glomerular anionic sites reveals that the maximum concentration of stainable lamina rara externa (lre) sites (21/10,000 A GBM) occurs 60 minutes after PEI injection with a site-site interspacing of 460 A. Lamina rara interna (lri) sites similarly demonstrate a maximum concentration (20/10,000 A GBM) at 60 minutes with a periodicity of 497 A. The concentration and distribution of anionic sites within the lri was irregular in pattern and markedly decreased in number, while the lre possesses an electrical field that is highly regular at all time intervals analyzed (15, 30, 60, 120, 180, 240, and 300 minutes). Immersion and perfusion of renal tissue with PEI reveals additional heavy staining of the epithelial and endothelial cell sialoprotein coatings. PEI appears to bind to glomerular anionic sites reversibly: ie, between 60 and 180 minutes the concentration of stained sites decreases. At 300 minutes, the interspacing once again approaches the 60-minute concentration. This suggests a dynamic turnover or dissociation followed by a reassociation of glomerular negatively charged PEI binding sites. In contrast, morphometric analysis of anionic sites stained with lysozyme and protamine sulfate reveals interspacings of 642 A and 585 A, respectively; in addition, these tracers produce major glomerular ultrastructural alterations and induce transient proteinuria. PEI does not induce proteinuria in rats, nor does it produce glomerular morphologic alterations when ten times the tracer dosage is administered intravenously. These findings indicate that the choice of ultrastructural charge tracer, the method of administering the tracer, and the time selected for analysis of tissue after administration of tracer significantly influences results. Morphometric analysis of the distribution of glomerular anionic sites in nonproteinuric rats provides a method of evaluating quantitative alterations of the glomerular charge barrier in renal disease models.

PAS-cal: a Generic Recombinant Peptide Calibration Standard for Mass Spectrometry

NASA Astrophysics Data System (ADS)

Breibeck, Joscha; Serafin, Adam; Reichert, Andreas; Maier, Stefan; Küster, Bernhard; Skerra, Arne

2014-08-01

We describe the design, preparation, and mass-spectrometric characterization of a new recombinant peptide calibration standard with uniform biophysical and ionization characteristics for mass spectrometry. "PAS-cal" is an artificial polypeptide concatamer of peptide cassettes with varying lengths, each composed of the three small, chemically stable amino acids Pro, Ala, and Ser, which are interspersed by Arg residues to allow site-specific cleavage with trypsin. PAS-cal is expressed at high yields in Escherichia coli as a Small Ubiquitin-like MOdifier (SUMO) fusion protein, which is easily purified and allows isolation of the PAS-cal moiety after SUMO protease cleavage. Upon subsequent in situ treatment with trypsin, the PAS-cal polypeptide yields a set of four defined homogeneous peptides in the range from 2 to 8 kDa with equal mass spacing. ESI-MS analysis revealed a conveniently interpretable raw spectrum, which after deconvolution resulted in a very simple pattern of four peaks with similar ionization signals. MALDI-MS analysis of a PAS-cal peptide mixture comprising both the intact polypeptide and its tryptic fragments revealed not only the four standard peptides but also the singly and doubly charged states of the intact concatamer as well as di- and trimeric adduct ion species between the peptides, thus augmenting the observable m/z range. The advantageous properties of PAS-cal are most likely a result of the strongly hydrophilic and conformationally disordered PEG-like properties of the PAS sequences. Therefore, PAS-cal offers an inexpensive and versatile recombinant peptide calibration standard for mass spectrometry in protein/peptide bioanalytics and proteomics research, the composition of which may be further adapted to fit individual needs.

View From a Megacity: Aerosol Light Absorption and Scattering at Four Sites in and Near Mexico City.

NASA Astrophysics Data System (ADS)

Paredes-Miranda, G.; Arnott, W. P.; Gaffney, J. S.; Marley, N. A.

2006-12-01

As part of the Megacity Impacts on Regional and Global Environments, MIRAGE-Mex deployment to Mexico City in the period of 30 days, March 2006, a suite of photoacoustic spectrometers (PAS) were installed to measure at ground level the light absorption and scattering by aerosols at four sites: an urban site at Instituto Mexicano del Petroleo (Mexican Oil Institute, denoted by IMP), a suburban site at the Technological University of Tecamac, a rural site at "La Biznaga" ranch, and a site at the Paseo de Cortes (altitude 3,810 meters ASL) in the rural area above Amecameca in the State of Mexico, on the saddle between the volcanoes Popocatepetl and Iztaccihuatl. The IMP site gave in-situ characterization of the Mexico City plume under favorable wind conditions while the other sites provided characterization of the plume, mixed in with any local sources. The second and third sites are north of Mexico City, and the fourth site is south. The PAS used at IMP operates at 532 nm, and conveniently allowed for characterization of gaseous absorption at this wavelength as well. Instruments at the second and third sites operate at 870 nm, and the one at the fourth site at 780 nm. Light scattering measurements are accomplished within the PAS by the reciprocal nephelometery method. In the urban site the aerosol absorption coefficient typically varies between 40 and 250 Mm-1 during the course of the day and significant diurnal variation of the aerosol single scattering albedo was observed. Comparisons with TSI nephelometer scattering and Aetholemeter absorption measurements at the T0 site will be presented. We will present a broad overview of the diurnal variation of the scattering and absorption as well as the single scattering albedo and fraction of absorption due to gases at the IMP site. Insight on the dynamical connections will be discussed.

Selection Rule of Preferred Doping Site for n-Type Oxides

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

Li, C.; Li, J.; Li, S. S.

2012-06-25

Using first-principles calculations and analysis, we show that to create shallow n-type dopants in oxides, anion site doping is preferred for more covalent oxides such as SnO{sub 2} and cation site doping is preferred for more ionic oxides such as ZnO. This is because for more ionic oxides, the conduction band minimum (CBM) state actually contains a considerable amount of O 3s orbitals, thus anion site doping can cause large perturbation on the CBM and consequently produces deeper donor levels. We also show that whether it is cation site doping or anion site doping, the oxygen-poor condition should always bemore » used.« less

Molecular Characterization of Monoclonal Antibodies that Inhibit Acetylcholinesterase by Targeting the Peripheral Site and Backdoor Region

PubMed Central

Essono, Sosthène; Mondielli, Grégoire; Lamourette, Patricia; Boquet, Didier; Grassi, Jacques; Marchot, Pascale

2013-01-01

The inhibition properties and target sites of monoclonal antibodies (mAbs) Elec403, Elec408 and Elec410, generated against Electrophorus electricus acetylcholinesterase (AChE), have been defined previously using biochemical and mutagenesis approaches. Elec403 and Elec410, which bind competitively with each other and with the peptidic toxin inhibitor fasciculin, are directed toward distinctive albeit overlapping epitopes located at the AChE peripheral anionic site, which surrounds the entrance of the active site gorge. Elec408, which is not competitive with the other two mAbs nor fasciculin, targets a second epitope located in the backdoor region, distant from the gorge entrance. To characterize the molecular determinants dictating their binding site specificity, we cloned and sequenced the mAbs; generated antigen-binding fragments (Fab) retaining the parental inhibition properties; and explored their structure-function relationships using complementary x-ray crystallography, homology modeling and flexible docking approaches. Hypermutation of one Elec403 complementarity-determining region suggests occurrence of antigen-driven selection towards recognition of the AChE peripheral site. Comparative analysis of the 1.9Å-resolution structure of Fab408 and of theoretical models of its Fab403 and Fab410 congeners evidences distinctive surface topographies and anisotropic repartitions of charges, consistent with their respective target sites and inhibition properties. Finally, a validated, data-driven docking model of the Fab403-AChE complex suggests a mode of binding at the PAS that fully correlates with the functional data. This comprehensive study documents the molecular peculiarities of Fab403 and Fab410, as the largest peptidic inhibitors directed towards the peripheral site, and those of Fab408, as the first inhibitor directed toward the backdoor region of an AChE and a unique template for the design of new, specific modulators of AChE catalysis. PMID:24146971

Estimating the contributions of mobile sources of PAH to urban air using real-time PAH monitoring.

PubMed

Dunbar, J C; Lin, C I; Vergucht, I; Wong, J; Duran, J L

2001-11-12

Motor vehicles are a significant source of airborne polycyclic aromatic hydrocarbons (PAH) in many urban areas. Traditional approaches used in determining the relative contributions of individual vehicle types to the total amount of PAH in air have been based on the analysis of integrated samples of airborne particles and gases for the presence of chemical tracers indicative of the vehicles from which the chemicals derived. As an alternative, we have used a photoelectric aerosol sensor (PAS) capable of measuring PAH levels in real-time in the emissions plumes from motor vehicles. We placed the PAS near a traffic-light in Kenmore Square, a busy crossroads in downtown Boston (MA, USA). A video camera co-located at the site recorded the vehicles passing the sensor, and this record was correlated with the PAS data. During a 5-day monitoring period (approximately 59 h) in the summer of 1998, over 34,000 motor vehicles were counted and classified and over 24,000 PAS readings were recorded (frequency = 1/8.6 s). The composition of the vehicle population was 94% passenger vehicles, 1.4% buses, 2.6% small trucks, 1.3% medium trucks, 0.35% large trucks, and 0.45% garbage and construction trucks. In analyzing the PAS data, it was assumed that the highest PAS measurements--those that exceeded the 95% critical level of the 5-min moving average of all the PAS measurements--were indicative of primary vehicular emissions. We found that approximately 46% of the mass of particle-bound PAH (i.e. approximately 46% of the integrated area under the PAS signal vs. time plots) was attributable to primary emissions from motor vehicles passing the sensor. Of this, 35-61% was attributable to passenger vehicles (cars, pickup trucks, and sports utility vehicles) and 39-65% was attributable to non-passenger vehicles [buses (14-23%), small trucks (12-20%), medium trucks (8.4-14%), large trucks (2.9-4.8%) and garbage and construction trucks (1.9-3.2%)]. Our results suggest that on a per vehicle basis, buses and trucks--the majority of which run on diesel fuel--emitted greater amounts of particle-bound PAH than passenger vehicles. Overall, we found that real-time photoelectric aerosol sensing (in combination with video photography) is useful for estimating the contributions of airborne PAB from different vehicle types. Due to the physical constraints of our monitoring site and the high volumes of traffic, however, it was not possible to uniquely attribute PAS signals to individual vehicles.

Changes at the KinA PAS-A Dimerization Interface Influence Histidine Kinase Function

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

Lee, James; Tomchick, Diana R.; Brautigam, Chad A.

2008-11-12

The Bacillus subtilis KinA protein is a histidine protein kinase that controls the commitment of this organism to sporulate in response to nutrient deprivation and several other conditions. Prior studies indicated that the N-terminal Per-ARNT-Sim domain (PAS-A) plays a critical role in the catalytic activity of this enzyme, as demonstrated by the significant decrease of the autophosphorylation rate of a KinA protein lacking this domain. On the basis of the environmental sensing role played by PAS domains in a wide range of proteins, including other bacterial sensor kinases, it has been suggested that the PAS-A domain plays an important regulatorymore » role in KinA function. We have investigated this potential by using a combination of biophysical and biochemical methods to examine PAS-A structure and function, both in isolation and within the intact protein. Here, we present the X-ray crystal structure of the KinA PAS-A domain, showing that it crystallizes as a homodimer using {beta}-sheet/{beta}-sheet packing interactions as observed for several other PAS domain complexes. Notably, we observed two dimers with tertiary and quaternary structure differences in the crystalline lattice, indicating significant structural flexibility in these domains. To confirm that KinA PAS-A also forms dimers in solution, we used a combination of NMR spectroscopy, gel filtration chromatography, and analytical ultracentrifugation, the results of which are all consistent with the crystallographic results. We experimentally tested the importance of several residues at the dimer interface using site-directed mutagenesis, finding changes in the PAS-A domain that significantly alter KinA enzymatic activity in vitro and in vivo. These results support the importance of PAS domains within KinA and other histidine kinases and suggest possible routes for natural or artificial regulation of kinase activity.« less

Synthesis, characterization, X-ray crystallography, acetyl cholinesterase inhibition and antioxidant activities of some novel ketone derivatives of gallic hydrazide-derived Schiff bases.

PubMed

Gwaram, Nura Suleiman; Ali, Hapipah Mohd; Abdulla, Mahmood Ameen; Buckle, Michael J C; Sukumaran, Sri Devi; Chung, Lip Yong; Othman, Rozana; Alhadi, Abeer A; Yehye, Wageeh A; Hadi, A Hamid A; Hassandarvish, Pouya; Khaledi, Hamid; Abdelwahab, Siddig Ibrahim

2012-02-28

Alzheimer's disease (AD) is the most common form of dementia among older people and the pathogenesis of this disease is associated with oxidative stress. Acetylcholinesterase inhibitors with antioxidant activities are considered potential treatments for AD. Some novel ketone derivatives of gallic hydrazide-derived Schiff bases were synthesized and examined for their antioxidant activities and in vitro and in silico acetyl cholinesterase inhibition. The compounds were characterized using spectroscopy and X-ray crystallography. The ferric reducing antioxidant power (FRAP) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays revealed that all the compounds have strong antioxidant activities. N-(1-(5-bromo-2-hydroxyphenyl)-ethylidene)-3,4,5-trihydroxybenzohydrazide (2) was the most potent inhibitor of human acetyl cholinesterase, giving an inhibition rate of 77% at 100 μM. Molecular docking simulation of the ligand-enzyme complex suggested that the ligand may be positioned in the enzyme's active-site gorge, interacting with residues in the peripheral anionic subsite (PAS) and acyl binding pocket (ABP). The current work warrants further preclinical studies to assess the potential for these novel compounds for the treatment of AD.

Locations of Halide Ions in Tetragonal Lysozyme Crystals

NASA Technical Reports Server (NTRS)

Lim, Kap; Adimurthy, Ganapathi; Nadarajah, Arunan; Forsythe, Elizabeth L.; Pusey, Marc L.

1998-01-01

Anions play an important role in the crystallization of lysozyme, and are known to bind to the crystalline protein. Previous studies employing X-ray crystallography had found one chloride ion binding site in the tetragonal crystal form of the protein and four nitrate ion binding sites in the monoclinic form. Studies using other approaches have reported more chloride ion binding sites, but their locations were not known. Knowing the precise location of these anions is also useful in determining the correct electrostatic fields surrounding the protein. In the first part of this study the anion positions in the tetragonal form were determined from the difference Fourier map obtained from the lysozyme crystals grown in bromide and chloride solutions under identical conditions. The anion locations were then obtained from standard crystallographic methods and five possible anion binding sites were found in this manner. The sole chloride ion binding site found in previous studies was confirmed. The remaining four sites were new ones for tetragonal lysozyme crystals. However, three of these new sites and the previously found one corresponded to the four unique binding sites found for nitrate ions in monoclinic crystals. This suggests that most of the anion binding sites in lysozyme remain unchanged, even when different anions and different crystal forms of lysozyme are employed. It is unlikely that there are many more anions in the tetragonal lysozyme crystal structure. Assuming osmotic equilibrium it can be shown that there are at most three more anions in the crystal channels. Some of the new anion binding sites found in this study were, as expected, in pockets containing basic residues. However, some of them were near neutral, but polar, residues. Thus, the study also showed the importance of uncharged, but polar groups, on the protein surface in determining its electrostatic field. This was important for the second part of this study where the electrostatic field surrounding the protein was accurately determined. This was achieved by solving the linearized version of the Poisson-Boltzmann equation for the protein in solution. The solution was computed employing the commercial code Delphi which uses a finite difference technique. This has recently become available as a module in the general protein visualization code Insight II. Partial charges were assigned to the polar groups of lysozyme for the calculations done here. The calculations showed the complexity of the electrostatic field surrounding the protein. Although most of the region near the protein surface had a positive field strength, the active site cleft was negatively charged and this was projected a considerable distance. This might explain the occurrence of "head-to-side" interactions in the formation of lysozyme aggregates in solution. Pockets of high positive field strength were also found in the vicinity of the anion locations obtained from the crystallographic part of this study, confirming the validity of these calculations. This study clearly shows not only the importance of determining the counterion locations in protein crystals and the electrostatic fields surrounding the protein, but also the advantage of performing them together.

Global evaluation and calibration of a passive air sampler for gaseous mercury

NASA Astrophysics Data System (ADS)

McLagan, David S.; Mitchell, Carl P. J.; Steffen, Alexandra; Hung, Hayley; Shin, Cecilia; Stupple, Geoff W.; Olson, Mark L.; Luke, Winston T.; Kelley, Paul; Howard, Dean; Edwards, Grant C.; Nelson, Peter F.; Xiao, Hang; Sheu, Guey-Rong; Dreyer, Annekatrin; Huang, Haiyong; Hussain, Batual Abdul; Lei, Ying D.; Tavshunsky, Ilana; Wania, Frank

2018-04-01

Passive air samplers (PASs) for gaseous mercury (Hg) were deployed for time periods between 1 month and 1 year at 20 sites across the globe with continuous atmospheric Hg monitoring using active Tekran instruments. The purpose was to evaluate the accuracy of the PAS vis-à-vis the industry standard active instruments and to determine a sampling rate (SR; the volume of air stripped of gaseous Hg per unit of time) that is applicable across a wide range of conditions. The sites spanned a wide range of latitudes, altitudes, meteorological conditions, and gaseous Hg concentrations. Precision, based on 378 replicated deployments performed by numerous personnel at multiple sites, is 3.6 ± 3.0 %1, confirming the PAS's excellent reproducibility and ease of use. Using a SR previously determined at a single site, gaseous Hg concentrations derived from the globally distributed PASs deviate from Tekran-based concentrations by 14.2 ± 10 %. A recalibration using the entire new data set yields a slightly higher SR of 0.1354 ± 0.016 m3 day-1. When concentrations are derived from the PAS using this revised SR the difference between concentrations from active and passive sampling is reduced to 8.8 ± 7.5 %. At the mean gaseous Hg concentration across the study sites of 1.54 ng m-3, this represents an ability to resolve concentrations to within 0.13 ng m-3. Adjusting the sampling rate to deployment specific temperatures and wind speeds does not decrease the difference in active-passive concentration further (8.7 ± 5.7 %), but reduces its variability by leading to better agreement in Hg concentrations measured at sites with very high and very low temperatures and very high wind speeds. This value (8.7 ± 5.7 %) represents a conservative assessment of the overall uncertainty of the PAS due to inherent uncertainties of the Tekran instruments. Going forward, the recalibrated SR adjusted for temperature and wind speed should be used, especially if conditions are highly variable or deviate considerably from the average of the deployments in this study (9.89 °C, 3.41 m s-1). Overall, the study demonstrates that the sampler is capable of recording background gaseous Hg concentrations across a wide range of environmental conditions with accuracy similar to that of industry standard active sampling instruments. Results at sites with active speciation units were inconclusive on whether the PASs take up total gaseous Hg or solely gaseous elemental Hg primarily because gaseous oxidized Hg concentrations were in a similar range as the uncertainty of the PAS. 1Subscripted numbers are not significant, but are reported to reduce rounding errors in subsequent studies (see Sect. 2.3 for details).

Comparison of atmospheric concentrations of currently used pesticides between urban and rural areas during intensive application period in Alsace (France) by using XAD-2® based passive samplers.

PubMed

Liaud, Celine; Schwartz, Jean-Jacques; Millet, Maurice

2017-07-03

XAD-2® passive samplers (PAS) have been exposed simultaneously for 14 days on two sites, one rural and one urban, situated in Alsace (East of France) during intensive pesticides application in agriculture (between March and September). PAS have been extracted and analyzed for current-used pesticides and lindane with an analytical method coupling accelerated solvent extraction (ASE), solid-phase microextraction (SPME) and GC/MS/MS. Results show the detection of pesticides is linked to the period of application and spatial and temporal variabilities can be observed with these PAS during the selected sampling period. The spatial and temporal variability is comparable to the one previously observed by comparing data obtained with PAS with data from Hi.-Vol. samplers in an urban area. Sampling rates were calculated for some pesticides and values are comparable to the data already available in the literature. From these sampling rates, concentrations in ng m -3 of pesticides in PAS have been calculated and are in the same order of magnitude as those obtained with Hi.Vol. sampling during the same period of time.

The role of the peripheral anionic site and cation-pi interactions in the ligand penetration of the human AChE gorge.

PubMed

Branduardi, Davide; Gervasio, Francesco Luigi; Cavalli, Andrea; Recanatini, Maurizio; Parrinello, Michele

2005-06-29

We study the ligand (tetramethylammonium) recognition by the peripheral anionic site and its penetration of the human AChE gorge by using atomistic molecular dynamics simulations and our recently developed metadynamics method. The role of both the peripheral anionic site and the formation of cation-pi interactions in the ligand entrance are clearly shown. In particular, a simulation with the W286A mutant shows the fundamental role of this residue in anchoring the ligand at the peripheral anionic site of the enzyme and in positioning it prior to the gorge entrance. Once the ligand is properly oriented, the formation of specific and synchronized cation-pi interactions with W86, F295, and Y341 enables the gorge penetration. Eventually, the ligand is stabilized in a free energy basin by means of cation-pi interactions with W86.

Structural integration in hypoxia-inducible factors

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

Wu, Dalei; Potluri, Nalini; Lu, Jingping

The hypoxia-inducible factors (HIFs) coordinate cellular adaptations to low oxygen stress by regulating transcriptional programs in erythropoiesis, angiogenesis and metabolism. These programs promote the growth and progression of many tumours, making HIFs attractive anticancer targets. Transcriptionally active HIFs consist of HIF-alpha and ARNT (also called HIF-1 beta) subunits. Here we describe crystal structures for each of mouse HIF-2 alpha-ARNT and HIF-1 alpha-ARNT heterodimers in states that include bound small molecules and their hypoxia response element. A highly integrated quaternary architecture is shared by HIF-2 alpha-ARNT and HIF-1 alpha-ARNT, wherein ARNT spirals around the outside of each HIF-alpha subunit. Five distinctmore » pockets are observed that permit small-molecule binding, including PAS domain encapsulated sites and an interfacial cavity formed through subunit heterodimerization. The DNA-reading head rotates, extends and cooperates with a distal PAS domain to bind hypoxia response elements. HIF-alpha mutations linked to human cancers map to sensitive sites that establish DNA binding and the stability of PAS domains and pockets.« less

The Polar and Electrical Nature of Dye Binding Sites on Human Red Blood Cell Membranes.

DTIC Science & Technology

positive charges at the binding sites. By increasing the concentration of the anionic BPB (or by the addition of the anionic detergent sodium lauryl ... sulfate ) these positive charges appear to be successively titrated, rendering the membrane binding sites electrically neutral at this pH. The average

Aerosol Light Absorption and Scattering at Four Sites in and Near Mexico City: Comparison with Las Vegas, Nevada, USA

NASA Astrophysics Data System (ADS)

Arnott, W. P.; Miranda, G. P.; Gaffney, J. S.; Marley, N. A.

2007-05-01

Four photoacoustic spectrometers (PAS) for aerosol light scattering and absorption measurements were deployed in and near Mexico City in March 2006 as part of the Megacity Impacts on Regional and Global Environments (MIRAGE). The four sites included: an urban site at Instituto Mexicano del Petroleo (Mexican Oil Institute, denoted by IMP); a suburban site at the Technological University of Tecamac; a rural site at "La Biznaga" ranch; and a site at the Paseo de Cortes (altitude 3,810 meters ASL) in the rural area above Amecameca in the State of Mexico, on the saddle between the volcanoes Popocatepetl and Iztaccihuatl. A similar campaign was held in Las Vegas, Nevada, USA in January-February, 2003. The IMP site gave in-situ characterization of the Mexico City plume under favorable wind conditions while the other sites provided characterization of the plume, mixed in with any local sources. The second and third sites are north of Mexico City, and the fourth site is south. The PAS used at IMP operates at 532 nm, and conveniently allowed for characterization of gaseous absorption at this wavelength as well. Instruments at the second and third sites operate at 870 nm, and the one at the fourth site at 780 nm. Light scattering measurements are accomplished within the PAS by the reciprocal nephelometery method. In the urban site the aerosol absorption coefficient typically varies between 20 and 180 Mm-1 during the course of the day and significant diurnal variation of the aerosol single scattering albedo was observed probably as a consequence of secondary aerosol formation. Comparisons with TSI nephelometer scattering at the T0 site will be presented. We will present the diurnal variation of the scattering and absorption as well as the single scattering albedo and fraction of absorption due to gases at the IMP site and compare with Las Vegas diurnal variation. Mexico City 'breaths' more during the course of the day than Las Vegas, Nevada in part because the latitude of Mexico City resulted in more direct solar radiation. Further insight on the meteorological connections will be discussed.

Evaluation of the Alphasense Optical Particle Counter (OPC-N2) and the Grimm Portable Aerosol Spectrometer (PAS-1.108)

PubMed Central

Sousan, Sinan; Koehler, Kirsten; Hallett, Laura; Peters, Thomas M.

2017-01-01

We compared the performance of a low-cost (∼$500), compact optical particle counter (OPC, OPC-N2, Alphasense) to another OPC (PAS-1.108, Grimm Technologies) and reference instruments. We measured the detection efficiency of the OPCs by size from 0.5 to 5 μm for monodispersed, polystyrene latex (PSL) spheres. We then compared number and mass concentrations measured with the OPCs to those measured with reference instruments for three aerosols: salt, welding fume and Arizona road dust. The OPC-N2 detection efficiency for monodispersed was similar to the PAS-1.108 for particles larger than 0.8 μm (minimum of 79% at 1 μm and maximum of 101% at 3 μm). For 0.5-μm particles, the detection efficiency of OPCN2 was underestimated at 78%, whereas PAS-1.108 overestimated concentrations by 183%. The mass concentrations from the OPCs were linear (r ≥ 0.97) with those from the reference instruments for all aerosols, although the slope and intercept were different. The mass concentrations were overestimated for dust (OPC-N2, slope = 1.6; PAS-1.108, slope = 2.7) and underestimated for welding fume (OPC-N2, slope = 0.05; PAS-1.108, slope = 0.4). The coefficient of variation (CV, precision) for OPC-N2 for all experiments was between 4.2% and 16%. These findings suggest that, given site-specific calibrations, the OPC-N2 can provide number and mass concentrations similar to the PAS-1.108 for particles larger than 1 μm. PMID:28871213

Evaluation of the Alphasense Optical Particle Counter (OPC-N2) and the Grimm Portable Aerosol Spectrometer (PAS-1.108).

PubMed

Sousan, Sinan; Koehler, Kirsten; Hallett, Laura; Peters, Thomas M

2016-01-01

We compared the performance of a low-cost (∼$500), compact optical particle counter (OPC, OPC-N2, Alphasense) to another OPC (PAS-1.108, Grimm Technologies) and reference instruments. We measured the detection efficiency of the OPCs by size from 0.5 to 5 μm for monodispersed, polystyrene latex (PSL) spheres. We then compared number and mass concentrations measured with the OPCs to those measured with reference instruments for three aerosols: salt, welding fume and Arizona road dust. The OPC-N2 detection efficiency for monodispersed was similar to the PAS-1.108 for particles larger than 0.8 μm (minimum of 79% at 1 μm and maximum of 101% at 3 μm). For 0.5-μm particles, the detection efficiency of OPCN2 was underestimated at 78%, whereas PAS-1.108 overestimated concentrations by 183%. The mass concentrations from the OPCs were linear (r ≥ 0.97) with those from the reference instruments for all aerosols, although the slope and intercept were different. The mass concentrations were overestimated for dust (OPC-N2, slope = 1.6; PAS-1.108, slope = 2.7) and underestimated for welding fume (OPC-N2, slope = 0.05; PAS-1.108, slope = 0.4). The coefficient of variation (CV, precision) for OPC-N2 for all experiments was between 4.2% and 16%. These findings suggest that, given site-specific calibrations, the OPC-N2 can provide number and mass concentrations similar to the PAS-1.108 for particles larger than 1 μm.

Molecular Basis for Differential Anion Binding and Proton Coupling in the Cl−/H+ Exchanger ClC-ec1

PubMed Central

Jiang, Tao; Han, Wei; Maduke, Merritt; Tajkhorshid, Emad

2016-01-01

Cl−/H+ transporters of the CLC superfamily form a ubiquitous class of membrane proteins that catalyze stoichiometrically coupled exchange of Cl− and H+ across biological membranes. CLC transporters exchange H+ for halides and certain polyatomic anions, but exclude cations, F−, and larger physiological anions, such as PO43− and SO42−. Despite comparable transport rates of different anions, the H+ coupling in CLC transporters varies significantly depending on the chemical nature of the transported anion. Although the molecular mechanism of exchange remains unknown, studies on bacterial ClC-ec1 transporter revealed that Cl− binding to the central anion-binding site (Scen) is crucial for the anion-coupled H+ transport. Here, we show that Cl−, F−, NO3−, and SCN− display distinct binding coordinations at the Scen site and are hydrated in different manners. Consistent with the observation of differential bindings, ClC-ec1 exhibits markedly variable ability to support the formation of the transient water wires, which are necessary to support the connection of the two H+ transfer sites (Gluin and Gluex), in the presence of different anions. While continuous water wires are frequently observed in the presence of physiologically transported Cl−, binding of F− or NO3− leads to the formation of pseudo-water-wires that are substantially different from the wires formed with Cl−. Binding of SCN−, however, eliminates the water wires altogether. These findings provide structural details of anion binding in ClC-ec1 and reveal a putative atomic-level mechanism for the decoupling of H+ transport to the transport of anions other than Cl−. PMID:26880377

Theoretical study of native point defects in strained-layer superlattice systems

NASA Astrophysics Data System (ADS)

Krishnamurthy, S.; Yu, Zhi Gang

2018-04-01

We developed a theoretical approach that employs first-principles Hamiltonians, tight-binding Hamiltonians, and Green's function techniques to obtain energy levels arising from native point defects (NPDs) in InAs-GaSb and InAs-InAs1-xSbx strained layer superlattice (SLS) systems. In InAs and GaSb regions, we considered four types of NPDs—anion vacancy, cation vacancy, anion anti-site, and cation anti-site—as well as isoelectronic substitution at anion sites (Sb at the As site and As at the Sb site). Additionally, we considered three types of defects—the cation at the second anion site, the second anion at the cation site, and second anion vacancy—in the InAs1-xSbx alloy region of the SLS. For a selected few designs, we studied NPDs both in the bulk region and near the interfaces of the SLS. We have considered 12 designs of InAs-GaSb systems and two designs of InAs-InAs0.7Sb0.3 systems lattice-matched to the GaSb substrate. The calculated defect levels not only agreed well with available measurements, but also revealed the connection between mid-gap levels and specific NPDs. We further calculated defect formation energies both in compounds and in all superlattices considered above. Since the absolute value of defect formation energy depends considerably on growth conditions, we evaluated the formation energies in SLS with respect to their value in the corresponding bulk or alloy. The calculated defect formation energies, together with defect energy level results, allow us to identify a few promising SLS designs for high-performing photodetectors.

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

Aoyagi, Yasuyuki; Department of Genome Research and Clinical Application, Graduate School of Medicine, Chiba University, Chiba; Kuroda, Masayuki, E-mail: kurodam@faculty.chiba-u.jp

Adipose tissue is expected to provide a source of cells for protein replacement therapies via auto-transplantation. However, the conditioning of the environment surrounding the transplanted adipocytes for their long-term survival and protein secretion properties has not been established. We have recently developed a preparation procedure for preadipocytes, ceiling culture-derived proliferative adipocytes (ccdPAs), as a therapeutic gene vehicle suitable for stable gene product secretion. We herein report the results of our evaluation of using fibrin glue as a scaffold for the transplanted ccdPAs for the expression of a transduced gene in a three-dimensional culture system. The ccdPAs secreted the functional proteinmore » translated from an exogenously transduced gene, as well as physiological adipocyte proteins, and the long viability of ccdPAs (up to 84 days) was dependent on the fibrinogen concentrations. The ccdPAs spontaneously accumulated lipid droplets, and their expression levels of the transduced exogenous gene with its product were maintained for at least 56 days. The fibrinogen concentration modified the adipogenic differentiation of ccdPAs and their exogenous gene expression levels, and the levels of exogenously transduced gene expression at the different fibrinogen concentrations were dependent on the extent of adipogenic differentiation in the gel. These results indicate that fibrin glue helps to maintain the high adipogenic potential of cultured adipocytes after passaging in a 3D culture system, and suggests that once they are successfully implanted at the transplantation site, the cells exhibit increased expression of the transduced gene with adipogenic differentiation.« less

Introduction of Participatory Conservation in Croatia, Residents' Perceptions: A Case Study from the Istrian Peninsula

NASA Astrophysics Data System (ADS)

Sladonja, Barbara; Brščić, Kristina; Poljuha, Danijela; Fanuko, Neda; Grgurev, Marin

2012-06-01

Croatia, like many other transition countries has undergone radical changes in its nature protection models. This paper discusses a historical overview, present situation and future possibilities for nature conservation in Croatia. A conservative top-down approach to nature protection was applied in the past in Croatia and is now being replaced by a prevalent bottom-up approach. Social context is crucial to introducing participatory conservation, therefore special concern is given to the perception of the local population towards protected area management in Istria as a case study in Croatia. Survey data were used to assess the conservation knowledge of local populations and their perception towards Protected Areas (PAs), leadership activities and management authorities in Istria County. This paper examines the perceptions of 313 residents living in and around six natural PAs located in Istria. The results revealed a moderate general knowledge about PAs in Istria and environmental issues, and a low awareness of institutions managing PAs, eagerness to participate in the activities of PAs and general support for the conservation cause. Understanding the perception of local residents enables the creation of feasible, long-term strategies for the implementation of participatory conservation. The research identifies the need for greater human, technical and financial efforts to strengthen the management capabilities of local agencies responsible for PAs. The process of participatory conservation optimization in Croatia is underway and world experiences must be observed in order to create a congruent, site-specific model with the best possible results.

Extinction, seeing and sky transparency monitoring at the Observatorio Astrofísico de Javalambre for J-PAS and J-PLUS calibration and scheduling

NASA Astrophysics Data System (ADS)

Vázquez Ramió, H.; Díaz-Martín, M. C.; Varela, J.; Ederoclite, A.; Maícas, N. Lamadrid, J. L.; Abril, J.; Iglesias-Marzoa, R.; Rodríguez, S.; Tilve, V.; Cenarro, A. J.; Antón Bravo, J. L.; Bello Ferrer, R.; Cristóbal-Hornillos, D.; Guillén Civera, L.; Hernández-Fuertes, J.; Jiménez Mejías, D.; Lasso-Cabrera, N. M.; López Alegre, G.; López Sainz, A.; Luis-Simoes, R. M.; Marín-Franch, A.; Moles, M.; Rueda-Teruel, F.; Rueda-Teruel, S.; Suárez López, O.; Yanes-Díaz, A.

2015-05-01

The Javalambre-Physics of the Accelerating Universe Astrophysical Survey (J-PAS; see Benítez et al. 2014) and the Javalambre-Photometric Local Universe Survey (J-PLUS) will be conducted at the brand-new Observatorio Astrofísico de Javalambre (OAJ) in Teruel, Spain. J-PLUS is planned to start by the first half of 2015 while J-PAS first light is expected to happen along 2015. Besides the two main telescopes (with 2.5 m and 80 cm apertures), several smaller-sized facilities are present at the OAJ devoted to site characterization and supporting measurements to be used to calibrate the J-PAS and J-PLUS photometry and to feed up the OAJ's Sequencer with the integrated seeing and the sky transparency. These instruments are: i) an extinction monitor, an 11 " telescope estimating the atmospheric extinction to finally obtain the OAJ extinction curve, which is the initial step to J-PAS overall photometric calibration procedure; ii) an 8 " telescope implementing the Differential Image Motion Monitor (DIMM) technique to obtain the integrated seeing; and iii) an All-Sky Transmission MONitor (ASTMON), a roughly all-sky instrument providing the sky transparency as well as sky brightness and the atmospheric extinction too.

Pyrrolizidine Alkaloids from Echium vulgare in Honey Originate Primarily from Floral Nectar.

PubMed

Lucchetti, Matteo A; Glauser, Gaetan; Kilchenmann, Verena; Dübecke, Arne; Beckh, Gudrun; Praz, Christophe; Kast, Christina

2016-06-29

Pyrrolizidine alkaloids (PAs) in honey can be a potential human health risk. So far, it has remained unclear whether PAs in honey originate from pollen or floral nectar. We obtained honey, nectar, and plant pollen from two observation sites where Echium vulgare L. was naturally abundant. The PA concentration of honey was determined by targeted analysis using a high pressure liquid chromatography-mass spectrometry system (HPLC-MS/MS), allowing the quantification of six different PAs and PA-N-oxides present in E. vulgare. Echium-type PAs were detected up to 0.153 μg/g in honey. Nectar and plant pollen were analyzed by nontargeted analysis using ultrahigh pressure liquid chromatography-high resolution-mass spectrometry (UHPLC-HR-MS), allowing the detection of 10 alkaloids in small size samples. Echium-type PAs were detected between 0.3-95.1 μg/g in nectar and 500-35000 μg/g in plant pollen. The PA composition in nectar and plant pollen was compared to the composition in honey. Echimidine (+N-oxide) was the main alkaloid detected in honey and nectar samples, while echivulgarine (+N-oxide) was the main PA found in plant pollen. These results suggest that nectar contributes more significantly to PA contamination in honey than plant pollen.

Determining the use of prophylactic antibiotics in breast cancer surgeries: a survey of practice

PubMed Central

2012-01-01

Background Prophylactic antibiotics (PAs) are beneficial to breast cancer patients undergoing surgery because they prevent surgical site infection (SSI), but limited information regarding their use has been published. This study aims to determine the use of PAs prior to breast cancer surgery amongst breast surgeons in Colombia. Methods An online survey was distributed amongst the breast surgeon members of the Colombian Association of Mastology, the only breast surgery society of Colombia. The scope of the questions included demographics, clinical practice characteristics, PA prescription characteristics, and the use of PAs in common breast surgical procedures. Results The survey was distributed amongst eighty-eight breast surgeons of whom forty-seven responded (response rate: 53.4%). Forty surgeons (85.1%) reported using PAs prior to surgery of which >60% used PAs during mastectomy, axillary lymph node dissection, and/or breast reconstruction. Surgeons reported they targeted the use of PAs in cases in which patients had any of the following SSI risk factors: diabetes mellitus, drains in situ, obesity, and neoadjuvant therapy. The distribution of the self-reported PA dosing regimens was as follows: single pre-operative fixed-dose (27.7%), single preoperative dose followed by a second dose if the surgery was prolonged (44.7%), single preoperative dose followed by one or more postoperative doses for >24 hours (10.6%), and single preoperative weight-adjusted dose (2.1%). Conclusion Although this group of breast surgeons is aware of the importance of PAs in breast cancer surgery there is a discrepancy in how they use it, specifically with regards to prescription and timeliness of drug administration. Our findings call for targeted quality-improvement initiatives, such as standardized national guidelines, which can provide sufficient evidence for all stakeholders and therefore facilitate best practice medicine for breast cancer surgery. PMID:22937833

Determining the use of prophylactic antibiotics in breast cancer surgeries: a survey of practice.

PubMed

Acuna, Sergio A; Angarita, Fernando A; Escallon, Jaime; Tawil, Mauricio; Torregrosa, Lilian

2012-08-31

Prophylactic antibiotics (PAs) are beneficial to breast cancer patients undergoing surgery because they prevent surgical site infection (SSI), but limited information regarding their use has been published. This study aims to determine the use of PAs prior to breast cancer surgery amongst breast surgeons in Colombia. An online survey was distributed amongst the breast surgeon members of the Colombian Association of Mastology, the only breast surgery society of Colombia. The scope of the questions included demographics, clinical practice characteristics, PA prescription characteristics, and the use of PAs in common breast surgical procedures. The survey was distributed amongst eighty-eight breast surgeons of whom forty-seven responded (response rate: 53.4%). Forty surgeons (85.1%) reported using PAs prior to surgery of which >60% used PAs during mastectomy, axillary lymph node dissection, and/or breast reconstruction. Surgeons reported they targeted the use of PAs in cases in which patients had any of the following SSI risk factors: diabetes mellitus, drains in situ, obesity, and neoadjuvant therapy. The distribution of the self-reported PA dosing regimens was as follows: single pre-operative fixed-dose (27.7%), single preoperative dose followed by a second dose if the surgery was prolonged (44.7%), single preoperative dose followed by one or more postoperative doses for >24 hours (10.6%), and single preoperative weight-adjusted dose (2.1%). Although this group of breast surgeons is aware of the importance of PAs in breast cancer surgery there is a discrepancy in how they use it, specifically with regards to prescription and timeliness of drug administration. Our findings call for targeted quality-improvement initiatives, such as standardized national guidelines, which can provide sufficient evidence for all stakeholders and therefore facilitate best practice medicine for breast cancer surgery.

When Animators Attack

ERIC Educational Resources Information Center

Read, Brock

2006-01-01

College administrators across the US are learning that chatter on e-mail, blogs, and social-networking sites can turn even minor faux pas into major controversies. The issue is discussed with reference to the firing of a teaching assistant whose Web site lampooned the president of Columbia College Chicago and left the institution facing serious…

The effects of cations and anions on hydrogen chemisorption at Pt

NASA Technical Reports Server (NTRS)

Huang, J. C.; Ogrady, W. E.; Yeager, E.

1977-01-01

Experimental evidence based on linear sweep voltammetry is presented to substantiate the view that ionic adsorption substantially shifts electrode potentials in addition to the relative heights of the hydrogen adsorption peaks. HClO4 and HF are chosen as better reference electrolytes for anion studies. The voltammetry curves for 0.1M HF and 0.1M HClO4 as well as the effect of adding successively increasing amounts of H2SO4 to these electrolytes are discussed. The measurements are also extended to alkaline solutions. Mechanisms whereby the addition of various cations and anions to electrolytes such as HF and HClO4 can induce changes in the structure of the hydrogen adsorption region in the voltammetry curves are identified: (1) blocking of sites by anion adsorption and coupling of hydrogen adsorption and anion desorption, (2) modification in the hydrogen adsorption energies for sites adjacent to adsorbed anions, (3) changes in the potential distribution across the interface, and (4) surface restructuring.

Pattern-based detection of anion pollutants in water with DNA polyfluorophores† †Electronic supplementary information (ESI) available: Additional figures and tables and experimental details. See DOI: 10.1039/c4sc03992k Click here for additional data file.

PubMed Central

Kwon, Hyukin; Jiang, Wei

2015-01-01

Many existing irrigation, industrial and chemical storage sites are currently introducing hazardous anions into groundwater, making the monitoring of such sites a high priority. Detecting and quantifying anions in water samples typically requires complex instrumentation, adding cost and delaying analysis. Here we address these challenges by development of an optical molecular method to detect and discriminate a broad range of anionic contaminants with DNA-based fluorescent sensors. A library of 1296 tetrameric-length oligodeoxyfluorosides (ODFs) composed of metal ligand and fluorescence modulating monomers was constructed with a DNA synthesizer on PEG-polystyrene microbeads. These oligomers on beads were incubated with YIII or ZnII ions to provide affinity and responsiveness to anions. Seventeen anions were screened with the library under an epifluorescence microscope, ultimately yielding eight chemosensors that could discriminate 250 μM solutions of all 17 anions in buffered water using their patterns of response. This sensor set was able to identify two unknown anion samples from ten closely-responding anions and could also function quantitatively, determining unknown concentrations of anions such as cyanide (as low as 1 mM) and selenate (as low as 50 μM). Further studies with calibration curves established detection limits of selected anions including thiocyanate (detection limit ∼300 μM) and arsenate (∼800 μM). The results demonstrate DNA-like fluorescent chemosensors as versatile tools for optically analyzing environmentally hazardous anions in aqueous environments. PMID:26146537

Diseno de puertas moleculares controladas a nivel nanoscopico

NASA Astrophysics Data System (ADS)

Casasus Lis, Rosa

The present thesis has been developed between the frontiers of different disciplines such as Coordination and Supramolecular Chemistry and Material Science. The main objective has been the design and construction of nanosupramolecular gate-ensemble, which can be defined as a basis device that modulate the access to a certain site and whose state (opened or closed) can be controlled at will by certain external stimuli, for example ionically, electrochemically and photochemically. One of the most important ideas of this thesis is the development of molecular gates using organic-inorganic hybrid systems. We have been working with a mesoporous siliceous matrix MCM-41 type and UVM-7 that possesses preorganized cavities, in that sense the porous system are homogeneous in size even in shape and periodicity. Furthermore, it has been possible to obtain systems highly functionalized due to its high specific surfaces areas (internal and external). First of all, it has been studying the design of ionically-controlled nanoscopic molecular gates. The idealized open-closed mechanism would arise from simple interactions between amines (open-gate) and Coulombic repulsion between ammonium groups (closed-gate). When protonated the open-chain polyamines in the external surface would adopt a rigid-like conformation and would be pushed away towards the pore openings due to repulsion between ammonium groups charged positively. A fundamental aspect related to molecular gates was the demonstration of specific functions like "open-close" could be controlled wilfully by certain external stimuli. In this sense, we used two different approximations to prove how works the molecular machine: (a) detect the access (controlled by external stimuli) to the pores of certain species in solution and (b) study the release of some molecules entrapped from the pore voids into the bulk solution. The first approximation, the most difficult to control, has been carried out by using a coupled reaction that would give one observable and easy signal such as change of colour and even more the only way to occur was if the studied species came inside the nanometric porous. In second place it was reported a complete study of the behaviour of a pH-driven and anion-controlled nano-supramolecular gate-like ensemble obtained by anchoring suitable polyamines on the pore outlets of mesoporous materials of the type MCM-41. The release of an entrapped dye (Ru(bipy)3 2+) from the pore voids into the bulk solution allows us to study the gating effect. This study was carried out by monitoring the dye released from the pore voids of the solid at a certain pH in the presence of a range of anions with different structural dimensions and charges, including chloride, sulphate, phosphate, and ATP. The choice of a certain anionic guest results in a different gate-like ensemble behaviour, ranging from basically no action (chloride) to complete (ATP) or partial pore blockage, depending on the pH (sulphate and phosphate). Molecular dynamics simulations using force field methods have been carried out to explain the pH-driven open/close mechanism and selectivity patterns have been discussed in terms of kinetic rates of the liberation of the dye. Furthermore, it has been applied the potential use of molecular gatelike systems as a new strategy for the chromogenic signalling of the target anions in aqueous solutions. The idea involves molecular-recognition events coupled with the control of dye transport. It entails the use of solids with nanoscopic 3D organized surfaces (mesoporous solids) that have been functionalized at the outer surface with certain binding moieties (for example amines) and additionally the pores have been loaded with a suitable dye. In absence of any species to detect there is an opened gatelike system that is able to deliver the enclosed dye to the solution. The addition of a target anionic guest capable of forming a suitable complex with the binding site might "close the gate" which would lead to recognition, thus signalling the target anion by the inhibition of the mass-delivery process. In this work we have confirmed the ATP recognition and signalling by inhibiting dye release with nanoscopic supramolecular gatelike systems on mesoporous MCM-41 supports. Finally, a dual functional hybrid material was designed for the simultaneous chromo-fluorogenic detection and removal of Hg2+ in aqueous environment. The mesoporous solid is functionalized with thiol groups that have been further reacted with the squaraine dye, resulting in the formation of a 2,4-bis(4-dialkylaminophenyl)-3-hydroxy-4-alkylsulfanylcyclobut-2-enone (PAS) derivative being anchored to the inorganic silica matrix. When the species to detect, the Hg2+ cation, is present in the solution this reacts with the PAS fragment in the solid, releasing the squaraine dye to the solution that turned deep blue and highly fluorescent. This allows a straightforward "naked-eye" detection of Hg2+ employing an easy-to-use procedure.

Polyamines Interact with Hydroxyl Radicals in Activating Ca2+ and K+ Transport across the Root Epidermal Plasma Membranes1[W

PubMed Central

Zepeda-Jazo, Isaac; Velarde-Buendía, Ana María; Enríquez-Figueroa, René; Bose, Jayakumar; Shabala, Sergey; Muñiz-Murguía, Jesús; Pottosin, Igor I.

2011-01-01

Reactive oxygen species (ROS) are integral components of the plant adaptive responses to environment. Importantly, ROS affect the intracellular Ca2+ dynamics by activating a range of nonselective Ca2+-permeable channels in plasma membrane (PM). Using patch-clamp and noninvasive microelectrode ion flux measuring techniques, we have characterized ionic currents and net K+ and Ca2+ fluxes induced by hydroxyl radicals (OH•) in pea (Pisum sativum) roots. OH•, but not hydrogen peroxide, activated a rapid Ca2+ efflux and a more slowly developing net Ca2+ influx concurrent with a net K+ efflux. In isolated protoplasts, OH• evoked a nonselective current, with a time course and a steady-state magnitude similar to those for a K+ efflux in intact roots. This current displayed a low ionic selectivity and was permeable to Ca2+. Active OH•-induced Ca2+ efflux in roots was suppressed by the PM Ca2+ pump inhibitors eosine yellow and erythrosine B. The cation channel blockers gadolinium, nifedipine, and verapamil and the anionic channel blockers 5-nitro-2(3-phenylpropylamino)-benzoate and niflumate inhibited OH•-induced ionic currents in root protoplasts and K+ efflux and Ca2+ influx in roots. Contrary to expectations, polyamines (PAs) did not inhibit the OH•-induced cation fluxes. The net OH•-induced Ca2+ efflux was largely prolonged in the presence of spermine, and all PAs tested (spermine, spermidine, and putrescine) accelerated and augmented the OH•-induced net K+ efflux from roots. The latter effect was also observed in patch-clamp experiments on root protoplasts. We conclude that PAs interact with ROS to alter intracellular Ca2+ homeostasis by modulating both Ca2+ influx and efflux transport systems at the root cell PM. PMID:21980172

An uptake of cationized ferritin by alveolar type I cells in airway-instilled goat lung: distribution of anionic sites on the epithelial surface.

PubMed

Atwal, O S; Viel, L; Minhas, K J

1990-07-01

The present study has investigated ultrastructural localization of anionic sites on the luminal surface of the alveolar epithelium of goat lung by direct airway instillation of cationized ferritin (CF) in the cranial lobe of the right lung through a bronchoscope. The cationic probe decorated preferentially the luminal plasmalemmal vesicles and plasmalemma proper of alveolar type I cell. This indicated the presence of highly charged anionic microdomains at these binding sites. The ligand was internalized in the free plasmalemmal vesicles of alveolar type I cell within 2 min. Heavy decoration of vesicles at 5 min of perfusion indicated that the amount of CF internalization increased with its concentration in the alveoli. It is suggested that exposure of alveolar surface to several gases of ruminal-origin induces changes in the surface charge of luminal plasmalemma of alveolar type I cells. The significance of these anionic plasmalemmal sites is discussed in relation to the adjustment of osmotic pressure gradient across the alveolar-capillary membrane of the ruminant lung.

Distinct regulation of alternative polyadenylation and gene expression by nuclear poly(A) polymerases

PubMed Central

Li, Wencheng; Laishram, Rakesh S.; Hoque, Mainul; Ji, Zhe

2017-01-01

Abstract Polyadenylation of nascent RNA by poly(A) polymerase (PAP) is important for 3′ end maturation of almost all eukaryotic mRNAs. Most mammalian genes harbor multiple polyadenylation sites (PASs), leading to expression of alternative polyadenylation (APA) isoforms with distinct functions. How poly(A) polymerases may regulate PAS usage and hence gene expression is poorly understood. Here, we show that the nuclear canonical (PAPα and PAPγ) and non-canonical (Star-PAP) PAPs play diverse roles in PAS selection and gene expression. Deficiencies in the PAPs resulted in perturbations of gene expression, with Star-PAP impacting lowly expressed mRNAs and long-noncoding RNAs to the greatest extent. Importantly, different PASs of a gene are distinctly regulated by different PAPs, leading to widespread relative expression changes of APA isoforms. The location and surrounding sequence motifs of a PAS appear to differentiate its regulation by the PAPs. We show Star-PAP-specific PAS usage regulates the expression of the eukaryotic translation initiation factor EIF4A1, the tumor suppressor gene PTEN and the long non-coding RNA NEAT1. The Star-PAP-mediated APA of PTEN is essential for DNA damage-induced increase of PTEN protein levels. Together, our results reveal a PAS-guided and PAP-mediated paradigm for gene expression in response to cellular signaling cues. PMID:28911096

Hydrothermally tailor-made chitosan fiber for micro-solid phase extraction of petroleum acids in crude oils.

PubMed

Zhu, Gang-Tian; Hu, Xiao-Li; He, Sheng; He, Xiao-Mei; Zhu, Shu-Kui; Feng, Yu-Qi

2018-06-05

Tailor-made chitosan fiber was prepared via hydrothermal treatment to serve as a micro-solid phase extraction (micro-SPE) sorbent for the analysis of petroleum acids (PAs) in crude oils. Chitosan fiber, which is commercial and cheap, has a diameter of about 10 μm and a length of a few centimeters. The fibrous property of the sorbent enables the micro-SPE to deal with viscous crude oil samples because of the low back-pressure during extraction, while the abundant hydroxyl groups and amino groups on the surface of chitosan fiber can provide high density of specific sites for adsorption of PAs. Moreover, it was found that hydrothermal treatment at certain conditions could tune the surface properties of chitosan fiber, leading to significant improvement of the capacity of the fiber in adsorption of PAs. Using hydrothermally treated chitosan fiber as sorbent, the micro-SPE was applied to the determination of PAs in crude oils, with the advantages of easy-operation, rapidness and high sensitivity (the limits of detection range from 0.7 ng/g to 5.4 ng/g). Furthermore, coupled with comprehensive two dimensional gas chromatography-mass spectrometry (GC × GCMS), the treated chitosan fiber packed micro-SPE method showed a great potential for comprehensive profiling of PAs in crude oils. Copyright © 2018 Elsevier B.V. All rights reserved.

PABPN1-Dependent mRNA Processing Induces Muscle Wasting

PubMed Central

Raz, Yotam; van Putten, Maaike; Paniagua-Soriano, Guillem; Krom, Yvonne D.; Florea, Bogdan I.; Raz, Vered

2016-01-01

Poly(A) Binding Protein Nuclear 1 (PABPN1) is a multifunctional regulator of mRNA processing, and its expression levels specifically decline in aging muscles. An expansion mutation in PABPN1 is the genetic cause of oculopharyngeal muscle dystrophy (OPMD), a late onset and rare myopathy. Moreover, reduced PABPN1 expression correlates with symptom manifestation in OPMD. PABPN1 regulates alternative polyadenylation site (PAS) utilization. However, the impact of PAS utilization on cell and tissue function is poorly understood. We hypothesized that altered PABPN1 expression levels is an underlying cause of muscle wasting. To test this, we stably down-regulated PABPN1 in mouse tibialis anterior (TA) muscles by localized injection of adeno-associated viruses expressing shRNA to PABPN1 (shPab). We found that a mild reduction in PABPN1 levels causes muscle pathology including myofiber atrophy, thickening of extracellular matrix and myofiber-type transition. Moreover, reduced PABPN1 levels caused a consistent decline in distal PAS utilization in the 3’-UTR of a subset of OPMD-dysregulated genes. This alternative PAS utilization led to up-regulation of Atrogin-1, a key muscle atrophy regulator, but down regulation of proteasomal genes. Additionally reduced PABPN1 levels caused a reduction in proteasomal activity, and transition in MyHC isotope expression pattern in myofibers. We suggest that PABPN1-mediated alternative PAS utilization plays a central role in aging-associated muscle wasting. PMID:27152426

Competitive regulation of alternative splicing and alternative polyadenylation by hnRNP H and CstF64 determines acetylcholinesterase isoforms

PubMed Central

Nazim, Mohammad; Masuda, Akio; Rahman, Mohammad Alinoor; Nasrin, Farhana; Takeda, Jun-ichi; Ohe, Kenji; Ohkawara, Bisei; Ito, Mikako

2017-01-01

Abstract Acetylcholinesterase (AChE), encoded by the ACHE gene, hydrolyzes the neurotransmitter acetylcholine to terminate synaptic transmission. Alternative splicing close to the 3΄ end generates three distinct isoforms of AChET, AChEH and AChER. We found that hnRNP H binds to two specific G-runs in exon 5a of human ACHE and activates the distal alternative 3΄ splice site (ss) between exons 5a and 5b to generate AChET. Specific effect of hnRNP H was corroborated by siRNA-mediated knockdown and artificial tethering of hnRNP H. Furthermore, hnRNP H competes for binding of CstF64 to the overlapping binding sites in exon 5a, and suppresses the selection of a cryptic polyadenylation site (PAS), which additionally ensures transcription of the distal 3΄ ss required for the generation of AChET. Expression levels of hnRNP H were positively correlated with the proportions of the AChET isoform in three different cell lines. HnRNP H thus critically generates AChET by enhancing the distal 3΄ ss and by suppressing the cryptic PAS. Global analysis of CLIP-seq and RNA-seq also revealed that hnRNP H competitively regulates alternative 3΄ ss and alternative PAS in other genes. We propose that hnRNP H is an essential factor that competitively regulates alternative splicing and alternative polyadenylation. PMID:28180311

Competitive regulation of alternative splicing and alternative polyadenylation by hnRNP H and CstF64 determines acetylcholinesterase isoforms.

PubMed

Nazim, Mohammad; Masuda, Akio; Rahman, Mohammad Alinoor; Nasrin, Farhana; Takeda, Jun-Ichi; Ohe, Kenji; Ohkawara, Bisei; Ito, Mikako; Ohno, Kinji

2017-02-17

Acetylcholinesterase (AChE), encoded by the ACHE gene, hydrolyzes the neurotransmitter acetylcholine to terminate synaptic transmission. Alternative splicing close to the 3΄ end generates three distinct isoforms of AChET, AChEH and AChER. We found that hnRNP H binds to two specific G-runs in exon 5a of human ACHE and activates the distal alternative 3΄ splice site (ss) between exons 5a and 5b to generate AChET. Specific effect of hnRNP H was corroborated by siRNA-mediated knockdown and artificial tethering of hnRNP H. Furthermore, hnRNP H competes for binding of CstF64 to the overlapping binding sites in exon 5a, and suppresses the selection of a cryptic polyadenylation site (PAS), which additionally ensures transcription of the distal 3΄ ss required for the generation of AChET. Expression levels of hnRNP H were positively correlated with the proportions of the AChET isoform in three different cell lines. HnRNP H thus critically generates AChET by enhancing the distal 3΄ ss and by suppressing the cryptic PAS. Global analysis of CLIP-seq and RNA-seq also revealed that hnRNP H competitively regulates alternative 3΄ ss and alternative PAS in other genes. We propose that hnRNP H is an essential factor that competitively regulates alternative splicing and alternative polyadenylation.

The role of the anionic and cationic pt sites in the adsorption site preference of water and ethanol on defected Pt4/Pt(111) substrates: A density functional theory investigation within the D3 van der waals corrections

NASA Astrophysics Data System (ADS)

Seminovski, Yohanna; Amaral, Rafael C.; Tereshchuk, Polina; Da Silva, Juarez L. F.

2018-01-01

Platinum (Pt) atoms in the bulk face-centered cubic structure have neutral charge because they are equivalent by symmetry, however, in clean Pt surfaces, the effective charge on Pt atoms can turn slightly negative (anionic) or positive (cationic) while increasing substantially in magnitude for defected (low-coordinated) Pt sites. The effective charge affect the adsorption properties of molecular species on Pt surfaces and it can compete in importance with the coupling of the substrate-molecule electronic states. Although several studies have been reported due to the importance of Pt for catalysis, our understanding of the role played by low-coordinated sites is still limited. Here, we employ density functional theory within the Perdew-Burke-Ernzerhof exchange-correlation functional and the D3 van der Waals (vdW) correction to investigate the role of the cationic and anionic Pt sites on the adsorption properties of ethanol and water on defected Pt4/Pt(111) substrates. Four substrates were carefully selected, namely, two two-dimensional (2D) Pt4 configurations (2D-strand and 2D-island) and two tri-dimensional (3D) Pt4 (3D-fcc and 3D-hcp), to understand the role of coordination, effective charge, and coupling of the electronic states in the adsorption properties. From the Bader charge analysis, we identified the cationic and anionic sites among the Pt atoms exposed to the vacuum region in the Pt4/Pt(111) substrates. We found that ethanol and water bind via the anionic O atoms to the low-coordinated defected Pt sites of the substrates, where the angle PtOH is nearly 100° for most configurations. In the 3D-fcc or 3D-hcp defected configurations, the lowest-coordinated Pt atoms are anionic, hence, those Pt sites are not preferable for the adsorption of O atoms. The charge transfer from water and ethanol to the Pt substrates has similar magnitude for all cases, which implies similar Coulomb contribution to the adsorption energy. Moreover, we found a correlation of the adsorption energy with the shift of the center of gravity of the occupied d-states of Pt sites.

Poly(A) code analyses reveal key determinants for tissue-specific mRNA alternative polyadenylation

PubMed Central

Weng, Lingjie; Li, Yi; Xie, Xiaohui; Shi, Yongsheng

2016-01-01

mRNA alternative polyadenylation (APA) is a critical mechanism for post-transcriptional gene regulation and is often regulated in a tissue- and/or developmental stage-specific manner. An ultimate goal for the APA field has been to be able to computationally predict APA profiles under different physiological or pathological conditions. As a first step toward this goal, we have assembled a poly(A) code for predicting tissue-specific poly(A) sites (PASs). Based on a compendium of over 600 features that have known or potential roles in PAS selection, we have generated and refined a machine-learning algorithm using multiple high-throughput sequencing-based data sets of tissue-specific and constitutive PASs. This code can predict tissue-specific PASs with >85% accuracy. Importantly, by analyzing the prediction performance based on different RNA features, we found that PAS context, including the distance between alternative PASs and the relative position of a PAS within the gene, is a key feature for determining the susceptibility of a PAS to tissue-specific regulation. Our poly(A) code provides a useful tool for not only predicting tissue-specific APA regulation, but also for studying its underlying molecular mechanisms. PMID:27095026

Ce{sub 11}Ge{sub 3.73(2)}In{sub 6.27}: Solid-state synthesis, crystal structure and site-preference

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

Jeon, Beom-Yong; Nam, Gnu; Lee, Dong Woo

A novel intermetallic compound of Ce{sub 11}Ge{sub 3.73(2)}In{sub 6.27} has been synthesized through the high-temperature solid-state reaction using Nb-ampoules. A batch of well grown block-/short bar-shaped single-crystals has been obtained, and the crystal structure of the title compound has been characterized by single-crystal X-ray diffraction analyses. Ce{sub 11}Ge{sub 3.73(2)}In{sub 6.27} adopts the Ho{sub 11}Ge{sub 10}-type structure belonging to the tetragonal space group I4/mmm (Z=4, Pearson symbol tI84) with nine crystallographically unique atomic positions in the asymmetric unit. The lattice parameters are a=12.0163(1) Å and c=16.5396(2) Å. The overall crystal structure can simply be depicted as an assembly of three differentmore » types of co-facial cationic polyhedra centered by anions, which is further enclosed by the three-dimensional (3-D) cage-like anionic framework. The extra amount of In is observed in one of three isolated anionic sites resulting in introducing the Ge/In-mixed site at the Wyckoff 4e site. This unique site-preference of In substitution for Ge at the 4e site has been enlightened via the atomic size-aspect which was fully supported and rationalized by the site- and bond-energies analyses using tight-binding linear muffin-tin orbital (TB-LMTO) calculations. Energy-dispersive X-ray spectroscopy (EDS), density of states (DOS), crystal orbital Hamilton population (COHP), and electron localization function (ELF) analyses for the title compound are also presented. Magnetic susceptibility measurement proves that an antiferromagnetic ordering of Ce atoms at a low temperature with a paramagnetic Curie temperature of −23.2 K. - Graphical abstract: Reported is experimental and theoretical investigations for Ce{sub 11}Ge{sub 3.73(2)}In{sub 6.27}, which is the first reported example having the extra amounts of In substitution for Ge at one of three “isolated” anionic sites in the Ho{sub 11}Ge{sub 10}-type phase. The observed In site-preference toward the particular anionic site was rationalized via the atomic size-aspect supported by comprehensive analyses for the site-energies including the Wyckoff 4e and 8j sites. - Highlights: • Block or short-bar shaped single-crystals of Ce{sub 11}Ge{sub 3.73(2)}In{sub 6.27} were synthesized. • The first example of having the In/Ge mixture at the “isolated” anionic site. • The site-preference of In was rationalized by the site- and bond-energies.« less

Anion-Regulated Selective Generation of Cobalt Sites in Carbon: Toward Superior Bifunctional Electrocatalysis

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

Wan, Gang; Yang, Ce; Zhao, Wanpeng

The introduction of active transition metal sites (TMSs) in carbon enables the synthesis of noble-metal-free electrocatalysts for clean energy conversion applications, however, there are often multiple existing forms of TMSs, which are of different natures and catalytic models. Regulating the evolution of distinctive TMSs is highly desirable but remains challenging to date. Anions, as essential elements involved in the synthesis, have been totally neglected previously in the construction of TMSs. Herein, the effects of anions on the creation of different types of TMSs is investigated for the first time. It is found that the active cobalt-nitrogen sites tend to bemore » selectively constructed on the surface of N-doped carbon by using chloride, while metallic cobalt nanoparticles encased in protective graphite layers are the dominant forms of cobalt species with nitrate ions. The obtained catalysts demonstrate cobalt-sites-dependent activity for ORR and HER in acidic media. And the remarkably enhanced catalytic activities approaching that of benchmark Pt/C in acidic medium has been obtained on the catalyst dominated with cobalt-nitrogen sites, confirmed by the advanced spectroscopic . Our finding demonstrates a general paradigm of anion-regulated evolution of distinctive TMSs, providing a new pathway for enhancing performances of various targeted reactions related with TMSs.« less

Virtual screening and biological evaluation of piperazine derivatives as human acetylcholinesterase inhibitors.

PubMed

Varadaraju, Kavitha Raj; Kumar, Jajur Ramanna; Mallesha, Lingappa; Muruli, Archana; Mohana, Kikkeri Narasimha Shetty; Mukunda, Chethan Kumar; Sharanaiah, Umesha

2013-01-01

The piperazine derivatives have been shown to inhibit human acetylcholinesterase. Virtual screening by molecular docking of piperazine derivatives 1-(1,4-benzodioxane-2-carbonyl) piperazine (K), 4-(4-methyl)-benzenesulfonyl-1-(1,4-benzodioxane-2-carbonyl) piperazine (S1), and 4-(4-chloro)-benzenesulfonyl-1-(1,4-benzodioxane-2-carbonyl) piperazine (S3) has been shown to bind at peripheral anionic site and catalytic sites, whereas 4-benzenesulfonyl-1-(1,4-benzodioxane-2-carbonyl) piperazine (S4) and 4-(2,5-dichloro)-benzenesulfonyl-1-(1,4-benzodioxane-2-carbonyl) piperazine (S7) do not bind either to peripheral anionic site or catalytic site with hydrogen bond. All the derivatives have differed in number of H-bonds and hydrophobic interactions. The peripheral anionic site interacting molecules have proven to be potential therapeutics in inhibiting amyloid peptides aggregation in Alzheimer's disease. All the piperazine derivatives follow Lipinski's rule of five. Among all the derivatives 1-(1,4-benzodioxane-2-carbonyl) piperazine (K) was found to have the lowest TPSA value.

Virtual Screening and Biological Evaluation of Piperazine Derivatives as Human Acetylcholinesterase Inhibitors

PubMed Central

Varadaraju, Kavitha Raj; Kumar, Jajur Ramanna; Mallesha, Lingappa; Muruli, Archana; Mohana, Kikkeri Narasimha Shetty; Mukunda, Chethan Kumar; Sharanaiah, Umesha

2013-01-01

The piperazine derivatives have been shown to inhibit human acetylcholinesterase. Virtual screening by molecular docking of piperazine derivatives 1-(1,4-benzodioxane-2-carbonyl) piperazine (K), 4-(4-methyl)-benzenesulfonyl-1-(1,4-benzodioxane-2-carbonyl) piperazine (S1), and 4-(4-chloro)-benzenesulfonyl-1-(1,4-benzodioxane-2-carbonyl) piperazine (S3) has been shown to bind at peripheral anionic site and catalytic sites, whereas 4-benzenesulfonyl-1-(1,4-benzodioxane-2-carbonyl) piperazine (S4) and 4-(2,5-dichloro)-benzenesulfonyl-1-(1,4-benzodioxane-2-carbonyl) piperazine (S7) do not bind either to peripheral anionic site or catalytic site with hydrogen bond. All the derivatives have differed in number of H-bonds and hydrophobic interactions. The peripheral anionic site interacting molecules have proven to be potential therapeutics in inhibiting amyloid peptides aggregation in Alzheimer's disease. All the piperazine derivatives follow Lipinski's rule of five. Among all the derivatives 1-(1,4-benzodioxane-2-carbonyl) piperazine (K) was found to have the lowest TPSA value. PMID:24288651

Properties of the anion-binding site of pharaonis Halorhodopsin studied by ultrafast pump-probe spectroscopy and low-temperature FTIR spectroscopy.

PubMed

Nakashima, Keisuke; Nakamura, Takumi; Takeuchi, Satoshi; Shibata, Mikihiro; Demura, Makoto; Tahara, Tahei; Kandori, Hideki

2009-06-18

Halorhodopsin (HR) is a light-driven chloride pump. Cl(-) is bound in the Schiff base region of the retinal chromophore, and unidirectional Cl(-) transport is probably enforced by the specific hydrogen-bonding interaction with the protonated Schiff base and internal water molecules. It is known that HR from Natronobacterium pharaonis (pHR) also pumps NO(3)(-) with similar efficiency, suggesting that NO(3)(-) binds to the Cl(-)-binding site. In the present study, we investigated the properties of the anion-binding site by means of ultrafast pump-probe spectroscopy and low-temperature FTIR spectroscopy. The obtained data were surprisingly similar between pHR-NO(3)(-) and pHR-Cl(-), even though the shapes and sizes of the two anions are quite different. Femtosecond pump-probe spectroscopy showed very similar excited-state dynamics between pHR-NO(3)(-) and pHR-Cl(-). Low-temperature FTIR spectroscopy of unlabeled and [zeta-(15)N]Lys-labeled pHR revealed almost identical hydrogen-bonding strengths of the protonated retinal Schiff base between pHR-NO(3)(-) and pHR-Cl(-), which is similarly strengthened after retinal isomerization. There were spectral variations for water stretching vibrations between pHR-NO(3)(-) and pHR-Cl(-), suggesting that the water molecules hydrate each anion. Nevertheless, the overall spectral features were similar for the two species. These observations strongly suggest that the anion-binding site has a flexible structure and that the interaction between retinal and the anions is weak, despite the presence of an electrostatic interaction. Such a flexible hydrogen-bonding network in the Schiff base region in HR appears to be in remarkable contrast to that in light-driven proton-pumping proteins.

Infrared spectra and crystal chemistry of scapolites: implications for Martian mineralogy

USGS Publications Warehouse

Swayze, G.A.; Clark, R.N.

1990-01-01

Near-infrared and midinfrared spectra of a wide range of scapolite compositions were studied to determine the cause of the 2.36-??m features that have been correlated with similar features in the near-IR spectrum of Mars. We attribute the 2.36-??m features to vibrations caused by HCO-3 and HSO-4 in the anion sites of scapolite. The 2.36-??m absorption complex consists of four overlapping bands. The relative intensities of all four bands vary according to the HCO-3/HSO-4 ratio and disordered anion site occupancy. The positional disorder of HCO-3 and HSO4 in the low-symmetry anion site of scapolite gives the 2.36-??m band complex a unique spectral signature not likely to be duplicated in any other mineral. -from Authors

Superfund Hazard Ranking System Training Course

EPA Pesticide Factsheets

The Hazard Ranking System (HRS) training course is a four and ½ day, intermediate-level course designed for personnel who are required to compile, draft, and review preliminary assessments (PAs), site inspections (SIs), and HRS documentation records/packag

Flavan-3-ols Are an Effective Chemical Defense against Rust Infection1[OPEN

PubMed Central

Unsicker, Sybille B.; Fellenberg, Christin; Schmidt, Axel

2017-01-01

Phenolic secondary metabolites are often thought to protect plants against attack by microbes, but their role in defense against pathogen infection in woody plants has not been investigated comprehensively. We studied the biosynthesis, occurrence, and antifungal activity of flavan-3-ols in black poplar (Populus nigra), which include both monomers, such as catechin, and oligomers, known as proanthocyanidins (PAs). We identified and biochemically characterized three leucoanthocyanidin reductases and two anthocyanidin reductases from P. nigra involved in catalyzing the last steps of flavan-3-ol biosynthesis, leading to the formation of catechin [2,3-trans-(+)-flavan-3-ol] and epicatechin [2,3-cis-(−)-flavan-3-ol], respectively. Poplar trees that were inoculated with the biotrophic rust fungus (Melampsora larici-populina) accumulated higher amounts of catechin and PAs than uninfected trees. The de novo-synthesized catechin and PAs in the rust-infected poplar leaves accumulated significantly at the site of fungal infection in the lower epidermis. In planta concentrations of these compounds strongly inhibited rust spore germination and reduced hyphal growth. Poplar genotypes with constitutively higher levels of catechin and PAs as well as hybrid aspen (Populus tremula × Populus alba) overexpressing the MYB134 transcription factor were more resistant to rust infection. Silencing PnMYB134, on the other hand, decreased flavan-3-ol biosynthesis and increased susceptibility to rust infection. Taken together, our data indicate that catechin and PAs are effective antifungal defenses in poplar against foliar rust infection. PMID:29070515

Flavan-3-ols Are an Effective Chemical Defense against Rust Infection.

PubMed

Ullah, Chhana; Unsicker, Sybille B; Fellenberg, Christin; Constabel, C Peter; Schmidt, Axel; Gershenzon, Jonathan; Hammerbacher, Almuth

2017-12-01

Phenolic secondary metabolites are often thought to protect plants against attack by microbes, but their role in defense against pathogen infection in woody plants has not been investigated comprehensively. We studied the biosynthesis, occurrence, and antifungal activity of flavan-3-ols in black poplar ( Populus nigra ), which include both monomers, such as catechin, and oligomers, known as proanthocyanidins (PAs). We identified and biochemically characterized three leucoanthocyanidin reductases and two anthocyanidin reductases from P. nigra involved in catalyzing the last steps of flavan-3-ol biosynthesis, leading to the formation of catechin [2,3-trans-(+)-flavan-3-ol] and epicatechin [2,3-cis-(-)-flavan-3-ol], respectively. Poplar trees that were inoculated with the biotrophic rust fungus ( Melampsora larici-populina ) accumulated higher amounts of catechin and PAs than uninfected trees. The de novo-synthesized catechin and PAs in the rust-infected poplar leaves accumulated significantly at the site of fungal infection in the lower epidermis. In planta concentrations of these compounds strongly inhibited rust spore germination and reduced hyphal growth. Poplar genotypes with constitutively higher levels of catechin and PAs as well as hybrid aspen ( Populus tremula × Populus alba ) overexpressing the MYB134 transcription factor were more resistant to rust infection. Silencing PnMYB134 , on the other hand, decreased flavan-3-ol biosynthesis and increased susceptibility to rust infection. Taken together, our data indicate that catechin and PAs are effective antifungal defenses in poplar against foliar rust infection. © 2017 American Society of Plant Biologists. All Rights Reserved.

Capturing the Alternative Cleavage and Polyadenylation Sites of 14 NAC Genes in Populus Using a Combination of 3'-RACE and High-Throughput Sequencing.

PubMed

Wang, Haoran; Wang, Mingxiu; Cheng, Qiang

2018-03-08

Detection of complex splice sites (SSs) and polyadenylation sites (PASs) of eukaryotic genes is essential for the elucidation of gene regulatory mechanisms. Transcriptome-wide studies using high-throughput sequencing (HTS) have revealed prevalent alternative splicing (AS) and alternative polyadenylation (APA) in plants. However, small-scale and high-depth HTS aimed at detecting genes or gene families are very few and limited. We explored a convenient and flexible method for profiling SSs and PASs, which combines rapid amplification of 3'-cDNA ends (3'-RACE) and HTS. Fourteen NAC (NAM, ATAF1/2, CUC2) transcription factor genes of Populus trichocarpa were analyzed by 3'-RACE-seq. Based on experimental reproducibility, boundary sequence analysis and reverse transcription PCR (RT-PCR) verification, only canonical SSs were considered to be authentic. Based on stringent criteria, candidate PASs without any internal priming features were chosen as authentic PASs and assumed to be PAS-rich markers. Thirty-four novel canonical SSs, six intronic/internal exons and thirty 3'-UTR PAS-rich markers were revealed by 3'-RACE-seq. Using 3'-RACE and real-time PCR, we confirmed that three APA transcripts ending in/around PAS-rich markers were differentially regulated in response to plant hormones. Our results indicate that 3'-RACE-seq is a robust and cost-effective method to discover SSs and label active regions subjected to APA for genes or gene families. The method is suitable for small-scale AS and APA research in the initial stage.

Aza-Bambusurils En Route to Anion Transporters.

PubMed

Singh, Mandeep; Solel, Ephrath; Keinan, Ehud; Reany, Ofer

2016-06-20

Previous calculations of anion binding with various bambusuril analogs predicted that the replacement of oxygen by nitrogen atoms to produce semiaza-bambus[6]urils would award these new cavitands with multiple anion binding properties. This study validates the hypothesis by efficient synthesis, crystallography, thermogravimetric analysis and calorimetry. These unique host molecules are easily accessible from the corresponding semithio-bambusurils in a one-pot reaction, which converts a single anion receptor into a potential anion channel. Solid-state structures exhibit simultaneous accommodation of three anions, linearly positioned within the cavity along the main symmetry axis. The ability to hold anions at a short distance of about 4 Å is reminiscent of natural chloride channels in E. coli, which exhibit similar distances between their adjacent anion binding sites. The calculated transition-state energy for double-anion movement through the channel suggests that although these host-guest complexes are thermodynamically stable they enjoy high kinetic flexibility to render them efficient anion channels. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Phytolacca americana from contaminated and noncontaminated soils of South Korea: Effects of elevated temperature, CO2 and simulated acid rain on plant growth response

USGS Publications Warehouse

Kim, Y.-O.; Rodriguez, R.J.; Lee, E.J.; Redman, R.S.

2008-01-01

Chemical analyses performed on the invasive weed Phytolacca americana (pokeweed) growing in industrially contaminated (Ulsan) and noncontaminated (Suwon) sites in South Korea indicated that the levels of phenolic compounds and various elements that include some heavy metals (Al, As, B, Cd, Co, Cu, Fe, Mn, Ni, Pb, and Zn) were statistically higher in Ulsan soils compared to Suwon soils with Al being the highest (>1,116 mg/l compared to 432 mg/l). Analysis of metals and nutrients (K, Na, Ca, Mg, Cl, NH4, N, P, S) in plant tissues indicated that accumulation occurred dominantly in plant leaves with Al levels being 33.8 times higher in Ulsan plants (PaU) compared to Suwon plants (PaS). The ability of PaU and PaS to tolerate stress was evaluated under controlled conditions by varying atmospheric CO2 and temperature and soil pH. When grown in pH 6.4 soils, the highest growth rate of PaU and PaS plants occurred at elevated (30??C) and non-elevated (25??C) temperatures, respectively. Both PaU and PaS plants showed the highest and lowest growth rates when exposed to atmospheric CO2 levels of 360 and 650 ppm, respectively. The impact of soil pH (2-6.4) on seed germination rates, plant growth, chlorophyll content, and the accumulation of phenolics were measured to assess the effects of industrial pollution and global-warming-related stresses on plants. The highest seed germination rate and chlorophyll content occurred at pH 2.0 for both PaU and PaS plants. Increased pH from 2-5 correlated to increased phenolic compounds and decreased chlorophyll content. However, at pH 6.4, a marked decrease in phenolic compounds, was observed and chlorophyll content increased. These results suggest that although plants from Ulsan and Suwon sites are the same species, they differ in the ability to deal with various stresses. ?? 2008 Springer Science+Business Media, LLC.

Superfund Hazard Ranking System Training Course: Table of Contents

EPA Pesticide Factsheets

The Hazard Ranking System (HRS) training course is a four and ½ day, intermediate-level course designed for personnel who are required to compile, draft, and review preliminary assessments (PAs), site inspections (SIs), and HRS documentation records/packag

Identification of a Second Site of Pyrrolizidine Alkaloid Biosynthesis in Comfrey to Boost Plant Defense in Floral Stage1,2[OPEN

PubMed Central

Stegemann, Thomas; Sievert, Christian

2017-01-01

Pyrrolizidine alkaloids (PAs) are toxic secondary metabolites that are found in several distantly related families of the angiosperms. The first specific step in PA biosynthesis is catalyzed by homospermidine synthase (HSS), which has been recruited several times independently by duplication of the gene encoding deoxyhypusine synthase, an enzyme involved in the posttranslational activation of the eukaryotic initiation factor 5A. HSS shows highly diverse spatiotemporal gene expression in various PA-producing species. In comfrey (Symphytum officinale; Boraginaceae), PAs are reported to be synthesized in the roots, with HSS being localized in cells of the root endodermis. Here, we show that comfrey plants activate a second site of HSS expression when inflorescences start to develop. HSS has been localized in the bundle sheath cells of specific leaves. Tracer feeding experiments have confirmed that these young leaves express not only HSS but the whole PA biosynthetic route. This second site of PA biosynthesis results in drastically increased PA levels within the inflorescences. The boost of PA biosynthesis is proposed to guarantee optimal protection especially of the reproductive structures. PMID:28275146

Suppression of H-/O2- exchange by incorporated nitride anions in the perovskite lattice

NASA Astrophysics Data System (ADS)

Takeiri, Fumitaka; Yajima, Takeshi; Yamamoto, Takafumi; Kobayashi, Yoji; Matsui, Toshiaki; Hester, James; Kageyama, Hiroshi

2017-12-01

We investigate the low temperature anion exchange behavior of hydride and oxide in perovskite oxynitrides. CaH2 reduction of (Sr1-xLax)Ti(O3-xNx) (0

The minimal structure containing the band 3 anion transport site. A 35Cl NMR study.

PubMed

Falke, J J; Kanes, K J; Chan, S I

1985-10-25

35Cl NMR, which enables observation of chloride binding to the anion transport site on band 3, is used in the present study to determine the minimal structure containing the intact transport site. Removal of cytoskeletal and other nonintegral membrane proteins, or removal of the 40-kDa cytoskeletal domain of band 3, each leave the transport site intact. Similarly, cleavage of the 52-kDa transport domain into 17- and 35-kDa fragments by chymotrypsin leaves the transport site intact. Extensive proteolysis by papain reduces the integral red cell membrane proteins to their transmembrane segments. Papain treatment removes approximately 60% of the extramembrane portion of the transport domain and produces small fragments primarily in the range 3-7 kDa, with 5 kDa being most predominant. Papain treatment damages, but does not destroy, chloride binding to the transport site; thus, the minimal structure containing the transport site is composed solely of transmembrane segments. In short, the results are completely consistent with a picture in which the transport site is buried in the membrane where it is protected from proteolysis; the transmembrane segments that surround the transport site are held together by strong attractive forces within the bilayer; and the transport site is accessed by solution chloride via an anion channel leading from the transport site to the solution.

Cytochemical analysis of alkaline phosphatase and esterase activities and of lectin-binding and anionic sites in rat and mouse Peyer's patch M cells.

PubMed

Owen, R L; Bhalla, D K

1983-10-01

M cells in Peyer's patch follicle epithelium endocytose and transport luminal materials to intraepithelial lymphocytes. We examined (1) enzymatic characteristics of the epithelium covering mouse and rat Peyer's patches by using cytochemical techniques, (2) distribution of lectin-binding sites by peroxidase-labeled lectins, and (3) anionic site distribution by using cationized ferritin to develop a profile of M cell surface properties. Alkaline phosphatase activity resulted in deposits of dense reaction product over follicle surfaces but was markedly reduced over M cells, unlike esterase which formed equivalent or greater product over M cells. Concanavalin A, ricinus communis agglutinin, wheat germ agglutinin and peanut agglutinin reacted equally with M cells and with surrounding enterocytes over follicle surfaces. Cationized ferritin distributed in a random fashion along microvillus membranes of both M cells and enterocytes, indicating equivalent anionic site distribution. Staining for alkaline phosphatase activity provides a new approach for distinguishing M cells from enterocytes at the light microscopic level. Identical binding of lectins indicates that M cells and enterocytes share common glycoconjugates even though molecular groupings may differ. Lectin binding and anionic charge similarities of M cells and enterocytes may facilitate antigen sampling by M cells of particles and compounds that adhere to intestinal surfaces in non-Peyer's patch areas.

De-tabooing dying control - a grounded theory study

PubMed Central

2013-01-01

Background Dying is inescapable yet remains a neglected issue in modern health care. The research question in this study was “what is going on in the field of dying today?” What emerged was to eventually present a grounded theory of control of dying focusing specifically on how people react in relation to issues about euthanasia and physician-assisted suicide (PAS). Methods Classic grounded theory was used to analyze interviews with 55 laypersons and health care professionals in North America and Europe, surveys on attitudes to PAS among physicians and the Swedish general public, and scientific literature, North American discussion forum websites, and news sites. Results Open awareness of the nature and timing of a patient’s death became common in health care during the 1960s in the Western world. Open dying awareness contexts can be seen as the start of a weakening of a taboo towards controlled dying called de-tabooing. The growth of the hospice movement and palliative care, but also the legalization of euthanasia and PAS in the Benelux countries, and PAS in Montana, Oregon and Washington further represents de-tabooing dying control. An attitude positioning between the taboo of dying control and a growing taboo against questioning patient autonomy and self-determination called de-paternalizing is another aspect of de-tabooing. When confronted with a taboo, people first react emotionally based on “gut feelings” - emotional positioning. This is followed by reasoning and label wrestling using euphemisms and dysphemisms - reflective positioning. Rarely is de-tabooing unconditional but enabled by stipulated positioning as in soft laws (palliative care guidelines) and hard laws (euthanasia/PAS legislation). From a global perspective three shapes of dying control emerge. First, suboptimal palliative care in closed awareness contexts seen in Asian, Islamic and Latin cultures, called closed dying. Second, palliative care and sedation therapy, but not euthanasia or PAS, is seen in Europe and North America, called open dying with reversible medical control. Third, palliative care, sedation therapy, and PAS or euthanasia occurs together in the Benelux countries, Oregon, Washington and Montana, called open dying with irreversible medical control. Conclusions De-tabooing dying control is an assumed secular process starting with open awareness contexts of dying half a century ago, and continuing with the growth of the palliative care movement and later euthanasia and PAS legislation. PMID:23496849

Solubilization Behavior of Polyene Antibiotics in Nanomicellar System: Insights from Molecular Dynamics Simulation of the Amphotericin B and Nystatin Interactions with Polysorbate 80.

PubMed

Mobasheri, Meysam; Attar, Hossein; Rezayat Sorkhabadi, Seyed Mehdi; Khamesipour, Ali; Jaafari, Mahmoud Reza

2015-12-24

Amphotericin B (AmB) and Nystatin (Nys) are the drugs of choice for treatment of systemic and superficial mycotic infections, respectively, with their full clinical potential unrealized due to the lack of high therapeutic index formulations for their solubilized delivery. In the present study, using a coarse-grained (CG) molecular dynamics (MD) simulation approach, we investigated the interaction of AmB and Nys with Polysorbate 80 (P80) to gain insight into the behavior of these polyene antibiotics (PAs) in nanomicellar solution and derive potential implications for their formulation development. While the encapsulation process was predominantly governed by hydrophobic forces, the dynamics, hydration, localization, orientation, and solvation of PAs in the micelle were largely controlled by hydrophilic interactions. Simulation results rationalized the experimentally observed capability of P80 in solubilizing PAs by indicating (i) the dominant kinetics of drugs encapsulation over self-association; (ii) significantly lower hydration of the drugs at encapsulated state compared with aggregated state; (iii) monomeric solubilization of the drugs; (iv) contribution of drug-micelle interactions to the solubilization; (v) suppressed diffusivity of the encapsulated drugs; (vi) high loading capacity of the micelle; and (vii) the structural robustness of the micelle against drug loading. Supported from the experimental data, our simulations determined the preferred location of PAs to be the core-shell interface at the relatively shallow depth of 75% of micelle radius. Deeper penetration of PAs was impeded by the synergistic effects of (i) limited diffusion of water; and (ii) perpendicular orientation of these drug molecules with respect to the micelle radius. PAs were solvated almost exclusively in the aqueous poly-oxyethylene (POE) medium due to the distance-related lack of interaction with the core, explaining the documented insensitivity of Nys solubilization to drug-core compatibility in detergent micelles. Based on the obtained results, the dearth of water at interior sites of micelle and the large lateral occupation space of PAs lead to shallow insertion, broad radial distribution, and lack of core interactions of the amphiphilic drugs. Hence, controlled promotion of micelle permeability and optimization of chain crowding in palisade layer may help to achieve more efficient solubilization of the PAs.

Molecular anions.

PubMed

Simons, Jack

2008-07-24

The experimental and theoretical study of molecular anions has undergone explosive growth over the past 40 years. Advances in techniques used to generate anions in appreciable numbers as well as new ion-storage, ion-optics, and laser spectroscopic tools have been key on the experimental front. Theoretical developments on the electronic structure and molecular dynamics fronts now allow one to achieve higher accuracy and to study electronically metastable states, thus bringing theory in close collaboration with experiment in this field. In this article, many of the experimental and theoretical challenges specific to studying molecular anions are discussed. Results from many research groups on several classes of molecular anions are overviewed, and both literature citations and active (in online html and pdf versions) links to numerous contributing scientists' Web sites are provided. Specific focus is made on the following families of anions: dipole-bound, zwitterion-bound, double-Rydberg, multiply charged, metastable, cluster-based, and biological anions. In discussing each kind of anion, emphasis is placed on the structural, energetic, spectroscopic, and chemical-reactivity characteristics that make these anions novel, interesting, and important.

Raman and IR studies and DFT calculations of the vibrational spectra of 2,4-Dithiouracil and its cation and anion

NASA Astrophysics Data System (ADS)

Singh, R.; Yadav, R. A.

2014-09-01

Raman and FTIR spectra of solid 2,4-Dithiouracil (DTU) at room temperature have been recorded. DFT calculations were carried out to compute the optimized molecular geometries, GAPT charges and fundamental vibrational frequencies along with their corresponding IR intensities, Raman activities and depolarization ratios of the Raman bands for the neutral DTU molecule and its cation (DTU+) and anion (DTU-) using the Gaussian-03 software. Addition of one electron leads to increase in the atomic charges on the sites N1 and N3 and decrease in the atomic charges on the sites S8 and S10. Due to ionization of DTU molecule, the charge at the site C6 decreases in the cationic and anionic radicals of DTU as compared to its neutral species. As a result of anionic radicalization, the C5sbnd C6 bond length increases and loses its double bond character while the C4sbnd C5 bond length decreases. In the case of the DTU+ ion the IR and Raman band corresponding to the out-of-phase coupled Nsbnd H stretching mode is strongest amongst the three species. The anionic DTU radical is found to be the most stable. The two NH out-of-plane bending modes are found to originate due to out-of-phase and in-phase coupling of the two NH bonds in the anion and cation contrary to the case of the neutral DTU molecule in which the out-of-plane bending motions of the two NH bonds are not coupled.

Raman and IR studies and DFT calculations of the vibrational spectra of 2,4-Dithiouracil and its cation and anion.

PubMed

Singh, R; Yadav, R A

2014-09-15

Raman and FTIR spectra of solid 2,4-Dithiouracil (DTU) at room temperature have been recorded. DFT calculations were carried out to compute the optimized molecular geometries, GAPT charges and fundamental vibrational frequencies along with their corresponding IR intensities, Raman activities and depolarization ratios of the Raman bands for the neutral DTU molecule and its cation (DTU+) and anion (DTU-) using the Gaussian-03 software. Addition of one electron leads to increase in the atomic charges on the sites N1 and N3 and decrease in the atomic charges on the sites S8 and S10. Due to ionization of DTU molecule, the charge at the site C6 decreases in the cationic and anionic radicals of DTU as compared to its neutral species. As a result of anionic radicalization, the C5C6 bond length increases and loses its double bond character while the C4C5 bond length decreases. In the case of the DTU+ ion the IR and Raman band corresponding to the out-of-phase coupled NH stretching mode is strongest amongst the three species. The anionic DTU radical is found to be the most stable. The two NH out-of-plane bending modes are found to originate due to out-of-phase and in-phase coupling of the two NH bonds in the anion and cation contrary to the case of the neutral DTU molecule in which the out-of-plane bending motions of the two NH bonds are not coupled. Copyright © 2014 Elsevier B.V. All rights reserved.

Design and synthesis of some new carboxamide and propanamide derivatives bearing phenylpyridazine as a core ring and the investigation of their inhibitory potential on in-vitro acetylcholinesterase and butyrylcholinesterase.

PubMed

Kilic, Burcu; Gulcan, Hayrettin O; Aksakal, Fatma; Ercetin, Tugba; Oruklu, Nihan; Umit Bagriacik, E; Dogruer, Deniz S

2018-05-08

A series of new carboxamide and propanamide derivatives bearing phenylpyridazine as a core ring were designed, synthesized and evaluated for their ability to inhibit both cholinesterase enzymes. In addition, a series of carboxamide and propanamide derivatives bearing biphenyl instead of phenylpyridazine were also synthesized to examine the inhibitory effect of pyridazine moiety on both cholinesterase enzymes. The inhibitory activity results revealed that compounds 5b, 5f, 5h, 5j, 5l pyridazine-3-carboxamide derivative, exhibited selective acetylcholinesterase (AChE) inhibition with IC 50 values ranging from 0.11 to 2.69 µM. Among them, compound 5h was the most active one (IC 50  = 0.11 µM) without cytotoxic effect at its effective concentration against AChE. Additionally, pyridazine-3-carboxamide derivative 5d (IC 50 for AChE = 0.16 µM and IC 50 for BChE = 9.80 µM) and biphenyl-4-carboxamide derivative 6d (IC 50 for AChE = 0.59 µM and IC 50 for BChE = 1.48 µM) displayed dual cholinesterase inhibitory activity. Besides, active compounds were also tested for their ability to inhibit Aβ aggregation. Theoretical physicochemical properties of the compounds were calculated by using Molinspiration Program as well. The Lineweaver-Burk plot and docking study showed that compound 5 h targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. Copyright © 2018 Elsevier Inc. All rights reserved.

Synthesis, biological assessment and molecular modeling of new multipotent MAO and cholinesterase inhibitors as potential drugs for the treatment of Alzheimer's disease.

PubMed

Samadi, Abdelouahid; Chioua, Mourad; Bolea, Irene; de Los Ríos, Cristóbal; Iriepa, Isabel; Moraleda, Ignacio; Bastida, Agatha; Esteban, Gerard; Unzeta, Mercedes; Gálvez, Enrique; Marco-Contelles, José

2011-09-01

The synthesis, biological evaluation and molecular modeling of new multipotent inhibitors of type I and type II, able to simultaneously inhibit monoamine oxidases (MAO) as well as acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), is described. Compounds of type I were prepared by sequential reaction of 2,6-dichloro-4-phenylpyridine-3,5-dicarbonitrile (14) [or 2,6-dichloropyridine-3,5-dicarbonitrile (15)] with prop-2-yn-1-amine (or N-methylprop-2-yn-1-amine) and 2-(1-benzyl-piperidin-4-yl)alkylamines 22-25. Compounds of type II were prepared by Friedländer type reaction of 6-amino-5-formyl-2-(methyl(prop-2-yn-1-yl)amino)nicotinonitriles 32 and 33 with 4-(1-benzylpiperidin-4-yl)butan-2-one (31). The biological evaluation of molecules 1-11 showed that most of these compounds are potent, in the nanomolar range, and selective AChEI, with moderate and equipotent selectivity for MAO-A and MAO-B inhibition. Kinetic studies of compound 8 proved that this is a EeAChE mixed type inhibitor (IC(50) = 16 ± 2; Ki = 12 ± 3 nM). Molecular modeling investigation on compound 8 confirmed its dual AChE inhibitory profile, binding simultaneously at the catalytic active site (CAS) and at the peripheric anionic site (PAS). In overall, compound 11, as a potent and selective dual AChEI, showing a moderate and selective MAO-A inhibitory profile, can be considered as an attractive multipotent drug for further development on two key pharmacological targets playing key roles in the therapy of Alzheimer's disease. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Mixed mode HILIC/anion exchange separations on latex coated silica monoliths.

PubMed

Ibrahim, Mohammed E A; Lucy, Charles A

2012-10-15

Bare silica monoliths do not possess anion exchange sites hence they show low retention for anions. Moreover, bare silica monoliths show low retention in hydrophilic interaction liquid chromatography (HILIC). Coating the silica surface with cationic nanoparticles e.g. AS9-SC (latex A), AS12A (latex B) and DNApac (latex C) increases the thickness of the water layer on the Onyx silica monolith 8-10 times enabling HILIC retention when a high % acetonitrile (ACN) mobile phase is used. The formed water layer by itself is not sufficient to perform good separation of the studied anions (acetate, formate, nitrate, bromate, thiocyanate and iodide). On the other hand, the latex nanoparticles introduce positively charged sites, making anion exchange chromatography possible, with the anion exchange capacity varying with the latex adsorbed (44.1 ± 0.2, 4.4 ± 0.1 and 14.0 ± 0.7 μeq/column for latex A, B and C, respectively). Latex A nanoparticles which provided the highest ion exchange capacity separated all tested anions with reasonable resolution. Fast separation (2.5 min) of acetate, formate, nitrate, bromate, thiocyanate and iodide was performed using the latex A coated silica monolith. The obtained efficiencies are 13,000-50,000 plates/m at 3 mL/min with a minimum resolution of 0.85. Retention is mixed mode under HILIC conditions with HILIC dominating for the kosmotropic anions and ion exchange dominating for the chaotropic anions. The two different brands of silica monoliths (Merck Chromolith and Phenomenex Onyx) coated with the same latex A nanoparticles displayed similar water layer volumes, ion exchange capacity and selectivity. Copyright © 2012 Elsevier B.V. All rights reserved.

Computational insights into crystal plane dependence of thermal activity of anion (C and N)-substituted titania.

PubMed

V, Sai Phani Kumar; Arya, Rahul; Deshpande, Parag A

2017-11-29

Geometry optimizations of anion (C and N) doped anatase TiO 2 were carried out by using DFT+U calculations. Various anion vacancy sites were examined to study the synergistic effects of anion doping accompanied with anion vacancy formation on lattice oxygen activation. Two non-identical crystal planes (0 0 1) and (1 0 0) were chosen for C and N substitutions. Energetically favoured N-vacancy pairs were identified on TiO 2 surfaces. Substitution of N along with anion vacancies at various sites was energetically more favoured than that of C-doping in bulk TiO 2 while the energies were comparable for surface substitutions. Bond length distributions due to the formation of differential bonds were determined. Net oxygen activation and accompanying reversible oxygen exchange capacities were compared for TiO 2-2x C x and TiO 2-3x N 2x . Substitution of C in the surface exposed (1 0 0) plane of TiO 2 resulted in 47.6% and 23.8% of bond elongation and compression, respectively, resulting in 23.8% of net oxygen activation which was higher when compared to N substitution in the (1 0 0) plane of TiO 2 resulting in a net oxygen activation of 17%.

7 CFR 1220.619 - Time and Place for Requesting a Referendum.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Section 1220.619 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE... an online search of FSA's web site at www.fsa.usda.gov/pas/default.asp. (c) Each eligible person...

7 CFR 1220.619 - Time and Place for Requesting a Referendum.

Code of Federal Regulations, 2013 CFR

2013-01-01

... Section 1220.619 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE... an online search of FSA's web site at www.fsa.usda.gov/pas/default.asp. (c) Each eligible person...

7 CFR 1220.619 - Time and Place for Requesting a Referendum.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Section 1220.619 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE... an online search of FSA's web site at www.fsa.usda.gov/pas/default.asp. (c) Each eligible person...

7 CFR 1220.619 - Time and Place for Requesting a Referendum.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Section 1220.619 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE... an online search of FSA's web site at www.fsa.usda.gov/pas/default.asp. (c) Each eligible person...

7 CFR 1220.619 - Time and Place for Requesting a Referendum.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Section 1220.619 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE... an online search of FSA's web site at www.fsa.usda.gov/pas/default.asp. (c) Each eligible person...

Tetraammine(carbonato-κ(2) O,O')cobalt(III) perchlorate.

PubMed

Mohan, Singaravelu Chandra; Jenniefer, Samson Jegan; Muthiah, Packianathan Thomas; Jothivenkatachalam, Kandasamy

2013-01-01

In the title complex, [Co(CO3)(NH3)4]ClO4, both the cation and anion lie on a mirror plane. The Co(III) ion is coordinated by two NH3 ligands and a chelating carbonato ligand in the equatorial sites and by two NH3 groups in the axial sites, forming a distorted octa-hedral geometry. In the crystal, N-H⋯O hydrogen bonds connect the anions and cations, forming a three-dimensional network.

A lecithin phosphatidylserine and phosphatidic acid complex (PAS) reduces symptoms of the premenstrual syndrome (PMS): Results of a randomized, placebo-controlled, double-blind clinical trial.

PubMed

Schmidt, Katja; Weber, Nicole; Steiner, Meir; Meyer, Nadin; Dubberke, Anne; Rutenberg, David; Hellhammer, Juliane

2018-04-01

Many women experience emotional and physical symptoms around the time of ovulation and more so before menstruation interfering with their daily normal life also known as premenstrual syndrome (PMS). Recent observational data suggest that supplementation with Lipogen's phosphatidylserine (PS) and phosphatidic acid (PA) complex (PAS) alleviates these PMS symptoms. The aim of this study was to confirm these observations on the effects of PAS on PMS symptom severity within a controlled clinical trial setting. Forty women aged 18-45 years with a diagnosis of PMS were assigned to either take PAS (containing 400 mg PS & 400 mg PA per day) or a matching placebo. The study comprised 5 on-site visits including 1 baseline menstrual cycle followed by 3 treatment cycles. Treatment intake was controlled for by using an electronic device, the Medication Event Monitoring System (MEMS ® ). Primary outcome of the study was the PMS symptoms severity as assessed by using the Daily Record of Severity of Problems (DRSP). Further, SIPS questionnaire (a German version of the Premenstrual Symptoms Screening Tool (PSST)), salivary hormone levels (cortisol awakening response (CAR) and evening cortisol levels) as well as serum levels (cortisol, estradiol, progesterone and corticosteroid binding globulin (CBG)) were assessed. PMS symptoms as assessed by the DRSP Total score showed a significantly better improvement (p = 0.001) over a 3 cycles PAS intake as compared to placebo. In addition, PAS treated women reported a greater improvement in physical (p = 0.002) and depressive symptoms (p = 0.068). They also reported a lower reduction of productivity (p = 0.052) and a stronger decrease in interference with relationships with others (p = 0.099) compared to the placebo group. No other DRSP scale or item showed significant results. Likewise, the reduction in the number of subjects fulfilling PMS or premenstrual dysphoric disorder (PMDD) criteria as classified by the SIPS did not differ between the PAS and the placebo group. For the biomarkers, the salivary cortisol percentage increase of the CAR was significantly less pronounced in the follicular phase of cycle 4 than in the follicular phase of cycle 1 for subjects taking PAS when compared to subjects taking placebo (p = 0.018). Furthermore, the change of serum cortisol levels between visit 1 and visit 5 differed significantly between groups (p = 0.043). While serum cortisol levels of PAS treated females slightly decreased between visit 1 and visit 5, cortisol levels of females treated with placebo increased. For all other biomarkers, no treatment effects were observed over the 4 cycles study period. Overall, this study confirms that a daily intake of PAS, containing 400 mg PS and 400 mg PA, can be considered as safe. Results substantiate the efficacy of PAS in reducing symptoms of PMS. In view of the recent inclusion of severe PMS symptoms (PMDD) in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), the positive results of this clinical study merits consideration of developing the PAS complex as a botanical drug for treatment of PMDD. The study is registered at Deutsches Register Klinischer Studien with the registration number DRKS00009005. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Bright blue-shifted fluorescent proteins with Cys in the GAF domain engineered from bacterial phytochromes: fluorescence mechanisms and excited-state dynamics.

PubMed

Hontani, Yusaku; Shcherbakova, Daria M; Baloban, Mikhail; Zhu, Jingyi; Verkhusha, Vladislav V; Kennis, John T M

2016-11-18

Near-infrared fluorescent proteins (NIR FPs) engineered from bacterial phytochromes (BphPs) are of great interest for in vivo imaging. They utilize biliverdin (BV) as a chromophore, which is a heme degradation product, and therefore they are straightforward to use in mammalian tissues. Here, we report on fluorescence properties of NIR FPs with key alterations in their BV binding sites. BphP1-FP, iRFP670 and iRFP682 have Cys residues in both PAS and GAF domains, rather than in the PAS domain alone as in wild-type BphPs. We found that NIR FP variants with Cys in the GAF or with Cys in both PAS and GAF show blue-shifted emission with long fluorescence lifetimes. In contrast, mutants with Cys in the PAS only or no Cys residues at all exhibit red-shifted emission with shorter lifetimes. Combining these results with previous biochemical and BphP1-FP structural data, we conclude that BV adducts bound to Cys in the GAF are the origin of bright blue-shifted fluorescence. We propose that the long fluorescence lifetime follows from (i) a sterically more constrained thioether linkage, leaving less mobility for ring A than in canonical BphPs, and (ii) that π-electron conjugation does not extend on ring A, making excited-state deactivation less sensitive to ring A mobility.

Characterization of two passive air samplers for per- and polyfluoroalkyl substances.

PubMed

Ahrens, Lutz; Harner, Tom; Shoeib, Mahiba; Koblizkova, Martina; Reiner, Eric J

2013-12-17

Two passive air sampler (PAS) media were characterized under field conditions for the measurement of per- and polyfluoroalkyl substances (PFASs) in the atmosphere. The PASs, consisting of polyurethane foam (PUF) and sorbent-impregnated PUF (SIP) disks, were deployed for over one year in parallel with high volume active air samplers (HV-AAS) and low volume active air samplers (LV-AAS). Samples were analyzed for perfluoroalkyl carboxylic acids (PFCAs), perfluoroalkane sulfonic acids (PFSAs), fluorotelomer alcohols (FTOHs), fluorotelomer methacrylates (FTMACs), fluorotelomer acrylates (FTACs), perfluorooctane sulfonamides (FOSAs), and perfluorooctane sulfonamidoethanols (FOSEs). Sampling rates and the passive sampler medium (PSM)-air partition coefficient (KPSM-A) were calculated for individual PFASs. Sampling rates were similar for PFASs present in the gas phase and particle phase, and the linear sampling rate of 4 m(-3) d(-1) is recommended for calculating effective air sample volumes in the SIP-PAS and PUF-PAS for PFASs except for the FOSAs and FOSEs in the PUF-PAS. SIP disks showed very good performance for all tested PFASs while PUF disks were suitable only for the PFSAs and their precursors. Experiments evaluating the suitability of different isotopically labeled fluorinated depuration compounds (DCs) revealed that (13)C8-perfluorooctanoic acid (PFOA) was suitable for the calculation of site-specific sampling rates. Ambient temperature was the dominant factor influencing the seasonal trend of PFASs.

Viscosities of implantable biomaterials in vocal fold augmentation surgery.

PubMed

Chan, R W; Titze, I R

1998-05-01

Vocal fold vibration depends critically on the viscoelasticity of vocal fold tissues. For instance, phonation threshold pressure, a measure of the "ease" of phonation, has been shown to be directly related to the viscosity of the vibrating mucosa. Various implantable biomaterials have been used in vocal fold augmentation surgery, with implantation sites sometimes close to or inside the mucosa. Yet their viscosities or other mechanical properties are seldom known. This study attempts to provide data on viscosities of commonly used phonosurgical biomaterials. Using a parallel-plate rotational rheometer, oscillatory shear experiments were performed on implantable polytetrafluoroethylene (Teflon or Polytef; Mentor Inc., Hingham, MA), collagen (Zyderm; Collagen Corp., Palo Alto, CA), glutaraldehyde crosslinked (GAX) collagen (Phonagel or Zyplast; Collagen Corp.), absorbable gelatin (Gelfoam; Upjohn Co., Kalamazoo, MI), and human abdominal subcutaneous fat. Samples of human vocal fold mucosal tissues were also tested. Under sinusoidal oscillatory shear at 10 Hz and at 37 degrees C, the dynamic viscosity was 116 Pascal-seconds (Pa-s) for polytetrafluoroethylene, 21 Pa-s for gelatin, 8-13 Pa-s for the two types of collagen, 3 Pa-s for fat, and 1 to 3 Pa-s for vocal fold mucosa. Results extrapolated to 100 Hz also show similar differences among the biomaterials, but all values are an order of magnitude lower because of the typical inverse frequency relation (shear thinning effect) for polymeric and biologic materials. The data suggest that the use of fat for vocal fold augmentation may be more conducive to the "ease" of phonation because of its relatively low viscosity, which is closest to physiologic levels. This implication is probably the most relevant in predicting initial outcome of the postoperative voice before there is any significant assimilation (e.g., resorption and fibrosis) of the implanted biomaterial.

Personal assistance services in the workplace: A literature review.

PubMed

Dowler, Denetta L; Solovieva, Tatiana I; Walls, Richard T

2011-10-01

Personal assistance services (PAS) can be valuable adjuncts to the complement of accommodations that support workers with disabilities. This literature review explored the professional literature on the use of PAS in the workplace. Bibliographic sources were used to locate relevant research studies on the use of PAS in the workplace. The studies in this review used both qualitative and quantitative methods to identify current definitions of work-related and personal care-related PAS, agency-directed versus consumer-directed PAS, long-term and short-term funding issues, development of PAS policy, and barriers to successful implementation of PAS. The studies uncovered issues related to (a) recruiting, training, and retaining personal assistants, (b) employer concerns, (c) costs and benefits of workplace PAS, (d) wages and incentives for personal assistants, and (e) sources for financing PAS as a workplace accommodation. The findings reveal the value and benefits of effective PAS on the job. PAS can lead to successful employment of people with disabilities when other accommodations cannot provide adequate workplace support. Additionally, the evolution of workplace PAS is dependent on development of realistic PAS policy and funding options. Published by Elsevier Inc.

Disordering and dynamic self-organization in stoichiometric UO2 at high temperatures

NASA Astrophysics Data System (ADS)

Annamareddy, Ajay; Eapen, Jacob

2017-01-01

Neutron scattering experiments show significant oxygen disorder in UO2 at temperatures above 2000 K. The nature of the disorder, however, has not been ascertained with certainty. Using atomistic simulations and metrics from statistical mechanics we show that the oxygen anions predominantly hop from one native (tetrahedral) lattice site to another, above a characteristic temperature Tα (∼2000 K). Interestingly, we discover two types of disorder - the first one, which is a measure of the fraction of anions that are displaced from their native sites, portrays a monotonic increase with temperature and shows excellent conformity to neutron scattering data. The second metric based on the mean square displacement of the anions in an isoconfigurational ensemble demonstrates a dynamic self-organization behavior in which the anions are spatially correlated to those with similar mobility. This dynamic self-organization, however, experiences a non-monotonic variation with temperature depicting a maximum near the Bredig or λ-transition. We further establish that the thermodynamic metric cp/T, which is equal to the rate of change of entropy with temperature, is a key entropic indicator of the dynamic self-organization among the oxygen anions in UO2 at high temperatures.

When to suspect tinea; a histopathologic study of 103 cases of PAS-positive tinea.

PubMed

Elbendary, Amira; Valdebran, Manuel; Gad, AbdAllah; Elston, Dirk M

2016-10-01

The histopathologic features of tinea vary widely and its diagnosis could be easily missed if the index of suspicion is not high. We aimed in this study to detect histopathologic features that could be a clue for diagnosis We retrospectively reviewed 103 cases of tinea, confirmed by Periodic acid-Schiff (PAS) staining. For each case, gender, biopsy site, and pre-biopsy suspicion were recorded. The presence or absence of 17 microscopic features was noted. Concordance between pre-biopsy and histopathologic diagnosis was noted in 57.28% of cases, suggesting that the diagnosis is often not suspected clinically. Among the histopathologic features studied, a compact stratum corneum (either uniform or forming a layer beneath a basket weave stratum corneum), parakeratosis, mild spongiosis and neutrophils in the stratum corneum and within the blood vessels were the most frequent features noted. This study suggests histopathologic clues that should prompt the pathologist to order a PAS stain, especially when diagnosis is not suspected clinically. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Sandia National Laboratories performance assessment methodology for long-term environmental programs : the history of nuclear waste management.

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

Marietta, Melvin Gary; Anderson, D. Richard; Bonano, Evaristo J.

2011-11-01

Sandia National Laboratories (SNL) is the world leader in the development of the detailed science underpinning the application of a probabilistic risk assessment methodology, referred to in this report as performance assessment (PA), for (1) understanding and forecasting the long-term behavior of a radioactive waste disposal system, (2) estimating the ability of the disposal system and its various components to isolate the waste, (3) developing regulations, (4) implementing programs to estimate the safety that the system can afford to individuals and to the environment, and (5) demonstrating compliance with the attendant regulatory requirements. This report documents the evolution of themore » SNL PA methodology from inception in the mid-1970s, summarizing major SNL PA applications including: the Subseabed Disposal Project PAs for high-level radioactive waste; the Waste Isolation Pilot Plant PAs for disposal of defense transuranic waste; the Yucca Mountain Project total system PAs for deep geologic disposal of spent nuclear fuel and high-level radioactive waste; PAs for the Greater Confinement Borehole Disposal boreholes at the Nevada National Security Site; and PA evaluations for disposal of high-level wastes and Department of Energy spent nuclear fuels stored at Idaho National Laboratory. In addition, the report summarizes smaller PA programs for long-term cover systems implemented for the Monticello, Utah, mill-tailings repository; a PA for the SNL Mixed Waste Landfill in support of environmental restoration; PA support for radioactive waste management efforts in Egypt, Iraq, and Taiwan; and, most recently, PAs for analysis of alternative high-level radioactive waste disposal strategies including repositories deep borehole disposal and geologic repositories in shale and granite. Finally, this report summarizes the extension of the PA methodology for radioactive waste disposal toward development of an enhanced PA system for carbon sequestration and storage systems. These efforts have produced a generic PA methodology for the evaluation of waste management systems that has gained wide acceptance within the international community. This report documents how this methodology has been used as an effective management tool to evaluate different disposal designs and sites; inform development of regulatory requirements; identify, prioritize, and guide research aimed at reducing uncertainties for objective estimations of risk; and support safety assessments.« less

Euthanasia or physician-assisted suicide? A survey from the Netherlands.

PubMed

Kouwenhoven, Pauline S C; van Thiel, Ghislaine J M W; Raijmakers, Natasja J H; Rietjens, Judith A C; van der Heide, Agnes; van Delden, Johannes J M

2014-03-01

Legalizing euthanasia or physician-assisted suicide (PAS) is a current topic of debate in many countries. The Netherlands is the only country where legislation covers both. To study physicians' experiences and attitudes concerning the choice between euthanasia and PAS. A questionnaire including vignettes was sent to a random sample of 1955 Dutch general practitioners, elderly care physicians and medical specialists. In total, 793 physicians (41%) participated. There was no clear preference for euthanasia (36%) or PAS (34%). Two thirds of physicians thought that PAS underlines the autonomy and responsibility of the patient and considered this a reason to choose PAS. Reasons for not choosing PAS were expected practical problems. A minority (22%) discussed the possibility of PAS with their patient in case of a request for assistance in dying. Patients receiving PAS more often experienced psychosocial suffering in comparison with patients receiving euthanasia. In vignettes of patients with a request for assistance in dying due to psychosocial suffering, physicians agreed more often with the performance of PAS than with euthanasia. Dutch physicians perceive a difference between euthanasia and PAS. Although they believe PAS underlines patient autonomy and responsibility, the option of PAS is rarely discussed with the patient. The more psychosocial in nature the patient's suffering, the more physicians choose PAS. In these cases, PAS seems to fulfil physicians' preferences to emphasize patient autonomy and responsibility. Expected technical problems and unfamiliarity with PAS also play a role. Paradoxically, the choice for PAS is predominantly a physician's one.

Tetraammine(carbonato-κ2 O,O′)cobalt(III) perchlorate

PubMed Central

Mohan, Singaravelu Chandra; Jenniefer, Samson Jegan; Muthiah, Packianathan Thomas; Jothivenkatachalam, Kandasamy

2013-01-01

In the title complex, [Co(CO3)(NH3)4]ClO4, both the cation and anion lie on a mirror plane. The CoIII ion is coordinated by two NH3 ligands and a chelating carbonato ligand in the equatorial sites and by two NH3 groups in the axial sites, forming a distorted octa­hedral geometry. In the crystal, N—H⋯O hydrogen bonds connect the anions and cations, forming a three-dimensional network. PMID:24109252

Spanish validation of the Premorbid Adjustment Scale (PAS-S).

PubMed

Barajas, Ana; Ochoa, Susana; Baños, Iris; Dolz, Montse; Villalta-Gil, Victoria; Vilaplana, Miriam; Autonell, Jaume; Sánchez, Bernardo; Cervilla, Jorge A; Foix, Alexandrina; Obiols, Jordi E; Haro, Josep Maria; Usall, Judith

2013-02-01

The Premorbid Adjustment Scale (PAS) has been the most widely used scale to quantify premorbid status in schizophrenia, coming to be regarded as the gold standard of retrospective assessment instruments. To examine the psychometric properties of the Spanish version of the PAS (PAS-S). Retrospective study of 140 individuals experiencing a first episode of psychosis (n=77) and individuals who have schizophrenia (n=63), both adult and adolescent patients. Data were collected through a socio-demographic questionnaire and a battery of instruments which includes the following scales: PAS-S, PANSS, LSP, GAF and DAS-sv. The Cronbach's alpha was performed to assess the internal consistency of PAS-S. Pearson's correlations were performed to assess the convergent and discriminant validity. The Cronbach's alpha of the PAS-S scale was 0.85. The correlation between social PAS-S and total PAS-S was 0.85 (p<0.001); while for academic PAS-S and total PAS-S it was 0.53 (p<0.001). Significant correlations were observed between all the scores of each age period evaluated across the PAS-S scale, with a significance value less than 0.001. There was a relationship between negative symptoms and social PAS-S (0.20, p<0.05) and total PAS-S (0.22, p<0.05), but not with academic PAS-S. However, there was a correlation between academic PAS-S and general subscale of the PANSS (0.19, p<0.05). Social PAS-S was related to disability measures (DAS-sv); and academic PAS-S showed discriminant validity with most of the variables of social functioning. PAS-S did not show association with the total LSP scale (discriminant validity). The Spanish version of the Premorbid Adjustment Scale showed appropriate psychometric properties in patients experiencing a first episode of psychosis and who have a chronic evolution of the illness. Moreover, each domain of the PAS-S (social and academic premorbid functioning) showed a differential relationship to other characteristics such as psychotic symptoms, disability or social functioning after onset of illness. Copyright © 2013 Elsevier Inc. All rights reserved.

Nurse Practitioners, Physician Assistants and Certified Nurse Midwives in California.

ERIC Educational Resources Information Center

California Univ., San Francisco. Center for California Health Workforce Studies.

Surveys were mailed to all nurse practitioners (NPs), physician assistants (PAs) and certified nurse midwives (CNMs) registered in California, asking questions about education, labor force participation, specialty, and location and type of practice site, as well as the demographic characteristics of these professionals and their patients. Response…

The ammonium sulfate inhibition of human angiogenin.

PubMed

Chatzileontiadou, Demetra S M; Tsirkone, Vicky G; Dossi, Kyriaki; Kassouni, Aikaterini G; Liggri, Panagiota G V; Kantsadi, Anastassia L; Stravodimos, George A; Balatsos, Nikolaos A A; Skamnaki, Vassiliki T; Leonidas, Demetres D

2016-09-01

In this study, we investigate the inhibition of human angiogenin by ammonium sulfate. The inhibitory potency of ammonium sulfate for human angiogenin (IC50 = 123.5 ± 14.9 mm) is comparable to that previously reported for RNase A (119.0 ± 6.5 mm) and RNase 2 (95.7 ± 9.3 mm). However, analysis of two X-ray crystal structures of human angiogenin in complex with sulfate anions (in acidic and basic pH environments, respectively) indicates an entirely distinct mechanism of inhibition. While ammonium sulfate inhibits the ribonucleolytic activity of RNase A and RNase 2 by binding to the active site of these enzymes, sulfate anions bind only to peripheral substrate anion-binding subsites of human angiogenin, and not to the active site. © 2016 Federation of European Biochemical Societies.

Regulation of superoxide anion production by NADPH oxidase in monocytes/macrophages: contributions to atherosclerosis.

PubMed

Cathcart, Martha K

2004-01-01

Monocyte extravasation into the vessel wall has been shown to be a critical step in the development of atherosclerosis. Upon activation, monocytes produce a burst of superoxide anion due to activation of the NADPH oxidase enzyme complex. Monocyte-derived superoxide anion contributes to oxidant stress in inflammatory sites, is required for monocyte-mediated LDL oxidation, and alters basic cell functions such as adhesion and proliferation. We hypothesize that monocyte-derived superoxide anion production contributes to atherosclerotic lesion formation. In this brief review, we summarize our current understanding of the signal transduction pathways regulating NADPH oxidase activation and related superoxide anion production in activated human monocytes. Novel pathways are identified that may serve as future targets for therapeutic intervention in this pathogenic process. The contributions of superoxide anion and NADPH oxidase to atherogenesis are discussed. Future experiments are needed to clarify the exact role of NADPH oxidase-derived superoxide anion in atherogenesis, particularly that derived from monocytes.

Selective Nitrate Recognition by a Halogen-Bonding Four-Station [3]Rotaxane Molecular Shuttle.

PubMed

Barendt, Timothy A; Docker, Andrew; Marques, Igor; Félix, Vítor; Beer, Paul D

2016-09-05

The synthesis of the first halogen bonding [3]rotaxane host system containing a bis-iodo triazolium-bis-naphthalene diimide four station axle component is reported. Proton NMR anion binding titration experiments revealed the halogen bonding rotaxane is selective for nitrate over the more basic acetate, hydrogen carbonate and dihydrogen phosphate oxoanions and chloride, and exhibits enhanced recognition of anions relative to a hydrogen bonding analogue. This elaborate interlocked anion receptor functions via a novel dynamic pincer mechanism where upon nitrate anion binding, both macrocycles shuttle from the naphthalene diimide stations at the periphery of the axle to the central halogen bonding iodo-triazolium station anion recognition sites to form a unique 1:1 stoichiometric nitrate anion-rotaxane sandwich complex. Molecular dynamics simulations carried out on the nitrate and chloride halogen bonding [3]rotaxane complexes corroborate the (1) H NMR anion binding results. © 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Cost of workplace accommodations for individuals with disabilities: with or without personal assistance services.

PubMed

Solovieva, Tatiana I; Walls, Richard T; Hendricks, Deborah J; Dowler, Denetta L

2009-10-01

This study compared the expense associated with use of personal assistance services (PAS) for individuals with disabilities to the expense incurred by individuals with disabilities who did not use PAS. The intent of this investigation was to assess the disability accommodation costs and benefits of PAS and non-PAS cases. The study uses 1,182 follow-up telephone surveys and 24 telephone interviews of employers who had previously contacted the Job Accommodation Network (JAN) to discuss disability-related accommodations for an employee or potential employee that were conducted from January 2004 through December 2006. The survey included 69 employers who had considered PAS. The surveys were conducted by the University of Iowa's Law, Health Policy, and Disability Center, which contacted employers who had previously contacted JAN for consultation on workplace accommodations. The interviews were conducted by the International Center for Disability Information at West Virginia University. Key findings point to the costs associated with PAS cases and with cases not involving PAS accommodations. As reported by the employers, the median "one-time cost" of accommodations (not $0) for non-PAS cases was $500. The median "one-time cost" of accommodations (not $0) for PAS cases was $1,850. When $0 cost of accommodations on PAS cases was factored in with "one-time cost" of accommodations for PAS cases, the median cost was $0. For non-PAS cases of accommodations, when $0 cost of accommodations was considered, the outcome was a median cost of $0. The annual cost for PAS accommodations was a median cost of $8,000 in comparison to $2,000 for non-PAS. The median dollar amount estimates of direct benefits were $1,600 for PAS accommodations, similar to $1,500 for non-PAS. The most frequently mentioned benefits from PAS accommodations were (a) increased productivity, (b) increased diversity, (c) retention of a valued employee, (d) improved interactions with co-workers, (e) increased overall company morale, and (f) increased overall company productivity. The findings heighten awareness of the cost and benefits aspects associated with PAS for people with disabilities. Many non-PAS accommodations cost nothing to the employer (e.g., changing the work schedule, moving the individual to another location). When dollar cost was involved, the costs for PAS accommodations were more than three times greater than non-PAS accommodations.

Selective Nitrate Recognition by a Halogen‐Bonding Four‐Station [3]Rotaxane Molecular Shuttle

PubMed Central

Barendt, Timothy A.; Docker, Andrew; Marques, Igor; Félix, Vítor

2016-01-01

Abstract The synthesis of the first halogen bonding [3]rotaxane host system containing a bis‐iodo triazolium‐bis‐naphthalene diimide four station axle component is reported. Proton NMR anion binding titration experiments revealed the halogen bonding rotaxane is selective for nitrate over the more basic acetate, hydrogen carbonate and dihydrogen phosphate oxoanions and chloride, and exhibits enhanced recognition of anions relative to a hydrogen bonding analogue. This elaborate interlocked anion receptor functions via a novel dynamic pincer mechanism where upon nitrate anion binding, both macrocycles shuttle from the naphthalene diimide stations at the periphery of the axle to the central halogen bonding iodo‐triazolium station anion recognition sites to form a unique 1:1 stoichiometric nitrate anion–rotaxane sandwich complex. Molecular dynamics simulations carried out on the nitrate and chloride halogen bonding [3]rotaxane complexes corroborate the 1H NMR anion binding results. PMID:27436297

Anion complexation and the Hofmeister effect.

PubMed

Carnegie, Ryan S; Gibb, Corinne L D; Gibb, Bruce C

2014-10-20

The (1)H NMR spectroscopic analysis of the binding of the ClO4(-) anion to the hydrophobic, concave binding site of a deep-cavity cavitand is presented. The strength of association between the host and the ClO4(-) anion is controlled by both the nature and concentration of co-salts in a manner that follows the Hofmeister series. A model that partitions this trend into the competitive binding of the co-salt anion to the hydrophobic pocket of the host and counterion binding to its external carboxylate groups successfully accounts for the observed changes in ClO4(-) affinity. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Functionalized UO[sub 2] salenes. Neutral receptors for anions

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

Rudkevich, D.M.; Verboom, W.; Brzozka, Z.

1994-05-18

A novel class of neutral receptors for anions that contain a unique combination of an immobilized Lewis acidic binding site (UO[sub 2][sup 2+]) and additional amide C(O)NH groups, which can form a favorable H-bond with a coordinated anion guest, has been developed. The unique combination of a Lewis acidic UO[sub 2] center and amide C(O)NH groups in one receptor leads to highly specific H[sub 2]PO[sub 4[sup [minus

2-Phenylacetylenesulfonamide (PAS) induces p53-independent apoptotic killing of B-chronic lymphocytic leukemia (CLL) cells.

PubMed

Steele, Andrew J; Prentice, Archibald G; Hoffbrand, A Victor; Yogashangary, Birunthini C; Hart, Stephen M; Lowdell, Mark W; Samuel, Edward R; North, Janet M; Nacheva, Elisabeth P; Chanalaris, Anastasios; Kottaridis, Panagiotis; Cwynarski, Kate; Wickremasinghe, R Gitendra

2009-08-06

We studied the actions of 2-phenylacetylenesulfonamide (PAS) on B-chronic lymphocytic leukemia (CLL) cells. PAS (5-20 microM) initiated apoptosis within 24 hours, with maximal death at 48 hours asassessed by morphology, cleavage of poly(ADP-ribose) polymerase (PARP), caspase 3 activation, and annexin V staining. PAS treatment induced Bax proapoptotic conformational change, Bax movement from the cytosol to the mitochondria, and cytochrome c release, indicating that PAS induced apoptosis via the mitochondrial pathway. PAS induced approximately 3-fold up-regulation of proapoptotic Noxa protein and mRNA levels. In addition, Noxa was found unexpectedly to be bound to Bcl-2 in PAS-treated cells. PAS treatment of CLL cells failed to up-regulate p53, suggesting that PAS induced apoptosis independently of p53. Furthermore, PAS induced apoptosis in CLL isolates with p53 gene deletion in more than 97% of cells. Normal B lymphocytes were as sensitive to PAS-induced Noxa up-regulation and apoptosis as were CLL cells. However, both T lymphocytes and bone marrow hematopoietic progenitor cells were relatively resistant to PAS. Our data suggest that PAS may represent a novel class of drug that induces apoptosis in CLL cells independently of p53 status by a mechanism involving Noxa up-regulation.

A comparison of consumer-directed and agency-directed personal assistance services programmes.

PubMed

Hagglund, Kristofer; Clark, Mary; Farmer, Janet; Sherman, Ashley

2004-05-06

To compare a consumer-directed personal assistance services (PAS) programme with an agency-directed PAS programme. A convenience sample was used for this cross-sectional study with one data collection point. Outcomes were compared for consumer-directed and agency-directed PAS. Hierarchical regressions were also used to determine the predictors of outcomes across PAS programmes. In-home interviews were conducted by a trained data collector from April 2000 to December 2001. Participants in the consumer-directed programme reported more choices over PAS and satisfaction with PAS. Self-reported outcomes were primarily predicted by the following variables: service arrangement, type of provider, importance of directing PAS, health status, number of personal assistants used in past 12 months, sufficient PAS hours received, and social support. Consumer-directed PAS enhances outcomes for many persons with disabilities. Self-reported outcomes are affected by many factors that could be addressed in PAS programme development.

Personal Assistance Services (PAS) for individuals with disabilities: self-care at the workplace.

PubMed

Solovieva, Tatiana I; Walls, Richard T; Dowler, Denetta L

2010-01-01

The intent of this investigation was to identify current definitions, issues, and strategies related to the use of Personal Assistance Services (PAS) in the workplace. The participants were employees with disabilities who used PAS in the workplace as well as employers who participated in research studies over the past 20 years. More than 30 articles were reviewed to determine PAS definitions, use, policies, and outcomes. A comprehensive search of bibliographic resources (e.g., EBSCOhost) was conducted to identify appropriate articles. The articles revealed current definitions of workplace PAS, demonstrated an increasing need for PAS, and highlighted fiscal and societal barriers to the full implementation of PAS at work. The outcomes clarify the historical components, but also identify questions that remain. These questions concern the effectiveness of PAS, best practices for funding PAS, and the need for national and local policies to support the use of PAS for workers with disabilities.

Photoelectron spectroscopy and density functional theory studies of (FeS)mH- (m = 2-4) cluster anions: effects of the single hydrogen.

PubMed

Yin, Shi; Bernstein, Elliot R

2017-12-20

Single hydrogen containing iron hydrosulfide cluster anions (FeS) m H - (m = 2-4) are studied by photoelectron spectroscopy (PES) at 3.492 eV (355 nm) and 4.661 eV (266 nm) photon energies, and by Density Functional Theory (DFT) calculations. The structural properties, relative energies of different spin states and isomers, and the first calculated vertical detachment energies (VDEs) of different spin states for these (FeS) m H - (m = 2-4) cluster anions are investigated at various reasonable theory levels. Two types of structural isomers are found for these (FeS) m H - (m = 2-4) clusters: (1) the single hydrogen atom bonds to a sulfur site (SH-type); and (2) the single hydrogen atom bonds to an iron site (FeH-type). Experimental and theoretical results suggest such available different SH- and FeH-type structural isomers should be considered when evaluating the properties and behavior of these single hydrogen containing iron sulfide clusters in real chemical and biological systems. Compared to their related, respective pure iron sulfur (FeS) m - clusters, the first VDE trend of the diverse type (FeS) m H 0,1 - (m = 1-4) clusters can be understood through (1) the different electron distribution properties of their highest singly occupied molecular orbital employing natural bond orbital analysis (NBO/HSOMO), and (2) the partial charge distribution on the NBO/HSOMO localized sites of each cluster anion. Generally, the properties of the NBO/HSOMOs play the principal role with regard to the physical and chemical properties of all the anions. The change of cluster VDE from low to high is associated with the change in nature of their NBO/HSOMO from a dipole bound and valence electron mixed character, to a valence p orbital on S, to a valence d orbital on Fe, and to a valence p orbital on Fe or an Fe-Fe delocalized valence bonding orbital. For clusters having the same properties for NBO/HSOMOs, the partial charge distributions at the NBO/HSOMO localized sites additionally affect their VDEs: a more negative or less positive localized charge distribution is correlated with a lower first VDE. The single hydrogen in these (FeS) m H - (m = 2-4) cluster anions is suggested to affect their first VDEs through the different structure types (SH- or FeH-), the nature of the NBO/HSOMOs at the local site, and the value of partial charge number at the local site of the NBO/HSOMO.

Aerosol Light Absorption and Scattering in Mexico City: Comparison With Las Vegas, NV, and Los Angeles, CA.

NASA Astrophysics Data System (ADS)

Paredes-Miranda, G.; Arnott, W. P.; Gaffney, J. S.; Marley, N. A.; Campbell, D.; Fujita, E.

2007-12-01

Aerosol light scattering and absorption measurements were deployed in and near Mexico City in March 2006 as part of the Megacity Impacts on Regional and Global Environments (MIRAGE). The primary site in Mexico City was an urban site at Instituto Mexicano del Petroleo (Mexican Oil Institute, denoted by IMP). Similar campaigns were held in Las Vegas, NV in January-February, 2003; and Los Angeles, CA at numerous sites during all seasons from 2003 through 2007. The IMP site gave in-situ characterization of the Mexico City plume under favorable wind conditions. The photoacoustic instrument (PAS) used at IMP operates at 532 nm, and conveniently allowed for characterization of gaseous absorption at this wavelength as well. Light scattering measurements are accomplished within the PAS by the reciprocal nephelometery method. In Mexico City the aerosol absorption coefficient typically varies between 20 and 180 Mm-1 during the course of the day and significant diurnal variation of the aerosol single scattering albedo was observed probably as a consequence of secondary aerosol formation. We will present the diurnal variation of the scattering and absorption as well as the single scattering albedo and fraction of absorption due to gases at the IMP site and compare with Las Vegas diurnal variation. Mexico City 'breaths' more during the course of the day than Las Vegas, Nevada in part because the latitude of Mexico City resulted in more direct solar radiation. Further insight on the meteorological connections and population dynamics will be discussed.

Assessing the academic and professional needs of trauma nurse practitioners and physician assistants.

PubMed

Wilson, Laurie N; Wainwright, Gail A; Stehly, Christy D; Stoltzfus, Jill; Hoff, William S

2013-01-01

Because of multiple changes in the health care environment, the use of services of physician assistants (PAs) and nurse practitioners (NPs) in trauma and critical care has expanded. Appropriate training and ongoing professional development for these providers are essential to optimize clinical outcomes. This study offers a baseline assessment of the academic and professional needs of the contemporary trauma PAs/NPs in the United States. A 14-question electronic survey, using SurveyMonkey, was distributed to PAs/NPs at trauma centers identified through the American College of Surgeons Web site and other online resources. Demographic questions included trauma center level, provider type, level of education, and professional affiliations. Likert scale questions were incorporated to assess level of mentorship, comfort level with training, and individual perceived needs for academic and professional development. There were 120 survey respondents: 60 NPs and 60 PAs. Sixty-two respondents (52%) worked at level I trauma centers and 95 (79%) were hospital-employed. Nearly half (49%) reported working in trauma centers for 3 years or less. One hundred nineteen respondents (99%) acknowledged the importance of trauma-specific education; 98 (82%) were required by their institution to obtain such training. Thirty-five respondents (32%) reported receiving $1000 per year or less as a continuing medical education benefit. Insufficient mentorship, professional development, and academic development were identified by 22 (18%), 16 (13%), and 30 (25%) respondents, respectively. Opportunities to network with trauma PAs/NPs outside their home institution were identified as insufficient by 79 (66%). While PAs/NPs in trauma centers recognize the importance of continued contemporary trauma care and evidence-based practices, attending trauma-related education is not universally required by their employers. Financial restrictions may pose an additional impediment to academic development. Therefore, resource-efficient opportunities should be a prime consideration for advanced practitioners education, especially since half of the reported workforce has 3 years or less experience. The Eastern Association of Trauma and other organizations can provide an ideal venue for mentorship, academic development, and networking that is vital to PA/NP professional development and, ultimately, quality patient care.

Multi-PAS domain-mediated protein oligomerization of PpsR from Rhodobacter sphaeroides

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

Heintz, Udo; Meinhart, Anton; Winkler, Andreas, E-mail: andreas.winkler@mpimf-heidelberg.mpg.de

2014-03-01

Crystal structures of two truncated variants of the transcription factor PpsR from R. sphaeroides are presented that enabled the phasing of a triple PAS domain construct. Together, these structures reveal the importance of α-helical PAS extensions for multi-PAS domain-mediated protein oligomerization and function. Per–ARNT–Sim (PAS) domains are essential modules of many multi-domain signalling proteins that mediate protein interaction and/or sense environmental stimuli. Frequently, multiple PAS domains are present within single polypeptide chains, where their interplay is required for protein function. Although many isolated PAS domain structures have been reported over the last decades, only a few structures of multi-PAS proteinsmore » are known. Therefore, the molecular mechanism of multi-PAS domain-mediated protein oligomerization and function is poorly understood. The transcription factor PpsR from Rhodobacter sphaeroides is such a multi-PAS domain protein that, in addition to its three PAS domains, contains a glutamine-rich linker and a C-terminal helix–turn–helix DNA-binding motif. Here, crystal structures of two N-terminally and C-terminally truncated PpsR variants that comprise a single (PpsR{sub Q-PAS1}) and two (PpsR{sub N-Q-PAS1}) PAS domains, respectively, are presented and the multi-step strategy required for the phasing of a triple PAS domain construct (PpsR{sub ΔHTH}) is illustrated. While parts of the biologically relevant dimerization interface can already be observed in the two shorter constructs, the PpsR{sub ΔHTH} structure reveals how three PAS domains enable the formation of multiple oligomeric states (dimer, tetramer and octamer), highlighting that not only the PAS cores but also their α-helical extensions are essential for protein oligomerization. The results demonstrate that the long helical glutamine-rich linker of PpsR results from a direct fusion of the N-cap of the PAS1 domain with the C-terminal extension of the N-domain that plays an important role in signal transduction.« less

Protic ammonium carboxylate ionic liquids: insight into structure, dynamics and thermophysical properties by alkyl group functionalization.

PubMed

Reddy, Th Dhileep N; Mallik, Bhabani S

2017-04-19

This study is aimed at characterising the structure, dynamics and thermophysical properties of five alkylammonium carboxylate ionic liquids (ILs) from classical molecular dynamics simulations. The structural features of these ILs were characterised by calculating the site-site radial distribution functions, g(r), spatial distribution functions and structure factors. The structural properties demonstrate that ILs show greater interaction between cations and anions when alkyl chain length increases on the cation or anion. In all ILs, spatial distribution functions show that the anion is close to the acidic hydrogen atoms of the ammonium cation. We determined the role of alkyl group functionalization of the charged entities, cations and anions, in the dynamical behavior and the transport coefficients of this family of ionic liquids. The dynamics of ILs are described by studying the mean square displacement (MSD) of the centres of mass of the ions, diffusion coefficients, ionic conductivities and hydrogen bonds as well as residence dynamics. The diffusion coefficients and ionic conductivity decrease with an increase in the size of the cation or anion. The effect of alkyl chain length on ionic conductivity calculated in this article is consistent with the findings of other experimental studies. Hydrogen bond lifetimes and residence times along with structure factors were also calculated, and are related to alkyl chain length.

Problems in developing an instrument for the rapid assessment of personality status.

PubMed

Van Horn, E; Manley, C; Leddy, D; Cicchetti, D; Tyrer, P

2000-06-01

To assess the validity of a quick assessment instrument (10 minutes) for assessing personality status, the Rapid Personality Assessment Schedule (PAS-R). The PAS-R was evaluated in psychotic patients recruited in one of the centres involved in a multicentre randomised controlled trial of intensive vs standard case management (the UK700 case management trial). Patients were assessed using both a full version of the PAS (PAS-I - ICD version) and the PAS-R. The weighted kappa statistic was used to gauge the (criterion-related) validity of the PAS-R using the PAS-I as the gold standard. Both measure code personality status using a four-point rating of severity in addition to recording individual categories of personality disorder. One hundred fifty-five (77%) of 201 patients recruited were assessed with both instruments. The weighted kappa statistic was 0.31, suggesting only moderate agreement between the PAS-I and PAS-R instruments under the four-point rating format, and 0.39 for the dichotomous personality disorder/no disorder separation. The sensitivity (64%) and specificity (82%) of the PAS-R in predicting PAS-I personality disorder were as satisfactory as for other screening instruments but still somewhat disappointing, and the PAS-R had an overall diagnostic accuracy of 78%. The PAS-R is a quick and rough method of detecting personality abnormality but is not a substitute for a fuller assessment.

HPLC analysis of para-aminosalicylic acid and its metabolite in plasma, cerebrospinal fluid and brain tissues

PubMed Central

Hong, Lan; Jiang, Wendy; Zheng, Wei; Zeng, Su

2011-01-01

Para-aminosalicylic acid (PAS), an approved drug for treatment of tuberculosis, is a promising therapeutic agent for treatment of manganese (Mn)-induced parkinsonian syndromes. Lack of a quantifying method, however, has hindered the clinical evaluation of its efficacy and thereupon new drug development. This study was aimed at developing a simple and effective method to quantify PAS and its major metabolite, N-acetyl-para-aminosalicylic acid (AcPAS), in plasma, cerebrospinal fluid (CSF) and tissues. Biological samples underwent one-step protein precipitation. The supernatant was fractionated on a reversed-phase C18 column with a gradient mobile system, followed by on-line fluorescence detection. The lower limits of quantification for both PAS and AcPAS were 50 ng/ml of plasma and 17 ng/g of tissues. The intra-day and inter-day precision values did not exceed 5% and 8%, respectively, in all three matrices. The method was used to quantify PAS and AcPAS in rat plasma and brain following a single iv injection of PAS. Data showed a greater amount of PAS than AcPAS in plasma, while a greater amount of AcPAS than PAS was found in brain tissues. The method has been proven to be sensitive, reproducible, and practically useful for laboratory and clinical investigations of PAS in treatment of Mn Parkinsonism. PMID:21159459

Pyrrole based Schiff bases as colorimetric and fluorescent chemosensors for fluoride and hydroxide anions.

PubMed

Velmathi, Sivan; Reena, Vijayaraghavan; Suganya, Sivalingam; Anandan, Sambandam

2012-01-01

An efficient colorimetric sensor with pyrrole-NH moiety as binding site and nitro group as a signaling unit has been synthesized by a one step procedure and characterized by spectroscopic techniques, which displays excellent selectivity and sensitivity for fluoride and hydroxide ions. The hydrogen bonding with these anions provides remarkable colorimetric responses. (1)H NMR and FT IR studies has been carried out to confirm the hydrogen bonding. UV-vis and fluorescence spectral changes can be exploited for real time and on site application.

Modification of quinone electrochemistry by the proteins in the biological electron transfer chains: examples from photosynthetic reaction centers

PubMed Central

Gunner, M. R.; Madeo, Jennifer; Zhu, Zhenyu

2009-01-01

Quinones such as ubiquinone are the lipid soluble electron and proton carriers in the membranes of mitochondria, chloroplasts and oxygenic bacteria. Quinones undergo controlled redox reactions bound to specific sites in integral membrane proteins such as the cytochrome bc1 oxidoreductase. The quinone reactions in bacterial photosynthesis are amongst the best characterized, presenting a model to understand how proteins modulate cofactor chemistry. The free energy of ubiquinone redox reactions in aqueous solution and in the QA and QB sites of the bacterial photosynthetic reaction centers (RCs) are compared. In the primary QA site ubiquinone is reduced only to the anionic semiquinone (Q•−) while in the secondary QB site the product is the doubly reduced, doubly protonated quinol (QH2). The ways in which the protein modifies the relative energy of each reduced and protonated intermediate are described. For example, the protein stabilizes Q•− while destabilizing Q= relative to aqueous solution through electrostatic interactions. In addition, kinetic and thermodynamic mechanisms for stabilizing the intermediate semiquinones are compared. Evidence for the protein sequestering anionic compounds by slowing both on and off rates as well as by binding the anion more tightly is reviewed. PMID:18979192

Assessing shortfalls and complementary conservation areas for national plant biodiversity in South Korea.

PubMed

Choe, Hyeyeong; Thorne, James H; Huber, Patrick R; Lee, Dongkun; Quinn, James F

2018-01-01

Protected areas (PAs) are often considered the most important biodiversity conservation areas in national plans, but PAs often do not represent national-scale biodiversity. We evaluate the current conservation status of plant biodiversity within current existing PAs, and identify potential additional PAs for South Korea. We modeled species ranges for 2,297 plant species using Multivariate Adaptive Regression Splines and compared the level of mean range representation in South Korea's existing PAs, which comprise 5.7% of the country's mainland area, with an equal-area alternative PA strategy selected with the reserve algorithm Marxan. We also used Marxan to model two additional conservation scenarios that add lands to approach the Aichi Biodiversity Target objectives (17% of the country). Existing PAs in South Korea contain an average of 6.3% of each plant species' range, compared to 5.9% in the modeled equal-area alternative. However, existing PAs primarily represent a high percentage of the ranges for high-elevation and small range size species. The additional PAs scenario that adds lands to the existing PAs covers 14,587.55 km2, and would improve overall plant range representation to a mean of 16.8% of every species' range. The other additional PAs scenario, which selects new PAs from all lands and covers 13,197.35 km2, would improve overall plant range representation to a mean of 13.5%. Even though the additional PAs that includes existing PAs represents higher percentages of species' ranges, it is missing many biodiversity hotspots in non-mountainous areas and the additional PAs without locking in the existing PAs represent almost all species' ranges evenly, including low-elevation ones with larger ranges. Some priority conservation areas we identified are expansions of, or near, existing PAs, especially in northeastern and southern South Korea. However, lowland coastal areas and areas surrounding the capital city, Seoul, are also critical for biodiversity conservation in South Korea.

Assessing shortfalls and complementary conservation areas for national plant biodiversity in South Korea

PubMed Central

Thorne, James H.; Huber, Patrick R.; Lee, Dongkun; Quinn, James F.

2018-01-01

Protected areas (PAs) are often considered the most important biodiversity conservation areas in national plans, but PAs often do not represent national-scale biodiversity. We evaluate the current conservation status of plant biodiversity within current existing PAs, and identify potential additional PAs for South Korea. We modeled species ranges for 2,297 plant species using Multivariate Adaptive Regression Splines and compared the level of mean range representation in South Korea’s existing PAs, which comprise 5.7% of the country’s mainland area, with an equal-area alternative PA strategy selected with the reserve algorithm Marxan. We also used Marxan to model two additional conservation scenarios that add lands to approach the Aichi Biodiversity Target objectives (17% of the country). Existing PAs in South Korea contain an average of 6.3% of each plant species’ range, compared to 5.9% in the modeled equal-area alternative. However, existing PAs primarily represent a high percentage of the ranges for high-elevation and small range size species. The additional PAs scenario that adds lands to the existing PAs covers 14,587.55 km2, and would improve overall plant range representation to a mean of 16.8% of every species’ range. The other additional PAs scenario, which selects new PAs from all lands and covers 13,197.35 km2, would improve overall plant range representation to a mean of 13.5%. Even though the additional PAs that includes existing PAs represents higher percentages of species’ ranges, it is missing many biodiversity hotspots in non-mountainous areas and the additional PAs without locking in the existing PAs represent almost all species’ ranges evenly, including low-elevation ones with larger ranges. Some priority conservation areas we identified are expansions of, or near, existing PAs, especially in northeastern and southern South Korea. However, lowland coastal areas and areas surrounding the capital city, Seoul, are also critical for biodiversity conservation in South Korea. PMID:29474355

Resonant inelastic x-ray scattering probes the electron-phonon coupling in the spin liquid κ -(BEDT-TTF)2Cu2(CN) 3

NASA Astrophysics Data System (ADS)

Ilakovac, V.; Carniato, S.; Foury-Leylekian, P.; Tomić, S.; Pouget, J.-P.; Lazić, P.; Joly, Y.; Miyagawa, K.; Kanoda, K.; Nicolaou, A.

2017-11-01

Resonant inelastic x-ray scattering at the N K edge reveals clearly resolved harmonics of the anion plane vibrations in the κ -(BEDT-TTF) 2Cu2 (CN) 3 spin-liquid insulator. Tuning the incoming light energy at the K edge of two distinct N sites permits us to excite different sets of phonon modes. The cyanide (CN) stretching mode is selected at the edge of the ordered N sites which are more strongly connected to the bis(ethylenedithio)tetrathiafulvalene (BEDT-TTF) molecules, while positionally disordered N sites show multimode excitation. Combining measurements with calculations on an anion plane cluster permits us to estimate the site-dependent electron-phonon coupling of the modes related to nitrogen excitation.

Protected areas facilitate species’ range expansions

PubMed Central

Thomas, Chris D.; Gillingham, Phillipa K.; Bradbury, Richard B.; Roy, David B.; Anderson, Barbara J.; Baxter, John M.; Bourn, Nigel A. D.; Crick, Humphrey Q. P.; Findon, Richard A.; Fox, Richard; Hodgson, Jenny A.; Holt, Alison R.; Morecroft, Mike D.; O’Hanlon, Nina J.; Oliver, Tom H.; Pearce-Higgins, James W.; Procter, Deborah A.; Thomas, Jeremy A.; Walker, Kevin J.; Walmsley, Clive A.; Wilson, Robert J.; Hill, Jane K.

2012-01-01

The benefits of protected areas (PAs) for biodiversity have been questioned in the context of climate change because PAs are static, whereas the distributions of species are dynamic. Current PAs may, however, continue to be important if they provide suitable locations for species to colonize at their leading-edge range boundaries, thereby enabling spread into new regions. Here, we present an empirical assessment of the role of PAs as targets for colonization during recent range expansions. Records from intensive surveys revealed that seven bird and butterfly species have colonized PAs 4.2 (median) times more frequently than expected from the availability of PAs in the landscapes colonized. Records of an additional 256 invertebrate species with less-intensive surveys supported these findings and showed that 98% of species are disproportionately associated with PAs in newly colonized parts of their ranges. Although colonizing species favor PAs in general, species vary greatly in their reliance on PAs, reflecting differences in the dependence of individual species on particular habitats and other conditions that are available only in PAs. These findings highlight the importance of current PAs for facilitating range expansions and show that a small subset of the landscape receives a high proportion of colonizations by range-expanding species. PMID:22893689

Peptide-incorporated 3D porous alginate scaffolds with enhanced osteogenesis for bone tissue engineering.

PubMed

Luo, Zuyuan; Yang, Yue; Deng, Yi; Sun, Yuhua; Yang, Hongtao; Wei, Shicheng

2016-07-01

Good bioactivity and osteogenesis of three-dimensional porous alginate scaffolds (PAS) are critical for bone tissue engineering. In this work, alginate and bone-forming peptide-1 (BFP-1), derived from bone morphogenetic protein-7 (BMP-7), have been combined together (without carbodiimide chemistry treatment) to develop peptide-incorporated PAS (p-PAS) for promoting bone repairing ability. The mechanical properties and SEM images show no difference between pure PAS and p-PAS. The release kinetics of the labeled peptide with 6-carboxy tetramethyl rhodamine from the PAS matrix suggests that the peptide is released in a relatively sustained manner. In the cell experiment, p-PAS show higher cell adhesion, spreading, proliferation and alkaline phosphatase (ALP) activity than the pristine PAS group, indicating that the BFP-1 released from p-PAS could significantly promote the aggregation and differentiation of osteoblasts, especially at 10μg/mL of trapped peptide concentration (p-PAS-10). Furthermore, p-PAS-10 was implanted into Beagle calvarial defects and bone regeneration was analyzed after 4 weeks. New bone formation was assessed by calcein and Masson's trichrome staining. The data reveal that p-PAS group exhibits significantly enhanced oseto-regenerative capability in vivo. The peptide-modified PAS with promoted bioactivity and osteogenic differentiation in vitro as well as bone formation ability in vivo could be promising tissue engineering materials for repairing and regeneration of bone defects. Copyright © 2016 Elsevier B.V. All rights reserved.

Schizotypal Perceptual Aberrations of Time: Correlation between Score, Behavior and Brain Activity

PubMed Central

Arzy, Shahar; Mohr, Christine; Molnar-Szakacs, Istvan; Blanke, Olaf

2011-01-01

A fundamental trait of the human self is its continuum experience of space and time. Perceptual aberrations of this spatial and temporal continuity is a major characteristic of schizophrenia spectrum disturbances – including schizophrenia, schizotypal personality disorder and schizotypy. We have previously found the classical Perceptual Aberration Scale (PAS) scores, related to body and space, to be positively correlated with both behavior and temporo-parietal activation in healthy participants performing a task involving self-projection in space. However, not much is known about the relationship between temporal perceptual aberration, behavior and brain activity. To this aim, we composed a temporal Perceptual Aberration Scale (tPAS) similar to the traditional PAS. Testing on 170 participants suggested similar performance for PAS and tPAS. We then correlated tPAS and PAS scores to participants' performance and neural activity in a task of self-projection in time. tPAS scores correlated positively with reaction times across task conditions, as did PAS scores. Evoked potential mapping and electrical neuroimaging showed self-projection in time to recruit a network of brain regions at the left anterior temporal cortex, right temporo-parietal junction, and occipito-temporal cortex, and duration of activation in this network positively correlated with tPAS and PAS scores. These data demonstrate that schizotypal perceptual aberrations of both time and space, as reflected by tPAS and PAS scores, are positively correlated with performance and brain activation during self-projection in time in healthy individuals along the schizophrenia spectrum. PMID:21267456

Field calibration of polyurethane foam (PUF) disk passive air samplers for PCBs and OC pesticides.

PubMed

Chaemfa, Chakra; Barber, Jonathan L; Gocht, Tilman; Harner, Tom; Holoubek, Ivan; Klanova, Jana; Jones, Kevin C

2008-12-01

Different passive air sampler (PAS) strategies have been developed for sampling in remote areas and for cost-effective simultaneous spatial mapping of POPs (persistent organic pollutants) over differing geographical scales. The polyurethane foam (PUF) disk-based PAS is probably the most widely used. In a PUF-based PAS, the PUF disk is generally mounted inside two stainless steel bowls to buffer the air flow to the disk and to shield it from precipitation and light. The field study described in this manuscript was conducted to: compare performance of 3 different designs of sampler; to further calibrate the sampler against the conventional active sampler; to derive more information on field-based uptake rates and equilibrium times of the samplers. Samplers were also deployed at different locations across the field site, and at different heights up a meteorological tower, to investigate the possible influence of sampler location. Samplers deployed <5m above ground, and not directly sheltered from the wind gave similar uptake rates. Small differences in dimensions between the 3 designs of passive sampler chamber had no discernable effect on accumulation rates, allowing comparison with previously published data.

Bifunctional anion-exchange resins with improved selectivity and exchange kinetics

DOEpatents

Alexandratos, Spiro D.; Brown, Gilbert M.; Bonnesen, Peter V.; Moyer, Bruce A.

2000-01-01

Disclosed herein are a class of anion exchange resins containing two different exchange sites with improved selectivity and sorptive capability for chemical species in solution, such as heptavalent technetium (as pertechnetate anion, TcO.sub.4.sup.-). The resins are prepared by first reacting haloalkylated crosslinked copolymer beads with a large tertiary amine in a solvent in which the resin beads can swell, followed by reaction with a second, smaller, tertiary amine to more fully complete the functionalization of the resin. The resins have enhanced selectivity, capacity, and exchange kinetics.

Protected area coverage of threatened vertebrates and ecoregions in Peru: Comparison of communal, private and state reserves.

PubMed

Shanee, Sam; Shanee, Noga; Monteferri, Bruno; Allgas, Nestor; Alarcon Pardo, Alejandro; Horwich, Robert H

2017-11-01

Protected areas (PAs) are a conservation mainstay and arguably the most effective conservation strategy for species protection. As a 'megadiverse' country, Peru is a priority for conservation actions. Peruvian legislation allows for the creation of state PAs and private/communal PAs. Using publicly available species distribution and protected area data sets we evaluated the coverage of Threatened terrestrial vertebrate species distributions and ecoregions provided by both kinds of PA in Peru. Peru's state PA system covers 217,879 km 2 and private/communal PAs cover 16,588 km 2 . Of the 462 species of Threatened and Data Deficient species we evaluated, 75% had distributions that overlapped with at least one PA but only 53% had ≥10% of their distributions within PAs, with inclusion much reduced at higher coverage targets. Of the species we evaluated, 118 species are only found in national PAs and 29 species only found in private/communal PAs. Of the 17 terrestrial ecoregions found in Peru all are represented in PAs; the national PA system included coverage of 16 and private/communal PAs protect 13. One ecoregion is only protected in private/communal PAs, whereas four are only covered in national PAs. Our results show the important role private/communal PAs can play in the protection of ecological diversity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Unveiling N-protonation and anion-binding effects on Fe/N/C-catalysts for O2 reduction in PEM fuel cells

PubMed Central

Herranz, Juan; Jaouen, Frédéric; Lefèvre, Michel; Kramm, Ulrike I.; Proietti, Eric; Dodelet, Jean-Pol; Bogdanoff, Peter; Fiechter, Sebastian; Abs-Wurmbach, Irmgard; Bertrand, Patrick; Arruda, Thomas M.; Mukerjee, Sanjeev

2013-01-01

The high cost of proton-exchange-membrane fuel cells would be considerably reduced if platinumbased catalysts were replaced by iron-based substitutes, which have recently demonstrated comparable activity for oxygen reduction, but whose cause of activity decay in acidic medium has been elusive. Here, we reveal that the activity of Fe/N/C-catalysts prepared through a pyrolysis in NH3 is mostly imparted by acid-resistant FeN4-sites whose turnover frequency for the O2 reduction can be regulated by fine chemical changes of the catalyst surface. We show that surface N-groups protonate at pH 1 and subsequently bind anions. This results in decreased activity for the O2 reduction. The anions can be removed chemically or thermally, which restores the activity of acid-resistant FeN4-sites. These results are interpreted as an increased turnover frequency of FeN4-sites when specific surface N-groups protonate. These unprecedented findings provide new perspective for stabilizing the most active Fe/N/C-catalysts known to date. PMID:24179561

Unveiling N-protonation and anion-binding effects on Fe/N/C-catalysts for O2 reduction in PEM fuel cells.

PubMed

Herranz, Juan; Jaouen, Frédéric; Lefèvre, Michel; Kramm, Ulrike I; Proietti, Eric; Dodelet, Jean-Pol; Bogdanoff, Peter; Fiechter, Sebastian; Abs-Wurmbach, Irmgard; Bertrand, Patrick; Arruda, Thomas M; Mukerjee, Sanjeev

2011-11-18

The high cost of proton-exchange-membrane fuel cells would be considerably reduced if platinumbased catalysts were replaced by iron-based substitutes, which have recently demonstrated comparable activity for oxygen reduction, but whose cause of activity decay in acidic medium has been elusive. Here, we reveal that the activity of Fe/N/C-catalysts prepared through a pyrolysis in NH 3 is mostly imparted by acid-resistant FeN 4 -sites whose turnover frequency for the O 2 reduction can be regulated by fine chemical changes of the catalyst surface. We show that surface N-groups protonate at pH 1 and subsequently bind anions. This results in decreased activity for the O 2 reduction. The anions can be removed chemically or thermally, which restores the activity of acid-resistant FeN 4 -sites. These results are interpreted as an increased turnover frequency of FeN 4 -sites when specific surface N-groups protonate. These unprecedented findings provide new perspective for stabilizing the most active Fe/N/C-catalysts known to date.

Adsorption of selenium by amorphous iron oxyhydroxide and manganese dioxide

USGS Publications Warehouse

Balistrieri, L.S.; Chao, T.T.

1990-01-01

This work compares and models the adsorption of selenium and other anions on a neutral to alkaline surface (amorphous iron oxyhydroxide) and an acidic surface (manganese dioxide). Selenium adsorption on these oxides is examined as a function of pH, particle concentration, oxidation state, and competing anion concentration in order to assess how these factors might influence the mobility of selenium in the environment. The data indicate that 1. 1) amorphous iron oxyhydroxide has a greater affinity for selenium than manganese dioxide, 2. 2) selenite [Se(IV)] adsorption increases with decreasing pH and increasing particle concentration and is stronger than selenate [Se(VI)] adsorption on both oxides, and 3. 3) selenate does not adsorb on manganese dioxide. The relative affinity of selenate and selenite for the oxides and the lack of adsorption of selenate on a strongly acidic surface suggests that selenate forms outer-sphere complexes while selenite forms inner-sphere complexes with the surfaces. The data also indicate that the competition sequence of other anions with respect to selenite adsorption at pH 7.0 is phosphate > silicate > molybdate > fluoride > sulfate on amorphous iron oxyhydroxide and molybdate ??? phosphate > silicate > fluoride > sulfate on manganese dioxide. The adsorption of phosphate, molybdate, and silicate on these oxides as a function of pH indicates that the competition sequences reflect the relative affinities of these anions for the surfaces. The Triple Layer surface complexation model is used to provide a quantitative description of these observations and to assess the importance of surface site heterogeneity on anion adsorption. The modeling results suggest that selenite forms binuclear, innersphere complexes with amorphous iron oxyhydroxide and monodentate, inner-sphere complexes with manganese dioxide and that selenate forms outer-sphere, monodentate complexes with amorphous iron oxyhydroxide. The heterogeneity of the oxide surface sites is reflected in decreasing equilibrium constants for selenite with increasing adsorption density and both experimental observations and modeling results suggest that manganese dioxide has fewer sites of higher energy for selenite adsorption than amorphous iron oxyhydroxide. Modeling and interpreting the adsorption of phosphate, molybdate, and silicate on the oxides are made difficult by the lack of constraint in choosing surface species and the fact that equally good fits can be obtained with different surface species. Finally, predictions of anion competition using the model results from single adsorbate systems are not very successful because the model does not account for surface site heterogeneity. Selenite adsorption data from a multi-adsorbate system could be fit if the equilibrium constant for selenite is decreased with increasing anion adsorption density. ?? 1990.

4-Benzyl-4-methyl­morpholinium hexa­fluoro­phosphate

PubMed Central

Su, Qiu-hong; Zang, Hong-Jun; Xu, Tian-lin; Ren, Yuan-Lin

2010-01-01

In the title compound, C12H18NO+·PF6 −, the asymmetric unit consists of two cation–anion pairs. The six F atoms of one anion are disordered over two sets of sites in a 0.592 (6):0.408 (6) ratio. The morpholinium rings adopt chair conformations. PMID:21587663

Can I help you? A qualitative study of pharmacist and pharmacy assistant views on the role of pharmacy assistants in New Zealand.

PubMed

Sheridan, Janie; Kelly, Fiona; Basheer, Mariam; Jan, Reem; Lee, Alice

2011-08-01

To begin to explore the role of PAs more fully in a New Zealand context, through semi-structured interviews with PAs and pharmacists. Semi-structured, qualitative interviews with a convenience sample of pairs of PAs and pharmacists working in a pharmacy together. Pharmacists and PAs both described important roles for PAs. The PAs tended to see themselves as the first point of contact for customers, and that they fulfilled an important healthcare role for the public. Pharmacists agreed that they were the first point of contact yet viewed this more as a gatekeeper role to the pharmacist. Views were also expressed about the difference between PAs and other retail employees. Pharmacists and PAs noted that the 'public' expected PAs to have a basic knowledge of non-prescription medicines and their uses. PAs described difficulties when requesting personal information from customers or asking essential questions where the customer had made a specific product request. Being able to know when to refer to the pharmacist was seen as a key role. Despite being able to describe a number of roles for PAs, these were highly variable. The lack of mandatory training and a clearly articulated role for PAs in New Zealand meant that in some cases PAs might be seen as little more than general retail assistants--a view not in line with their actual roles and practices. Attention to these issues may well help to resolve this, as will public education about the PA's role. © 2011 The Authors. IJPP © 2011 Royal Pharmaceutical Society.

Effect of molecular weight profile of sorghum proanthocyanidins on resistant starch formation.

PubMed

Barros, Frederico; Awika, Joseph; Rooney, Lloyd W

2014-04-01

There is a growing interest to increase resistant starch (RS) in foods through natural modification of starch. Sorghum tannins (proanthocyanidins, PAs) were recently reported to interact with starch, increasing RS. However, there is no information about how the molecular weight profile of PAs affects RS formation. This study investigated how different-molecular-weight PAs from sorghum affected RS formation in different starch models. The levels of RS were higher (331-437 mg g(-1)) when high-amylose starch was cooked with phenolic extracts containing mostly high-molecular-weight PAs compared with extracts containing lower-molecular-weight PAs or monomeric catechin (249-285 mg g(-1)). In general, binding capacity of PAs with amylose increased proportionally with molecular weight. For example, the percentage of PAs bound to amylose increased from 45% (PAs with degree of polymerization (DP) = 6) to 94% (polymeric PAs, DP > 10). The results demonstrate that molecular weight of the PAs directly affects their interaction with starch: the higher the molecular weight, the stronger the binding to amylose and the higher the RS formation. Polymeric PAs from sorghum can naturally modify starch by interacting strongly with amylose and are thus most suitable to produce foods with higher RS. © 2013 Society of Chemical Industry.

Pedunculated Pulmonary Artery Sarcoma Suggested by Transthoracic Echocardiography.

PubMed

Wang, Xiaobing; Ren, Weidong; Yang, Jun

2016-04-01

Pulmonary artery sarcoma (PAS) is an extremely rare malignancy. It is usually found after it grows large enough to occupy almost the entire lumen of the pulmonary artery and causes serious clinical symptoms. Thus, it is usually difficult to distinguish PAS from pulmonary thromboembolism based on imaging examinations. Few case reports had shown the attachment of PAS to pulmonary artery, a key characteristic for diagnosis, and differential diagnosis of PAS. In this case, we found a PAS, which did not cause local obstruction and some tumor emboli, which obstructed the branches of the pulmonary arteries and caused pulmonary hypertension and clinical symptoms. Transthoracic echocardiography (TTE) revealed a part of the tumor attached to the intima of the main pulmonary artery with a peduncle and had obvious mobility, which was suggestive of PAS and differentiated it from the pulmonary thromboembolism. To our knowledge, this is the first case report of a pedunculated PAS suggested by TTE. Combined with pulmonary artery computed tomography angiography, the diagnosis of PAS is strongly suggested before the operation. This case indicates that TTE could reveal the attachment and mobility of PAS in the main pulmonary and may provide useful information for the diagnosis and differential diagnosis of PAS, especially a pedunculated PAS. © 2015, Wiley Periodicals, Inc.

Are satisfaction with and self-management of personal assistance services associated with the life satisfaction of persons with physical disabilities?

PubMed

Fleming-Castaldy, Rita P

2011-01-01

To examine the relationships between satisfaction with and self-management of personal assistance services (PAS) and the quality of life (QoL) of persons with disabilities. To test the postulate that consumer-directed PAS can fulfil the human need for control and contribute to a satisfactory life. A survey compared the perspectives of persons using consumer-directed PAS versus those using agency-directed. A Personal Data Form obtained demographics and PAS characteristics. The Quality of Life Inventory measured life satisfaction. A PAS questionnaire measured perceptions about the management of, desire for control of, and satisfaction with PAS. Data were analysed using SPSS®- 14. Significant relationships were found between QoL and satisfaction with PAS (p < 0.001) and between perceived control of PAS and satisfaction with PAS (p < 0.001). Significant group differences were also found. Consumer-directed participants reported higher satisfaction with their PAS (p < 0.01), greater control over services (p < 0.001) and greater QoL than agency-directed participants, (p = 0.001). The relationships found between self-management, PAS satisfaction, and QoL support the value of consumer-directed programmes. Rehabilitation professionals can use this knowledge to develop, implement and research practises that enable self-management.

Protected areas offer refuge from invasive species spreading under climate change.

PubMed

Gallardo, Belinda; Aldridge, David C; González-Moreno, Pablo; Pergl, Jan; Pizarro, Manuel; Pyšek, Petr; Thuiller, Wilfried; Yesson, Christopher; Vilà, Montserrat

2017-12-01

Protected areas (PAs) are intended to provide native biodiversity and habitats with a refuge against the impacts of global change, particularly acting as natural filters against biological invasions. In practice, however, it is unknown how effective PAs will be in shielding native species from invasions under projected climate change. Here, we investigate the current and future potential distributions of 100 of the most invasive terrestrial, freshwater, and marine species in Europe. We use this information to evaluate the combined threat posed by climate change and invasions to existing PAs and the most susceptible species they shelter. We found that only a quarter of Europe's marine and terrestrial areas protected over the last 100 years have been colonized by any of the invaders investigated, despite offering climatically suitable conditions for invasion. In addition, hotspots of invasive species and the most susceptible native species to their establishment do not match at large continental scales. Furthermore, the predicted richness of invaders is 11%-18% significantly lower inside PAs than outside them. Invasive species are rare in long-established national parks and nature reserves, which are actively protected and often located in remote and pristine regions with very low human density. In contrast, the richness of invasive species is high in the more recently designated Natura 2000 sites, which are subject to high human accessibility. This situation may change in the future, since our models anticipate important shifts in species ranges toward the north and east of Europe at unprecedented rates of 14-55 km/decade, depending on taxonomic group and scenario. This may seriously compromise the conservation of biodiversity and ecosystem services. This study is the first comprehensive assessment of the resistance that PAs provide against biological invasions and climate change on a continental scale and illustrates their strategic value in safeguarding native biodiversity. © 2017 John Wiley & Sons Ltd.

Impacts of glycolate and formate radiolysis and thermolysis on hydrogen generation rate calculations for the Savannah River Site tank farm

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

Crawford, C. L.; King, W. D.

Savannah River Remediation (SRR) personnel requested that the Savannah River National Laboratory (SRNL) evaluate available data and determine its applicability to defining the impact of planned glycolate anion additions to Savannah River Site (SRS) High Level Waste (HLW) on Tank Farm flammability (primarily with regard to H 2 production). Flammability evaluations of formate anion, which is already present in SRS waste, were also needed. This report describes the impacts of glycolate and formate radiolysis and thermolysis on Hydrogen Generation Rate (HGR) calculations for the SRS Tank Farm.

Supramolecular hydrogen-bonding networks in bis(adeninium) phthalate phthalic acid 1.45-hydrate.

PubMed

Sridhar, Balasubramanian; Ravikumar, Krishnan

2007-04-01

In the title compound, 2C(5)H(6)N(5)(+).C(8)H(4)O(4)(2-).C(8)H(6)O(4).1.45H(2)O, the asymmetric unit comprises two adeninium cations, two half phthalate anions with crystallographic C(2) symmetry, one neutral phthalic acid molecule, and one fully occupied and one partially occupied site (0.45) for water molecules. The adeninium cations form N-H...O hydrogen bonds with the phthalate anions. The cations also form infinite one-dimensional polymeric ribbons via N-H...N interactions. In the crystal packing, hydrogen-bonded columns of cations, anions and phthalate anions extend parallel to the c axis. The water molecules crosslink adjacent columns into hydrogen-bonded layers.

Blood-nerve barrier: distribution of anionic sites on the endothelial plasma membrane and basal lamina of dorsal root ganglia.

PubMed

Bush, M S; Reid, A R; Allt, G

1991-09-01

Previous investigations of the blood-nerve barrier have correlated the greater permeability of ganglionic endoneurial vessels, compared to those of nerve trunks, with the presence of fenestrations and open intercellular junctions. Recent studies have demonstrated reduced endothelial cell surface charge in blood vessels showing greater permeability. To determine the distribution of anionic sites on the plasma membranes and basal laminae of endothelial cells in dorsal root ganglia, cationic colloidal gold and cationic ferritin were used. Electron microscopy revealed the existence of endothelial microdomains with differing labelling densities. Labelling indicated that caveolar and fenestral diaphragms and basal laminae are highly anionic at physiological pH, luminal plasma membranes and endothelial processes are moderately charged and abluminal plasma membranes are weakly anionic. Tracers did not occur in caveolae or cytoplasmic vesicles. In vitro tracer experiments at pH values of 7.3, 5.0, 3.5 and 2.0 indicated that the anionic charge on the various endothelial domains was contributed by chemical groups with differing pKa values. In summary, the labelling of ganglionic and sciatic nerve vessels was similar except for the heavy labelling of diaphragms in a minority of endoneurial vessels in ganglia. This difference is likely to account in part for the greater permeability of ganglionic endoneurial vessels. The results are discussed with regard to the blood-nerve and -brain barriers and vascular permeability in other tissues and a comparison made between the ultrastructure and anionic microdomains of epi-, peri- and endoneurial vessels of dorsal root ganglia and sciatic nerves.

Clinical assessment and management of general surgery patients via synchronous telehealth.

PubMed

Cain, Steven M; Moore, Robert; Sturm, Lauren; Mason, Travis; Fuhrman, Caitlin; Smith, Robin; Bojicic, Irfan; Carter, Brandon

2017-02-01

Objective This paper describes how a clinical team at Landstuhl Regional Medical Center (LRMC) successfully integrated synchronous telehealth (TH) into their routine clinical practice. Methods and materials Synchronous TH encounters were performed using Polycom® software on surgeons' computers with high-definition (HD) cameras on monitors at distant sites and PolyCom HDX9000® Telehealth Practitioner Carts at originating sites. Patients provided consented and were presented to general surgeons by nurses and medical technicians at Army health clinics throughout the European Theater. Results In calendar year (CY) 2014, five general surgeons and two surgical physician assistants (PAs) at Landstuhl Regional Medical Center along with registered nurses (RNs) at six originating clinic sites throughout Europe completed 130 synchronous TH encounters for 101 general surgery patients resulting in 73 completed and 16 recommended surgeries. Eighty-eight percent of patients had a completed or recommended surgery. No surgeries or procedures planned after initial TH evaluation were cancelled. Originating site clinics ranged in distance from 68 miles to 517 miles. Acceptance by providers, patients and clinic staff was high. Conclusion Synchronous TH was effective and safe in evaluating common general surgical conditions. We excluded sensitive and complex conditions requiring a nuanced physical examination. The TH efforts of the general surgery staff have resulted in high-quality, seamless and predictable TH activities that continue to expand into other surgical and medical specialties beyond general surgery. Seven surgeons and two PAs use synchronous TH regularly serving patients over a broad geographic area.

The Transmembrane Region of Guard Cell SLAC1 Channels Perceives CO2 Signals via an ABA-Independent Pathway in Arabidopsis.

PubMed

Yamamoto, Yoshiko; Negi, Juntaro; Wang, Cun; Isogai, Yasuhiro; Schroeder, Julian I; Iba, Koh

2016-02-01

The guard cell S-type anion channel, SLOW ANION CHANNEL1 (SLAC1), a key component in the control of stomatal movements, is activated in response to CO2 and abscisic acid (ABA). Several amino acids existing in the N-terminal region of SLAC1 are involved in regulating its activity via phosphorylation in the ABA response. However, little is known about sites involved in CO2 signal perception. To dissect sites that are necessary for the stomatal CO2 response, we performed slac1 complementation experiments using transgenic plants expressing truncated SLAC1 proteins. Measurements of gas exchange and stomatal apertures in the truncated transgenic lines in response to CO2 and ABA revealed that sites involved in the stomatal CO2 response exist in the transmembrane region and do not require the SLAC1 N and C termini. CO2 and ABA regulation of S-type anion channel activity in guard cells of the transgenic lines confirmed these results. In vivo site-directed mutagenesis experiments targeted to amino acids within the transmembrane region of SLAC1 raise the possibility that two tyrosine residues exposed on the membrane are involved in the stomatal CO2 response. © 2016 American Society of Plant Biologists. All rights reserved.

The Transmembrane Region of Guard Cell SLAC1 Channels Perceives CO2 Signals via an ABA-Independent Pathway in Arabidopsis

PubMed Central

Yamamoto, Yoshiko; Negi, Juntaro; Isogai, Yasuhiro; Schroeder, Julian I.; Iba, Koh

2016-01-01

The guard cell S-type anion channel, SLOW ANION CHANNEL1 (SLAC1), a key component in the control of stomatal movements, is activated in response to CO2 and abscisic acid (ABA). Several amino acids existing in the N-terminal region of SLAC1 are involved in regulating its activity via phosphorylation in the ABA response. However, little is known about sites involved in CO2 signal perception. To dissect sites that are necessary for the stomatal CO2 response, we performed slac1 complementation experiments using transgenic plants expressing truncated SLAC1 proteins. Measurements of gas exchange and stomatal apertures in the truncated transgenic lines in response to CO2 and ABA revealed that sites involved in the stomatal CO2 response exist in the transmembrane region and do not require the SLAC1 N and C termini. CO2 and ABA regulation of S-type anion channel activity in guard cells of the transgenic lines confirmed these results. In vivo site-directed mutagenesis experiments targeted to amino acids within the transmembrane region of SLAC1 raise the possibility that two tyrosine residues exposed on the membrane are involved in the stomatal CO2 response. PMID:26764376

Paired associative stimulation modulates corticomotor excitability in chronic stroke: A preliminary investigation.

PubMed

Palmer, Jacqueline A; Wolf, Steven L; Borich, Michael R

2018-01-01

Paired associative stimulation (PAS) combining repeated pairing of electrical stimulation of a peripheral nerve with transcranial magnetic stimulation (TMS) over the primary motor cortex (M1) can induce neuroplastic adaptations in the human brain and enhance motor learning in neurologically-intact individuals. However, the extent to which PAS is an effective technique for inducing associative plasticity and improving motor function in individuals post-stroke is unclear. The objective of this pilot study was to investigate the effects of a single session of PAS to modulate corticomotor excitability and motor skill performance in individuals post-stroke. Seven individuals with chronic stroke completed two separate visits separated by at least one week. We assessed general corticomotor excitability, intracortical network activity and behavioral outcomes prior to and at three time points following PAS and compared these outcomes to those following a sham PAS condition (PASSHAM). Following PAS, we found increased general corticomotor excitability but no significant difference in behavioral measures between PAS conditions. There was a relationship between PAS-induced corticomotor excitability increase and enhanced motor skill performance across post-PAS testing time points. These results provide preliminary evidence for the potential of PAS to increase corticomotor excitability that could favorably impact motor skill performance in chronic individuals post-stroke and are an important first step for future studies investigating the clinical application and behavioral relevance of PAS interventions in post stroke patient populations.

Determinants of Oregon hospice chaplains' views on physician-assisted suicide.

PubMed

Goy, Elizabeth R; Carlson, Bryant; Simopoulos, Nicole; Jackson, Ann; Ganzini, Linda

2006-01-01

Although religiousness is a strong predictor of attitudes towards physician-assisted suicide (PAS), Oregon hospice chaplains express wide variation in their opposition to or support for legalized PAS. We explored factors associated with chaplains' views on PAS. A mailed survey to chaplains from 51 Oregon hospices. Fifty of 77 eligible hospice chaplains (65%) returned surveys. Views on PAS were associated with views on suicide in general. Moral and theological beliefs were the most important influences on views on PAS. Chaplains who were opposed to PAS believed that God alone may take life, that life is an absolute good, and that suffering has a divine purpose. Those who supported PAS placed emphasis on the importance of self-determination and sanctity of life as defined by quality of life. Oregon hospice chaplains' diverse views towards PAS are closely related to their views on suicide in general, and their personal and theological beliefs.

Density functional theory and conductivity studies of boron-based anion receptors

DOE PAGES

Leung, Kevin; Chaudhari, Mangesh I.; Rempe, Susan B.; ...

2015-07-10

Anion receptors that bind strongly to fluoride anions in organic solvents can help dissolve the lithium fluoride discharge products of primary carbon monofluoride (CFx) batteries, thereby preventing the clogging of cathode surfaces and improving ion conductivity. The receptors are also potentially beneficial to rechargeable lithium ion and lithium air batteries. We apply Density Functional Theory (DFT) to show that an oxalate-based pentafluorophenyl-boron anion receptor binds as strongly, or more strongly, to fluoride anions than many phenyl-boron anion receptors proposed in the literature. Experimental data shows marked improvement in electrolyte conductivity when this oxalate anion receptor is present. The receptor ismore » sufficiently electrophilic that organic solvent molecules compete with F – for boron-site binding, and specific solvent effects must be considered when predicting its F – affinity. To further illustrate the last point, we also perform computational studies on a geometrically constrained boron ester that exhibits much stronger gas-phase affinity for both F – and organic solvent molecules. After accounting for specific solvent effects, however, its net F – affinity is about the same as the simple oxalate-based anion receptor. Lastly, we propose that LiF dissolution in cyclic carbonate organic solvents, in the absence of anion receptors, is due mostly to the formation of ionic aggregates, not isolated F – ions.« less

Anterior chamber angle imaging with swept-source optical coherence tomography: measuring peripheral anterior synechia in glaucoma.

PubMed

Lai, Isabel; Mak, Heather; Lai, Gilda; Yu, Marco; Lam, Dennis S C; Leung, Christopher K S

2013-06-01

To investigate the use of swept-source optical coherence tomography (OCT) for measuring the area and degree of peripheral anterior synechia (PAS) involvement in patients with angle-closure glaucoma. Cross-sectional study. Twenty-three eyes with PAS (detected by indentation gonioscopy) from 20 patients with angle-closure glaucoma (20 eyes had primary angle-closure glaucoma and 3 eyes had angle-closure glaucoma secondary to chronic anterior uveitis [n = 2] and Axenfeld-Rieger syndrome [n = 1]). The anterior chamber angles were evaluated with indentation gonioscopy and imaged by swept-source OCT (Casia OCT, Tomey, Nagoya, Japan) in room light and in the dark using the "angle analysis" protocol, which was composed of 128 radial B-scans each with 512 A-scans (16-mm scan length). The area and degree of PAS involvement were measured in each eye after manual detection of the scleral spur and the anterior irido-angle adhesion by 2 masked observers. The interobserver variability of the PAS measurements was calculated. The agreement of PAS assessment by gonioscopy and OCT, the area and the degree of PAS involvement, and the intraclass correlation coefficient (ICC) of interobserver PAS measurements. The area of PAS (mean ± standard deviation) was 20.8 ± 16.9 mm(2) (range, 3.9-74.9 mm(2)), and the degree of PAS involvement was 186.5 ± 79.9 degrees (range, 42-314 degrees). There was no difference in the area of PAS (P = 0.90) and the degree of PAS involvement (P = 0.95) between images obtained in room light and in the dark. The interobserver ICCs were 0.99 (95% confidence interval [CI], 0.98-1.00) for the area of PAS and 0.99 (95% CI, 0.97-1.00) for the degree of PAS involvement. There was good agreement of PAS assessment between gonioscopy and OCT images (kappa = 0.79; 95% CI, 0.67-0.91). Swept-source OCT allows visualization and reproducible measurements of the area and degree of PAS involvement, providing a new paradigm for evaluation of PAS progression and risk assessment for development of angle-closure glaucoma. The author(s) have no proprietary or commercial interest in any materials discussed in this article. Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

DAC-3 Pointing Stability Analysis Results for SAGE 3 and Other Users of the International Space Station (ISS) Payload Attachment Sites (PAS)

NASA Technical Reports Server (NTRS)

Woods-Vedeler, Jessica A.; Rombado, Gabriel

1997-01-01

The purpose of this paper is to provide final results of a pointing stability analysis for external payload attachment sites (PAS) on the International Space Station (ISS). As a specific example, the pointing stability requirement of the SAGE III atmospheric science instrument was examined in this paper. The instrument requires 10 arcsec stability over 2 second periods. SAGE 3 will be mounted on the ISS starboard side at the lower, outboard FIAS. In this engineering analysis, an open-loop DAC-3 finite element model of ISS was used by the Microgravity Group at Johnson Space Flight Center to generate transient responses at PAS to a limited number of disturbances. The model included dynamics up to 50 Hz. Disturbance models considered included operation of the solar array rotary joints, thermal radiator rotary joints, and control moment gyros. Responses were filtered to model the anticipated vibration attenuation effects of active control systems on the solar and thermal radiator rotary joints. A pointing stability analysis was conducted by double integrating acceleration transient over a 2 second period. Results of the analysis are tabulated for ISS X, Y, and Z Axis rotations. These results indicate that the largest excursions in rotation during pointing occurred due to rapid slewing of the thermal radiator. Even without attenuation at the rotary joints, the resulting pointing error was limited to less than 1.6 arcsec. With vibration control at the joints, to a maximum 0.5 arcsec over a 2 second period. Based on this current level of model definition, it was concluded that between 0 - 50 Hz, the pointing stability requirement for SAGE 3 will not be exceeded by the disturbances evaluated in this study.

Transcription elongation rate has a tissue-specific impact on alternative cleavage and polyadenylation in Drosophila melanogaster.

PubMed

Liu, Xiaochuan; Freitas, Jaime; Zheng, Dinghai; Oliveira, Marta S; Hoque, Mainul; Martins, Torcato; Henriques, Telmo; Tian, Bin; Moreira, Alexandra

2017-12-01

Alternative polyadenylation (APA) is a mechanism that generates multiple mRNA isoforms with different 3'UTRs and/or coding sequences from a single gene. Here, using 3' region extraction and deep sequencing (3'READS), we have systematically mapped cleavage and polyadenylation sites (PASs) in Drosophila melanogaster , expanding the total repertoire of PASs previously identified for the species, especially those located in A-rich genomic sequences. Cis -element analysis revealed distinct sequence motifs around fly PASs when compared to mammalian ones, including the greater enrichment of upstream UAUA elements and the less prominent presence of downstream UGUG elements. We found that over 75% of mRNA genes in Drosophila melanogaster undergo APA. The head tissue tends to use distal PASs when compared to the body, leading to preferential expression of APA isoforms with long 3'UTRs as well as with distal terminal exons. The distance between the APA sites and intron location of PAS are important parameters for APA difference between body and head, suggesting distinct PAS selection contexts. APA analysis of the RpII215 C4 mutant strain, which harbors a mutant RNA polymerase II (RNAPII) with a slower elongation rate, revealed that a 50% decrease in transcriptional elongation rate leads to a mild trend of more usage of proximal, weaker PASs, both in 3'UTRs and in introns, consistent with the "first come, first served" model of APA regulation. However, this trend was not observed in the head, suggesting a different regulatory context in neuronal cells. Together, our data expand the PAS collection for Drosophila melanogaster and reveal a tissue-specific effect of APA regulation by RNAPII elongation rate. © 2017 Liu et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

Novel fragmentation pathways of anionic adducts of steroids formed by electrospray anion attachment involving regioselective attachment, regiospecific decompositions, charge-induced pathways, and ion-dipole complex intermediates.

PubMed

Rannulu, Nalaka S; Cole, Richard B

2012-09-01

The analysis of several bifunctional neutral steroids, 5-α-pregnane diol (5-α-pregnane-3α-20βdiol), estradiol (3,17α-dihydroxy-1,3,5(10)-estratriene), progesterone (4-pregnene-3,20-dione), lupeol (3β-hydroxy-20(29)-lupene), pregnenolone (5-pregnen-3β-ol-20-one), and pregnenolone acetate (5-pregnen-3β-ol-20-one acetate) was accomplished by negative ion electrospray mass spectrometry (ESI-MS) employing adduct formation with various anions: fluoride, bicarbonate, acetate, and chloride. Fluoride yielded higher abundances of anionic adducts and more substantial abundances of deprotonated molecules compared with other investigated anions. Collision-induced dissociation (CID) of precursor [M + anion](-) adducts of these steroids revealed that fluoride adduct [M + F](-) precursors first lose HF to produce [M - H](-) and then undergo consecutive decompositions to yield higher abundances of structurally-informative product ions than the other tested anions. In addition to charge-remote fragmentations, the majority of CID pathways of estradiol are deduced to occur via charge-induced fragmentation. Most interestingly, certain anions exhibit preferential attachment to a specific site on these bifunctional steroid molecules, which we are calling "regioselective anion attachment." Regioselective anion attachment is evidenced by subsequent regiospecific decomposition. Regioselective attachment of fluoride (and acetate) anions to low (and moderate) acidity functional groups of pregnenolone, respectively, is demonstrated using deuterated compounds. Moreover, the formation of unique intermediate ion-dipole complexes leading to novel fragmentation pathways of fluoride adducts of pregnenolone acetate, and bicarbonate adducts of d(4)-pregnenolone, are also discussed.

Novel Fragmentation Pathways of Anionic Adducts of Steroids Formed by Electrospray Anion Attachment Involving Regioselective Attachment, Regiospecific Decompositions, Charge-Induced Pathways, and Ion-Dipole Complex Intermediates

NASA Astrophysics Data System (ADS)

Rannulu, Nalaka S.; Cole, Richard B.

2012-09-01

The analysis of several bifunctional neutral steroids, 5-α-pregnane diol (5-α-pregnane-3α-20βdiol), estradiol (3,17α-dihydroxy-1,3,5(10)-estratriene), progesterone (4-pregnene-3,20-dione), lupeol (3β-hydroxy-20(29)-lupene), pregnenolone (5-pregnen-3β-ol-20-one), and pregnenolone acetate (5-pregnen-3β-ol-20-one acetate) was accomplished by negative ion electrospray mass spectrometry (ESI-MS) employing adduct formation with various anions: fluoride, bicarbonate, acetate, and chloride. Fluoride yielded higher abundances of anionic adducts and more substantial abundances of deprotonated molecules compared with other investigated anions. Collision-induced dissociation (CID) of precursor [M + anion]- adducts of these steroids revealed that fluoride adduct [M + F]- precursors first lose HF to produce [M - H]- and then undergo consecutive decompositions to yield higher abundances of structurally-informative product ions than the other tested anions. In addition to charge-remote fragmentations, the majority of CID pathways of estradiol are deduced to occur via charge-induced fragmentation. Most interestingly, certain anions exhibit preferential attachment to a specific site on these bifunctional steroid molecules, which we are calling "regioselective anion attachment." Regioselective anion attachment is evidenced by subsequent regiospecific decomposition. Regioselective attachment of fluoride (and acetate) anions to low (and moderate) acidity functional groups of pregnenolone, respectively, is demonstrated using deuterated compounds. Moreover, the formation of unique intermediate ion-dipole complexes leading to novel fragmentation pathways of fluoride adducts of pregnenolone acetate, and bicarbonate adducts of d4-pregnenolone, are also discussed.

Determination of the Bridging Ligand in the Active Site of Tyrosinase.

PubMed

Zou, Congming; Huang, Wei; Zhao, Gaokun; Wan, Xiao; Hu, Xiaodong; Jin, Yan; Li, Junying; Liu, Junjun

2017-10-28

Tyrosinase is a type-3 copper enzyme that is widely distributed in plants, fungi, insects, and mammals. Developing high potent inhibitors against tyrosinase is of great interest in diverse fields including tobacco curing, food processing, bio-insecticides development, cosmetic development, and human healthcare-related research. In the crystal structure of Agaricus bisporus mushroom tyrosinase, there is an oxygen atom bridging the two copper ions in the active site. It is unclear whether the identity of this bridging oxygen is a water molecule or a hydroxide anion. In the present study, we theoretically determine the identity of this critical bridging oxygen by performing first-principles hybrid quantum mechanics/molecular mechanics/Poisson-Boltzmann-surface area (QM/MM-PBSA) calculations along with a thermodynamic cycle that aim to improve the accuracy. Our results show that the binding with water molecule is energy favored and the QM/MM-optimized structure is very close to the crystal structure, whereas the binding with hydroxide anions causes the increase of energy and significant structural changes of the active site, indicating that the identity of the bridging oxygen must be a water molecule rather than a hydroxide anion. The different binding behavior between water and hydroxide anions may explain why molecules with a carboxyl group or too many negative charges have lower inhibitory activity. In light of this, the design of high potent active inhibitors against tyrosinase should satisfy both the affinity to the copper ions and the charge neutrality of the entire molecule.

Ion pair and solvation dynamics of [Bmim][BF4 ] + water system.

PubMed

Cascão, João; Silva, Wagner; Ferreira, Ana S D; Cabrita, Eurico J

2018-02-01

In this work, 1-butyl-3-methylimidazolium tetrafluoroborate/water mixtures were analysed over the whole water composition (x w ) in order to study the rotational and translational behaviour of the ions. We employed a multinuclear NMR approach to determine anion/cation/water diffusion coefficients and longitudinal relaxation rates at different water content. In neat ionic liquids (IL), the cation diffuses faster than the anion, and at low x w , anions and cations share almost the same diffusion coefficient, but above a critical water concentration, the anion begins to diffuse faster than the cation. We identified this composition as approximately 10% x w where the ions share the same diffusion coefficient. We found that the water at this composition seems to have a much more dramatic effect in the rotational diffusion of the anion that decreases substantially and approaches that of the anion in the diluted IL. Translational and rotational dynamics of the ions suggest that water is first incorporated in pockets in the nanostructure of the IL allowing the ions to maintain most of the cation/anion interactions present in neat IL but already disrupting some anion/cation interactions due to preferential interaction with the anion. HOESY and NOESY data show that water displays contacts both with the cation and the anion in a positive NOE regime in contrary to the negative regime found for the cation/anion and cation/cation cross-relaxation. This is in accordance with the high relative diffusion coefficient of water and suggests that water molecules can exchange between preferential location sites that allow water to maintain contacts both with the anion and cation. Copyright © 2017 John Wiley & Sons, Ltd.

Factors affecting the conversion of apple polyphenols to phenolic acids and fruit matrix to short-chain fatty acids by human faecal microbiota in vitro.

PubMed

Bazzocco, Sarah; Mattila, Ismo; Guyot, Sylvain; Renard, Catherine M G C; Aura, Anna-Marja

2008-12-01

Proanthocyanidins (PAs) in apples are condensed tannins comprised mostly of (-)-epicatechin units with some terminal (+)-catechins. PAs, especially those having a long chain-length, are absorbed in the upper intestine only to a small extent and are passed to the colon. In the colon they are subjected to microbial metabolism by colonic microbiota. In the present article, the ability of human microbiota to ferment apple PAs is studied. Freeze-dried fruit preparations (apple, enzymatically digested apple, isolated cell-walls, isolated PAs or ciders) from two varieties, Marie Ménard and Avrolles, containing PAs of different chain lengths, were compared. Fermentation studies were performed in an in vitro colon model using human faecal microbiota as an inoculum. The maximal extent of conversion to known microbial metabolites, was observed at late time point for Marie Ménard cider, having short PAs. In this case, the initial dose also contributed to the extent of conversion. Long-chain PAs were able to inhibit the in vitro microbial metabolism of PAs shown as low maxima at early time points. Presence of isolated PAs also suppressed SCFA formation from carbohydrates as compared with that from apple cell wall or faecal suspension without substrates. The low maximal extents at early time points suggest that there is a competition between the inhibitory effect of the PAs on microbial activity, and the ability to convert PAs by the microbiota.

Measuring Individual Differences in the Perfect Automation Schema.

PubMed

Merritt, Stephanie M; Unnerstall, Jennifer L; Lee, Deborah; Huber, Kelli

2015-08-01

A self-report measure of the perfect automation schema (PAS) is developed and tested. Researchers have hypothesized that the extent to which users possess a PAS is associated with greater decreases in trust after users encounter automation errors. However, no measure of the PAS currently exists. We developed a self-report measure assessing two proposed PAS factors: high expectations and all-or-none thinking about automation performance. In two studies, participants responded to our PAS measure, interacted with imperfect automated aids, and reported trust. Each of the two PAS measure factors demonstrated fit to the hypothesized factor structure and convergent and discriminant validity when compared with propensity to trust machines and trust in a specific aid. However, the high expectations and all-or-none thinking scales showed low intercorrelations and differential relationships with outcomes, suggesting that they might best be considered two separate constructs rather than two subfactors of the PAS. All-or-none thinking had significant associations with decreases in trust following aid errors, whereas high expectations did not. Results therefore suggest that the all-or-none thinking scale may best represent the PAS construct. Our PAS measure (specifically, the all-or-none thinking scale) significantly predicted the severe trust decreases thought to be associated with high PAS. Further, it demonstrated acceptable psychometric properties across two samples. This measure may be used in future work to assess levels of PAS in users of automated systems in either research or applied settings. © 2015, Human Factors and Ergonomics Society.

Solvation of the fluorine containing anions and their lithium salts in propylene carbonate and dimethoxyethane.

PubMed

Chaban, Vitaly

2015-07-01

Electrolyte solutions based on the propylene carbonate (PC)-dimethoxyethane (DME) mixtures are of significant importance and urgency due to emergence of lithium-ion batteries. Solvation and coordination of the lithium cation in these systems have been recently attended in detail. However, analogous information concerning anions (tetrafluoroborate, hexafluorophosphate) is still missed. This work reports PM7-MD simulations (electronic-structure level of description) to include finite-temperature effects on the anion solvation regularities in the PC-DME mixture. The reported result evidences that the anions appear weakly solvated. This observation is linked to the absence of suitable coordination sites in the solvent molecules. In the concentrated electrolyte solutions, both BF4(-) and PF6(-) prefer to exist as neutral ion pairs (LiBF4, LiPF6).

Anion Binding to Hydrophobic Concavity is Central to the Salting-in Effects of Hofmeister Chaotropes

PubMed Central

Gibb, Corinne L. D.; Gibb, Bruce C.

2011-01-01

For over 120 years it has been appreciated that certain salts (kosmotropes) cause the precipitation of proteins, whilst others (chaotropes) increase their solubility. The cause of this, “Hofmeister effect” is still unclear; especially with the original concept that kosmotropic anions “make” water structure and chaotropes “break” it being countered by recent studies suggesting otherwise. Here, we present the first direct evidence that chaotropic anions have an affinity for hydrophobic concavity, and that it is competition between a convex hydrophobe and the anion for a binding site that leads to the apparent weakening of the hydrophobic effect by chaotropes. In combination, these results suggest that chaotropes primarily induce protein solubilization by direct binding to concavity in the molten globule state of a protein. PMID:21524086

Spectroscopy and computational studies on the interaction of octyl, dodecyl, and hexadecyl derivatives of anionic and cationic surfactants with adenosine deaminase.

PubMed

Ajloo, Davood; Mahmoodabadi, Najmeh; Ghadamgahi, Maryam; Saboury, Ali Akbar

2016-07-01

Effects of sodium (octyl, dodecyl, hexadecyl) sulfate and their cationic analogous on the structure of adenosine deaminase (ADA) were investigated by fluorescence and circular dichroism spectroscopy as well as molecular dynamics simulation and docking calculation. Root-mean-square derivations, radius of gyration, solvent accessible surface area, and radial distribution function were obtained. The results showed that anionic and cationic surfactants reduce protein stability. Cationic surfactants have more effect on the ADA structure in comparison with anionic surfactants. More concentration and longer surfactants are parallel to higher denaturation. Furthermore, aggregation in the presence of anionic surfactants is more than cationic surfactants. Docking data showed that longer surfactants have more interaction energy and smaller ones bound to the active site.

Conformational Preference of ‘CαNN’ Short Peptide Motif towards Recognition of Anions

PubMed Central

Banerjee, Raja

2013-01-01

Among several ‘anion binding motifs’, the recently described ‘CαNN’ motif occurring in the loop regions preceding a helix, is conserved through evolution both in sequence and its conformation. To establish the significance of the conserved sequence and their intrinsic affinity for anions, a series of peptides containing the naturally occurring ‘CαNN’ motif at the N-terminus of a designed helix, have been modeled and studied in a context free system using computational techniques. Appearance of a single interacting site with negative binding free-energy for both the sulfate and phosphate ions, as evidenced in docking experiments, establishes that the ‘CαNN’ segment has an intrinsic affinity for anions. Molecular Dynamics (MD) simulation studies reveal that interaction with anion triggers a conformational switch from non-helical to helical state at the ‘CαNN’ segment, which extends the length of the anchoring-helix by one turn at the N-terminus. Computational experiments substantiate the significance of sequence/structural context and justify the conserved nature of the ‘CαNN’ sequence for anion recognition through “local” interaction. PMID:23516403

Cache domains that are homologous to, but different from PAS domains comprise the largest superfamily of extracellular sensors in prokaryotes

DOE PAGES

Upadhyay, Amit A.; Fleetwood, Aaron D.; Adebali, Ogun; ...

2016-04-06

Cellular receptors usually contain a designated sensory domain that recognizes the signal. Per/Arnt/Sim (PAS) domains are ubiquitous sensors in thousands of species ranging from bacteria to humans. Although PAS domains were described as intracellular sensors, recent structural studies revealed PAS-like domains in extracytoplasmic regions in several transmembrane receptors. However, these structurally defined extracellular PAS-like domains do not match sequence-derived PAS domain models, and thus their distribution across the genomic landscape remains largely unknown. Here we show that structurally defined extracellular PAS-like domains belong to the Cache superfamily, which is homologous to, but distinct from the PAS superfamily. Our newly builtmore » computational models enabled identification of Cache domains in tens of thousands of signal transduction proteins including those from important pathogens and model organisms.Moreover, we show that Cache domains comprise the dominant mode of extracellular sensing in prokaryotes.« less

Cache domains that are homologous to, but different from PAS domains comprise the largest superfamily of extracellular sensors in prokaryotes

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

Upadhyay, Amit A.; Fleetwood, Aaron D.; Adebali, Ogun

Cellular receptors usually contain a designated sensory domain that recognizes the signal. Per/Arnt/Sim (PAS) domains are ubiquitous sensors in thousands of species ranging from bacteria to humans. Although PAS domains were described as intracellular sensors, recent structural studies revealed PAS-like domains in extracytoplasmic regions in several transmembrane receptors. However, these structurally defined extracellular PAS-like domains do not match sequence-derived PAS domain models, and thus their distribution across the genomic landscape remains largely unknown. Here we show that structurally defined extracellular PAS-like domains belong to the Cache superfamily, which is homologous to, but distinct from the PAS superfamily. Our newly builtmore » computational models enabled identification of Cache domains in tens of thousands of signal transduction proteins including those from important pathogens and model organisms.Moreover, we show that Cache domains comprise the dominant mode of extracellular sensing in prokaryotes.« less

Context-dependent modulation of Pol II CTD phosphatase SSUP-72 regulates alternative polyadenylation in neuronal development

PubMed Central

Chen, Fei; Zhou, Yu; Qi, Yingchuan B.; Khivansara, Vishal; Li, Hairi; Chun, Sang Young; Kim, John K.; Fu, Xiang-Dong; Jin, Yishi

2015-01-01

Alternative polyadenylation (APA) is widespread in neuronal development and activity-mediated neural plasticity. However, the underlying molecular mechanisms are largely unknown. We used systematic genetic studies and genome-wide surveys of the transcriptional landscape to identify a context-dependent regulatory pathway controlling APA in the Caenorhabditis elegans nervous system. Loss of function in ssup-72, a Ser5 phosphatase for the RNA polymerase II (Pol II) C-terminal domain (CTD), dampens transcription termination at a strong intronic polyadenylation site (PAS) in unc-44/ankyrin yet promotes termination at the weak intronic PAS of the MAP kinase dlk-1. A nuclear protein, SYDN-1, which regulates neuronal development, antagonizes the function of SSUP-72 and several nuclear polyadenylation factors. This regulatory pathway allows the production of a neuron-specific isoform of unc-44 and an inhibitory isoform of dlk-1. Dysregulation of the unc-44 and dlk-1 mRNA isoforms in sydn-1 mutants impairs neuronal development. Deleting the intronic PAS of unc-44 results in increased pre-mRNA processing of neuronal ankyrin and suppresses sydn-1 mutants. These results reveal a mechanism by which regulation of CTD phosphorylation controls coding region APA in the nervous system. PMID:26588990

The dynamic Atg13-free conformation of the Atg1 EAT domain is required for phagophore expansion.

PubMed

Lin, Mary G; Schöneberg, Johannes; Davies, Christopher W; Ren, Xuefeng; Hurley, James H

2018-05-15

Yeast macroautophagy begins with the de novo formation of a double-membrane phagophore at the preautophagosomal structure/phagophore assembly site (PAS), followed by its expansion into the autophagosome responsible for cargo engulfment. The kinase Atg1 is recruited to the PAS by Atg13 through interactions between the EAT domain of the former and the tMIM motif of the latter. Mass-spectrometry data have shown that, in the absence of Atg13, the EAT domain structure is strikingly dynamic, but the function of this Atg13-free dynamic state has been unclear. We used structure-based mutational analysis and quantitative and superresolution microscopy to show that Atg1 is present on autophagic puncta at, on average, twice the stoichiometry of Atg13. Moreover, Atg1 colocalizes with the expanding autophagosome in a manner dependent on Atg8 but not Atg13. We used isothermal titration calorimetry and crystal structure information to design an EAT domain mutant allele ATG1 DD that selectively perturbs the function of the Atg13-free state. Atg1 DD shows reduced PAS formation and does not support phagophore expansion, showing that the EAT domain has an essential function that is separate from its Atg13-dependent role in autophagy initiation.

Molecular Evolution of Slow and Quick Anion Channels (SLACs and QUACs/ALMTs)

PubMed Central

Dreyer, Ingo; Gomez-Porras, Judith Lucia; Riaño-Pachón, Diego Mauricio; Hedrich, Rainer; Geiger, Dietmar

2012-01-01

Electrophysiological analyses conducted about 25 years ago detected two types of anion channels in the plasma membrane of guard cells. One type of channel responds slowly to changes in membrane voltage while the other responds quickly. Consequently, they were named SLAC, for SLow Anion Channel, and QUAC, for QUick Anion Channel. Recently, genes SLAC1 and QUAC1/ALMT12, underlying the two different anion current components, could be identified in the model plant Arabidopsis thaliana. Expression of the gene products in Xenopus oocytes confirmed the quick and slow current kinetics. In this study we provide an overview on our current knowledge on slow and quick anion channels in plants and analyze the molecular evolution of ALMT/QUAC-like and SLAC-like channels. We discovered fingerprints that allow screening databases for these channel types and were able to identify 192 (177 non-redundant) SLAC-like and 422 (402 non-redundant) ALMT/QUAC-like proteins in the fully sequenced genomes of 32 plant species. Phylogenetic analyses provided new insights into the molecular evolution of these channel types. We also combined sequence alignment and clustering with predictions of protein features, leading to the identification of known conserved phosphorylation sites in SLAC1-like channels along with potential sites that have not been yet experimentally confirmed. Using a similar strategy to analyze the hydropathicity of ALMT/QUAC-like channels, we propose a modified topology with additional transmembrane regions that integrates structure and function of these membrane proteins. Our results suggest that cross-referencing phylogenetic analyses with position-specific protein properties and functional data could be a very powerful tool for genome research approaches in general. PMID:23226151

Molecular Evolution of Slow and Quick Anion Channels (SLACs and QUACs/ALMTs).

PubMed

Dreyer, Ingo; Gomez-Porras, Judith Lucia; Riaño-Pachón, Diego Mauricio; Hedrich, Rainer; Geiger, Dietmar

2012-01-01

Electrophysiological analyses conducted about 25 years ago detected two types of anion channels in the plasma membrane of guard cells. One type of channel responds slowly to changes in membrane voltage while the other responds quickly. Consequently, they were named SLAC, for SLow Anion Channel, and QUAC, for QUick Anion Channel. Recently, genes SLAC1 and QUAC1/ALMT12, underlying the two different anion current components, could be identified in the model plant Arabidopsis thaliana. Expression of the gene products in Xenopus oocytes confirmed the quick and slow current kinetics. In this study we provide an overview on our current knowledge on slow and quick anion channels in plants and analyze the molecular evolution of ALMT/QUAC-like and SLAC-like channels. We discovered fingerprints that allow screening databases for these channel types and were able to identify 192 (177 non-redundant) SLAC-like and 422 (402 non-redundant) ALMT/QUAC-like proteins in the fully sequenced genomes of 32 plant species. Phylogenetic analyses provided new insights into the molecular evolution of these channel types. We also combined sequence alignment and clustering with predictions of protein features, leading to the identification of known conserved phosphorylation sites in SLAC1-like channels along with potential sites that have not been yet experimentally confirmed. Using a similar strategy to analyze the hydropathicity of ALMT/QUAC-like channels, we propose a modified topology with additional transmembrane regions that integrates structure and function of these membrane proteins. Our results suggest that cross-referencing phylogenetic analyses with position-specific protein properties and functional data could be a very powerful tool for genome research approaches in general.

A history of US Army PAs.

PubMed

Chalupa, Robyn L; Marble, W Sanders

2017-11-01

The US military has a long tradition of using physician assistants (PAs). The Army began using PAs in 1971 in an effort to supplement the physicians and surgeons in the medical corps. As their numbers grew, PAs gradually replaced general medical officers assigned to battalions. Later, specialty positions developed in aviation medicine, orthopedics, and emergency medicine. The need for a PA serving as an adviser in the major commands slowly developed at all levels of leadership. In 2015, the Army removed limitations on female PAs assigned to combat units. PAs lead in tactical and clinical settings, filling command roles, senior clinical positions, and administrative leadership roles.

Panic attacks and hoarding disorder: an initial investigation.

PubMed

Raines, Amanda M; Oglesby, Mary E; Short, Nicole A; Albanese, Brian J; Schmidt, Norman B

2014-08-01

Panic attacks (PAs) defined as a discrete period of intense fear or discomfort, occur in the context of numerous anxiety and mood related disorders. Research has suggested that PAs serve as a significant indicator and prognostic factor for overall symptom severity, course, and comorbidity within various conditions. Consequently, a PA specifier is now applicable to all DSM-5 disorders. Despite these clinical and nosological implications, no research to date has examined associations between PAs and hoarding disorder. The current investigation evaluated relationships between PA endorsement and hoarding severity within a sample of 32 patients with hoarding disorder. Findings suggested a high rate of panic history among those with hoarding disorder (56%). Hoarders with co-occurring PAs, compared to those without PAs, evidenced significantly higher symptom severity. Moreover, PAs continued to significantly predict hoarding severity even after controlling for relevant covariates. When examining the specific relationships among PAs and hoarding symptoms (i.e., acquiring, difficulty discarding, and clutter), the endorsement of PAs was associated with increased acquiring and difficulty discarding symptoms. These findings add considerably to a growing body of literature on hoarding disorder. Implications for the assessment and treatment of PAs that co-occur with hoarding disorder are discussed. Copyright © 2014 Elsevier Inc. All rights reserved.

A novel ultra-performance liquid chromatography hyphenated with quadrupole time of flight mass spectrometry method for rapid estimation of total toxic retronecine-type of pyrrolizidine alkaloids in herbs without requiring corresponding standards.

PubMed

Zhu, Lin; Ruan, Jian-Qing; Li, Na; Fu, Peter P; Ye, Yang; Lin, Ge

2016-03-01

Nearly 50% of naturally-occurring pyrrolizidine alkaloids (PAs) are hepatotoxic, and the majority of hepatotoxic PAs are retronecine-type PAs (RET-PAs). However, quantitative measurement of PAs in herbs/foodstuffs is often difficult because most of reference PAs are unavailable. In this study, a rapid, selective, and sensitive UHPLC-QTOF-MS method was developed for the estimation of RET-PAs in herbs without requiring corresponding standards. This method is based on our previously established characteristic and diagnostic mass fragmentation patterns and the use of retrorsine for calibration. The use of a single RET-PA (i.e. retrorsine) for construction of calibration was based on high similarities with no significant differences demonstrated by the calibration curves constructed by peak areas of extract ion chromatograms of fragment ion at m/z 120.0813 or 138.0919 versus concentrations of five representative RET-PAs. The developed method was successfully applied to measure a total content of toxic RET-PAs of diversified structures in fifteen potential PA-containing herbs. Copyright © 2014 Elsevier Ltd. All rights reserved.

Reductive evolution and the loss of PDC/PAS domains from the genus Staphylococcus

PubMed Central

2013-01-01

Background The Per-Arnt-Sim (PAS) domain represents a ubiquitous structural fold that is involved in bacterial sensing and adaptation systems, including several virulence related functions. Although PAS domains and the subclass of PhoQ-DcuS-CitA (PDC) domains have a common structure, there is limited amino acid sequence similarity. To gain greater insight into the evolution of PDC/PAS domains present in the bacterial kingdom and staphylococci in specific, the PDC/PAS domains from the genomic sequences of 48 bacteria, representing 5 phyla, were identified using the sensitive search method based on HMM-to-HMM comparisons (HHblits). Results A total of 1,007 PAS domains and 686 PDC domains distributed over 1,174 proteins were identified. For 28 Gram-positive bacteria, the distribution, organization, and molecular evolution of PDC/PAS domains were analyzed in greater detail, with a special emphasis on the genus Staphylococcus. Compared to other bacteria the staphylococci have relatively fewer proteins (6–9) containing PDC/PAS domains. As a general rule, the staphylococcal genomes examined in this study contain a core group of seven PDC/PAS domain-containing proteins consisting of WalK, SrrB, PhoR, ArlS, HssS, NreB, and GdpP. The exceptions to this rule are: 1) S. saprophyticus lacks the core NreB protein; 2) S. carnosus has two additional PAS domain containing proteins; 3) S. epidermidis, S. aureus, and S. pseudintermedius have an additional protein with two PDC domains that is predicted to code for a sensor histidine kinase; 4) S. lugdunensis has an additional PDC containing protein predicted to be a sensor histidine kinase. Conclusions This comprehensive analysis demonstrates that variation in PDC/PAS domains among bacteria has limited correlations to the genome size or pathogenicity; however, our analysis established that bacteria having a motile phase in their life cycle have significantly more PDC/PAS-containing proteins. In addition, our analysis revealed a tremendous amount of variation in the number of PDC/PAS-containing proteins within genera. This variation extended to the Staphylococcus genus, which had between 6 and 9 PDC/PAS proteins and some of these appear to be previously undescribed signaling proteins. This latter point is important because most staphylococcal proteins that contain PDC/PAS domains regulate virulence factor synthesis or antibiotic resistance. PMID:23902280

Reductive evolution and the loss of PDC/PAS domains from the genus Staphylococcus.

PubMed

Shah, Neethu; Gaupp, Rosmarie; Moriyama, Hideaki; Eskridge, Kent M; Moriyama, Etsuko N; Somerville, Greg A

2013-07-31

The Per-Arnt-Sim (PAS) domain represents a ubiquitous structural fold that is involved in bacterial sensing and adaptation systems, including several virulence related functions. Although PAS domains and the subclass of PhoQ-DcuS-CitA (PDC) domains have a common structure, there is limited amino acid sequence similarity. To gain greater insight into the evolution of PDC/PAS domains present in the bacterial kingdom and staphylococci in specific, the PDC/PAS domains from the genomic sequences of 48 bacteria, representing 5 phyla, were identified using the sensitive search method based on HMM-to-HMM comparisons (HHblits). A total of 1,007 PAS domains and 686 PDC domains distributed over 1,174 proteins were identified. For 28 Gram-positive bacteria, the distribution, organization, and molecular evolution of PDC/PAS domains were analyzed in greater detail, with a special emphasis on the genus Staphylococcus. Compared to other bacteria the staphylococci have relatively fewer proteins (6-9) containing PDC/PAS domains. As a general rule, the staphylococcal genomes examined in this study contain a core group of seven PDC/PAS domain-containing proteins consisting of WalK, SrrB, PhoR, ArlS, HssS, NreB, and GdpP. The exceptions to this rule are: 1) S. saprophyticus lacks the core NreB protein; 2) S. carnosus has two additional PAS domain containing proteins; 3) S. epidermidis, S. aureus, and S. pseudintermedius have an additional protein with two PDC domains that is predicted to code for a sensor histidine kinase; 4) S. lugdunensis has an additional PDC containing protein predicted to be a sensor histidine kinase. This comprehensive analysis demonstrates that variation in PDC/PAS domains among bacteria has limited correlations to the genome size or pathogenicity; however, our analysis established that bacteria having a motile phase in their life cycle have significantly more PDC/PAS-containing proteins. In addition, our analysis revealed a tremendous amount of variation in the number of PDC/PAS-containing proteins within genera. This variation extended to the Staphylococcus genus, which had between 6 and 9 PDC/PAS proteins and some of these appear to be previously undescribed signaling proteins. This latter point is important because most staphylococcal proteins that contain PDC/PAS domains regulate virulence factor synthesis or antibiotic resistance.

The practice of euthanasia and physician-assisted suicide in the United States: adherence to proposed safeguards and effects on physicians.

PubMed

Emanuel, E J; Daniels, E R; Fairclough, D L; Clarridge, B R

1998-08-12

Despite intense debates about legalization, there are few data examining the details of actual euthanasia and physician-assisted suicide (PAS) cases in the United States. To determine whether the practices of euthanasia and PAS are consistent with proposed safeguards and the effect on physicians of having performed euthanasia or PAS. Structured in-depth telephone interviews. Randomly selected oncologists in the United States. Adherence to primary and secondary safeguards for the practice of euthanasia and PAS; regret, comfort, and fear of prosecution from performing euthanasia or PAS. A total of 355 oncologists (72.6% response rate) were interviewed on euthanasia and PAS. On 2 screening questions, 56 oncologists (15.8%) reported participating in euthanasia or PAS; 53 oncologists (94.6% response rate) participated in in-depth interviews. Thirty-eight of 53 oncologists described clearly defined cases of euthanasia or PAS. Twenty-three patients (60.5%) both initiated and repeated their request for euthanasia or PAS, but 6 patients (15.8%) did not participate in the decision for euthanasia or PAS. Thirty-seven patients (97.4%) were experiencing unremitting pain or such poor physical functioning they could not perform self-care. Physicians sought consultation in 15 cases (39.5%). Overall, oncologists adhered to all 3 main safeguards in 13 cases (34.2%): (1) having the patient initiate and repeat the request for euthanasia or PAS, (2) ensuring the patient was experiencing extreme physical pain or suffering, and (3) consulting with a colleague. Those who adhered to the safeguards had known their patients longer and tended to be more religious. In 28 cases (73.7%), the family supported the decision. In all cases of pain, patients were receiving narcotic analgesia. Fifteen patients (39.5%) were enrolled in a hospice. While 19 oncologists (52.6%) received comfort from having helped a patient with euthanasia or PAS, 9 (23.7%) regretted having performed euthanasia or PAS, and 15 (39.5%) feared prosecution. Intractable pain or poor physical functioning seem to be nearly absolute requirements for physicians to perform euthanasia or PAS. Only one third of cases are performed consistently with proposed safeguards. For some patients, end-of-life care that includes opioid analgesia and hospice care does not obviate their desire for euthanasia or PAS. While the majority of physicians seem comforted by their actions, some experience adverse consequences from having performed euthanasia or PAS.

Anion ordering, magnetic structure and properties of the vacancy ordered perovskite Ba{sub 3}Fe{sub 3}O{sub 7}F

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

Clemens, Oliver, E-mail: oliver.clemens@nano.tu-darmstadt.de; Karlsruher Institut für Technologie, Institut für Nanotechnologie, Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen; University of Birmingham, School of Chemistry, Birmingham B152TT

2016-11-15

This article describes a detailed investigation of the crystallographic and magnetic structure of perovskite type Ba{sub 3}Fe{sub 3}O{sub 7}F by a combined analysis of X-ray and neutron powder diffraction data. Complete ordering of vacancies within the perovskite lattice could be confirmed. In addition, the structure of the anion sublattice was studied by means of the valence bond method, which suggested partial ordering of the fluoride ions on two of the six crystallographically different anion sites. Moreover, the compound was found to show G-type antiferromagnetic ordering of Fe moments, in agreement with magnetometric measurements as well as previously recorded {sup 57}Femore » Mössbauer spectroscopy data. - Graphical abstract: The vacancy and anion ordered structure of Ba{sub 3}Fe{sub 3}O{sub 7}F is described together with its magnetic properties. - Highlights: • Ba{sub 3}Fe{sub 3}O{sub 7}F possesses a unique vacancy order not found for other perovskite type compounds. • The valence bond method was used to locate oxide and fluoride ions. • Fluoride ions are distributed only on two of the six anion sites in Ba{sub 3}Fe{sub 3}O{sub 7}F. • The compound shows G-type antiferromagnetic ordering of magnetic moments. • The magnetic structure could be refined in one of the maximal magnetic subgroups of the nuclear structure.« less

Pu Anion Exchange Process Intensification

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

Taylor-Pashow, Kathryn M. L.

This research is focused on improving the efficiency of the anion exchange process for purifying plutonium. While initially focused on plutonium, the technology could also be applied to other ion-exchange processes. Work in FY17 focused on the improvement and optimization of porous foam columns that were initially developed in FY16. These foam columns were surface functionalized with poly(4-vinylpyridine) (PVP) to provide the Pu specific anion-exchange sites. Two different polymerization methods were explored for maximizing the surface functionalization with the PVP. The open-celled polymeric foams have large open pores and large surface areas available for sorption. The fluid passes through themore » large open pores of this material, allowing convection to be the dominant mechanism by which mass transport takes place. These materials generally have very low densities, open-celled structures with high cell interconnectivity, small cell sizes, uniform cell size distributions, and high structural integrity. These porous foam columns provide advantages over the typical porous resin beads by eliminating the slow diffusion through resin beads, making the anion-exchange sites easily accessible on the foam surfaces. The best performing samples exceeded the Pu capacity of the commercially available resin, and also offered the advantage of sharper elution profiles, resulting in a more concentrated product, with less loss of material to the dilute heads and tails cuts. An alternate approach to improving the efficiency of this process was also explored through the development of a microchannel array system for performing the anion exchange.« less

Exterior Site Occupancy Infers Chloride-Induced Proton Gating in a Prokaryotic Homolog of the ClC Chloride Channel

PubMed Central

Bostick, David L.; Berkowitz, Max L.

2004-01-01

The ClC family of anion channels mediates the efficient, selective permeation of Cl− across the biological membranes of living cells under the driving force of an electrochemical gradient. In some eukaryotes, these channels are known to exhibit a unique gating mechanism, which appears to be triggered by the permeant Cl− anion. We infer details of this gating mechanism by studying the free energetics of Cl− occupancy in the pore of a prokaryotic ClC homolog. These free energetics were gleaned from 30 ns of molecular dynamics simulation on an ∼133,000-atom system consisting of a hydrated membrane embedded StClC transporter. The binding sites for Cl− in the transporter were determined for the cases where the putative gating residue, Glu148, was protonated and unprotonated. When the glutamate gate is protonated, Cl− favorably occupies an exterior site, Sext, to form a queue of anions in the pore. However, when the glutamate gate is unprotonated, Cl− cannot occupy this site nor, consequently, pass through the pore. An additional, previously undetected, site was found in the pore near the outer membrane that exists regardless of the protonation state of Glu148. Although this suggests that, for the prokaryotic homolog, protonation of Glu148 may be the first step in transporting Cl− at the expense of H+ transport in the opposite direction, an evolutionary argument might suggest that Cl− opens the ClC gate in eukaryotic channels by inducing the conserved glutamate's protonation. During an additional 20 ns free dynamics simulation, the newly discovered outermost site, Sout, and the innermost site, Sint, were seen to allow spontaneous exchange of Cl− ions with the bulk electrolyte while under depolarization conditions. PMID:15345547

Effects of Anticholinesterases on Catalysis and Induced Conformational Change of the Peripheral Anionic Site of Murine Acetylcholinesterase

PubMed Central

Tong, Fan; Islam, Rafique M.; Carlier, Paul R.; Ma, Ming; Ekström, Fredrik; Bloomquist, Jeffrey R.

2013-01-01

Conventional insecticides targeting acetylcholinesterase (AChE) typically show high mammalian toxicities and because there is resistance to these compounds in many insect species, alternatives to established AChE inhibitors used for pest control are needed. Here we used a fluorescence method to monitor interactions between various AChE inhibitors and the AChE peripheral anionic site, which is a novel target for new insecticides acting on this enzyme. The assay uses thioflavin-T as a probe, which binds to the peripheral anionic site of AChE and yields an increase in fluorescent signal. Three types of AChE inhibitors were studied: catalytic site inhibitors (carbamate insecticides, edrophonium, and benzylpiperidine), peripheral site inhibitors (tubocurarine, ethidium bromide, and propidium iodide), and bivalent inhibitors (donepezil, BW284C51, and a series of bis(n)-tacrines). All were screened on murine AChE to compare and contrast changes of peripheral site conformation in the TFT assay with catalytic inhibition. All the inhibitors reduced thioflavin-T fluorescence in a concentration-dependent manner with potencies (IC50) ranging from 8 nM for bis(6)-tacrine to 159 μM for benzylpiperidine. Potencies in the fluorescence assay were correlated well with their potencies for enzyme inhibition (R2 = 0.884). Efficacies for reducing thioflavin-T fluorescence ranged from 23–36% for catalytic site inhibitors and tubocurarine to near 100% for ethidium bromide and propidium iodide. Maximal efficacies could be reconciled with known mechanisms of interaction of the inhibitors with AChE. When extended to pest species, we anticipate these findings will assist in the discovery and development of novel, selective bivalent insecticides acting on AChE. PMID:24003261

Anion capture and sensing with cationic boranes: on the synergy of Coulombic effects and onium ion-centred Lewis acidity.

PubMed

Zhao, Haiyan; Leamer, Lauren A; Gabbaï, François P

2013-06-21

Stimulated by the growing importance and recognized toxicity of anions such as fluoride, cyanide and azides, we have, in the past few years, developed a family of Lewis acidic triarylboranes that can be used for the complexation of these anions in organic and protic solvents, including water. A central aspect of our approach lies in the decoration of the boranes with peripheral ammonium, phosphonium, sulfonium stibonium or telluronium groups. The presence of these cationic groups provides a Coulombic drive for the capture of the anion, leading to boranes that can be used in aqueous solutions where anion hydration and/or protonation are usually competitive. The anion affinity of these boranes can be markedly enhanced by narrowing the separation between the anion binding site (i.e. the boron atom) and the onium ion. In such systems, the latent Lewis acidity of the onium ion also plays a role as manifested by the formation of B-X→E (E = P, S, Sb, or Te; X = F, CN or N3) chelate motifs that provide additional stability to the resulting complexes. These effects, which are maximum in stibonium and telluronium boranes, show that the Lewis acidity of heavy onium ions can be exploited for anion coordination and capture. The significance of these advances is illustrated by the development of applications in anion sensing, fluorination chemistry and (18)F radiolabeling for positron emission tomography.

Alpha-Synuclein Pathology in Sensory Nerve Terminals of the Upper Aerodigestive Tract of Parkinson’s Disease Patients

PubMed Central

Mu, Liancai; Chen, Jingming; Sobotka, Stanislaw; Nyirenda, Themba; Benson, Brian; Gupta, Fiona; Sanders, Ira; Adler, Charles H.; Caviness, John N.; Shill, Holly A.; Sabbagh, Marwan; Samanta, Johan E.; Sue, Lucia I.; Beach, Thomas G.

2015-01-01

Dysphagia is common in Parkinson’s disease (PD) and causes significant morbidity and mortality. PD dysphagia has usually been explained as dysfunction of central motor control, much like other motor symptoms that are characteristic of the disease. However, PD dysphagia does not correlate with severity of motor symptoms nor does it respond to motor therapies. It is known that PD patients have sensory deficits in the pharynx, and that impaired sensation may contribute to dysphagia. However, the underlying cause of the pharyngeal sensory deficits in PD is not known. We hypothesized that PD dysphagia with sensory deficits may be due to degeneration of the sensory nerve terminals in the upper aerodigestive tract (UAT). We have previously shown that Lewy-type synucleinopathy (LTS) is present in the main pharyngeal sensory nerves of PD patients, but not in controls. In this study, the sensory terminals in UAT mucosa were studied to discern the presence and distribution of LTS. Whole-mount specimens (tongue-pharynx-larynx-upper esophagus) were obtained from 10 deceased human subjects with clinically diagnosed and neuropathologically confirmed PD (five with dysphagia and five without) and four age-matched healthy controls. Samples were taken from six sites and immunostained for phosphorylated α-synuclein (PAS). The results showed the presence of PAS-immunoreactive (PAS-ir) axons in all the PD subjects and in none of the controls. Notably, PD patients with dysphagia had more PAS-ir axons in the regions that are critical for initiating the swallowing reflex. These findings suggest that Lewy pathology affects mucosal sensory axons in specific regions of the UAT and may be related to PD dysphagia. PMID:26041249

Alpha-Synuclein Pathology in Sensory Nerve Terminals of the Upper Aerodigestive Tract of Parkinson's Disease Patients.

PubMed

Mu, Liancai; Chen, Jingming; Sobotka, Stanislaw; Nyirenda, Themba; Benson, Brian; Gupta, Fiona; Sanders, Ira; Adler, Charles H; Caviness, John N; Shill, Holly A; Sabbagh, Marwan; Samanta, Johan E; Sue, Lucia I; Beach, Thomas G

2015-08-01

Dysphagia is common in Parkinson's disease (PD) and causes significant morbidity and mortality. PD dysphagia has usually been explained as dysfunction of central motor control, much like other motor symptoms that are characteristic of the disease. However, PD dysphagia does not correlate with severity of motor symptoms nor does it respond to motor therapies. It is known that PD patients have sensory deficits in the pharynx, and that impaired sensation may contribute to dysphagia. However, the underlying cause of the pharyngeal sensory deficits in PD is not known. We hypothesized that PD dysphagia with sensory deficits may be due to degeneration of the sensory nerve terminals in the upper aerodigestive tract (UAT). We have previously shown that Lewy-type synucleinopathy (LTS) is present in the main pharyngeal sensory nerves of PD patients, but not in controls. In this study, the sensory terminals in UAT mucosa were studied to discern the presence and distribution of LTS. Whole-mount specimens (tongue-pharynx-larynx-upper esophagus) were obtained from 10 deceased human subjects with clinically diagnosed and neuropathologically confirmed PD (five with dysphagia and five without) and four age-matched healthy controls. Samples were taken from six sites and immunostained for phosphorylated α-synuclein (PAS). The results showed the presence of PAS-immunoreactive (PAS-ir) axons in all the PD subjects and in none of the controls. Notably, PD patients with dysphagia had more PAS-ir axons in the regions that are critical for initiating the swallowing reflex. These findings suggest that Lewy pathology affects mucosal sensory axons in specific regions of the UAT and may be related to PD dysphagia.

Studies of protonated and anionic artemisinin in the gas-phase by infrared multi-photon dissociation and by negative ion photoelectron spectroscopies

NASA Astrophysics Data System (ADS)

Seydou, M.; Gillet, J. C.; Li, X.; Wang, H.; Posner, G. H.; Grégoire, G.; Schermann, J. P.; Bowen, K. H.; Desfrançois, C.

2007-12-01

Protonated and anionic artemisinin in the gas phase have respectively been studied by infrared multi-photon dissociation (IRMPD) spectroscopy and by anion photoelectron spectroscopy. Comparison of the measured IRMPD spectrum with calculated spectra of various conformations showed that the two lowest-energy protonated structures, both corresponding to protonation at the C dbnd O 14 carbonyl site, were observed experimentally. The calculations also indicated that the peroxide bridge in artemisinin is only slightly modified by protonation. Additionally, stable, intact (parent) artemisinin radical anions have been obtained for the first time in the gas phase and the photoelectron spectrum supports the computational finding that the excess electron is mainly localized on the σ ∗ orbital of the peroxide bond. The vertical detachment energy and adiabatic electron affinity, calculated at the MP2/6-31+G ∗ level, are in good agreement with the experimental data and the O-O distance is calculated to be stretched by more than 50% in the anion.

The tautomerization between keto- to phenol-hydrazone induced by anions in the solution

NASA Astrophysics Data System (ADS)

Shang, Xuefang; Yuan, Jianmei; Wang, Yingling; Zhang, Jinlian; Xu, Xiufang

2012-02-01

Two simple anion receptors, 2-[(2-hydroxy-5-nitrophenyl)methylene]hydrazone (1) and 2-[(3,5-dibromo-2-hydroxyphenyl)methylene]hydrazone (2) with -OH binding sites, were synthesized and characterized. The anion binding ability of receptors 1 and 2 with halide anions (F-, Cl-, Br- and I-), AcO- and HPO4- was investigated using visual (naked-eye), UV-vis titration experiments in dry DMSO together with DFT theoretical calculation. The addition of F-, AcO- and HPO4- to the host solution resulted in a red shift of the charge-transfer absorbance band accompanied by a color change from yellow to orange in the naked-eye experiments. Receptor 1 containing a nitro group at the para position and receptor 2 containing two bromine groups at the ortho and para positions both showed strong binding ability for HPO4- ion in the form of phenol-hydrazone. Moreover, receptor 1, induced by anion species in the solution, converted to the form of phenol-hydrazone from keto-hydrazone.

Isolation of peroxisome-deficient mutants of Saccharomyces cerevisiae.

PubMed Central

Erdmann, R; Veenhuis, M; Mertens, D; Kunau, W H

1989-01-01

Two mutants of Saccharomyces cerevisiae affected in peroxisomal assembly (pas mutants) have been isolated and characterized. Each strain contains a single mutation that results in (i) the inability to grow on oleic acid, (ii) accumulation of peroxisomal matrix enzymes in the cytosol, and (iii) absence of detectable peroxisomes at the ultrastructural level. These lesions (pas1-1 and pas2) are shown to be nonallelic and recessive. Crossing of pas1-1 and pas2 strains resulted in diploid cells that had regained the ability to grow on oleic acid as sole carbon source and to form peroxisomes. These pas mutants may provide useful tools for future studies on the molecular mechanisms involved in peroxisomal assembly. Images PMID:2568633

Loss of benzene to generate an enolate anion by a site-specific double-hydrogen transfer during CID fragmentation of o-alkyl ethers of ortho-hydroxybenzoic acids.

PubMed

Attygalle, Athula B; Bialecki, Jason B; Nishshanka, Upul; Weisbecker, Carl S; Ruzicka, Josef

2008-09-01

Collision-induced dissociation of anions derived from ortho-alkyloxybenzoic acids provides a facile way of producing gaseous enolate anions. The alkyloxyphenyl anion produced after an initial loss of CO(2) undergoes elimination of a benzene molecule by a double-hydrogen transfer mechanism, unique to the ortho isomer, to form an enolate anion. Deuterium labeling studies confirmed that the two hydrogen atoms transferred in the benzene loss originate from positions 1 and 2 of the alkyl chain. An initial transfer of a hydrogen atom from the C-1 position forms a phenyl anion and a carbonyl compound, both of which remain closely associated as an ion/neutral complex. The complex breaks either directly to give the phenyl anion by eliminating the neutral carbonyl compound, or to form an enolate anion by transferring a hydrogen atom from the C-2 position and eliminating a benzene molecule in the process. The pronounced primary kinetic isotope effect observed when a deuterium atom is transferred from the C-1 position, compared to the weak effect seen for the transfer from the C-2 position, indicates that the first transfer is the rate determining step. Quantum mechanical calculations showed that the neutral loss of benzene is a thermodynamically favorable process. Under the conditions used, only the spectra from ortho isomers showed peaks at m/z 77 for the phenyl anion and m/z 93 for the phenoxyl anion, in addition to that for the ortho-specific enolate anion. Under high collision energy, the ortho isomers also produce a peak at m/z 137 for an alkene loss. The spectra of meta and para compounds show a peak at m/z 92 for the distonic anion produced by the homolysis of the O-C bond. Moreover, a small peak at m/z 136 for a distonic anion originating from an alkyl radical loss allows the differentiation of para compounds from meta isomers.

Ford Partnership for Advanced Studies (Ford PAS)

ERIC Educational Resources Information Center

Carrier, Cheryl

2006-01-01

This article features the Ford Partnership for Advanced Studies (Ford PAS) program that helps students gain knowledge about real-life business issues. Ford PAS is an educational program that combines college-prep academics with the critical 21st century skills students will need to succeed in college and in the workplace. The Ford PAS program uses…

Ethical Issues in the Social Worker's Role in Physician-Assisted Suicide.

ERIC Educational Resources Information Center

Manetta, Ameda A.; Wells, Janice G.

2001-01-01

Presents results of an exploratory study of social workers' views on physician-assisted suicide (PAS), situations in which PAS would be favored, and whether there is a difference in education or training on mental health issues, ethics, or suicide between social workers who favor PAS and those who oppose PAS. (BF)

Proanthocyanidins of mountain birch leaves: quantification and properties.

PubMed

Ossipova, S; Ossipov, V; Haukioja, E; Loponen, J; Pihlaja, K

2001-01-01

Proanthocyanidins (PAs; condensed tannins) are present in mountain birch leaves in soluble and cell wall-bound forms. Crude preparations of soluble PAs were isolated from birch leaves and purified by chromatography on a Sephadex LH-20 column with a yield of about 7% of leaf dry mass. Some chemical characteristics were elucidated with 13C-NMR and HPLC-ECI-MS. Birch leaf PAs were mainly delphinidin type oligo- and polymers with average molecular mass of about 3000. In order to quantify PAs, the method involving heating PA-containing materials in 1-butanol:hydrochloric acid (95:5, v/v), and spectrophotometric determination of the anthocyanidin monomers so formed was modified and optimised. Mature leaves were characterised by a relatively high content of PAs: mean values for soluble and bound PAs were 103 and 40 mg/g dry mass, respectively. In mature leaves the soluble PAs determined the total protein precipitation capacity (PPC) of extracts. In young leaves, the contribution of PAs to the total content of phenolics and the total PPC of tannins was about 20-25% only.

PAS positivity of erythroid precursor cells is associated with a poor prognosis in newly diagnosed myelodysplastic syndrome patients.

PubMed

Masuda, Kenta; Shiga, Shuichi; Kawabata, Hiroshi; Takaori-Kondo, Akifumi; Ichiyama, Satoshi; Kamikubo, Yasuhiko

2018-07-01

Myelodysplastic syndrome (MDS) is a group of clonal stem cell disorders characterized by hematopoietic insufficiency. The accurate risk stratification of patients with MDS is essential for selection of appropriate therapies. We herein conducted a retrospective cohort study to examine the prognostic value of periodic acid-Schiff (PAS) reaction-positive erythroblasts in MDS patients. We examined the PAS positivity of the bone marrow erythroblasts of 144 patients newly diagnosed with MDS; 26 (18.1%) of them had PAS-positive erythroblasts, whereas 118 (81.9%) did not. The PAS-positive group showed significantly poorer karyotypes as defined in the revised International Prognostic Scoring System (IPSS-R) and higher scores in age-adjusted IPSS-R (IPSS-RA) than the PAS-negative group. Overall survival (OS) and leukemia-free survival (LFS) were also significantly shorter in the PAS-positive group than in the PAS-negative group. Similar results were obtained when only high- and very high risk groups were analyzed using IPSS-RA. This retrospective study suggested that the PAS positivity of erythroblasts is an additional prognostic factor combined with other risk scores for OS and LFS in MDS, and our results may contribute to improved clinical decision-making and rapid risk stratification.

Understanding protected area resilience: a multi-scale, social-ecological approach.

PubMed

Cumming, Graeme S; Allen, Craig R; Ban, Natalie C; Biggs, Duan; Biggs, Harry C; Cumming, David H M; De Vos, Alta; Epstein, Graham; Etienne, Michel; Maciejewski, Kristine; Mathevet, Raphaël; Moore, Christine; Nenadovic, Mateja; Schoon, Michael

2015-03-01

Protected areas (PAs) remain central to the conservation of biodiversity. Classical PAs were conceived as areas that would be set aside to maintain a natural state with minimal human influence. However, global environmental change and growing cross-scale anthropogenic influences mean that PAs can no longer be thought of as ecological islands that function independently of the broader social-ecological system in which they are located. For PAs to be resilient (and to contribute to broader social-ecological resilience), they must be able to adapt to changing social and ecological conditions over time in a way that supports the long-term persistence of populations, communities, and ecosystems of conservation concern. We extend Ostrom's social-ecological systems framework to consider the long-term persistence of PAs, as a form of land use embedded in social-ecological systems, with important cross-scale feedbacks. Most notably, we highlight the cross-scale influences and feedbacks on PAs that exist from the local to the global scale, contextualizing PAs within multi-scale social-ecological functional landscapes. Such functional landscapes are integral to understand and manage individual PAs for long-term sustainability. We illustrate our conceptual contribution with three case studies that highlight cross-scale feedbacks and social-ecological interactions in the functioning of PAs and in relation to regional resilience. Our analysis suggests that while ecological, economic, and social processes are often directly relevant to PAs at finer scales, at broader scales, the dominant processes that shape and alter PA resilience are primarily social and economic.

Understanding protected area resilience: a multi-scale, social-ecological approach

USGS Publications Warehouse

Cumming, Graeme S.; Allen, Craig R.; Ban, Natalie C.; Biggs, Duan; Biggs, Harry C.; Cumming, David H.M; De Vos, Alta; Epstein, Graham; Etienne, Michel; Maciejewski, Kristine; Mathevet, Raphael; Moore, Christine; Nenadovic, Mateja; Schoon, Michael

2015-01-01

Protected areas (PAs) remain central to the conservation of biodiversity. Classical PAs were conceived as areas that would be set aside to maintain a natural state with minimal human influence. However, global environmental change and growing cross-scale anthropogenic influences mean that PAs can no longer be thought of as ecological islands that function independently of the broader social-ecological system in which they are located. For PAs to be resilient (and to contribute to broader social-ecological resilience), they must be able to adapt to changing social and ecological conditions over time in a way that supports the long-term persistence of populations, communities, and ecosystems of conservation concern. We extend Ostrom's social-ecological systems framework to consider the long-term persistence of PAs, as a form of land use embedded in social-ecological systems, with important cross-scale feedbacks. Most notably, we highlight the cross-scale influences and feedbacks on PAs that exist from the local to the global scale, contextualizing PAs within multi-scale social-ecological functional landscapes. Such functional landscapes are integral to understand and manage individual PAs for long-term sustainability. We illustrate our conceptual contribution with three case studies that highlight cross-scale feedbacks and social-ecological interactions in the functioning of PAs and in relation to regional resilience. Our analysis suggests that while ecological, economic, and social processes are often directly relevant to PAs at finer scales, at broader scales, the dominant processes that shape and alter PA resilience are primarily social and economic.

Advanced practice registered nurses and physician assistants in sleep centers and clinics: a survey of current roles and educational background.

PubMed

Colvin, Loretta; Cartwright, Ann; Collop, Nancy; Freedman, Neil; McLeod, Don; Weaver, Terri E; Rogers, Ann E

2014-05-15

To survey Advanced Practice Registered Nurse (APRN) and Physician Assistant (PA) utilization, roles and educational background within the field of sleep medicine. Electronic surveys distributed to American Academy of Sleep Medicine (AASM) member centers and APRNs and PAs working within sleep centers and clinics. Approximately 40% of responding AASM sleep centers reported utilizing APRNs or PAs in predominantly clinical roles. Of the APRNs and PAs surveyed, 95% reported responsibilities in sleep disordered breathing and more than 50% in insomnia and movement disorders. Most APRNs and PAs were prepared at the graduate level (89%), with sleep-specific education primarily through "on the job" training (86%). All APRNs surveyed were Nurse Practitioners (NPs), with approximately double the number of NPs compared to PAs. APRNs and PAs were reported in sleep centers at proportions similar to national estimates of NPs and PAs in physicians' offices. They report predominantly clinical roles, involving common sleep disorders. Given current predictions that the outpatient healthcare structure will change and the number of APRNs and PAs will increase, understanding the role and utilization of these professionals is necessary to plan for the future care of patients with sleep disorders. Surveyed APRNs and PAs reported a significant deficiency in formal and standardized sleep-specific education. Efforts to provide formal and standardized educational opportunities for APRNs and PAs that focus on their clinical roles within sleep centers could help fill a current educational gap.

Impact of glycolate anion on aqueous corrosion in DWPF and downstream facilities

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

Mickalonis, J. I.

2015-12-15

Glycolic acid is being evaluated as an alternate reductant in the preparation of high level waste for the Defense Waste Processing Facility (DWPF) at the Savannah River Site (SRS). During processing, the glycolic acid may not be completely consumed with small quantities of the glycolate anion being carried forward to other high level waste (HLW) facilities. The impact of the glycolate anion on the corrosion of the materials of construction (MoC) throughout the waste processing system has not been previously evaluated. A literature review had revealed that corrosion data were not available for the MoCs in glycolic-bearing solutions applicable tomore » SRS systems. Data on the material compatibility with only glycolic acid or its derivative products were identified; however, data were limited for solutions containing glycolic acid or the glycolate anion.« less

Evaluation and application of a passive air sampler for polycylic aromatic hydrocarbons (PAHs).

PubMed

Esen, Fatma; Evci, Yildiz M; Tasdemir, Yucel

2017-08-24

Sampling of 15 PAHs by the use of both passive air sampler developed (D-PAS) in our research group and PAS (C-PAS) having widespread use in the literature was conducted to compare the performances of the samplers. Sampling was carried out for 1-year period (February 2013-February 2014), in different sampling periods by employing D-PAS and C-PAS. D-PAS and C-PAS were run in parallel for 10, 20, 30, 40 and 60 days. Sampling rates were calculated for both PASs by the use of concentration values obtained from a high-volume air sampler (HVAS). It was determined that calculated sampling values are different from each other by definition of design of C-PAS and D-PAS and difference in environment as velocity of wind and temperature are having different effects upon sampling rates. Collected σ 15 PAHs amounts of 10-day periods in spring, summer, autumn and winter were obtained as 576 ± 333, 209 ± 29, 2402 ± 910 and 664 ± 246 ng for D-PAS and 1070 ± 522, 318 ± 292, 6062 ± 1501 and 6089 ± 4018 ng for C-PAS, respectively. In addition, according to seasons, when collected PAHs in two different samplers were considered, similar results were obtained for the summer time in which no combustion takes place with the aim of domestic heating, while there were differences determined for the seasons with combustion in need of domestic heating. Gas-phase σ 15 PAHs' concentrations were reported depending on seasons in the spring, summer, autumn and winter sequences as 46 ± 32, 9 ± 3, 367 ± 207 and 127 ± 93 ng m -3 for HVAS, respectively.

Evolution Of USDOE Performance Assessments Over 20 Years

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

Seitz, Roger R.; Suttora, Linda C.

2013-02-26

Performance assessments (PAs) have been used for many years for the analysis of post-closure hazards associated with a radioactive waste disposal facility and to provide a reasonable expectation of the ability of the site and facility design to meet objectives for the protection of members of the public and the environment. The use of PA to support decision-making for LLW disposal facilities has been mandated in United States Department of Energy (USDOE) directives governing radioactive waste management since 1988 (currently DOE Order 435.1, Radioactive Waste Management). Prior to that time, PAs were also used in a less formal role. Overmore » the past 20+ years, the USDOE approach to conduct, review and apply PAs has evolved into an efficient, rigorous and mature process that includes specific requirements for continuous improvement and independent reviews. The PA process has evolved through refinement of a graded and iterative approach designed to help focus efforts on those aspects of the problem expected to have the greatest influence on the decision being made. Many of the evolutionary changes to the PA process are linked to the refinement of the PA maintenance concept that has proven to be an important element of USDOE PA requirements in the context of supporting decision-making for safe disposal of LLW. The PA maintenance concept represents the evolution of the graded and iterative philosophy and has helped to drive the evolution of PAs from a deterministic compliance calculation into a systematic approach that helps to focus on critical aspects of the disposal system in a manner designed to provide a more informed basis for decision-making throughout the life of a disposal facility (e.g., monitoring, research and testing, waste acceptance criteria, design improvements, data collection, model refinements). A significant evolution in PA modeling has been associated with improved use of uncertainty and sensitivity analysis techniques to support efficient implementation of the graded and iterative approach. Rather than attempt to exactly predict the migration of radionuclides in a disposal unit, the best PAs have evolved into tools that provide a range of results to guide decision-makers in planning the most efficient, cost effective, and safe disposal of radionuclides.« less

Extracellular determinants of anion discrimination of the Cl-/H+ antiporter protein CLC-5.

PubMed

De Stefano, Silvia; Pusch, Michael; Zifarelli, Giovanni

2011-12-23

Mammalian CLC proteins comprise both Cl- channels and Cl-/H+ antiporters that carry out fundamental physiological tasks by transporting Cl- across plasma membrane and intracellular compartments. The NO3- over Cl- preference of a plant CLC transporter has been pinpointed to a conserved serine residue located at Scen and it is generally assumed that the other two binding sites of CLCs, Sext and Sin, do not substantially contribute to anion selectivity. Here we show for the Cl-/H+ antiporter CLC-5 that the conserved and extracellularly exposed Lys210 residue is critical to determine the anion specificity for transport activity. In particular, mutations that neutralize or invert the charge at this position reverse the NO3- over Cl- preference of WT CLC-5 at a concentration of 100 mm, but do not modify the coupling stoichiometry with H+. The importance of the electrical charge is shown by chemical modification of K210C with positively charged cysteine-reactive compounds that reintroduce the WT preference for Cl-. At saturating extracellular anion concentrations, neutralization of Lys210 is of little impact on the anion preference, suggesting an important role of Lys210 on the association rate of extracellular anions to Sext.

Dynamics of Pseudomonas aeruginosa association with anionic hydrogel surfaces in the presence of aqueous divalent-cation salts

PubMed Central

Tran, Victoria B.; Sung, Ye Suel; Fleiszig, Suzanne M.J.; Evans, David J.; Radke, C.J.

2013-01-01

Binding of bacteria to solid surfaces is complex with many aspects incompletely understood. We investigate Pseudomonas aeruginosa uptake kinetics onto hydrogel surfaces representative of soft-contact lenses made of nonionic poly(2-hydroxyethylmethacrylate) (p-HEMA), anionic poly(methacrylic acid) (p-MAA), and anionic poly(acrylic acid) (p-AA). Using a parallel-plate flow cell under phase-contrast microscopy, we document a kinetic “burst” at the anionic hydrogel surface: dilute aqueous P. aeruginosa first rapidly accumulates and then rapidly depletes. Upon continuing flow, divalent cations in the suspending solution sorb into the hydrogel network causing the previously surface-accumulated bacteria to desorb. The number of bacteria eventually bound to the surface is low compared to the nonionic p-HEMA hydrogel. We propose that the kinetic burst is due to reversible divalent-cation bridging between the anionic bacteria and the negatively charged hydrogel surface. The number of surface bridging sites diminishes as divalent cations impregnate into and collapse the gel. P. aeruginosa association with the surface then falls. Low eventual binding of P. aeruginosa to the anionic hydrogel is ascribed to increased surface hydrophilicity compared to the counterpart nonionic p-HEMA hydrogel. PMID:21723562

Identifying Preservation and Restoration Priority Areas for Desert Fishes in an Increasingly Invaded World

NASA Astrophysics Data System (ADS)

Pool, Thomas K.; Strecker, Angela L.; Olden, Julian D.

2013-03-01

A commonly overlooked aspect of conservation planning assessments is that wildlife managers are increasingly focused on habitats that contain non-native species. We examine this management challenge in the Gila River basin (150,730 km2), and present a new planning strategy for fish conservation. By applying a hierarchical prioritization algorithm to >850,000 fish records in 27,181 sub-watersheds we first identified high priority areas (PAs) termed "preservation PAs" with high native fish richness and low non-native richness; these represent traditional conservation targets. Second, we identified "restoration PAs" with high native fish richness that also contained high numbers of non-native species; these represent less traditional conservation targets. The top 10 % of preservation and restoration PAs contained common native species (e.g., Catostomus clarkii, desert sucker; Catostomus insignis, Sonora sucker) in addition to native species with limited distributions (i.e., Xyrauchen texanus, razorback sucker; Oncorhynchus gilae apache, Apache trout). The top preservation and restoration PAs overlapped by 42 %, indicating areas with high native fish richness range from minimally to highly invaded. Areas exclusively identified as restoration PAs also encompassed a greater percentage of native species ranges than would be expected by the random addition of an equivalent basin area. Restoration PAs identified an additional 19.0 and 26.6 % of the total ranges of two federally endangered species— Meda fulgida (spikedace) and Gila intermedia (Gila chub), respectively, compared to top preservation PAs alone—despite adding only 5.8 % of basin area. We contend that in addition to preservation PAs, restoration PAs are well suited for complementary management activities benefiting native fishes.

Legal physician-assisted suicide in Oregon and The Netherlands: evidence concerning the impact on patients in vulnerable groups--another perspective on Oregon's data.

PubMed

Finlay, I G; George, R

2011-03-01

Battin et al examined data on deaths from physician-assisted suicide (PAS) in Oregon and on PAS and voluntary euthanasia (VE) in The Netherlands. This paper reviews the methodology used in their examination and questions the conclusions drawn from it-namely, that there is for the most part 'no evidence of heightened risk' to vulnerable people from the legalisation of PAS or VE. This critique focuses on the evidence about PAS in Oregon. It suggests that vulnerability to PAS cannot be categorised simply by reference to race, gender or other socioeconomic status and that the impetus to seek PAS derives from factors, including emotional state, reactions to loss, personality type and situation and possibly to PAS contagion, all factors that apply across the social spectrum. It also argues, on the basis of official reports from the Oregon Health Department on the working of the Oregon Death with Dignity Act since 2008, that, contrary to the conclusions drawn by Battin et al, the highest resort to PAS in Oregon is among the elderly and, on the basis of research published since Battin et al reported, that there is reason to believe that some terminally ill patients in Oregon are taking their own lives with lethal drugs supplied by doctors despite having had depression at the time when they were assessed and cleared for PAS.

Histopathological examination of nail clippings using PAS staining (HPE-PAS): gold standard in diagnosis of Onychomycosis.

PubMed

Jeelani, Shazia; Ahmed, Qazi Masood; Lanker, Audil Mohmad; Hassan, Iffat; Jeelani, Nasir; Fazili, Tawheeda

2015-01-01

Onychomycosis is fungal infection of one or more of the nail units. However, because fungi cause only about half of all nail dystrophies, the use of appropriate diagnostic techniques is important to ensure correct diagnosis and treatment. Aim of the present study was to compare direct microscopy, culture and HPE-PAS for diagnosis of onychomycosis by evaluating their sensitivity and various other relevant statistical parameters. A prospective, hospital-based, cross-sectional study was conducted on 216 patients with a high degree of clinical suspicion of onychomycosis. Nail specimens were evaluated using three diagnostic methods, i.e. direct microscopy using 20% Potassium hydroxide (KOH) & 40% Di-methyl-suphoxide (DMSO), culture and histopathological examination using PAS stain (HPE-PAS). Of 216 patients direct microscopy was positive in 138 (63.9%), culture in 147 (68%) and HPE-PAS in 164 patients (76%). One hundred and seventy-nine patients fitted into the criteria set for confirmed diagnosis of onychomycosis. Using this as a denominator; direct microscopy, culture and HPE-PAS had sensitivities of 77.1%, 70% and 91.6% respectively. Also, HPE-PAS showed the highest sensitivity of 94.7% in 19 cases with prediagnostic antimycotic treatment compared to direct microscopy (42.1%) or culture (57.9%). HPE-PAS shows high sensitivity for diagnosis of onychomycosis and can be considered as a gold standard in the diagnosis of onychomycosis. © 2014 Blackwell Verlag GmbH.

Assessment of Light Pollution Impact on Protected Areas in China

NASA Astrophysics Data System (ADS)

Jiang, W.; He, G.; Ni, Y.

2017-09-01

The Protected Areas (PAs) with natural, ecological and cultural value play important role in biological processes, biodiversity and ecosystem service. During the past years of rapid urban expansion in China, the spatial range and intensity of light pollution unprecedented increase. Historically, optical remote sensing and field survey data had been used to reveal that human activities impacted on PAs for individual areas and few papers documented the issue of light pollution impact on PAs at national scale. Here, time series night-time light satellite images of Defense Meteorological Satellite Program Operational Linescan System (DMSP-OLS) were selected to assess the light pollution impacted on PAs in China. The method we proposed can be effectively applied to assess the impact of light pollution on PAs and the percent of dark PAs decreased by 35.38 % from 1992 to 2012 at nationwide. The trend of light pollution of most PAs in stable, however, light pollution of the local area is increase significantly, especially in northern Xinjiang, Gansu, Xizang, Yunnan, Jiangsu and Shandong. Considering the current status of light pollution encroach into PAs, two strategies of appropriate buffer zone and wide measured for light pollution are also recommend.

Associative plasticity in intracortical inhibitory circuits in human motor cortex.

PubMed

Russmann, Heike; Lamy, Jean-Charles; Shamim, Ejaz A; Meunier, Sabine; Hallett, Mark

2009-06-01

Paired associative stimulation (PAS) is a transcranial magnetic stimulation technique inducing Hebbian-like synaptic plasticity in the human motor cortex (M1). PAS is produced by repetitive pairing of a peripheral nerve shock and a transcranial magnetic stimulus (TMS). Its effect is assessed by a change in size of a motor evoked response (MEP). MEP size results from excitatory and inhibitory influences exerted on cortical pyramidal cells, but no robust effects on inhibitory networks have been demonstrated so far. In 38 healthy volunteers, we assessed whether a PAS intervention influences three intracortical inhibitory circuits: short (SICI) and long (LICI) intracortical inhibitions reflecting activity of GABA(A) and GABA(B) interneurons, respectively, and long afferent inhibition (LAI) reflecting activity of somatosensory inputs. After PAS, MEP sizes, LICI and LAI levels were significantly changed while changes of SICI were inconsistent. The changes in LICI and LAI lasted 45 min after PAS. Their direction depended on the delay between the arrival time of the afferent volley at the cortex and the TMS-induced cortical activation during the PAS. PAS influences inhibitory circuits in M1. PAS paradigms can demonstrate Hebbian-like plasticity at selected inhibitory networks as well as excitatory networks.

Bacteriocidal activity of sanitizers against Enterococcus faecium attached to stainless steel as determined by plate count and impedance methods.

PubMed

Andrade, N J; Bridgeman, T A; Zottola, E A

1998-07-01

Enterococcus faecium attached to stainless steel chips (100 mm2) was treated with the following sanitizers: sodium hypochlorite, peracetic acid (PA), peracetic acid plus an organic acid (PAS), quaternary ammonium, organic acid, and anionic acid. The effectiveness of sanitizer solutions on planktonic cells (not attached) was evaluated by the Association of Official Analytical Chemists (AOAC) suspension test. The number of attached cells was determined by impedance measurement and plate count method after vortexing. The decimal reduction (DR) in numbers of the E. faecium population was determined for the three methods and was analyzed by analysis of variance (P < 0.05) using Statview software. The adhered cells were more resistant (P < 0.05) than nonadherent cells. The DR averages for all of the sanitizers for 30 s of exposure were 6.4, 2.2, and 2.5 for the AOAC suspension test, plate count method after vortexing, and impedance measurement, respectively. Plate count and impedance methods showed a difference (P < 0.05) after 30 s of sanitizer exposure but not after 2 min. The impedance measurement was the best method to measure adherent cells. Impedance measurement required the development of a quadratic regression. The equation developed from 82 samples is as follows: log CFU/chip = 0.2385T2-0.96T + 9.35, r2 = 0.92, P < 0.05, T = impedance detection time in hours. This method showed that the sanitizers PAS and PA were more effective against E. faecium than the other sanitizers. At 30 s, the impedance method recovered about 25 times more cells than the plate count method after vortexing. These data suggest that impedance measurement is the method of choice when evaluating the number of bacterial cells adhered to a surface.

Proanthocyanidin oxidation of Arabidopsis seeds is altered in mutant of the high-affinity nitrate transporter NRT2.7

PubMed Central

David, Laure C.; Dechorgnat, Julie; Ferrario-Méry, Sylvie

2014-01-01

NRT2.7 is a seed-specific high-affinity nitrate transporter controlling nitrate content in Arabidopsis mature seeds. The objective of this work was to analyse further the consequences of the nrt2.7 mutation for the seed metabolism. This work describes a new phenotype for the nrt2.7-2 mutant allele in the Wassilewskija accession, which exhibited a distinctive pale-brown seed coat that is usually associated with a defect in flavonoid oxidation. Indeed, this phenotype resembled those of tt10 mutant seeds defective in the laccase-like enzyme TT10/LAC15, which is involved in the oxidative polymerization of flavonoids such as the proantocyanidins (PAs) (i.e. epicatechin monomers and PA oligomers) and flavonol glycosides. nrt2.7-2 and tt10-2 mutant seeds displayed the same higher accumulation of PAs, but were partially distinct, since flavonol glycoside accumulation was not affected in the nrt2.7-2 seeds. Moreover, measurement of in situ laccase activity excluded a possibility of the nrt2.7-2 mutation affecting the TT10 enzymic activity at the early stage of seed development. Functional complementation of the nrt2.7-2 mutant by overexpression of a full-length NRT2.7 cDNA clearly demonstrated the link between the nrt2.7 mutation and the PA phenotype. However, the PA-related phenotype of nrt2.7-2 seeds was not strictly correlated to the nitrate content of seeds. No correlation was observed when nitrate was lowered in seeds due to limited nitrate nutrition of plants or to lower nitrate storage capacity in leaves of clca mutants deficient in the vacuolar anionic channel CLCa. All together, the results highlight a hitherto-unknown function of NRT2.7 in PA accumulation/oxidation. PMID:24532452

Physician-assisted suicide-a clean bill of health?

PubMed

Preston, Robert

2017-09-01

Physician-assisted suicide (PAS) laws have been enacted in five US States and, along with physician-administered euthanasia, in Canada and the Netherlands. Annual reports of the Oregon Health Authority and published research papers. Not all recipients of lethal drugs use them to end their lives. Improvements in palliative care provision. Rising numbers of deaths from PAS. Emergence of 'doctor shopping' and multiple-prescribing. Absence of qualitative scrutiny of assessment process. No re-assessment or oversight when prescribed drugs are ingested. Recent pressures to extend Oregon's PAS law. Reasons given for seeking PAS indicate this is a societal rather than a clinical issue and raise the question whether adjudicating on requests for legalized PAS is an appropriate role for doctors. Research into quality of decision-making in requests for PAS and into potential role of doctors as expert witnesses rather than judges in requests for PAS. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

The Role of Glia in Stress: Polyamines and Brain Disorders

PubMed Central

Skatchkov, Serguei; Woodbury, Michel; Eaton, Misty

2014-01-01

Synopsis This review focuses on the roles of glia and polyamines (PAs) in brain function and dysfunction, highlighting how PAs are one of the principal differences between glia and neurons as they are surprisingly stored, but not synthesized, almost exclusively in glial cells from which they can be released to regulate neuronal synaptic activity. The review includes the novel role of PAs, such as putrescine (PUT), spermidine (SPD) and spermine (SPM) and their precursors and derivatives. However: (i) PAs have not yet been a focus of much glial research; (ii) PAs affect many neuronal and glial receptors, channels and transporters; (iii) PAs are therefore key elements in the development of many diseases and syndromes (iv) thus forming the rationale for PA and glia focused therapy for these conditions. PMID:25455070

Tuning anion-functionalized ionic liquids for improved SO2 capture.

PubMed

Cui, Guokai; Zheng, Junjie; Luo, Xiaoyan; Lin, Wenjun; Ding, Fang; Li, Haoran; Wang, Congmin

2013-09-27

You can have your cake and eat it too: A "dual-tuning" strategy for improving the capture of SO2 was developed by introducing electron-withdrawing sites on the anions to produce several kinds of functionalized ionic liquids. Those functionalized with a halogen group exhibited improved performance over their non-halogenated counterparts, leading to highly efficient and reversible capture. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Electronic structures and spectra of two antioxidants: uric acid and ascorbic acid

NASA Astrophysics Data System (ADS)

Shukla, M. K.; Mishra, P. C.

1996-04-01

Electronic absorption and fluorescence spectra of aqueous solutions of two well known antioxidants, uric acid and ascorbic acid (vitamin C), have been studied at different pH. The observed spectra have been interpreted in terms of neutral and anionic forms of the molecules with the help of molecular orbital calculations. The N 3 site of uric acid has been shown to be the most acidic. Fluorescence of uric acid seems to originate from an anion of the molecule in a wide pH range. Around pH 3, both the neutral and anionic forms of ascorbic acid appear to be present in aqueous solutions. In aqueous media, ascorbic acid appears to get converted easily to its dehydro form and this conversion does not seem to be reversible. An anion of dehydroascorbic acid seems to be formed on heating dehydroascorbic acid in aqueous solutions.

47 CFR Appendix B to Part 64 - Priority Access Service (PAS) for National Security and Emergency Preparedness (NSEP)

Code of Federal Regulations, 2013 CFR

2013-10-01

... providers as necessary to maintain the viability of the PAS system. 5. Maintain a database for PAS related... NSEP PAS database only to those having a need-to-know or who will not use the information for economic... selected for this priority should be responsible for ensuring the viability or reconstruction of the basic...

47 CFR Appendix B to Part 64 - Priority Access Service (PAS) for National Security and Emergency Preparedness (NSEP)

Code of Federal Regulations, 2011 CFR

2011-10-01

... providers as necessary to maintain the viability of the PAS system. 5. Maintain a database for PAS related... NSEP PAS database only to those having a need-to-know or who will not use the information for economic... selected for this priority should be responsible for ensuring the viability or reconstruction of the basic...

47 CFR Appendix B to Part 64 - Priority Access Service (PAS) for National Security and Emergency Preparedness (NSEP)

Code of Federal Regulations, 2014 CFR

2014-10-01

... providers as necessary to maintain the viability of the PAS system. 5. Maintain a database for PAS related... NSEP PAS database only to those having a need-to-know or who will not use the information for economic... selected for this priority should be responsible for ensuring the viability or reconstruction of the basic...

47 CFR Appendix B to Part 64 - Priority Access Service (PAS) for National Security and Emergency Preparedness (NSEP)

Code of Federal Regulations, 2012 CFR

2012-10-01

... providers as necessary to maintain the viability of the PAS system. 5. Maintain a database for PAS related... NSEP PAS database only to those having a need-to-know or who will not use the information for economic... selected for this priority should be responsible for ensuring the viability or reconstruction of the basic...

Changes in Quaternary Structure in the Signaling Mechanisms of PAS Domains

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

Ayers, Rebecca A.; Moffat, Keith

2008-12-15

FixL from Bradyrhizobium japonicum is a PAS sensor protein in which two PAS domains covalently linked to a histidine kinase domain are responsible for regulating nitrogen fixation in an oxygen-dependent manner. The more C-terminal PAS domain, denoted bjFixLH, contains a heme cofactor that binds diatomic molecules such as carbon monoxide and oxygen and regulates the activity of the FixL histidine kinase as part of a two-component signaling system. We present the structures of ferric, deoxy, and carbon monoxide-bound bjFixLH in a new space group (P1) and at resolutions (1.5--1.8 {angstrom}) higher than the resolutions of those previously obtained. Interestingly, bjFixLHmore » can form two different dimers (in P1 and R32 crystal forms) in the same crystallization solution, where the monomers in one dimer are rotated {approx}175 deg. relative to the second. This suggests that PAS monomers are plastic and that two quite distinct quaternary structures are closely similar in free energy. We use screw rotation analysis to carry out a quantitative pairwise comparison of PAS quaternary structures, which identifies five different relative orientations adopted by isolated PAS monomers. We conclude that PAS monomer arrangement is context-dependent and could differ depending on whether the PAS domains are isolated or are part of a full-length protein. Structurally homologous residues comprise a conserved dimer interface. Using network analysis, we find that the architecture of the PAS dimer interface is continuous rather than modular; the network of residues comprising the interface is strongly connected. A continuous dimer interface is consistent with the low dimer-monomer dissociation equilibrium constant. Finally, we quantitate quaternary structural changes induced by carbon monoxide binding to a bjFixLH dimer, in which monomers rotate by up to 2 deg. relative to each other. We relate these changes to those in other dimeric PAS domains and discuss the role of quaternary structural changes in the signaling mechanisms of PAS sensor proteins.« less

Snake Cytotoxins Bind to Membranes via Interactions with Phosphatidylserine Head Groups of Lipids

PubMed Central

Konshina, Anastasia G.; Boldyrev, Ivan A.; Utkin, Yuri N.; Omel'kov, Anton V.; Efremov, Roman G.

2011-01-01

The major representatives of Elapidae snake venom, cytotoxins (CTs), share similar three-fingered fold and exert diverse range of biological activities against various cell types. CT-induced cell death starts from the membrane recognition process, whose molecular details remain unclear. It is known, however, that the presence of anionic lipids in cell membranes is one of the important factors determining CT-membrane binding. In this work, we therefore investigated specific interactions between one of the most abundant of such lipids, phosphatidylserine (PS), and CT 4 of Naja kaouthia using a combined, experimental and modeling, approach. It was shown that incorporation of PS into zwitterionic liposomes greatly increased the membrane-damaging activity of CT 4 measured by the release of the liposome-entrapped calcein fluorescent dye. The CT-induced leakage rate depends on the PS concentration with a maximum at approximately 20% PS. Interestingly, the effects observed for PS were much more pronounced than those measured for another anionic lipid, sulfatide. To delineate the potential PS binding sites on CT 4 and estimate their relative affinities, a series of computer simulations was performed for the systems containing the head group of PS and different spatial models of CT 4 in aqueous solution and in an implicit membrane. This was done using an original hybrid computational protocol implementing docking, Monte Carlo and molecular dynamics simulations. As a result, at least three putative PS-binding sites with different affinities to PS molecule were delineated. Being located in different parts of the CT molecule, these anion-binding sites can potentially facilitate and modulate the multi-step process of the toxin insertion into lipid bilayers. This feature together with the diverse binding affinities of the sites to a wide variety of anionic targets on the membrane surface appears to be functionally meaningful and may adjust CT action against different types of cells. PMID:21559494

Pyrrolizidine and tropane alkaloids in teas and the herbal teas peppermint, rooibos and chamomile in the Israeli market.

PubMed

Shimshoni, Jakob Avi; Duebecke, Arne; Mulder, Patrick P J; Cuneah, Olga; Barel, Shimon

2015-01-01

Dehydro pyrrolizidine alkaloids (dehydro PAs) are carcinogenic phytotoxins prevalent in the Boraginaceae, Asteraceae and Fabaceae families. Dehydro PAs enter the food and feed chain by co-harvesting of crops intended for human and animal consumption as well as by carry-over into animal-based products such as milk, eggs and honey. Recently the occurrence of dehydro PAs in teas and herbal teas has gained increasing attention from the EU, due to the high levels of dehydro PAs found in commercially available teas and herbal teas in Germany and Switzerland. Furthermore, several tropane alkaloids (TAs, e.g. scopolamine and hyoscyamine) intoxications due to the consumption of contaminated herbal teas were reported in the literature. The aim of the present study was to determine the dehydro PAs and TAs levels in 70 pre-packed teabags of herbal and non-herbal tea types sold in supermarkets in Israel. Chamomile, peppermint and rooibos teas contained high dehydro PAs levels in almost all samples analysed. Lower amounts were detected in black and green teas, while no dehydro PAs were found in fennel and melissa herbal teas. Total dehydro PAs concentrations in chamomile, peppermint and rooibos teas ranged from 20 to 1729 μg/kg. Except for black tea containing only mono-ester retrorsine-type dehydro PAs, all other teas and herbal teas showed mixed patterns of dehydro PA ester types, indicating a contamination by various weed species during harvesting and/or production. The TA levels per teabag were below the recommended acute reference dose; however, the positive findings of TAs in all peppermint tea samples warrant a more extensive survey. The partially high levels of dehydro PAs found in teas and herbal teas present an urgent warning letter to the regulatory authorities to perform routine quality control analysis and implement maximum residual levels for dehydro PAs.

Structural basis of control of inward rectifier Kir2 channel gating by bulk anionic phospholipids

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

Lee, Sun-Joo; Ren, Feifei; Zangerl-Plessl, Eva-Maria

2016-08-15

Inward rectifier potassium (Kir) channel activity is controlled by plasma membrane lipids. Phosphatidylinositol-4,5-bisphosphate (PIP 2) binding to a primary site is required for opening of classic inward rectifier Kir2.1 and Kir2.2 channels, but interaction of bulk anionic phospholipid (PL -) with a distinct second site is required for high PIP 2sensitivity. Here we show that introduction of a lipid-partitioning tryptophan at the second site (K62W) generates high PIP 2sensitivity, even in the absence of PL -. Furthermore, high-resolution x-ray crystal structures of Kir2.2[K62W], with or without added PIP 2(2.8- and 2.0-Å resolution, respectively), reveal tight tethering of the C-terminal domainmore » (CTD) to the transmembrane domain (TMD) in each condition. Our results suggest a refined model for phospholipid gating in which PL -binding at the second site pulls the CTD toward the membrane, inducing the formation of the high-affinity primary PIP 2site and explaining the positive allostery between PL -binding and PIP 2sensitivity.« less

Reactive sites influence in PMMA oligomers reactivity: a DFT study

NASA Astrophysics Data System (ADS)

Paz, C. V.; Vásquez, S. R.; Flores, N.; García, L.; Rico, J. L.

2018-01-01

In this work, we present a theoretical study of methyl methacrylate (MMA) living anionic polymerization. The study was addressed to understanding two important experimental observations made for Michael Szwarc in 1956. The unexpected effect of reactive sites concentration in the propagation rate, and the self-killer behavior of MMA (deactivating of living anionic polymerization). The theoretical calculations were performed by density functional theory (DFT) to obtain the frontier molecular orbitals values. These values were used to calculate and analyze the chemical interaction descriptors in DFT-Koopmans’ theorem. As a result, it was observed that the longest chain-length species (related with low concentration of reactive sites) exhibit the highest reactivity (behavior associated with the increase of the propagation rate). The improvement in this reactivity was attributed to the crosslinking produced in the polymethyl methacrylate chains. Meanwhile, the self-killer behavior was associated with the intermolecular forces present in the reactive sites. This behavior was associated to an obstruction in solvation, since the active sites remained active through all propagation species. The theoretical results were in good agreement with the Szwarc experiments.

Structural basis of control of inward rectifier Kir2 channel gating by bulk anionic phospholipids.

PubMed

Lee, Sun-Joo; Ren, Feifei; Zangerl-Plessl, Eva-Maria; Heyman, Sarah; Stary-Weinzinger, Anna; Yuan, Peng; Nichols, Colin G

2016-09-01

Inward rectifier potassium (Kir) channel activity is controlled by plasma membrane lipids. Phosphatidylinositol-4,5-bisphosphate (PIP2) binding to a primary site is required for opening of classic inward rectifier Kir2.1 and Kir2.2 channels, but interaction of bulk anionic phospholipid (PL(-)) with a distinct second site is required for high PIP2 sensitivity. Here we show that introduction of a lipid-partitioning tryptophan at the second site (K62W) generates high PIP2 sensitivity, even in the absence of PL(-) Furthermore, high-resolution x-ray crystal structures of Kir2.2[K62W], with or without added PIP2 (2.8- and 2.0-Å resolution, respectively), reveal tight tethering of the C-terminal domain (CTD) to the transmembrane domain (TMD) in each condition. Our results suggest a refined model for phospholipid gating in which PL(-) binding at the second site pulls the CTD toward the membrane, inducing the formation of the high-affinity primary PIP2 site and explaining the positive allostery between PL(-) binding and PIP2 sensitivity. © 2016 Lee et al.

Analysis of periplasmic sensor domains from Anaeromyxobacter dehalogenans 2CP-C: Structure of one sensor domain from a histidine kinase and another from a chemotaxis protein

PubMed Central

Pokkuluri, P Raj; Dwulit-Smith, Jeff; Duke, Norma E; Wilton, Rosemarie; Mack, Jamey C; Bearden, Jessica; Rakowski, Ella; Babnigg, Gyorgy; Szurmant, Hendrik; Joachimiak, Andrzej; Schiffer, Marianne

2013-01-01

Anaeromyxobacter dehalogenans is a δ-proteobacterium found in diverse soils and sediments. It is of interest in bioremediation efforts due to its dechlorination and metal-reducing capabilities. To gain an understanding on A. dehalogenans' abilities to adapt to diverse environments we analyzed its signal transduction proteins. The A. dehalogenans genome codes for a large number of sensor histidine kinases (HK) and methyl-accepting chemotaxis proteins (MCP); among these 23 HK and 11 MCP proteins have a sensor domain in the periplasm. These proteins most likely contribute to adaptation to the organism's surroundings. We predicted their three-dimensional folds and determined the structures of two of the periplasmic sensor domains by X-ray diffraction. Most of the domains are predicted to have either PAS-like or helical bundle structures, with two predicted to have solute-binding protein fold, and another predicted to have a 6-phosphogluconolactonase like fold. Atomic structures of two sensor domains confirmed the respective fold predictions. The Adeh_2942 sensor (HK) was found to have a helical bundle structure, and the Adeh_3718 sensor (MCP) has a PAS-like structure. Interestingly, the Adeh_3718 sensor has an acetate moiety bound in a binding site typical for PAS-like domains. Future work is needed to determine whether Adeh_3718 is involved in acetate sensing by A. dehalogenans. PMID:23897711

Identifying preservation and restoration priority areas for desert fishes in an increasingly invaded world.

PubMed

Pool, Thomas K; Strecker, Angela L; Olden, Julian D

2013-03-01

A commonly overlooked aspect of conservation planning assessments is that wildlife managers are increasingly focused on habitats that contain non-native species. We examine this management challenge in the Gila River basin (150,730 km(2)), and present a new planning strategy for fish conservation. By applying a hierarchical prioritization algorithm to >850,000 fish records in 27,181 sub-watersheds we first identified high priority areas (PAs) termed "preservation PAs" with high native fish richness and low non-native richness; these represent traditional conservation targets. Second, we identified "restoration PAs" with high native fish richness that also contained high numbers of non-native species; these represent less traditional conservation targets. The top 10 % of preservation and restoration PAs contained common native species (e.g., Catostomus clarkii, desert sucker; Catostomus insignis, Sonora sucker) in addition to native species with limited distributions (i.e., Xyrauchen texanus, razorback sucker; Oncorhynchus gilae apache, Apache trout). The top preservation and restoration PAs overlapped by 42 %, indicating areas with high native fish richness range from minimally to highly invaded. Areas exclusively identified as restoration PAs also encompassed a greater percentage of native species ranges than would be expected by the random addition of an equivalent basin area. Restoration PAs identified an additional 19.0 and 26.6 % of the total ranges of two federally endangered species-Meda fulgida (spikedace) and Gila intermedia (Gila chub), respectively, compared to top preservation PAs alone-despite adding only 5.8 % of basin area. We contend that in addition to preservation PAs, restoration PAs are well suited for complementary management activities benefiting native fishes.

Arranging for personal assistance services and assistive technology at work. A report of the rehabilitation research and training center on personal assistance services.

PubMed

Stoddard, Susan; Kraus, Lewis

2006-01-01

For an employee with a disability, reasonable accommodation can make the difference in finding work, maintaining employment, and succeeding on the job. Today, employers and employees alike are more aware that appropriate accommodation, including workplace personal assistance services (PAS) as well as assistive technology, improves an employee's ability to succeed. While assistive technology is in widespread use as an accommodation, workplace personal assistance is less understood. The goal of the study was to learn more about how workplace PAS and AT are arranged for in the workplace, and the issues that arise. Structured phone interviews were conducted with 20 workplace PAS users, 21 employers familiar with workplace PAS, and 19 employment organizations. Interview transcripts are the basis for the qualitative analysis of findings. Requirements for personal assistance accommodations focus on task-related needs. Personal care needs at work are not included in the Americans with Disabilities act but may be needed by the employee. Employers and PAS users have developed many creative ways to address PAS need. Organizations can construct an approach that fits the needs, abilities, and constraints of each organization. The interview respondents have identified a number of practices that are succeeding, including establishment of policies for arranging for PAS; centralization of accommodation budgets to remove work unit disincentives; and providing a shared personal assistant for interpreting or for task-related and personal care tasks. A number of important research questions remain. What is the extent of the need for PAS in the workplace? Will an expanded PAS supply increase the employment opportunities for people with disabilities? Will better models of workplace PAS be adopted by employers?

Advanced Practice Registered Nurses and Physician Assistants in Sleep Centers and Clinics: A Survey of Current Roles and Educational Background

PubMed Central

Colvin, Loretta; Cartwright, Ann; Collop, Nancy; Freedman, Neil; McLeod, Don; Weaver, Terri E.; Rogers, Ann E.

2014-01-01

Study Objectives: To survey Advanced Practice Registered Nurse (APRN) and Physician Assistant (PA) utilization, roles and educational background within the field of sleep medicine. Methods: Electronic surveys distributed to American Academy of Sleep Medicine (AASM) member centers and APRNs and PAs working within sleep centers and clinics. Results: Approximately 40% of responding AASM sleep centers reported utilizing APRNs or PAs in predominantly clinical roles. Of the APRNs and PAs surveyed, 95% reported responsibilities in sleep disordered breathing and more than 50% in insomnia and movement disorders. Most APRNs and PAs were prepared at the graduate level (89%), with sleep-specific education primarily through “on the job” training (86%). All APRNs surveyed were Nurse Practitioners (NPs), with approximately double the number of NPs compared to PAs. Conclusions: APRNs and PAs were reported in sleep centers at proportions similar to national estimates of NPs and PAs in physicians' offices. They report predominantly clinical roles, involving common sleep disorders. Given current predictions that the outpatient healthcare structure will change and the number of APRNs and PAs will increase, understanding the role and utilization of these professionals is necessary to plan for the future care of patients with sleep disorders. Surveyed APRNs and PAs reported a significant deficiency in formal and standardized sleep-specific education. Efforts to provide formal and standardized educational opportunities for APRNs and PAs that focus on their clinical roles within sleep centers could help fill a current educational gap. Citation: Colvin L, Cartwright Ann, Collop N, Freedman N, McLeod D, Weaver TE, Rogers AE. Advanced practice registered nurses and physician assistants in sleep centers and clinics: a survey of current roles and educational background. J Clin Sleep Med 2014;10(5):581-587. PMID:24812545

Structure of a Premicellar Complex of Alkyl Sulfates with the Interfacial Binding Surfaces of 4 Subunits of Phospholipase A2✰

PubMed Central

Pan, Ying H.; Bahnson, Brian J.

2010-01-01

The properties of three discrete premicellar complexes (E1#, E2#, E3#) of pig pancreatic group-IB secreted phospholipase A2 (sPLA2) with monodisperse alkyl sulfates has been characterized [Berg, O. G., et al., Biochemistry 43, 7999–8013, 2004]. Here we have solved the 2.7 Å crystal structure of group-IB sPLA2 complexed with 12 molecules of octyl sulfate (C8S) in a form consistent with a tetrameric oligomeric that exists during the E1# phase of premicellar complexes. The alkyl tails of the C8S molecules are centered in the middle of the tetrameric cluster of sPLA2 subunits. Three of the four sPLA2 subunits also contain a C8S molecule in the active site pocket. The sulfate oxygen of a C8S ligand is complexed to the active site calcium in 3 of the 4 protein active sites. The interactions of the alkyl sulfate head group with Arg-6 and Lys-10, as well as the backbone amide of Met-20, are analogous to those observed in the previously solved sPLA2 crystal structures with bound phosphate and sulfate anions. The cluster of three anions found in the present structure is postulated to be the site for nucleating the binding of anionic amphiphiles to the interfacial surface of the protein, and therefore this binding interaction has implications for interfacial activation of the enzyme. PMID:20302975

Long-term trends of changes in pine and oak foliar nitrogen metabolism in response to chronic nitrogen amendments at Harvard Forest, MA

Treesearch

Rakesh Minocha; Swathi A. Turlapati; Stephanie Long; William H. McDowell; Subhash C. Minocha

2015-01-01

We evaluated the long-term (1995-2008) trends in foliar and sapwood metabolism, soil solution chemistry and tree mortality rates in response to chronic nitrogen (N) additions to pine and hardwood stands at the Harvard Forest Long Term Ecological Research (LTER) site. Common stress-related metabolites like polyamines (PAs), free amino acids (AAs) and inorganic elements...

Mapping of Residues Forming the Voltage Sensor of the Voltage-Dependent Anion-Selective Channel

NASA Astrophysics Data System (ADS)

Thomas, Lorie; Blachly-Dyson, Elizabeth; Colombini, Marco; Forte, Michael

1993-06-01

Voltage-gated ion-channel proteins contain "voltage-sensing" domains that drive the conformational transitions between open and closed states in response to changes in transmembrane voltage. We have used site-directed mutagenesis to identify residues affecting the voltage sensitivity of a mitochondrial channel, the voltage-dependent anion-selective channel (VDAC). Although charge changes at many sites had no effect, at other sites substitutions that increased positive charge also increased the steepness of voltage dependance and substitutions that decreased positive charge decreased voltage dependance by an appropriate amount. In contrast to the plasma membrane K^+ and Na^+ channels, these residues are distributed over large parts of the VDAC protein. These results have been used to define the conformational transitions that accompany voltage gating of an ion channel. This gating mechanism requires the movement of large portions of the VDAC protein through the membrane.

Identification of substitutional Li in n-type ZnO and its role as an acceptor

NASA Astrophysics Data System (ADS)

Johansen, K. M.; Zubiaga, A.; Makkonen, I.; Tuomisto, F.; Neuvonen, P. T.; Knutsen, K. E.; Monakhov, E. V.; Kuznetsov, A. Yu.; Svensson, B. G.

2011-06-01

Monocrystalline n-type zinc oxide (ZnO) samples prepared by different techniques and containing various amounts of lithium (Li) have been studied by positron annihilation spectroscopy (PAS) and secondary ion mass spectrometry. A distinct PAS signature of negatively charged Li atoms occupying a Zn-site (LiZn-), so-called substitutional Li, is identified and thus enables a quantitative determination of the content of LiZn. In hydrothermally grown samples with a total Li concentration of ~2×1017cm-3,LiZn is found to prevail strongly, with only minor influence, by other possible configurations of Li. Also in melt grown samples doped with Li to a total concentration as high as 1.5×1019cm-3, a considerable fraction of the Li atoms (at least 20%) is shown to reside on the Zn-site, but despite the corresponding absolute acceptor concentration of ⩾(2-3)×1018cm-3, the samples did not exhibit any detectable p-type conductivity. The presence of LiZn is demonstrated to account for the systematic difference in positron lifetime of 10-15 ps between Li-rich and Li-lean ZnO materials as found in the literature, but further work is needed to fully elucidate the role of residual hydrogen impurities and intrinsic open volume defects.

Specialty distribution of physician assistants and nurse practitioners in North Carolina.

PubMed

Fraher, Erin P; Morgan, Perri; Johnson, Anna

2016-04-01

Physician workforce projections often include scenarios that forecast physician shortages under different assumptions about the deployment of physician assistants (PAs) and nurse practitioners (NPs). These scenarios generally assume that PAs and NPs are an interchangeable resource and that their specialty distributions do not change over time. This study investigated changes in PA and NP specialty distribution in North Carolina between 1997 and 2013. The data show that over the study period, PAs and NPs practiced in a wide range of specialties, but each profession had a specific pattern. The proportion of PAs-but not NPs-reporting practice in primary care dropped significantly. PAs were more likely than NPs to report practice in urgent care, emergency medicine, and surgical subspecialties. Physician workforce models need to account for the different and changing specialization trends of NPs and PAs.

Comparing oncologist, nurse, and physician assistant attitudes toward discussions of negative emotions with patients.

PubMed

Morgan, Perri A; de Oliveira, Justine Strand; Alexander, Stewart C; Pollak, Kathryn I; Jeffreys, Amy S; Olsen, Maren K; Olson, Maren K; Arnold, Robert M; Abernethy, Amy P; Rodriguez, Keri L; Rodrigues, Keri L; Tulsky, James A

2010-01-01

Although research shows that empathic communication improves patient outcomes, physicians often fail to respond empathically to patients. Nurses and physician assistants (PAs) may be able to help fill the need for empathic communication. Our study compares the attitudes of oncologists, nurses, and PAs toward communication with patients who demonstrate negative emotions. We analyzed surveys from 48 oncologists, 26 PAs, and 22 nurses who participated in the Studying Communication in Oncologist-Patient Encounters trial. Surveys included previously validated items that examined attitudes toward communication with patients about emotion. The mean age of oncology physicians was higher (49 years) than that of PAs (40 years) or nurses (43 years), and 19% of physicians, 81% of PAs, and 100% of nurses were female. Race, years of oncology experience, and previous communication training were similar across provider types. Most nurses (82%) and PAs (68%) described themselves as having a socioemotional orientation, while most oncologists (70%) reported a technological/scientific orientation (p < .0001). PAs and nurses indicated more comfort with psychosocial talk than did oncologists (p < .0001). Discomfort with disclosing uncertainty and provider confidence and expectations when addressing patient concerns were similar across provider types. PAs and nurses were more oriented toward socioemotional aspects of medicine and were more comfortable with psychosocial talk than were oncologists. Future studies should examine whether these differences are attributable to other factors, including gender, and whether nurses and PAs are more likely than physicians to demonstrate empathic behaviors when patients express negative emotions.

Induction of cortical plasticity for reciprocal muscles by paired associative stimulation

PubMed Central

Suzuki, Makoto; Kirimoto, Hikari; Sugawara, Kazuhiro; Watanabe, Makoto; Shimizu, Shinobu; Ishizaka, Ikuyo; Yamada, Sumio; Matsunaga, Atsuhiko; Fukuda, Michinari; Onishi, Hideaki

2014-01-01

Background Paired associative stimulation (PAS) is widely used to induce plasticity in the human motor cortex. Although reciprocal inhibition of antagonist muscles plays a fundamental role in human movements, change in cortical circuits for reciprocal muscles by PAS is unknown. Methods We investigated change in cortical plasticity for reciprocal muscles during PAS. PAS consisted of 200 pairs of peripheral electric stimulation of the right median nerve at the wrist at a frequency of 0.25 Hz followed by transcranial magnetic stimulation of the left M1 at the midpoint between the center of gravities of the flexor carpi radialis (FCR) and extensor carpi radialis (ECR) muscles. Measures of motor cortical excitability included resting motor threshold (RMT), GABAA-mediated short-interval intracortical inhibition (SICI), and GABAB-mediated long-interval intracortical inhibition (LICI). Results Motor evoked potential amplitude-conditioned LICI for the FCR muscle was significantly decreased after PAS (P = 0.020), whereas that for the ECR muscle was significantly increased (P = 0.033). Changes in RMT and SICI for the FCR and ECR muscles were not significantly different before and after PAS. Corticospinal excitability for both reciprocal muscles was increased during PAS, but GABAB-mediated cortical inhibitory functions for the agonist and antagonist muscles were reciprocally altered after PAS. Conclusion These results implied that the cortical excitability for reciprocal muscles including GABAB-ergic inhibitory systems within human M1 could be differently altered by PAS. PMID:25365805

Tailoring peptide amphiphiles and their assemblies for biomedical applications

NASA Astrophysics Data System (ADS)

Lin, Brian

Peptide amphiphiles (PAs) are molecules composed of a peptide conjugated to a hydrophobic moiety, commonly a fatty acid. They closely resemble the structure of naturally occurring lipopeptides, produced by microbes as signaling and antimicrobial agents. The amphiphilic nature of PAs in concert with the large number of discovered functional peptides inspired scientists to exploit this molecular architecture for producing synthetic self-assembled bioactive materials. PA assemblies are sought after for a wide breadth of applications including disease therapy, regenerative medicine, and catalysis. However, with PAs, the peptide chemistry is a double-edged sword. The peptide component contributes significantly to both the activity and self-assembly. The physiochemical properties of different PAs lead to unique aggregation stability and morphological characteristics which are unpredictable, a priori. Therefore it is challenging to design bioactive PAs and control their self-assembly, simultaneously. This limitation slows the development of PAs for medical use. In this dissertation, methods to control the self-assembly of PAs and the effects of acylating a functional peptide will be discussed. In one part, efforts to direct the self-assembly of PAs into small spherical aggregates, a morphology infrequently observed, will be described. In another section, a strategy to control the stability of PA assemblies will be discussed. In the last section, a pH-responsive membrane perturbing peptide was modified with fatty acid tails and the properties of the resulting PAs will be presented. This dissertation provides some fundamental insight for the use and design of PA self-assemblies.

Physician-Assisted Suicide: Considering the Evidence, Existential Distress, and an Emerging Role for Psychiatry.

PubMed

Gopal, Abilash A

2015-06-01

Physician-assisted suicide (PAS) is one of the most provocative topics facing society today. Given the great responsibility conferred on physicians by recent laws allowing PAS, a careful examination of this subject is warranted by psychiatrists and other specialists who may be consulted during a patient's request for PAS. In this article, recent evidence regarding the implementation of PAS in the United States and The Netherlands is reviewed. Support is found for some concerns about PAS, such as the possibility that mental illness occurs at higher rates in patients requesting PAS, but not for other concerns, such as the fear that PAS will be practiced more frequently on vulnerable populations (the slippery-slope argument). These data and common arguments for and against PAS are discussed with an emphasis on the tension between values, such as maximizing patient autonomy and adhering to professional obligations, as well as the need for additional research that focuses more directly on the patient-centered perspective. Implications of the available evidence are discussed and lead to a consideration of mental anguish in terminally ill patients including aspects of existential distress and an acknowledgment of the importance of tailoring end-of-life care to the distinct set of values and experiences that shape each patient's perspective. The article concludes with a discussion of an expanding role for psychiatrists in evaluating patients who request PAS. © 2015 American Academy of Psychiatry and the Law.

Paired associative stimulation induces change in presynaptic inhibition of Ia terminals in wrist flexors in humans.

PubMed

Lamy, Jean-Charles; Russmann, Heike; Shamim, Ejaz A; Meunier, Sabine; Hallett, Mark

2010-08-01

Enhancements in the strength of corticospinal projections to muscles are induced in conscious humans by paired associative stimulation (PAS) to the motor cortex. Although most of the previous studies support the hypothesis that the increase of the amplitude of motor evoked potentials (MEPs) by PAS involves long-term potentiation (LTP)-like mechanism in cortical synapses, changes in spinal excitability after PAS have been reported, suggestive of parallel modifications in both cortical and spinal excitability. In a first series of experiments (experiment 1), we confirmed that both flexor carpi radialis (FCR) MEPs and FCR H reflex recruitment curves are enhanced by PAS. To elucidate the mechanism responsible for this change in the H reflex amplitude, we tested, using the same subjects, the hypothesis that enhanced H reflexes are caused by a down-regulation of the efficacy of mechanisms controlling Ia afferent discharge, including presynaptic Ia inhibition and postactivation depression. To address this question, amounts of both presynaptic Ia inhibition of FCR Ia terminals (D1 and D2 inhibitions methods; experiment 2) and postactivation depression (experiment 3) were determined before and after PAS. Results showed that PAS induces a significant decrease of presynaptic Ia inhibition of FCR terminals, which was concomitant with the facilitation of the H reflex. Postactivation depression was unaffected by PAS. It is argued that enhancement of segmental excitation by PAS relies on a selective effect of PAS on the interneurons controlling presynaptic inhibition of Ia terminals.

Evidence of Multiple Sorption Modes in Layered Double Hydroxides Using Mo As Structural Probe.

PubMed

Ma, Bin; Fernandez-Martinez, Alejandro; Grangeon, Sylvain; Tournassat, Christophe; Findling, Nathaniel; Claret, Francis; Koishi, Ayumi; Marty, Nicolas C M; Tisserand, Delphine; Bureau, Sarah; Salas-Colera, Eduardo; Elkaïm, Erik; Marini, Carlo; Charlet, Laurent

2017-05-16

Layered double hydroxides (LDHs) have been considered as effective phases for the remediation of aquatic environments, to remove anionic contaminants mainly through anion exchange mechanisms. Here, a combination of batch isotherm experiments and X-ray techniques was used to examine molybdate (MoO 4 2- ) sorption mechanisms on CaAl LDHs with increasing loadings of molybdate. Advanced modeling of aqueous data shows that the sorption isotherm can be interpreted by three retention mechanisms, including two types of edge sites complexes, interlayer anion exchange, and CaMoO 4 precipitation. Meanwhile, Mo geometry evolves from tetrahedral to octahedral on the edge, and back to tetrahedral coordination at higher Mo loadings, indicated by Mo K-edge X-ray absorption spectra. Moreover, an anion exchange process on both CaAl LDHs was followed by in situ time-resolved synchrotron-based X-ray diffraction, remarkably agreeing with the sorption isotherm. This detailed molecular view shows that different uptake mechanisms-edge sorption, interfacial dissolution-reprecipitation-are at play and control anion uptake under environmentally relevant conditions, which is contrast to the classical view of anion exchange as the primary retention mechanism. This work puts all these mechanisms in perspective, offering a new insight into the complex interplay of anion uptake mechanisms by LDH phases, by using changes in Mo geometry as powerful molecular-scale probe.

Fluoride-selective colorimetric sensor based on thiourea binding site and anthraquinone reporter.

PubMed

Wu, Fang-ying; Hu, Mei-hua; Wu, Yu-mei; Tan, Xiao-fang; Zhao, Yong-qiang; Ji, Zhao-jun

2006-11-01

A structurally simple colorimetric sensor, N-4-nitrobenzene-N'-1'-anthraquinone-thiourea (1), for anions was synthesized and characterized by (1)H NMR, ESI mass and IR methods. In acetonitrile, the addition of F(-) changed 1 solution from colorless to yellow. In the presence of other anions such as CH(3)CO(2)(-), H(2)PO(4)(-), HSO(4)(-) and Cl(-), however, the absorption spectrum of 1 was slightly red shifted with no obvious color changes observed. The association constants of anionic complexes followed the order of F(-)>CH(3)CO(2)(-)>H(2)PO(4)(-)>HSO(4)(-)>Cl(-)>Br(-), which was different from the order of anion basicity. AM1 calculation results indicated that the most stable configuration of 1 existed in the Z-E-conformation with a six-membered ring via intramolecular hydrogen bond. This made thiourea moiety of 1 in an unfavorable conformation to bond with oxygen-anionic substrates such as CH(3)CO(2)(-) and H(2)PO(4)(-), thus leading to a high selectivity and sensitivity for the detection of F(-).

Attitudes towards, and wishes for, euthanasia in advanced cancer patients at a palliative medicine unit.

PubMed

Johansen, Sissel; Hølen, Jacob Chr; Kaasa, Stein; Loge, Håvard Jon; Materstvedt, Lars Johan

2005-09-01

Most studies on attitudes towards euthanasia and physician-assisted suicide (PAS) have been conducted in healthy populations. The aim of this study is to explore and describe attitudes towards, and wishes for, euthanasia/PAS in cancer patients with short life expectancy. Semi-structured interviews with 18 cancer patients with a life expectancy of less than nine months. All patients were recruited from an inpatient palliative medicine unit. Patients holding a positive attitude towards euthanasia/PAS do not necessarily want euthanasia/PAS for themselves. Wishes are different from requests for euthanasia/PAS. Fear of future pain and a painful death were the main reasons given for a possible wish for euthanasia/PAS. Worries about minimal quality of life and lack of hope also contributed to such thoughts. Wishes for euthanasia/PAS were hypothetical; they were future oriented and with a prerequisite that intense pain, lack of quality of life and/or hope had to be present. Additionally, wishes were fluctuating and ambivalent. The wish to die in these patients does not seem to be constant. Rather, this wish is more appropriately seen as an ambivalent and fluctuating mental 'solution' for the future. Health care providers should be aware of this when responding to utterances regarding euthanasia/PAS.

para-Aminosalicylic acid is a prodrug targeting dihydrofolate reductase in Mycobacterium tuberculosis.

PubMed

Zheng, Jun; Rubin, Eric J; Bifani, Pablo; Mathys, Vanessa; Lim, Vivian; Au, Melvin; Jang, Jichan; Nam, Jiyoun; Dick, Thomas; Walker, John R; Pethe, Kevin; Camacho, Luis R

2013-08-09

para-Aminosalicylic acid (PAS) is one of the antimycobacterial drugs currently used for multidrug-resistant tuberculosis. Although it has been in clinical use for over 60 years, its mechanism(s) of action remains elusive. Here we report that PAS is a prodrug targeting dihydrofolate reductase (DHFR) through an unusual and novel mechanism of action. We provide evidences that PAS is incorporated into the folate pathway by dihydropteroate synthase (DHPS) and dihydrofolate synthase (DHFS) to generate a hydroxyl dihydrofolate antimetabolite, which in turn inhibits DHFR enzymatic activity. Interestingly, PAS is recognized by DHPS as efficiently as its natural substrate para-amino benzoic acid. Chemical inhibition of DHPS or mutation in DHFS prevents the formation of the antimetabolite, thereby conferring resistance to PAS. In addition, we identified a bifunctional enzyme (riboflavin biosynthesis protein (RibD)), a putative functional analog of DHFR in a knock-out strain. This finding is further supported by the identification of PAS-resistant clinical isolates encoding a RibD overexpression mutation displaying cross-resistance to genuine DHFR inhibitors. Our findings reveal that a metabolite of PAS inhibits DHFR in the folate pathway. RibD was shown to act as a functional analog of DHFR, and as for DHFS, both were shown to be associated in PAS resistance in laboratory strains and clinical isolates.

Concentrations of proanthocyanidins in common foods and estimations of normal consumption.

PubMed

Gu, Liwei; Kelm, Mark A; Hammerstone, John F; Beecher, Gary; Holden, Joanne; Haytowitz, David; Gebhardt, Susan; Prior, Ronald L

2004-03-01

Proanthocyanidins (PAs) have been shown to have potential health benefits. However, no data exist concerning their dietary intake. Therefore, PAs in common and infant foods from the U.S. were analyzed. On the bases of our data and those from the USDA's Continuing Survey of Food Intakes by Individuals (CSFII) of 1994-1996, the mean daily intake of PAs in the U.S. population (>2 y old) was estimated to be 57.7 mg/person. Monomers, dimers, trimers, and those above trimers contribute 7.1, 11.2, 7.8, and 73.9% of total PAs, respectively. The major sources of PAs in the American diet are apples (32.0%), followed by chocolate (17.9%) and grapes (17.8%). The 2- to 5-y-old age group (68.2 mg/person) and men >60 y old (70.8 mg/person) consume more PAs daily than other groups because they consume more fruit. The daily intake of PAs for 4- to 6-mo-old and 6- to 10-mo-old infants was estimated to be 1.3 mg and 26.9 mg, respectively, based on the recommendations of the American Academy of Pediatrics. This study supports the concept that PAs account for a major fraction of the total flavonoids ingested in Western diets.

Physician-assisted suicide: the legal slippery slope.

PubMed

Walker, R M

2001-01-01

In Oregon, physicians can prescribe lethal amounts of medication only if requested by competent, terminally ill patients. However, the possibility of extending the practice to patients who lack decisional capacity exists. This paper examines why the legal extension of physician-assisted suicide (PAS) to incapacitated patients is possible, and perhaps likely. The author reviews several pivotal court cases that have served to define the distinctions and legalities among "right-to-die" cases and the various forms of euthanasia and PAS. Significant public support exists for legalizing PAS and voluntary euthanasia in the United States. The only defenses against sliding from PAS to voluntary euthanasia are adhering to traditional physician morality that stands against it and keeping the issue of voluntary euthanasia legally framed as homicide. However, if voluntary euthanasia evolves euphemistically as a medical choice issue, then the possibility of its legalization exists. If courts allow PAS to be framed as a basic personal right akin to the right to refuse treatment, and if they rely on right-to-die case precedents, then they will likely extend PAS to voluntary euthanasia and nonvoluntary euthanasia. This would be done by extending the right to PAS to incapacitated patients, who may or may not have expressed a choice for PAS prior to incapacity.

Physician assistants as servant leaders: meeting the needs of the underserved.

PubMed

Huckabee, Michael J; Wheeler, Daniel W

2011-01-01

The purpose of this study was to determine if the level of servant leader characteristics in clinically practicing physician assistants (PAs) in underserved populations differed from PAs serving in other locales. Five subscales of servant leadership: altruistic calling, emotional healing, wisdom, persuasive mapping, and organizational stewardship, were measured in a quantitative study of clinically practicing PAs using a self-rating survey and a similar survey by others rating the PA. Of 777 PAs invited, 321 completed the survey. On a scale of 1 to 5, mean PA self-ratings ranged from 3.52 (persuasive mapping) to 4.05 (wisdom). Other raters' scores paired with the self-rated PA scores were comparable in all subscales except wisdom, which was rated higher by the other raters (4.32 by other raters, 4.01 by PAs, P= .002). There was no significant difference in the measures of servant leadership reported by PAs serving the underserved compared to PAs serving in other populations. Servant leader subscales were higher for PAs compared to previous studies of other health care or community leader populations. The results found that the PA population studied had a prominent level of servant leadership characteristics that did not differ between those working with underserved and nonunderserved populations.

Expression pattern of the type 1 sigma receptor in the brain and identity of critical anionic amino acid residues in the ligand-binding domain of the receptor.

PubMed

Seth, P; Ganapathy, M E; Conway, S J; Bridges, C D; Smith, S B; Casellas, P; Ganapathy, V

2001-07-25

The type 1 sigma receptor (sigmaR1) has been shown to participate in a variety of functions in the central nervous system. To identify the specific regions of the brain that are involved in sigmaR1 function, we analyzed the expression pattern of the receptor mRNA in the mouse brain by in situ hybridization. SigmaR1 mRNA was detectable primarily in the cerebral cortex, hippocampus, and Purkinje cells of cerebellum. To identify the critical anionic amino acid residues in the ligand-binding domain of sigmaR1, we employed two different approaches: chemical modification of anionic amino acid residues and site-directed mutagenesis. Chemical modification of anionic amino acids in sigmaR1 with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide reduced the ligand-binding activity markedly. Since it is known that a splice variant of this receptor which lacks exon 3 does not have the ability to bind sigma ligands, the ligand-binding domain with its critical anionic amino acid residues is likely to be present in or around the region coded by exon 3. Therefore, each of the anionic amino acids in this region was mutated individually and the influence of each mutation on ligand binding was assessed. These studies have identified two anionic amino acids, D126 and E172, that are obligatory for ligand binding. Even though the ligand-binding function was abolished by these two mutations, the expression of these mutants was normal at the protein level. These results show that sigmaR1 is expressed at high levels in specific areas of the brain that are involved in memory, emotion and motor functions. The results also provide important information on the chemical nature of the ligand-binding site of sigmaR1 that may be of use in the design of sigmaR1-specific ligands with potential for modulation of sigmaR1-related brain functions.

Defects in doped LaGaO3 anionic conductors: linking NMR spectral features, local environments, and defect thermodynamics.

PubMed

Blanc, Frédéric; Middlemiss, Derek S; Gan, Zhehong; Grey, Clare P

2011-11-09

Doped lanthanum gallate perovskites (LaGaO(3)) constitute some of the most promising electrolyte materials for solid oxide fuel cells operating in the intermediate temperature regime. Here, an approach combining experimental multinuclear NMR spectroscopy with density functional theory total energy and GIPAW NMR calculations yields a comprehensive understanding of the structural and defect chemistries of Sr- and Mg-doped LaGaO(3) anionic conductors. The DFT energetics demonstrate that Ga-V(O)-Ga (V(O) = oxygen vacancy) environments are favored (vs Ga-V(O)-Mg, Mg-V(O)-Mg and Mg-O-Mg-V(O)-Ga) across a range y = 0.0625, 0.125, and 0.25 of fractional Mg contents in LaGa(1-y)Mg(y)O(3-y/2). The results are interpreted in terms of doping and mean phase formation energies (relative to binary oxides) and are compared with previous calculations and experimental calorimetry data. Experimental multinuclear NMR data reveal that while Mg sites remain six-fold coordinated across the range of phase stoichiometries, albeit with significant structural disorder, a stoichiometry-dependent minority of the Ga sites resonate at a shift consistent with Ga(V) coordination, demonstrating that O vacancies preferentially locate in the first anion coordination shell of Ga. The strong Mg-V(O) binding inferred by previous studies is not observed here. The (17)O NMR spectra reveal distinct resonances that can be assigned by using the GIPAW NMR calculations to anions occupying equatorial and axial positions with respect to the Ga(V)-V(O) axis. The disparate shifts displayed by these sites are due to the nature and extent of the structural distortions caused by the O vacancies.

Corrosion Control through a Better Understanding of the Metallic Substrate/Organic Coating Interface

DTIC Science & Technology

1990-03-16

electrically coupling steel electrodes in different pH solutions. Anodic and cathodic sites beneath a coating are known to produce acidic and alkaline...9,16]. Lead-steel couples were used to model the interactions between metallic lead and steel. Both acidic and alkaline solutions were used because the...acetate solution can be altered by the addition of acid or base without precipitation of the anion. Other anions such as chlorides and sulfates are

Final Technical Report: Targeting DOE-Relevant Ions with Supramolecular Strategies, DE-SC0010555

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

Bowman-James, Kristin

The effectiveness of three popular supramolecular strategies to selectively target negatively charged ions (anions) was evaluated. Ions of interest included oxo anions, particularly sulfate, that hamper nuclear waste remediation. Three objectives were pursued using a simple building block strategies and by strategically placing anion-binding sites at appropriate positions on organic host molecules. The goal of the first objective was to assess the influence of secondary, tertiary and quaternized amines on binding tetrahedral anions using mixed amide/amine macrocyclic and urea/amine hosts containing aromatic or heteroaromatic spacers. Objective 2 focused on the design of ion pair hosts, using mixed macrocyclic anion hostsmore » joined through polyether linkages. Objective 3 was to explore the synthesis of new metal-linked extended macrocyclic frameworks to leverage anion binding. Key findings were that smaller 24-membered macrocycles provided the most complementary binding for sulfate ion and mixed urea/amine chelates showed enhanced binding over amide corollaries in addition to being highly selective for SO 4 2- in the presence of small quantities of water. In addition to obtaining prototype metal-linked macrocyclic anion hosts, a new dipincer ligand was designed that can be used to link macrocyclic or other supramolecular hosts in extended frameworks. When the tetraamide-based pincers are bound to two metal ions, an interesting phenomenon occurs. Upon deprotonation of the amides, two new protons appear between adjacent carbonyl pairs on the ligand, which may modify the chemistry, and metal-metal interactions in the complexes. Gel formation occurred for some of these extended hosts, and the physical properties are currently under investigation. The new tetracarboxamide-based pincers can also provide basic frameworks for double macrocycles capable of binding ion pairs as well as for binding metal ions and exploring intermetallic interactions through the pyrazine π system. Additionally appendages capable of influencing solvation effects can be introduced, and a number of other potential applications can be realized in areas such as soft materials chemistry, catalysis, sensing, and proton switches, the latter for binding and release of targeted guests. These findings provide a better foundation for understanding the selective binding of anions by targeted placement of hydrogen binding sites, and the strengths and weaknesses of various functional groups, that will allow for more the design of more effective anion sequestering agents. Our design strategy also used simple, cost-effective building blocks for host synthesis to allow for scale-up should real-world applications be forthcoming.« less

Artificial ligand binding within the HIF2[alpha] PAS-B domain of the HIF2 transcription factor

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

Scheuermann, Thomas H.; Tomchick, Diana R.; Machius, Mischa

2009-05-12

The hypoxia-inducible factor (HIF) basic helix-loop-helix Per-aryl hydrocarbon receptor nuclear translocator (ARNT)-Sim (bHLH-PAS) transcription factors are master regulators of the conserved molecular mechanism by which metazoans sense and respond to reductions in local oxygen concentrations. In humans, HIF is critically important for the sustained growth and metastasis of solid tumors. Here, we describe crystal structures of the heterodimer formed by the C-terminal PAS domains from the HIF2{alpha} and ARNT subunits of the HIF2 transcription factor, both in the absence and presence of an artificial ligand. Unexpectedly, the HIF2{alpha} PAS-B domain contains a large internal cavity that accommodates ligands identified frommore » a small-molecule screen. Binding one of these ligands to HIF2{alpha} PAS-B modulates the affinity of the HIF2{alpha}:ARNT PAS-B heterodimer in vitro. Given the essential role of PAS domains in forming active HIF heterodimers, these results suggest a presently uncharacterized ligand-mediated mechanism for regulating HIF2 activity in endogenous and clinical settings.« less

Locating the Anion-selectivity Filter of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Chloride Channel

PubMed Central

Cheung, Min; Akabas, Myles H.

1997-01-01

The cystic fibrosis transmembrane conductance regulator forms an anion-selective channel; the site and mechanism of charge selectivity is unknown. We previously reported that cysteines substituted, one at a time, for Ile331, Leu333, Arg334, Lys335, Phe337, Ser341, Ile344, Arg347, Thr351, Arg352, and Gln353, in and flanking the sixth membrane-spanning segment (M6), reacted with charged, sulfhydryl-specific, methanethiosulfonate (MTS) reagents. We inferred that these residues are on the water-accessible surface of the protein and may line the ion channel. We have now measured the voltage-dependence of the reaction rates of the MTS reagents with the accessible, engineered cysteines. By comparing the reaction rates of negatively and positively charged MTS reagents with these cysteines, we measured the extent of anion selectivity from the extracellular end of the channel to eight of the accessible residues. We show that the major site determining anion vs. cation selectivity is near the cytoplasmic end of the channel; it favors anions by ∼25-fold and may involve the residues Arg347 and Arg352. From the voltage dependence of the reaction rates, we calculated the electrical distance to the accessible residues. For the residues from Leu333 to Ser341 the electrical distance is not significantly different than zero; it is significantly different than zero for the residues Thr351 to Gln353. The maximum electrical distance measured was 0.6 suggesting that the channel extends more cytoplasmically and may include residues flanking the cytoplasmic end of the M6 segment. Furthermore, the electrical distance calculations indicate that R352C is closer to the extracellular end of the channel than either of the adjacent residues. We speculate that the cytoplasmic end of the M6 segment may loop back into the channel narrowing the lumen and thereby forming both the major resistance to current flow and the anion-selectivity filter. PMID:9089437

Spectral Fluorescence Properties of an Anionic Oxacarbocyanine Dye in Complexes with Human Serum Albumin

NASA Astrophysics Data System (ADS)

Pronkin, P. G.; Tatikolov, A. S.

2015-07-01

The spectral fluorescence properties of the anionic oxacarbocyanine dye 3,3'-di-(γ-sulfopropyl)-5,5'-diphenyl-9-ethyloxacarbocyanine betaine (OCC) were studied in solutions and in complexes with human serum albumin (HSA). Interaction with HSA leads to a significant increase in the fluorescence of the dye. We studied quenching of the fluorescence of OCC in a complex with HSA by ibuprofen and warfarin. Data on quenching of fluorescence by ibuprofen indicate binding of the dye to binding site II of subdomain IIIA in the HSA molecule. Synchronous fluorescence spectra of human serum albumin in the presence of OCC showed that complexation with OCC does not lead to appreciable rearrangement of the protein molecule at the binding site.

Bromidotetra-kis-(1H-2-ethyl-5-methyl-imidazole-κN)copper(II) bromide.

PubMed

Godlewska, Sylwia; Baranowska, Katarzyna; Socha, Joanna; Dołęga, Anna

2011-12-01

The Cu(II) ion in the title compound, [CuBr(C(6)H(10)N(2))(4)]Br, is coordinated in a square-based-pyramidal geometry by the N atoms of four imidazole ligands and a bromide anion in the apical site. Both the Cu(II) and Br(-) atoms lie on a crystallographic fourfold axis. In the crystal, the [CuBr(C(6)H(10)N(2))(4)](+) complex cations are linked to the uncoordinated Br(-) anions (site symmetry [Formula: see text]) by N-H⋯Br hydrogen bonds, generating a three-dimensional network. The ethyl group of the imidazole ligand was modelled as disordered over two orientations with occupancies of 0.620 (8) and 0.380 (8).

The geography of hotspots of rarity-weighted richness of birds and their coverage by Natura 2000

PubMed Central

de Albuquerque, Fábio Suzart; Gregory, Andrew

2017-01-01

A major challenge for biogeographers and conservation planners is to identify where to best locate or distribute high-priority areas for conservation and to explore whether these areas are well represented by conservation actions such as protected areas (PAs). We aimed to identify high-priority areas for conservation, expressed as hotpots of rarity-weighted richness (HRR)–sites that efficiently represent species–for birds across EU countries, and to explore whether HRR are well represented by the Natura 2000 network. Natura 2000 is an evolving network of PAs that seeks to conserve biodiversity through the persistence of the most patrimonial species and habitats across Europe. This network includes Sites of Community Importance (SCI) and Special Areas of Conservation (SAC), where the latter regulated the designation of Special Protected Areas (SPA). Distribution maps for 416 bird species and complementarity-based approaches were used to map geographical patterns of rarity-weighted richness (RWR) and HRR for birds. We used species accumulation index to evaluate whether RWR was efficient surrogates to identify HRRs for birds. The results of our analysis support the proposition that prioritizing sites in order of RWR is a reliable way to identify sites that efficiently represent birds. HRRs were concentrated in the Mediterranean Basin and alpine and boreal biogeographical regions of northern Europe. The cells with high RWR values did not correspond to cells where Natura 2000 was present. We suggest that patterns of RWR could become a focus for conservation biogeography. Our analysis demonstrates that identifying HRR is a robust approach for prioritizing management actions, and reveals the need for more conservation actions, especially on HRR. PMID:28379991

The geography of hotspots of rarity-weighted richness of birds and their coverage by Natura 2000.

PubMed

Albuquerque, Fábio Suzart de; Gregory, Andrew

2017-01-01

A major challenge for biogeographers and conservation planners is to identify where to best locate or distribute high-priority areas for conservation and to explore whether these areas are well represented by conservation actions such as protected areas (PAs). We aimed to identify high-priority areas for conservation, expressed as hotpots of rarity-weighted richness (HRR)-sites that efficiently represent species-for birds across EU countries, and to explore whether HRR are well represented by the Natura 2000 network. Natura 2000 is an evolving network of PAs that seeks to conserve biodiversity through the persistence of the most patrimonial species and habitats across Europe. This network includes Sites of Community Importance (SCI) and Special Areas of Conservation (SAC), where the latter regulated the designation of Special Protected Areas (SPA). Distribution maps for 416 bird species and complementarity-based approaches were used to map geographical patterns of rarity-weighted richness (RWR) and HRR for birds. We used species accumulation index to evaluate whether RWR was efficient surrogates to identify HRRs for birds. The results of our analysis support the proposition that prioritizing sites in order of RWR is a reliable way to identify sites that efficiently represent birds. HRRs were concentrated in the Mediterranean Basin and alpine and boreal biogeographical regions of northern Europe. The cells with high RWR values did not correspond to cells where Natura 2000 was present. We suggest that patterns of RWR could become a focus for conservation biogeography. Our analysis demonstrates that identifying HRR is a robust approach for prioritizing management actions, and reveals the need for more conservation actions, especially on HRR.

Adapting environmental function analysis for management of protected areas in small islands--case of Pico Island (the Azores).

PubMed

Calado, Helena; Bragagnolo, Chiara; Silva, Susana; Vergílio, Marta

2016-04-15

Protected areas (PAs) are considered key priorities for ensuring long-term sustainability of small islands. The traditional approach of conservation versus development is currently being replaced by an approach of "win-win" relationships. During the last decades PAs have been increasingly requested to simultaneously ensure biodiversity conservation, mainstream ecosystem services into main development policies, and accounting for leisure-related revenues to sustain local and regional economies. Following this new paradigm, the Smartparks project (Planning and Management System for Small Islands Protected Areas), encompassing this study, aimed at an innovative approach for supporting the management of PAs in small islands. In this study, we propose a methodology based on Environmental Functional Analyses (EFA) to compare the potential for conservation and the potential for use of PAs that can be used not only on small islands but also in other territories. For this purpose, a set of environmental and socio-economic components was defined and selected indicators describing each component to calculate conservation and use/development functions of PAs were established. Pico Island, in the Azores archipelago (Portugal), was selected as the case study for testing the methodology. The EFA for all PAs of Pico Island was performed identifying those with more potential for conservation or for development of human activities, and also those with high levels of conflict. A total of 34 indicators was applied (assigning a value from 1 to 3) to the 22 PAs composing the INP of Pico Island: 44% were scored with a value of 1, in both ecological and social components; 22% and 29% were scored 3 in ecological and social components respectively. Social indicators were generally considered less important than environmental ones. In general, PAs presented higher values for conservation. The results further show that the potential for conservation and/or development was consistent with the IUCN category and the objectives assigned to each PA at the time of its classification. However, most PAs are located in the conflict zone of the EFA matrix, revealing a high interaction between PAs conservation objectives and human activities, which brings concern to decision makers and PAs managers. Despite several limitations, the method allowed the performances of PAs to be compared, providing a suitable tool to support rapid assessments and monitoring of PA networks in small islands. The adaptation of the EFA to the PA domain traces a new path for estimating the multiple values of PAs and it may contribute to improve PA management and decision-making. The method could be further included as part of scenario exercise and adaptive management, supporting the prediction of the future evolution of PAs and assessing their potential for conservation in the future throughout the proposed indicators. Thus, the methodology is not exclusive for small islands contexts and, with necessary adaptations and rescaling, it could be a powerful tool in PAs network management worldwide. Copyright © 2016 Elsevier Ltd. All rights reserved.

Wildlife population trends in protected areas predicted by national socio-economic metrics and body size

PubMed Central

Barnes, Megan D.; Craigie, Ian D.; Harrison, Luke B.; Geldmann, Jonas; Collen, Ben; Whitmee, Sarah; Balmford, Andrew; Burgess, Neil D.; Brooks, Thomas; Hockings, Marc; Woodley, Stephen

2016-01-01

Ensuring that protected areas (PAs) maintain the biodiversity within their boundaries is fundamental in achieving global conservation goals. Despite this objective, wildlife abundance changes in PAs are patchily documented and poorly understood. Here, we use linear mixed effect models to explore correlates of population change in 1,902 populations of birds and mammals from 447 PAs globally. On an average, we find PAs are maintaining populations of monitored birds and mammals within their boundaries. Wildlife population trends are more positive in PAs located in countries with higher development scores, and for larger-bodied species. These results suggest that active management can consistently overcome disadvantages of lower reproductive rates and more severe threats experienced by larger species of birds and mammals. The link between wildlife trends and national development shows that the social and economic conditions supporting PAs are critical for the successful maintenance of their wildlife populations. PMID:27582180

Designing universal primers for the isolation of DNA sequences encoding Proanthocyanidins biosynthetic enzymes in Crataegus aronia

PubMed Central

2012-01-01

Background Hawthorn is the common name of all plant species in the genus Crataegus, which belongs to the Rosaceae family. Crataegus are considered useful medicinal plants because of their high content of proanthocyanidins (PAs) and other related compounds. To improve PAs production in Crataegus tissues, the sequences of genes encoding PAs biosynthetic enzymes are required. Findings Different bioinformatics tools, including BLAST, multiple sequence alignment and alignment PCR analysis were used to design primers suitable for the amplification of DNA fragments from 10 candidate genes encoding enzymes involved in PAs biosynthesis in C. aronia. DNA sequencing results proved the utility of the designed primers. The primers were used successfully to amplify DNA fragments of different PAs biosynthesis genes in different Rosaceae plants. Conclusion To the best of our knowledge, this is the first use of the alignment PCR approach to isolate DNA sequences encoding PAs biosynthetic enzymes in Rosaceae plants. PMID:22883984

Designing universal primers for the isolation of DNA sequences encoding Proanthocyanidins biosynthetic enzymes in Crataegus aronia.

PubMed

Zuiter, Afnan Saeid; Sawwan, Jammal; Al Abdallat, Ayed

2012-08-10

Hawthorn is the common name of all plant species in the genus Crataegus, which belongs to the Rosaceae family. Crataegus are considered useful medicinal plants because of their high content of proanthocyanidins (PAs) and other related compounds. To improve PAs production in Crataegus tissues, the sequences of genes encoding PAs biosynthetic enzymes are required. Different bioinformatics tools, including BLAST, multiple sequence alignment and alignment PCR analysis were used to design primers suitable for the amplification of DNA fragments from 10 candidate genes encoding enzymes involved in PAs biosynthesis in C. aronia. DNA sequencing results proved the utility of the designed primers. The primers were used successfully to amplify DNA fragments of different PAs biosynthesis genes in different Rosaceae plants. To the best of our knowledge, this is the first use of the alignment PCR approach to isolate DNA sequences encoding PAs biosynthetic enzymes in Rosaceae plants.

Wildlife population trends in protected areas predicted by national socio-economic metrics and body size

NASA Astrophysics Data System (ADS)

Barnes, Megan D.; Craigie, Ian D.; Harrison, Luke B.; Geldmann, Jonas; Collen, Ben; Whitmee, Sarah; Balmford, Andrew; Burgess, Neil D.; Brooks, Thomas; Hockings, Marc; Woodley, Stephen

2016-09-01

Ensuring that protected areas (PAs) maintain the biodiversity within their boundaries is fundamental in achieving global conservation goals. Despite this objective, wildlife abundance changes in PAs are patchily documented and poorly understood. Here, we use linear mixed effect models to explore correlates of population change in 1,902 populations of birds and mammals from 447 PAs globally. On an average, we find PAs are maintaining populations of monitored birds and mammals within their boundaries. Wildlife population trends are more positive in PAs located in countries with higher development scores, and for larger-bodied species. These results suggest that active management can consistently overcome disadvantages of lower reproductive rates and more severe threats experienced by larger species of birds and mammals. The link between wildlife trends and national development shows that the social and economic conditions supporting PAs are critical for the successful maintenance of their wildlife populations.

Ruthenium(II) 2,2'-bibenzimidazole complex as a second-sphere receptor for anions interaction and colorimeter.

PubMed

Cui, Ying; Niu, Yan-Li; Cao, Man-Li; Wang, Ke; Mo, Hao-Jun; Zhong, Yong-Rui; Ye, Bao-Hui

2008-07-07

A ruthenium(II) complex [Ru(bpy) 2(H 2bbim)](PF 6) 2 ( 1) as anions receptor has been exploited, where Ru(II)-bpy moiety acts as a chromophore and the H 2bbim ligand as an anion binding site. A systematic study suggests that 1 interacts with the Cl (-), Br (-), I (-), NO 3 (-), HSO 4 (-), and H 2PO 4 (-) anions via the formation of hydrogen bonds. Whereas 1 undergoes a stepwise process with the addition of F (-) and OAc (-) anions: formation of the monodeprotonated complex [Ru(bpy) 2(Hbbim)] with a low anion concentration, followed by the double-deprotonated complex [Ru(bpy) 2(bbim)], in the presence of a high anion concentration. These stepwise processes concomitant with the changes of vivid colors from yellow to orange brown and then to violet can be used for probing the F (-) and OAc (-) anions by naked eye. The deprotonation processes are not only determined by the basicity of the anion but also related to the strength of hydrogen bonding, as well as the stability of the formed compounds. Moreover, a double-deprotonated complex [Ru(bpy) 2(bbim)].CH 3OH.H 2O ( 3) has been synthesized, and the structural changes induced by the deprotonation has also been investigated. In addition, complexes [Ru(bpy) 2(Hbbim)] 2(HOAc) 3Cl 2.12H 2O ( 2), [Ru(bpy) 2(Hbbim)](HCCl 3CO 2)(CCl 3CO 2).2H 2O ( 4), and [Ru(bpy) 2(H 2bbim)](CF 3CO 2) 2.4H 2O ( 5) have been synthesized to observe the second sphere coordination between the Ru(II)-H 2bbim moiety and carboxylate groups via hydrogen bonds in the solid state.

Extracellular Determinants of Anion Discrimination of the Cl−/H+ Antiporter Protein CLC-5*

PubMed Central

De Stefano, Silvia; Pusch, Michael; Zifarelli, Giovanni

2011-01-01

Mammalian CLC proteins comprise both Cl− channels and Cl−/H+ antiporters that carry out fundamental physiological tasks by transporting Cl− across plasma membrane and intracellular compartments. The NO3− over Cl− preference of a plant CLC transporter has been pinpointed to a conserved serine residue located at Scen and it is generally assumed that the other two binding sites of CLCs, Sext and Sin, do not substantially contribute to anion selectivity. Here we show for the Cl−/H+ antiporter CLC-5 that the conserved and extracellularly exposed Lys210 residue is critical to determine the anion specificity for transport activity. In particular, mutations that neutralize or invert the charge at this position reverse the NO3− over Cl− preference of WT CLC-5 at a concentration of 100 mm, but do not modify the coupling stoichiometry with H+. The importance of the electrical charge is shown by chemical modification of K210C with positively charged cysteine-reactive compounds that reintroduce the WT preference for Cl−. At saturating extracellular anion concentrations, neutralization of Lys210 is of little impact on the anion preference, suggesting an important role of Lys210 on the association rate of extracellular anions to Sext. PMID:21921031

Why do we lose protected areas? Factors influencing protected area downgrading, downsizing and degazettement in the tropics and subtropics.

PubMed

Symes, William S; Rao, Madhu; Mascia, Michael B; Carrasco, L Roman

2016-02-01

Protected areas (PAs) are an essential tool for the conservation of biodiversity globally. Previous studies have focussed on the effectiveness of PAs and the design of optimal PA networks. However, not all PAs remain intact permanently; many PAs undergo downgrading, downsizing and/or degazettement (PADDD), a fact largely ignored until recently. The drivers of enacted PADDD events and the factors influencing its spatial occurrence are poorly understood, potentially undermining the efficacy of PAs and PA networks. Here we examine the spatial relationship between PADDD and economic, demographic and structural variables, using a 110-year data set of 342 enacted PADDD events across 44 countries in the tropics and subtropics. We find that the probability of an enacted PADDD event increases with the size of the PA and through a synergistic interaction between PA size and local population densities. Our results are robust to the under-reporting of enacted PADDD events that occur among smaller PAs and in regions with lower population density. We find an economic motive for PADDD events, given that the opportunity costs associated with larger PAs are higher, on average, than smaller PAs. Our findings suggest a need for conservation practitioners to better consider PA characteristics, as well as the social, economic and political context in which PAs are situated, to aid the creation of more efficient and sustainable PA networks. In particular, the dynamics of enacted PADDD events highlight the need to explicitly consider PA robustness as a core component of systematic conservation planning for PA networks. © 2015 John Wiley & Sons Ltd.

The effects of paired associative stimulation on knee extensor motor excitability of individuals post-stroke: A pilot study

PubMed Central

Rogers, Lynn M.; Brown, David A.; Stinear, James W.

2012-01-01

Objective Paired associative stimulation (PAS) modulates bilateral distal lower limb motor pathways during walking. We assessed the effects of inhibitory PAS applied to the vastus medialis (VM) motor pathways of chronic stroke patients. Methods PAS consisted of 120 electrical stimuli applied to the femoral nerve paired with transcranial magnetic stimulation (TMS) of the lower limb primary motor cortex so that the estimated arrival of the afferent volley occurred 8 ms after delivery of the magnetic stimulus. Stimulus pairs were delivered to the non-paretic VM motor system of 11 chronic stroke patients and the right limb motor system of 11 non-impaired subjects at 0.19 Hz. The effects of PAS on VM motor pathway excitability and muscle activity were assessed during pedaling. TMS-induced motor evoked potential (MEP) amplitudes and the percent of VM activity in the flexion phase of active pedaling (%FLEXVM) was examined before and after PAS. Results Inhibitory PAS reduced VM MEP amplitudes in the target limb (p < 0.05) of both groups, while post-PAS paretic VM MEP amplitudes increased for some patients and decreased for others. Group mean paretic limb %FLEXVM was not altered by inhibitory PAS. Conclusions These results indicate PAS can be used to manipulate motor cortical excitability in proximal lower limb representations, however the sign of induced modulation was unpredictable and cyclic muscle activity was not modified. Significance The study has important implications for the development of therapies involving non-invasive brain stimulation to modify abnormal motor behavior following stroke. PMID:21130032

Predictive Modeling the Physician Assistant Supply: 2010–2025

PubMed Central

Hooker, Roderick S.; Cawley, James F.; Everett, Christine M.

2011-01-01

Objective A component of health-care reform in 2010 identified physician assistants (PAs) as needed to help mitigate the expected doctor shortage. We modeled their number to predict rational estimates for workforce planners. Methods The number of PAs in active clinical practice in 2010 formed the baseline. We used graduation rates and program expansion to project annual growth; attrition estimates offset these amounts. A simulation model incorporated historical trends, current supply, and graduation amounts. Sensitivity analyses were conducted to systematically adjust parameters in the model to determine the effects of such changes. Results As of 2010, there were 74,476 PAs in the active workforce. The mean age was 42 years and 65% were female. There were 154 accredited educational programs; 99% had a graduating class and produced an average of 44 graduates annually (total n=6,776). With a 7% increase in graduate entry rate and a 5% annual attrition rate, the supply of clinically active PAs will grow to 93,099 in 2015, 111,004 in 2020, and 127,821 in 2025. This model holds clinically active PAs in primary care at 34%. Conclusions The number of clinically active PAs is projected to increase by almost 72% in 15 years. Attrition rates, especially retirement patterns, are not well understood for PAs, and variation could affect future supply. While the majority of PAs are in the medical specialties and subspecialties fields, new policy steps funding PA education and promoting primary care may add more PAs in primary care than the model predicts. PMID:21886331

Interservice Physician Assistant Program: Educators for an Expanding Profession.

PubMed

Brock, Douglas M; Orrahood, Scott A; Cooper, Christopher K; Alvitre, John J; Tozier, William

2017-10-01

The number of physician assistant (PA) programs has increased exponentially across the past decade, and the demand for PAs will likely remain strong through 2025. Because of this rapid growth, both new and established PA programs face significant challenges in recruiting experienced educators. We describe the value of using PAs trained through the Interservice Physician Assistant Program (IPAP) as civilian PA educators. The literature on IPAP and its graduates proved too limited to conduct a formal systematic review. We searched the PubMed and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases for works speaking to the value that IPAP-trained PAs may bring to civilian PA training. Those findings were supplemented with informal conversations with IPAP-trained PAs currently employed in the military and those working in civilian PA education. Themes were identified supporting the potential value of IPAP-trained PAs in civilian training. Military PAs work within hierarchical organizations and may transition easily to academic settings. They leave military service not only as highly trained and proficient primary care providers but also as experienced educators. Military PAs must demonstrate professionalism across their entire military careers. They serve as leaders and work in teams, but they are also experienced in negotiating up chains of command. They are trained in and apply the latest innovations in health care delivery and have provided care with a degree of autonomy uncommon in civilian PA practice. The PAs trained through IPAP leave the service with skills and experiences valuable to civilian PA training. Employing these PAs in civilian education honors their service contributions while addressing emerging PA educator workforce demands.

The effects of paired associative stimulation on knee extensor motor excitability of individuals post-stroke: a pilot study.

PubMed

Rogers, Lynn M; Brown, David A; Stinear, James W

2011-06-01

Paired associative stimulation (PAS) modulates bilateral distal lower limb motor pathways during walking. We assessed the effects of inhibitory PAS applied to the vastus medialis (VM) motor pathways of chronic stroke patients. PAS consisted of 120 electrical stimuli applied to the femoral nerve paired with transcranial magnetic stimulation (TMS) of the lower limb primary motor cortex so that the estimated arrival of the afferent volley occurred 8 ms after delivery of the magnetic stimulus. Stimulus pairs were delivered to the non-paretic VM motor system of 11 chronic stroke patients and the right limb motor system of 11 non-impaired subjects at 0.19 Hz. The effects of PAS on VM motor pathway excitability and muscle activity were assessed during pedaling. TMS-induced motor evoked potential (MEP) amplitudes and the percent of VM activity in the flexion phase of active pedaling (% FLEXVM) was examined before and after PAS. Inhibitory PAS reduced VM MEP amplitudes in the target limb (p<0.05) of both groups, while post-PAS paretic VM MEP amplitudes increased for some patients and decreased for others. Group mean paretic limb % FLEXVM was not altered by inhibitory PAS. These results indicate PAS can be used to manipulate motor cortical excitability in proximal lower limb representations, however the sign of induced modulation was unpredictable and cyclic muscle activity was not modified. The study has important implications for the development of therapies involving non-invasive brain stimulation to modify abnormal motor behavior following stroke. Copyright © 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

How electronic health records can unmask the hidden value of PAs.

PubMed

Ogunfiditimi, Folusho; Sherry, Scott P; Foote, Monica; Christie, Sarah L; Shock, Lisa P; Cawley, James; Browne, Aaron

2017-06-01

The Fee for Value (FFV) Task Force, a subgroup of the American Academy of PAs' Research and Strategic Initiatives Commission, has examined tools and mechanisms aimed at better clarifying the volume and value of PA work and how that work contributes to improving access to high-quality care. Establishing the value of PAs has been a challenging task for many healthcare providers. Often, PA value has been defined by their clinical productivity, without any clear direction as to what constitutes value versus productivity. The objective of this article is to unmask the value of PAs through the role of electronic health records and highlight PAs' ability to produce services that are value-oriented and quantifiably productive.

Carbon dioxide is tightly bound in the [Co(Pyridine)(CO2)]- anionic complex

NASA Astrophysics Data System (ADS)

Graham, Jacob D.; Buytendyk, Allyson M.; Zhang, Xinxing; Kim, Seong K.; Bowen, Kit H.

2015-11-01

The [Co(Pyridine)(CO2)]- anionic complex was studied through the combination of photoelectron spectroscopy and density functional theory calculations. This complex was envisioned as a primitive model system for studying CO2 binding to negatively charged sites in metal organic frameworks. The vertical detachment energy (VDE) measured via the photoelectron spectrum is 2.7 eV. Our calculations imply a structure for [Co(Pyridine)(CO2)]- in which a central cobalt atom is bound to pyridine and CO2 moieties on either sides. This structure was validated by acceptable agreement between the calculated and measured VDE values. Based on our calculations, we found CO2 to be bound within the anionic complex by 1.4 eV.

Carbon dioxide is tightly bound in the [Co(Pyridine)(CO2)](-) anionic complex.

PubMed

Graham, Jacob D; Buytendyk, Allyson M; Zhang, Xinxing; Kim, Seong K; Bowen, Kit H

2015-11-14

The [Co(Pyridine)(CO2)](-) anionic complex was studied through the combination of photoelectron spectroscopy and density functional theory calculations. This complex was envisioned as a primitive model system for studying CO2 binding to negatively charged sites in metal organic frameworks. The vertical detachment energy (VDE) measured via the photoelectron spectrum is 2.7 eV. Our calculations imply a structure for [Co(Pyridine)(CO2)](-) in which a central cobalt atom is bound to pyridine and CO2 moieties on either sides. This structure was validated by acceptable agreement between the calculated and measured VDE values. Based on our calculations, we found CO2 to be bound within the anionic complex by 1.4 eV.

Latin American protected areas: Protected from chemical pollution?

PubMed

Rodríguez-Jorquera, Ignacio A; Siroski, Pablo; Espejo, Winfred; Nimptsch, Jorge; Choueri, Paloma Gusso; Choueri, Rodrigo Brasil; Moraga, Claudio A; Mora, Miguel; Toor, Gurpal S

2017-03-01

Protected areas (PAs) are critically important means to preserve species and maintain natural ecosystems. However, the potential impacts of chemical pollution on PAs are seldom mentioned in the scientific literature. Research on the extent of the occurrence of chemical pollution inside PAs and in-depth assessments of how chemical contaminants may adversely affect the maintenance of species abundance, species survival, and ecosystem functions are scarce to nonexistent. We investigated 1) the occurrence of chemical contaminants inside 119 PAs in Latin America from publically available databases, and 2) reviewed case studies of chemical contaminants and pollution in 4 Latin American PAs. Cases of chemical pollution and contamination inside Latin American PAs mostly originated from sources such as mining, oil, and gas extraction. To date, the focus of the research on chemical pollution research inside Latin American PAs has been primarily on the detection of contamination, typically limited to trace metals. Where management actions have occurred, they have been reactive rather than proactive. Protected areas established in wetlands are the most affected by chemical pollution. Based on the information from the pollution and/or contamination occurrence and the case studies analyzed, Latin American PAs are not well safeguarded from chemical pollution, resulting in both challenges and opportunities to conserve biodiversity and ecosystems. Integr Environ Assess Manag 2017;13:360-370. © 2016 SETAC. © 2016 SETAC.

Low-dose radiation pretreatment improves survival of human ceiling culture-derived proliferative adipocytes (ccdPAs) under hypoxia via HIF-1 alpha and MMP-2 induction

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

Adachi, Naoki; Kubota, Yoshitaka, E-mail: kubota-cbu@umin.ac.jp; Kosaka, Kentarou

2015-08-07

Poor survival is a major problem of adipocyte transplantation. We previously reported that VEGF and MMPs secreted from transplanted adipocytes are essential for angiogenesis and adipogenesis. Pretreatment with low-dose (5 Gy) radiation (LDR) increased VEGF, MMP-2, and HIF-1 alpha mRNA expression in human ceiling culture-derived proliferative adipocytes (hccdPAs). Gene expression after LDR differed between adipose-derived stem cells (hASCs) and hccdPAs. Pretreatment with LDR improved the survival of hccdPAs under hypoxia, which is inevitable in the early stages after transplantation. Upregulation of VEGF and MMP-2 after LDR in hccdPAs is mediated by HIF-1 alpha expression. Our results suggest that pretreatment with LDRmore » may improve adipocyte graft survival in a clinical setting through upregulation of VEGF and MMP-2 via HIF-1 alpha. - Highlights: • Ceiling culture-derived proliferative adipocytes (ccdPAs) react to radiation. • Low-dose radiation (LDR) pretreatment improves survival of ccdPAs under hypoxia. • Gene expression after LDR differs between ccdPAs and adipose-derived stem cells. • LDR-induced increase in MMP-2 and VEGF is dependent on HIF-1 alpha induction. • LDR pretreatment may improve the adipocyte graft survival rate in clinical settings.« less

Role of the Cytoplasmic N-terminal Cap and Per-Arnt-Sim (PAS) Domain in Trafficking and Stabilization of Kv11.1 Channels*

PubMed Central

Ke, Ying; Hunter, Mark J.; Ng, Chai Ann; Perry, Matthew D.; Vandenberg, Jamie I.

2014-01-01

The N-terminal cytoplasmic region of the Kv11.1a potassium channel contains a Per-Arnt-Sim (PAS) domain that is essential for the unique slow deactivation gating kinetics of the channel. The PAS domain has also been implicated in the assembly and stabilization of the assembled tetrameric channel, with many clinical mutants in the PAS domain resulting in reduced stability of the domain and reduced trafficking. Here, we use quantitative Western blotting to show that the PAS domain is not required for normal channel trafficking nor for subunit-subunit interactions, and it is not necessary for stabilizing assembled channels. However, when the PAS domain is present, the N-Cap amphipathic helix must also be present for channels to traffic to the cell membrane. Serine scan mutagenesis of the N-Cap amphipathic helix identified Leu-15, Ile-18, and Ile-19 as residues critical for the stabilization of full-length proteins when the PAS domain is present. Furthermore, mutant cycle analysis experiments support recent crystallography studies, indicating that the hydrophobic face of the N-Cap amphipathic helix interacts with a surface-exposed hydrophobic patch on the core of the PAS domain to stabilize the structure of this critical gating domain. Our data demonstrate that the N-Cap amphipathic helix is critical for channel stability and trafficking. PMID:24695734

Antifouling composites with self-adaptive controlled release based on an active compound intercalated into layered double hydroxides

NASA Astrophysics Data System (ADS)

Yang, Miaosen; Gu, Lianghua; Yang, Bin; Wang, Li; Sun, Zhiyong; Zheng, Jiyong; Zhang, Jinwei; Hou, Jian; Lin, Cunguo

2017-12-01

This paper reports a novel method to prepare the antifouling composites with properties of self-adaptive controlled release (defined as control the release rate autonomously and adaptively according to the change of environmental conditions) by intercalation of sodium paeonolsilate (PAS) into MgAl and ZnAl layered double hydroxide (LDH) with the molar ratio (M2+/M3+) of 2:1 and 3:1, respectively. The powder X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR) confirm the intercalation of PAS into the galleries of LDH. The controlled release behavior triggered by temperature for the PAS-LDH composites has been investigated, and the results show that the release rate of all PAS-LDH composites increases as the increase of temperature. However, the MgAl-PAS-LDH composites (Mg2Al-PAS-LDH and Mg3Al-PAS-LDH) exhibit the increased release rate of 0.21 ppm/°C from 15 to 30 °C in 3.5% NaCl solution, more than three times of the ZnAl-PAS-LDH composites (0.06 ppm/°C), owing to the confined microenvironment influenced by metal types in LDH layers. In addition, a possible diffusion-controlled process with surface diffusion, bulk diffusion and heterogeneous flat surface diffusion has been revealed via fitting four kinetic equations. Moreover, to verify the practical application of the PAS-LDH composites, a model coating denoted as Mg2Al-PAS-LDH coating was fabricated. The release result displays that the release rate increases or decreases as temperature altered at 15 and 25 °C alternately, indicating its self-adaptive controlled release behavior with temperature. Moreover, the superior resistance to the settlement of Ulva spores at 15 and 25 °C was observed for the Mg2Al-PAS-LDH coating, as a result of the controllable release of antifoulant. Therefore, this work provides a facile and effective method for the fabrication of antifouling composites with self-adaptive controlled release behavior in response to temperature, which can be used to prolong the lifetime of antifouling coatings.

Assessment of Surface Water Contamination from Coalbed Methane Fracturing-Derived Volatile Contaminants in Sullivan County, Indiana, USA.

PubMed

Meszaros, Nicholas; Subedi, Bikram; Stamets, Tristan; Shifa, Naima

2017-09-01

There is a growing concern over the contamination of surface water and the associated environmental and public health consequences from the recent proliferation of hydraulic fracturing in the USA. Petroleum hydrocarbon-derived contaminants of concern [benzene, toluene, ethylbenzene, and xylenes (BTEX)] and various dissolved cations and anions were spatially determined in surface waters around 15 coalbed methane fracking wells in Sullivan County, IN, USA. At least one BTEX compound was detected in 69% of sampling sites (n = 13) and 23% of sampling sites were found to be contaminated with all of the BTEX compounds. Toluene was the most common BTEX compound detected across all sampling sites, both upstream and downstream from coalbed methane fracking wells. The average concentration of toluene at a reservoir and its outlet nearby the fracking wells was ~2× higher than other downstream sites. However, one of the upstream sites was found to be contaminated with BTEX at similar concentrations as in a reservoir site nearby the fracking well. Calcium (~60 ppm) and sulfates (~175 ppm) were the dominant cations and anions, respectively, in surface water around the fracking sites. This study represents the first report of BTEX contamination in surface water from coalbed methane hydraulic fracturing wells.

Assessing levels and seasonal variations of current-use pesticides (CUPs) in the Tuscan atmosphere, Italy, using polyurethane foam disks (PUF) passive air samplers.

PubMed

Estellano, Victor H; Pozo, Karla; Efstathiou, Christos; Pozo, Katerine; Corsolini, Simonetta; Focardi, Silvano

2015-10-01

Polyurethane foam disks (PUF) passive air samplers (PAS) were deployed over 4 sampling periods of 3-5-months (≥ 1 year) at ten urban and rural locations throughout the Tuscany Region. The purpose was to assess the occurrence and seasonal variations of ten current-use pesticides (CUPs). PUF disk extracts were analyzed using GC-MS. The organophosphates insecticides; chlorpyrifos (3-580 pg m(-3)) and chlorpyrifos-methyl (below detection limit - to 570 pg m(-3)) presented the highest levels in air, and showed seasonal fluctuation coinciding with the growing seasons. The relative proportion urban/(urban + rural) ranged from 0.4 to 0.7 showing no differences between urban and rural concentrations. Air back trajectories analysis showed air masses passing over agricultural fields and potentially enhancing the drift of pesticides into the urban sites. This study represents the first information regarding CUPs in the atmosphere of Tuscany region using PAS-PUF disk. Copyright © 2015 Elsevier Ltd. All rights reserved.

Embankment Criteria and Performance Report. Salt Creek and Tributaries, Nebraska, Site 18, Branched Oak Dam and Lake.

DTIC Science & Technology

1984-05-01

Before work began, all vegetation, such as brush, heavy sod, heavy growth of grass, and all decayed vegetable matter , rubbish, road surfacing, and other...Wegh t of activ eg eI ht of pasIve eg ’.A. EffectIve feOs n the slide plan and 𔃿the diretio In whichItsacig E, C.. SCALE 1-30 TON 4 -L Tok 11,FAC

Geochemical Data from Produced Water Contamination Investigations: Osage-Skiatook Petroleum Environmental Research (OSPER) Sites, Osage County, Oklahoma

DTIC Science & Technology

2007-01-01

density polyethylene bottles prerinsed with deionized water for anions, and prerinsed with 5% nitric acid (HNO3) then deionized water for metals and...silica. The aliquots for metal and silica were acidified to pH ~1 with ultrex-grade nitric acid (HNO3). Sample aliquots for dissolved organic carbon (DOC...Br, NO3, PO4, SO4, and organic carboxylic acid anions (acetate, butyrate, formate, malonate, oxalate , propionate, and succinate) were determined by

Bacterial growth kinetics in ACD-A apheresis platelets: comparison of plasma and PAS III storage.

PubMed

Dumont, Larry J; Wood, Tammara A; Housman, Molly; Herschel, Louise; Brantigan, Barbara; Heber, Cheryl; Houghton, Jaime

2011-05-01

Our objective was to determine the growth kinetics of bacteria in leukoreduced apheresis platelets (LR-AP) in a platelet (PLT) additive solution (PAS; InterSol, Fenwal, Inc.) compared to LR-AP stored in plasma. Hyperconcentrated, double-dose LR-AP were collected from healthy donors with a separator (AMICUS, Fenwal, Inc.). LR-AP were evenly divided, InterSol was added to half (65% InterSol:35% plasma [PAS]), and PLTs in autologous plasma were used for a paired control (PL). Bacteria were inoculated into each LR-AP PAS/PL pair (0.5-1.6 colony-forming units [CFUs]/mL), and bacterial growth was followed for up to 7 days. Time to the end of the lag phase, doubling times, maximum concentration (conc-max), and time to maximum concentration (time-max) were estimated. Streptococcus viridans did not grow to detectable levels in either PAS or PL units. The other bacteria had no significant overall difference in the conc-max (p = 0.47) or time-max (p = 0.7) between PL and PAS LR-AP; PL had a 0.14 hours faster doubling rate (p = 0.023); and PAS had a 4.7 hours shorter lag time (p = 0.016). We observed that five index organisms will grow in LR-AP stored in a 35%:65% ratio of plasma to InterSol where initial bacterial concentrations are 0.5 to 1.6 CFUs/mL. The more rapid initiation of log-phase growth for bacteria within a PAS storage environment resulted in a bacterial concentration up to 4 logs higher in the PAS units compared to the plasma units at 24 hours, but with no difference in the conc-max. This may present an early bacterial detection advantage for PAS-stored PLTs. © 2010 American Association of Blood Banks.

A Cost Analysis of School-Based Lifestyle Interventions.

PubMed

Oosterhoff, Marije; Bosma, Hans; van Schayck, Onno C P; Joore, Manuela A

2018-05-31

A uniform approach for costing school-based lifestyle interventions is currently lacking. The objective of this study was to develop a template for costing primary school-based lifestyle interventions and apply this to the costing of the "Healthy Primary School of the Future" (HPSF) and the "Physical Activity School" (PAS), which aim to improve physical activity and dietary behaviors. Cost-effectiveness studies were reviewed to identify the cost items. Societal costs were reflected by summing up the education, household and leisure, labor and social security, and health perspectives. Cost inputs for HPSF and PAS were obtained for the first year after implementation. In a scenario analysis, the costs were explored for a hypothetical steady state. From a societal perspective, the per child costs were €2.7/$3.3 (HPSF) and €- 0.3/$- 0.4 (PAS) per day during the first year after implementation, and €1.0/$1.2 and €- 1.3/$- 1.6 in a steady state, respectively (2016 prices). The highest costs were incurred by the education perspective (first year: €8.7/$10.6 (HPSF) and €4.0/$4.9 (PAS); steady state: €6.1/$7.4 (HPSF) and €2.1/$2.6 (PAS)), whereas most of the cost offsets were received by the household and leisure perspective (first year: €- 6.0/$- 7.3 (HPSF) and €- 4.4/$- 5.4 (PAS); steady state: €- 5.0/$- 6.1 (HPSF) and €- 3.4/$- 4.1 (PAS)). The template proved helpful for costing HPSF and PAS from various stakeholder perspectives. The costs for the education sector were fully (PAS) and almost fully (HPSF) compensated by the savings within the household sector. Whether the additional costs of HPSF over PAS represent value for money will depend on their relative effectiveness.

Toxin-Antitoxin Systems Are Important for Niche-Specific Colonization and Stress Resistance of Uropathogenic Escherichia coli

PubMed Central

Norton, J. Paul; Mulvey, Matthew A.

2012-01-01

Toxin-antitoxin (TA) systems are prevalent in many bacterial genomes and have been implicated in biofilm and persister cell formation, but the contribution of individual chromosomally encoded TA systems during bacterial pathogenesis is not well understood. Of the known TA systems encoded by Escherichia coli, only a subset is associated with strains of extraintestinal pathogenic E. coli (ExPEC). These pathogens colonize diverse niches and are a major cause of sepsis, meningitis, and urinary tract infections. Using a murine infection model, we show that two TA systems (YefM-YoeB and YbaJ-Hha) independently promote colonization of the bladder by the reference uropathogenic ExPEC isolate CFT073, while a third TA system comprised of the toxin PasT and the antitoxin PasI is critical to ExPEC survival within the kidneys. The PasTI TA system also enhances ExPEC persister cell formation in the presence of antibiotics and markedly increases pathogen resistance to nutrient limitation as well as oxidative and nitrosative stresses. On its own, low-level expression of PasT protects ExPEC from these stresses, whereas overexpression of PasT is toxic and causes bacterial stasis. PasT-induced stasis can be rescued by overexpression of PasI, indicating that PasTI is a bona fide TA system. By mutagenesis, we find that the stress resistance and toxic effects of PasT can be uncoupled and mapped to distinct domains. Toxicity was specifically linked to sequences within the N-terminus of PasT, a region that also promotes the development of persister cells. These results indicate discrete, multipurpose functions for a TA-associated toxin and demonstrate that individual TA systems can provide bacteria with pronounced fitness advantages dependent on toxin expression levels and the specific environmental niche occupied. PMID:23055930

Polyamines in the Context of Metabolic Networks.

PubMed

Wuddineh, Wegi; Minocha, Rakesh; Minocha, Subhash C

2018-01-01

Polyamines (PAs) are essential biomolecules that are known to be involved in the regulation of many plant developmental and growth processes as well as their response to different environmental stimuli. Maintaining the cellular pools of PAs or their metabolic precursors and by-products is critical to accomplish their normal functions. Therefore, the titre of PAs in the cells must be under tight regulation to enable cellular PA homeostasis. Polyamine homeostasis is hence achieved by the regulation of their input into the cellular PA pool, their conversion into secondary metabolites, their transport to other issues/organs, and their catabolism or turnover. The major contributors of input to the PA pools are their in vivo biosynthesis, interconversion between different PAs, and transport from other tissues/organs; while the output or turnover of PAs is facilitated by transport, conjugation and catabolism. Polyamine metabolic pathways including the biosynthesis, catabolism/turnover and conjugation with various organic molecules have been widely studied in all kingdoms. Discoveries on the molecular transporters facilitating the intracellular and intercellular translocation of PAs have also been reported. Numerous recent studies using transgenic approaches and mutagenesis have shown that plants can tolerate quite large concentrations of PAs in the cells; even though, at times, high cellular accumulation of PAs is quite detrimental, and so is high rate of catabolism. The mechanism by which plants tolerate such large quantities of PAs is still unclear. Interestingly, enhanced PA biosynthesis via manipulation of the PA metabolic networks has been suggested to contribute directly to increased growth and improvements in plant abiotic and biotic stress responses; hence greater biomass and productivity. Genetic manipulation of the PA metabolic networks has also been shown to improve plant nitrogen assimilation capacity, which may in turn lead to enhanced carbon assimilation. These potential benefits on top of the widely accepted role of PAs in improving plants' tolerance to biotic and abiotic stressors are invaluable tools for future plant improvement strategies.

The productivity of PAs, APRNs, and physicians in Utah.

PubMed

Pedersen, Donald M; Chappell, Boyd; Elison, Gar; Bunnell, Robert

2008-01-01

The physician assistant workforce in Utah is experiencing remarkable growth, with a 9% net annual rate of increase since 1998. An additional 84 PAs provided patient care in Utah in the 4-year period of 1998 through 2001, an average increase of 21 per year. The Utah Medical Education Council believes that the demand for PAs will be high over the next 10 to 15 years, with several factors fueling this growth. Productivity is one of these factors. Even though Utah PAs make up only approximately 6.3% of the state's combined clinician (physician, PA, advanced practice registered nurse [APRN]) workforce; the PAs contribute approximately 7.2% of the patient care full-time equivalents (FTE) in the state. This is in contrast to the 10% FTE contribution made by the state's APRN workforce, which has nearly triple the number of clinicians providing patient care in the state. The majority (73%) of Utah PAs work at least 36 hours per week. Utah PAs also spend a greater percentage of the total hours worked in patient care, when compared to the physician workforce. The rural PA workforce reported working a greater number of total hours and patient care hours when compared to the overall PA workforce.

Identifying appropriate protected areas for endangered fern species under climate change.

PubMed

Wang, Chun-Jing; Wan, Ji-Zhong; Zhang, Zhi-Xiang; Zhang, Gang-Min

2016-01-01

The management of protected areas (PAs) is widely used in the conservation of endangered plant species under climate change. However, studies that have identified appropriate PAs for endangered fern species are rare. To address this gap, we must develop a workflow to plan appropriate PAs for endangered fern species that will be further impacted by climate change. Here, we used endangered fern species in China as a case study, and we applied conservation planning software coupled with endangered fern species distribution data and distribution modeling to plan conservation areas with high priority protection needs under climate change. We identified appropriate PAs for endangered fern species under climate change based on the IUCN protected area categories (from Ia to VI) and planned additional PAs for endangered fern species. The high priority regions for protecting the endangered fern species were distributed throughout southern China. With decreasing temperature seasonality, the priority ranking of all endangered fern species is projected to increase in existing PAs. Accordingly, we need to establish conservation areas with low climate vulnerability in existing PAs and expand the conservation areas for endangered fern species in the high priority conservation regions.

Qualitative study of employment of physician assistants by physicians: benefits and barriers in the Ontario health care system.

PubMed

Taylor, Maureen T; Wayne Taylor, D; Burrows, Kristen; Cunnington, John; Lombardi, Andrea; Liou, Michelle

2013-11-01

To explore the experiences and perceptions of Ontario physician assistant (PA) employers about the barriers to and benefits of hiring PAs. A qualitative design using semistructured interviews. Rural and urban eastern and southwestern Ontario. Seven family physicians and 7 other specialists. The 14 physicians participated in semistructured interviews, which were audiorecorded and transcribed verbatim. An iterative approach using immersion and crystallization was employed for analysis. Physician-specific benefits to hiring PAs included increased flexibility, the opportunity to expand practice, the ability to focus more time on complex patients, overall reduction in work hours and stress, and an opportunity for professional fellowship. Physicians who hired PAs without government financial support said PAs were affordable as long as they were able to retain them. Barriers to hiring PAs included uncertainty about funding, the initial need for intensive supervision and training, and a lack of clarity around delegation of acts. Physicians are motivated to hire PAs to help deal with long wait times and long hours, but few are expecting to increase their income by taking on PAs. Governments, medical colleges, educators, and regulators must address the perceived barriers to PA hiring in order to expand and optimize this profession.

C2 Domain of Protein Kinase Cα: Elucidation of the Membrane Docking Surface by Site-Directed Fluorescence and Spin Labeling†

PubMed Central

Kohout, Susy C.; Corbalán-García, Senena; Gómez-Fernández, Juan C.; Falke, Joseph J.

2013-01-01

The C2 domain is a conserved signaling motif that triggers membrane docking in a Ca2+-dependent manner, but the membrane docking surfaces of many C2 domains have not yet been identified. Two extreme models can be proposed for the docking of the protein kinase Cα (PKCα) C2 domain to membranes. In the parallel model, the membrane-docking surface includes the Ca2+ binding loops and an anion binding site on β-strands 3–4, such that the β-strands are oriented parallel to the membrane. In the perpendicular model, the docking surface is localized to the Ca2+ binding loops and the β-strands are oriented perpendicular to the membrane surface. The present study utilizes site-directed fluorescence and spin-labeling to map out the membrane docking surface of the PKCα C2 domain. Single cysteine residues were engineered into 18 locations scattered over all regions of the protein surface, and were used as attachment sites for spectroscopic probes. The environmentally sensitive fluorescein probe identified positions where Ca2+ activation or membrane docking trigger measurable fluorescence changes. Ca2+ binding was found to initiate a global conformational change, while membrane docking triggered the largest fluorescein environmental changes at labeling positions on the three Ca2+ binding loops (CBL), thereby localizing these loops to the membrane docking surface. Complementary EPR power saturation measurements were carried out using a nitroxide spin probe to determine a membrane depth parameter, Φ, for each spin-labeled mutant. Positive membrane depth parameters indicative of membrane insertion were found for three positions, all located on the Ca2+ binding loops: N189 on CBL 1, and both R249 and R252 on CBL 3. In addition, EPR power saturation revealed that five positions near the anion binding site are partially protected from collisions with an aqueous paramagnetic probe, indicating that the anion binding site lies at or near the surface of the headgroup layer. Together, the fluorescence and EPR results indicate that the Ca2+ first and third Ca2+ binding loops insert directly into the lipid headgroup region of the membrane, and that the anion binding site on β-strands 3–4 lies near the headgroups. The data support a model in which the β-strands are tilted toward the parallel orientation relative to the membrane surface. PMID:12564928

Direct evidence for the ring opening of monosaccharide anions in the gas phase: photodissociation of aldohexoses and aldohexoses derived from disaccharides using variable-wavelength infrared irradiation in the carbonyl stretch region.

PubMed

Brown, Darin J; Stefan, Sarah E; Berden, Giel; Steill, Jeffrey D; Oomens, Jos; Eyler, John R; Bendiak, Brad

2011-11-08

All eight D-aldohexoses and aldohexoses derived from the non-reducing end of disaccharides were investigated by variable-wavelength infrared multiple-photon dissociation (IRMPD) as anions in the negative-ion mode. Spectroscopic evidence supports the existence of a relatively abundant open-chain configuration of the anions in the gas phase, based on the observation of a significant carbonyl absorption band near 1710 cm(-1). The abundance of the open-chain configuration of the aldohexose anions was approximately 1000-fold or greater than that of the neutral sugars in aqueous solution. This provides an explanation as to why it has not been possible to discriminate the anomeric configuration of aldohexose anions in the gas phase when derived from the non-reducing sugar of a disaccharide. Evidence from photodissociation spectra also indicates that the different aldohexoses yield product ions with maximal abundances at different wavelengths, and that the carbonyl stretch region is useful for differentiation of sugar stereochemistries. Quantum-chemical calculations indicate relatively low energy barriers to intramolecular proton transfer between hydroxyl groups and adjacent alkoxy sites located on open-chain sugar anions, suggesting that an ensemble of alkoxy charge locations contributes to their observed photodissociation spectra. Ring opening of monosaccharide anions and interconversion among configurations is an inherent property of the ions themselves and occurs in vacuo independent of solvent participation. Copyright © 2011 Elsevier Ltd. All rights reserved.

Probing Polyoxometalate-Protein Interactions Using Molecular Dynamics Simulations.

PubMed

Solé-Daura, Albert; Goovaerts, Vincent; Stroobants, Karen; Absillis, Gregory; Jiménez-Lozano, Pablo; Poblet, Josep M; Hirst, Jonathan D; Parac-Vogt, Tatjana N; Carbó, Jorge J

2016-10-17

The molecular interactions between the Ce IV -substituted Keggin anion [PW 11 O 39 Ce(OH 2 ) 4 ] 3- (CeK) and hen egg-white lysozyme (HEWL) were investigated by molecular dynamics simulations. The analysis of CeK was compared with the Ce IV -substituted Keggin dimer [(PW 11 O 39 ) 2 Ce] 10- (CeK 2 ) and the Zr IV -substituted Lindqvist anion [W 5 O 18 Zr(OH 2 )(OH)] 3- (ZrL) to understand how POM features such as shape, size, charge, or type of incorporated metal ion influence the POM⋅⋅⋅protein interactions. Simulations revealed two regions of the protein in which the CeK anion interacts strongly: cationic sites formed by Arg21 and by Arg45 and Arg68. The POMs chiefly interact with the side chains of the positively charged (arginines, lysines) and the polar uncharged residues (tyrosines, serines, aspargines) via electrostatic attraction and hydrogen bonding with the oxygen atoms of the POM framework. The CeK anion shows higher protein affinity than the CeK 2 and ZrL anions, because it is less hydrophilic and it has the right size and shape for establishing interactions with several residues simultaneously. The larger, more negatively charged CeK 2 anion has a high solvent-accessible surface, which is sub-optimal for the interaction, while the smaller ZrL anion is highly hydrophilic and cannot efficiently interact with several residues simultaneously. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Trends and determinants of end-of-life practices in ALS in the Netherlands.

PubMed

Maessen, M; Veldink, Jan H; Onwuteaka-Philipsen, B D; de Vries, J M; Wokke, J H J; van der Wal, G; van den Berg, L H

2009-09-22

In the Netherlands, the proportion of patients with amyotrophic lateral sclerosis (ALS) who choose the option of euthanasia or physician-assisted suicide (PAS) is relatively high (20%). The objective of this study was to determine which factors influence end-of-life practices in ALS and whether rates are changing over time. In a cohort survey, 204 physicians and 198 informal caregivers (response rates 75% and 80%) of patients with ALS who died between 2000 and 2005 filled out questionnaires of the end-of-life circumstances of the patient. Results were compared with those of a similar study performed during the period 1994-1998. In 2000-2005, 16.8% of the patients decided on euthanasia or PAS compared to 20.2% in 1994-1998. Thirty-one (14.8%) patients died during continuous deep sedation (CDS) in 2000-2005. Euthanasia or PAS, but not CDS, were significantly associated with religion not being important to the patient, being more educated, and dying at home. Euthanasia or PAS were not associated with quality of care items or symptoms of depression. Loss of function was similar in both groups. Informal caregivers of patients who died after euthanasia or PAS more frequently reported fear of choking (p = 0.003), no chance of improvement (p = 0.001), loss of dignity (p = 0.02), being dependent on others (p = 0.002), and fatigue (p = 0.018) as reasons for shortening life. Hopelessness was associated with euthanasia or PAS, as with CDS. The frequency of euthanasia or physician-assisted suicide (PAS) in amyotrophic lateral sclerosis (ALS) appeared stable over time and 1 in 7 patients died during CDS. CDS is relatively common in ALS, but appears to have other determinants than euthanasia or PAS. Subjective factors may be important in explaining euthanasia or PAS in ALS.

Learning modifies subsequent induction of long-term potentiation-like and long-term depression-like plasticity in human motor cortex.

PubMed

Ziemann, Ulf; Ilić, Tihomir V; Iliać, Tihomir V; Pauli, Christian; Meintzschel, Frank; Ruge, Diane

2004-02-18

Learning may alter rapidly the output organization of adult motor cortex. It is a long-held hypothesis that modification of synaptic strength along cortical horizontal connections through long-term potentiation (LTP) and long-term depression (LTD) forms one important mechanism for learning-induced cortical plasticity. Strong evidence in favor of this hypothesis was provided for rat primary motor cortex (M1) by showing that motor learning reduced subsequent LTP but increased LTD. Whether a similar relationship exists in humans is unknown. Here, we induced LTP-like and LTD-like plasticity in the intact human M1 by an established paired associative stimulation (PAS) protocol. PAS consisted of 200 pairs of electrical stimulation of the right median nerve, followed by focal transcranial magnetic stimulation of the hand area of the left M1 at an interval equaling the individual N20 latency of the median nerve somatosensory-evoked cortical potential (PAS(N20)) or N20-5 msec (PAS(N20-5)). PAS(N20) induced reproducibly a LTP-like long-lasting (>30 min) increase in motor-evoked potentials from the left M1 to a thumb abductor muscle of the right hand, whereas PAS(N20-5) induced a LTD-like decrease. Repeated fastest possible thumb abduction movements resulted in learning, defined by an increase in maximum peak acceleration of the practiced movements, and prevented subsequent PAS(N20)-induced LTP-like plasticity but enhanced subsequent PAS(N20-5)-induced LTD-like plasticity. The same number of repeated slow thumb abduction movements did not result in learning and had no effects on PAS-induced plasticity. Findings support the view that learning in human M1 occurs through LTP-like mechanisms.

[Attitudes and experiences regarding physician assisted suicide : A survey among members of the German Association for Palliative Medicine].

PubMed

Jansky, Maximiliane; Jaspers, Birgit; Radbruch, Lukas; Nauck, Friedemann

2017-01-01

The need to regulate physician-assisted suicide (PAS) and organizations offering assisted suicide has been controversially debated in Germany. Before the German parliament voted on various drafts in November 2015, the German Association for Palliative Medicine surveyed its members on their attitudes and experiences regarding PAS. Items for the survey were derived from the literature and consented in a focus group. 2005-2015 - PubMed: PAS [Title/Abstract] UND survey (all countries), grey literature. We invited 5152 members of the DGP to participate in the online/paper survey. Descriptive quantitative and content analytic qualitative analysis of data using SPSS and MaxQDA. We obtained 1811 valid data sets (response rate 36.9%). 33.7% of the participants were male, 43.6% were female, and 0.4% identifed as other. Physicians accounted for 48.5% of the respondents, 17.8% nurses, other professions 14.3%, and about 20% of the data was missing socio-demographic information. More than 90% agreed that "wishes for PAS may be ambivalent" and "are rather a wish to end an unbearable situation". Of the 833 participating physicians, 56% refused participating in PAS and 74.2% had been asked to perform PAS. PAS was actually performed by 3%. Of all participating members, 56% approved of a legal ban of organizations offering assisted suicide. More than 60% of all professions agreed that PAS is not a part of palliative care. The respondents show a broad spectrum of attitudes, only partly supporting statements of relevant bodies, such as DGP. Because many are confronted with the issue, PAS is relevant to professionals in palliative care.

Attitudes of young neurosurgeons and neurosurgical residents towards euthanasia and physician-assisted suicide.

PubMed

Broekman, M L D; Verlooy, J S A

2013-11-01

Euthanasia and physician assisted suicide (PAS) are two controversial topics in neurosurgical practice. Personal attitudes and opinions on these important issues may vary between professionals, and may also depend on their location since current legislation differs between European countries. As these issues may have significant impact on clinical practice, the goal of the present study was to survey the opinions of neurosurgical residents and young neurosurgeons across Europe with respect to euthanasia and physician assisted suicide. We performed a survey among the participants of the European Association of Neurosurgical Societies (EANS) training courses (2011-2012), asking residents and young neurosurgeons nine questions on euthanasia and PAS. For the analysis of this survey, we divided all 295 participants into four European regions (North, South, East, West). We found that even though most residents are aware of regulations about euthanasia or PAS in their country or hospital, a substantial number were not aware of the regulations. We observed no significant differences in terms of their opinions on euthanasia and PAS among the four European regions. While most are actually in favor of euthanasia or PAS, if legally allowed, under appropriate circumstances, very few neurosurgeons would be willing to actively participate in these end-of-life practices. The results of this first survey on neurosurgical residents' attitudes towards euthanasia and PAS show that a significant number of residents is not familiar with national and/or local regulations regarding euthanasia and PAS. If legally allowed, most residents would be in favor of euthanasia and PAS, but only a minority would be willing to actively participate in these practices. We did not observe a difference in stances on euthanasia and PAS among residents from different regions in Europe.

Impaired induction of long-term potentiation-like plasticity in patients with high-functioning autism and Asperger syndrome.

PubMed

Jung, Nikolai H; Janzarik, Wibke G; Delvendahl, Igor; Münchau, Alexander; Biscaldi, Monica; Mainberger, Florian; Bäumer, Tobias; Rauh, Reinhold; Mall, Volker

2013-01-01

We aimed to investigate the induction of long-term potentiation (LTP)-like plasticity by paired associative stimulation (PAS) in patients with high-functioning autism and Asperger syndrome (HFA/AS). PAS with an interstimulus interval between electrical and transcranial magnetic stimulation of 25 ms (PAS(25)) was performed in patients with HFA/AS (n=9; eight males, one female; mean age 17 y 11 mo, SD 4 y 5 mo) and in typically developing age-matched volunteers (n=9; five males, four females; mean age 22 y 4 mo, SD 5 y 2 mo). The amplitude of motor-evoked potentials was measured before PAS(25), immediately after stimulation, and 30 minutes and 60 minutes later. A PAS protocol adapted to individual N20 latency (PAS(N20+2)) was performed in six additional patients with HFA/AS. Short-interval intracortical inhibition was measured using paired-pulse stimulation. In contrast to the typically developing participants, the patients with HFA/AS did not show a significant increase in motor-evoked potentials after PAS(25). This finding could also be demonstrated after adaptation for N20 latency. Short-interval intracortical inhibition of patients with HFA/AS was normal compared with the comparison group and did not correlate with PAS effect. Our results show a significant impairment of LTP-like plasticity induced by PAS in individuals with HFA/AS compared with typically developing participants. This finding is in accordance with results from animal studies as well as human studies. Impaired LTP-like plasticity in patients with HFA/AS points towards reduced excitatory synaptic connectivity and deficits in sensory-motor integration in these patients. © The Authors. Developmental Medicine & Child Neurology © 2012 Mac Keith Press.

Stimulus uncertainty enhances long-term potentiation-like plasticity in human motor cortex.

PubMed

Sale, Martin V; Nydam, Abbey S; Mattingley, Jason B

2017-03-01

Plasticity can be induced in human cortex using paired associative stimulation (PAS), which repeatedly and predictably pairs a peripheral electrical stimulus with transcranial magnetic stimulation (TMS) to the contralateral motor region. Many studies have reported small or inconsistent effects of PAS. Given that uncertain stimuli can promote learning, the predictable nature of the stimulation in conventional PAS paradigms might serve to attenuate plasticity induction. Here, we introduced stimulus uncertainty into the PAS paradigm to investigate if it can boost plasticity induction. Across two experimental sessions, participants (n = 28) received a modified PAS paradigm consisting of a random combination of 90 paired stimuli and 90 unpaired (TMS-only) stimuli. Prior to each of these stimuli, participants also received an auditory cue which either reliably predicted whether the upcoming stimulus was paired or unpaired (no uncertainty condition) or did not predict the upcoming stimulus (maximum uncertainty condition). Motor evoked potentials (MEPs) evoked from abductor pollicis brevis (APB) muscle quantified cortical excitability before and after PAS. MEP amplitude increased significantly 15 min following PAS in the maximum uncertainty condition. There was no reliable change in MEP amplitude in the no uncertainty condition, nor between post-PAS MEP amplitudes across the two conditions. These results suggest that stimulus uncertainty may provide a novel means to enhance plasticity induction with the PAS paradigm in human motor cortex. To provide further support to the notion that stimulus uncertainty and prediction error promote plasticity, future studies should further explore the time course of these changes, and investigate what aspects of stimulus uncertainty are critical in boosting plasticity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Recurrent gain-of-function USP8 mutations in Cushing's disease

PubMed Central

Ma, Zeng-Yi; Song, Zhi-Jian; Chen, Jian-Hua; Wang, Yong-Fei; Li, Shi-Qi; Zhou, Liang-Fu; Mao, Ying; Li, Yi-Ming; Hu, Rong-Gui; Zhang, Zhao-Yun; Ye, Hong-Ying; Shen, Ming; Shou, Xue-Fei; Li, Zhi-Qiang; Peng, Hong; Wang, Qing-Zhong; Zhou, Dai-Zhan; Qin, Xiao-Lan; Ji, Jue; Zheng, Jie; Chen, Hong; Wang, Yin; Geng, Dao-Ying; Tang, Wei-Jun; Fu, Chao-Wei; Shi, Zhi-Feng; Zhang, Yi-Chao; Ye, Zhao; He, Wen-Qiang; Zhang, Qi-Lin; Tang, Qi-Sheng; Xie, Rong; Shen, Jia-Wei; Wen, Zu-Jia; Zhou, Juan; Wang, Tao; Huang, Shan; Qiu, Hui-Jia; Qiao, Ni-Dan; Zhang, Yi; Pan, Li; Bao, Wei-Min; Liu, Ying-Chao; Huang, Chuan-Xin; Shi, Yong-Yong; Zhao, Yao

2015-01-01

Cushing's disease, also known as adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas (PAs) that cause excess cortisol production, accounts for up to 85% of corticotrophin-dependent Cushing's syndrome cases. However, the genetic alterations in this disease are unclear. Here, we performed whole-exome sequencing of DNA derived from 12 ACTH-secreting PAs and matched blood samples, which revealed three types of somatic mutations in a candidate gene, USP8 (encoding ubiquitin-specific protease 8), exclusively in exon 14 in 8 of 12 ACTH-secreting PAs. We further evaluated somatic USP8 mutations in additional 258 PAs by Sanger sequencing. Targeted sequencing further identified a total of 17 types of USP8 variants in 67 of 108 ACTH-secreting PAs (62.04%). However, none of these mutations was detected in other types of PAs (n = 150). These mutations aggregate within the 14-3-3 binding motif of USP8 and disrupt the interaction between USP8 and 14-3-3 protein, resulting in an elevated capacity to protect EGFR from lysosomal degradation. Accordingly, PAs with mutated USP8 display a higher incidence of EGFR expression, elevated EGFR protein abundance and mRNA expression levels of POMC, which encodes the precursor of ACTH. PAs with mutated USP8 are significantly smaller in size and have higher ACTH production than wild-type PAs. In surgically resected primary USP8-mutated tumor cells, USP8 knockdown or blocking EGFR effectively attenuates ACTH secretion. Taken together, somatic gain-of-function USP8 mutations are common and contribute to ACTH overproduction in Cushing's disease. Inhibition of USP8 or EGFR is promising for treating USP8-mutated corticotrophin adenoma. Our study highlights the potentially functional mutated gene in Cushing's disease and provides insights into the therapeutics of this disease. PMID:25675982

Global patterns of protection of elevational gradients in mountain ranges.

PubMed

Elsen, Paul R; Monahan, William B; Merenlender, Adina M

2018-05-21

Protected areas (PAs) that span elevational gradients enhance protection for taxonomic and phylogenetic diversity and facilitate species range shifts under climate change. We quantified the global protection of elevational gradients by analyzing the elevational distributions of 44,155 PAs in 1,010 mountain ranges using the highest resolution digital elevation models available. We show that, on average, mountain ranges in Africa and Asia have the lowest elevational protection, ranges in Europe and South America have intermediate elevational protection, and ranges in North America and Oceania have the highest elevational protection. We use the Convention on Biological Diversity's Aichi Target 11 to assess the proportion of elevational gradients meeting the 17% suggested minimum target and examine how different protection categories contribute to elevational protection. When considering only strict PAs [International Union for Conservation of Nature (IUCN) categories I-IV, n = 24,706], nearly 40% of ranges do not contain any PAs, roughly half fail to meet the 17% target at any elevation, and ∼75% fail to meet the target throughout ≥50% of the elevational gradient. Observed elevational protection is well below optimal, and frequently below a null model of elevational protection. Including less stringent PAs (IUCN categories V-VI and nondesignated PAs, n = 19,449) significantly enhances elevational protection for most continents, but several highly biodiverse ranges require new or expanded PAs to increase elevational protection. Ensuring conservation outcomes for PAs with lower IUCN designations as well as strategically placing PAs to better represent and connect elevational gradients will enhance ecological representation and facilitate species range shifts under climate change. Copyright © 2018 the Author(s). Published by PNAS.

The education, role, distribution, and compensation of physician assistants in orthopedic surgery.

PubMed

Chalupa, Robyn L; Hooker, Roderick S

2016-05-01

Physician assistants (PAs) have worked alongside surgeons since the 1970s, yet little is known about their postgraduate education, roles, distribution, and compensation. In 2015, an estimated 8,900 PAs were employed in orthopedics (9.4% of all clinically active PAs in the United States). This study analyzed surveys undertaken by Physician Assistants in Orthopaedic Surgery (PAOS) from 2009 to 2015 and found that most PAs working in orthopedics (85%) reported regularly assisting in surgery. Demand for PAs in orthopedics is expected to grow because of population growth, increasing incidence of musculoskeletal conditions, shortages of surgeons, and changing technology. Improved data acquisition and more detailed analyses are needed to better understand the nature of this specialized workforce.

Structure of a premicellar complex of alkyl sulfates with the interfacial binding surfaces of four subunits of phospholipase A2.

PubMed

Pan, Ying H; Bahnson, Brian J

2010-07-01

The properties of three discrete premicellar complexes (E1#, E2#, E3#) of pig pancreatic group-IB secreted phospholipase A2 (sPLA2) with monodisperse alkyl sulfates have been characterized [Berg, O. G. et al., Biochemistry 43, 7999-8013, 2004]. Here we have solved the 2.7 A crystal structure of group-IB sPLA2 complexed with 12 molecules of octyl sulfate (C8S) in a form consistent with a tetrameric oligomeric that exists during the E1# phase of premicellar complexes. The alkyl tails of the C8S molecules are centered in the middle of the tetrameric cluster of sPLA2 subunits. Three of the four sPLA2 subunits also contain a C8S molecule in the active site pocket. The sulfate oxygen of a C8S ligand is complexed to the active site calcium in three of the four protein active sites. The interactions of the alkyl sulfate head group with Arg-6 and Lys-10, as well as the backbone amide of Met-20, are analogous to those observed in the previously solved sPLA2 crystal structures with bound phosphate and sulfate anions. The cluster of three anions found in the present structure is postulated to be the site for nucleating the binding of anionic amphiphiles to the interfacial surface of the protein, and therefore this binding interaction has implications for interfacial activation of the enzyme. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Evolution of US DOE Performance Assessments Over 20 Years - 13597

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

Suttora, Linda C.; Seitz, Roger R.

2013-07-01

Performance assessments (PAs) have been used for many years for the analysis of post-closure hazards associated with a radioactive waste disposal facility and to provide a reasonable expectation of the ability of the site and facility design to meet objectives for the protection of members of the public and the environment. The use of PA to support decision-making for LLW disposal facilities has been mandated in United States Department of Energy (US DOE) directives governing radioactive waste management since 1988 (currently DOE Order 435.1, Radioactive Waste Management). Prior to that time, PAs were also used in a less formal role.more » Over the past 20+ years, the US DOE approach to conduct, review and apply PAs has evolved into an efficient, rigorous and mature process that includes specific requirements for continuous improvement and independent reviews. The PA process has evolved through refinement of a graded and iterative approach designed to help focus efforts on those aspects of the problem expected to have the greatest influence on the decision being made. Many of the evolutionary changes to the PA process are linked to the refinement of the PA maintenance concept that has proven to be an important element of US DOE PA requirements in the context of supporting decision-making for safe disposal of LLW. The PA maintenance concept is central to the evolution of the graded and iterative philosophy and has helped to drive the evolution of PAs from a deterministic compliance calculation into a systematic approach that helps to focus on critical aspects of the disposal system in a manner designed to provide a more informed basis for decision-making throughout the life of a disposal facility (e.g., monitoring, research and testing, waste acceptance criteria, design improvements, data collection, model refinements). A significant evolution in PA modeling has been associated with improved use of uncertainty and sensitivity analysis techniques to support efficient implementation of the graded and iterative approach. Rather than attempt to exactly predict the migration of radionuclides in a disposal unit, the best PAs have evolved into tools that provide a range of results to guide decision-makers in planning the most efficient, cost effective, and safe disposal of radionuclides. (authors)« less

Complementary approaches to the assessment of personality disorder. The Personality Assessment Schedule and Adult Personality Functioning Assessment compared.

PubMed

Hill, J; Fudge, H; Harrington, R; Pickles, A; Rutter, M

2000-05-01

Current concepts and measures of personality disorder are in many respects unsatisfactory. To establish agreement between two contrasting measures of personality disorder, and to compare subject-informant agreement on each. To examine the extent to which trait abnormality can be separated from interpersonal and social role dysfunction. Fifty-six subjects and their closest informants were interviewed and rated independently. Personality functioning was assessed using a modified Personality Assessment Schedule (M-PAS), and the Adult Personality Functioning Assessment (APFA). Subject-informant agreement on the M-PAS was moderately good, and agreement between the M-PAS and the APFA, across and within subjects and informants, was comparable to that for the M-PAS. This was equally the case when M-PAS trait plus impairment scores and trait abnormality scores were used. The M-PAS and the APFA are probably assessing similar constructs. Trait abnormalities occur predominantly in an interpersonal context and could be assessed within that context.

Pyrrolizidine alkaloids (PAs) in honey and pollen-legal regulation of PA levels in food and animal feed required.

PubMed

Kempf, Michael; Reinhard, Annika; Beuerle, Till

2010-01-01

Pyrrolizidine alkaloids (PAs) are secondary plant constituents that comprise about 400 different structures and occur in two major forms, a tertiary form and the corresponding N-oxide. PAs containing a 1,2-double bond are pre-toxins and metabolically activated by the action of hepatic P-450 enzymes to toxic pyrroles. Besides the acute toxic effects, the genotoxic and tumorigenicity potential of PAs was demonstrated in some eukaryotic model systems. Recently, the potential PA contamination of food and feeding stuff attracted recurrent great deals of attention. Humans are exposed to these toxins by consumption of herbal medicine, herbal teas, dietary supplements or food containing PA plant material. In numerous studies the potential threat to human health by PAs is stated. In pharmaceuticals, the use of these plants is regulated. Considering the PA concentrations observed especially in authentic honey from PA producing plants and pollen products, the results provoke an international regulation of PAs in food.

Uptake of plant-derived specific alkaloids allows males of a butterfly to copulate.

PubMed

Honda, Keiichi; Matsumoto, Junya; Sasaki, Ken; Tsuruta, Yoshiaki; Honda, Yasuyuki

2018-04-03

Certain butterflies utilize plant-acquired alkaloids for their own chemical defense and/or for producing male sex pheromone; a trait known as pharmacophagy. Males of the danaine butterfly, Parantica sita, have been reported to ingest pyrrolizidine alkaloids (PAs) as adults to produce two PA-derived sex pheromone components, viz. danaidone (major) and 7R-hydroxydanaidal. We found, however, that not all PAs that can be precursors for the pheromone serve for mating success of males. Here we show that although the sex pheromone is regarded as a requisite for successful mating, uptake of specific PA(s) (lycopsamine-type PAs) is also imperative for the males to achieve copulation. The increase in the levels of two biogenic amines, octopamine and/or serotonin, in the brain and thoracic ganglia of males fed with specific PA(s) suggested that these alkaloids most likely enhance male mating activity. The results can present new evidence for the evolutionary provenance of pharmacophagous acquisition of PAs in PA-adapted insects.

Emergency physician evaluation of PA and NP practice patterns.

PubMed

Phillips, Andrew W; Klauer, Kevin M; Kessler, Chad S

2018-05-01

The unprecedented surge in physician assistants (PAs) and NPs in the ED developed quickly in recent years, but scope of practice and practice patterns are not well described. We conducted two cross-sectional electronic surveys of the American College of Emergency Physicians' council. Survey construction was informed by interviews and evaluated with validity and reliability studies. Univariate analyses to establish associations also were performed. Most councilors' departments employ PAs and NPs (72.4% of 163 responses). Supervisory requirements varied greatly among respondents for the same emergency severity index (ESI) level. Regardless of experience level, NPs were reported to use significantly more resources than PAs; chi-square(4) = 105.292, P < .001 for less-experienced PAs or NPs; chi-square(4) = 120.415, P < .001 for more experienced PAs or NPs. Councilors reported great variation in PA and NP scope of practice. The results also suggest that new graduate PAs may be more clinically prepared to practice in the ED than new graduate NPs.

The phenomenology of the first panic attack in clinical and community-based samples.

PubMed

Pané-Farré, Christiane A; Stender, Jan P; Fenske, Kristin; Deckert, Jürgen; Reif, Andreas; John, Ulrich; Schmidt, Carsten Oliver; Schulz, Andrea; Lang, Thomas; Alpers, Georg W; Kircher, Tilo; Vossbeck-Elsebusch, Anna N; Grabe, Hans J; Hamm, Alfons O

2014-08-01

The purpose of the study was to contrast first panic attacks (PAs) of patients with panic disorder (PD) with vs. without agoraphobia and to explore differences between first PAs leading to the development of PD and those that remain isolated. Data were drawn from a community survey (N=2259 including 88 isolated PAs and 75 PD cases). An additional sample of 234 PD patients was recruited in a clinical setting. A standardized interview assessed the symptoms of the first PA, context of its occurrence and subsequent coping attempts. Persons who developed PD reported more severe first PAs, more medical service utilization and exposure-limiting coping attempts than those with isolated PAs. The context of the first PA did not differ between PD and isolated PAs. PD with agoraphobia was specifically associated with greater symptom severity and occurrence of first attacks in public. Future research should validate these findings using a longitudinal approach. Copyright © 2014 Elsevier Ltd. All rights reserved.

Adsorption of O2, SO2, and SO3 on nickel oxide. Mechanism for sulfate formation

NASA Technical Reports Server (NTRS)

Mehandru, S. P.; Anderson, A. B.

1985-01-01

Calculations based on the atom superposition and electron delocalization molecular orbital (ASED-MO) technique suggest that O2 will adsorb perferentially end-on at an angle 45 deg from normal on a nickel cation site on the (100) surface of NiO. SO2 adsorption is also stronger on the nickel site; SO2 bonds through the sulfur atom is a plane perpendicular to the surface. Adsorption energies for SO3 on the nickel and oxygen sites are comparable in the perferred orientation in which the SO3 plane is parallel to the surface. On activation, SO3 adsorbed to an O2(-) site forms a trigonal pyramidal SO4 species which yields, with a low barrier, a tetrahedral sulfate anion. Subsequently the anion reorients on the surface. Possibilities for alternative mechanisms which require the formation of Ni3(+) or O2(-) are discussed. NiSO4 thus formed leads to the corrosion of Ni at high temperatures in the SO2+O2/SO3 The SO2+O2/SO3 atmosphere, as discussed in the experimental literature.

A “cation-anion regulation” synergistic anode host for dendrite-free lithium metal batteries

PubMed Central

Zhang, Weidong; Zhuang, Houlong L.; Fan, Lei; Gao, Lina; Lu, Yingying

2018-01-01

Dendritic Li deposition has been “a Gordian knot” for almost half a century, which significantly hinders the practical use of high-energy lithium metal batteries (LMBs). The underlying mechanisms of this dendrite formation are related to the preferential lithium deposition on the tips of the protuberances of the anode surface and also associated with the concentration gradient or even depletion of anions during cycling. Therefore, a synergistic regulation of cations and anions at the interface is vital to promoting dendrite-free Li anodes. An ingenious molecular structure is designed to realize the “cation-anion regulation” with strong interactions between adsorption sites and ions at the molecular level. A quaternized polyethylene terephthalate interlayer with a “lithiophilic” ester building block and an “anionphilic” quaternary ammonium functional block can guide ions to form dendrite-free Li metal deposits at an ultrahigh current density of 10 mA cm−2, enabling stable LMBs. PMID:29507888

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

Trump, Benjamin A., E-mail: btrump1@jhu.edu; Department of Physics and Astronomy, Institute for Quantum Matter, Johns Hopkins University, Baltimore, MD 21218; McQueen, Tyrel M., E-mail: mcqueen@jhu.edu

The synthesis and physical properties of the new distorted-Hollandite PbIr{sub 4}Se{sub 8} are reported. Powder X-ray diffraction and transmission electron microscopy show that the structure consists of edge- and corner-sharing IrSe{sub 6} octahedra, with one-dimensional channels occupied by Pb. The structure contains Se-Se anion-anion bonding, leading to an electron count of Pb{sup 2+}(Ir{sup 3+}){sub 4}(Se{sub 2}){sup 2-}(Se{sup 2−}){sub 6}, confirmed by bond-valence sums and diamagnetic behavior. Structural and heat capacity measurements demonstrate disorder on the Pb site, due to the combination of lone-pair effects and the large size of the one-dimensional channels. Comparisons are made to known Hollandite and pseudo-Hollanditemore » structures, which demonstrates that the anion-anion bonding in PbIr{sub 4}Se{sub 8} distorts its structure, to accommodate the Ir{sup 3+} state. An electronic structure calculation indicates semiconductor character with a band gap of 0.76(11) eV.« less

Bromidotetra­kis­(1H-2-ethyl-5-methyl­imidazole-κN 3)copper(II) bromide

PubMed Central

Godlewska, Sylwia; Baranowska, Katarzyna; Socha, Joanna; Dołęga, Anna

2011-01-01

The CuII ion in the title compound, [CuBr(C6H10N2)4]Br, is coordinated in a square-based-pyramidal geometry by the N atoms of four imidazole ligands and a bromide anion in the apical site. Both the CuII and Br− atoms lie on a crystallographic fourfold axis. In the crystal, the [CuBr(C6H10N2)4]+ complex cations are linked to the uncoordinated Br− anions (site symmetry ) by N—H⋯Br hydrogen bonds, generating a three-dimensional network. The ethyl group of the imidazole ligand was modelled as disordered over two orientations with occupancies of 0.620 (8) and 0.380 (8). PMID:22199662

Clusterization Effects in III-V Nitrides: Nitrogen Vacancies, and Si and Mg Impurities in Aluminum Nitride and Gallium Nitride

NASA Astrophysics Data System (ADS)

Gubanov, V. A.; Pentaleri, E. A.; Boekema, C.; Fong, C. Y.; Klein, B. M.

1997-03-01

We have investigated clusterization of nitrogen vacancies and Si and Mg doping impurities in zinc-blende aluminum nitride (c-AlN) and gallium nitride (c-GaN) by the tight-binding LMTO technique. The calculations used 128-site supercells. Si and Mg atoms replacing ions in both the cation and anion sublattices of the host lattices of the host crystals have been considered. The Mg impurity at cation sites is found to form partially occupied states at the valence-band edge, and may result in p-type conductivity. When Si substitutes for Ga, the impurity band is formed at the conduction-band edge, resulting in n-type conductivity. Si impurities at cation sites, and Mg impurity at anion sites are able to form resonance states in the gap. The influence of impurity clusterization in the host lattice and interstitial sites on electronic properties of c-AlN and c-GaN crystals are modeled. The changes in vacancy- and impurity-state energies, bonding type, localization, density of states at the Fermi level in different host lattices, their dependence on impurity/vacancy concentration are analyzed and compared with the experimental data.

Creating Protected Areas on Public Lands: Is There Room for Additional Conservation?

PubMed

Arriagada, Rodrigo A; Echeverria, Cristian M; Moya, Danisa E

2016-01-01

Most evaluations of the effectiveness of PAs have relied on indirect estimates based on comparisons between protected and unprotected areas. Such methods can be biased when protection is not randomly assigned. We add to the growing literature on the impact of PAs by answering the following research questions: What is the impact of Chilean PAs on deforestation which occurred between 1986 and 2011? How do estimates of the impact of PAs vary when using only public land as control units? We show that the characteristics of the areas in which protected and unprotected lands are located differ significantly. To satisfactorily estimate the effects of PAs, we use matching methods to define adequate control groups, but not as in previous research. We construct control groups using separately non-protected private areas and non-protected public lands. We find that PAs avoid deforestation when using unprotected private lands as valid controls, however results show no impact when the control group is based only on unprotected public land. Different land management regimes, and higher levels of enforcement inside public lands may reduce the opportunity to add additional conservation benefits when the national systems for PAs are based on the protection of previously unprotected public lands. Given that not all PAs are established to avoid deforestation, results also admit the potential for future studies to include other outcomes including forest degradation (not just deforestation), biodiversity, wildlife, primary forests (not forests in general), among others.

Impact of extended maceration and regulated deficit irrigation (RDI) in Cabernet Sauvignon wines: characterization of proanthocyanidin distribution, anthocyanin extraction, and chromatic properties.

PubMed

Casassa, L Federico; Larsen, Richard C; Beaver, Christopher W; Mireles, Maria S; Keller, Markus; Riley, William R; Smithyman, Russell; Harbertson, James F

2013-07-03

The impact of extended maceration (EM) was studied in Cabernet Sauvignon grapes sourced from a vineyard subjected to four regulated deficit irrigation (RDI) treatments: (I) 100% replenishment of crop evapotranspiration (100% ETc), (II) 70% ETc, (III) 25% ETc until véraison, followed by 100% ETc until harvest, and IV) 25% ETc. Each vineyard replicate was made into wine with two replicates designated as controls (10-day skin contact) and two as extended maceration (EM, 30-day skin contact). The mean degree of polymerization (mDP), size distribution, concentration, and composition of wine proanthocyanidins (PAs) and monomeric flavan-3-ols of 90 fractions were characterized by preparative and analytical HPLC techniques. The maceration length imparted a larger effect on most chemical parameters. The RDI treatment had no effect on the extraction patterns of anthocyanins, PAs, and/or on the origin of the PAs extracted into the wines. Conversely, EM led to anthocyanin losses and increased PA extraction during maceration, with ~73% of seed-derived PAs. Accordingly, the concentration of monomeric flavan-3-ols, oligomeric (2 ≤ mDP < 5) and polymeric PAs (mDP ≥ 5) was higher in EM wines. The size distribution of the wines' PAs revealed two major peaks as a function of concentration at mDP 2 (22-27% of total PAs mass) and at mDP 6-7 (12-17% of total PAs mass) and was found to follow a non-normal Rayleigh-type distribution.

Creating Protected Areas on Public Lands: Is There Room for Additional Conservation?

PubMed Central

Arriagada, Rodrigo A.; Echeverria, Cristian M.; Moya, Danisa E.

2016-01-01

Most evaluations of the effectiveness of PAs have relied on indirect estimates based on comparisons between protected and unprotected areas. Such methods can be biased when protection is not randomly assigned. We add to the growing literature on the impact of PAs by answering the following research questions: What is the impact of Chilean PAs on deforestation which occurred between 1986 and 2011? How do estimates of the impact of PAs vary when using only public land as control units? We show that the characteristics of the areas in which protected and unprotected lands are located differ significantly. To satisfactorily estimate the effects of PAs, we use matching methods to define adequate control groups, but not as in previous research. We construct control groups using separately non-protected private areas and non-protected public lands. We find that PAs avoid deforestation when using unprotected private lands as valid controls, however results show no impact when the control group is based only on unprotected public land. Different land management regimes, and higher levels of enforcement inside public lands may reduce the opportunity to add additional conservation benefits when the national systems for PAs are based on the protection of previously unprotected public lands. Given that not all PAs are established to avoid deforestation, results also admit the potential for future studies to include other outcomes including forest degradation (not just deforestation), biodiversity, wildlife, primary forests (not forests in general), among others. PMID:26848856

Promoting Motor Cortical Plasticity with Acute Aerobic Exercise: A Role for Cerebellar Circuits

PubMed Central

Mang, Cameron S.; Brown, Katlyn E.; Neva, Jason L.; Snow, Nicholas J.; Campbell, Kristin L.; Boyd, Lara A.

2016-01-01

Acute aerobic exercise facilitated long-term potentiation-like plasticity in the human primary motor cortex (M1). Here, we investigated the effect of acute aerobic exercise on cerebellar circuits, and their potential contribution to altered M1 plasticity in healthy individuals (age: 24.8 ± 4.1 years). In Experiment   1, acute aerobic exercise reduced cerebellar inhibition (CBI) (n = 10, p = 0.01), elicited by dual-coil paired-pulse transcranial magnetic stimulation. In Experiment   2, we evaluated the facilitatory effects of aerobic exercise on responses to paired associative stimulation, delivered with a 25 ms (PAS25) or 21 ms (PAS21) interstimulus interval (n = 16 per group). Increased M1 excitability evoked by PAS25, but not PAS21, relies on trans-cerebellar sensory pathways. The magnitude of the aerobic exercise effect on PAS response was not significantly different between PAS protocols (interaction effect: p = 0.30); however, planned comparisons indicated that, relative to a period of rest, acute aerobic exercise enhanced the excitatory response to PAS25 (p = 0.02), but not PAS21 (p = 0.30). Thus, the results of these planned comparisons indirectly provide modest evidence that modulation of cerebellar circuits may contribute to exercise-induced increases in M1 plasticity. The findings have implications for developing aerobic exercise strategies to “prime” M1 plasticity for enhanced motor skill learning in applied settings. PMID:27127659

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

Guo, Yirui; Scheuermann, Thomas H.; Partch, Carrie L.

The hypoxia-inducible factor complex (HIF-α·aryl hydrocarbon receptor nuclear translocator (ARNT)) requires association with several transcription coactivators for a successful cellular response to hypoxic stress. In addition to the conventional global transcription coactivator CREB-binding protein/p300 (CBP/p300) that binds to the HIF-α transactivation domain, a new group of transcription coactivators called the coiled-coil coactivators (CCCs) interact directly with the second PER-ARNT-SIM (PAS) domain of ARNT (ARNT PAS-B). These less studied transcription coactivators play essential roles in the HIF-dependent hypoxia response, and CCC misregulation is associated with several forms of cancer. To better understand CCC protein recruitment by the heterodimeric HIF transcription factor,more » we used x-ray crystallography, NMR spectroscopy, and biochemical methods to investigate the structure of the ARNT PAS-B domain in complex with the C-terminal fragment of a coiled-coil coactivator protein, transforming acidic coiled-coil coactivator 3 (TACC3). We found that the HIF-2α PAS-B domain also directly interacts with TACC3, motivating an NMR data-derived model suggesting a means by which TACC3 could form a ternary complex with HIF-2α PAS-B and ARNT PAS-B via β-sheet/coiled-coil interactions. Furthermore, these findings suggest that TACC3 could be recruited as a bridge to cooperatively mediate between the HIF-2α PAS-B·ARNT PAS-B complex, thereby participating more directly in HIF-dependent gene transcription than previously anticipated.« less

Electric field effect on the electronic structure of 2D Y2C electride

NASA Astrophysics Data System (ADS)

Oh, Youngtek; Lee, Junsu; Park, Jongho; Kwon, Hyeokshin; Jeon, Insu; Wng Kim, Sung; Kim, Gunn; Park, Seongjun; Hwang, Sung Woo

2018-07-01

Electrides are ionic compounds in which electrons confined in the interstitial spaces serve as anions and are attractive owing to their exotic physical and chemical properties in terms of their low work function and efficient charge-transfer characteristics. Depending on the topology of the anionic electrons, the surface electronic structures of electrides can be significantly altered. In particular, the electronic structures of two-dimensional (2D) electride surfaces are of interest because the localized anionic electrons at the interlayer space can be naturally exposed to cleaved surfaces. In this paper, we report the electronic structure of 2D Y2C electride surface using scanning tunneling microscopy (STM) and first-principles calculations, which reveals that anionic electrons at a cleaved surface are absorbed by the surface and subsequently resurged onto the surface due to an applied electric field. We highlight that the estranged anionic electrons caused by the electric field occupy the slightly shifted crystallographic site compared with a bulk Y2C electride. We also measure the work function of the Y2C single crystal, and it shows a slightly lower value than the calculated one, which appears to be due to the electric field from the STM junction.

Can collision-induced negative-ion fragmentations of [M-H](-) anions be used to identify phosphorylation sites in peptides?

PubMed

Tran, T T Nha; Wang, Tianfang; Hack, Sandra; Hoffmann, Peter; Bowie, John H

2011-12-15

A joint experimental and theoretical investigation of the fragmentation behaviour of energised [M-H](-) anions from selected phosphorylated peptides has confirmed some of the most complex rearrangement processes yet to be reported for peptide negative ions. In particular: pSer and pThr (like pTyr) may transfer phosphate groups to C-terminal carboxyl anions and to the carboxyl anion side chains of Asp and Glu, and characteristic nucleophilic/cleavage reactions accompany or follow these rearrangements. pTyr may transfer phosphate to the side chains of Ser and Thr. The reverse reaction, namely transfer of a phosphate group from pSer or pThr to Tyr, is energetically unfavourable in comparison. pSer can transfer phosphate to a non-phosphorylated Ser. The non-rearranged [M-H](-) species yields more abundant product anions than its rearranged counterpart. If a peptide containing any or all of Ser, Thr and Tyr is not completely phosphorylated, negative-ion cleavages can determine the number of phosphated residues, and normally the positions of Ser, Thr and Tyr, but not which specific residues are phosphorylated. This is in accord with comments made earlier by Lehmann and coworkers. Copyright © 2011 John Wiley & Sons, Ltd.

Electron interaction with phosphate cytidine oligomer dCpdC: base-centered radical anions and their electronic spectra.

PubMed

Gu, Jiande; Wang, Jing; Leszczynski, Jerzy

2014-01-30

Computational chemistry approach was applied to explore the nature of electron attachment to cytosine-rich DNA single strands. An oligomer dinucleoside phosphate deoxycytidylyl-3',5'-deoxycytidine (dCpdC) was selected as a model system for investigations by density functional theory. Electron distribution patterns for the radical anions of dCpdC in aqueous solution were explored. The excess electron may reside on the nucleobase at the 5' position (dC(•-)pdC) or at the 3' position (dCpdC(•-)). From comparison with electron attachment to the cytosine related DNA fragments, the electron affinity for the formation of the cytosine-centered radical anion in DNA is estimated to be around 2.2 eV. Electron attachment to cytosine sites in DNA single strands might cause perturbations of local structural characteristics. Visible absorption spectroscopy may be applied to validate computational results and determine experimentally the existence of the base-centered radical anion. The time-dependent DFT study shows the absorption around 550-600 nm for the cytosine-centered radical anions of DNA oligomers. This indicates that if such species are detected experimentally they would be characterized by a distinctive color.

Practical solution for control of the pre-analytical phase in decentralized clinical laboratories for meeting the requirements of the medical laboratory accreditation standard DIN EN ISO 15189.

PubMed

Vacata, Vladimir; Jahns-Streubel, Gerlinde; Baldus, Mirjana; Wood, William Graham

2007-01-01

This report was written in response to the article by Wood published recently in this journal. It describes a practical solution to the problems of controlling the pre-analytical phase in the clinical diagnostic laboratory. As an indicator of quality in the pre-analytical phase of sample processing, a target analyte was chosen which is sensitive to delay in centrifugation and/or analysis. The results of analyses of the samples sent by satellite medical practitioners were compared with those from an on-site hospital laboratory with a controllable optimized pre-analytical phase. The aim of the comparison was: (a) to identify those medical practices whose mean/median sample values significantly deviate from those of the control situation in the hospital laboratory due to the possible problems in the pre-analytical phase; (b) to aid these laboratories in the process of rectifying these problems. A Microsoft Excel-based Pre-Analytical Survey tool (PAS tool) has been developed which addresses the above mentioned problems. It has been tested on serum potassium which is known to be sensitive to delay and/or irregularities in sample treatment. The PAS tool has been shown to be one possibility for improving the quality of the analyses by identifying the sources of problems within the pre-analytical phase, thus allowing them to be rectified. Additionally, the PAS tool has an educational value and can also be adopted for use in other decentralized laboratories.

Deep Sclerectomy with Goniosynechiolysis Ab Interno for Chronic Glaucoma Associated with Peripheral Anterior Synechiae

PubMed Central

Raak, Peter; Ponto, Katharina; Stoffelns, Bernhard; Lorenz, Katrin; Scharioth, Gábor B.

2015-01-01

Purpose. To report one-year results of phacoemulsification combined with deep sclerectomy and goniosynechiolysis ab interno for chronic glaucoma associated with peripheral anterior synechiae (PAS). Methods. We retrospectively analyzed medical charts of 16 patients (20 eyes) treated by one-site combined phacoemulsification and deep sclerectomy with goniosynechiolysis ab interno. PAS were transected by a spatula introduced into the anterior chamber through a paracentesis. To account for the correlation of right and left eyes a linear mixed model with unstructured covariance structure was calculated. Results. The mean preoperative intraocular pressure (IOP) was 20.3 ± 5.2 mmHg with 2.4 ± 1.0 medications. One year postoperatively, the mean IOP was 15.3 ± 3.3 mmHg (P = 0.004, paired t-test) with 0.6 ± 1.0 medications. A postoperative IOP of ≤21 mmHg without medication was achieved in 17 of 19 eyes (89.5%) and in 12/19 eyes (63.2%) at 3 and 12 months after surgery, respectively. In the remaining eyes (10.5% at 3 months and 36.8% at 12 months), additional medication led to an IOP ≤21 mmHg or the target pressure. No case required further glaucoma surgery. In one eye, conversion of the surgery to trabeculectomy was necessary due to Descemet's window rupture. Conclusions. With goniosynechiolysis ab interno, effective and safe nonpenetrating glaucoma surgery is possible in presence of PAS. PMID:26199738

Improvement of calcium mineral separation contrast using anionic reagents: electrokinetics properties and flotation

NASA Astrophysics Data System (ADS)

Lafhaj, Z.; Filippov, L. O.; Filippova, I. V.

2017-07-01

The flotation separation of salt type calcium minerals is problematic, due to the similarities in their same active Ca2+ related site for interaction with anionic collectors and similar physicochemical characteristics such as solubility, zero-point charge, surface speciation and Ca-site density. The work was performed to achieve effective and selective separation of the calcium-minerals using pure minerals samples: orange calcite with Mg impurities, optic calcite with impurities level and an apatite. The pure samples surface was examined using techniques sensitive near-surface like infrared spectroscopy (FTIR) and chemical composition was obtained by ICPMS. The isoelectric point (IEP) and point of zero charge (PZC) in electrolyte were recorded using electrophoresis method at different ionic strengths of the solution. Mechanisms of charge development at the mineral-water interface are discussed. The time of contact as important parameter for the charge equilibrium was deduced from kinetics study and fixed to 30 minutes. The difference in the values obtained between IEP and PZSE can be explained by the presence of a specific adsorption of cations and anions on the surface. The effect of pure anionic collectors such as oleic and linoleic acid were studied. At low pH, both collectors lead to a good recovery for the calcites. The flotation recovery of optic calcite at pH 9 with sodium oleate is higher than with sodium linoleate. At alkaline pH, apatite showed a better recovery with sodium linoleate.

Communicating Performance Assessments Results - 13609

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

Layton, Mark

2013-07-01

The F-Area Tank Farms (FTF) and H-Area Tank Farm (HTF) are owned by the U.S. Department of Energy (DOE) and operated by Savannah River Remediation LLC (SRR), Liquid Waste Operations contractor at DOE's Savannah River Site (SRS). The FTF and HTF are active radioactive waste storage and treatment facilities consisting of 51 carbon steel waste tanks and ancillary equipment such as transfer lines, evaporators and pump tanks. Performance Assessments (PAs) for each Tank Farm have been prepared to support the eventual closure of the underground radioactive waste tanks and ancillary equipment. PAs provide the technical bases and results to bemore » used in subsequent documents to demonstrate compliance with the pertinent requirements for final closure of the Tank Farms. The Tank Farms are subject to a number of regulatory requirements. The State regulates Tank Farm operations through an industrial waste water permit and through a Federal Facility Agreement approved by the State, DOE and the Environmental Protection Agency (EPA). Closure documentation will include State-approved Tank Farm Closure Plans and tank-specific closure modules utilizing information from the PAs. For this reason, the State of South Carolina and the EPA must be involved in the performance assessment review process. The residual material remaining after tank cleaning is also subject to reclassification prior to closure via a waste determination pursuant to Section 3116 of the Ronald W. Reagan National Defense Authorization Act of Fiscal Year 2005. PAs are performance-based, risk-informed analyses of the fate and transport of FTF and HTF residual wastes following final closure of the Tank Farms. Since the PAs serve as the primary risk assessment tools in evaluating readiness for closure, it is vital that PA conclusions be communicated effectively. In the course of developing the FTF and HTF PAs, several lessons learned have emerged regarding communicating PA results. When communicating PA results it is important to stress that the primary goal of the PA results is to provide risk understanding, recognizing the magnitude of risk and identifying the conceptual model decisions and critical assumptions that most impact the results. Conceptual models that describe reality using simplified, mathematical approaches, and their roles in arriving at the PA results, must also be communicated. When presenting PA results, evaluations will typically be focused on a single baseline (or Base Case) to provide a foundation for discussion. The PA results are supplemented by other studies (alternate configurations, uncertainty analyses, and sensitivity analyses) which provide a breadth of modeling to supplement the Base Case. The suite of information offered by the various modeling cases and studies provides confidence that the overall risk is understood along with the underlying parameters and conditions that contribute to risk. (author)« less

Personal Assistance Services (PAS): Toward Universal Access to Support. Annotated Bibliography.

ERIC Educational Resources Information Center

Racino, Julie Ann

This annotated bibliography provides approximately 100 summaries and evaluations of documents, published from 1979 to 1995, on personal assistance services (PAS) for individuals with disabilities. Studies and articles were selected for inclusion based upon their capacity to inform the development of PAS models, including conceptual, policy, and…

Development and Validation of the Poverty Attributions Survey

ERIC Educational Resources Information Center

Bennett, Robert M.; Raiz, Lisa; Davis, Tamara S.

2016-01-01

This article describes the process of developing and testing the Poverty Attribution Survey (PAS), a measure of poverty attributions. The PAS is theory based and includes original items as well as items from previously tested poverty attribution instruments. The PAS was electronically administered to a sample of state-licensed professional social…

The punctal apposition syndrome: a new surgical approach.

PubMed

Francis, I C; Wan, M K

2002-11-01

To assess the punctal apposition syndrome (PAS) and its response to lateral canthal tendon (LCT) repair. In this retrospective, interventional case series, five patients (seven symptomatic eyes) with PAS were managed. Lateral canthal tendon repair was performed in all seven eyes. The main outcome measure was correction of watery eye symptomatology. All five patients achieved symptomatic resolution. Conjunctivochalasis and functional nasolacrimal duct obstruction were associated with the PAS. This new surgical approach to the PAS, using a LCT repair, was successful in all patients. Two patients (three eyes) required conjunctivochalasis excision.

2013 Annual Summary Report for the Area 3 and Area 5 Radioactive Waste Management Sites at the Nevada National Security Site, Nye County, Nevada; Review of the Performance Assessments and Composite Analyses

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

Shott, Gregory

2014-03-01

The Maintenance Plan for the Performance Assessments and Composite Analyses for the Area 3 and Area 5 Radioactive Waste Management Sites at the Nevada Test Site (National Security Technologies, LLC 2007a) requires an annual review to assess the adequacy of the performance assessments (PAs) and composite analyses (CAs), with the results submitted to the U.S. Department of Energy (DOE) Office of Environmental Management. The Disposal Authorization Statements for the Area 3 and Area 5 Radioactive Waste Management Sites (RWMSs) also require that such reviews be made and that secondary or minor unresolved issues be tracked and addressed as part ofmore » the maintenance plan (DOE 1999a, 2000). The U.S. Department of Energy, National Nuclear Security Administration Nevada Field Office performed an annual review of the Area 3 and Area 5 RWMS PAs and CAs for fiscal year (FY) 2013. This annual summary report presents data and conclusions from the FY 2013 review, and determines the adequacy of the PAs and CAs. Operational factors (e.g., waste forms and containers, facility design, and waste receipts), closure plans, monitoring results, and research and development (R&D) activities were reviewed to determine the adequacy of the PAs. Likewise, the environmental restoration activities at the Nevada National Security Site (NNSS) relevant to the sources of residual radioactive material that are considered in the CAs, the land-use planning, and the results of the environmental monitoring and R&D activities were reviewed to determine the adequacy of the CAs. Important developments in FY 2013 include the following: • Development of a new Area 5 RWMS closure inventory estimate based on disposals through FY 2013 • Evaluation of new or revised waste streams by special analysis • Development of version 4.115 of the Area 5 RWMS GoldSim PA/CA model The Area 3 RWMS has been in inactive status since July 1, 2006, with the last shipment received in April 2006. The FY 2013 review of operations, facility design, closure plans, monitoring results, and R&D results for the Area 3 RWMS indicates no changes that would impact PA validity. The conclusion of the annual review is that all performance objectives can be met and the Area 3 RWMS PA remains valid. There is no need to the revise the Area 3 RWMS PA. Review of Area 5 RWMS operations, design, closure plans, monitoring results, and R&D activities indicates that no significant changes have occurred. The FY 2013 PA results, generated with the Area 5 RWMS v4.115 GoldSim PA model, indicate that there continues to be a reasonable expectation of meeting all performance objectives. The results and conclusions of the Area 5 RWMS PA are judged valid, and there is no need to the revise the PA. A review of changes potentially impacting the CAs indicates that no significant changes occurred in FY 2013. The continuing adequacy of the CAs was evaluated with the new models, and no significant changes that would alter the CAs results or conclusions were found. The revision of the Area 3 RWMS CA, which will include the Yucca Flat Underground Test Area (Corrective Action Unit [CAU] 97) source term, is scheduled for FY 2024, following the completion of the Corrective Action Decision Document/Corrective Action Plan in FY 2015. Inclusion of the Frenchman Flat Underground Test Area (CAU 98) results in the Area 5 RWMS CA is scheduled for FY 2016, pending the completion of the CAU 98 Closure Report in FY 2015. Near-term R&D efforts will focus on continuing development of the PA, CA, and inventory models for the Area 3 and Area 5 RWMS.« less

[A case of parental alienation].

PubMed

Menz, Wolfgang

2014-01-01

The clinical term "Parental Alienation Syndrome" (PAS) was introduced in 1984 by Richard Gardner, an American psychiatrist. Gardner described PAS and its symptoms, as a personality disorder, which appears chiefly in connection to child custody disputes wherein a child turns suddenly and massively against the non-custodial parent without reasonable grounds for doing so. This action by the child is a result of the custodial parent's emotionally abusive attempts to incite the child against the non-custodial parent.Where the child's rejection is based on some real past experience, there is not PAS. PAS only occurs as a result of the custodial parent's actions. Despite intensive effort, PAS was not included in the new DSM-V. In this case, a particularly impressive case history of parental alienation is described and discussed.

Aircraft noise prediction program propeller analysis system IBM-PC version user's manual version 2.0

NASA Technical Reports Server (NTRS)

Nolan, Sandra K.

1988-01-01

The IBM-PC version of the Aircraft Noise Prediction Program (ANOPP) Propeller Analysis System (PAS) is a set of computational programs for predicting the aerodynamics, performance, and noise of propellers. The ANOPP-PAS is a subset of a larger version of ANOPP which can be executed on CDC or VAX computers. This manual provides a description of the IBM-PC version of the ANOPP-PAS and its prediction capabilities, and instructions on how to use the system on an IBM-XT or IBM-AT personal computer. Sections within the manual document installation, system design, ANOPP-PAS usage, data entry preprocessors, and ANOPP-PAS functional modules and procedures. Appendices to the manual include a glossary of ANOPP terms and information on error diagnostics and recovery techniques.

A study of Canadian hospice palliative care volunteers' attitudes toward physician-assisted suicide.

PubMed

Claxton-Oldfield, Stephen; Miller, Kathryn

2015-05-01

The purpose of this study was to examine the attitudes of hospice palliative care (HPC) volunteers who provide in-home support (n = 47) and members of the community (n = 58) toward the issue of physician-assisted suicide (PAS). On the first part of the survey, participants responded to 15 items designed to assess their attitudes toward PAS. An examination of individual items revealed differences in opinions among members of both the groups. Responses to additional questions revealed that the majority of volunteers and community members (1) support legalizing PAS; (2) would choose HPC over PAS for themselves if they were terminally ill; and (3) think Canadians should place more priority on developing HPC rather than on legalizing PAS. The implications of these findings are discussed. © The Author(s) 2014.

Power, Avionics and Software - Phase 1.0:. [Subsystem Integration Test Report

NASA Technical Reports Server (NTRS)

Ivancic, William D.; Sands, Obed S.; Bakula, Casey J.; Oldham, Daniel R.; Wright, Ted; Bradish, Martin A.; Klebau, Joseph M.

2014-01-01

This report describes Power, Avionics and Software (PAS) 1.0 subsystem integration testing and test results that occurred in August and September of 2013. This report covers the capabilities of each PAS assembly to meet integration test objectives for non-safety critical, non-flight, non-human-rated hardware and software development. This test report is the outcome of the first integration of the PAS subsystem and is meant to provide data for subsequent designs, development and testing of the future PAS subsystems. The two main objectives were to assess the ability of the PAS assemblies to exchange messages and to perform audio testing of both inbound and outbound channels. This report describes each test performed, defines the test, the data, and provides conclusions and recommendations.

Qualitative study of employment of physician assistants by physicians

PubMed Central

Taylor, Maureen T.; Wayne Taylor, D.; Burrows, Kristen; Cunnington, John; Lombardi, Andrea; Liou, Michelle

2013-01-01

Abstract Objective To explore the experiences and perceptions of Ontario physician assistant (PA) employers about the barriers to and benefits of hiring PAs. Design A qualitative design using semistructured interviews. Setting Rural and urban eastern and southwestern Ontario. Participants Seven family physicians and 7 other specialists. Methods The 14 physicians participated in semistructured interviews, which were audiorecorded and transcribed verbatim. An iterative approach using immersion and crystallization was employed for analysis. Main findings Physician-specific benefits to hiring PAs included increased flexibility, the opportunity to expand practice, the ability to focus more time on complex patients, overall reduction in work hours and stress, and an opportunity for professional fellowship. Physicians who hired PAs without government financial support said PAs were affordable as long as they were able to retain them. Barriers to hiring PAs included uncertainty about funding, the initial need for intensive supervision and training, and a lack of clarity around delegation of acts. Conclusion Physicians are motivated to hire PAs to help deal with long wait times and long hours, but few are expecting to increase their income by taking on PAs. Governments, medical colleges, educators, and regulators must address the perceived barriers to PA hiring in order to expand and optimize this profession. PMID:24235209

The Effect of Proanthocyanidins on Growth and Alcoholic Fermentation of Wine Yeast under Copper Stress.

PubMed

Jia, Bo; Liu, Xingyan; Zhan, Jicheng; Li, Jingyuan; Huang, Weidong

2015-06-01

Proanthocyanidins (PAs) derived from the grape skin, as well as from grape seeds, grape stems, are an important group of polyphenols in wine. The aim of this study was to understand the effect of PAs (0.1, 1.0 g/L) on growth and alcoholic fermentation of 2 strains of Saccharomyces cerevisiae (commercial strain FREDDO and newly selected strain BH8) during copper-stress fermentation, using a simple model fermentation system. Our results showed that both PAs and Cu(2+) could pose significant inhibition effects on the growth of yeast cells, CO2 release, sugar consumption, and ethanol production during the initial phase of the fermentation. Compared to PAs, Cu(2+) performed more obvious inhibition on the yeast growth and fermentation. However, adding 1.0 g/L PAs increased in the vitality and metabolism activity of yeast cells at the mid-exponential phase of fermentation in the mediums with no copper and 0.1 mM Cu(2+) added, shortened the period of wine fermentation, and decreased the copper residues. It indicated that PAs could improve the ability of wine yeast to resist detrimental effects under copper-stress fermentation condition, maintaining cells metabolic activity, and fermentation could be controlled by manipulating PAs supplementation. © 2015 Institute of Food Technologists®

Assessment of pyrrolizidine alkaloid-induced toxicity in an in vitro screening model.

PubMed

Li, Yan Hong; Kan, Winnie Lai Ting; Li, Na; Lin, Ge

2013-11-25

Pyrrolizidine alkaloids (PAs) are a group of heterocyclic phytotoxins present in a wide range of plants. The consumption of PA-containing medicinal herbs or PA-contaminated foodstuffs has long been reported to cause human hepatotoxicity. However, the degrees of hepatotoxicity of different PAs are unknown, which makes it difficult to determine a universal threshold of toxic dose of individual PAs for safe regulation of PA-containing natural products. The aim of the present study is to develop a simple and convenient in vitro model to assess the hepatotoxicity of different PAs. Six common cytotoxicity assays were used to evaluate the hepatotoxicity of different PAs in human hepatocellular carcinoma HepG2 cells. The combination of MTT and bromodeoxyuridine incorporation (BrdU) assays demonstrated to be a suitable method to evaluate the toxic potencies of various PAs in HepG2 cells, and the results indicated that otonecine-type PA (clivorine: IC₂₀=0.013 ± 0.004 mM (MTT), 0.066 ± 0.031 mM (BrdU)) exhibited significantly higher cytotoxic and anti-proliferative effects than retronecine-type PA (retrorsine: IC₂₀=0.27 ± 0.07 mM (MTT), 0.19 ± 0.03 mM (BrdU)). While as expected, the known less toxic platyphylline-type PA (platyphylline: IC₂₀=0.85 ± 0.11 mM (MTT), 1.01 ± 0.40 mM (BrdU)) exhibited significantly less toxicity. The different cytotoxic and anti-proliferative potencies of various PAs in the same retronecine-type could also be discriminated by using the combined MTT and BrdU assays. In addition, the developed assays were further utilized to test alkaloid extract of Gynura segetum, a senecionine and seneciphylline-containing herb, the overall cytotoxicity of two PAs in the extract was comparable to that of these two PAs tested individually. Using the developed in vitro model, the cytotoxicity of different PAs and the extract of a PA-containing herb were investigated in parallel in one system, and their different hepatotoxic potencies were determined and directly compared for the first time. The results suggested that the developed model has a great potential to be applied for the quick screening of the toxicity of PAs and PA-containing natural products. © 2013 Elsevier Ireland Ltd. All rights reserved.

Solo emergency care by a physician assistant versus an ambulance nurse: a cross-sectional document study.

PubMed

Bloemhoff, Anneke; Schoonhoven, Lisette; de Kreek, Arjan J L; van Grunsven, Pierre M; Laurant, Miranda G H; Berben, Sivera A A

2016-06-29

This study compares the assessment, treatment, referral, and follow up contact with the dispatch centre of emergency patients treated by two types of solo emergency care providers in ambulance emergency medical services (EMS) in the Netherlands: the physician assistant (PA), educated in the medical domain, and the ambulance registered nurse (RN), educated in the nursing domain. The hypothesis of this study was that there is no difference in outcome of care between the patients of PAs and RNs. In a cross-sectional document study in two EMS regions we included 991 patients, treated by two PAs (n = 493) and 23 RNs (n = 498). The inclusion period was October 2010-December 2012 for region 1 and January 2013-March 2014 for region 2. Emergency care data were drawn from predefined and free text fields in the electronic patient records. Data were analysed using descriptive statistics. We used χ (2) and Mann-Whitney U tests to analyse for differences in outcome of care. Statistical significance was assumed at a level of P <0.05. Patients treated by PAs and RNs were similar with respect to patient characteristics. In general, diagnostic measurements according to the national EMS standard were applied by RNs and by PAs. In line with the medical education, PAs used a medical diagnostic approach (16 %, n = 77) and a systematic physical exam of organ tract systems (31 %, n = 155). PAs and RNs provided similar interventions. Additionally, PAs consulted more often other medical specialists (33 %) than RNs (17 %) (χ (2)  = 35.5, P <0.0001). PAs referred less patients to the general practitioner or emergency department (50 %) compared to RNs (73 %) (χ (2)  = 52.9, P <0.0001). Patient follow up contact with the dispatch centre within 72 h after completion of the emergency care on scene showed no variation between PAs (5 %) and RNs (4 %). In line with their medical education, PAs seemed to operate from a more general medical perspective. They used a medical diagnostic approach, consulted more medical specialists, and referred significantly less patients to other health care professionals compared to RNs. While the patients of the PAs did not contact the dispatch centre more often afterwards.

A Global Analysis of Deforestation in Moist Tropical Forest Protected Areas.

PubMed

Spracklen, B D; Kalamandeen, M; Galbraith, D; Gloor, E; Spracklen, D V

2015-01-01

Protected areas (PAs) have been established to conserve tropical forests, but their effectiveness at reducing deforestation is uncertain. To explore this issue, we combined high resolution data of global forest loss over the period 2000-2012 with data on PAs. For each PA we quantified forest loss within the PA, in buffer zones 1, 5, 10 and 15 km outside the PA boundary as well as a 1 km buffer within the PA boundary. We analysed 3376 tropical and subtropical moist forest PAs in 56 countries over 4 continents. We found that 73% of PAs experienced substantial deforestation pressure, with >0.1% a(-1) forest loss in the outer 1 km buffer. Forest loss within PAs was greatest in Asia (0.25% a(-1)) compared to Africa (0.1% a(-1)), the Neotropics (0.1% a(-1)) and Australasia (Australia and Papua New Guinea; 0.03% a(-1)). We defined performance (P) of a PA as the ratio of forest loss in the inner 1 km buffer compared to the loss that would have occurred in the absence of the PA, calculated as the loss in the outer 1 km buffer corrected for any difference in deforestation pressure between the two buffers. To remove the potential bias due to terrain, we analysed a subset of PAs (n = 1804) where slope and elevation in inner and outer 1 km buffers were similar (within 1° and 100 m, respectively). We found 41% of PAs in this subset reduced forest loss in the inner buffer by at least 25% compared to the expected inner buffer forest loss (P<0.75). Median performance (P) of subset reserves was 0.87, meaning a reduction in forest loss within the PA of 13%. We found PAs were most effective in Australasia (P = 0.16), moderately successful in the Neotropics (P = 0.72) and Africa (p = 0.83), but ineffective in Asia (P = 1). We found many countries have PAs that give little or no protection to forest loss, particularly in parts of Asia, west Africa and central America. Across the tropics, the median effectiveness of PAs at the national level improved with gross domestic product per capita. Whilst tropical and subtropical moist forest PAs do reduce forest loss, widely varying performance suggests substantial opportunities for improved protection, particularly in Asia.

Photoelectron Spectroscopy of the Doubly-Charged Anions [MIVO(mnt)2]2- (M=Mo, W; mnt=S2C2(CN)22-): Access to the Ground and Excited States of the [MvO(mnt)2]-Anion

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

Waters, Tom; Wang, Xue B.; Yang, Xin

2004-04-21

Photodetachment photoelectron spectroscopy was used to investigate the electronic structure of the doubly charged complexes [MIVO(mnt)2]2- (M=Mo, W;mnt=1,2 dicyanoethenedithiolato). These dianions are stable in the gas phase and are minimal models for the active sites of the dimethyl sulfoxide reductase family of molybdenum enzymes and of related tungsten enzymes. Adiabatic and vertical electron binding energies for both species were measured, providing detailed information about molecular orbital energy levels of the parent dianions as well as the ground and excited states of the product anions [MvO(mnt)2]. Density functional theory calculations were used to assist assignment of the detachment features.

NO3- anions can act as Lewis acid in the solid state

NASA Astrophysics Data System (ADS)

Bauzá, Antonio; Frontera, Antonio; Mooibroek, Tiddo J.

2017-02-01

Identifying electron donating and accepting moieties is crucial to understanding molecular aggregation, which is of pivotal significance to biology. Anions such as NO3- are typical electron donors. However, computations predict that the charge distribution of NO3- is anisotropic and minimal on nitrogen. Here we show that when the nitrate's charge is sufficiently dampened by resonating over a larger area, a Lewis acidic site emerges on nitrogen that can interact favourably with electron rich partners. Surveys of the Cambridge Structural Database and Protein Data Bank reveal geometric preferences of some oxygen and sulfur containing entities around a nitrate anion that are consistent with this `π-hole bonding' geometry. Computations reveal donor-acceptor orbital interactions that confirm the counterintuitive Lewis π-acidity of nitrate.

Effects of redox-active interlayer anions on the oxygen evolution reactivity of NiFe-layered double hydroxide nanosheets

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

Zhou, Daojin; Cai, Zhao; Bi, Yongmin

Nickel-iron layered double hydroxide (NiFe-LDH) nanosheets have shown optimal oxygen evolution reaction (OER) performance; however, the role of the intercalated ions in the OER activity remains unclear. In this work, we show that the activity of the NiFe-LDHs can be tailored by the intercalated anions with different redox potentials. The intercalation of anions with low redox potential (high reducing ability), such as hypophosphites, leads to NiFe-LDHs with low OER overpotential of 240 mV and a small Tafel slope of 36.9 mV/dec, whereas NiFe-LDHs intercalated with anions of high redox potential (low reducing ability), such as fluorion, show a high overpotentialmore » of 370 mV and a Tafel slope of 80.8 mV/dec. The OER activity shows a surprising linear correlation with the standard redox potential. Density functional theory calculations and X-ray photoelectron spectroscopy analysis indicate that the intercalated anions alter the electronic structure of metal atoms which exposed at the surface. Anions with low standard redox potential and strong reducing ability transfer more electrons to the hydroxide layers. Finally, this increases the electron density of the surface metal sites and stabilizes their high-valence states, whose formation is known as the critical step prior to the OER process.« less

Site-Specific Description of the Enhanced Recognition Between Electrogenerated Nitrobenzene Anions and Dihomooxacalix[4]arene Bidentate Ureas.

PubMed

Martínez-González, Eduardo; Armendáriz-Vidales, Georgina; Ascenso, José R; Marcos, Paula M; Frontana, Carlos

2015-05-01

Electron transfer controlled hydrogen bonding was studied for a series of nitrobenzene derivative radical anions, working as large guest anions, and substituted ureas, including dihomooxacalix[4]arene bidentate urea derivatives, in order to estimate binding constants (Kb) for the hydrogen-bonding process. Results showed enhanced Kb values for the interaction with phenyl-substituted bidentate urea, which is significantly larger than for the remaining compounds, e.g., in the case of 4-methoxynitrobenzene a 28-fold larger Kb value was obtained for the urea bearing a phenyl (Kb ∼ 6888) vs tert-butyl (Kb ∼ 247) moieties. The respective nucleophilic and electrophilic characters of the participant anion radical and urea hosts were parametrized with global and local electrodonating (ω(-)) and electroaccepting (ω(+)) powers, derived from DFT calculations. ω(-) data were useful for describing trends in structure–activity relationships when comparing nitrobenzene radical anions. However, ω(+) for the host urea structures lead to unreliable explanations of the experimental data. For the latter case, local descriptors ωk(+)(r) were estimated for the atoms within the urea region in the hosts [∑kωk(+)(r)]. By compiling all the theoretical and experimental data, a Kb-predictive contour plot was built considering ω(-) for the studied anion radicals and ∑kωk(+)(r) which affords good estimations.

Effects of redox-active interlayer anions on the oxygen evolution reactivity of NiFe-layered double hydroxide nanosheets

DOE PAGES

Zhou, Daojin; Cai, Zhao; Bi, Yongmin; ...

2018-02-02

Nickel-iron layered double hydroxide (NiFe-LDH) nanosheets have shown optimal oxygen evolution reaction (OER) performance; however, the role of the intercalated ions in the OER activity remains unclear. In this work, we show that the activity of the NiFe-LDHs can be tailored by the intercalated anions with different redox potentials. The intercalation of anions with low redox potential (high reducing ability), such as hypophosphites, leads to NiFe-LDHs with low OER overpotential of 240 mV and a small Tafel slope of 36.9 mV/dec, whereas NiFe-LDHs intercalated with anions of high redox potential (low reducing ability), such as fluorion, show a high overpotentialmore » of 370 mV and a Tafel slope of 80.8 mV/dec. The OER activity shows a surprising linear correlation with the standard redox potential. Density functional theory calculations and X-ray photoelectron spectroscopy analysis indicate that the intercalated anions alter the electronic structure of metal atoms which exposed at the surface. Anions with low standard redox potential and strong reducing ability transfer more electrons to the hydroxide layers. Finally, this increases the electron density of the surface metal sites and stabilizes their high-valence states, whose formation is known as the critical step prior to the OER process.« less

A strategy for acquisition and analysis of complex natural abundance (33)S solid-state NMR spectra of a disordered tetrathio transition-metal anion.

PubMed

Jakobsen, Hans J; Bildsøe, Henrik; Skibsted, Jørgen; Brorson, Michael; Gor'kov, Peter; Gan, Zhehong

2010-02-01

A strategy, involving (i) sensitivity enhancement for the central transition (CT) by population transfer (PT) employing WURST inversion pulses to the satellite transitions (STs) in natural abundance (33)S MAS NMR for two different MAS frequencies (nu(r)=5.0 and 10.0kHz) at 14.1T and (ii) a (33)S static QCPMG experiment at 19.6T, has allowed acquisition and analysis of very complex solid-state (33)S CT NMR spectra for the disordered tetrathioperrhenate anion ReS(4)(-) in [(C(2)H(5))(4)N][ReS(4)]. This strategy of different NMR experiments combined with spectral analysis/simulations has allowed determination of precise values for two sets of quadrupole coupling parameters (C(Q) and eta(Q)) assigned to the two different S sites for the four sulfur atoms in the ReS(4)(-) anion in the ratio S1:S2=1:3. These sets of C(Q), eta(Q) values for the S1 and S2 site are quite similar and the magnitudes of the quadrupole coupling constants (C(Q)=2.2-2.5MHz) are a factor of about three larger than observed for other tetrathiometalates A(2)MS(4) (A=NH(4), Cs, Rb and M=W, Mo). In addition, the spectral analysis also leads to a determination of the chemical shift anisotropy (CSA) parameters (delta(sigma) and eta(sigma)) for the S1 and S2 site, however, with much lower precisions (about 20% error margins) compared to those for C(Q), eta(Q), because the magnitudes of the two CSAs (i.e., delta(sigma)=60-90ppm) are about a factor of six smaller than observed for the other tetrathiometalates mentioned above. This large difference in the magnitudes of the anisotropic parameters C(Q) and delta(sigma) for the ReS(4)(-) anion, compared to those for the WS(4)(2-) and MoS(4)(2-) anions determined previously under identical experimental conditions, accounts for the increased complexity of the PT-enhanced (33)S MAS spectra observed for the ReS(4)(-) anion in this study. This difference in C(Q) also contributes significantly to the intensity distortions observed in the outer wings of the CTs when employing PT from the STs under conditions of slow-speed MAS. Copyright 2009 Elsevier Inc. All rights reserved.

Water oxidation by Ruthenium complexes incorporating multifunctional biipyridyl diphosphonate ligands

DOE PAGES

Xie, Yan; Shaffer, David W.; Lewandowska-Andralojc, Anna; ...

2016-05-11

Here, we describe herein the synthesis and characterization of ruthenium complexes with multifunctional bipyridyl diphosphonate ligands as well as initial water oxidation studies. In these complexes, the phosphonate groups provide redox-potential leveling through charge compensation and σ donation to allow facile access to high oxidation states. These complexes display unique pH-dependent electrochemistry associated with deprotonation of the phosphonic acid groups. The position of these groups allows them to shuttle protons in and out of the catalytic site and reduce activation barriers. A mechanism for water oxidation by these catalysts is proposed on the basis of experimental results and DFT calculations.more » The unprecedented attack of water at a neutral six-coordinate [Ru IV] center to yield an anionic seven-coordinate [Ru IV–OH] – intermediate is one of the key steps of a single-site mechanism in which all species are anionic or neutral. These complexes are among the fastest single-site catalysts reported to date.« less

K(3)TaF(8) from laboratory X-ray powder data.

PubMed

Smrcok, Lubomír; Cerný, Radovan; Boca, Miroslav; Macková, Iveta; Kubíková, Blanka

2010-02-01

The crystal structure of tripotassium octafluoridotantalate, K(3)TaF(8), determined from laboratory powder diffraction data by the simulated annealing method and refined by total energy minimization in the solid state, is built from discrete potassium cations, fluoride anions and monocapped trigonal-prismatic [TaF(7)](2-) ions. All six atoms in the asymmetric unit are in special positions of the P6(3)mc space group: the Ta and one F atom in the 2b (3m) sites, the K and two F atoms in the 6c (m) sites, and one F atom in the 2a (3m) site. The structure consists of face-sharing K(6) octahedra with a fluoride anion at the center of each octahedron, forming chains of composition [FK(3)](2+) running along [001] with isolated [TaF(7)](2-) trigonal prisms in between. The structure of the title compound is different from the reported structure of Na(3)TaF(8) and represents a new structure type.

Robust, sensitive and facile method for detection of F-, CN- and Ac- anions

NASA Astrophysics Data System (ADS)

Madhusudhana Reddy, P.; Hsieh, Shih-Rong; Chen, Jem-Kun; Chang, Chi-Jung; Kang, Jing-Yuan; Chen, Chih-Hsien

2017-11-01

Sensing of F-, CN- and Ac- is important from the viewpoint of both medically and environmentally. Particularly, sensing of the anions in 100% water by a colorimetric chemical sensor is a highly difficult task as water molecules interfere the sensing mechanism. In this regard, sensor R1, having azo and nitrophenyl groups as signaling units and thiourea as a binding site was prepared. This sensor exclusively detected CN- ion over other testing anions in 30% aq. DMSO solution by exhibiting distinct spectral and visual color changes. However, in 15% aq. DMSO solution, R1 exhibited obvious spectral and color changes in response to F-, CN- and Ac-. On the other hand, we have also designed sensor, R2, having same signaling units of R1, but a different binding site of urea group. Surprisingly, in contrast to R1, R2 exhibited obvious spectral and color changes in 5% aq. DMSO solution only. Further, economically viable ;test stripes; were prepared in a facile mode to detect the CN- in 100% aqueous solution. Such stripes can serve as a practical colorimetric probe for ;in the field; detection of the ions and thus avoid additional expensive equipment.

PASBio: predicate-argument structures for event extraction in molecular biology

PubMed Central

Wattarujeekrit, Tuangthong; Shah, Parantu K; Collier, Nigel

2004-01-01

Background The exploitation of information extraction (IE), a technology aiming to provide instances of structured representations from free-form text, has been rapidly growing within the molecular biology (MB) research community to keep track of the latest results reported in literature. IE systems have traditionally used shallow syntactic patterns for matching facts in sentences but such approaches appear inadequate to achieve high accuracy in MB event extraction due to complex sentence structure. A consensus in the IE community is emerging on the necessity for exploiting deeper knowledge structures such as through the relations between a verb and its arguments shown by predicate-argument structure (PAS). PAS is of interest as structures typically correspond to events of interest and their participating entities. For this to be realized within IE a key knowledge component is the definition of PAS frames. PAS frames for non-technical domains such as newswire are already being constructed in several projects such as PropBank, VerbNet, and FrameNet. Knowledge from PAS should enable more accurate applications in several areas where sentence understanding is required like machine translation and text summarization. In this article, we explore the need to adapt PAS for the MB domain and specify PAS frames to support IE, as well as outlining the major issues that require consideration in their construction. Results We introduce PASBio by extending a model based on PropBank to the MB domain. The hypothesis we explore is that PAS holds the key for understanding relationships describing the roles of genes and gene products in mediating their biological functions. We chose predicates describing gene expression, molecular interactions and signal transduction events with the aim of covering a number of research areas in MB. Analysis was performed on sentences containing a set of verbal predicates from MEDLINE and full text journals. Results confirm the necessity to analyze PAS specifically for MB domain. Conclusions At present PASBio contains the analyzed PAS of over 30 verbs, publicly available on the Internet for use in advanced applications. In the future we aim to expand the knowledge base to cover more verbs and the nominal form of each predicate. PMID:15494078

Pyrrolizidine alkaloids in food: a spectrum of potential health consequences.

PubMed

Edgar, J A; Colegate, S M; Boppré, M; Molyneux, R J

2011-03-01

Contamination of grain with 1,2-dehydropyrrolizidine ester alkaloids (dehydroPAs) and their N-oxides is responsible for large incidents of acute and subacute food poisoning, with high morbidity and mortality, in Africa and in central and south Asia. Herbal medicines and teas containing dehydroPAs have also caused fatalities in both developed and developing countries. There is now increasing recognition that some staple and widely consumed foods are sometimes contaminated by dehydroPAs and their N-oxides at levels that, while insufficient to cause acute poisoning, greatly exceed maximum tolerable daily intakes and/or maximum levels determined by a number of independent risk assessment authorities. This suggests that there may have been cases of disease in the past not recognised as resulting from dietary exposure to dehydroPAs. A review of the literature shows that there are a number of reports of liver disease where either exposure to dehydroPAs was suspected but no source was identified or a dehydroPA-aetiology was not considered but the symptoms and pathology suggests their involvement. DehydroPAs also cause progressive, chronic diseases such as cancer and pulmonary arterial hypertension but proof of their involvement in human cases of these chronic diseases, including sources of exposure to dehydroPAs, has generally been lacking. Growing recognition of hazardous levels of dehydroPAs in a range of common foods suggests that physicians and clinicians need to be alert to the possibility that these contaminants may, in some cases, be a possible cause of chronic diseases such as cirrhosis, pulmonary hypertension and cancer in humans.

Chemical Affinity between Tannin Size and Salivary Protein Binding Abilities: Implications for Wine Astringency

PubMed Central

Ma, Wen; Waffo-Teguo, Pierre; Jourdes, Michael; Li, Hua

2016-01-01

Astringency perception, as an essential parameter for high-quality red wine, is principally elicited by condensed tannins in diversified chemical structures. Condensed tannins, which are also known as proanthocyanidins (PAs), belong to the flavonoid class of polyphenols and are incorporated by multiple flavan-3-ols units according to their degree of polymerization (DP). However, the influence of DP size of PAs on astringency perception remains unclear for decades. This controversy was mainly attributed to the lack of efficient strategies to isolate the PAs in non-galloylated forms and with individual degree size from grape/wine. In the present study, the astringency intensity of purified and identified grape oligomeric tannins (DP ranged from 1 to 5) was firstly explored. A novel non-solid phase strategy was used to rapidly exclude the galloylated PAs from the non-galloylated PAs and fractionate the latter according to their DP size. Then, a series of PAs with individual DP size and galloylation were purified by an approach of preparative hydrophilic interaction chromatography. Furthermore, purified compounds were identified by both normal phase HPLC-FLD and reverse phase UHPLC-ESI-Q-TOF. Finally, the contribution of the astringency perception of the individual purified tannins was examined with a salivary protein binding ability test. The results were observed by HPLC-FLD and quantified by changes in PA concentration remaining in the filtrate. In summary, a new approach without a solid stationary phase was developed to isolate PAs according to their DP size. And a positive relationship between the DP of PAs and salivary protein affinity was revealed. PMID:27518822

The ecological context of pyrrolizidine alkaloids in food, feed and forage: an overview.

PubMed

Boppré, Michael

2011-03-01

Plant-produced 1,2-dehydropyrrolizidine ester alkaloids and their N-oxides (PAs) not only cause acute poisoning of humans and livestock, but also the likely harmful cryptic effects of chronic exposure pose particular food safety risks that need to be addressed for consumer protection. In natural contexts, however, PAs cause few or no problems. Rather, these plant secondary metabolites are important elements of ecosystems and plant-animal relationships; the existence and persistence of many PA-adapted organisms, in various ways, depends on the presence of PA-containing plants or even on PAs as such. PA plants are widely distributed among unrelated families of the plant kingdom; there is great structural diversity of PAs, and the amounts of PAs produced are subject to great variation due to multiple causes. These realities, coupled with many deficiencies in our scientific understanding, make the presence and roles of PAs in nature a subject with limited potential for valid generalisations and predictions, and complex and difficult to summarise. PAs, their producer plants and their users are integral parts of ecosystems worldwide, and we have to learn to live with these allelochemicals by accepting the presence of some harmful natural chemicals in the environment and by taking regulatory action to reduce health risks to humans. Regulations for consumer protection are long overdue. However, any such measures must be flexible enough to accommodate the findings of future research. Transdisciplinary efforts are required to fill gaps in the knowledge and to come up with additional means to monitor the presence of PAs in food and feed.

Chemical Affinity between Tannin Size and Salivary Protein Binding Abilities: Implications for Wine Astringency.

PubMed

Ma, Wen; Waffo-Teguo, Pierre; Jourdes, Michael; Li, Hua; Teissedre, Pierre-Louis

2016-01-01

Astringency perception, as an essential parameter for high-quality red wine, is principally elicited by condensed tannins in diversified chemical structures. Condensed tannins, which are also known as proanthocyanidins (PAs), belong to the flavonoid class of polyphenols and are incorporated by multiple flavan-3-ols units according to their degree of polymerization (DP). However, the influence of DP size of PAs on astringency perception remains unclear for decades. This controversy was mainly attributed to the lack of efficient strategies to isolate the PAs in non-galloylated forms and with individual degree size from grape/wine. In the present study, the astringency intensity of purified and identified grape oligomeric tannins (DP ranged from 1 to 5) was firstly explored. A novel non-solid phase strategy was used to rapidly exclude the galloylated PAs from the non-galloylated PAs and fractionate the latter according to their DP size. Then, a series of PAs with individual DP size and galloylation were purified by an approach of preparative hydrophilic interaction chromatography. Furthermore, purified compounds were identified by both normal phase HPLC-FLD and reverse phase UHPLC-ESI-Q-TOF. Finally, the contribution of the astringency perception of the individual purified tannins was examined with a salivary protein binding ability test. The results were observed by HPLC-FLD and quantified by changes in PA concentration remaining in the filtrate. In summary, a new approach without a solid stationary phase was developed to isolate PAs according to their DP size. And a positive relationship between the DP of PAs and salivary protein affinity was revealed.

Anxiety in early Parkinson's disease: Validation of the Italian observer-rated version of the Parkinson Anxiety Scale (OR-PAS).

PubMed

Santangelo, Gabriella; Falco, Fabrizia; D'Iorio, Alfonsina; Cuoco, Sofia; Raimo, Simona; Amboni, Marianna; Pellecchia, Maria Teresa; Longo, Katia; Vitale, Carmine; Barone, Paolo

2016-08-15

Anxiety disorders are common in Parkinson's Disease (PD) and their identification is relevant even at early stages. The Parkinson Anxiety Scale (PAS) evaluates anxiety in PD; it was used only in the original validation study in PD patients mainly at 2-3 stages of Hoehn & Yahr system (H&Y). The study aimed to investigate psychometric properties of observer-rated version of the PAS (OR-PAS), prevalence rate of anxiety and its features, compared with diagnostic criteria in early PD patients. A sample of 101 PD patients with H&Y:1-2 underwent the OR-PAS. To assess convergent and divergent validity, PD patients underwent Beck Anxiety Inventory, and scales assessing depression, apathy, anhedonia and cognition. To diagnose anxiety disorders, Mini International Neuropsychiatric Inventory was used as gold standard. A "receiver operating characteristics" curve was obtained; positive and negative predictive values were calculated for different cut-off points of the OR-PAS and its subscales. There was no missing data, no floor and ceiling effects; mean score was 12.2±10.1; Cronbach's alpha was 0.899. The OR-PAS showed good convergent and divergent validity. Maximum discrimination was obtained with a cut-off score of 8.5. The anxiety occurred in 59 patients (58.4%). The OR-PAS is a reliable and valid screening instrument for assessing anxiety in patients at early PD. Anxiety was found in 58.4% of PD patients, demonstrating that anxiety occurs even at early stages. Copyright © 2016 Elsevier B.V. All rights reserved.

How Does Legalization of Physician-Assisted Suicide Affect Rates of Suicide?

PubMed

Jones, David Albert; Paton, David

2015-10-01

Several US states have legalized or decriminalized physician-assisted suicide (PAS) while others are considering permitting PAS. Although it has been suggested that legalization could lead to a reduction in total suicides and to a delay in those suicides that do occur, to date no research has tested whether these effects can be identified in practice. The aim of this study was to fill this gap by examining the association between the legalization of PAS and state-level suicide rates in the United States between 1990 and 2013. We used regression analysis to test the change in rates of nonassisted suicides and total suicides (including assisted suicides) before and after the legalization of PAS. Controlling for various socioeconomic factors, unobservable state and year effects, and state-specific linear trends, we found that legalizing PAS was associated with a 6.3% (95% confidence interval 2.70%-9.9%) increase in total suicides (including assisted suicides). This effect was larger in the individuals older than 65 years (14.5%, CI 6.4%-22.7%). Introduction of PAS was neither associated with a reduction in nonassisted suicide rates nor with an increase in the mean age of nonassisted suicide. Legalizing PAS has been associated with an increased rate of total suicides relative to other states and no decrease in nonassisted suicides. This suggests either that PAS does not inhibit (nor acts as an alternative to) nonassisted suicide, or that it acts in this way in some individuals but is associated with an increased inclination to suicide in other individuals.

[Euthanasia and physician-assisted suicide : Attitudes of physicians and nurses].

PubMed

Zenz, J; Tryba, M; Zenz, M

2015-04-01

The current debate about end-of-life decisions in Germany focuses on physician-assisted suicide (PAS). However, there is only limited information available on physicians' attitudes towards euthanasia or PAS, and no data on nurses' attitudes. The aim is to explore attitudes of physicians and nurses with a special interest in palliative care and pain medicine using a case-related questionnaire. An anonymous questionnaire, consisting of eight questions, was distributed to all participants of a palliative care congress and a pain symposium. The questions focused on two scenarios: (1) a patient with an incurable fatal illness, (2) a patient with an incurable but nonfatal illness. The question was: Should euthanasia or physician-assisted suicide (PAS) be allowed. In addition, the participants were asked what they wanted for themselves if they were the patient concerned. A total of 317 questionnaires were analyzed; the return rate was 70 %. The general support for euthanasia and PAS was high: 40.5 % supported euthanasia in case of a fatal illness ("definitely…", "probably should be allowed"), 53.5 % supported PAS. The support decreased in case of a nonfatal illness; however, it increased when the participants were asked about their attitudes if they were the patient concerned. Nurses were more open towards euthanasia and PAS. In physicians the rejection of PAS was directly related to a higher level of qualification in the field of palliative care. The fact that nurses had a more positive attitude towards euthanasia and PAS and that all respondents accepted life-ending acts for themselves more than for their patients hints to still existing severe deficits in Germany.

A global assessment of the social and conservation outcomes of protected areas.

PubMed

Oldekop, J A; Holmes, G; Harris, W E; Evans, K L

2016-02-01

Protected areas (PAs) are a key strategy for protecting biological resources, but they vary considerably in their effectiveness and are frequently reported as having negative impacts on local people. This has contributed to a divisive and unresolved debate concerning the compatibility of environmental and socioeconomic development goals. Elucidating the relationship between positive and negative social impacts and conservation outcomes of PAs is key for the development of more effective and socially just conservation. We conducted a global meta-analysis on 165 PAs using data from 171 published studies. We assessed how PAs affect the well-being of local people, the factors associated with these impacts, and crucially the relationship between PAs' conservation and socioeconomic outcomes. Protected areas associated with positive socioeconomic outcomes were more likely to report positive conservation outcomes. Positive conservation and socioeconomic outcomes were more likely to occur when PAs adopted comanagement regimes, empowered local people, reduced economic inequalities, and maintained cultural and livelihood benefits. Whereas the strictest regimes of PA management attempted to exclude anthropogenic influences to achieve biological conservation objectives, PAs that explicitly integrated local people as stakeholders tended to be more effective at achieving joint biological conservation and socioeconomic development outcomes. Strict protection may be needed in some circumstances, yet our results demonstrate that conservation and development objectives can be synergistic and highlight management strategies that increase the probability of maximizing both conservation performance and development outcomes of PAs. © 2015 The Authors. Conservation Biology published by Wiley Periodicals, Inc. on behalf of Society for Conservation Biology.

How do protected landscapes associated with high biodiversity and population levels change?

PubMed Central

Echeverria, Cristian

2017-01-01

Most protected areas (PA) try to limit logging of forests by means of restrictions on access and use, especially in areas where local communities coexist with the forests and depend on resources derived from PAs. In such contexts, achieving full or effective protection of the forests is almost impossible. This fact has led to researching beyond PAs boundaries in order to examine large surrounding landscapes with multiple forms of properties and restriction on forests use. The present study assessed the change in forest cover and fragmentation between 1990 and 2014, in addition to the drivers that explain such changes in a landscape with the presence of PAs and high-density population belonging to the Chocó-Darien biodiversity hotspot. Results indicated differences in the extent and spatial patterns of change in forest cover of PAs and their surrounding landscapes. Two PAs exhibited a tendency to increase fragmentation and lose their forests in comparison with the stable protection of the forests in other PAs during this period. However, the greatest change in forest cover and fragmentation was observed in the surrounding landscapes, where the best connection to markets and transport networks were the dominating deforestation drivers. Our findings corroborated that the PAs were a shield against the deforestation of the tropical Andean forest, especially in landscapes with high-density population. However, the fragmentation of the forest cannot be avoided around the PAs limits. It is expected that, if this tendency continues in the future, the biodiversity in the Chocó-Darien hotspot will be seriously affected. PMID:28672002

Surgical and clinical aspects of cerebellar pilomyxoid-spectrum astrocytomas in children.

PubMed

El Beltagy, Mohamed A; Atteya, Mostafa M E; El-Haddad, Alaa; Awad, Madiha; Taha, Hala; Kamal, Mohamed; El Naga, Sherif Abou

2014-06-01

Cerebellar pilomyxoid astrocytomas (PMAs) and intermediate pilomyxoid astrocytomas (IPAs) are collectively called "pilomyxoid-spectrum astrocytomas (PMSAs)." Cerebellar PMSAs are thought to behave more aggressively than pilocytic astrocytomas (PAs). Our objective is to compare PMSAs to PAs in terms of surgical and clinical profiles. This retrospective study included 66 cases (35 males and 31 females) with cerebellar astrocytomas treated between July 2007 and December 2012 at Children's Cancer Hospital Egypt (CCHE 57357) with a mean age of 7 (±1.5) years. Cases were divided into three subgroups as follows: 44 PAs, 10 IPAs, and 12 PMAs. Comparison between all groups was focusing on brain stem invasion, intrinsic necrotic cavitation, extent of resection, recurrence, leptomeningeal dissemination (LD), metastases, need for CSF diversion, and cerebellar mutism (CM). Cerebellar PMAs and IPAs separately and collectively had higher incidence of brain stem invasion, intrinsic necrotic cavitation, tumor recurrence, and LD when compared to PAs (P < 0.001). Gross total resection was 13.6 % in PMSAs versus 90.9 % in PAs (P < 0.001). PMAs had a higher incidence of tumor recurrence than IPAs (66.7 versus 20 %, P < 0.001). Incidence of recurrence in PAs was 9.1 % in partially resected cases. Mean interval to recurrence was 9 (±1.5) months in PMSAs and 42 (±2) months in PAs. Cerebellar PMSAs express an aggressive clinical behavior and impose more operative challenges than PAs. These tumors may represent a clinical spectrum-at its benign end lies PA, while PMA lies at the aggressive end, with IPA lying just behind. Such concepts could be used to guide management in the future.

Coiled-coil coactivators play a structural role mediating interactions in hypoxia-inducible factor heterodimerization

DOE PAGES

Guo, Yirui; Scheuermann, Thomas H.; Partch, Carrie L.; ...

2015-01-27

The hypoxia-inducible factor complex (HIF-α·aryl hydrocarbon receptor nuclear translocator (ARNT)) requires association with several transcription coactivators for a successful cellular response to hypoxic stress. In addition to the conventional global transcription coactivator CREB-binding protein/p300 (CBP/p300) that binds to the HIF-α transactivation domain, a new group of transcription coactivators called the coiled-coil coactivators (CCCs) interact directly with the second PER-ARNT-SIM (PAS) domain of ARNT (ARNT PAS-B). These less studied transcription coactivators play essential roles in the HIF-dependent hypoxia response, and CCC misregulation is associated with several forms of cancer. To better understand CCC protein recruitment by the heterodimeric HIF transcription factor,more » we used x-ray crystallography, NMR spectroscopy, and biochemical methods to investigate the structure of the ARNT PAS-B domain in complex with the C-terminal fragment of a coiled-coil coactivator protein, transforming acidic coiled-coil coactivator 3 (TACC3). We found that the HIF-2α PAS-B domain also directly interacts with TACC3, motivating an NMR data-derived model suggesting a means by which TACC3 could form a ternary complex with HIF-2α PAS-B and ARNT PAS-B via β-sheet/coiled-coil interactions. Furthermore, these findings suggest that TACC3 could be recruited as a bridge to cooperatively mediate between the HIF-2α PAS-B·ARNT PAS-B complex, thereby participating more directly in HIF-dependent gene transcription than previously anticipated.« less

A comprehensive protein-protein interactome for yeast PAS kinase 1 reveals direct inhibition of respiration through the phosphorylation of Cbf1.

PubMed

DeMille, Desiree; Bikman, Benjamin T; Mathis, Andrew D; Prince, John T; Mackay, Jordan T; Sowa, Steven W; Hall, Tacie D; Grose, Julianne H

2014-07-15

Per-Arnt-Sim (PAS) kinase is a sensory protein kinase required for glucose homeostasis in yeast, mice, and humans, yet little is known about the molecular mechanisms of its function. Using both yeast two-hybrid and copurification approaches, we identified the protein-protein interactome for yeast PAS kinase 1 (Psk1), revealing 93 novel putative protein binding partners. Several of the Psk1 binding partners expand the role of PAS kinase in glucose homeostasis, including new pathways involved in mitochondrial metabolism. In addition, the interactome suggests novel roles for PAS kinase in cell growth (gene/protein expression, replication/cell division, and protein modification and degradation), vacuole function, and stress tolerance. In vitro kinase studies using a subset of 25 of these binding partners identified Mot3, Zds1, Utr1, and Cbf1 as substrates. Further evidence is provided for the in vivo phosphorylation of Cbf1 at T211/T212 and for the subsequent inhibition of respiration. This respiratory role of PAS kinase is consistent with the reported hypermetabolism of PAS kinase-deficient mice, identifying a possible molecular mechanism and solidifying the evolutionary importance of PAS kinase in the regulation of glucose homeostasis. © 2014 DeMille et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

SOURCE APPORTIONMENT OF PM2.5 IN SEATTLE, WA URBAN IMPROVE SITE: COMPARISON OF THREE RECEPTOR MODELS AND SOURCE PROFILES

EPA Science Inventory

IMPROVE protocol data were collected at the urban Beacon Hill monitoring site in Seattle, WA from 1996-99. The 289 sets of PM2.5 filters were analyzed for: metals using PIXIE and XRF, anions using ion chromatography, elemental hydrogen (H) by proton scattering, and elemental an...

A recombinant fusion protein and DNA vaccines against foot-and-mouth disease virus type Asia 1 infection in guinea pigs.

PubMed

Zhang, Q; Zhu, M W; Yang, Y Q; Shao, M; Zhang, Z Y; Lan, H Y; Yan, W Y; Wu, J J; Zheng, Z X

2003-01-01

On the basis of amino acid (aa) sequence of the tandem repeat 133-158-20-34-133-158 which consisted of aa 133-158 of VP1 and aa 20-34 of VP4 of Foot-and-mouth disease virus (FMDV) type Asia 1 a recombinant prokaryotic expression vector pAS1-P encoding a fusion protein and eukaryotic expression vectors pAS1-E and pAS1-EdeltaCpG-ODN representing DNA vaccines were constructed. Guinea pigs immunized with these vaccines showed both neutralizing antibody and T cell proliferation responses. FMDV challenge tests for the first time showed that the recombinant fusion protein and pAS1-E and pAS1-EdeltaCpG-ODN vaccines protected 86%, 60% and 43% of guinea pigs from FMDV type Asia1 challenge, respectively. The results also indicated that the immune response of animals treated with the vector pAS1-E containing an oligodeoxynucleotide (ODN), which consisted of immunostimulatory cytosine-phosphate-guanosine (CpG) motifs, was augmented by CpG ODN.

Experimental study on spatio-temporal behavior of a single particle forming a particle accumulation structure (PAS) in half-zone liquid bridge

NASA Astrophysics Data System (ADS)

Oba, Takeru; Ueno, Ichiro; Kaneko, Toshihiro

2017-11-01

We focus on particle behavior due to thermocapillary-driven convection in a half-zone liquid bridge of high-Prandtl number fluid. It has been known that the suspended particles exhibit a unique solid-like structure known as 'particle accumulation structure (PAS)' in a rotating frame of reference with traveling-type hydrothermal wave. It is said that PAS is caused by interaction between particles and the free surface of a half-zone liquid bridge. Such structures arise even under small Stokes number conditions. When observing PAS two-dimensionally, it looks like a closed single string, but the actual movement of particles is different. Therefore we employ three-dimensional particle tracking velocimetry to the half-zone liquid bridge of 2.5 mm in radius and 1.7 mm in height, and detect the particle behaviors close to the free surface. We explain the spatio-temporal correlation between the solid-like global structure of PAS and the local particle motions, and make comparisons with proposed physical models of PAS formation.

Toxicity of plant extracts containing pyrrolizidine alkaloids using alternative invertebrate models.

PubMed

Seremet, Oana Cristina; Olaru, Octavian Tudorel; Gutu, Claudia Maria; Nitulescu, George Mihai; Ilie, Mihaela; Negres, Simona; Zbarcea, Cristina Elena; Purdel, Carmen Nicoleta; Spandidos, Demetrios A; Tsatsakis, Aristides M; Coleman, Michael D; Margina, Denisa Marilena

2018-06-01

Pyrrolizidine alkaloids (PAs) are a widespread class of hepatotoxic heterocyclic organic compounds found in approximately 3% of world flora. Some PAs have been shown to have genotoxic and carcinogenic effects. The present study focuses on the toxicity effects of four dry extracts obtained from medicinal plants (Senecio vernalis, Symphytum officinale, Petasites hybridus and Tussilago farfara), on two aquatic organisms, Artemia salina and Daphnia magna, and the correlation with their PAs content. A new GC‑MS method, using a retention time (TR)‑5MS type capillary column was developed. PAs Kovats retention indices, for this type of column were computed for the first time. The lethal dose 50% (LC50) values for the two invertebrate models were correlated (Pearson 's coefficient, >0.9) and the toxicity was PA concentration-dependent, for three of the four extracts. All tested extracts were found to be toxic in both aquatic organism models. The results can be used to develop a GC‑MS validated method for the assay of PAs in medicinal plants with a further potential application in the risk assessment study of PAs toxicity in humans.

Toxicity of plant extracts containing pyrrolizidine alkaloids using alternative invertebrate models

PubMed Central

Seremet, Oana Cristina; Olaru, Octavian Tudorel; Gutu, Claudia Maria; Nitulescu, George Mihai; Ilie, Mihaela; Negres, Simona; Zbarcea, Cristina Elena; Purdel, Carmen Nicoleta; Spandidos, Demetrios A.; Tsatsakis, Aristides M.; Coleman, Michael D.; Margina, Denisa Marilena

2018-01-01

Pyrrolizidine alkaloids (PAs) are a widespread class of hepatotoxic heterocyclic organic compounds found in approximately 3% of world flora. Some PAs have been shown to have genotoxic and carcinogenic effects. The present study focuses on the toxicity effects of four dry extracts obtained from medicinal plants (Senecio vernalis, Symphytum officinale, Petasites hybridus and Tussilago farfara), on two aquatic organisms, Artemia salina and Daphnia magna, and the correlation with their PAs content. A new GC-MS method, using a retention time (TR)-5MS type capillary column was developed. PAs Kovats retention indices, for this type of column were computed for the first time. The lethal dose 50% (LC50) values for the two invertebrate models were correlated (Pearson's coefficient, >0.9) and the toxicity was PA concentration-dependent, for three of the four extracts. All tested extracts were found to be toxic in both aquatic organism models. The results can be used to develop a GC-MS validated method for the assay of PAs in medicinal plants with a further potential application in the risk assessment study of PAs toxicity in humans. PMID:29620235

Walk on the wild side: estimating the global magnitude of visits to protected areas.

PubMed

Balmford, Andrew; Green, Jonathan M H; Anderson, Michael; Beresford, James; Huang, Charles; Naidoo, Robin; Walpole, Matt; Manica, Andrea

2015-02-01

How often do people visit the world's protected areas (PAs)? Despite PAs covering one-eighth of the land and being a major focus of nature-based recreation and tourism, we don't know. To address this, we compiled a globally-representative database of visits to PAs and built region-specific models predicting visit rates from PA size, local population size, remoteness, natural attractiveness, and national income. Applying these models to all but the very smallest of the world's terrestrial PAs suggests that together they receive roughly 8 billion (8 x 109) visits/y-of which more than 80% are in Europe and North America. Linking our region-specific visit estimates to valuation studies indicates that these visits generate approximately US $600 billion/y in direct in-country expenditure and US $250 billion/y in consumer surplus. These figures dwarf current, typically inadequate spending on conserving PAs. Thus, even without considering the many other ecosystem services that PAs provide to people, our findings underscore calls for greatly increased investment in their conservation.

Walk on the Wild Side: Estimating the Global Magnitude of Visits to Protected Areas

PubMed Central

Balmford, Andrew; Green, Jonathan M. H.; Anderson, Michael; Beresford, James; Huang, Charles; Naidoo, Robin; Walpole, Matt; Manica, Andrea

2015-01-01

How often do people visit the world’s protected areas (PAs)? Despite PAs covering one-eighth of the land and being a major focus of nature-based recreation and tourism, we don’t know. To address this, we compiled a globally-representative database of visits to PAs and built region-specific models predicting visit rates from PA size, local population size, remoteness, natural attractiveness, and national income. Applying these models to all but the very smallest of the world’s terrestrial PAs suggests that together they receive roughly 8 billion (8 x 109) visits/y—of which more than 80% are in Europe and North America. Linking our region-specific visit estimates to valuation studies indicates that these visits generate approximately US $600 billion/y in direct in-country expenditure and US $250 billion/y in consumer surplus. These figures dwarf current, typically inadequate spending on conserving PAs. Thus, even without considering the many other ecosystem services that PAs provide to people, our findings underscore calls for greatly increased investment in their conservation. PMID:25710450

Structural study of surfactant-dependent interaction with protein

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

Mehan, Sumit; Aswal, Vinod K., E-mail: vkaswal@barc.gov.in; Kohlbrecher, Joachim

2015-06-24

Small-angle neutron scattering (SANS) has been used to study the complex structure of anionic BSA protein with three different (cationic DTAB, anionic SDS and non-ionic C12E10) surfactants. These systems form very different surfactant-dependent complexes. We show that the structure of protein-surfactant complex is initiated by the site-specific electrostatic interaction between the components, followed by the hydrophobic interaction at high surfactant concentrations. It is also found that hydrophobic interaction is preferred over the electrostatic interaction in deciding the resultant structure of protein-surfactant complexes.

Structural study of surfactant-dependent interaction with protein

NASA Astrophysics Data System (ADS)

Mehan, Sumit; Aswal, Vinod K.; Kohlbrecher, Joachim

2015-06-01

Small-angle neutron scattering (SANS) has been used to study the complex structure of anionic BSA protein with three different (cationic DTAB, anionic SDS and non-ionic C12E10) surfactants. These systems form very different surfactant-dependent complexes. We show that the structure of protein-surfactant complex is initiated by the site-specific electrostatic interaction between the components, followed by the hydrophobic interaction at high surfactant concentrations. It is also found that hydrophobic interaction is preferred over the electrostatic interaction in deciding the resultant structure of protein-surfactant complexes.

An anionic rhodium eta4-quinonoid complex as a multifunctional catalyst for the arylation of aldehydes with arylboronic acids.

PubMed

Son, Seung Uk; Kim, Sang Bok; Reingold, Jeffrey A; Carpenter, Gene B; Sweigart, Dwight A

2005-09-07

The pi-bonded rhodium quinonoid complex, K+[(1,4-benzoquinone)Rh(COD)]-, functions as a good catalyst for the coupling of arylboronic acid and aldehydes to afford diaryl alcohols. The catalysis is heterobimetallic in that both the transition metal and concomitant alkali metal counterion play an integral part in the reaction. In addition, the anionic quinonoid catalyst itself plays a bifunctional role by acting as a ligand to the boronic acid and as a Lewis acid receptor site for the transferring aryl group.

Chemical fingerprinting identifies Echium vulgare, Eupatorium cannabinum and Senecio spp. as plant species mainly responsible for pyrrolizidine alkaloids in bee-collected pollen.

PubMed

Kast, Christina; Kilchenmann, Verena; Reinhard, Hans; Droz, Benoit; Lucchetti, Matteo Angelo; Dübecke, Arne; Beckh, Gudrun; Zoller, Otmar

2018-02-01

Various studies have shown that bee-collected pollen sold as nutritional supplements may contain toxic pyrrolizidine alkaloids (PAs) and, thus, pose a potential health risk for consumers. The level of contamination may vary according to its geographical and botanical origin. Here, the PA content of pollen produced in Switzerland was studied and 32 commercially available bee-collected pollen supplements produced between 2010 and 2014 were analysed. In addition, at what time period bees collect PA-containing pollen was investigated. Hence, this study looked into the occurrence of PAs in pollen samples collected daily during two-to-three consecutive seasons. Furthermore, the PA spectrum in pollen was compared to the spectrum found in flower heads of PA-plants to unambiguously identify plants responsible for PA contamination of pollen. The PA concentration of commercial and daily collected pollen was determined by target analysis using an HPLC-MS/MS system, allowing the detection of 18 different PAs and PA N-oxides found in the genera Echium, Eupatorium and Senecio, while the comparison of the PA spectrum in pollen and flower heads was performed by LC-HR-MS, allowing the detection of all PA types in a sample, including saturated, non-carcinogenic PAs. Of the commercially available pollen, 31% contained PAs with a mean concentration of 319 ng/g, mainly Echium- and Eupatorium-type PAs, while the PA concentrations were below the limit of quantitation (LOQ) in 69% of the pollen samples. Bees collected pollen containing Echium-type PAs mainly in June and July, while they gathered pollen containing Eupatorium-type PAs from mid-July to August. Senecio-type PAs appeared from June to September. Comparison of the PA array in pollen and plants identified E. vulgare and E. cannabinum as the main plants responsible for PA contamination of Swiss bee-collected pollen, and to a lesser extent also identified plants belonging to the genus Senecio.

Effects of high latitude protected areas on bird communities under rapid climate change.

PubMed

Santangeli, Andrea; Rajasärkkä, Ari; Lehikoinen, Aleksi

2017-06-01

Anthropogenic climate change is rapidly becoming one of the main threats to biodiversity, along with other threats triggered by human-driven land-use change. Species are already responding to climate change by shifting their distributions polewards. This shift may create a spatial mismatch between dynamic species distributions and static protected areas (PAs). As protected areas represent one of the main pillars for preserving biodiversity today and in the future, it is important to assess their contribution in sheltering the biodiversity communities, they were designated to protect. A recent development to investigate climate-driven impacts on biological communities is represented by the community temperature index (CTI). CTI provides a measure of the relative temperature average of a community in a specific assemblage. CTI value will be higher for assemblages dominated by warm species compared with those dominated by cold-dwelling species. We here model changes in the CTI of Finnish bird assemblages, as well as changes in species densities, within and outside of PAs during the past four decades in a large boreal landscape under rapid change. We show that CTI has markedly increased over time across Finland, with this change being similar within and outside PAs and five to seven times slower than the temperature increase. Moreover, CTI has been constantly lower within than outside of PAs, and PAs still support communities, which show colder thermal index than those outside of PAs in the 1970s and 1980s. This result can be explained by the higher relative density of northern species within PAs than outside. Overall, our results provide some, albeit inconclusive, evidence that PAs may play a role in supporting the community of northern species. Results also suggest that communities are, however, shifting rapidly, both inside and outside of PAs, highlighting the need for adjusting conservation measures before it is too late. © 2016 John Wiley & Sons Ltd.

Families as catalysts for peer adherence support in enhancing hope for people living with HIV/AIDS in South Africa

PubMed Central

Masquillier, Caroline; Wouters, Edwin; Mortelmans, Dimitri; Booysen, Frederik le Roux

2014-01-01

Introduction Hope is an essential dimension of successful coping in the context of illnesses such as HIV/AIDS, because positive expectations for the future alleviate emotional distress, enhance quality of life and have been linked to the capacity for behavioural change. The social environment (e.g. family, peers) is a regulator of hope for people living with HIV/AIDS (PLWHA). In this regard, the dual aim of this article is (1) to analyze the influence of a peer adherence support (PAS) intervention and the family environment on the state of hope in PLWHA and (2) to investigate the interrelationship between the two determinants. Methods The Effective AIDS Treatment and Support in the Free State study is a prospective randomized controlled trial. Participants were recruited from 12 public antiretroviral treatment (ART) clinics across five districts in the Free State Province of South Africa. Each of these patients was assigned to one of the following groups: a control group receiving standard care, a group receiving additional biweekly PAS or a group receiving PAS and nutritional support. Latent cross-lagged modelling (Mplus) was used to analyse the impact of PAS and the family environment on the level of hope in PLWHA. Results The results of the study indicate that neither PAS nor the family environment has a direct effect on the level of hope in PLWHA. Subsequent analysis reveals a positive significant interaction between family functioning and PAS at the second follow-up, indicating that better family functioning increases the positive effect of PAS on the state of hope in PLWHA. Conclusions The interplay between well-functioning families and external PAS generates higher levels of hope, which is an essential dimension in the success of lifelong treatment. This study provides additional insight into the important role played by family dynamics in HIV/AIDS care, and it underscores the need for PAS interventions that are sensitive to the contexts in which they are implemented. PMID:24702797

Families as catalysts for peer adherence support in enhancing hope for people living with HIV/AIDS in South Africa.

PubMed

Masquillier, Caroline; Wouters, Edwin; Mortelmans, Dimitri; Booysen, Frederik le Roux

2014-01-01

Hope is an essential dimension of successful coping in the context of illnesses such as HIV/AIDS, because positive expectations for the future alleviate emotional distress, enhance quality of life and have been linked to the capacity for behavioural change. The social environment (e.g. family, peers) is a regulator of hope for people living with HIV/AIDS (PLWHA). In this regard, the dual aim of this article is (1) to analyze the influence of a peer adherence support (PAS) intervention and the family environment on the state of hope in PLWHA and (2) to investigate the interrelationship between the two determinants. The Effective AIDS Treatment and Support in the Free State study is a prospective randomized controlled trial. Participants were recruited from 12 public antiretroviral treatment (ART) clinics across five districts in the Free State Province of South Africa. Each of these patients was assigned to one of the following groups: a control group receiving standard care, a group receiving additional biweekly PAS or a group receiving PAS and nutritional support. Latent cross-lagged modelling (Mplus) was used to analyse the impact of PAS and the family environment on the level of hope in PLWHA. The results of the study indicate that neither PAS nor the family environment has a direct effect on the level of hope in PLWHA. Subsequent analysis reveals a positive significant interaction between family functioning and PAS at the second follow-up, indicating that better family functioning increases the positive effect of PAS on the state of hope in PLWHA. The interplay between well-functioning families and external PAS generates higher levels of hope, which is an essential dimension in the success of lifelong treatment. This study provides additional insight into the important role played by family dynamics in HIV/AIDS care, and it underscores the need for PAS interventions that are sensitive to the contexts in which they are implemented.

Cross-national Epidemiology of Panic Disorder and Panic Attacks in the World Mental Health Surveys

PubMed Central

de Jonge, Peter; Roest, Annelieke M.; Lim, Carmen C.W.; Florescu, Silvia E.; Bromet, Evelyn; Stein, Dan; Harris, Meredith; Nakov, Vladimir; Caldas-de-Almeida, Jose Miguel; Levinson, Daphna; Al-Hamzawi, Ali O.; Haro, Josep Maria; Viana, Maria Carmen; Borges, Gui; O’Neill, Siobhan; de Girolamo, Giovanni; Demyttenaere, Koen; Gureje, Oye; Iwata, Noboru; Lee, Sing; Hu, Chiyi; Karam, Aimee; Moskalewicz, Jacek; Kovess-Masfety, Viviane; Navarro-Mateu, Fernando; Browne, Mark Oakley; Piazza, Maria; Posada-Villa, José; Torres, Yolanda; ten Have, Margreet L.; Kessler, Ronald C.; Scott, Kate M.

2016-01-01

Context The scarcity of cross-national reports and the changes in DSM-5 regarding panic disorder (PD) and panic attacks (PAs) call for new epidemiological data on PD and PAs and its subtypes in the general population. Objective To present representative data about the cross-national epidemiology of PD and PAs in accordance with DSM-5 definitions. Design and Setting Nationally representative cross-sectional surveys using the World Health Organization Composite International Diagnostic Interview version 3.0. Participants Respondents (n=142,949) from 25 high, middle and lower-middle income countries across the world aged 18 years or older. Main Outcome Measures PD and presence of single and recurrent PAs. Results Lifetime prevalence of PAs was 13.2% (s.e. 0.1%). Among persons that ever had a PA, the majority had recurrent PAs (66.5%; s.e. 0.5%), while only 12.8% fulfilled DSM-5 criteria for PD. Recurrent PAs were associated with a subsequent onset of a variety of mental disorders (OR 2.0; 95% CI 1.8–2.2) and their course (OR 1.3; 95% CI 1.2–2.4) whereas single PAs were not (OR 1.1; 95% CI 0.9–1.3 and OR 0.7; 95% CI 0.6–0.8). Cross-national lifetime prevalence estimates were 1.7% (s.e. 0.0%) for PD with a median age of onset of 32 (IQR 20–47). Some 80.4% of persons with lifetime PD had a lifetime comorbid mental disorder. Conclusions We extended previous epidemiological data to a cross-national context. The presence of recurrent PAs in particular is associated with subsequent onset and course of mental disorders beyond agoraphobia and PD, and might serve as a generic risk marker for psychopathology. PMID:27775828

Mycobacterium tuberculosis Arylamine N-Acetyltransferase Acetylates and Thus Inactivates para-Aminosalicylic Acid.

PubMed

Wang, Xude; Yang, Shanshan; Gu, Jing; Deng, Jiaoyu

2016-12-01

Mycobacterium tuberculosis arylamine N-acetyltransferase (TBNAT) is able to acetylate para-aminosalicylic acid (PAS) both in vitro and in vivo as determined by high-performance liquid chromatography (HPLC) and electrospray ionization-mass spectrometry (ESI-MS) techniques. The antituberculosis activity of the acetylated PAS is significantly reduced. As a result, overexpression of TBNAT in M. tuberculosis results in PAS resistance, as determined by MIC tests and drug exposure experiments. Taken together, our results suggest that TBNAT from M. tuberculosis is able to inactivate PAS by acetylating the compound. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

The current state of personal assistance services: implications for policy and future research.

PubMed

Hagglund, Kristofer J; Clark, Mary J; Mokelke, Emily K; Stout, Brian J

2004-01-01

Personal assistant services (PAS) are designed to support persons with disabilities in their routine performance of activities of daily living (ADLs) and to provide individuals with disability the opportunity to go to school, volunteer, obtain active employment, and participate in social and recreational activities. PAS are primary and essential to the realization of societal inclusion and personal freedom among persons with severe, disabling conditions. This paper reviews the personal assistance literature for persons with spinal cord injury and other disabilities. Evidence-based recommendations are made for PAS policy initiatives and future directions in PAS research.

Mental health and other clinical correlates of euthanasia attitudes in an Australian outpatient cancer population.

PubMed

Carter, G L; Clover, K A; Parkinson, L; Rainbird, K; Kerridge, I; Ravenscroft, P; Cavenagh, J; McPhee, J

2007-04-01

A majority of patients with cancer have been reported to endorse euthanasia and physician assisted suicide (PAS) in general and a substantial proportion endorse these for themselves. However, the potential influence of mental health and other clinical variables on these decisions is not well understood. This study of 228 outpatients attending an oncology clinic in Newcastle, Australia used a cross-sectional design and logistic regression modelling to examine the relationship of demographic, disease status, mental health and quality of life variables to attitudes toward euthanasia and PAS. The majority reported support for euthanasia (79%, n=179), for PAS (69%, n=158) and personal support for euthanasia/PAS (68%, n=156). However, few reported having asked their doctor for euthanasia (2%, n=5) or PAS (2%, n=5). Three outcomes were modelled: support for euthanasia was associated with active religious belief (adjusted odds ratio (AOR) 0.21, 95% CI: 0.10-0.46); support for PAS was associated with active religious belief (AOR 0.35, 95% CI: 18-0.70) and recent pain (AOR 0.87, 95% CI: 0.0.76-0.99); and personal support for euthanasia/PAS was associated with active religious belief (AOR 0.26, 95% CI: 0.14-0.48). Depression, anxiety, recent suicidal ideation, and lifetime suicide attempt were not independently associated with any of the three outcomes modelled. Copyright (c) 2007 John Wiley & Sons, Ltd.

Glucose-independent segmental phase angles from multi-frequency bioimpedance analysis to discriminate diabetes mellitus.

PubMed

Jun, Min-Ho; Kim, Soochan; Ku, Boncho; Cho, JungHee; Kim, Kahye; Yoo, Ho-Ryong; Kim, Jaeuk U

2018-01-12

We investigated segmental phase angles (PAs) in the four limbs using a multi-frequency bioimpedance analysis (MF-BIA) technique for noninvasively diagnosing diabetes mellitus. We conducted a meal tolerance test (MTT) for 45 diabetic and 45 control subjects stratified by age, sex and body mass index (BMI). HbA1c and the waist-to-hip-circumference ratio (WHR) were measured before meal intake, and we measured the glucose levels and MF-BIA PAs 5 times for 2 hours after meal intake. We employed a t-test to examine the statistical significance and the area under the curve (AUC) of the receiver operating characteristics (ROC) to test the classification accuracy using segmental PAs at 5, 50, and 250 kHz. Segmental PAs were independent of the HbA1c or glucose levels, or their changes caused by the MTT. However, the segmental PAs were good indicators for noninvasively screening diabetes In particular, leg PAs in females and arm PAs in males showed best classification accuracy (AUC = 0.827 for males, AUC = 0.845 for females). Lastly, we introduced the PA at maximum reactance (PAmax), which is independent of measurement frequencies and can be obtained from any MF-BIA device using a Cole-Cole model, thus showing potential as a useful biomarker for diabetes.

Characterization of an apically derived epithelial membrane glycoprotein from bovine milk, which is expressed in capillary endothelia in diverse tissues.

PubMed

Greenwalt, D E; Mather, I H

1985-02-01

A glycoprotein (PAS IV) of apparent Mr 76,000 was purified from bovine milk-fat-globule membrane and partially characterized. PAS IV contained mannose, galactose, and sialic acid as principal sugars (approximately 5.3% total carbohydrate [wt/wt]) and existed in milk in at least four isoelectric variants. The glycoprotein appeared to be an integral membrane protein by several criteria. PAS IV was recovered in the detergent phase of Triton X-114 extracts of milk-fat-globule membrane at room temperature. When bound to membrane, PAS IV was resistant to digestion by a number of proteinases, although after solubilization with non-ionic detergents, the protein was readily degraded. Amino acid analysis of the purified protein revealed a high percentage of amino acids with nonpolar residues. The location of PAS IV was determined in bovine tissues by using immunofluorescence techniques. In mammary tissue, PAS IV was located on both the apical surfaces of secretory epithelial cells and endothelial cells of capillaries. This glycoprotein was also detected in endothelial cells of heart, liver, spleen, pancreas, salivary gland, and small intestine. In addition to mammary epithelial cells, PAS IV was also located in certain other epithelial cells, most notably the bronchiolar epithelial cells of lung. The potential usefulness of this protein as a specific marker of capillary endothelial cells in certain tissues is discussed.

Surgical physician assistants help solve contemporary problems.

PubMed

Blumm, Robert M; Condit, Doug

2003-06-01

Recent surveys performed by the AAPA estimate that in 2002 approximately 183 million visits were made to PAs and 223 million medications were prescribed or recommended by PAs. The AAPA estimates that just more than 46,000 PAs currently are in clinical practice, with New York and California having the largest numbers of practicing PAs. Helen Keller said, "The most pathetic person in the world is the person who has sight but no vision." Most individuals accept life and its shortcomings, but visionaries are different. They see not only that which is evident, but also that which exists in imagination. Visionary physicians and surgeons who aided in the creation of the physician assistant and use of PAs in surgery include: Eugene Stead, MD; John Kirklin, MD, FACS; E. Harvey Estes, Jr., MD; Richard Smith, MD, FACS; and Marvin Giledman, MD. They believed that well-educated nonphysicians could work alongside physicians as a team and, thus, expand the delivery of health care in America. PAs have crossed into the new millennium with new challenges. Together, as a team with supervising surgeons, PAs can meet the challenges and establish new alliances that will alleviate today's constraints. As Rear Adm. Kenneth P. Moritsugu, MD, MPH, Deputy Surgeon General, said, "Physician assistants are ideal partners and professionals in the nation's health system. They are colleagues with physicians to assure improved access to quality health care in a cost-effective manner.

Does DSM-IV Have Equivalents for the Parental Alienation Syndrome (PAS) Diagnosis?

ERIC Educational Resources Information Center

Gardner, Richard A.

2003-01-01

Child custody evaluators commonly find themselves confronted with resistance when they attempt to use the term parental alienation syndrome (PAS) in courts of law. The purpose of this article is to elucidate the reasons for the reluctance to use the PAS diagnosis and the applicability of parental alienation, as well as current DSM-IV substitute…

Perceptions of physician assistants regarding direct-to-consumer advertising.

PubMed

Anzalone, Justin; Mathews, Asha; Suprenant, Michael; Herman, Lawrence

2012-02-01

Of 1,254 practicing physician assistants (PAs) who completed a survey, 91% were familiar with direct-to-consumer advertising (DTCA). When asked about their general perception, 96% of PAs were neutral or unfavorable towards DTCA. PAs felt that DTCA encouraged patients to make atypical medication requests, overlook the PA's medical opinion, and seek other health care providers.

A chromatographic estimate of the degree of heterogeneity of RPLC packing materials. 1. Non-endcapped polymeric C30-bonded stationary phase

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

Gritti, Fabrice; Guiochon, Georges A

2006-01-01

A new chromatographic method estimating the degree of heterogeneity of RPLC packing materials is based on the results of systematic measurements of the adsorption data in a wide concentration range for selected probe compounds. These data are acquired by frontal analysis (FA), modeled, and used for the calculation of the adsorption energy distribution (AED). Four compounds were used, two neutral compounds of different molecular sizes (caffeine and phenol) and two ionizable compounds of opposite charges, 2-naphthalene sulfonate, an anion, and propranololium, a cation. This work was done on a C{sub 30}-bonded silica stationary phase (Prontosil-C{sub 30}), using the same aqueousmore » mobile phase (30% methanol, v/v) for all compounds, except that sodium chloride (25 mM) was added to elute the ionizable compounds. All four adsorption isotherms have Langmuirian behavior. The AEDs are tri-modal for phenol, quadri-modal for caffeine. The total saturation capacity of the stationary phase is four-fold lower for caffeine than for phenol, due in part to its larger molecular size. The equilibrium constants on the low-energy sites of types 1 and 2 are eight-fold larger. These two types of sites characterize the heterogeneity of the bonded layer itself. The density of the high-energy sites of types 3 and 4 is higher for caffeine, suggesting that caffeine molecules can be accommodated in some hydrophobic cages into which smaller molecules like phenol cannot. These high-energy types of sites characterize the heterogeneity of the whole stationary phase (silica support included). The ionizable compounds have larger molecules than the neutral ones and, accordingly, a lower relative density of sites of type 2 to sites of type 1. A tri-modal and a quadri-modal energy distributions were observed for the 2-naphthalene sulfonate anion and the propranololium cation, respectively. The fourth types of sites measured and its unusually high equilibrium constant are most probably due to ion-exchange interactions between the non-endcapped ionized silanols and the propranololium ion. No such strong interactions are observed with the anionic compound.« less

Stable Nighttime Light Decreased in Protected Area of California: Findings from DMSP-OLS Observations and the Importance for Protected Area Policy Making

NASA Astrophysics Data System (ADS)

Jia, S.; Gillespie, T. W.

2016-12-01

Stable nighttime light, an indicator of persisting human activity and light pollution is a well-recognized disturbance to the wilderness of protected areas (PAs). Mostly supported by in situ observations, very limited studies of light pollution for PAs focused at a regional level and on a continuous time span to support policy making effectively. DMSP-OLS stable nighttime series provide continuous observation of nightlight and have been widely applied in studies focusing on human activities. In this study, we employed inter-calibrated DMSP-OLS nightlight series from 1992 to 2012 to evaluate the change of intensity and extension of stable nighttime light inside California PAs. We observed a decrease of stable nighttime light and a shrinkage in spatial extent in PAs located in all ecoregions from 1992 to 2012, especially before 2004. Such decrease and shrinkage occurred mostly in southern California and the Bay Area where mega metropolitan clusters locate. The successful application of protecting strategies in PAs and the improved technologies of lighting may contribute to the relieving of light pollution in PAs. However, the stable nighttime light slightly increased since 2004, when there was limited room for stricter protective regulations and the pressure from population growth persisted. Population density explained most spatial distribution of nightlight in years with census tract level demographic data available, except PAs with the highest wilderness such as Sierra Nevada Mts. We anticipate to improve the models with the newest remote sensing nighttime product from NASA Suomi-NPP and annually updated demographic data from American Community Survey at census tract level in the future to provide a cost-effective evaluation on protecting strategies. Such evaluation will support land managers of PAs and local policy-makers for modification and proposal of policies.

Polyamines in chemiosmosis in vivo: A cunning mechanism for the regulation of ATP synthesis during growth and stress

PubMed Central

Ioannidis, Nikolaos E.; Kotzabasis, Kiriakos

2014-01-01

Polyamines (PAs) are low molecular weight amines that occur in every living organism. The three main PAs (putrescine, spermidine, and spermine) are involved in several important biochemical processes covered in recent reviews. As rule of thumb, increase of the cellular titer of PAs in plants is related to cell growth and cell tolerance to abiotic and biotic stress. In the present contribution, we describe recent findings from plant bioenergetics that bring to light a previously unrecognized dynamic behavior of the PA pool. Traditionally, PAs are described by many authors as organic polycations, when in fact they are bases that can be found in a charged or uncharged form. Although uncharged forms represent less than 0.1% of the total pool, we propose that their physiological role could be crucial in chemiosmosis. This process describes the formation of a PA gradient across membranes within seconds and is difficult to be tested in vivo in plants due to the relatively small molecular weight of PAs and the speed of the process. We tested the hypothesis that PAs act as permeable buffers in intact leaves by using recent advances in vivo probing. We found that an increase of PAs increases the electric component (Δψ) and decreases the ΔpH component of the proton motive force. These findings reveal an important modulation of the energy production process and photoprotection of the chloroplast by PAs. We explain in detail the theory behind PA pumping and ion trapping in acidic compartments (such as the lumen in chloroplasts) and how this regulatory process could improve either the photochemical efficiency of the photosynthetic apparatus and increase the synthesis of ATP or fine tune antenna regulation and make the plant more tolerant to stress. PMID:24592272

First evidence of pyrrolizidine alkaloid N-oxide-induced hepatic sinusoidal obstruction syndrome in humans.

PubMed

Yang, Mengbi; Ruan, Jianqing; Gao, Hong; Li, Na; Ma, Jiang; Xue, Junyi; Ye, Yang; Fu, Peter Pi-Cheng; Wang, Jiyao; Lin, Ge

2017-12-01

Pyrrolizidine alkaloids (PAs) are among the most potent phytotoxins widely distributed in plant species around the world. PA is one of the major causes responsible for the development of hepatic sinusoidal obstruction syndrome (HSOS) and exerts hepatotoxicity via metabolic activation to form the reactive metabolites, which bind with cellular proteins to generate pyrrole-protein adducts, leading to hepatotoxicity. PA N-oxides coexist with their corresponding PAs in plants with varied quantities, sometimes even higher than that of PAs, but the toxicity of PA N-oxides remains unclear. The current study unequivocally identified PA N-oxides as the sole or predominant form of PAs in 18 Gynura segetum herbal samples ingested by patients with liver damage. For the first time, PA N-oxides were recorded to induce HSOS in human. PA N-oxide-induced hepatotoxicity was further confirmed on mice orally dosed of herbal extract containing 170 μmol PA N-oxides/kg/day, with its hepatotoxicity similar to but potency much lower than the corresponding PAs. Furthermore, toxicokinetic study after a single oral dose of senecionine N-oxide (55 μmol/kg) on rats revealed the toxic mechanism that PA N-oxides induced hepatotoxicity via their biotransformation to the corresponding PAs followed by the metabolic activation to form pyrrole-protein adducts. The remarkable differences in toxicokinetic profiles of PAs and PA N-oxides were found and attributed to their significantly different hepatotoxic potency. The findings of PA N-oxide-induced hepatotoxicity in humans and rodents suggested that the contents of both PAs and PA N-oxides present in herbs and foods should be regulated and controlled in use.

Sodium p-Aminosalicylic Acid Reverses Sub-Chronic Manganese-Induced Impairments of Spatial Learning and Memory Abilities in Rats, but Fails to Restore γ-Aminobutyric Acid Levels.

PubMed

Li, Shao-Jun; Ou, Chao-Yan; He, Sheng-Nan; Huang, Xiao-Wei; Luo, Hai-Lan; Meng, Hao-Yang; Lu, Guo-Dong; Jiang, Yue-Ming; Vieira Peres, Tanara; Luo, Yi-Ni; Deng, Xiang-Fa

2017-04-10

Excessive manganese (Mn) exposure is not only a health risk for occupational workers, but also for the general population. Sodium para-aminosalicylic acid (PAS-Na) has been successfully used in the treatment of manganism, but the involved molecular mechanisms have yet to be determined. The present study aimed to investigate the effects of PAS-Na on sub-chronic Mn exposure-induced impairments of spatial learning and memory, and determine the possible involvements of γ-aminobutyric acid (GABA) metabolism in vivo. Sprague-Dawley male rats received daily intraperitoneal injections MnCl₂ (as 6.55 mg/kg Mn body weight, five days per week for 12 weeks), followed by daily subcutaneous injections of 100, 200, or 300 mg/kg PAS-Na for an additional six weeks. Mn exposure significantly impaired spatial learning and memory ability, as noted in the Morris water maze test, and the following PAS-Na treatment successfully restored these adverse effects to levels indistinguishable from controls. Unexpectedly, PAS-Na failed to recover the Mn-induced decrease in the overall GABA levels, although PAS-Na treatment reversed Mn-induced alterations in the enzyme activities directly responsible for the synthesis and degradation of GABA (glutamate decarboxylase and GABA-transaminase, respectively). Moreover, Mn exposure caused an increase of GABA transporter 1 (GAT-1) and decrease of GABA A receptor (GABA A ) in transcriptional levels, which could be reverted by the highest dose of 300 mg/kg PAS-Na treatment. In conclusion, the GABA metabolism was interrupted by sub-chronic Mn exposure. However, the PAS-Na treatment mediated protection from sub-chronic Mn exposure-induced neurotoxicity, which may not be dependent on the GABA metabolism.

Investigation of targeted pyrrolizidine alkaloids in traditional Chinese medicines and selected herbal teas sourced in Ireland using LC-ESI-MS/MS.

PubMed

Griffin, Caroline T; Gosetto, Francesca; Danaher, Martin; Sabatini, Stefano; Furey, Ambrose

2014-01-01

Publications linking hepatotoxicity to the use of herbal preparations are escalating. Herbal teas, traditional Chinese medicines (TCMs) and dietary supplements have been shown to contain pyrrolizidine alkaloids (PAs). Acute PA toxicosis of the liver can result in sinusoidal-obstruction syndrome, also known as veno-occlusive disease (VOD). This paper describes a sensitive and robust method for the detection of targeted PAs and their N-oxides (PANOs) in herbal products (selected herbal teas and TCMs) sourced within Ireland. The sample preparation includes a simple acidic extraction with clean-up via solid-phase extraction (SPE). Sample extracts were accurately analysed by using LC-ESI-MS/MS applying for the first time a pentafluorophenyl (PFP) core-shell column to the chromatographic separation of PAs and PANOs. The method was validated for selectivity, taking into consideration matrix effects, specificity, linearity, precision and trueness. Limits of detection (LOD) and limits of quantitation (LOQ) were quantified for all PAs and PANOs ranging from 0.4 to 1.9 µg kg⁻¹ and from 1.3 to 6.3 µg kg⁻¹, respectively. In this study 10 PAs and four PANOs were targeted because they are commercially available as reference standards. Therefore, this study can only report the levels of these PAs and PANOs analysed in the herbal teas and TCMs. The results reported represent the minimum levels of PAs and PANOs present in the samples analysed; commercially available herbal teas (n = 18) and TCMs (n = 54). A total of 50% herbal teas and 78% Chinese medicines tested positive for one or more PAs and/or PANOs included within this study, ranging from 10 to 1733 and from 13 to 3668 µg kg⁻¹, respectively.

Experience with physician assistants in a Canadian arthroplasty program.

PubMed

Bohm, Eric R; Dunbar, Michael; Pitman, David; Rhule, Chris; Araneta, Jose

2010-04-01

Recent increases in orthopedic surgical services in Canada have added further demand to an already stretched orthopedic workforce. Various initiatives have been undertaken across Canada to meet this demand. One successful model has been the use of physician assistants (PAs) within the Winnipeg Regional Health Authority (WRHA). This study documents the effect of PAs working in an arthroplasty practice from the perspective of patients and health care providers. We also describe the costs, time savings for surgeons and the effects on surgical throughput and waiting times. We calculated time savings by the use of a daily diary kept by the PAs. Surgeons', residents', nurses' and patients' opinions about PAs were recorded by use of a self administered questionnaire. We calculated costs using forgone general practitioner (GP) surgical assist fees and salary costs for PAs. We obtained information about surgical throughput and wait times from the WRHA waitlist database. In this study, PAs "saved" their supervising physician about 204 hours per year; this time can be used for other clinical, administrative or research duties. Physician assistants are regarded as important members of the health care team by surgeons, nurses, orthopedic residents and patients. When we compared the billing costs with those that would have been generated by the use of GP surgical assists, PAs were essentially cost neutral. Furthermore, they potentially freed GPs from the operating room to spend more time delivering primary care. We found that use of the double operating room model facilitated by PAs increased the surgical throughput of primary hip and knee replacements by 42%, and median wait times decreased from 44 weeks to 30 weeks compared with the preceding year. Physician assistants integrate well into the care team and can increase surgical volumes to reduce wait times in a cost-effective manner.

Sodium p-Aminosalicylic Acid Reverses Sub-Chronic Manganese-Induced Impairments of Spatial Learning and Memory Abilities in Rats, but Fails to Restore γ-Aminobutyric Acid Levels

PubMed Central

Li, Shao-Jun; Ou, Chao-Yan; He, Sheng-Nan; Huang, Xiao-Wei; Luo, Hai-Lan; Meng, Hao-Yang; Lu, Guo-Dong; Jiang, Yue-Ming; Vieira Peres, Tanara; Luo, Yi-Ni; Deng, Xiang-Fa

2017-01-01

Excessive manganese (Mn) exposure is not only a health risk for occupational workers, but also for the general population. Sodium para-aminosalicylic acid (PAS-Na) has been successfully used in the treatment of manganism, but the involved molecular mechanisms have yet to be determined. The present study aimed to investigate the effects of PAS-Na on sub-chronic Mn exposure-induced impairments of spatial learning and memory, and determine the possible involvements of γ-aminobutyric acid (GABA) metabolism in vivo. Sprague-Dawley male rats received daily intraperitoneal injections MnCl2 (as 6.55 mg/kg Mn body weight, five days per week for 12 weeks), followed by daily subcutaneous injections of 100, 200, or 300 mg/kg PAS-Na for an additional six weeks. Mn exposure significantly impaired spatial learning and memory ability, as noted in the Morris water maze test, and the following PAS-Na treatment successfully restored these adverse effects to levels indistinguishable from controls. Unexpectedly, PAS-Na failed to recover the Mn-induced decrease in the overall GABA levels, although PAS-Na treatment reversed Mn-induced alterations in the enzyme activities directly responsible for the synthesis and degradation of GABA (glutamate decarboxylase and GABA-transaminase, respectively). Moreover, Mn exposure caused an increase of GABA transporter 1 (GAT-1) and decrease of GABA A receptor (GABAA) in transcriptional levels, which could be reverted by the highest dose of 300 mg/kg PAS-Na treatment. In conclusion, the GABA metabolism was interrupted by sub-chronic Mn exposure. However, the PAS-Na treatment mediated protection from sub-chronic Mn exposure-induced neurotoxicity, which may not be dependent on the GABA metabolism. PMID:28394286

Evaluation results for the positive deep-UV resist AZ DX 46

NASA Astrophysics Data System (ADS)

Spiess, Walter; Lynch, Thomas J.; Le Cornec, Charles; Escher, Gary C.; Kinoshita, Yoshiaki; Kochan, John; Kudo, Takanori; Masuda, Seiya; Mourier, Thierry; Nozaki, Yuko; Olson, Setha G.; Okazaki, Hiroshi; Padmanaban, Munirathna; Pawlowski, Georg; Przybilla, Klaus J.; Roeschert, Horst; Suehiro, Natusmi; Vinet, Francoise; Wengenroth, Horst

1994-05-01

This contribution emphasizes resist application site by communicating lithographic results for AZ DX 46, obtained using the GCA XLS 7800/31 stepper, NA equals 0.53, equipped with krypton fluoride excimer laser ((lambda) equals 248 nm), model 4500 D, as exposure source, delivered by Cymer Laser Technologies. As far as delay time experiments are concerned ASM-L PAS 5500/70 stepper, NA equals 0.42, was used in combination with Lambda Physik excimer laser, model 248 L.

Predicate Argument Structure Frames for Modeling Information in Operative Notes

PubMed Central

Wang, Yan; Pakhomov, Serguei; Melton, Genevieve B.

2015-01-01

The rich information about surgical procedures contained in operative notes is a valuable data source for improving the clinical evidence base and clinical research. In this study, we propose a set of Predicate Argument Structure (PAS) frames for surgical action verbs to assist in the creation of an information extraction (IE) system to automatically extract details about the techniques, equipment, and operative steps from operative notes. We created PropBank style PAS frames for the 30 top surgical action verbs based on examination of randomly selected sample sentences from 3,000 Laparoscopic Cholecystectomy notes. To assess completeness of the PAS frames to represent usage of same action verbs, we evaluated the PAS frames created on sample sentences from operative notes of 6 other gastrointestinal surgical procedures. Our results showed that the PAS frames created with one type of surgery can successfully denote the usage of the same verbs in operative notes of broader surgical categories. PMID:23920664

Antimycobacterial, antimicrobial, and biocompatibility properties of para-aminosalicylic acid with zinc layered hydroxide and Zn/Al layered double hydroxide nanocomposites

PubMed Central

Saifullah, Bullo; El Zowalaty, Mohamed E; Arulselvan, Palanisamy; Fakurazi, Sharida; Webster, Thomas J; Geilich, Benjamin M; Hussein, Mohd Zobir

2014-01-01

The treatment of tuberculosis by chemotherapy is complicated due to multiple drug prescriptions, long treatment duration, and adverse side effects. We report here for the first time an in vitro therapeutic effect of nanocomposites based on para-aminosalicylic acid with zinc layered hydroxide (PAS-ZLH) and zinc-aluminum layered double hydroxides (PAS-Zn/Al LDH), against mycobacteria, Gram-positive bacteria, and Gram-negative bacteria. The nanocomposites demonstrated good antimycobacterial activity and were found to be effective in killing Gram-positive and Gram-negative bacteria. A biocompatibility study revealed good biocompatibility of the PAS-ZLH nanocomposites against normal human MRC-5 lung cells. The para-aminosalicylic acid loading was quantified with high-performance liquid chromatography analysis. In summary, the present preliminary in vitro studies are highly encouraging for further in vivo studies of PAS-ZLH and PAS-Zn/Al LDH nanocomposites to treat tuberculosis. PMID:25114509

The spread of 'Post Abortion Syndrome' as social diagnosis.

PubMed

Kelly, Kimberly

2014-02-01

This paper examines the content of Post Abortion Syndrome (PAS) claims, the social actors involved and how this social diagnosis bypassed professional dissent and diffused into public policy in the United States. Previous works on the spread of PAS focus on almost exclusively on anti-abortion think tanks and policymakers. Missing from these analyses, however, is an emphasis on the grassroots-level actions undertaken by evangelical crisis pregnancy center (CPC) activists in introducing and circulating PAS claims. The CPC movement introduced PAS claims and provided the fodder for anti-abortion think tanks to construct evidence of pro-life claims. Despite dissent from health professionals and academic researchers, CPC PAS claims successfully diffused into federal and state abortion policy. I draw upon Brown et al.'s social diagnosis framework and Armstrong's five-stage model of diagnosis development to frame this account. Copyright © 2013. Published by Elsevier Ltd.

Changes of free, soluble conjugated and bound polyamine titers of jojoba explants under sodium chloride salinity in vitro.

PubMed

Roussos, Peter A; Pontikis, Constantine A

2007-07-01

Jojoba (Simmondsia chinensis L.) single node explants were cultured in a basal medium supplemented with 17.8 microM 6-benzyladenine and four levels of sodium chloride concentration (0, 56.41, 112.82 and 169.23 mM). The free, the soluble conjugated and the insoluble bound forms of polyamines (PAs) (putrescine (Put), spermidine (Spd) and spermine (Spm)) were determined monthly during a 3-month proliferation stage. Free Put and Spd were found in higher levels in the control treatment, while Spm content was higher in the salt treatments. All soluble conjugated PAs were found to be in lower concentrations in explants growing on medium supplemented with salt, while the opposite was true for the insoluble bound PAs. It appeared that certain PAs and PAs forms could play a significant role in the adaptation mechanism of jojoba under saline conditions.

Panic disorder: a review of DSM-IV panic disorder and proposals for DSM-V.

PubMed

Craske, Michelle G; Kircanski, Katharina; Epstein, Alyssa; Wittchen, Hans-Ulrich; Pine, Danny S; Lewis-Fernández, Roberto; Hinton, Devon

2010-02-01

This review covers the literature since the publication of DSM-IV on the diagnostic criteria for panic attacks (PAs) and panic disorder (PD). Specific recommendations are made based on the evidence available. In particular, slight changes are proposed for the wording of the diagnostic criteria for PAs to ease the differentiation between panic and surrounding anxiety; simplification and clarification of the operationalization of types of PAs (expected vs. unexpected) is proposed; and consideration is given to the value of PAs as a specifier for all DSM diagnoses and to the cultural validity of certain symptom profiles. In addition, slight changes are proposed for the wording of the diagnostic criteria to increase clarity and parsimony of the criteria. Finally, based on the available evidence, no changes are proposed with regard to the developmental expression of PAs or PD. This review presents a number of options and preliminary recommendations to be considered for DSM-V.

Activator anion binding site in pyridoxal phosphorylase b: the binding of phosphite, phosphate, and fluorophosphate in the crystal.

PubMed Central

Oikonomakos, N. G.; Zographos, S. E.; Tsitsanou, K. E.; Johnson, L. N.; Acharya, K. R.

1996-01-01

It has been established that phosphate analogues can activate glycogen phosphorylase reconstituted with pyridoxal in place of the natural cofactor pyridoxal 5'-phosphate (Change YC. McCalmont T, Graves DJ. 1983. Biochemistry 22:4987-4993). Pyridoxal phosphorylase b has been studied by kinetic, ultracentrifugation, and X-ray crystallographic experiments. In solution, the catalytically active species of pyridoxal phosphorylase b adopts a conformation that is more R-state-like than that of native phosphorylase b, but an inactive dimeric species of the enzyme can be stabilized by activator phosphite in combination with the T-state inhibitor glucose. Co-crystals of pyridoxal phosphorylase b complexed with either phosphite, phosphate, or fluorophosphate, the inhibitor glucose, and the weak activator IMP were grown in space group P4(3)2(1)2, with native-like unit cell dimensions, and the structures of the complexes have been refined to give crystallographic R factors of 18.5-19.2%, for data between 8 and 2.4 A resolution. The anions bind tightly at the catalytic site in a similar but not identical position to that occupied by the cofactor 5'-phosphate group in the native enzyme (phosphorus to phosphorus atoms distance = 1.2 A). The structural results show that the structures of the pyridoxal phosphorylase b-anion-glucose-IMP complexes are overall similar to the glucose complex of native T-state phosphorylase b. Structural comparisons suggest that the bound anions, in the position observed in the crystal, might have a structural role for effective catalysis. PMID:8976550

Tuning of protein-surfactant interaction to modify the resultant structure.

PubMed

Mehan, Sumit; Aswal, Vinod K; Kohlbrecher, Joachim

2015-09-01

Small-angle neutron scattering and dynamic light scattering studies have been carried out to examine the interaction of bovine serum albumin (BSA) protein with different surfactants under varying solution conditions. We show that the interaction of anionic BSA protein (pH7) with surfactant and the resultant structure are strongly modified by the charge head group of the surfactant, ionic strength of the solution, and mixed surfactants. The protein-surfactant interaction is maximum when two components are oppositely charged, followed by components being similarly charged through the site-specific binding, and no interaction in the case of a nonionic surfactant. This interaction of protein with ionic surfactants is characterized by the fractal structure representing a bead-necklace structure of micellelike clusters adsorbed along the unfolded protein chain. The interaction is enhanced with ionic strength only in the case of site-specific binding of an anionic surfactant with an anionic protein, whereas it is almost unchanged for other complexes of cationic and nonionic surfactants with anionic proteins. Interestingly, the interaction of BSA protein with ionic surfactants is significantly suppressed in the presence of nonionic surfactant. These results with mixed surfactants thus can be used to fold back the unfolded protein as well as to prevent surfactant-induced protein unfolding. For different solution conditions, the results are interpreted in terms of a change in fractal dimension, the overall size of the protein-surfactant complex, and the number of micelles attached to the protein. The interplay of electrostatic and hydrophobic interactions is found to govern the resultant structure of complexes.

Tuning of protein-surfactant interaction to modify the resultant structure

NASA Astrophysics Data System (ADS)

Mehan, Sumit; Aswal, Vinod K.; Kohlbrecher, Joachim

2015-09-01

Small-angle neutron scattering and dynamic light scattering studies have been carried out to examine the interaction of bovine serum albumin (BSA) protein with different surfactants under varying solution conditions. We show that the interaction of anionic BSA protein (p H 7 ) with surfactant and the resultant structure are strongly modified by the charge head group of the surfactant, ionic strength of the solution, and mixed surfactants. The protein-surfactant interaction is maximum when two components are oppositely charged, followed by components being similarly charged through the site-specific binding, and no interaction in the case of a nonionic surfactant. This interaction of protein with ionic surfactants is characterized by the fractal structure representing a bead-necklace structure of micellelike clusters adsorbed along the unfolded protein chain. The interaction is enhanced with ionic strength only in the case of site-specific binding of an anionic surfactant with an anionic protein, whereas it is almost unchanged for other complexes of cationic and nonionic surfactants with anionic proteins. Interestingly, the interaction of BSA protein with ionic surfactants is significantly suppressed in the presence of nonionic surfactant. These results with mixed surfactants thus can be used to fold back the unfolded protein as well as to prevent surfactant-induced protein unfolding. For different solution conditions, the results are interpreted in terms of a change in fractal dimension, the overall size of the protein-surfactant complex, and the number of micelles attached to the protein. The interplay of electrostatic and hydrophobic interactions is found to govern the resultant structure of complexes.

Increments to chiral recognition facilitating enantiomer separations of chiral acids, bases, and ampholytes using Cinchona-based zwitterion exchanger chiral stationary phases.

PubMed

Wernisch, Stefanie; Pell, Reinhard; Lindner, Wolfgang

2012-07-01

The intramolecular distances of anion and cation exchanger sites of zwitterionic chiral stationary phases represent potential tuning sites for enantiomer selectivity. In this contribution, we investigate the influence of alkanesulfonic acid chain length and flexibility on enantiomer separations of chiral acids, bases, and amphoteric molecules for six Cinchona alkaloid-based chiral stationary phases in comparison with structurally related anion and cation exchangers. Employing polar-organic elution conditions, we observed an intramolecular counterion effect for acidic analytes which led to reduced retention times but did not impair enantiomer selectivities. Retention of amphoteric analytes is based on simultaneous double ion pairing of their charged functional groups with the acidic and basic sites of the zwitterionic selectors. A chiral center in the vicinity of the strong cation exchanger site is vital for chiral separations of bases. Sterically demanding side chains are beneficial for separations of free amino acids. Enantioseparations of free (un-derivatized) peptides were particularly successful in stationary phases with straight-chain alkanesulfonic acid sites, pointing to a beneficial influence of more flexible moieties. In addition, we observed pseudo-enantiomeric behavior of quinine and quinidine-derived chiral stationary phases facilitating reversal of elution orders for all analytes. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Controlled Neutralization of Anions in Cryogenic Matrices by Near-Threshold Photodetachment

NASA Astrophysics Data System (ADS)

Ludwig, Ryan M.; Moore, David T.

2014-06-01

Using matrix isolation FTIR, we have observed the formation of anionic copper carbonyl complexes [Cu(CO)n]- (n=1-3) following co-deposition of Cu- and counter-cations (Ar+ or Kr+) into argon matrices doped with CO. The infrared bands have been previously assigned in argon matrix studies employing laser ablation, however they were quite weak compared to the bands for the corresponding neutral species. In the current study, when the deposition is carried out in fully darkened conditions at 10 K with high CO concentrations (1-2%), only the bands for the anionic complexes are observed initially via FTIR. However, upon mild irradiation with broadband visible light, the anionic bands are rapidly depleted, with concomitant appearance of bands corresponding to neutral copper carbonyl complexes. This photo-triggered neutralization is attributed to photodetachment of electrons from the anions, which then "flow" through the solid argon matrix to recombine in the matrix with non-adjacent trapping sites. This mechanism is supported by the appearance of a new band near 1515 wn, assigned to the (CO)2- species in argon. The wavelength dependence of the photodetachment will be discussed in detail, although preliminary indications are that the thresholds for the copper carbonyls, which are normally in the infrared, are shifted into the visible region of the spectrum in argon matrices. This likely occurs because the conduction band of solid argon is known to lie about 1 eV above the vacuum level, and thus the electron must have at least this much energy in order to escape into the matrix and find a trapping site. Funding support from NSF CAREER Award CHE-0955637 is gratefully acknowledged Ryan M. Ludwig and David T. Moore, J. Chem. Phys. 139, 244202 (2013) Zhou, M.; Andrews, L., J. Chem. Phys. 111, 4548 (1999). Thompson, W.E.; Jacox, M.E.; J. Chem. Phys. 91, 735 (1991). Stanzel, J. et al.; Collect. Czech. Chem. Comm. 72, 1 (2007). Harbich, W. et al.; Phys. Rev. B. 76, 104306 (2007).

Imidazolium- and Triazine-Based Porous Organic Polymers for Heterogeneous Catalytic Conversion of CO2 into Cyclic Carbonates.

PubMed

Zhong, Hong; Su, Yanqing; Chen, Xingwei; Li, Xiaoju; Wang, Ruihu

2017-12-22

CO 2 adsorption and concomitant catalytic conversion into useful chemicals are promising approaches to alleviate the energy crisis and effects of global warming. This is highly desirable for developing new types of heterogeneous catalytic materials containing CO 2 -philic groups and catalytic active sites for CO 2 chemical transformation. Here, we present an imidazolium- and triazine-based porous organic polymer with counter chloride anion (IT-POP-1). The porosity and CO 2 affinity of IT-POP-1 may be modulated at the molecular level through a facile anion-exchange strategy. Compared with the post-modified polymers with iodide and hexafluorophosphate anions, IT-POP-1 possesses the highest surface area and the best CO 2 uptake capacity with excellent adsorption selectivity over N 2 . The roles of the task-specific components such as triazine, imidazolium, hydroxyl, and counter anions in CO 2 absorption and catalytic performance were illustrated. IT-POP-1 exhibits the highest catalytic activity and excellent recyclability in solvent- and additive-free cycloaddition reaction of CO 2 with epoxides. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Label-Free Pyrophosphate Recognition with Functionalized Asymmetric Nanopores.

PubMed

Ali, Mubarak; Ahmed, Ishtiaq; Ramirez, Patricio; Nasir, Saima; Niemeyer, Christof M; Mafe, Salvador; Ensinger, Wolfgang

2016-04-01

The label-free detection of pyrophosphate (PPi) anions with a nanofluidic sensing device based on asymmetric nanopores is demonstrated. The pore surface is functionalized with zinc complexes based on two di(2-picolyl)amine [bis(DPA)] moieties using carbodiimide coupling chemistry. The complexation of zinc (Zn(2+) ) ion is achieved by exposing the modified pore to a solution of zinc chloride to form bis(Zn(2+) -DPA) complexes. The chemical functionalization is demonstrated by recording the changes in the observed current-voltage (I-V) curves before and after pore modification. The bis(Zn(2+) -DPA) complexes on the pore walls serve as recognition sites for pyrophosphate anion. The experimental results show that the proposed nanofluidic sensor has the ability to sense picomolar concentrations of PPi anion in the surrounding environment. On the contrary, it does not respond to other phosphate anions, including monohydrogen phosphate, dihydrogen phosphate, adenosine monophosphate, adenosine diphosphate, and adenosine triphosphate. The experimental results are described theoretically by using a model based on the Poisson-Nernst-Planck equations. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Impact of Glycolate Anion on Aqueous Corrosion in DWPF and Downstream Facilities

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

Mickalonis, J.

Glycolic acid is being evaluated as an alternate reductant in the preparation of high level waste for the Defense Waste Processing Facility (DWPF) at the Savannah River Site (SRS). During processing, the glycolic acid may not be completely consumed with small quantities of the glycolate anion being carried forward to other high level waste (HLW) facilities. The SRS liquid waste contractor requested an assessment of the impact of the glycolate anion on the corrosion of the materials of construction (MoC) throughout the waste processing system since this impact had not been previously evaluated. A literature review revealed that corrosion datamore » were not available for the MoCs in glycolic-bearing solutions applicable to SRS systems. Data on the material compatibility with only glycolic acid or its derivative products were identified; however, data were limited for solutions containing glycolic acid or the glycolate anion. For the proprietary coating systems applied to the DWPF concrete, glycolic acid was deemed compatible since the coatings were resistant to more aggressive chemistries than glycolic acid. Additionally, similar coating resins showed acceptable resistance to glycolic acid.« less

Impact of Glycolate Anion on Aqueous Corrosion in DWPF and Downstream Facilities

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

Mickalonis, J.

Glycolic acid is being evaluated as an alternate reductant in the preparation of high level waste for the Defense Waste Processing Facility (DWPF) at the Savannah River Site (SRS). During processing, the glycolic acid may not be completely consumed with small quantities of the glycolate anion being carried forward to other high level waste (HLW) facilities. The SRS liquid waste contractor requested an assessment of the impact of the glycolate anion on the corrosion of the materials of construction (MoC) throughout the waste processing system since this impact had not been previously evaluated. A literature review revealed that corrosion datamore » were not available for the MoCs in glycolic-bearing solutions applicable to SRS systems. Data on the material compatibility with only glycolic acid or its derivative products were identified; however, data were limited for solutions containing glycolic acid or the glycolate anion. For the proprietary coating systems applied to the DWPF concrete, glycolic acid was deemed compatible since the coatings were resistant to more aggressive chemistries than glycolic acid. Additionally similar coating resins showed acceptable resistance to glycolic acid.« less

Highly efficient SO2 capture through tuning the interaction between anion-functionalized ionic liquids and SO2.

PubMed

Wang, Congmin; Zheng, Junjie; Cui, Guokai; Luo, Xiaoyan; Guo, Yan; Li, Haoran

2013-02-11

A strategy to improve SO(2) capture through tuning the electronegativity of the interaction site in ILs has been presented. Two types of imidazolium ionic liquids that include less electronegative sulfur or carbon sites were used for the capture of SO(2), which exhibit extremely highly available capacity, rapid absorption rate and excellent reversibility.

Carbon-dot-based fluorescent turn-on sensor for selectively detecting sulfide anions in totally aqueous media and imaging inside live cells.

PubMed

Hou, Xianfeng; Zeng, Fang; Du, Fangkai; Wu, Shuizhu

2013-08-23

Sulfide anions are generated not only as a byproduct from industrial processes but also in biosystems. Hence, robust fluorescent sensors for detecting sulfide anions which are fast-responding, water soluble and biocompatible are highly desirable. Herein, we report a carbon-dot-based fluorescent sensor, which features excellent water solubility, low cytotoxicity and a short response time. This sensor is based on the ligand/Cu(II) approach so as to achieve fast sensing of sulfide anions. The carbon dot (CD) serves as the fluorophore as well as the anchoring site for the ligands which bind with copper ions. For this CD-based system, as copper ions bind with the ligands which reside on the surface of the CD, the paramagnetic copper ions efficiently quench the fluorescence of the CD, affording the system a turn-off sensor for copper ions. More importantly, the subsequently added sulfide anions can extract Cu(2+) from the system and form very stable CuS with Cu(2+), resulting in fluorescence enhancement and affording the system a turn-on sensor for sulfide anions. This fast-responding and selective sensor can operate in totally aqueous solution or in physiological milieu with a low detection limit of 0.78 μM. It displays good biocompatibility, and excellent cell membrane permeability, and can be used to monitor S(2-) levels in running water and living cells.

Adsorption of O2, SO2, and SO3, on nickel oxide - Mechanism for sulfate formation

NASA Technical Reports Server (NTRS)

Mehandru, S. P.; Anderson, A. B.

1986-01-01

Calculations based on the atom superposition and electron delocalization molecular orbital technique suggest that O2 will adsorb preferentially end-on at an angle 45 deg from normal on a nickel cation site on the (100) surface of NiO. SO2 adsorption is also stronger on the nickel site; SO2 bonds through the sulfur atom in a plane perpendicular to the surface. Adsorption energies for SO3 on the nickel and oxygen sites are comparable in the preferred orientation in which the SO3 plane is parallel to the surface. The calculations suggest that the strength of adsorption varies as O2 greater than SO2 greater than SO3. On activation, SO3 adsorbed to an O(2-) site forms a trigonal pyramidal SO4 species which yields, with a low barrier, a tetrahedral sulfate anion. Subsequently the anion reorients on the surface. Alternative mechanisms which require the formation of Ni(3+) or O(-) are discussed. NiSO4 thus formed may play a passivating role for the corrosion of Ni at low temperatures in the SO2 + O2 + SO3 atmospheres and an active role at high temperatures, as discussed in the experimental literature.

Designing a protected area network for conservation planning in Jhum landscapes of Garo Hills, Meghalaya

Treesearch

A. Kumar; Bruce Marcot; G. Talukdar

2010-01-01

We studied vegetation and land cover characteristics within the existing array of protected areas (PAs) in South Garo Hills of Meghalaya, northeast India and introduce the concept of protected area network (PAN) and methods to determine linkages of forests among existing PAs. We describe and analyze potential elements of a PAN, including PAs, reserved forests,...

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

Michael, Alicia K.; Fribourgh, Jennifer L.; Chelliah, Yogarany

The basic helix-loop-helix PAS domain (bHLH-PAS) transcription factor CLOCK:BMAL1 (brain and muscle Arnt-like protein 1) sits at the core of the mammalian circadian transcription/translation feedback loop. Precise control of CLOCK:BMAL1 activity by coactivators and repressors establishes the ~24-h periodicity of gene expression. Formation of a repressive complex, defined by the core clock proteins cryptochrome 1 (CRY1):CLOCK:BMAL1, plays an important role controlling the switch from repression to activation each day. Here in this paper, we show that CRY1 binds directly to the PAS domain core of CLOCK: BMAL1, driven primarily by interaction with the CLOCK PAS-B domain. Integrative modeling and solutionmore » X-ray scattering studies unambiguously position a key loop of the CLOCK PAS-B domain in the secondary pocket of CRY1, analogous to the antenna chromophore-binding pocket of photolyase. CRY1 docks onto the transcription factor alongside the PAS domains, extending above the DNA-binding bHLH domain. Single point mutations at the interface on either CRY1 or CLOCK disrupt formation of the ternary complex, highlighting the importance of this interface for direct regulation of CLOCK:BMAL1 activity by CRY1.« less

Physician-Assisted Suicide and Euthanasia in the Intensive Care Unit: A Dialogue on Core Ethical Issues

PubMed Central

Goligher, Ewan C.; Ely, E. Wesley; Sulmasy, Daniel P.; Bakker, Jan; Raphael, John; Volandes, Angelo E.; Patel, Bhavesh M.; Payne, Kate; Hosie, Annmarie; Churchill, Larry; White, Douglas B.; Downar, James

2016-01-01

Objective Many patients are admitted to the intensive care unit at or near the end of their lives. Consequently, the increasingly common debate regarding physician-assisted suicide and euthanasia (PAS/E) holds implications for the practice of critical care medicine. The objective of this manuscript is to explore core ethical issues related to PAS/E from the perspective of healthcare professionals and ethicists on both sides of the debate. Synthesis We identified four issues highlighting the key areas of ethical tension central to evaluating PAS/E in medical practice: (1) the benefit or harm of death itself, (2) the relationship between PAS/E and withholding or withdrawing life support, (3) the morality of a physician deliberately causing death, and (4) the management of conscientious objection related to PAS/E in the critical care setting. We present areas of common ground as well as important unresolved differences. Conclusions We reached differing positions on the first three core ethical questions and achieved significant agreement on how critical care clinicians should manage conscientious objections related to PAS/E. The alternative positions presented in this paper may serve to promote open and informed dialogue within the critical care community. PMID:28098622

Synthesis of phosphonic acid silver-graphene oxide nanomaterials with photocatalytic activity through ultrasonic-assisted method.

PubMed

Li, Yongshen; Song, Yunna; Ma, Zheng; Niu, Shuai; Li, Jihui; Li, Ning

2018-06-01

In this article, phosphonic acid silver-graphene oxide nanomaterials (Nano-PAS-GO) was synthesized from silver nitrate (AgNO 3 ) solution and phosphoric graphene oxide (PGO) via the convenient ultrasonic-assisted method, and the structure and morphology were characterized, and the photocatalytic activity and recyclability were evaluated through photocatalyzing degradation of Rhodamin B (RhB) aqueous solution, and the possible photocatalytic mechanism was also discussed. Based on those, it was confirmed that Nano-PAS-GO has been synthesized from AgNO 3 solution and PGO colloidal suspension under ultrasonic-assisted condition, and Nano-PAS-GO has consisted of phosphoric acid silver nanoparticles and GO with 2D lattice (2D GO lattice) connected in the form of C-P bonds, and the photodegradation rate of Nano-PAS-GO for RhB aqueous solution has reached 93.99%, and Nano-PAS-GO has possessed the nicer recyclability when the photocatalytic time was 50 min. From those results, the strong and stable interface . between PAS nanoparticles and 2D GO lattice connected in the form of the covalent bonds has effectively inhibited the occurrence of the photocorrosion phenomenon. Copyright © 2018 Elsevier B.V. All rights reserved.

Numerical simulation and sensitivity analysis of a low-Reynolds-number flow around a square cylinder controlled using plasma actuators

NASA Astrophysics Data System (ADS)

Anzai, Yosuke; Fukagata, Koji; Meliga, Philippe; Boujo, Edouard; Gallaire, François

2017-04-01

Flow around a square cylinder controlled using plasma actuators (PAs) is numerically investigated by direct numerical simulation in order to clarify the most effective location of actuator installation and to elucidate the mechanism of control effect. The Reynolds number based on the cylinder diameter and the free-stream velocity is set to be 100 to study the fundamental effect of PAs on two-dimensional vortex shedding, and three different locations of PAs are considered. The mean drag and the root-mean-square of lift fluctuations are found to be reduced by 51% and 99% in the case where two opposing PAs are aligned vertically on the rear surface. In that case, a jet flow similar to a base jet is generated by the collision of the streaming flows induced by the two opposing PAs, and the vortex shedding is completely suppressed. The simulation results are ultimately revisited in the frame of linear sensitivity analysis, whose computational cost is much lower than that of performing the full simulation. A good agreement is reported for low control amplitudes, which allows further discussion of the linear optimal arrangement for any number of PAs.

[Validation of French versions of magical ideation and perceptual aberrations questionnaires].

PubMed

Dumas, P; Bouafia, S; Gutknecht, C; Saoud, M; Daléry, J; d'Amato, T

2000-01-01

Chapman and colleagues have developed symptom-oriented scales based on Meehl's manual of schizotypy, such as the Social Anhedonia (SA) and Physical Anhedonia (PhA) Scales, the Magical Ideation Scale (MIS), and the Perceptual Aberration Scale (PAS). Whereas Chapman's scales of psychosis proneness are the most internationally used instruments for the assessment of schizotypy, some of them, such as MIS and PAS, were still not available in French. We reported here the validation study of the MIS and the PAS French versions that we had published previously. This study was conducted in a sample of 233 students (males: n = 108; females: n = 125; mean age: 21.17 +/- 1.47; mean educational level: 13.36 +/- 1.06). The French versions of the MIS and the PAS have high internal reliability (MIS: Cronbach's alpha = 0.85; PAS: Cronbach's alpha = 0.88). French norms are given for each of these scales. They are respectively 19/30 for the MIS and 17/35 for the PAS high cutoff scores without any difference when gender was considered. These results are very closed to those found by Chapman and colleagues for University of Wisconsin undergraduate students.

Physician-Assisted Suicide and Midwest Social Workers: Where Do They Stand?

PubMed

Gaston, N Rose; Randall, Jill M; Kiesel, Lisa R

2018-01-01

Physician-assisted suicide (PAS) is explicitly legal in five states and by court decision in one. Legislative bills have been introduced in other states including Minnesota, Iowa, and Wisconsin. This quantitative study was designed to understand Midwest, hospice and palliative care at end-of-life social workers' attitudes toward PAS, preferred terminology, perception of preparedness for the implementation, and awareness of PAS legislation in their state. Sixty-two social workers from Minnesota, Iowa, and Wisconsin completed an anonymous online survey. The results indicated that over one-half of the participants supported PAS legislation and is consistent with previous research on social workers across the country. While there was a range of perceived preparedness for implementation, a majority felt moderately to very prepared. Professional and personal values as well as professional experience influenced their perceived preparedness. Few social workers had accurate awareness of PAS legislation in their state or had attended workshops/events for further education or as a policy advocate. To practice competently and advocate at all levels of practice, hospice and palliative care at end-of-life social workers' need to understand their own attitudes and values toward PAS and pursue additional education around this ethical issue.

Attitudes and Usage of the Food and Drug Administration Adverse Event Reporting System Among Gastroenterology Nurse Practitioners and Physician Assistants.

PubMed

Salk, Allison; Ehrenpreis, Eli D

2016-01-01

The Food and Drug Administration Adverse Event Reporting System (FAERS) is used for postmarketing pharmacovigilance. Our study sought to assess attitudes and usage of the FAERS among gastroenterology nurse practitioners (NPs) and physician assistants (PAs). A survey was administered at the August 2012 Principles of Gastroenterology for the Nurse Practitioner and Physician Assistant course, held in Chicago, IL. Of the 128 respondents, 123 (96%) reported a specialty in gastroenterology or hepatology and were included in analysis. Eighty-nine participants were NPs and 32 PAs, whereas 2 did not report their profession. Although 119 (98%) agreed or strongly agreed with the statement that accurately reporting adverse drug reactions is an important process to optimize patient safety, the majority of participants (54% NPs and 81% PAs) were unfamiliar with the FAERS. In addition, only 20% of NPs and 9% of PAs reported learning about the FAERS in NP or PA schooling. Our study shows enthusiasm among gastroenterology NPs and PAs for the reporting of adverse drug reactions, coupled with a lack of familiarity with the FAERS. This presents an opportunity for enhanced education about reporting of adverse drug reactions for gastroenterology NPs and PAs.

Thermochemistry of the specific binding of C12 surfactants to bovine serum albumin.

PubMed

Nielsen, A D; Borch, K; Westh, P

2000-06-15

The specific binding to bovine serum albumin (BSA) of anionic and non-ionic surfactants with C12 acyl chains has been studied by high sensitivity isothermal titration calorimetry. This method proved particularly effective in resolving the binding of anionic surfactants into separate classes of sites with different affinity. For sodium dodecylsulfate (SDS) the measured binding curves could be rationalized as association to two classes (high affinity/low affinity) of sites comprising, respectively, three and six similar (i.e. thermodynamically equivalent), independent sites. Changes in the thermodynamic functions enthalpy, standard free energy, standard entropy and heat capacity could be discerned for each class of binding site, as well as for micelle formation. These data suggest that binding to low affinity sites (in analogy with micelle formation) exhibits energetic parameters; in particular, a large negative change in heat capacity, which is characteristic of hydrophobic interactions. The thermodynamics of high affinity binding, on the other hand, is indicative of other dominant forces; most likely electrostatic interactions. Other anionic ligands investigated (laurate and dodecyl benzylsulfonate) showed a behavior similar to SDS, the most significant difference being the high affinity binding of the alkylbenzyl sulfonate. For this ligand, the thermodynamic data is indicative of a more loosely associated complex than for SDS and laurate. BSA was found to bind one or two of the non-ionic surfactants (NIS) hepta- or penta(ethylene glycol) monododecyl ether (C12EO7 and C12EO5) with binding constants about three orders of magnitude lower than for SDS. Hence, the free energy of the surfactant in the weakly bound BSA-NIS complex is only slightly favored over the micellar state. The binding process is characterized by very large exothermic enthalpy changes (larger than for the charged surfactants) and a large, positive increment in heat capacity. These observations cannot be reconciled with a molecular picture based on simple hydrophobic condensation onto non-polar patches on the protein surface.

Electronic characterization of defects in narrow gap semiconductors

NASA Technical Reports Server (NTRS)

Patterson, James D.

1994-01-01

We use a Green's function technique to calculate the position of deep defects in narrow gap semiconductors. We consider substitutional (including antisite), vacancy, and interstitial (self and foreign) deep defects. We also use perturbation theory to look at the effect of nonparabolic bands on shallow defect energies and find nonparabolicity can increase the binding by 10 percent or so. We consider mercury cadmium telluride (MCT), mercury zinc telluride (MZT), and mercury zinc selenide (MZS). For substitutional and interstitial defects we look at the situation with and without relaxation. For substitutional impurities in MCT, MZT, and MZS, we consider x (the concentration of Cd or Zn) in the range 0.1 less than x less than 0.3 and also consider appropriate x so E(sub g) = 0.1 eV for each of the three compounds. We consider several cation site s-like deep levels and anion site p-like levels. For E(sub g) = 0.1 eV, we also consider the effects of relaxation. Similar comments apply to the interstitial deep levels whereas no relaxation is considered for the ideal vacancy model. Relaxation effects can be greater for the interstitial than the substitutional cases. Specific results are given in figures and tables and comparison to experiment is made in a limited number of cases. We find, for example, that I, Se, S, Rn, and N are possible cation site, s-like deep levels in MCT and Zn and Mg are for anion site, p-like levels (both levels for substitutional cases). The corresponding cation and anion site levels for interstitial deep defects are (Au, Ag, Hg, Cd, Cu, Zn) and (N, Ar, O, F). For the substitutional cases we have some examples of relaxation moving the levels into the band gap, whereas for the interstitial case we have examples where relaxation moves it out of the band gap. Future work involves calculating the effects of charge state interaction and seeing the effect of relaxation on vacancy levels.

Molecular Dynamics Simulation of Resin Adsorption at Kaolinite Edge Sites: Effect of Surface Deprotonation on Interfacial Structure

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

Zeitler, T. R.; Greathouse, J. A.; Cygan, R. T.

Low-salinity water flooding, a method of enhanced oil recovery, consists of injecting low ionic strength fluids into an oil reservoir in order to detach oil from mineral surfaces in the underlying formation. Although highly successful in practice, the approach is not completely understood at the molecular scale. Molecular dynamics simulations have been used to investigate the effect of surface protonation on the adsorption of an anionic crude oil component on clay mineral edge surfaces. A set of interatomic potentials appropriate for edge simulations has been applied to the kaolinite (010) surface in contact with an aqueous nanopore. Decahydro-2-napthoic acid inmore » its deprotonated form (DHNA –) was used as a representative resin component of crude oil, with monovalent and divalent counterions, to test the observed trends in low-salinity water flooding experiments. Surface models include fully protonated (neutral) and deprotonated (negative) edge sites, which require implementation of a new deprotonation scheme. The surface adsorptive properties of the kaolinite edge under neutral and deprotonated conditions have been investigated for low and high DHNA – concentrations with Na + and Ca 2+ as counterions. The tendency of DHNA – ions to coordinate with divalent (Ca 2+) rather than monovalent (Na +) ions greatly influences adsorption tendencies of the anion. Additionally, the formation of net positively charged surface sites due to Ca 2+ at deprotonated sites results in increased DHNA – adsorption. Divalent cations such as Ca 2+ are able to efficiently bridge surface sites and organic anions. Replacing those cations with monovalent cations such as Na + diminishes the bridging mechanism, resulting in reduced adsorption of the organic species. As a result, a clear trend of decreased DHNA – adsorption is observed in the simulations as Ca 2+ is replaced by Na + for deprotonated surfaces, as would be expected for oil detachment from reservoir formations following a low-salinity flooding event.« less

Molecular Dynamics Simulation of Resin Adsorption at Kaolinite Edge Sites: Effect of Surface Deprotonation on Interfacial Structure

DOE PAGES

Zeitler, T. R.; Greathouse, J. A.; Cygan, R. T.; ...

2017-10-05

Low-salinity water flooding, a method of enhanced oil recovery, consists of injecting low ionic strength fluids into an oil reservoir in order to detach oil from mineral surfaces in the underlying formation. Although highly successful in practice, the approach is not completely understood at the molecular scale. Molecular dynamics simulations have been used to investigate the effect of surface protonation on the adsorption of an anionic crude oil component on clay mineral edge surfaces. A set of interatomic potentials appropriate for edge simulations has been applied to the kaolinite (010) surface in contact with an aqueous nanopore. Decahydro-2-napthoic acid inmore » its deprotonated form (DHNA –) was used as a representative resin component of crude oil, with monovalent and divalent counterions, to test the observed trends in low-salinity water flooding experiments. Surface models include fully protonated (neutral) and deprotonated (negative) edge sites, which require implementation of a new deprotonation scheme. The surface adsorptive properties of the kaolinite edge under neutral and deprotonated conditions have been investigated for low and high DHNA – concentrations with Na + and Ca 2+ as counterions. The tendency of DHNA – ions to coordinate with divalent (Ca 2+) rather than monovalent (Na +) ions greatly influences adsorption tendencies of the anion. Additionally, the formation of net positively charged surface sites due to Ca 2+ at deprotonated sites results in increased DHNA – adsorption. Divalent cations such as Ca 2+ are able to efficiently bridge surface sites and organic anions. Replacing those cations with monovalent cations such as Na + diminishes the bridging mechanism, resulting in reduced adsorption of the organic species. As a result, a clear trend of decreased DHNA – adsorption is observed in the simulations as Ca 2+ is replaced by Na + for deprotonated surfaces, as would be expected for oil detachment from reservoir formations following a low-salinity flooding event.« less

[Observation in situ of differentiation from PGC to hematopoietic system cells in chicken embryo].

PubMed

Zhou, Dong-Yu; Liu, Rong-Xiu; Pei, Yue-Hu

2009-02-01

To study the relationship between hematopoiesis and primordial germ cells, chick embryos at different developing stages were flatbed and located. After fixed by glutaral, the embryos were PAS and HE stained respectively, dehydrated serially, transparent, mounted, and were observed in situ or in cut sheet condition. The results showed: (1) the cellule amorphous and the disposition in chick embryo of PGCs were coincident no matter stained by PAS or HE staining, and HE staining could disclose the morphologic characteristics more clearly, exactly and completely; (2) genesis of blood island could be observed at the boundary of light and dark region of the extraembryonic blastoderm at about 26 hours; (3) both the blood vessel endothelium cells and free cells of the blood island were differentiated from PGCs. The generating of genuine yolk sac was at about 44 - 48 hours. It is concluded that the initial anatomic site of blood island genesis may be is mesoblast of extraembryonic blastoderm rather than the yolk sac; the blood vessel endothelium cells and the blood cells are generated parallel; the PGCs are the common ancestry of angioblast and HSC.

MtPAR MYB transcription factor acts as an on switch for proanthocyanidin biosynthesis in Medicago truncatula

PubMed Central

Verdier, Jerome; Zhao, Jian; Torres-Jerez, Ivone; Ge, Shujun; Liu, Chenggang; He, Xianzhi; Mysore, Kirankumar S.; Dixon, Richard A.; Udvardi, Michael K.

2012-01-01

MtPAR (Medicago truncatula proanthocyanidin regulator) is an MYB family transcription factor that functions as a key regulator of proanthocyanidin (PA) biosynthesis in the model legume Medicago truncatula. MtPAR expression is confined to the seed coat, the site of PA accumulation. Loss-of-function par mutants contained substantially less PA in the seed coat than the wild type, whereas levels of anthocyanin and other specialized metabolites were normal in the mutants. In contrast, massive accumulation of PAs occurred when MtPAR was expressed ectopically in transformed hairy roots of Medicago. Transcriptome analysis of par mutants and MtPAR-expressing hairy roots, coupled with yeast one-hybrid analysis, revealed that MtPAR positively regulates genes encoding enzymes of the flavonoid–PA pathway via a probable activation of WD40-1. Expression of MtPAR in the forage legume alfalfa (Medicago sativa) resulted in detectable levels of PA in shoots, highlighting the potential of this gene for biotechnological strategies to increase PAs in forage legumes for reduction of pasture bloat in ruminant animals. PMID:22307644

Positron annihilation spectroscopy of vacancy-related defects in CdTe:Cl and CdZnTe:Ge at different stoichiometry deviations

PubMed Central

Šedivý, L.; Čížek, J.; Belas, E.; Grill, R.; Melikhova, O.

2016-01-01

Positron annihilation spectroscopy (PAS) was used to examine the effect of defined Cd-rich and Te-rich annealing on point defects in Cl-doped CdTe and Ge-doped CdZnTe semi-insulating single crystals. The as-grown crystals contain open-volume defects connected with Cd vacancies . It was found that the Cd vacancies agglomerate into clusters coupled with Cl in CdTe:Cl, and in CdZnTe:Ge they are coupled with Ge donors. While annealing in Cd pressure reduces of the density, subsequent annealing in Te pressure restores . The CdTe:Cl contains negatively-charged shallow traps interpreted as Rydberg states of A-centres and representing the major positron trapping sites at low temperature. Positrons confined in the shallow traps exhibit lifetime, which is shorter than the CdTe bulk lifetime. Interpretation of the PAS data was successfully combined with electrical resistivity, Hall effect measurements and chemical analysis, and allowed us to determine the principal point defect densities. PMID:26860684

Structural evidence of the species-dependent albumin binding of the modified cyclic phosphatidic acid with cytotoxic properties

PubMed Central

Sekula, Bartosz; Ciesielska, Anna; Rytczak, Przemyslaw; Koziołkiewicz, Maria; Bujacz, Anna

2016-01-01

Cyclic phosphatidic acids (cPAs) are naturally occurring, very active signalling molecules, which are involved in several pathological states, such as cancer, diabetes or obesity. As molecules of highly lipidic character found in the circulatory system, cPAs are bound and transported by the main extracellular lipid binding protein–serum albumin. Here, we present the detailed interactions between human serum albumin (HSA) and equine serum albumin (ESA) with a derivative of cPA, 1-O-myristoyl-sn-glycerol-2,3-cyclic phosphorodithioate (Myr-2S-cPA). Initial selection of the ligand used for the structural study was made by the analysis of the therapeutically promising properties of the sulfur containing analogues of cPA in respect to the unmodified lysophospholipids (LPLs). Substitution of one or two non-bridging oxygen atoms in the phosphate group with one or two sulfur atoms increases the cytotoxic effect of cPAs up to 60% on the human prostate cancer (PC) cells. Myr-2S-cPA reduces cancer cell viability in a dose-dependent manner, with IC50 value of 29.0 μM after 24 h incubation, which is almost 30% lower than IC50 of single substituted phosphorothioate cPA. Although, the structural homology between HSA and ESA is big, their crystal complexes with Myr-2S-cPA demonstrate significantly different mode of binding of this LPL analogue. HSA binds three molecules of Myr-2S-cPA, whereas ESA only one. Moreover, none of the identified Myr-2S-cPA binding sites overlap in both albumins. PMID:27129297

Graphene oxide for solid-phase extraction of bioactive phenolic acids.

PubMed

Hou, Xiudan; Wang, Xusheng; Sun, Yingxin; Wang, Licheng; Guo, Yong

2017-05-01

A solid-phase extraction (SPE) method for the efficient analysis of trace phenolic acids (PAs, caffeic acid, ferulic acid, protocatechuic acid, cinnamic acid) in urine was established. In this work, a graphene oxide (GO) coating was grafted onto pure silica to be investigated as SPE material. The prepared GO surface had a layered and wrinkled structure that was rough and well organized, which could provide more open adsorption sites. Owing to its hydrophilicity and polarity, GO showed higher extraction efficiency toward PAs than reduced GO did, in agreement with the theoretical calculation results performed by Gaussian 09 software. The adsorption mechanism of PAs on GO@Sil was also investigated through static state and kinetic state adsorption experiments, which showed a monolayer surface adsorption. Extraction capacity of the as-prepared material was optimized using the response surface methodology. Under the optimized conditions, the as-established method provided wide linearity range (2-50 μg L -1 for protocatechuic acid and 1-50 μg L -1 for caffeic acid, ferulic acid, and cinnamic acid) and low limits of detection (0.25-1 μg L -1 ). Finally, the established method was applied for the analysis of urine from two healthy volunteers. The results indicate that the prepared material is a practical, cost-effective medium for the extraction and determination of phenolic acids in complex matrices. Graphical Abstract A graphene oxide coating was grafted onto pure silica as the SPE material for the extraction of phenolic acids in urines and the extraction mechanism was also mainly investigated.

Positron Annihilation Spectroscopy and Small Angle Neutron Scattering Characterization of Nanostructural Features in Irradiated Fe-Cu-Mn Alloys

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

Wirth, B D; Asoka-Kumar, P; Howell, R H

2001-01-01

Radiation embrittlement of nuclear reactor pressure vessel steels results from a high number density of nanometer sized Cu-Mn-Ni rich precipitates (CRPs) and sub-nanometer matrix features, thought to be vacancy-solute cluster complexes (VSC). However, questions exist regarding both the composition of the precipitates and the defect character and composition of the matrix features. We present results of positron annihilation spectroscopy (PAS) and small angle neutron scattering (SANS) characterization of irradiated and thermally aged Fe-Cu and Fe-Cu-Mn alloys. These complementary techniques provide insight into the composition and character of both types of nanoscale features. The SANS measurements indicate populations of CRPs andmore » VSCs in both alloys. The CRPs are coarser in the Fe-Cu alloy and the number densities of CRP and VSC increase with the addition of Mn. The PAS involved measuring both the positron lifetimes and the Doppler broadened annihilation spectra in the high momentum region to provide elemental sensitivity at the annihilation site. The spectra in Fe-Cu-Mn specimens thermally aged to peak hardness at 450 C and irradiated at 288 C are nearly identical to elemental Cu. Positron lifetime and spectrum measurements in Fe-Cu specimens irradiated at 288 C clearly show the existence of long lifetime ({approx}500 ps) open volume defects, which also contain Cu. Thus the SANS and PAS provide a self-consistent picture of nanostructures composed of CRPs and VSCs and tend to discount high Fe concentrations in the CRPs.« less

Contrasting nitrate adsorption in Andisols of two coffee plantations in Costa Rica.

PubMed

Ryan, M C; Graham, G R; Rudolph, D L

2001-01-01

Fertilizer use in coffee plantations is a suspected cause of rising ground water nitrate concentrations in the ground water-dependent Central Valley of Costa Rica. Nitrate adsorption was evaluated beneath two coffee (Coffea arabica L.) plantations in the Central Valley. Previous work at one site had identified unsaturated zone nitrate retardation relative to a tritium tracer. Differences in nitrate adsorption were assessed in cores to 4 m depth in Andisols at this and one other plantation using differences in KCl- and water-extractable nitrate as an index. Significant adsorption was confirmed at the site of the previous tracer test, but not at the second site. Anion exchange capacity, X-ray diffraction data, extractable Al and Si, and soil pH in NaF corroborated that differences in adsorption characteristics were related to subtle differences in clay mineralogy. Soils at the site with significant nitrate adsorption showed an Al-rich allophane clay content compared with a more weathered, Si-rich allophane and halloysite clay mineral content at the site with negligible adsorption. At the site with significant nitrate adsorption, nitrate occupied less than 10% of the total anion adsorption capacity, suggesting that adsorption may provide long-term potential for mitigation or delay of nitrate leaching. Evaluation of nitrate sorption potential of soil at local and landscape scales would be useful in development of nitrogen management practices to reduce nitrate leaching to ground water.

Goethite surface reactivity: a macroscopic investigation unifying proton, chromate, carbonate, and lead(II) adsorption.

PubMed

Villalobos, Mario; Pérez-Gallegos, Ayax

2008-10-15

The goethite surface structure has been extensively studied, but no convincing quantitative description of its highly variable surface reactivity as inversely related to its specific surface area (SSA) has been found. The present study adds experimental evidence and provides a unified macroscopic explanation to this anomalous behavior from differences in average adsorption capacities, and not in average adsorption affinities. We investigated the chromate anion and lead(II) cation adsorption behavior onto three different goethites with SSA varying from 50 to 94 m(2)/g, and analyzed an extensive set of published anion adsorption and proton charging data for variable SSA goethites. Maximum chromate adsorption was found to occupy on average from 3.1 to 9.7 sites/nm(2), inversely related to SSA. Congruency of oxyanion and Pb(II) adsorption behavior based on fractional site occupancy using these values, and a site density analysis suggest that: (i) ion binding occurs to singly and doubly coordinated sites, (ii) proton binding occurs to singly and triply coordinated sites (ranging from 6.2 to 8 total sites/nm(2), in most cases), and (iii) a predominance of (210) and/or (010) faces explains the high reactivity of low SSA goethites. The results imply that the macroscopic goethite adsorption behavior may be predicted without a need to investigate extensive structural details of each specific goethite of interest.

Veterinary surgeons' attitudes towards physician-assisted suicide: an empirical study of Swedish experts on euthanasia.

PubMed

Lerner, Henrik; Lindblad, Anna; Algers, Bo; Lynöe, Niels

2011-05-01

To examine the hypothesis that knowledge about physician-assisted suicide (PAS) and euthanasia is associated with a more restrictive attitude towards PAS. A questionnaire about attitudes towards PAS, including prioritization of arguments pro and contra, was sent to Swedish veterinary surgeons. The results were compared with those from similar surveys of attitudes among the general public and physicians. All veterinary surgeons who were members of the Swedish Veterinary Association and had provided an email address (n=2421). Similarities or differences in response pattern between veterinary surgeons, physicians and the general public. The response pattern among veterinary surgeons and the general public was almost similar in all relevant aspects. Of the veterinarians 75% (95% CI 72% to 78%) were in favour of PAS, compared with 73% (95% CI 69% to 77%) among the general public. Only 10% (95% CI 5% to 15%) of the veterinary surgeons were against PAS, compared with 12% (95% CI 5% to 19%) among the general public. Finally, 15% (95% CI 10% to 21%) of veterinarians were undecided, compared with 15% (95% CI 8% to 22%) among the general public. Physicians had a more restrictive attitude to PAS than the general public. Since veterinary surgeons have frequent practical experience of euthanasia in animals, they do have knowledge about what euthanasia really is. Veterinary surgeons and the general public had an almost similar response pattern. Accordingly it seems difficult to maintain that knowledge about euthanasia is unambiguously associated with a restrictive attitude towards PAS.

Protective effects of ebselen (Ebs) and para-aminosalicylic acid (PAS) against manganese (Mn)-induced neurotoxicity

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

Marreilha dos Santos, A.P., E-mail: apsantos@ff.ul.pt; Lucas, Rui L.; Andrade, Vanda

2012-02-01

Chronic, excessive exposure to manganese (Mn) may induce neurotoxicity and cause an irreversible brain disease, referred to as manganism. Efficacious therapies for the treatment of Mn are lacking, mandating the development of new interventions. The purpose of the present study was to investigate the efficacy of ebselen (Ebs) and para-aminosalicylic acid (PAS) in attenuating the neurotoxic effects of Mn in an in vivo rat model. Exposure biomarkers, inflammatory and oxidative stress biomarkers, as well as behavioral parameters were evaluated. Co-treatment with Mn plus Ebs or Mn plus PAS caused a significant decrease in blood and brain Mn concentrations (compared tomore » rats treated with Mn alone), concomitant with reduced brain E{sub 2} prostaglandin (PGE{sub 2}) and enhanced brain glutathione (GSH) levels, decreased serum prolactin (PRL) levels, and increased ambulation and rearing activities. Taken together, these results establish that both PAS and Ebs are efficacious in reducing Mn body burden, neuroinflammation, oxidative stress and locomotor activity impairments in a rat model of Mn-induced toxicity. -- Highlights: ► The manuscript is unique in its approach to the neurotoxicity of Mn. ► The manuscript incorporates molecular, cellular and functional (behavioral) analyses. ► Both PAS and Ebs are effective in restoring Mn behavioral function. ► Both PAS and Ebs are effective in reducing Mn-induced oxidative stress. ► Both PAS and Ebs led to a decrease in Mn-induced neuro-inflammation.« less

The PAS domains of the major sporulation kinase in Bacillus subtilis play a role in tetramer formation that is essential for the autokinase activity.

PubMed

Kiehler, Brittany; Haggett, Lindsey; Fujita, Masaya

2017-08-01

Sporulation in Bacillus subtilis is induced upon starvation. In a widely accepted model, an N-terminal "sensor" domain of the major sporulation kinase KinA recognizes a hypothetical starvation signal(s) and autophosphorylates a histidine residue to activate the master regulator Spo0A via a multicomponent phosphorelay. However, to date no confirmed signal has been found. Here, we demonstrated that PAS-A, the most N-terminal of the three PAS domains (PAS-ABC), is dispensable for the activity, contrary to a previous report. Our data indicated that the autokinase activity is dependent on the formation of a functional tetramer, which is mediated by, at least, PAS-B and PAS-C. Additionally, we ruled out the previously proposed notion that NAD + /NADH ratio controls KinA activity through the PAS-A domain by demonstrating that the cofactors show no effects on the kinase activity in vitro. In support of these data, we found that the cofactors exist in approximately 1000-fold excess of KinA in the cell and the cofactors' ratio does not change significantly during growth and sporulation, suggesting that changes in the cofactor ratio might not play a role in controlling KinA activity. These data may refute the widely-held belief that the activity of KinA is regulated in response to an unknown starvation signal(s). © 2017 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

Physician-Assisted Suicide and Euthanasia: Emerging Issues From a Global Perspective.

PubMed

Sprung, Charles L; Somerville, Margaret A; Radbruch, Lukas; Collet, Nathalie Steiner; Duttge, Gunnar; Piva, Jefferson P; Antonelli, Massimo; Sulmasy, Daniel P; Lemmens, Willem; Ely, E Wesley

2018-01-01

Medical professional societies have traditionally opposed physician-assisted suicide and euthanasia (PAS-E), but this opposition may be shifting. We present 5 reasons why physicians shouldn't be involved in PAS-E. 1. Slippery slopes: There is evidence that safeguards in the Netherlands and Belgium are ineffective and violated, including administering lethal drugs without patient consent, absence of terminal illness, untreated psychiatric diagnoses, and nonreporting; 2. Lack of self-determination: Psychological and social motives characterize requests for PAS-E more than physical symptoms or rational choices; many requests disappear with improved symptom control and psychological support; 3. Inadequate palliative care: Better palliative care makes most patients physically comfortable. Many individuals requesting PAS-E don't want to die but to escape their suffering. Adequate treatment for depression and pain decreases the desire for death; 4. Medical professionalism: PAS-E transgresses the inviolable rule that physicians heal and palliate suffering but never intentionally inflict death; 5. Differences between means and ends: Proeuthanasia advocates look to the ends (the patient's death) and say the ends justify the means; opponents disagree and believe that killing patients to relieve suffering is different from allowing natural death and is not acceptable. Physicians have a duty to eliminate pain and suffering, not the person with the pain and suffering. Solutions for suffering lie in improving palliative care and social conditions and addressing the reasons for PAS-E requests. They should not include changing medical practice to allow PAS-E.

PAs in orthopedics in the VHA's community-based outpatient clinics.

PubMed

Reed, Daniel O; Hooker, Roderick S

2017-04-01

In the Veterans Health Administration (VHA) system, most orthopedic care takes place in the VA medical centers (VAMCs). Because most patients receiving orthopedic care were referred by adult medicine providers, more widely deploying physician assistants (PAs) in orthopedic medicine might help offset this workload. An orthopedic medicine demonstration project recruited, trained, and positioned PAs in community-based outpatient clinics (CBOCs) to improve access to care. The project involved surgeons at the Houston VAMC instructing five newly employed PAs in a wide range of orthopedic evaluation and management strategies before their assignment to a CBOC. An administrative assessment compared encounter data pre- and postproject (2012 and 2014) to determine if this strategy modified orthopedic workload and improved patient access to care. By 2014, orthopedic patient visit volume had increased 31%-10% at the VAMC and 21% at the five CBOCs. Overall, the five deployed PAs managed 28% of all orthopedic encounters spread over 1 year and only 3.2% of visits required VAMC referral for further evaluation or treatment. During the project, the total volume of patient visits increased throughout the Houston VAMC region but access to care for this specialty service also increased, with more veteran musculoskeletal care being met at the five CBOCs, off-loading visit demand centrally. The adaptability and flexibility of new roles has been identified as one of the defining characteristics of PAs. That the VHA can take advantage of this role malleability suggests that employing PAs is useful in meeting medical service needs of veterans.

Hyperglycosylated hCG and Placenta Accreta Spectrum.

PubMed

Einerson, Brett D; Straubhar, Alli; Soisson, Sean; Szczotka, Kathryn; Dodson, Mark K; Silver, Robert M; Soisson, Andrew P

2018-02-28

 We aimed to evaluate the relationship between hyperglycosylated human chorionic gonadotropin (hCG-H) and placenta accreta spectrum (PAS) in the second and third trimesters of pregnancy.  This was a case-control study of PAS and controls. hCG-H was measured in the second and third trimesters of pregnancy in women with pathologically confirmed cases of PAS and in gestational age-matched controls without PAS. We compared serum hCG-H levels in cases and controls, calculated summary statistics for diagnostic accuracy, and used receiver operating characteristic (ROC) curves to define an optimal cut-point for diagnosis of PAS using hCG-H.  Thirty case samples and 30 control samples were evaluated for hCG-H. Mean hCG-H was lower in the case compared with control group (7.8 ± 5.9 μg/L vs. 11.8 ± 8.8 μg/L, p  = 0.03). At an optimal cut-point for hCG-H of ≤7.6 μg/L, the sensitivity, specificity, positive likelihood ratios, negative likelihood ratios, and area under the ROC curve were 66.7%, 69.7%, 2.20%, 0.48%, and 0.68%, respectively.  Hyperglycosylated hCG levels in the second and third trimesters of pregnancy were lower in patients with PAS than in controls, but hCG-H showed only modest capability as a diagnostic test for PAS. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

The presence of glutamate residues on the PAS sequence of the stimuli-sensitive nano-ferritin improves in vivo biodistribution and mitoxantrone encapsulation homogeneity.

PubMed

Falvo, Elisabetta; Malagrinò, Francesca; Arcovito, Alessandro; Fazi, Francesco; Colotti, Gianni; Tremante, Elisa; Di Micco, Patrizio; Braca, Aldo; Opri, Roberta; Giuffrè, Alessandro; Fracasso, Giulio; Ceci, Pierpaolo

2018-04-10

A genetically engineered human ferritin heavy chain (HFt)-based construct has been recently shown by our group to efficiently entrap and deliver doxorubicin to cancer cells. This construct, named HFt-MP-PAS, contained a tumor-selective sequence (MP) responsive to proteolytic cleavage by tumor proteases (MMPs), located between each HFt subunit and an outer shielding polypeptide sequence rich in proline (P), serine (S) and alanine (A) residues (PAS). HFt-MP-PAS displayed excellent therapeutic efficacy in xenogenic pancreatic and head and neck cancer models in vivo, leading to a significant increase in overall animal survivals. Here we report a new construct obtained by the genetic insertion of two glutamate residues in the PAS sequence of HFt-MP-PAS. Such new construct, named HFt-MP-PASE, is characterized by improved performances as drug biodistribution in a xenogenic pancreatic cancer model in vivo. Moreover, HFt-MP-PASE efficiently encapsulates the anti-cancer drug mitoxantrone (MIT), and the resulting MIT-loaded nanoparticles proved to be more soluble and monodispersed than the HFt-MP-PAS counterparts. Importantly, in vitro MIT-loaded HFt-MP-PASE kills several cancer cell lines of different origin (colon, breast, sarcoma and pancreas) at least as efficiently as the free drug. Finally, our MIT loaded protein nanocages allowed in vivo an impressive incrementing of the drug accumulation in the tumor with respect to the free drug. Copyright © 2018 Elsevier B.V. All rights reserved.

French hospital nurses' opinion about euthanasia and physician-assisted suicide: a national phone survey.

PubMed

Bendiane, M K; Bouhnik, A-D; Galinier, A; Favre, R; Obadia, Y; Peretti-Watel, P

2009-04-01

Hospital nurses are frequently the first care givers to receive a patient's request for euthanasia or physician-assisted suicide (PAS). In France, there is no consensus over which medical practices should be considered euthanasia, and this lack of consensus blurred the debate about euthanasia and PAS legalisation. This study aimed to investigate French hospital nurses' opinions towards both legalisations, including personal conceptions of euthanasia and working conditions and organisation. A phone survey conducted among a random national sample of 1502 French hospital nurses. We studied factors associated with opinions towards euthanasia and PAS, including contextual factors related to hospital units with random-effects logistic models. Overall, 48% of nurses supported legalisation of euthanasia and 29%, of PAS. Religiosity, training in pallative care/pain management and feeling competent in end-of-life care were negatively correlated with support for legalisation of both euthanasia and PAS, while nurses working at night were more prone to support legalisation of both. The support for legalisation of euthanasia and PAS was also weaker in pain treatment/palliative care and intensive care units, and it was stronger in units not benefiting from interventions of charity/religious workers and in units with more nurses. Many French hospital nurses uphold the legalisation of euthanasia and PAS, but these nurses may be the least likely to perform what proponents of legalisation call "good" euthanasia. Improving professional knowledge of palliative care could improve the management of end-of-life situations and help to clarify the debate over euthanasia.

A small subset of protected areas are a highly significant source of carbon emissions

PubMed Central

Collins, Murray B.; Mitchard, Edward T. A.

2017-01-01

Protected areas (PAs) aim to protect multiple ecosystem services. However, not all are well protected. For the first time, using published carbon and forest loss maps, we estimate carbon emissions in large forest PAs in tropical countries (N = 2018). We found 36 ± 16 Pg C stored in PA trees, representing 14.5% of all tropical forest biomass carbon. However the PAs lost forest at a mean rate of 0.18% yr−1 from 2000–2012. Lower protection status areas experienced higher forest losses (e.g. 0.39% yr−1 in IUCN cat III), yet even highest status areas lost 0.13% yr−1 (IUCN Cat I). Emissions were not evenly distributed: 80% of emissions derived from 8.3% of PAs (112 ± 49.5 Tg CO2 yr−1; n = 171). Unsurprisingly the largest emissions derived from PAs that started with the greatest total forest area; accounting for starting forest area and relating that to carbon lost using a linear model (r2 = 0.41), we found 1.1% outlying PAs (residuals >2σ; N = 23), representing 1.3% of the total PA forest area, yet causing 27.3% of all PA emissions. These results suggest PAs have been a successful means of protecting biomass carbon, yet a subset causing a disproportionately high share of emissions should be an urgent priority for management interventions. PMID:28186155

Synchronization of finite-size particles by a traveling wave in a cylindrical flow

NASA Astrophysics Data System (ADS)

Melnikov, D. E.; Pushkin, D. O.; Shevtsova, V. M.

2013-09-01

Motion of small finite-size particles suspended in a cylindrical thermocapillary flow with an azimuthally traveling wave is studied experimentally and numerically. At certain flow regimes the particles spontaneously align in dynamic accumulation structures (PAS) of spiral shape. We find that long-time trajectories of individual particles in this flow fall into three basic categories that can be described, borrowing the dynamical systems terminology, as the stable periodic, the quasiperiodic, and the quasistable periodic orbits. Besides these basic types of orbits, we observe the "doubled" periodic orbits and shuttle-like particle trajectories. We find that ensembles of particles having periodic orbits give rise to one-dimensional spiral PAS, while ensembles of particles having quasiperiodic orbits form two-dimensional PAS of toroidal shape. We expound the reasons why these types of orbits and the emergence of the corresponding accumulation structures should naturally be anticipated based on the phase locking theory of PAS formation. We give a further discussion of PAS features, such as the finite thickness of PAS spirals and the probable scenarios of the spiral PAS destruction. Finally, in numerical simulations of inertial particles we observe formation of the spiral structures corresponding to the 3:1 "resonance" between the particle turnover frequency and the wave oscillations frequency, thus confirming another prediction of the phase locking theory. In view of the generality of the arguments involved, we expect the importance of this structure-forming mechanism to go far beyond the realm of the laboratory-friendly thermocapillary flows.

McMYB12 Transcription Factors Co-regulate Proanthocyanidin and Anthocyanin Biosynthesis in Malus Crabapple

PubMed Central

Tian, Ji; Zhang, Jie; Han, Zhen-yun; Song, Ting-ting; Li, Jin-yan; Wang, Ya-ru; Yao, Yun-cong

2017-01-01

The flavonoid compounds, proanthocyanidins (PAs), protect plants from biotic stresses, contribute to the taste of many fruits, and are beneficial to human health in the form of dietary antioxidants. In this study, we functionally characterized two Malus crabapple R2R3-MYB transcription factors, McMYB12a and McMYB12b, which co-regulate PAs and anthocyanin biosynthesis. McMYB12a was shown to be mainly responsible for upregulating the expression of anthocyanin biosynthetic genes by binding to their promoters, but to be only partially responsible for regulating PAs biosynthetic genes. In contrast, McMYB12b showed preferential binding to the promoters of PAs biosynthetic genes. Overexpression of McMYB12a and McMYB12b in tobacco (Nicotiana tabacum) altered the expression of flavonoid biosynthetic genes and promoted the accumulation of PAs and anthocyanins in tobacco petals. Conversely, transient silencing their expression in crabapple plants, using a conserved gene region, resulted in reduced PAs and anthocyanin production a green leaf phenotype. Meanwhile, transient overexpression of the two genes and silenced McMYB12s in apple (Malus domestica) fruit had a similar effect as overexpression in tobacco and silenced in crabapple. This study reveals a new mechanism for the coordinated regulation of PAs and anthocyanin accumulation in crabapple leaves, which depends on an auto-regulatory balance involving McMYB12a and McMYB12b expression. PMID:28255171

McMYB12 Transcription Factors Co-regulate Proanthocyanidin and Anthocyanin Biosynthesis in Malus Crabapple.

PubMed

Tian, Ji; Zhang, Jie; Han, Zhen-Yun; Song, Ting-Ting; Li, Jin-Yan; Wang, Ya-Ru; Yao, Yun-Cong

2017-03-03

The flavonoid compounds, proanthocyanidins (PAs), protect plants from biotic stresses, contribute to the taste of many fruits, and are beneficial to human health in the form of dietary antioxidants. In this study, we functionally characterized two Malus crabapple R2R3-MYB transcription factors, McMYB12a and McMYB12b, which co-regulate PAs and anthocyanin biosynthesis. McMYB12a was shown to be mainly responsible for upregulating the expression of anthocyanin biosynthetic genes by binding to their promoters, but to be only partially responsible for regulating PAs biosynthetic genes. In contrast, McMYB12b showed preferential binding to the promoters of PAs biosynthetic genes. Overexpression of McMYB12a and McMYB12b in tobacco (Nicotiana tabacum) altered the expression of flavonoid biosynthetic genes and promoted the accumulation of PAs and anthocyanins in tobacco petals. Conversely, transient silencing their expression in crabapple plants, using a conserved gene region, resulted in reduced PAs and anthocyanin production a green leaf phenotype. Meanwhile, transient overexpression of the two genes and silenced McMYB12s in apple (Malus domestica) fruit had a similar effect as overexpression in tobacco and silenced in crabapple. This study reveals a new mechanism for the coordinated regulation of PAs and anthocyanin accumulation in crabapple leaves, which depends on an auto-regulatory balance involving McMYB12a and McMYB12b expression.

The productivity of physician assistants and nurse practitioners and health work force policy in the era of managed health care.

PubMed

Scheffler, R M; Waitzman, N J; Hillman, J M

1996-01-01

Managed care is spreading rapidly in the United States and creating incentives for physician practices to find the most efficient combination of health professionals to deliver care to an enrolled population. Given these trends, it is appropriate to reexamine the roles of physician assistants (PAs) and nurse practitioners (NPs) in the health care workforce. This paper briefly reviews the literature on PA and NP productivity, managed care plans' use of PAs and NPs, and the potential impact of PAs and NPs on the size and composition of the future physician workforce. In general, the literature supports the idea that PAs and NPs could have a major impact on the future health care workforce. Studies show significant opportunities for increased physician substitution and even conservative assumptions about physician task delegation imply a large increase in the number of PAs and NPs that can be effectively deployed. However, the current literature has certain limitations that make it difficult to quantify the future impact of PAs and NPs. Among these limitations is the fact that virtually all formal productivity studies were conducted in fee-for-service settings during the 1970s, rather than managed care settings. In addition, the vast majority of PA and NP productivity studies have viewed PAs and NPs as physician substitutes rather than as members of interdisciplinary health care teams, which may become the dominant health care delivery model over the next 10-20 years.

The role of protected areas in land use/land cover change and the carbon cycle in the conterminous United States

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

Lu, Xiaoliang; Zhou, Yuyu; Liu, Yaling

Protected areas (PAs) cover about 22% of the conterminous United States. Understanding their role on historical land use and land cover change (LULCC) and on the carbon cycle is essential to provide guidance for environmental policies. In this study, we compiled historical LULCC and PAs data to explore these interactions within the terrestrial ecosystem model (TEM). We found that intensive LULCC occurred in the conterminous United States from 1700 to 2005. More than 3 million km2 of forest, grassland and shrublands were converted into agricultural lands, which caused 10,607 Tg C release from land ecosystems to atmosphere. PAs had experiencedmore » little LULCC as they were generally established in the 20th century after most of the agricultural expansion had occurred. PAs initially acted as a carbon source due to land use legacies, but their accumulated carbon budget switched to a carbon sink in the 1960s, sequestering an estimated 1,642 Tg C over 1700–2005, or 13.4% of carbon losses in non-PAs. We also find that PAs maintain larger carbon stocks and continue sequestering carbon in recent years (2001–2005), but at a lower rate due to increased heterotrophic respiration as well as lower productivity associated to aging ecosystems. It is essential to continue efforts to maintain resilient, biodiverse ecosystems and avoid large-scale disturbances that would release large amounts of carbon in PAs.« less

ESR study of electron reactions with esters and triglycerides

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

Sevilla, M.D.; Morehouse, K.M.; Swarts, S.

1981-04-02

Reactions which occurred after electron attachment at 77K to a number of small carboxylic acid esters and triglycerides in an aqueous glass are reported. Most ester anions are found to decay on warming to form alkyl radicals by ..beta.. scission: RC(O/sup -/)OR' ..-->.. RCO/sub 2//sup -/ + R'.. The alkyl radical (R'.) produced by annealing is found to abstract hydrogen from the parent ester at an ..cap alpha..-carbon site, R'.+ R''CH/sub 2/CO/sub 2/R' ..-->.. R''CHCO/sub 2/R', or in the case of ethyl formate from the formate hydrogen, CH/sub 3/CH/sub 2/.+ HCO/sub 2/C/sub 2/H/sub 5/ ..-->.. C/sub 2/H/sub 6/ +.CO/sub 2/C/submore » 2/H/sub 5/. Results found for the methyl formate anion suggest hydrogen abstraction by the anion itself may compete with alkyl radical formation. The anion of the triglyceride triacetin is found to undergo an analogous mechanism to the ester anions producing the propane diol diester radical, .CH/sub 2/CH(Ac)CH/sub 2/(Ac), Ac = acetate. This species subsequently abstracts hydrogen from the parent compound to produce the ..cap alpha..-carbon radical, .CH/sub 2/CO/sub 2/R. Results found after annealing the tripropionin radical anion give evidence for abstraction from the ..cap alpha.. carbon in the propionate side groups producing CH/sub 3/CHCO/sub 2/R. Studies of a ..gamma..-irradiated ester (ethyl myristate) and two triglycerides (tripalmitin and tristearin) yield results which suggest that the mechanism of ester anion decay found in aqueous glasses applies to ..gamma..-irradiated neat long-chain esters and triglycerides. Results found in this work are compared to the results of product analysis.« less

Global demand for gold is another threat for tropical forests

NASA Astrophysics Data System (ADS)

Alvarez-Berríos, Nora L.; Aide, T. Mitchell

2015-01-01

The current global gold rush, driven by increasing consumption in developing countries and uncertainty in financial markets, is an increasing threat for tropical ecosystems. Gold mining causes significant alteration to the environment, yet mining is often overlooked in deforestation analyses because it occupies relatively small areas. As a result, we lack a comprehensive assessment of the spatial extent of gold mining impacts on tropical forests. In this study, we provide a regional assessment of gold mining deforestation in the tropical moist forest biome of South America. Specifically, we analyzed the patterns of forest change in gold mining sites between 2001 and 2013, and evaluated the proximity of gold mining deforestation to protected areas (PAs). The forest cover maps were produced using the Land Mapper web application and images from the MODIS satellite MOD13Q1 vegetation indices 250 m product. Annual maps of forest cover were used to model the incremental change in forest in ˜1600 potential gold mining sites between 2001-2006 and 2007-2013. Approximately 1680 km2 of tropical moist forest was lost in these mining sites between 2001 and 2013. Deforestation was significantly higher during the 2007-2013 period, and this was associated with the increase in global demand for gold after the international financial crisis. More than 90% of the deforestation occurred in four major hotspots: Guianan moist forest ecoregion (41%), Southwest Amazon moist forest ecoregion (28%), Tapajós-Xingú moist forest ecoregion (11%), and Magdalena Valley montane forest and Magdalena-Urabá moist forest ecoregions (9%). In addition, some of the more active zones of gold mining deforestation occurred inside or within 10 km of ˜32 PAs. There is an urgent need to understand the ecological and social impacts of gold mining because it is an important cause of deforestation in the most remote forests in South America, and the impacts, particularly in aquatic systems, spread well beyond the actual mining sites.

Histochemical differences along the intestine of Corydoras paleatus (Siluriformes: Callichthyidae).

PubMed

Plaul, Silvia E; Barbeito, Claudio G; Díaz, Alcira O

2016-03-01

The Neotropical catfish Corydoras paleatus is a facultative air-breather and the caudal half of the intestine is involved in gas exchange. In South America, air-breathing fishes are found in tropical or sub-tropical freshwaters where the probability of hypoxia is high. The aim of this study was to characterize by traditional histochemical and lectinhistochemical methods the pattern of carbohydrate in the intestinal mucosa. Intestine samples were taken from 25 healthy adult specimens collected in Buenos Aires (Argentina). Samples were fixed by immersion in 10 % buffered formalin and routinely processed and embedded in paraffin wax. Subsequently, these sections were incubated in the biotinylated lectins battery. Labeled Streptavidin-Biotin (LSAB) system was used for detection, diaminobenzidine as chromogen and haematoxylin as a contrast. To locate and distinguish glycoconjugates (GCs) of the globet cells, we used the following histochemical methods: PAS; PAS*S; KOH/ PA*S; PA/Bh/KOH/PAS; KOH/PA*/Bh/PAS; Alcian Blue and Toluidine Blue at different pHs. Microscopically, the general structure of vertebrate intestine was observed and showed all the cell types characteristic of the intestinal epithelium. The cranial sector of catfish intestine is a site of digestion and absorption and its structure is similar to other fish groups. In contrast, enterocytes of the caudal portion are low cuboidal cells; and between these, globet cells and capillaries are observed, these latter may reach the mucosal lumen. Underlying the epithelium, observed a well-developed lamina propria-submucosa made of connective tissue; this layer was highly vascularized and did not exhibit glands. According to histochemistry, the diverse GCs elaborated and secreted in the intestine are associated with specific functions in relation to their physiological significance, with special reference to their role in lubrication, buffering effect and prevention of proteolytic damage to the epithelium together with other biological processes, such as osmoregulation and ion exchange. The lectinhistochemical analysis of the intestinal mucosa reveals the presence of terminal residues of glucose, mannose and galactose. In conclusion, this study has shown that GCs synthesized in the intestine of C. paleatus exhibit a high level of histochemical complexity and that the lectin binding pattern of the intestinal mucosa is characteristic of each species and the variations are related with the multiple functions performed by the mucus in the digestive tract. The information generated here may be a relevant biological tool for comparing and analyzing the possible glycosidic changes in the intestinal mucus under different conditions, such as changes in diet or different pathological stages.

2012 Annual Summary Report for the Area 3 and Area 5 Radioactive Waste Management Sites at the Nevada National Security Site, Nye County, Nevada: Review of the Performance Assessments and Composite Analyses

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

Shott, G.

2013-03-18

The Maintenance Plan for the Performance Assessments and Composite Analyses for the Area 3 and Area 5 Radioactive Waste Management Sites at the Nevada Test Site (National Security Technologies, LLC 2007a) requires an annual review to assess the adequacy of the performance assessments (PAs) and composite analyses (CAs), with the results submitted to the U.S. Department of Energy (DOE) Office of Environmental Management. The Disposal Authorization Statements for the Area 3 and Area 5 Radioactive Waste Management Sites (RWMSs) also require that such reviews be made and that secondary or minor unresolved issues be tracked and addressed as part ofmore » the maintenance plan (DOE 1999a, 2000). The U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office performed an annual review of the Area 3 and Area 5 RWMS PAs and CAs for fiscal year (FY) 2012. This annual summary report presents data and conclusions from the FY 2012 review, and determines the adequacy of the PAs and CAs. Operational factors (e.g., waste forms and containers, facility design, and waste receipts), closure plans, monitoring results, and research and development (R&D) activities were reviewed to determine the adequacy of the PAs. Likewise, the environmental restoration activities at the Nevada National Security Site (NNSS) relevant to the sources of residual radioactive material that are considered in the CAs, the land-use planning, and the results of the environmental monitoring and R&D activities were reviewed to determine the adequacy of the CAs. Important developments in FY 2012 include the following: Release of a special analysis for the Area 3 RWMS assessing the continuing validity of the PA and CA; Development of a new Area 5 RWMS closure inventory estimate based on disposals through FY 2012; Evaluation of new or revised waste streams by special analysis; and Development of version 4.114 of the Area 5 RWMS GoldSim PA model. The Area 3 RWMS has been in inactive status since July 1, 2006, with the last shipment received in April 2006. The FY 2012 review of operations, facility design, closure plans, monitoring results, and R&D results for the Area 3 RWMS indicates no changes that would impact PA validity. A special analysis using the Area 3 RWMS v2.102 GoldSim PA model was prepared to update the PA results for the Area 3 RWMS in FY 2012. The special analysis concludes that all performance objectives can be met and the Area 3 RWMS PA remains valid. There is no need to the revise the Area 3 RWMS PA. Review of Area 5 RWMS operations, design, closure plans, monitoring results, and R&D activities indicates no significant changes other than an increase in the inventory disposed. The FY 2012 PA results, generated with the Area 5 RWMS v4.114 GoldSim PA model, indicate that there continues to be a reasonable expectation of meeting all performance objectives. The results and conclusions of the Area 5 RWMS PA are judged valid, and there is no need to the revise the PA. A review of changes potentially impacting the CAs indicates that no significant changes occurred in FY 2012. The continuing adequacy of the CAs was evaluated with the new models, and no significant changes that would alter CA results or conclusions were found. The revision of the Area 3 RWMS CA, which will include the Underground Test Area source term (Corrective Action Unit [CAU] 97), is scheduled for FY 2024, following the completion of the Yucca Flat CAU 97 Corrective Action Decision Document/Corrective Action Plan in FY 2016. Inclusion of the Frenchman Flat CAU 98 results in the Area 5 RWMS CA is scheduled for FY 2016, pending the completion of the CAU 98 closure report in FY 2015. Near-term R&D efforts will focus on continuing development of the Area 3 and Area 5 RWMS GoldSim PA/CA and inventory models.« less

Crystal structure of the non-stoichiometric argyrodite compound Ag 7- xGeSe 5I 1- x ( x=0.31). A highly disordered silver superionic conducting material

NASA Astrophysics Data System (ADS)

Belin, Renaud; Aldon, Laurent; Zerouale, Abdel; Belin, Claude; Ribes, Michel

2001-03-01

Single crystals of the Ag 6.69GeSe 5I 0.69 phase have been obtained by iodine transport of the iodine-partially substituted stoichiometric argyrodite compound Ag 7GeSe 5I. This phase crystallizes in the cubic space group F4¯3 m (argyrodite γ-phase, a=10.921(2) Å at -100°C, a=10.972(3) Å at 25°C, Z=4). It is highly disordered both at anion and cation sites. Crystal structure refinements were completed by an anharmonic Gram-Charlier development of the atomic displacement factors of iodine and silver atoms. The structure of Ag 6.69GeSe 5I 0.69 was determined at -100°C and +25°C and was refined to R( F) values of 5.80 and 6.51%, respectively. Both iodine and selenium (Se1) anions have been found disordered and iodine is slightly defective on its crystallographic site. This is correlated to the disorder observed for the two Ag1 and Ag2 cations that provides this material with superionic conducting properties. Analysis of the joint probability density function allowed the visualization of the Ag + diffusion paths within the anionic framework.

Cooperativity and complexity in the binding of anions and cations to a tetratopic ion-pair host.

PubMed

Howe, Ethan N W; Bhadbhade, Mohan; Thordarson, Pall

2014-05-21

Cooperative interactions play a very important role in both natural and synthetic supramolecular systems. We report here on the cooperative binding properties of a tetratopic ion-pair host 1. This host combines two isophthalamide anion recognition sites with two unusual "half-crown/two carbonyl" cation recognition sites as revealed by the combination of single-crystal X-ray analysis of the free host and the 1:2 host:calcium cation complex, together with two-dimensional NMR and computational studies. By systematically comparing all of the binding data to several possible binding models and focusing on four different variants of the 1:2 binding model, it was in most cases possible to quantify these complex cooperative interactions. The data showed strong negative cooperativity (α = 0.01-0.05) of 1 toward chloride and acetate anions, while for cations the results were more variable. Interestingly, in the competitive (CDCl3/CD3OD (9:1, v/v)) solvent, the addition of calcium cations to the tetratopic ion-pair host 1 allosterically switched "on" chloride binding that is otherwise not present in this solvent system. The insight into the complexity of cooperative interactions revealed in this study of the tetratopic ion-pair host 1 can be used to design better cooperative supramolecular systems for information transfer and catalysis.

Female PAs-Where are we today?

PubMed

Curtis, L Gail; Dobbs, Lauren; Hildebrandt, Carol A

2017-09-01

As the physician assistant (PA) profession celebrates its 50th birthday, we can be proud of the gains our profession has accomplished. However, despite the positive reports of job satisfaction, a marked increase in female PA leaders, and overall gains in PA compensation, a significant wage gap remains between male and female PAs. The PA profession is flourishing but it is time female PAs are paid equitably.

Pediatric Eating Assessment Tool-10 as an indicator to predict aspiration in children with esophageal atresia.

PubMed

Soyer, Tutku; Yalcin, Sule; Arslan, Selen Serel; Demir, Numan; Tanyel, Feridun Cahit

2017-10-01

Airway aspiration is a common problem in children with esophageal atresia (EA). Pediatric Eating Assessment Tool-10 (pEAT-10) is a self-administered questionnaire to evaluate dysphagia symptoms in children. A prospective study was performed to evaluate the validity of pEAT-10 to predict aspiration in children with EA. Patients with EA were evaluated for age, sex, type of atresia, presence of associated anomalies, type of esophageal repair, time of definitive treatment, and the beginning of oral feeding. Penetration-aspiration score (PAS) was evaluated with videofluoroscopy (VFS) and parents were surveyed for pEAT-10, dysphagia score (DS) and functional oral intake scale (FOIS). PAS scores greater than 7 were considered as risk of aspiration. EAT-10 values greater than 3 were assessed as abnormal. Higher DS scores shows dysphagia whereas higher FOIS shows better feeding abilities. Forty patients were included. Children with PAS greater than 7 were assessed as PAS+ group, and scores less than 7 were constituted as PAS- group. Demographic features and results of surgical treatments showed no difference between groups (p>0.05). The median values of PAS, pEAT-10 and DS scores were significantly higher in PAS+ group when compared to PAS- group (p<0.05). The sensitivity and specificity of pEAT-10 to predict aspiration were 88% and 77%, and the positive and negative predictive values were 22% and 11%, respectively. Type-C cases had better pEAT-10 and FOIS scores with respect to type-A cases, and both scores were statistically more reliable in primary repair than delayed repair (p<0.05). Among the postoperative complications, only leakage had impact on DS, pEAT-10, PAS and FOIS scores (p<0.05). The pEAT-10 is a valid, simple and reliable tool to predict aspiration in children. Patients with higher pEAT-10 scores should undergo detailed evaluation of deglutitive functions and assessment of risks of aspiration to improve safer feeding strategies. Level II (Development of diagnostic criteria in a consecutive series of patients and a universally applied "gold standard"). Copyright © 2017 Elsevier Inc. All rights reserved.

Deciphering Dimerization Modes of PAS Domains: Computational and Experimental Analyses of the AhR:ARNT Complex Reveal New Insights Into the Mechanisms of AhR Transformation

PubMed Central

Corrada, Dario; Soshilov, Anatoly A.; Denison, Michael S.

2016-01-01

The Aryl hydrocarbon Receptor (AhR) is a transcription factor that mediates the biochemical response to xenobiotics and the toxic effects of a number of environmental contaminants, including dioxins. Recently, endogenous regulatory roles for the AhR in normal physiology and development have also been reported, thus extending the interest in understanding its molecular mechanisms of activation. Since dimerization with the AhR Nuclear Translocator (ARNT) protein, occurring through the Helix-Loop-Helix (HLH) and PER-ARNT-SIM (PAS) domains, is needed to convert the AhR into its transcriptionally active form, deciphering the AhR:ARNT dimerization mode would provide insights into the mechanisms of AhR transformation. Here we present homology models of the murine AhR:ARNT PAS domain dimer developed using recently available X-ray structures of other bHLH-PAS protein dimers. Due to the different reciprocal orientation and interaction surfaces in the different template dimers, two alternative models were developed for both the PAS-A and PAS-B dimers and they were characterized by combining a number of computational evaluations. Both well-established hot spot prediction methods and new approaches to analyze individual residue and residue-pairwise contributions to the MM-GBSA binding free energies were adopted to predict residues critical for dimer stabilization. On this basis, a mutagenesis strategy for both the murine AhR and ARNT proteins was designed and ligand-dependent DNA binding ability of the AhR:ARNT heterodimer mutants was evaluated. While functional analysis disfavored the HIF2α:ARNT heterodimer-based PAS-B model, most mutants derived from the CLOCK:BMAL1-based AhR:ARNT dimer models of both the PAS-A and the PAS-B dramatically decreased the levels of DNA binding, suggesting this latter model as the most suitable for describing AhR:ARNT dimerization. These novel results open new research directions focused at elucidating basic molecular mechanisms underlying the functional activity of the AhR. PMID:27295348

Deciphering Dimerization Modes of PAS Domains: Computational and Experimental Analyses of the AhR:ARNT Complex Reveal New Insights Into the Mechanisms of AhR Transformation.

PubMed

Corrada, Dario; Soshilov, Anatoly A; Denison, Michael S; Bonati, Laura

2016-06-01

The Aryl hydrocarbon Receptor (AhR) is a transcription factor that mediates the biochemical response to xenobiotics and the toxic effects of a number of environmental contaminants, including dioxins. Recently, endogenous regulatory roles for the AhR in normal physiology and development have also been reported, thus extending the interest in understanding its molecular mechanisms of activation. Since dimerization with the AhR Nuclear Translocator (ARNT) protein, occurring through the Helix-Loop-Helix (HLH) and PER-ARNT-SIM (PAS) domains, is needed to convert the AhR into its transcriptionally active form, deciphering the AhR:ARNT dimerization mode would provide insights into the mechanisms of AhR transformation. Here we present homology models of the murine AhR:ARNT PAS domain dimer developed using recently available X-ray structures of other bHLH-PAS protein dimers. Due to the different reciprocal orientation and interaction surfaces in the different template dimers, two alternative models were developed for both the PAS-A and PAS-B dimers and they were characterized by combining a number of computational evaluations. Both well-established hot spot prediction methods and new approaches to analyze individual residue and residue-pairwise contributions to the MM-GBSA binding free energies were adopted to predict residues critical for dimer stabilization. On this basis, a mutagenesis strategy for both the murine AhR and ARNT proteins was designed and ligand-dependent DNA binding ability of the AhR:ARNT heterodimer mutants was evaluated. While functional analysis disfavored the HIF2α:ARNT heterodimer-based PAS-B model, most mutants derived from the CLOCK:BMAL1-based AhR:ARNT dimer models of both the PAS-A and the PAS-B dramatically decreased the levels of DNA binding, suggesting this latter model as the most suitable for describing AhR:ARNT dimerization. These novel results open new research directions focused at elucidating basic molecular mechanisms underlying the functional activity of the AhR.

Accuracy of Skin Cancer Diagnosis by Physician Assistants Compared With Dermatologists in a Large Health Care System.

PubMed

Anderson, Alyce M; Matsumoto, Martha; Saul, Melissa I; Secrest, Aaron M; Ferris, Laura K

2018-05-01

Physician assistants (PAs) are increasingly used in dermatology practices to diagnose skin cancers, although, to date, their diagnostic accuracy compared with board-certified dermatologists has not been well studied. To compare diagnostic accuracy for skin cancer of PAs with that of dermatologists. Medical record review of 33 647 skin cancer screening examinations in 20 270 unique patients who underwent screening at University of Pittsburgh Medical Center-affiliated dermatology offices from January 1, 2011, to December 31, 2015. International Classification of Diseases, Ninth Revision code V76.43 and International Classification of Diseases and Related Health Problems, Tenth Revision code Z12.83 were used to identify pathology reports from skin cancer screening examinations by dermatologists and PAs. Examination performed by a PA or dermatologist. Number needed to biopsy (NNB) to diagnose skin cancer (nonmelanoma, invasive melanoma, or in situ melanoma). Of 20 270 unique patients, 12 722 (62.8%) were female, mean (SD) age at the first visit was 52.7 (17.4) years, and 19 515 patients (96.3%) self-reported their race/ethnicity as non-Hispanic white. To diagnose 1 case of skin cancer, the NNB was 3.9 for PAs and 3.3 for dermatologists (P < .001). Per diagnosed melanoma, the NNB was 39.4 for PAs and 25.4 for dermatologists (P = .007). Patients screened by a PA were significantly less likely than those screened by a dermatologist to be diagnosed with melanoma in situ (1.1% vs 1.8% of visits, P = .02), but differences were not significant for invasive melanoma (0.7% vs 0.8% of visits, P = .83) or nonmelanoma skin cancer (6.1% vs 6.1% of visits, P = .98). Compared with dermatologists, PAs performed more skin biopsies per case of skin cancer diagnosed and diagnosed fewer melanomas in situ, suggesting that the diagnostic accuracy of PAs may be lower than that of dermatologists. Although the availability of PAs may help increase access to care and reduce waiting times for appointments, these findings have important implications for the training, appropriate scope of practice, and supervision of PAs and other nonphysician practitioners in dermatology.

Ligand-induced perturbation of the HIF-2α:ARNT dimer dynamics

PubMed Central

Motta, Stefano

2018-01-01

Hypoxia inducible factors (HIFs) are transcription factors belonging to the basic helix−loop−helix PER-ARNT-SIM (bHLH-PAS) protein family with a role in sensing oxygen levels in the cell. Under hypoxia, the HIF-α degradation pathway is blocked and dimerization with the aryl hydrocarbon receptor nuclear translocator (ARNT) makes HIF-α transcriptionally active. Due to the common hypoxic environment of tumors, inhibition of this mechanism by destabilization of HIF-α:ARNT dimerization has been proposed as a promising therapeutic strategy. Following the discovery of a druggable cavity within the PAS-B domain of HIF-2α, research efforts have been directed to identify artificial ligands that can impair heterodimerization. Although the crystallographic structures of the HIF-2α:ARNT complex have elucidated the dimer architecture and the 0X3-inhibitor placement within the HIF-2α PAS-B, unveiling the inhibition mechanism requires investigation of how ligand-induced perturbations could dynamically propagate through the structure and affect dimerization. To this end, we compared evolutionary features, intrinsic dynamics and energetic properties of the dimerization interfaces of HIF-2α:ARNT in both the apo and holo forms. Residue conservation analysis highlighted inter-domain connecting elements that have a role in dimerization. Analysis of domain contributions to the dimerization energy demonstrated the importance of bHLH and PAS-A of both partners and of HIF-2α PAS-B domain in dimer stabilization. Among quaternary structure oscillations revealed by Molecular Dynamics simulations, the hinge-bending motion of the ARNT PAS-B domain around the flexible PAS-A/PAS-B linker supports a general model for ARNT dimerization in different heterodimers. Comparison of the HIF-2α:ARNT dynamics in the apo and 0X3-bound forms indicated a model of inhibition where the HIF-2α-PAS-B interfaces are destabilised as a result of water-bridged ligand-protein interactions and these local effects allosterically propagate to perturb the correlated motions of the domains and inter-domain communication. These findings will guide the design of improved inhibitors to contrast cell survival in tumor masses. PMID:29489822

Closure on the single scattering albedo in the WRF-Chem framework using data from the MILAGRO campaign

NASA Astrophysics Data System (ADS)

Barnard, J. C.; Fast, J. D.; Paredes-Miranda, G.; Arnott, W. P.

2009-02-01

Data from the MILAGRO field campaign, which took place in the Mexico City Metropolitan Area (MCMA) during March 2006, is used to perform a closure experiment between aerosol chemical properties and aerosol optical properties. Measured aerosol chemical properties, obtained from the MILAGRO T1 site, are fed to two different "chemical to optical properties" modules. One module uses a sectional approach and is identical to that used in the WRF-Chem model, while the other is based on a modal approach. This modal code is employed as an independent check on the WRF-Chem module. Both modules compute aerosol optical properties and, in particular, the single-scattering albedo, ϖ0, as a function of time. The single-scattering albedos are compared to independent measurements obtained from a photoacoustic spectrometer (PAS). Because chemical measurements of the aerosol coarse mode were not available, and the inlet of the PAS could not ingest aerosols larger than about 2 to 3 μm, we focus here on the fine-mode ϖ0. At 870 nm, the wavelength of the PAS measurements, the agreement between the computed (modal and WRF-Chem) and observed fine-mode ϖ0, averaged over the course of the campaign, is reasonably good. The observed ϖ0 value is 0.77, while for both modules, the calculated value was 0.75 resulting in a difference of 0.02 between observations and both computational approaches. This difference is less than the uncertainty of the observed ϖ0 values (6%, or 0.05), and therefore "closure" is achieved, at least for mean values. After adjusting some properties of black carbon absorption and mass concentration within plausible uncertainty limits, the two modules simulate well the diurnal variation of ϖ0, and the absorption coefficient, Babs, but are less successful in calculating the variation of the scattering coefficient, Bscat. This difficulty is probably caused by the presence of larger particles during the day when windblown dust is ubiquitous; this dust likely increases the proportion of large particles introduced into the PAS. The dust also contributes to a very large aerosol mass loading in the coarse mode, and neglect of the coarse mode may cause significant errors, estimated to be as large as 0.07, in the calculation and measurement of ambient ϖ0. Finally, the observed ϖ0 is compared to the ϖ0 computed by the full WRF-Chem model, which includes prognostic aerosol chemistry. Unlike the results discussed above, a comparison between observed and simulated ϖ0 values reveals major differences. This large discrepancy is probably due, in part, to poor characterization of emissions near the T1 site, particularly black carbon emissions.

Nature of the chemical bond and prediction of radiation tolerance in pyrochlore and defect fluorite compounds

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

Lumpkin, Gregory R.; Institute of Materials and Engineering Science, Australian Nuclear Science and Technology Organisation, Private Mail Bag 1, Menai, NSW 2234; Pruneda, Miguel

2007-04-15

The radiation tolerance of synthetic pyrochlore and defect fluorite compounds has been studied using ion irradiation. We show that the results can be quantified in terms of the critical temperature for amorphization, structural parameters, classical Pauling electronegativity difference, and disorder energies. Our results demonstrate that radiation tolerance is correlated with a change in the structure from pyrochlore to defect fluorite, a smaller unit cell dimension, and lower cation-anion disorder energy. Radiation tolerance is promoted by an increase in the Pauling cation-anion electronegativity difference or, in other words, an increase in the ionicity of the chemical bonds. A further analysis ofmore » the data indicates that, of the two possible cation sites in ideal pyrochlore, the smaller B-site cation appears to play the major role in bonding. This result is supported by ab initio calculations of the structure and bonding, showing a correlation between the Mulliken overlap populations of the B-site cation and the critical temperature. - Graphical abstract: Three-dimensional representation of the predicted critical amorphization temperature in pyrochlores.« less

Multiple Ligands Targeting Cholinesterases and β-Amyloid: Synthesis, Biological Evaluation of Heterodimeric Compounds with Benzylamine Pharmacophore.

PubMed

Szałaj, Natalia; Bajda, Marek; Dudek, Katarzyna; Brus, Boris; Gobec, Stanislav; Malawska, Barbara

2015-08-01

Alzheimer's disease (AD) is a fatal and complex neurodegenerative disorder for which effective treatment remains the unmet challenge. Using donepezil as a starting point, we aimed to develop novel potential anti-AD agents with a multidirectional biological profile. We designed the target compounds as dual binding site acetylcholinesterase inhibitors, where the N-benzylamine pharmacophore is responsible for interactions with the catalytic anionic site of the enzyme. The heteroaromatic fragment responsible for interactions with the peripheral anionic site was modified and three different heterocycles were introduced: isoindoline, isoindolin-1-one, and saccharine. Based on the results of the pharmacological evaluation, we identified compound 8b with a saccharine moiety as the most potent and selective human acetylcholinesterase inhibitor (IC50  = 33 nM) and beta amyloid aggregation inhibitor. It acts as a non-competitive acetylcholinesterase inhibitor and is able to cross the blood-brain barrier in vitro. We believe that compound 8b represents an important lead compound for further development as potential anti-AD agent. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Molecular recognition principles and stationary-phase characteristics of topoisomer-selective chemoaffinity materials for chromatographic separation of circular plasmid DNA topoisomers.

PubMed

Mahut, Marek; Lindner, Wolfgang; Lämmerhofer, Michael

2012-01-18

We recently discovered the molecular recognition capability of a quinine carbamate ligand attached to silica as a powerful chemoaffinity material for the chromatographic separation of circular plasmid topoisomers of different linking numbers. In this paper we develop structure-selectivity relationship studies to figure out the essential structural features for topoisomer recognition. By varying different moieties of the original cinchonan-derived selector, it was shown that intercalation by the quinoline moiety of the ligand as assumed initially as the working hypothesis is not an essential feature for topoisomer recognition during chromatography. We found that the key elements for topoisomer selectivity are the presence of a rigid weak anion-exchange site and a H-donor site separated from each other in a defined distance by a 4-atom spacer. Additionally, incorporation of the weak anion-exchange site into a cyclic ring structure provides greater rigidity of the ligand molecule and turned out to be advantageous, if not mandatory, for (close to) baseline separation. © 2011 American Chemical Society

Characterization of genome in tetraploid StY species of Elymus (Triticeae: Poaceae) using sequential FISH and GISH.

PubMed

Liu, Ruijuan; Wang, Richard R-C; Yu, Feng; Lu, Xingwang; Dou, Quanwen

2017-08-01

Genomes of ten species of Elymus, either presumed or known as tetraploid StY, were characterized using fluorescence in situ hybridization (FISH) and genomic in situ hybridization (GISH). These tetraploid species could be grouped into three categories. Type I included StY genome reported species-Roegneria pendulina, R. nutans, R. glaberrima, R. ciliaris, and Elymus nevskii, and StY genome presumed species-R. sinica, R. breviglumis, and R. dura, whose genome could be separated into two sets based on different GISH intensities. Type I genome constitution was deemed as putative StY. The St genome were mainly characterized with intense hybridization with pAs1, fewer AAG sites, and linked distribution of 5S rDNA and 18S-26S rDNA, while the Y genome with less intense hybridization with pAs1, more varied AAG sites, and isolated distribution of 5S rDNA and 18S-26S rDNA. Nevertheless, further genomic variations were detected among the different StY species. Type II included E. alashanicus, whose genome could be easily separated based on GISH pattern. FISH and GISH patterns suggested that E. alashanicus comprised a modified St genome and an unknown genome. Type III included E. longearistatus, whose genome could not be separated by GISH and was designated as St l Y l . Notably, a close relationship between S l and Y l genomes was observed.

Games network and application to PAs system.

PubMed

Chettaoui, C; Delaplace, F; Manceny, M; Malo, M

2007-02-01

In this article, we present a game theory based framework, named games network, for modeling biological interactions. After introducing the theory, we more precisely describe the methodology to model biological interactions. Then we apply it to the plasminogen activator system (PAs) which is a signal transduction pathway involved in cancer cell migration. The games network theory extends game theory by including the locality of interactions. Each game in a games network represents local interactions between biological agents. The PAs system is implicated in cytoskeleton modifications via regulation of actin and microtubules, which in turn favors cell migration. The games network model has enabled us a better understanding of the regulation involved in the PAs system.

Pain Amplification Syndrome: A Biopsychosocial Approach.

PubMed

Namerow, Lisa B; Kutner, Emily C; Wakefield, Emily C; Rzepski, Barbara R; Sahl, Robert A

2016-08-01

Pediatric neurologists frequently encounter patients who present with significant musculoskeletal pain that cannot be attributed to a specific injury or illness, which can often be defined as pain amplification syndrome (PAS). PAS in children and adolescents is the result of a heightened pain sensitivity pathway, which is intensified by significant biological, psychological, and social contributors. Appropriate assessment and multimodal intervention of PAS are crucial to treatment success, including neurology and behavioral health collaborative treatment plans to restore patient function and reduce pain perception. Pediatric neurologists are imperative in the identification of patients with PAS, providing the family assurance in diagnosis and validation of pain, and directing patients to the appropriate multidisciplinary treatment pathway. Copyright © 2016 Elsevier Inc. All rights reserved.

Tissue distribution, core biosynthesis and diversification of pyrrolizidine alkaloids of the lycopsamine type in three Boraginaceae species.

PubMed

Frölich, Cordula; Ober, Dietrich; Hartmann, Thomas

2007-04-01

Three species of the Boraginaceae were studied: greenhouse-grown plants of Heliotropium indicum and Agrobacterium rhizogenes transformed roots cultures (hairy roots) of Cynoglossum officinale and Symphytum officinale. The species-specific pyrrolizidine alkaloid (PA) profiles of the three systems were established by GC-MS. All PAs are genuinely present as N-oxides. In H. indicum the tissue-specific PA distribution revealed the presence of PAs in all tissues with the highest levels in the inflorescences which in a flowering plant may account for more than 70% of total plant alkaloid. The sites of PA biosynthesis vary among species. In H. indicum PAs are synthesized in the shoot but not roots whereas they are only made in shoots for C. officinale and in roots of S. officinale. Classical tracer studies with radioactively labelled precursor amines (e.g., putrescine, spermidine and homospermidine) and various necine bases (trachelanthamidine, supinidine, retronecine, heliotridine) and potential ester alkaloid intermediates (e.g., trachelanthamine, supinine) were performed to evaluate the biosynthetic sequences. It was relevant to perform these comparative studies since the key enzyme of the core pathway, homospermidine synthase, evolved independently in the Boraginaceae and, for instance, in the Asteraceae [Reimann, A., Nurhayati, N., Backenkohler, A., Ober, D., 2004. Repeated evolution of the pyrrolizidine alkaloid-mediated defense system in separate angiosperm lineages. Plant Cell 16, 2772-2784.]. These studies showed that the core pathway for the formation of trachelanthamidine from putrescine and spermidine via homospermidine is common to the pathway in Senecio ssp. (Asteraceae). In both pathways homospermidine is further processed by a beta-hydroxyethylhydrazine sensitive diamine oxidase. Further steps of PA biosynthesis starting with trachelanthamidine as common precursor occur in two successive stages. Firstly, the necine bases are structurally modified and either before or after this modification are converted into their O(9)-esters by esterification with one of the stereoisomers of 2,3-dihydroxy-2-isopropylbutyric acid, the unique necic acid of PAs of the lycopsamine type. Secondly, the necine O(9)-esters may be further diversified by O(7)- and/or O(3')-acylation.

Occurrence and geochemistry of radium in water from principal drinking-water aquifer systems of the United States

USGS Publications Warehouse

Szabo, Z.; dePaul, V.T.; Fischer, J.M.; Kraemer, T.F.; Jacobsen, E.

2012-01-01

A total of 1270 raw-water samples (before treatment) were collected from 15 principal and other major aquifer systems (PAs) used for drinking water in 45 states in all major physiographic provinces of the USA and analyzed for concentrations of the Ra isotopes 224Ra, 226Ra and 228Ra establishing the framework for evaluating Ra occurrence. The US Environmental Protection Agency Maximum Contaminant Level (MCL) of 0.185Bq/L (5pCi/L) for combined Ra ( 226Ra plus 228Ra) for drinking water was exceeded in 4.02% (39 of 971) of samples for which both 226Ra and 228Ra were determined, or in 3.15% (40 of 1266) of the samples in which at least one isotope concentration ( 226Ra or 228Ra) was determined. The maximum concentration of combined Ra was 0.755Bq/L (20.4pCi/L) in water from the North Atlantic Coastal Plain quartzose sand aquifer system. All the exceedences of the MCL for combined Ra occurred in water samples from the following 7PAs (in order of decreasing relative frequency of occurrence): the Midcontinent and Ozark Plateau Cambro-Ordovician dolomites and sandstones, the North Atlantic Coastal Plain, the Floridan, the crystalline rocks (granitic, metamorphic) of New England, the Mesozoic basins of the Appalachian Piedmont, the Gulf Coastal Plain, and the glacial sands and gravels (highest concentrations in New England).The concentration of Ra was consistently controlled by geochemical properties of the aquifer systems, with the highest concentrations most likely to be present where, as a consequence of the geochemical environment, adsorption of the Ra was slightly decreased. The result is a slight relative increase in Ra mobility, especially notable in aquifers with poor sorptive capacity (Fe-oxide-poor quartzose sands and carbonates), even if Ra is not abundant in the aquifer solids. The most common occurrence of elevated Ra throughout the USA occurred in anoxic water (low dissolved-O 2) with high concentrations of Fe or Mn, and in places, high concentrations of the competing ions Ca, Mg, Ba and Sr, and occasionally of dissolved solids, K, SO 4 and HCO 3. The other water type to frequently contain elevated concentrations of the Ra radioisotopes was acidic (low pH), and had in places, high concentrations of NO 3 and other acid anions, and on occasion, of the competing divalent cations, Mn and Al. One or the other of these broad water types was commonly present in each of the PAs in which elevated concentrations of combined Ra occurred. Concentrations of 226Ra or 228Ra or combined Ra correlated significantly with those of the above listed water-quality constituents (on the basis of the non-parametric Spearman correlation technique) and loaded on principal components describing the above water types from the entire data set and for samples from the PAs with the highest combined Ra concentrations.Concentrations of 224Ra and 226Ra were significantly correlated to those of 228Ra (Spearman's rank correlation coefficient, +0.236 and +0.326, respectively). Activity ratios of 224Ra/ 228Ra in the water samples were mostly near 1 when concentrations of both isotopes were greater than or equal to 0.037Bq/L (1pCi/L), the level above which analytical results were most reliable. Co-occurrence among these highest concentrations of the Ra radionuclides was most likely in those PAs where chemical conditions are most conducive to Ra mobility (e.g. acidic North Atlantic Coastal Plain). The concentrations of 224Ra were occasionally greater than 0.037Bq/L and the ratios of 224Ra/ 228Ra were generally highest in the PAs composed of alluvial sands and Cretaceous/Tertiary sandstones from the western USA, likely because concentrations of 224Ra are enhanced in solution relative to those of 228Ra by alpha recoil from the aquifer matrix. Rapid adsorption of the two Ra isotopes (controlled by the alkaline and oxic aquifer geochemistry) combined with preferential faster recoil of 224Ra generates a 224Ra/ 228Ra ratio much greater than

Design principles for solid-state lithium superionic conductors.

PubMed

Wang, Yan; Richards, William Davidson; Ong, Shyue Ping; Miara, Lincoln J; Kim, Jae Chul; Mo, Yifei; Ceder, Gerbrand

2015-10-01

Lithium solid electrolytes can potentially address two key limitations of the organic electrolytes used in today's lithium-ion batteries, namely, their flammability and limited electrochemical stability. However, achieving a Li(+) conductivity in the solid state comparable to existing liquid electrolytes (>1 mS cm(-1)) is particularly challenging. In this work, we reveal a fundamental relationship between anion packing and ionic transport in fast Li-conducting materials and expose the desirable structural attributes of good Li-ion conductors. We find that an underlying body-centred cubic-like anion framework, which allows direct Li hops between adjacent tetrahedral sites, is most desirable for achieving high ionic conductivity, and that indeed this anion arrangement is present in several known fast Li-conducting materials and other fast ion conductors. These findings provide important insight towards the understanding of ionic transport in Li-ion conductors and serve as design principles for future discovery and design of improved electrolytes for Li-ion batteries.

Ab initio correlated study of the Al13H- anion: Isomers, their kinetic stability and vertical detachment energies

NASA Astrophysics Data System (ADS)

Moc, Jerzy

2012-01-01

We report correlated ab initio calculations for the Al13H- cluster anion isomers, their kinetic stability and vertical detachment energies (VDEs). Of the two most energetically favored anion structures involving H atom in terminal and threefold bridged sites of the icosahedral Al13-, the higher energy ‘threefold bridged' isomer is shown to be of low kinetic stability. Our results are consistent with the recent photoelectron spectroscopy (PE) study of Grubisic et al. who observed two distinct Al13H- isomers, one of them identified as ‘metastable'. The VDE energies computed at the CCSD(T)/aug-cc-pVTZ//MP2/aug-cc-pVDZ level for the ‘terminal' and ‘threefold bridged' Al13H- isomers of 3.21 and 2.32 eV are in good agreement with those determined in the PE study.

Protected Areas' Impacts on Brazilian Amazon Deforestation: Examining Conservation-Development Interactions to Inform Planning.

PubMed

Pfaff, Alexander; Robalino, Juan; Herrera, Diego; Sandoval, Catalina

2015-01-01

Protected areas are the leading forest conservation policy for species and ecoservices goals and they may feature in climate policy if countries with tropical forest rely on familiar tools. For Brazil's Legal Amazon, we estimate the average impact of protection upon deforestation and show how protected areas' forest impacts vary significantly with development pressure. We use matching, i.e., comparisons that are apples-to-apples in observed land characteristics, to address the fact that protected areas (PAs) tend to be located on lands facing less pressure. Correcting for that location bias lowers our estimates of PAs' forest impacts by roughly half. Further, it reveals significant variation in PA impacts along development-related dimensions: for example, the PAs that are closer to roads and the PAs closer to cities have higher impact. Planners have multiple conservation and development goals, and are constrained by cost, yet still conservation planning should reflect what our results imply about future impacts of PAs.

Step-scan T cell-based differential Fourier transform infrared photoacoustic spectroscopy (DFTIR-PAS) for detection of ambient air contaminants

NASA Astrophysics Data System (ADS)

Liu, Lixian; Mandelis, Andreas; Huan, Huiting; Melnikov, Alexander

2016-10-01

A step-scan differential Fourier transform infrared photoacoustic spectroscopy (DFTIR-PAS) using a commercial FTIR spectrometer was developed theoretically and experimentally for air contaminant monitoring. The configuration comprises two identical, small-size and low-resonance-frequency T cells satisfying the conflicting requirements of low chopping frequency and limited space in the sample compartment. Carbon dioxide (CO2) IR absorption spectra were used to demonstrate the capability of the DFTIR-PAS method to detect ambient pollutants. A linear amplitude response to CO2 concentrations from 100 to 10,000 ppmv was observed, leading to a theoretical detection limit of 2 ppmv. The differential mode was able to suppress the coherent noise, thereby imparting the DFTIR-PAS method with a better signal-to-noise ratio and lower theoretical detection limit than the single mode. The results indicate that it is possible to use step-scan DFTIR-PAS with T cells as a quantitative method for high sensitivity analysis of ambient contaminants.

PA and NP productivity in the Veterans Health Administration.

PubMed

Moran, Eileen A; Basa, Edesha; Gao, Jian; Woodmansee, Denni; Almenoff, Peter L; Hooker, Roderick S

2016-07-01

This study assessed the 2014 clinical productivity of 5,959 physician assistants (PAs) and nurse practitioners (NPs) in the US Department of Veterans Affairs' Veterans Health Administration (VHA). Total work relative value units divided by the direct clinical full-time equivalent measured annual productivity, and correlated factors were examined using weighted analysis of variance. PAs and NPs in adult primary care roles were more productive than those in other specialties. Both providers were more productive in rural than in nonrural settings and less productive in teaching than nonteaching hospitals. Men were slightly more productive than women but age and years of VHA employment were not correlates of productivity. PAs were more productive when their scope of practice allowed significant autonomy; NP productivity was unaffected by supervisory requirements. PAs and NPs are an important component of the VHA provider workforce, and their productivity correlates with a number of factors. More organizational research is necessary to better understand the contributing roles PAs and NPs provide in a rapidly evolving, vertically integrated, national health delivery system.

Functional Characterization of a Dihydroflavanol 4-Reductase from the Fiber of Upland Cotton (Gossypium hirsutum).

PubMed

Wang, Le; Zhu, Yue; Wang, Peng; Fan, Qiang; Wu, Yao; Peng, Qing-Zhong; Xia, Gui-Xian; Wu, Jia-He

2016-01-26

Dihydroflavanol 4-reductase (DFR) is a key later enzyme involved in two polyphenols' (anthocyanins and proanthocyanidins (PAs)) biosynthesis, however it is not characterized in cotton yet. In present reports, a DFR cDNA homolog (designated as GhDFR1) was cloned from developing fibers of upland cotton. Silencing GhDFR1 in cotton by virus-induced gene silencing led to significant decrease in accumulation of anthocyanins and PAs. More interestingly, based on LC-MS analysis, two PA monomers, (-)-epicatachin and (-)-epigallocatachin, remarkably decreased in content in fibers of GhDFR1-silenced plants, but two new monomers, (-)-catachin and (-)-gallocatachin were present compared to the control plants infected with empty vector. The ectopic expression of GhDFR1 in an Arabidopsis TT3 mutant allowed for reconstruction of PAs biosynthesis pathway and led to accumulation of PAs in seed coat. Taken together, these data demonstrate that GhDFR1 contributes to the biosynthesis of anthocyanins and PAs in cotton.

Personality Assessment Screener, Childhood Abuse, and Adult Partner Violence in African American Women Using Primary Care.

PubMed

Porcerelli, John H; Hurrell, Kristen; Cogan, Rosemary; Jeffries, Keturah; Markova, Tsveti

2015-12-01

This study assessed the relationship between psychopathology with the Personality Assessment Screener (PAS) and childhood physical and sexual abuse and adult physical and sexual partner violence in a primary care sample of 98 urban-dwelling African American women. Patients completed the PAS, the Childhood Trauma Questionnaire, and the Conflict Tactics Scale. The PAS total score significantly correlated with all measures of childhood and adult abuse. Stepwise regression analyses revealed that PAS element scores of Suicidal Thinking and Hostile Control significantly predicted a history of childhood physical abuse; Suicidal Thinking, Hostile Control, and Acting Out significantly predicted a history of childhood sexual abuse; Suicidal Thinking, Negative Affect, and Alienation significantly predicted current adult partner physical violence; and Psychotic Features, Alcohol Problems, and Anger Control significantly predicted current adult sexual partner violence. The PAS appears to be a useful measure for fast-paced primary care settings for identifying patients who need a more thorough assessment for abuse. © The Author(s) 2015.

Efficiencies and Optimization of Weak Base Anion Ion-Exchange Resin for Groundwater Hexavalent Chromium Removal at Hanford

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

Nesham, Dean O.; Ivarson, Kristine A.; Hanson, James P.

2014-02-03

The U.S. Department of Energy’s (DOE’s) contractor, CH2M HILL Plateau Remediation Company, has successfully converted a series of groundwater treatment facilities to use a new treatment resin that is delivering more than $3 million in annual cost savings and efficiency in treating groundwater contamination at the DOE Hanford Site in southeastern Washington State. During the production era, the nuclear reactors at the Hanford Site required a continuous supply of high-quality cooling water during operations. Cooling water consumption ranged from about 151,417 to 378,541 L/min (40,000 to 100,000 gal/min) per reactor, depending on specific operating conditions. Water from the Columbia Rivermore » was filtered and treated chemically prior to use as cooling water, including the addition of sodium dichromate as a corrosion inhibitor. Hexavalent chromium was the primary component of the sodium dichromate and was introduced into the groundwater at the Hanford Site as a result of planned and unplanned discharges from the reactors starting in 1944. Groundwater contamination by hexavalent chromium and other contaminants related to nuclear reactor operations resulted in the need for groundwater remedial actions within the Hanford Site reactor areas. Beginning in 1995, groundwater treatment methods were evaluated, leading to the use of pump-and-treat facilities with ion exchange using Dowex™ 21K, a regenerable, strong-base anion exchange resin. This required regeneration of the resin, which was performed offsite. In 2008, DOE recognized that regulatory agreements would require significant expansion for the groundwater chromium treatment capacity. As a result, CH2M HILL performed testing at the Hanford Site in 2009 and 2010 to demonstrate resin performance in the specific groundwater chemistry at different waste sites. The testing demonstrated that a weak-base anion, single-use resin, specifically ResinTech SIR-700 ®, was effective at removing chromium, had a significantly higher capacity, could be disposed of efficiently onsite, and would eliminate the complexities and programmatic risks from sampling, packaging, transportation, and return of resin for regeneration.« less

Concurrent Automated Sequencing of the Glycan and Peptide Portions of O-Linked Glycopeptide Anions by Ultraviolet Photodissociation Mass Spectrometry

PubMed Central

Madsen, James A.; Ko, Byoung Joon; Xu, Hua; Iwashkiw, Jeremy A.; Robotham, Scott A.; Shaw, Jared B.; Feldman, Mario F.; Brodbelt, Jennifer S.

2013-01-01

O -glycopeptides are often acidic owing to the frequent occurrence of acidic saccharides in the glycan, rendering traditional proteomic workflows that rely on positive mode tandem mass spectrometry (MS/MS) less effective. In this report, we demonstrate the utility of negative mode ultraviolet photodissociation (UVPD) MS for the characterization of acidic O-linked glycopeptide anions. This method was evaluated for a series of singly- and multiply-deprotonated glycopeptides from the model glycoprotein kappa casein, resulting in production of both peptide and glycan product ions that afforded 100% sequence coverage of the peptide and glycan moieties from a single MS/MS event. The most abundant and frequent peptide sequence ions were a/x-type products, which, importantly, were found to retain the labile glycan modifications. The glycan-specific ions mainly arose from glycosidic bond cleavages (B, Y, C, and Z ions) in addition to some less common cross-ring cleavages. Based on the UVPD fragmentation patterns, an automated database searching strategy (based on the MassMatrix algorithm) was designed that is specific for the analysis of glycopeptide anions by UVPD. This algorithm was used to identify glycopeptides from mixtures of glycosylated and non-glycosylated peptides, sequence both glycan and peptide moieties simultaneously, and pinpoint the correct site(s) of glycosylation. This methodology was applied to uncover novel site-specificity of the O-linked glycosylated OmpA/MotB from the “superbug” A. baumannii to help aid in the elucidation of the functional role that protein glycosylation plays in pathogenesis. PMID:24006841

Structural, Chemical, and Dynamical Frustration: Origins of Superionic Conductivity in closo -Borate Solid Electrolytes

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

Kweon, Kyoung E.; Varley, Joel B.; Shea, Patrick

Li 2B 12H 12, Na 2B 12H 12, and their closo-borate relatives exhibit unusually high ionic conductivity, making them attractive as a new class of candidate electrolytes in solid-state Li- and Na-ion batteries. However, further optimization of these materials requires a deeper understanding of the fundamental mechanisms underlying ultrafast ion conduction. To this end, we use ab initio molecular dynamics simulations and density-functional calculations to explore the motivations for cation diffusion. We find that superionic behavior in Li 2B 12H 12 and Na 2B 12H 12 results from a combination of key structural, chemical, and dynamical factors that introduce intrinsicmore » frustration and disorder. A statistical metric is used to show that the structures exhibit a high density of accessible interstitial sites and site types, which correlates with the flatness of the energy landscape and the observed cation mobility. Furthermore, cations are found to dock to specific anion sites, leading to a competition between the geometric symmetry of the anion and the symmetry of the lattice itself, which can facilitate cation hopping. Finally, facile anion reorientations and other low-frequency thermal vibrations lead to fluctuations in the local potential that enhance cation mobility by creating a local driving force for hopping. In conclusion, we discuss the relevance of each factor for developing new ionic conductivity descriptors that can be used for discovery and optimization of closo-borate solid electrolytes, as well as superionic conductors more generally.« less

Structural, Chemical, and Dynamical Frustration: Origins of Superionic Conductivity in closo -Borate Solid Electrolytes

DOE PAGES

Kweon, Kyoung E.; Varley, Joel B.; Shea, Patrick; ...

2017-10-11

Li 2B 12H 12, Na 2B 12H 12, and their closo-borate relatives exhibit unusually high ionic conductivity, making them attractive as a new class of candidate electrolytes in solid-state Li- and Na-ion batteries. However, further optimization of these materials requires a deeper understanding of the fundamental mechanisms underlying ultrafast ion conduction. To this end, we use ab initio molecular dynamics simulations and density-functional calculations to explore the motivations for cation diffusion. We find that superionic behavior in Li 2B 12H 12 and Na 2B 12H 12 results from a combination of key structural, chemical, and dynamical factors that introduce intrinsicmore » frustration and disorder. A statistical metric is used to show that the structures exhibit a high density of accessible interstitial sites and site types, which correlates with the flatness of the energy landscape and the observed cation mobility. Furthermore, cations are found to dock to specific anion sites, leading to a competition between the geometric symmetry of the anion and the symmetry of the lattice itself, which can facilitate cation hopping. Finally, facile anion reorientations and other low-frequency thermal vibrations lead to fluctuations in the local potential that enhance cation mobility by creating a local driving force for hopping. In conclusion, we discuss the relevance of each factor for developing new ionic conductivity descriptors that can be used for discovery and optimization of closo-borate solid electrolytes, as well as superionic conductors more generally.« less

A concise entry into nonsymmetrical alkyl polyamines.

PubMed

Pirali, Tracey; Callipari, Grazia; Ercolano, Emanuela; Genazzani, Armando A; Giovenzana, Giovanni Battista; Tron, Gian Cesare

2008-10-02

The synthesis of nonsymmetrical polyamines (PAs) has, up to now, been problematic due to lengthy synthetic procedures, lack of regioselectivity, and very poor atom economy. An innovative synthetic protocol for nonsymmetrical PAs using a modified Ugi reaction ( N-split Ugi) which simplifies the synthesis of these tricky compounds is described. We believe that this new synthesis may open the door for the generation of new and pharmacologically active PAs.

Physician-assisted suicide of patients with dementia. A medical ethical analysis with a special focus on patient autonomy.

PubMed

Gather, Jakov; Vollmann, Jochen

2013-01-01

For many years there has been a controversial international debate on physician-assisted suicide (PAS). While proponents of PAS regularly refer to the unbearable suffering and the right of self-determination of incurably ill patients, critics often warn about the diverse risks of abuse. In our article, we aim to present ethical arguments for and against PAS for patients in an early stage of dementia. Our focus shall be on ethical questions of autonomy, conceptual and empirical findings on competence and the assessment of mental capacity to make health care decisions. While the capacity to make health care decisions represents an ethically significant precondition for PAS, it becomes more and more impaired in the course of the dementia process. We present conditions that should be met in order to ethically justify PAS for patients with dementia. From both a psychiatric and an ethical perspective, a thorough differential diagnosis and an adequate medical and psychosocial support for patients with dementia considering PAS and their relatives should be guaranteed. If, after due deliberation, the patient still wishes assistance with suicide, a transparent and documented assessment of competence should be conducted by a professional psychiatrist. Copyright © 2013 Elsevier Ltd. All rights reserved.

Conservation performance of different conservation governance regimes in the Peruvian Amazon.

PubMed

Schleicher, Judith; Peres, Carlos A; Amano, Tatsuya; Llactayo, William; Leader-Williams, Nigel

2017-09-12

State-controlled protected areas (PAs) have dominated conservation strategies globally, yet their performance relative to other governance regimes is rarely assessed comprehensively. Furthermore, performance indicators of forest PAs are typically restricted to deforestation, although the extent of forest degradation is greater. We address these shortfalls through an empirical impact evaluation of state PAs, Indigenous Territories (ITs), and civil society and private Conservation Concessions (CCs) on deforestation and degradation throughout the Peruvian Amazon. We integrated remote-sensing data with environmental and socio-economic datasets, and used propensity-score matching to assess: (i) how deforestation and degradation varied across governance regimes between 2006-2011; (ii) their proximate drivers; and (iii) whether state PAs, CCs and ITs avoided deforestation and degradation compared with logging and mining concessions, and the unprotected landscape. CCs, state PAs, and ITs all avoided deforestation and degradation compared to analogous areas in the unprotected landscape. CCs and ITs were on average more effective in this respect than state PAs, showing that local governance can be equally or more effective than centralized state regimes. However, there were no consistent differences between conservation governance regimes when matched to logging and mining concessions. Future impact assessments would therefore benefit from further disentangling governance regimes across unprotected land.

Formation of a repressive complex in the mammalian circadian clock is mediated by the secondary pocket of CRY1

DOE PAGES

Michael, Alicia K.; Fribourgh, Jennifer L.; Chelliah, Yogarany; ...

2017-01-31

The basic helix-loop-helix PAS domain (bHLH-PAS) transcription factor CLOCK:BMAL1 (brain and muscle Arnt-like protein 1) sits at the core of the mammalian circadian transcription/translation feedback loop. Precise control of CLOCK:BMAL1 activity by coactivators and repressors establishes the ~24-h periodicity of gene expression. Formation of a repressive complex, defined by the core clock proteins cryptochrome 1 (CRY1):CLOCK:BMAL1, plays an important role controlling the switch from repression to activation each day. Here in this paper, we show that CRY1 binds directly to the PAS domain core of CLOCK: BMAL1, driven primarily by interaction with the CLOCK PAS-B domain. Integrative modeling and solutionmore » X-ray scattering studies unambiguously position a key loop of the CLOCK PAS-B domain in the secondary pocket of CRY1, analogous to the antenna chromophore-binding pocket of photolyase. CRY1 docks onto the transcription factor alongside the PAS domains, extending above the DNA-binding bHLH domain. Single point mutations at the interface on either CRY1 or CLOCK disrupt formation of the ternary complex, highlighting the importance of this interface for direct regulation of CLOCK:BMAL1 activity by CRY1.« less

Sodic alkaline stress mitigation by interaction of nitric oxide and polyamines involves antioxidants and physiological strategies in Solanum lycopersicum.

PubMed

Gong, Biao; Li, Xiu; Bloszies, Sean; Wen, Dan; Sun, Shasha; Wei, Min; Li, Yan; Yang, Fengjuan; Shi, Qinghua; Wang, Xiufeng

2014-06-01

Nitric oxide (NO) and polyamines (PAs) are two kinds of important signal in mediating plant tolerance to abiotic stress. In this study, we observed that both NO and PAs decreased alkaline stress in tomato plants, which may be a result of their role in regulating nutrient balance and reactive oxygen species (ROS), thereby protecting the photosynthetic system from damage. Further investigation indicated that NO and PAs induced accumulation of each other. Furthermore, the function of PAs could be removed by a NO scavenger, cPTIO. On the other hand, application of MGBG, a PA synthesis inhibitor, did little to abolish the function of NO. To further elucidate the mechanism by which NO and PAs alleviate alkaline stress, the expression of several genes associated with abiotic stress was analyzed by qRT-PCR. NO and PAs significantly upregulated ion transporters such as the plasma membrane Na(+)/H(+) antiporter (SlSOS1), vacuolar Na(+)/H(+) exchanger (SlNHX1 and SlNHX2), and Na(+) transporter and signal components including ROS, MAPK, and Ca(2+) signal pathways, as well as several transcription factors. All of these play important roles in plant adaptation to stress conditions. Copyright © 2014 Elsevier Inc. All rights reserved.

Role of Brazilian Amazon protected areas in climate change mitigation

PubMed Central

Soares-Filho, Britaldo; Moutinho, Paulo; Nepstad, Daniel; Anderson, Anthony; Rodrigues, Hermann; Garcia, Ricardo; Dietzsch, Laura; Merry, Frank; Bowman, Maria; Hissa, Letícia; Silvestrini, Rafaella; Maretti, Cláudio

2010-01-01

Protected areas (PAs) now shelter 54% of the remaining forests of the Brazilian Amazon and contain 56% of its forest carbon. However, the role of these PAs in reducing carbon fluxes to the atmosphere from deforestation and their associated costs are still uncertain. To fill this gap, we analyzed the effect of each of 595 Brazilian Amazon PAs on deforestation using a metric that accounts for differences in probability of deforestation in areas of pairwise comparison. We found that the three major categories of PA (indigenous land, strictly protected, and sustainable use) showed an inhibitory effect, on average, between 1997 and 2008. Of 206 PAs created after the year 1999, 115 showed increased effectiveness after their designation as protected. The recent expansion of PAs in the Brazilian Amazon was responsible for 37% of the region's total reduction in deforestation between 2004 and 2006 without provoking leakage. All PAs, if fully implemented, have the potential to avoid 8.0 ± 2.8 Pg of carbon emissions by 2050. Effectively implementing PAs in zones under high current or future anthropogenic threat offers high payoffs for reducing carbon emissions, and as a result should receive special attention in planning investments for regional conservation. Nevertheless, this strategy demands prompt and predictable resource streams. The Amazon PA network represents a cost of US$147 ± 53 billion (net present value) for Brazil in terms of forgone profits and investments needed for their consolidation. These costs could be partially compensated by an international climate accord that includes economic incentives for tropical countries that reduce their carbon emissions from deforestation and forest degradation. PMID:20505122

Tax subsidization of personal assistance services.

PubMed

Mendelsohn, Steven; Myhill, William N; Morris, Michael

2012-04-01

Personal assistance services (PAS) is the term used to describe the range of assistance, services, and supports many people with disabilities and older Americans need to remain in their homes and communities. The Americans with Disabilities Act requires that people with disabilities receive essential services in the communities of their choice rather than in institutional settings. PAS availability often determines whether persons with disabilities become institutionalized or remain in their communities. PAS, however, are not inexpensive or broadly available. Strategies are needed to improve their availability to people with disabilities and the elderly. We sought to analyze 8 provisions of the Internal Revenue Code for their utility to make PAS more affordable and available. The authors conducted a legal analysis of 8 statutory provisions, as interpreted by regulations, court decisions, and other authoritative sources. Each of the tax provisions analyzed covers some PAS expenses incurred by an individual or family. Favorable tax treatment is impacted by the nature and amount of expenses and by the location and conditions of services. The current limitations and complexities of legal interpretations and the fact that many individuals with disabilities are uninformed about these tax provisions present challenges and opportunities. As the need for PAS grows, reform of tax policy is an important complement to health care and long-term services and supports for people with disabilities. To increase utilization of current beneficial tax provisions that subsidize the cost of PAS, individuals with disabilities and tax preparers must become better informed about using these provisions. Copyright © 2012 Elsevier Inc. All rights reserved.

Understanding the role of physician assistants in oncology.

PubMed

Ross, Alicia C; Polansky, Maura N; Parker, Patricia A; Palmer, J Lynn

2010-01-01

To understand the deployment of physician assistants (PAs) in oncology. A recent analysis of the oncology workforce in the United States commissioned by ASCO predicted a significant shortage of providers by 2020. A descriptive study was undertaken using a Web-based questionnaire survey. Invited participants, including all PAs listed in the national PA database (n = 855) and all PAs at The University of Texas M. D. Anderson Cancer Center (Houston, TX; n = 159), were mailed letters directing them to the Web-based survey. The study produced a 30% response rate. A total of 186 PAs worked in medical oncology (the population of interest). Of the respondents, 80% were women, mean age was 36 years, average time employed as a PA was 9.5 years (6.5 years in oncology), 55% had obtained a master's degree, four had completed a postgraduate oncology program, 91% reported that direct mentorship by a supervising physician was very important in obtaining oncology-based knowledge, and 61% reported that becoming fully competent in the practice of oncology required 1 to 2 years. The majority of PAs (78.5%) worked 33 to 50 hours per week, and 56% of those reported working 41 to 50 hours per week. Three fourths (77%) wrote chemotherapy orders, most requiring physician co-signature, and 69% prescribed schedule III to V controlled substances. Additional data were gathered regarding clinical duties, research, and teaching. Oncology PAs are used in multiple medical settings, and many assume high-level responsibilities. Future research addressing function and factors that limit use of PAs may allow for improved organizational efficiency and enhancement in the delivery of health care.