[Dental caries and early childhood development: a pilot study].

PubMed

Núñez, F Loreto; Sanz, B Javier; Mejía, L Gloria

2015-01-01

To investigate the association between dental caries and early childhood development in 3-year-olds from Talca, Chile. A pilot study with a convenience sample of 3-year-olds from Talca (n = 39) who attend public healthcare centers. Child development was measured by the Psychomotor Development Index (PDI), a screening tool used nationally among pre-school children to assess language development, fine motor skills and coordination areas. Dental caries prevalence was evaluated by decayed, missing, filled teeth (DFMT) and decayed, missing, filled tooth surfaces (DFMS) ceo-d and ceo-s indexes. The children were divided into two groups according to the PDIscore: those with a score of 40 or more were considered developmentally normal (n = 32), and those with a score below 40 were considered as having impaired development (n = 7). The severity of caries (DMFT) was negatively correlated with PDI (r = -0.82), and children with the lowest TEPSI score had the highest DFMT values. The average DMFT in children with normal development was 1.31, and 3.57 for those with impaired development. This pilot study indicates that the severity of dental caries is correlated with early childhood development. Copyright © 2015. Publicado por Elsevier España, S.L.U.

Cultural Prototypes and Differences in Simulation Debriefing.

PubMed

Ulmer, Francis F; Sharara-Chami, Rana; Lakissian, Zavi; Stocker, Martin; Scott, Ella; Dieckmann, Peter

2018-04-18

Culture is believed to play a role in education, safety, and patient outcome in healthcare. Hofstede's culture analysis permits a quantitative comparison between countries, along different culture dimensions, including power distance (PD). Power distance index (PDI) is a value reflecting social hierarchy in a country. We sought to explore the relation between PDI and self-reported behavior patterns of debriefers during simulation debriefings. We determined six culture-relevant debriefing characteristics and formulated six hypotheses on how these characteristics correlate with national PDIs. Low-PDI countries have a PDI of 50 or less, and high-PDI countries have a PDI of 51 or greater as defined by Hofstede. Interviews with simulation debriefers were used to investigate culture-relevant debriefing characteristics: debriefer/participant talking time, debriefer/participant interaction pattern, debriefer/participant interaction style, debriefer/participant initiative for interactions, debriefing content, and difficulty with which nontechnical skills can be discussed. During debriefing, in low-PDI countries, debriefers talked less and used more open-ended questions and focused more on nontechnical issues than on medical knowledge and simulation participants initiated most interactions. In low-PDI countries, debriefers felt that participants interacted more with each other and found it easier to address nontechnical skills such as speaking-up. Our results supported our hypotheses. National culture is related to debriefing practice. There is a clear relation between PDI and debriefer-participant behavior patterns as described by debriefers. The higher the PDI of a country, the more the debriefer determines the course of the debriefing and the more difficult it becomes to address nontechnical skills.

Development and evaluation of the PI-G: a three-scale measure based on the German translation of the PROMIS ® pain interference item bank.

PubMed

Farin, Erik; Nagl, Michaela; Gramm, Lukas; Heyduck, Katja; Glattacker, Manuela

2014-05-01

Study aim was to translate the PROMIS(®) pain interference (PI) item bank (41 items) into German, test its psychometric properties in patients with chronic low back pain and develop static subforms. We surveyed N = 262 patients undergoing rehabilitation who were asked to fill out questionnaires at the beginning and 2 weeks after the end of rehabilitation, applying the Oswestry Disability Index (ODI) and Pain Disability Index (PDI) in addition to the PROMIS(®) PI items. For psychometric testing, a 1-parameter item response theory (IRT) model was used. Exploratory and confirmatory factor analyses as well as reliability and construct validity analyses were conducted. The assumptions regarding IRT scaling of the translated PROMIS(®) PI item bank as a whole were not confirmed. However, we succeeded in devising three static subforms (PI-G scales: PI mental 13 items, PI functional 11 items, PI physical 4 items), revealing good psychometric properties. The PI-G scales in their static form can be recommended for use in German-speaking countries. Their strengths versus the ODI and PDI are that pain interference is assessed in a differentiated manner and that several psychometric values are somewhat better than those associated with the ODI and PDI (distribution properties, IRT model fit, reliability). To develop an IRT-scaled item bank of the German translations of the PROMIS(®) PI items, it would be useful to have additional studies (e.g., with larger sample sizes and using a 2-parameter IRT model).

Does Pedestrian Danger Mediate the Relationship between Local Walkability and Active Travel to Work?

PubMed

Slater, Sandy J; Nicholson, Lisa; Abu Zayd, Haytham; Chriqui, Jamie Friedman

2016-01-01

Environmental and policy factors play an important role in influencing people's lifestyles, physical activity (PA), and risks for developing obesity. Research suggests that more walkable communities are needed to sustain lifelong PA behavior, but there is a need to determine what local built environment features facilitate making being active the easy choice. This county-level study examined the association between local walkability (walkability and traffic calming scales), pedestrian danger, and the percent of adults who used active transport to work. Built environment and PA outcome measures were constructed for the 496 most populous counties representing 74% of the U.S. population. Geographic information system-based walkability scales were constructed and include a census of roads located within the counties using 2011 Navteq data. The pedestrian danger index (PDI) includes data collected from the Fatality Analysis Reporting System 2009-2011, and measures the likelihood of a pedestrian being hit and killed by a vehicle. Four continuous outcome measures were constructed using 2009-2013 American Community Survey county-level 5-year estimates. The measures represent the percentage of workers living in a county who worked away from home and (1) walked to work; (2) biked to work; (3) took public transit; and (4) used any form of active transport. Linear regression and mediation analyses were conducted to examine the association between walkability, PDI, and active transport. Models accounted for clustering within state with robust SEs, and controlled for median household income, families with children in poverty, race, ethnicity, urbanicity, and region. The walkability scale was significantly negatively associated with the PDI (β = -0.06, 95% CI = -0.111, -0.002). In all models, the PDI was significantly negatively associated with all active travel-related outcomes at the p < 0.01 level. The walkability scale was positively associated with all four outcomes at the p < 0.01 level. Results showed that the significant positive relationship between local walkability and the four active transport outcome measures was partially mediated by the PDI. We found no association between traffic calming, the PDI, and the active transport outcomes. Results from this study show that, at the county-level, walkability is associated with active travel, and this association is partially mediated by an index of pedestrian safety.

Identification of three protein disulfide isomerase members from Haemaphysalis longicornis tick.

PubMed

Liao, Min; Hatta, Takeshi; Umemiya, Rika; Huang, Penglong; Jia, Honglin; Gong, Haiyan; Zhou, Jinlin; Nishikawa, Yoshifumi; Xuan, Xuenan; Fujisaki, Kozo

2007-07-01

Three genes encoding putative protein disulfide isomerase (PDI) were isolated from the Haemaphysalis longicornis EST database and designed as HlPDI-1, HlPDI-2, and HlPDI-3. All three PDI genes contain two typical PDI active sites CXXC and encode putative 435, 499, and 488 amino acids, respectively. The recombinant proteins expressed in Escherichia coli all show PDI activities, and the activities were inhibited by a PDI-specific inhibitor, zinc bacitracin. Western blot analysis and real-time PCR revealed that three HlPDIs were present in all the developmental stages of the tick as well as in the midgut, salivary glands, ovary, hemolymph, and fatbody of adult female ticks, but the three genes were expressed at the highest level in the egg stage. HlPDI-1 is expressed primarily in the ovary and secondarily in the salivary glands. HlPDI-2 and HlPDI-3 are expressed primarily in the salivary gland, suggesting that the PDI genes are important for tick biology, especially for egg development, and that they play distinct roles in different tissues. Blood feeding induced significantly increased expression of HlPDI-1 and HlPDI-3 in both partially fed nymphs and adults. Babesia gibsoni-infected larval ticks expressed HlPDI-1 and HlPDI-3 2.0 and 4.0 times higher than uninfected normal larval ticks, respectively. The results indicate that HlPDI-1 and HlPDI-3 might be involved in tick blood feeding and Babesia parasite infection in ticks.

Hurricane destructive power predictions based on historical storm and sea surface temperature data.

PubMed

Bogen, Kenneth T; Jones, Edwin D; Fischer, Larry E

2007-12-01

Forecasting destructive hurricane potential is complicated by substantial, unexplained intraannual variation in storm-specific power dissipation index (PDI, or integrated third power of wind speed), and interannual variation in annual accumulated PDI (APDI). A growing controversy concerns the recent hypothesis that the clearly positive trend in North Atlantic Ocean (NAO) sea surface temperature (SST) since 1970 explains increased hurricane intensities over this period, and so implies ominous PDI and APDI growth as global warming continues. To test this "SST hypothesis" and examine its quantitative implications, a combination of statistical and probabilistic methods were applied to National Hurricane Center HURDAT best-track data on NAO hurricanes during 1880-2002, and corresponding National Oceanographic and Atmospheric Administration Extended Reconstruction SST estimates. Notably, hurricane behavior was compared to corresponding hurricane-specific (i.e., spatiotemporally linked) SST; previous similar comparisons considered only SST averaged over large NAO regions. Contrary to the SST hypothesis, SST was found to vary in a monthly pattern inconsistent with that of corresponding PDI, and to be at best weakly associated with PDI or APDI despite strong correlation with corresponding mean latitude (R(2)= 0.55) or with combined mean location and a approximately 90-year periodic trend (R(2)= 0.70). Over the last century, the lower 75% of APDIs appear randomly sampled from a nearly uniform distribution, and the upper 25% of APDIs from a nearly lognormal distribution. From the latter distribution, a baseline (SST-independent) stochastic model was derived predicting that over the next half century, APDI will not likely exceed its maximum value over the last half century by more than a factor of 1.5. This factor increased to 2 using a baseline model modified to assume SST-dependence conditioned on an upper bound of the increasing NAO SST trend observed since 1970. An additional model was developed that predicts PDI statistics conditional on APDI. These PDI and APDI models can be used to estimate upper bounds on indices of hurricane power likely to be realized over the next century, under divergent assumptions regarding SST influence.

Joint projections of US East Coast sea level and storm surge

NASA Astrophysics Data System (ADS)

Little, Christopher M.; Horton, Radley M.; Kopp, Robert E.; Oppenheimer, Michael; Vecchi, Gabriel A.; Villarini, Gabriele

2015-12-01

Future coastal flood risk will be strongly influenced by sea-level rise (SLR) and changes in the frequency and intensity of tropical cyclones. These two factors are generally considered independently. Here, we assess twenty-first century changes in the coastal hazard for the US East Coast using a flood index (FI) that accounts for changes in flood duration and magnitude driven by SLR and changes in power dissipation index (PDI, an integrated measure of tropical cyclone intensity, frequency and duration). Sea-level rise and PDI are derived from representative concentration pathway (RCP) simulations of 15 atmosphere-ocean general circulation models (AOGCMs). By 2080-2099, projected changes in the FI relative to 1986-2005 are substantial and positively skewed: a 10th-90th percentile range 4-75 times higher for RCP 2.6 and 35-350 times higher for RCP 8.5. High-end FI projections are driven by three AOGCMs that project the largest increases in SLR, PDI and upper ocean temperatures. Changes in PDI are particularly influential if their intra-model correlation with SLR is included, increasing the RCP 8.5 90th percentile FI by a further 25%. Sea-level rise from other, possibly correlated, climate processes (for example, ice sheet and glacier mass changes) will further increase coastal flood risk and should be accounted for in comprehensive assessments.

Joint Projections of US East Coast Sea Level and Storm Surge

NASA Technical Reports Server (NTRS)

Little, Christopher M.; Horton, Radley M.; Kopp, Robert E.; Oppenheimer, Michael; Vecchi, Gabriel A.; Villarini, Gabriele

2015-01-01

Future coastal flood risk will be strongly influenced by sea-level rise (SLR) and changes in the frequency and intensity of tropical cyclones. These two factors are generally considered independently. Here, we assess twenty-first century changes in the coastal hazard for the US East Coast using a flood index (FI) that accounts for changes in flood duration and magnitude driven by SLR and changes in power dissipation index (PDI, an integrated measure of tropical cyclone intensity, frequency and duration). Sea-level rise and PDI are derived from representative concentration pathway (RCP) simulations of 15 atmosphere- ocean general circulation models (AOGCMs). By 2080-2099, projected changes in the FI relative to 1986-2005 are substantial and positively skewed: a 10th-90th percentile range 4-75 times higher for RCP 2.6 and 35-350 times higher for RCP 8.5. High-end Fl projections are driven by three AOGCMs that project the largest increases in SLR, PDI and upper ocean temperatures. Changes in PDI are particularly influential if their intra-model correlation with SLR is included, increasing the RCP 8.5 90th percentile FI by a further 25%. Sea-level rise from other, possibly correlated, climate processes (for example, ice sheet and glacier mass changes) will further increase coastal flood risk and should be accounted for in comprehensive assessments.

Human milk intake in preterm infants and neurodevelopment at 18 months corrected age.

PubMed

Jacobi-Polishook, Talia; Collins, Carmel T; Sullivan, Thomas R; Simmer, Karen; Gillman, Matthew W; Gibson, Robert A; Makrides, Maria; Belfort, Mandy B

2016-10-01

The effect of human milk intake on neurodevelopment in preterm infants is uncertain. We analyzed data from 611 participants in the DHA for Improvement of Neurodevelopmental Outcomes study, enrolled at ≤33 wk gestation from five Australian perinatal centers. The main exposures were (i) average daily human milk intake during the neonatal hospitalization and (ii) total duration of human milk intake before and after discharge. Outcomes were Bayley Scales of Infant Development, 2nd Edition Mental (MDI), and Psychomotor (PDI) Development Indexes. Adjusting for confounders in linear regression, human milk intake was not associated with higher MDI (0.2 points per 25 ml/kg/d; 95% confidence interval (CI): -0.6, 1.0) or PDI (-0.3 points; 95% CI: -1.1, 0.4). Longer duration of human milk intake was also not associated with MDI (0.1 points per month; 95% CI: -0.2, 0.3) or PDI (-0.2 points per month; 95% CI: -0.5, 0.01) scores, except in infants born 29-33 wk gestation (n = 364, MDI 0.3 points higher per additional month, 95% CI: 0.1, 0.6). We found no associations of human milk intake during the neonatal hospitalization with neurodevelopment at 18 mo corrected age.

Nanovesicles for transdermal delivery of felodipine: Development, characterization, and pharmacokinetics

PubMed Central

Yusuf, Mohd; Sharma, Vijay; Pathak, Kamla

2014-01-01

Aim: The research traces development of nanovesicles to attain enhanced transdermal delivery of felodipine and also investigates parameters for optimization of variable membrane compositions containing soya- and egg lecithin and edge activator. Materials and Methods: Rotary evaporation sonication method was employed to obtain tranfersomal formulation that was characterized for vesicle shape and size, polydispersity index (PDI), zeta potential, entrapment and loading efficiency, deformability index and in vitro skin permeation. Results: Spherical nanovesicles of 75.71 ± 5.4 nm with PDI 0.228 and zeta potential of −49.8 were adjudged as the best formulation (MF8). MF8 displayed maximum entrapment and loading efficiency with a high deformability index of 119.68. In vitro permeation across rat skin by MF8 reported 256% enhancement in permeation (flux = 23.72 ± 0.64) when compared with transdermal control formulation and followed zero order kinetics (Case-II). Pharmacokinetic studies revealed that transdermal administration, in contrast to oral delivery provided relatively constant, sustained blood concentration with minimal plasma fluctuation, rapid and prolonged peak time. The relative bioavailability of felodipine was found 358.42% versus oral administration that was well supported by the outcomes of confocal laser scanning microscopic studies that suggested rapid permeation of drugs to across dermal layers. Conclusion: The results conclude that composition variation and method of preparation elicited significant effect on the vesicle characteristic and proved the transcendency of felodipine loaded transfersomes. PMID:25126525

Assessment by three-dimensional power Doppler ultrasound of cerebral blood flow perfusion in fetuses with congenital heart disease.

PubMed

Zeng, S; Zhou, J; Peng, Q; Tian, L; Xu, G; Zhao, Y; Wang, T; Zhou, Q

2015-06-01

To use three-dimensional (3D) power Doppler ultrasound to investigate cerebral blood flow perfusion in fetuses with congenital heart disease (CHD). The vascularization index (VI), flow index (FI) and vascularization flow index (VFI) in the total intracranial volume and the main arterial territories (middle cerebral artery (MCA), anterior cerebral artery (ACA) and posterior cerebral artery (PCA)) were evaluated prospectively and compared in 112 fetuses with CHD and 112 normal fetuses using 3D power Doppler. Correlations between the 3D power Doppler indices and neurodevelopment scores at 12 months of age were assessed in a subset of the CHD group, and values were compared with those of controls. Compared with the controls, the VI, FI and VFI of the total intracranial volume and the three main arteries were significantly higher in fetuses with hypoplastic left heart syndrome and left-sided obstructive lesions (P < 0.001), and the 3D power Doppler values in the ACA territory were significantly higher in fetuses with transposition of the great arteries (P < 0.01). The largest proportional increase in the blood flow perfusion indices in the fetuses with CHD relative to controls was observed in the ACA territory (P < 0.05). Among 41 cases with CHD that underwent testing, the mean Psychomotor Development Index (PDI) and Mental Development Index (MDI) scores were significantly lower than in 94 of the controls that were tested (P < 0.001). Among these CHD cases, total intracranial FI was positively correlated with PDI (r = 0.342, P = 0.029) and MDI (r = 0.339, P = 0.030), and ACA-VI and ACA-VFI were positively correlated with PDI (r = 0.377 and 0.389, P = 0.015 and 0.012, respectively) but were not correlated with MDI (r = 0.243 and 0.203, P = 0.126 and 0.204, respectively). Cerebral blood flow perfusion was increased relative to controls in most fetuses with CHD and was associated with neurodevelopment scores at 12 months. Prenatal 3D power Doppler ultrasound might help to identify cases of brain vasodilatation earlier and inform parental counseling. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Integration of social dimension in an index oriented methodology for consequence analysis of natural hazards: application to the Upper Guil Catchment (Southern French Alps)

NASA Astrophysics Data System (ADS)

Carlier, Benoit; Puissant, Anne; Dujarric, Constance

2017-04-01

Vulnerability assessment together with hazard exposure is generally accepted as the two main steps of risk analysis. If quantitative methods to estimate hazard exposure are now well-defined, it is not the case regarding vulnerability assessment. Vulnerability is a complex concept involving a variety of disciplines from physical and socio-economic sciences (i.e. engineering, economics, social and health sciences etc.). Currently, two opposite trends exist: the 'physical' approach in which vulnerability is analysed as potential impacts (i.e. structural and functional) on the elements at risk (building, network, land cover); and the 'social' approach in which vulnerability is a combination of socio-economic variables determining people's ability to anticipate before a catastrophic event, to react during it, and to recover after it. For a complete analysis of vulnerability it is essential to combine these two approaches but in reality few works exists. The objective of this research is to improve the Potential Damage Index (PDI), detailed in Puissant el al. (2013), originally developed to assess physical injury, structural and functional consequences of landslide hazard, by including socio-economic characteristics of population information. Data from the French Census data (INSEE, 2012) and a survey on risk perception (100 questionnaires obtained between 2014 and 2015/16) were used to propose an overall index taking into account the three main phases of risk management: preparedness, crisis management and recovery. This new index called Global Potential Damage Index (GPDI) is applied on the Upper Guil Catchment to assess potential torrential floods hazard in the context of the French funded project SAMCO (Society Adaptation for coping with Mountain risks in a global change Context). Results of the PDI are compared with the GPDI and show significant differences. GPDI scores mapping are lower than PDI scores indicating that resilient population may qualify results obtained for physical consequences. In GPDI the social and institutional component is expressed by a unique value applied for the overall stakes of a same community. Consequently, socio-economics differences between Upper Guil catchments communities are highlighted and make results easily understandable for local manager.

Maternal self-esteem, exposure to lead, and child neurodevelopment.

PubMed

Surkan, Pamela J; Schnaas, Lourdes; Wright, Rosalind J; Téllez-Rojo, Martha M; Lamadrid-Figueroa, Héctor; Hu, Howard; Hernández-Avila, Mauricio; Bellinger, David C; Schwartz, Joel; Perroni, Estela; Wright, Robert O

2008-03-01

The notion that maternal personality characteristics influence cognitive development in their children has been grounded in stress moderation theory. Maternal personality traits, such as self-esteem, may buffer maternal stressors or lead to improved maternal-child interactions that directly impact neurodevelopment. This can be extended to suggest that maternal personality may serve to attenuate or exacerbate the effects of other neurotoxicants, although this has not been studied directly. We examined whether mothers' self-esteem had a direct or main effect on their children's cognitive outcomes. We also explored the modifying effects of maternal self-esteem on the association between exposure to lead and neurodevelopment in these children. Study participants included 379 mother-child pairs from Mexico City. Data included the Coopersmith Self-Esteem Scale in mothers, children's Bayley's Scale of Infant Development (BSID) scores, and sociodemographic information. Linear regression was used to model the relationship between maternal self-esteem and the Bayley's Mental Development Index (MDI) and Psychomotor Development Index (PDI) scores at age 24 months using models stratified by levels of maternal self-esteem. In adjusted models, each point increase in maternal self-esteem was associated with children having 0.2 higher score on the Bayley's MDI (p=0.04). Similar results were observed using the PDI outcome. Moreover, there was evidence that maternal self-esteem attenuated the negative effects of lead exposure, although the interaction fell short of conventional levels of statistical significance.

MATERNAL SELF-ESTEEM, EXPOSURE TO LEAD, AND CHILD NEURODEVELOPMENT

PubMed Central

Surkan, Pamela J.; Schnaas, Lourdes; Wright, Rosalind J.; Téllez-Rojo, Martha M.; Lamadrid-Figueroa, Héctor; Hu, Howard; Hernández-Avila, E. Mauricio; Bellinger, David C.; Schwartz, Joel; Perroni, Estela; Wright, Robert O.

2008-01-01

The notion that maternal personality characteristics influence cognitive development in their children has been grounded in stress moderation theory. Maternal personality traits, such as self-esteem, may buffer maternal stressors or lead to improved maternal-child interactions that directly impact neurodevelopment. This can be extended to suggest that maternal personality may serve to attenuate or exacerbate the effects of other neurotoxicants, although this has not been studied directly. We examined whether mothers’ self-esteem had a direct or main effect on their children's cognitive outcomes. We also explored the modifying effects of maternal self-esteem on the association between exposure to lead and neurodevelopment in these children. Study participants included 379 mother-child pairs from Mexico City. Data included the Coopersmith self-esteem scale in mothers, children's Bayley's Scale of Infant Development (BSID) scores, and sociodemographic information. Linear regression was used to model the relationship between maternal self-esteem and the Bayley's Mental Development Index (MDI) and Psychomotor Development Index (PDI) scores at age 24 months using regression models stratified by levels of maternal self-esteem. In adjusted models, each point increase in maternal self-esteem was associated with children having 0.2 higher score on the Bayley's MDI (p=0.04). Similar results were observed using the PDI outcome. Moreover, there was evidence that maternal self-esteem attenuated the negative effects of lead exposure, although the interaction fell short of conventional levels of statistical significance. PMID:18261800

A protein disulfide isomerase gene fusion expression system that increases the extracellular productivity of Bacillus brevis.

PubMed

Kajino, T; Ohto, C; Muramatsu, M; Obata, S; Udaka, S; Yamada, Y; Takahashi, H

2000-02-01

We have developed a versatile Bacillus brevis expression and secretion system based on the use of fungal protein disulfide isomerase (PDI) as a gene fusion partner. Fusion with PDI increased the extracellular production of heterologous proteins (light chain of immunoglobulin G, 8-fold; geranylgeranyl pyrophosphate synthase, 12-fold). Linkage to PDI prevented the aggregation of the secreted proteins, resulting in high-level accumulation of fusion proteins in soluble and biologically active forms. We also show that the disulfide isomerase activity of PDI in a fusion protein is responsible for the suppression of the aggregation of the protein with intradisulfide, whereas aggregation of the protein without intradisulfide was prevented even when the protein was fused to a mutant PDI whose two active sites were disrupted, suggesting that another PDI function, such as chaperone-like activity, synergistically prevented the aggregation of heterologous proteins in the PDI fusion expression system.

A Protein Disulfide Isomerase Gene Fusion Expression System That Increases the Extracellular Productivity of Bacillus brevis

PubMed Central

Kajino, Tsutomu; Ohto, Chikara; Muramatsu, Masayoshi; Obata, Shusei; Udaka, Shigezo; Yamada, Yukio; Takahashi, Haruo

2000-01-01

We have developed a versatile Bacillus brevis expression and secretion system based on the use of fungal protein disulfide isomerase (PDI) as a gene fusion partner. Fusion with PDI increased the extracellular production of heterologous proteins (light chain of immunoglobulin G, 8-fold; geranylgeranyl pyrophosphate synthase, 12-fold). Linkage to PDI prevented the aggregation of the secreted proteins, resulting in high-level accumulation of fusion proteins in soluble and biologically active forms. We also show that the disulfide isomerase activity of PDI in a fusion protein is responsible for the suppression of the aggregation of the protein with intradisulfide, whereas aggregation of the protein without intradisulfide was prevented even when the protein was fused to a mutant PDI whose two active sites were disrupted, suggesting that another PDI function, such as chaperone-like activity, synergistically prevented the aggregation of heterologous proteins in the PDI fusion expression system. PMID:10653729

Chlorpyrifos Exposure and Urban Residential Environment Characteristics as Determinants of Early Childhood Neurodevelopment

PubMed Central

Quinn, James W.; Rauh, Virginia A.; Perera, Frederica P.; Andrews, Howard F.; Garfinkel, Robin; Hoepner, Lori; Whyatt, Robin; Rundle, Andrew

2011-01-01

Objectives. We evaluated whether neighborhood characteristics correlated with early neurodevelopment and whether these characteristics confounded the previously reported association between exposure to chlorpyrifos (an organophosphate insecticide) and neurodevelopment. Methods. We obtained prenatal addresses, chlorpyrifos exposure data, and 36-month Psychomotor Development Index (PDI) and Mental Development Index (MDI) scores for a birth cohort in New York City (born 1998–2002). We used data from the 2000 US Census to estimate measures of physical infrastructure, socioeconomic status, crowding, demographic composition, and linguistic isolation for 1-kilometer network areas around each child's prenatal address. Generalized estimating equations were adjusted for demographics, maternal education and IQ, prenatal exposure to tobacco smoke, caretaking environment quality, and building dilapidation. Results. Of 266 children included as participants, 47% were male, 59% were Dominican, and 41% were African American. For each standard deviation higher in neighborhood percent poverty, the PDI score was 2.6 points lower (95% confidence interval [CI] = −3.7, −1.5), and the MDI score was 1.7 points lower (95% CI = −2.6, −0.8). Neighborhood-level confounding of the chlorpyrifos-neurodevelopment association was not apparent. Conclusions. Neighborhood context and chlorpyrifos exposure were independently associated with neurodevelopment, thus providing distinct opportunities for health promotion. PMID:20299657

Diaphragmatic fatigue in man.

PubMed

Roussos, C S; Macklem, P T

1977-08-01

The time required (tlim) to produce fatigue of the diaphragm was determined in three normal seated subjects, breathing through a variety of high alinear, inspiratory resistances. During each breath in all experimental runs the subject generated a transdiaphragmatic pressure (Pdi) which was a predetermined fraction of his maximum inspiratory Pdi (Pdimax) at functional residual capacity. The breathing test was performed until the subject was unable to generate this Pdi. The relationship between Pdi/Pdimax and tlim was curvilinear so that when Pdi/Pdimax was small tlim increased markedly for little changes in Pdi/Pdimax. The value of Pdi/Pdimax that could be generated indefinitely (Pdicrit) was around 0.4. Hypoxia appeared to have no influence on Pdicrit, but probably led to a reduction in tlim at Pdi greater than Pdicrit for equal rates of energy consumption. Insofar as the behavior of the diaphragm reflects that of other respiratory muscles it appears that quite high inspiratory loads can be tolerated indefinitely. However, when the energy consumption of the respiratory muscles exceeds a critical level, fatigue should develop. This may be a mechanism of respiratory failure in a variety in a variety of lung diseases.

Associations of maternal long-chain polyunsaturated fatty acids, methyl mercury, and infant development in the Seychelles Child Development Nutrition Study.

PubMed

Strain, J J; Davidson, Philip W; Bonham, Maxine P; Duffy, Emeir M; Stokes-Riner, Abbie; Thurston, Sally W; Wallace, Julie M W; Robson, Paula J; Shamlaye, Conrad F; Georger, Lesley A; Sloane-Reeves, Jean; Cernichiari, Elsa; Canfield, Richard L; Cox, Christopher; Huang, Li Shan; Janciuras, Joanne; Myers, Gary J; Clarkson, Thomas W

2008-09-01

Fish consumption during gestation can provide the fetus with long-chain polyunsaturated fatty acids (LCPUFA) and other nutrients essential for growth and development of the brain. However, fish consumption also exposes the fetus to the neurotoxicant, methyl mercury (MeHg). We studied the association between these fetal exposures and early child development in the Seychelles Child Development Nutrition Study (SCDNS). Specifically, we examined a priori models of Omega-3 and Omega-6 LCPUFA measures in maternal serum to test the hypothesis that these LCPUFA families before or after adjusting for prenatal MeHg exposure would reveal associations with child development assessed by the BSID-II at ages 9 and 30 months. There were 229 children with complete outcome and covariate data available for analysis. At 9 months, the PDI was positively associated with total Omega-3 LCPUFA and negatively associated with the ratio of Omega-6/Omega-3 LCPUFA. These associations were stronger in models adjusted for prenatal MeHg exposure. Secondary models suggested that the MeHg effect at 9 months varied by the ratio of Omega-6/Omega-3 LCPUFA. There were no significant associations between LCPUFA measures and the PDI at 30 months. There were significant adverse associations, however, between prenatal MeHg and the 30-month PDI when the LCPUFA measures were included in the regression analysis. The BSID-II mental developmental index (MDI) was not associated with any exposure variable. These data support the potential importance to child development of prenatal availability of Omega-3 LCPUFA present in fish and of LCPUFA in the overall diet. Furthermore, they indicate that the beneficial effects of LCPUFA can obscure the determination of adverse effects of prenatal MeHg exposure in longitudinal observational studies.

Associations of maternal long chain polyunsaturated fatty acids, methyl mercury, and infant development in the Seychelles Child Development Nutrition Study

PubMed Central

Strain, J.J.; Davidson, Philip W.; Bonham, Maxine P.; Duffy, Emeir M.; Stokes-Riner, Abbie; Thurston, Sally W.; Wallace, Julie M.W.; Robson, Paula J.; Shamlaye, Conrad F.; Georger, Lesley A.; Sloane-Reeves, Jean; Cernichiari, Elsa; Canfield, Richard L.; Cox, Christopher; Huang, Li Shan; Janciuras, Joanne; Myers, Gary J.; Clarkson, Thomas W.

2008-01-01

Fish consumption during gestation can provide the fetus with long chain polyunsaturated fatty acids (LCPUFA) and other nutrients essential for growth and development of the brain. However, fish consumption also exposes the fetus to the neurotoxicant, methyl mercury (MeHg). We studied the association between these fetal exposures and early child development in the Seychelles Child Development Nutrition Study (SCDNS). Specifically, we examined a priori models of Ω-3 and Ω-6 LCPUFA measures in maternal serum to test the hypothesis that these LCPUFA families before or after adjusting for prenatal MeHg exposure would reveal associations with child development assessed by the BSID-II at ages 9 and 30 months. There were 229 children with complete outcome and covariate data available for analysis. At 9 months, the PDI was positively associated with total Ω-3 LCPUFA and negatively associated with the ratio of Ω-6/Ω-3 LCPUFA. These associations were stronger in models adjusted for prenatal MeHg exposure. Secondary models suggested that the MeHg effect at 9 months varied by the ratio of Ω-6/Ω-3 LCPUFA. There were no significant associations between LCPUFA measures and the PDI at 30 months. There were significant adverse associations, however, between prenatal MeHg and the 30 month PDI when the LCPUFA measures were included in the regression analysis. The BSID-II Mental Developmental Index (MDI) was not associated with any exposure variable. These data support the potential importance to child development of prenatal availability of Ω-3 LCPUFA present in fish and of LCPUFA in the overall diet. Furthermore, they indicate that the beneficial effects of LCPUFA can obscure the determination of adverse effects of prenatal MeHg exposure in longitudinal observational studies. PMID:18590765

Interferometric at-wavelength flare characterization of EUV optical systems

DOEpatents

Naulleau, Patrick P.; Goldberg, Kenneth Alan

2001-01-01

The extreme ultraviolet (EUV) phase-shifting point diffraction interferometer (PS/PDI) provides the high-accuracy wavefront characterization critical to the development of EUV lithography systems. Enhancing the implementation of the PS/PDI can significantly extend its spatial-frequency measurement bandwidth. The enhanced PS/PDI is capable of simultaneously characterizing both wavefront and flare. The enhanced technique employs a hybrid spatial/temporal-domain point diffraction interferometer (referred to as the dual-domain PS/PDI) that is capable of suppressing the scattered-reference-light noise that hinders the conventional PS/PDI. Using the dual-domain technique in combination with a flare-measurement-optimized mask and an iterative calculation process for removing flare contribution caused by higher order grating diffraction terms, the enhanced PS/PDI can be used to simultaneously measure both figure and flare in optical systems.

Recent decrease in typhoon destructive potential and global warming implications.

PubMed

Lin, I-I; Chan, Johnny C L

2015-05-20

Typhoons (tropical cyclones) severely impact the half-billion population of the Asian Pacific. Intriguingly, during the recent decade, typhoon destructive potential (Power Dissipation Index, PDI) has decreased considerably (by ∼ 35%). This decrease, paradoxically, has occurred despite the increase in typhoon intensity and ocean warming. Using the method proposed by Emanuel (in 2007), we show that the stronger negative contributions from typhoon frequency and duration, decrease to cancel the positive contribution from the increasing intensity, controlling the PDI. Examining the typhoons' environmental conditions, we find that although the ocean condition became more favourable (warming) in the recent decade, the atmospheric condition 'worsened' at the same time. The 'worsened' atmospheric condition appears to effectively overpower the 'better' ocean conditions to suppress PDI. This stronger negative contribution from reduced typhoon frequency over the increased intensity is also present under the global warming scenario, based on analysis of the simulated typhoon data from high-resolution modelling.

[Relationship between the level of sialic acid during perinatal period and early intelligence development of full term infants].

PubMed

Wu, Youjia; Shao, Zhili; Gao, Weiwei; Li, Haiying; Xu, Meiyu

2014-02-01

To investigate the correlation between the status of sialic acid (SA) during perinatal period and early intelligence development of healthy full term infant, and to explore the effect of SA on the early intelligence development. A total of 127 pairs of healthy mothers-neonates in the Affiliated Hospital of Nantong University were recruited randomly in this prospective cohort study. The levels of SA from body fluids of mothers-neonates were measured by enzyme-linked immunosorbent assay, such as the full-term maternal and cord blood and the colostrum. The questionnaire surveys were carried out in mothers and mental development evaluation according to Children's Development Center of China (CDCC) were carried out in infants 3 to 4 months of age to obtain the mental development index (MDI) and psycho-motor development index (PDI). A total of 120 pairs of maternal-neonatal subjects with complete data were included into statistical analysis. The levels of SA of maternal and cord blood and colostrum were (2.25 ± 0.02), (1.21 ± 0.01), and (5.01 ± 0.06) mmol/L respectively. MDI and PDI of infants 3 to 4 months of age were (99.40 ± 1.87) and (98.53 ± 1.96). The analysis using multiple linear regression indicated that MDI was associated with SA levels of cord blood and colostrum (β = 0.636, 0.175, P < 0.05), and PDI was also associated with them (β = 0.502, 0.262, P < 0.05). The levels of SA of cord blood and colostrums were individually divided into high-level group and low-level one according to the median level. MDI and PDI in high-level group of cord blood were both significantly higher than that in low-level group (111.85 ± 2.79) vs. (108.88 ± 2.0) , (101.08 ± 4.44) vs. (98.88 ± 2.0) P < 0.01. So were MDI and PDI in high-level group of colostrum compared with those in low-level group (111.71 ± 3.07) vs. (108.81 ± 1.56), P < 0.01; (101.29 ± 4.23) vs.(98.56 ± 1.79), P < 0.05. The analysis on correlation between the levels of maternal-neonatal body fluids showed that the level of SA of colostrum was positively correlated with that of cord blood (r = 0.507, P = 0.004). However, no correlation was found either between the level of SA of maternal and cord blood or between the level of SA of maternal blood and colostrums. Further division into high-level and low-level groups was done according to the median level of maternal blood. The levels of SA of colostrum and cord blood in high-level group were markedly higher than those in low-level one (5.12 ± 0.35) vs. (4.87 ± 0.22) and (1.21 ± 0.02) vs. (1.17 ± 0.01), P < 0.05. High levels of SA of cord blood and colostrums might be beneficial to the early intelligence development of full term infant. Abundant intake of SA during perinatal period and good function of placenta may play important role in early intelligence development.

[Effect of family integrate care on the development of preterm infants at 18 months of age].

PubMed

Li, Y; Gao, X Y; Xiang, X Y; Dai, H M; Yang, L; Shoo K, M Y; Hei, Mingyan

2016-12-02

Objective: To study the effect of family integrated care (FIC) in neonatal intensive care unit (NICU) to the development of preterm infants at 18 months of age. Method: This is a prospective parallel case-control study. Infants in FIC group were preterm infants enrolled in previous FIC study with gestational age (GA) 28-35 weeks. Study period was from July 2015 to July 2016. Subjects were all enrolled from Department of Child Healthcare in the Third Xiangya Hospital of Central South University. Infants in control group were gender, birth weight (BW), BW percentile and days of life (DOL) at follow-up matched (1∶1 ratio) preterm infants who did not enter FIC in NICU. The age at follow-up was 18 months. Study parameters were maternal education year, socioeconomic status (SES) by Graffar method, home observation for measurement of the environment (HOME), mental development index (MDI) and psychomotor development index (PDI) by mental and psychomotor Bayley scales of infant development (BSID). SPSS 20.0 of χ 2 test, t test, Pearson coefficient test and Spearman coefficient test were used for the statistical analysis. Result: Totally 67 infants were enrolled in each of FIC group and control group, with percentage of male gender 52% (35 infants) and 51% (34 infants), representatively. GA of FIC group and control group was (32.4±1.7) and (32.2±1.6) weeks, BW was (1 690±415) and (1 719±412) g. Weight at 18 months follow-up was (10±1) and (10±1) kg, maternal education year was (15±2) and (15±2) years, SES was (42±6) and (41±6) score, HOME was (31±5) and (32±5) score, representatively. There was no significant difference between FIC group and control group in the above parameters, making these 2 groups comparable. The MDI and PDI of FIC group were significantly higher than those of control group ((95±9) vs . (86±9), (87±9) vs . (80±8) score, t =5.506, 4.502, both P =0.000). The MDI and PDI of all groups were positively correlated to GA ( r =0.398 and 0.272, P =0.000 and 0.001), but the difference of MDI or PDI between FIC group and control group was not related to GA ( r =0.679 and -0.393, P =0.094 and 0.383). Conclusion: FIC in NICU is beneficial to the development of preterm infants at 18 months of age. It is worthwhile to promote FIC in NICU in China. Trial registration: Chinese Clinical Trial Registry, ChiCTR-TRC-14004736.

Necrotizing enterocolitis as a prognostic factor for the neurodevelopmental outcome of preterm infants - match control study after 2years.

PubMed

Allendorf, Antje; Dewitz, Ruth; Weber, Joy; Bakthiar, Shahrzad; Schloesser, Rolf; Rolle, Udo

2018-01-31

Necrotizing enterocolitis (NEC) in very low birth weight infants is a risk factor for developmental delay. To our knowledge, there are no studies published investigating the neurodevelopmental outcome of patients with NEC comparing surgically treated and conservatively treated patients versus match paired controls. The aim of this retrospective case control study was to measure the neurodevelopmental outcome of patients with NEC who were treated surgically or conservatively METHODS: All patients were identified, who have been diagnosed with NEC (ICD-10 code, P77) born between 2006 and 2013. Patients with NEC received antibiotic therapy, nasogastric decompression and fasting. Surgical treatment was indicated for patients with Bell stages IIIb. We excluded patients suffering from other relevant diseases with a possible impact on their neurodevelopmental outcome (e.g., intraventricular hemorrhage, associated malformations, asphyxia, focal intestinal perforation, short bowel syndrome). Patients were tested at the corrected gestational age of 24months according to the Bayley Scales of Infant Development II. Each participant was compared to a child of the same sex, gestational age at birth (+/-two days), birth weight (+/-10%), and age at neurodevelopmental testing (IRB approval, No. 14/2014). The outcome measures were the psychomotor index (PDI) and the mental developmental index (MDI). We included 13 conservatively and 24 surgically treated patients. The patients in group A (without surgery) achieved a mean PDI of 106, and those in group B (with surgery) a mean PDI of 90. These values were significantly higher in the conservative group A. The mean MDIs were 99 in the patient group A and 85 in patient group B. This difference was also significant. We found significantly lower MDIs and PDIs in children with surgical treatment of NEC. Further systematic prospective research on the prevention of NEC and systematic follow-ups at later stages in the patients' development are necessary in order to implement early intervention. case control study. III. Copyright © 2018. Published by Elsevier Inc.

Development of double emulsion nanoparticles for the encapsulation of bovine serum albumin.

PubMed

Martinez, Nelida Y; Andrade, Patricia F; Durán, Nelson; Cavalitto, Sebastian

2017-10-01

In the present work, a double emulsion was developed for the encapsulation of Bovine Serum Albumin (BSA) as a model protein for the future encapsulation of viral proteins. The first emulsion polydispersity index (PDI) was studied with increasing concentrations of poly (ε-caprolactone) (PCL) as stabilizer (from 16% w/v to 5% w/v) and polyvinyl alcohol (PVA) as the surfactant in the second emulsion at 1.5% w/v. Results suggest that at decreasing concentrations of PCL the PDI of the emulsion also decrease, indicating that viscosity of the emulsion is crucial in the homogeneity of the resultant size distribution of the nanoparticles. When PVA concentration in the second emulsion was increased from 1.5% w/v to 2.5% w/v the PDI also increased. To study the relationship between the structure of the surfactant in the second emulsion and the resultant BSA encapsulation, emulsions were prepared with Pluronic F68 and PVA both at 1.5% w/v and PCL in the first emulsion at 5% w/v. Results indicated that Pluronic F68 was a better stabilizer because at the same experimental conditions encapsulation of BSA was 1.5 higher than PVA. FTIR studies confirmed the presence of BSA in the nanoparticles. SEM and TEM microscopies showed a size distribution of 300nm-500nm size of nanoparticles. Circular dichroism studies demonstrated that the secondary structure of the protein was conserved after the encapsulation into the nanoparticles. Copyright © 2017 Elsevier B.V. All rights reserved.

Culture: The New Key Terrain Integrating Cultural Competence into JIPB

DTIC Science & Technology

2006-05-25

century of hegemony have done nothing to increase American’s understanding of other cultures. Therefore we are at a distinct disadvantage in the post-Cold...in the Netherlands has patented five cultural dimensions which he calls Personal Power Index (PDI), Individualism (IDV), Masculinity (MAS...group index it is only necessary to define Hofstede’s Masculinity index. Masculinity “focuses on the degree the society reinforces, or does not

Analysis of pain behavior profiles and functional disability in outpatient physical therapy clinics.

PubMed

Hankin, H A; Spencer, T; Kegerreis, S; Worrell, T; Rice, J M

2001-02-01

Descriptive, ex post facto. To determine the proportion of physical therapy outpatients with pain who exhibit various pain behavior profiles, and to determine whether there are differences in functional disability across the profiles. Physical therapists treat many patients who have chronic pain. Research suggests that early identification and multidisciplinary treatment are effective and economical for these patients. The Multidimensional Pain Inventory (MPI) and the Pain Disability Index (PDI) are potential screening tools that could be used in physical therapy clinics to determine which patients should be referred for multidisciplinary treatment. MPI and PDI data were gathered on 57 physical therapy outpatients (mean age 44.3 +/- 14.5 years, 22 men and 35 women) with pain of 3 or more months duration. ANOVA was used to analyze differences in mean PDI scores across the MPI profiles. Of all patients, 42.1% fit the Adaptive Coper profile, 29.8% fit the Interpersonally Distressed profile, and 28.1% fit the Dysfunctional profile. There were significant differences in PDI scores among profile groups. Post hoc analysis showed that the PDI scores of the Adaptive Coper and Interpersonally Distressed groups were different from the Dysfunctional group, but that there was no difference between the Adaptive Coper and Interpersonally Distressed groups. Many patients in outpatient physical therapy settings exhibit behavioral, affective, and cognitive characteristics associated with chronic pain. Thirty-three patients (57.9%) had MPI profiles (interpersonally distressed and dysfunctional) that suggest they might benefit from multidisciplinary treatment.

Antimicrobial photodynamic inactivation: a bright new technique to kill resistant microbes

PubMed Central

Hamblin, Michael R

2016-01-01

Photodynamic therapy (PDT) uses photosensitizers (non-toxic dyes) that are activated by absorption of visible light to form reactive oxygen species (including singlet oxygen) that can oxidize biomolecules and destroy cells. Antimicrobial photodynamic inactivation (aPDI) can treat localized infections. aPDI neither causes any resistance to develop in microbes, nor is affected by existing drug resistance status. We discuss some recent developments in aPDI. New photosensitizers including polycationic conjugates, stable synthetic bacteriochlorins and functionalized fullerenes are described. The microbial killing by aPDI can be synergistically potentiated (several logs) by harmless inorganic salts via photochemistry. Genetically engineered bioluminescent microbial cells allow PDT to treat infections in animal models. Photoantimicrobials have a promising future in the face of the unrelenting increase in antibiotic resistance. PMID:27421070

Long-Lived Charge Separation at Heterojunctions between Semiconducting Single-Walled Carbon Nanotubes and Perylene Diimide Electron Acceptors

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

Kang, Hyun Suk; Sisto, Thomas J.; Peurifoy, Samuel

Nonfullerene electron acceptors have facilitated a recent surge in the efficiencies of organic solar cells, although fundamental studies of the nature of exciton dissociation at interfaces with nonfullerene electron acceptors are still relatively sparse. Semiconducting single-walled carbon nanotubes (s-SWCNTs), unique one-dimensional electron donors with molecule-like absorption and highly mobile charges, provide a model system for studying interfacial exciton dissociation. Here, we investigate excited-state photodynamics at the heterojunction between (6,5) s-SWCNTs and two perylene diimide (PDI)-based electron acceptors. Each of the PDI-based acceptors, hPDI2-pyr-hPDI2 and Trip-hPDI2, is deposited onto (6,5) s-SWCNT films to form a heterojunction bilayer. Transient absorption measurements demonstratemore » that photoinduced hole/electron transfer occurs at the photoexcited bilayer interfaces, producing long-lived separated charges with lifetimes exceeding 1.0 us. Both exciton dissociation and charge recombination occur more slowly for the hPDI2-pyr-hPDI2 bilayer than for the Trip-hPDI2 bilayer. To explain such differences, we discuss the potential roles of the thermodynamic charge transfer driving force available at each interface and the different molecular structure and intermolecular interactions of PDI-based acceptors. As a result, detailed photophysical analysis of these model systems can develop the fundamental understanding of exciton dissociation between organic electron donors and nonfullerene acceptors, which has not been systematically studied.« less

Long-Lived Charge Separation at Heterojunctions between Semiconducting Single-Walled Carbon Nanotubes and Perylene Diimide Electron Acceptors

DOE PAGES

Kang, Hyun Suk; Sisto, Thomas J.; Peurifoy, Samuel; ...

2018-04-13

Nonfullerene electron acceptors have facilitated a recent surge in the efficiencies of organic solar cells, although fundamental studies of the nature of exciton dissociation at interfaces with nonfullerene electron acceptors are still relatively sparse. Semiconducting single-walled carbon nanotubes (s-SWCNTs), unique one-dimensional electron donors with molecule-like absorption and highly mobile charges, provide a model system for studying interfacial exciton dissociation. Here, we investigate excited-state photodynamics at the heterojunction between (6,5) s-SWCNTs and two perylene diimide (PDI)-based electron acceptors. Each of the PDI-based acceptors, hPDI2-pyr-hPDI2 and Trip-hPDI2, is deposited onto (6,5) s-SWCNT films to form a heterojunction bilayer. Transient absorption measurements demonstratemore » that photoinduced hole/electron transfer occurs at the photoexcited bilayer interfaces, producing long-lived separated charges with lifetimes exceeding 1.0 us. Both exciton dissociation and charge recombination occur more slowly for the hPDI2-pyr-hPDI2 bilayer than for the Trip-hPDI2 bilayer. To explain such differences, we discuss the potential roles of the thermodynamic charge transfer driving force available at each interface and the different molecular structure and intermolecular interactions of PDI-based acceptors. As a result, detailed photophysical analysis of these model systems can develop the fundamental understanding of exciton dissociation between organic electron donors and nonfullerene acceptors, which has not been systematically studied.« less

The novel polysaccharide deacetylase homologue Pdi contributes to virulence of the aquatic pathogen Streptococcus iniae

PubMed Central

Milani, Carlo J. E.; Aziz, Ramy K.; Locke, Jeffrey B.; Dahesh, Samira; Nizet, Victor; Buchanan, John T.

2010-01-01

The aquatic zoonotic pathogen Streptococcus iniae represents a threat to the worldwide aquaculture industry and poses a risk to humans who handle raw fish. Because little is known about the mechanisms of S. iniae pathogenesis or virulence factors, we established a high-throughput system combining whole-genome pyrosequencing and transposon mutagenesis that allowed us to identify virulence proteins, including Pdi, the polysaccharide deacetylase of S. iniae, that we describe here. Using bioinformatics tools, we identified a highly conserved signature motif in Pdi that is also conserved in the peptidoglycan deacetylase PgdA protein family. A Δpdi mutant was attenuated for virulence in the hybrid striped bass model and for survival in whole fish blood. Moreover, Pdi was found to promote bacterial resistance to lysozyme killing and the ability to adhere to and invade epithelial cells. On the other hand, there was no difference in the autolytic potential, resistance to oxidative killing or resistance to cationic antimicrobial peptides between S. iniae wild-type and Δpdi. In conclusion, we have demonstrated that pdi is involved in S. iniae adherence and invasion, lysozyme resistance and survival in fish blood, and have shown that pdi plays a role in the pathogenesis of S. iniae. Identification of Pdi and other S. iniae virulence proteins is a necessary initial step towards the development of appropriate preventive and therapeutic measures against diseases and economic losses caused by this pathogen. PMID:19762441

Can brief measures effectively screen for pain and somatic malingering? Examination of the Modified Somatic Perception Questionnaire and Pain Disability Index.

PubMed

Crighton, Adam H; Wygant, Dustin B; Applegate, Kathryn C; Umlauf, Robert L; Granacher, Robert P

2014-09-01

Recent rise in fraudulent disability claims in the United States has resulted in psychologists being increasingly called upon to use psychological tests to determine whether disability claims based on psychological or somatic/pain complaints are legitimate. To examine two brief measures, Modified Somatic Perception Questionnaire (MSPQ) and the Pain Disability Index (PDI), and their ability to screen for malingering in relation to the Bianchini et al. criteria for malingered pain-related disability published in The Spine Journal (2005). Examined brief self-report measures between litigating and nonlitigating pain samples. We compared 144 disability litigants, predominantly presenting a history of musculoskeletal injuries with psychiatric overlay, with 167 nonlitigating pain patients who were predominantly in treatment for chronic back pain issues and other musculoskeletal conditions. Modified Somatic Perception Questionnaire, Pain Disability Index, Minnesota Multiphasic Personality Inventory-2 Restructured Form, Test of Memory Malingering, Letter Memory Test, Victoria Symptom Validity Test, Structured Interview of Reported Symptoms-second edition, Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders somatoform disorders module. We examined a sample of 144 individuals undergoing compensation-seeking evaluations in relation to 167 nonlitigating pain patients. Group differences on both the MSPQ and PDI were calculated, as well as sensitivities, specificities, and positive and negative predictive powers for both measures at selected cutoffs. The results suggest that both the MSPQ and PDI are useful to screen for pain malingering in forensic evaluations, especially the MSPQ, which performed the best in differentiating between the groups. Copyright © 2014 Elsevier Inc. All rights reserved.

What Would Happen to Superstorm Sandy Under the Influence of a Substantially Warmer Atlantic Ocean?

NASA Technical Reports Server (NTRS)

Lau, William K. M.; Shi, J. J.; Tao, W. K.; Kim, K. M.

2016-01-01

Based on ensemble numerical simulations, we find that possible responses of Sandy-like superstorms under the influence of a substantially warmer Atlantic Ocean bifurcate into two groups. In the first group, storms are similar to present-day Sandy from genesis to extratropical transition, except they are much stronger, with peak Power Destructive Index (PDI) increased by 50-80%, heavy rain by 30-50%, and maximum storm size (MSS) approximately doubled. In the second group, storms amplify substantially over the interior of the Atlantic warm pool, with peak PDI increased by 100-160%, heavy rain by 70-180%, and MSS more than tripled compared to present-day Superstorm Sandy. These storms when exiting the warm pool, recurve northeastward out to sea, subsequently interact with the developing midlatitude storm by mutual counterclockwise rotation around each other and eventually amplify into a severe Northeastern coastal storm, making landfall over the extreme northeastern regions from Maine to Nova Scotia.

Intradiscal thermal annuloplasty for the treatment of lumbar discogenic pain in patients with multilevel degenerative disc disease.

PubMed

Kapural, Leonardo; Mekhail, Nagy; Korunda, Zdenko; Basali, Ayman

2004-08-01

Symptomatic degenerative disc disease (DDD) may lead to significant deterioration of quality of life and increased disability. Intradiscal thermal annuloplasty (IDTA) is a minimally invasive treatment for painful DDD. We hypothesized that there may be an improvement in pain scores and the pain disability index (PDI) of patients who have multilevel DDD after IDTA. Patients 24-66 yr old, male and female with multilevel DDD (MDDD) and matched 1 or 2 level DDD (1,2-DDD) patients were enrolled in the study. Visual analog pain scale (VAS) score and PDI were observed for 12 mo. The 1,2-DDD patient group had a 2.5 +/- 2.4 VAS score at 12 mo after annuloplasty compared to 7.7 +/- 2 before the procedure. The MDDD VAS score was 4.9 +/- 2.9 at 12 mo compared to 7.4 +/- 1.8 before the procedure. Similar improvements in PDI were found. The pain relief and PDI were significantly better in patients with 1,2-DDD than in the MDDD group (P = 0.0037 and P = 0.041, respectively). We concluded that IDTA is an effective treatment of discogenic pain and that the number of discs affected by degeneration is an important determinant of the procedure outcome.

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

Balaguru, Karthik; Leung, Lai-Yung R.; Yoon, Jin-Ho

Despite the strong dependence of the Power Dissipation Index (PDI), which is a measure of the intensity of Tropical Cyclone (TC) activity, on tropical sea-surface temperatures (SSTs), the variations in PDI are not completely explained by SST. Here we show, using an analysis of a string of observational data sets, that the variability of the thermocline depth (TD) in the east Pacific exerts a significant degree of control on the variability of PDI in that region. On average, a deep thermocline with a larger reservoir of heat favors TC intensification by reducing SST cooling while a shallow thermocline with amore » smaller heat reservoir promotes enhanced SST cooling that contributes to TC decay. At interannual time scales, the variability of basin-mean TD accounts for nearly 30% of the variability in the PDI during the TC season. Also, about 20% of the interannual variability in the east Pacific basin-mean TD is due to the El Niño and the Southern Oscillation (ENSO), a dominant climate signal in this region. This study suggests that a better understanding of the factors governing the interannual variability of the TD conditions in the east Pacific and how they may change over time, may lead to an improved projection of future east Pacific TC activity.« less

Comparing the Palmer Drought Index and the Standardized Precipitation Index for Zagreb-Gric Observatory

NASA Astrophysics Data System (ADS)

Pandzic, Kreso

2014-05-01

Conventional Palmer Drought Index (PDSI) and recent Standardized Precipitation Index (SPI) are compared for Zagreb-Gric weather station. Historical time series of PDSI and SPI are compared. For that purpose monthly precipitation, air temperature and air humidity data for Zagreb-Gric Observatory and period 1862-2010 are used. The results indicate that SPI is simpler for interpretation than PDI. On the other side, lack of temperature within SPI, make impossible use of it on climate change applications. Further development of both indices is required. Possible applications of them in irrigation scheduling system is considered as well for drought risk assessment. In addition, a comparison of PDSI and SPI for the periods from 1 to 24 months indicate the best agreement between PDSI and SPI for the periods from 6 to 12 months.

The Emergence of Manganese-Based Carbonyl Hydrosilylation Catalysts.

PubMed

Trovitch, Ryan J

2017-11-21

In recent years, interest in homogeneous manganese catalyst development has intensified because of the earth-abundant and nontoxic nature of this metal. Although compounds of Mn have largely been utilized for epoxidation reactions, recent efforts have revealed that Mn catalysts can mediate a broad range of reductive transformations. Low-valent Mn compounds have proven to be particularly effective for the hydrosilylation of carbonyl- and carboxylate-containing substrates, and this Account aims to highlight my research group's contributions to this field. In our initial 2014 communication, we reported that the bis(imino)pyridine-supported compound ( Ph2PPr PDI)Mn mediates ketone hydrosilylation with exceptional activity under solvent-free conditions. Silanes including Ph 2 SiH 2 , (EtO) 3 SiH, (EtO) 2 MeSiH, and (EtO)Me 2 SiH were found to partially reduce cyclohexanone in the presence of ( Ph2PPr PDI)Mn, while turnover frequencies of up to 1280 min -1 were observed using PhSiH 3 . This led us to evaluate the hydrosilylation of 11 additional ketones and allowed for the atom-efficient preparation of tertiary and quaternary silanes. At that time, it was also discovered that ( Ph2PPr PDI)Mn catalyzes the dihydrosilylation of esters (by way of acyl C-O bond hydrosilylation) to yield a mixture of silyl ethers with modest activity. Earlier this year, the scope of these transformations was extended to aldehydes and formates, and the observed hydrosilylation activities are among the highest obtained for any transition-metal catalyst. The effectiveness of three related catalysts has also been evaluated: ( Ph2PPr PDI)MnH, ( PyEt PDEA)Mn, and [( Ph2PEt PDI)Mn] 2 . To our surprise, ( Ph2PPr PDI)MnH was found to exhibit higher carboxylate dihydrosilylation activity than ( Ph2PPr PDI)Mn, while ( PyEt PDEA)Mn demonstrated remarkable carbonyl hydrosilylation activity considering that it lacks a redox-active supporting ligand. The evaluation of [( Ph2PEt PDI)Mn] 2 revealed competitive aldehyde hydrosilylation and formate dihydrosilylation turnover frequencies; however, this catalyst is significantly inhibited by pyridine and alkene donor groups. In our efforts to fully understand how ( Ph2PPr PDI)Mn operates, a thorough electronic structure evaluation was conducted, and the ground-state doublet calculated for this compound was found to exhibit nonclassical features consistent with a low-spin Mn(II) center supported by a singlet PDI dianion and an intermediate-spin Mn(II) configuration featuring antiferromagnetic coupling to PDI diradical dianion. A comprehensive mechanistic investigation of ( Ph2PPr PDI)Mn- and ( Ph2PPr PDI)MnH-mediated hydrosilylation has revealed two operable pathways, a modified Ojima pathway that is more active for carbonyl hydrosilylation and an insertion pathway that is more effective for carboxylate reduction. Although these efforts represent a small fraction of the recent advances made in Mn catalysis, this work has proven to be influential for the development of Mn-based reduction catalysts and is likely to inform future efforts to develop Mn catalysts that can be used to prepare silicones.

Inhibition of the Functional Interplay between Endoplasmic Reticulum (ER) Oxidoreduclin-1α (Ero1α) and Protein-disulfide Isomerase (PDI) by the Endocrine Disruptor Bisphenol A*

PubMed Central

Okumura, Masaki; Kadokura, Hiroshi; Hashimoto, Shoko; Yutani, Katsuhide; Kanemura, Shingo; Hikima, Takaaki; Hidaka, Yuji; Ito, Len; Shiba, Kohei; Masui, Shoji; Imai, Daiki; Imaoka, Susumu; Yamaguchi, Hiroshi; Inaba, Kenji

2014-01-01

Bisphenol A (BPA) is an endocrine disruptor that may have adverse effects on human health. We recently isolated protein-disulfide isomerase (PDI) as a BPA-binding protein from rat brain homogenates and found that BPA markedly inhibited PDI activity. To elucidate mechanisms of this inhibition, detailed structural, biophysical, and functional analyses of PDI were performed in the presence of BPA. BPA binding to PDI induced significant rearrangement of the N-terminal thioredoxin domain of PDI, resulting in more compact overall structure. This conformational change led to closure of the substrate-binding pocket in b′ domain, preventing PDI from binding to unfolded proteins. The b′ domain also plays an essential role in the interplay between PDI and ER oxidoreduclin 1α (Ero1α), a flavoenzyme responsible for reoxidation of PDI. We show that BPA inhibited Ero1α-catalyzed PDI oxidation presumably by inhibiting the interaction between the b′ domain of PDI and Ero1α; the phenol groups of BPA probably compete with a highly conserved tryptophan residue, located in the protruding β-hairpin of Ero1α, for binding to PDI. Consistently, BPA slowed down the reoxidation of PDI and caused the reduction of PDI in HeLa cells, indicating that BPA has a great impact on the redox homeostasis of PDI within cells. However, BPA had no effect on the interaction between PDI and peroxiredoxin-4 (Prx4), another PDI family oxidase, suggesting that the interaction between Prx4 and PDI is different from that of Ero1α and PDI. These results indicate that BPA, a widely distributed and potentially harmful chemical, inhibits Ero1-PDI-mediated disulfide bond formation. PMID:25122773

The C-terminal CGHC motif of protein disulfide isomerase supports thrombosis

PubMed Central

Zhou, Junsong; Wu, Yi; Wang, Lu; Rauova, Lubica; Hayes, Vincent M.; Poncz, Mortimer; Essex, David W.

2015-01-01

Protein disulfide isomerase (PDI) has two distinct CGHC redox-active sites; however, the contribution of these sites during different physiologic reactions, including thrombosis, is unknown. Here, we evaluated the role of PDI and redox-active sites of PDI in thrombosis by generating mice with blood cells and vessel wall cells lacking PDI (Mx1-Cre Pdifl/fl mice) and transgenic mice harboring PDI that lacks a functional C-terminal CGHC motif [PDI(ss-oo) mice]. Both mouse models showed decreased fibrin deposition and platelet accumulation in laser-induced cremaster arteriole injury, and PDI(ss-oo) mice had attenuated platelet accumulation in FeCl3-induced mesenteric arterial injury. These defects were rescued by infusion of recombinant PDI containing only a functional C-terminal CGHC motif [PDI(oo-ss)]. PDI infusion restored fibrin formation, but not platelet accumulation, in eptifibatide-treated wild-type mice, suggesting a direct role of PDI in coagulation. In vitro aggregation of platelets from PDI(ss-oo) mice and PDI-null platelets was reduced; however, this defect was rescued by recombinant PDI(oo-ss). In human platelets, recombinant PDI(ss-oo) inhibited aggregation, while recombinant PDI(oo-ss) potentiated aggregation. Platelet secretion assays demonstrated that the C-terminal CGHC motif of PDI is important for P-selectin expression and ATP secretion through a non-αIIbβ3 substrate. In summary, our results indicate that the C-terminal CGHC motif of PDI is important for platelet function and coagulation. PMID:26529254

Prenatal methamphetamine exposure and neurodevelopmental outcomes in children from 1 to 3 years

PubMed Central

Wouldes, Trecia A.; LaGasse, Linda L.; Huestis, Marilyn A.; DellaGrotta, Sheri; Dansereau, Lynne M.; Lester, Barry M.

2014-01-01

Background: Despite the evidence that women world-wide are using methamphetamine (MA) during pregnancy little is known about the neurodevelopment of their children. Design: The controlled, prospective longitudinal New Zealand (NZ) Infant Development, Environment and Lifestyle (IDEAL) study was carried out in Auckland, NZ. Participants were 103 children exposed to MA prenatally and 107 not exposed. The Mental Developmental Index (MDI) and the Psychomotor Developmental Index (PDI) of the Bayley Scales of Infant Development, Second Edition (BSID-II) measured cognitive and motor performance at ages 1, 2 and 3, and the Peabody Developmental Motor Scale, Second Edition (PDMS-II) measured gross and fine motor performance at 1 and 3. Measures of the child’s environment included the Home Observation of Measurement of the Environment and the Maternal Lifestyle Interview. The Substance Use Inventory measured maternal drug use. Results: After controlling for other drug use and contextual factors, prenatal MA exposure was associated with poorer motor performance at 1 and 2 years on the BSID-II. No differences were observed for cognitive development (MDI). Relative to non-MA exposed children, longitudinal scores on the PDI and the gross motor scale of the PDMS-2 were 4.3 and 3.2 points lower, respectively. Being male and of Maori descent predicted lower cognitive scores (MDI) and being male predicted lower fine motor scores (PDMS-2) Conclusions: Prenatal exposure to MA was associated with delayed gross motor development over the first 3 years, but not cognitive development. However, being male and of Maori descent were both associated with poorer cognitive outcomes. Males in general did more poorly on tasks related to fine motor development. PMID:24566524

Prenatal methamphetamine exposure and neurodevelopmental outcomes in children from 1 to 3 years.

PubMed

Wouldes, Trecia A; Lagasse, Linda L; Huestis, Marilyn A; Dellagrotta, Sheri; Dansereau, Lynne M; Lester, Barry M

2014-01-01

Despite the evidence that women world-wide are using methamphetamine (MA) during pregnancy little is known about the neurodevelopment of their children. The controlled, prospective longitudinal New Zealand (NZ) Infant Development, Environment and Lifestyle (IDEAL) study was carried out in Auckland, NZ. Participants were 103 children exposed to MA prenatally and 107 who were not exposed. The Mental Developmental Index (MDI) and the Psychomotor Developmental Index (PDI) of the Bayley Scales of Infant Development, Second Edition (BSID-II) measured cognitive and motor performances at ages 1, 2 and 3, and the Peabody Developmental Motor Scale, Second Edition (PDMS-II) measured gross and fine motor performances at 1 and 3. Measures of the child's environment included the Home Observation of Measurement of the Environment and the Maternal Lifestyle Interview. The Substance Use Inventory measured maternal drug use. After controlling for other drug use and contextual factors, prenatal MA exposure was associated with poorer motor performance at 1 and 2 years on the BSID-II. No differences were observed for cognitive development (MDI). Relative to non-MA exposed children, longitudinal scores on the PDI and the gross motor scale of the PDMS-2 were 4.3 and 3.2 points lower, respectively. Being male and of Maori descent predicted lower cognitive scores (MDI) and being male predicted lower fine motor scores (PDMS-2). Prenatal exposure to MA was associated with delayed gross motor development over the first 3 years, but not with cognitive development. However, being male and of Maori descent were both associated with poorer cognitive outcomes. Males in general did more poorly on tasks related to fine motor development. Copyright © 2014 Elsevier Inc. All rights reserved.

PON1 and Neurodevelopment in Children from the CHAMACOS Study Exposed to Organophosphate Pesticides in Utero

PubMed Central

Eskenazi, Brenda; Huen, Karen; Marks, Amy; Harley, Kim G.; Bradman, Asa; Barr, Dana Boyd; Holland, Nina

2010-01-01

Background Paraoxonase 1 (PON1) detoxifies oxon derivatives of some organophosphate (OP) pesticides, and its genetic polymorphisms influence enzyme activity and quantity. We previously reported that maternal urinary concentrations of dialkyl phosphate (DAP) metabolites, a marker of OP pesticide exposure, were related to poorer mental development and maternally reported symptoms consistent with pervasive developmental disorder (PDD) in 2-year-olds participating in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study. Objective We determined whether PON1 genotypes and enzyme measurements were associated with child neurobehavioral development and whether PON1 modified the association of in utero exposure to OPs (as assessed by maternal DAPs) and neurobehavior. Methods We measured DAP concentrations in maternal urine during pregnancy, PON1192 and PON1−108 genotypes in mothers and children, and arylesterase (ARYase) and paraoxonase (POase) in maternal, cord, and 2-year-olds’ blood. We assessed 353 2-year-olds on the Mental Development Index (MDI) and Psychomotor Development Index (PDI) of the Bayley Scales of Infant Development and queried their mothers on the Child Behavior Checklist to obtain a score for PDD. Results Children with the PON1−108T allele had poorer MDI scores and somewhat poorer PDI scores. Children were less likely to display PDD when they or their mothers had higher ARYase activity and when their mothers had higher POase activity. The association between DAPs and MDI scores was strongest in children with PON1−108T allele, but this and other interactions between DAPs and PON1 polymorphisms or enzymes were not significant. Conclusion PON1 was associated with child neurobehavioral development, but additional research is needed to confirm whether it modifies the relation with in utero OP exposure. PMID:21126941

Factors Influencing College Student Health: Development of the Psychological Distress Inventory.

ERIC Educational Resources Information Center

Lustman, Patrick J.; And Others

1984-01-01

Describes the three-phase development of the Psychological Distress Inventory (PDI), an instrument designed primarily to measure life stress in college students. Standard psychometric information is presented, including reliability, validity, and some effects of response set. The PDI allows users to separately assess degree of depression, anxiety,…

Expression and Localization of Plant Protein Disulfide Isomerase.

PubMed Central

Shorrosh, B. S.; Subramaniam, J.; Schubert, K. R.; Dixon, R. A.

1993-01-01

A cDNA clone encoding a putative protein disulfide isomerase (PDI, EC 5.3.4.1) from alfalfa (Medicago sativa L.) was expressed in Escherichia coli cells, and an antiserum was raised against the expressed PDI-active protein. The antiserum recognized a protein of approximately 60 kD in extracts from alfalfa, soybean, and tobacco roots and stems. Levels of this protein remained relatively constant on exposure of alfalfa cell suspension cultures to the protein glycosylation inhibitor tunicamycin, whereas a slightly lower molecular mass form, also detected by the antiserum, was induced by this treatment. A lower molecular mass form of PDI was also observed in roots of alfalfa seedlings during the first 5 weeks after germination. PDI levels increased in developing soybean seeds up to 17 d after fertilization and then declined. Tissue print immunoblots revealed highest levels of PDI protein in the cambial tissues of soybean stems and petioles and in epidermal, subepidermal, cortical, and pith tissues of stems of alfalfa and tobacco. Immunogold electron microscopy confirmed the localization of PDI to the endoplasmic reticulum in soybean root nodules. PMID:12231974

Assessment of Photodynamic Inactivation against Periodontal Bacteria Mediated by a Chitosan Hydrogel in a 3D Gingival Model

PubMed Central

Peng, Po-Chun; Hsieh, Chien-Ming; Chen, Chueh-Pin; Tsai, Tsuimin; Chen, Chin-Tin

2016-01-01

Chitosan hydrogels containing hydroxypropyl methylcellulose (HPMC) and toluidine blue O were prepared and assessed for their mucoadhesive property and antimicrobial efficacy of photodynamic inactivation (PDI). Increased HPMC content in the hydrogels resulted in increased mucoadhesiveness. Furthermore, we developed a simple In Vitro 3D gingival model resembling the oral periodontal pocket to culture the biofilms of Staphylococcus aureus (S. aureus), Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans), and Porphyromonas gingivalis (P. gingivalis). The PDI efficacy of chitosan hydrogel was examined against periodontal biofilms cultured in this 3D gingival model. We found that the PDI effectiveness was limited due to leaving some of the innermost bacteria alive at the non-illuminated site. Using this 3D gingival model, we further optimized PDI procedures with various adjustments of light energy and irradiation sites. The PDI efficacy of the chitosan hydrogel against periodontal biofilms can significantly improve via four sides of irradiation. In conclusion, this study not only showed the clinical applicability of this chitosan hydrogel but also the importance of the light irradiation pattern in performing PDI for periodontal disease. PMID:27809278

Assessment of Photodynamic Inactivation against Periodontal Bacteria Mediated by a Chitosan Hydrogel in a 3D Gingival Model.

PubMed

Peng, Po-Chun; Hsieh, Chien-Ming; Chen, Chueh-Pin; Tsai, Tsuimin; Chen, Chin-Tin

2016-11-01

Chitosan hydrogels containing hydroxypropyl methylcellulose (HPMC) and toluidine blue O were prepared and assessed for their mucoadhesive property and antimicrobial efficacy of photodynamic inactivation (PDI). Increased HPMC content in the hydrogels resulted in increased mucoadhesiveness. Furthermore, we developed a simple In Vitro 3D gingival model resembling the oral periodontal pocket to culture the biofilms of Staphylococcus aureus ( S. aureus ), Aggregatibacter actinomycetemcomitans ( A. actinomycetemcomitans ), and Porphyromonas gingivalis ( P. gingivalis ). The PDI efficacy of chitosan hydrogel was examined against periodontal biofilms cultured in this 3D gingival model. We found that the PDI effectiveness was limited due to leaving some of the innermost bacteria alive at the non-illuminated site. Using this 3D gingival model, we further optimized PDI procedures with various adjustments of light energy and irradiation sites. The PDI efficacy of the chitosan hydrogel against periodontal biofilms can significantly improve via four sides of irradiation. In conclusion, this study not only showed the clinical applicability of this chitosan hydrogel but also the importance of the light irradiation pattern in performing PDI for periodontal disease.

High-performance peroxidase mimics for rapid colorimetric detection of H2O2 and glucose derived from perylene diimides functionalized Co3O4 nanoparticles.

PubMed

Ding, Yanan; Chen, Miaomiao; Wu, Kaili; Chen, Mingxing; Sun, Lifang; Liu, Zhenxue; Shi, Zhiqiang; Liu, Qingyun

2017-11-01

N,N'-di-caboxy methyl perylene diimides (PDI), as one of the most promising functional materials in optional chemosensing, was first used to combine with Co 3 O 4 nanoparticles through a facile two-step hydrothermal method and obtain the PDI functionalized Co 3 O 4 nanocomposites (PDI-Co 3 O 4 NCs). PDI-Co 3 O 4 NCs were characterized by a series of technical analysis including transmission electron microscope (TEM), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR), respectively. The experimental results indicated that the as-prepared PDI-Co 3 O 4 NCs possessed the higher peroxidase-like activity than that of Co 3 O 4 nanoparticles without PDI, and could rapidly catalyze oxidation reaction of the chromogenic substrate TMB in the presence of H 2 O 2 to a blue product (oxTMB) observed by the naked eye. The improved catalytic activity of PDI-Co 3 O 4 NCs for colorimetric reactions could be attributed to the synergistic effects of PDI and Co 3 O 4 nanoparticles. On the basis of these experimental results, a convenient colorimetric system based on PDI-Co 3 O 4 as enzyme mimic that is highly sensitive and selective was developed for glucose detection. Meanwhile, the electron transfer between H 2 O 2 and TMB was responsible for the oxidation of TMB. The present work demonstrates a general strategy for the design of organic molecules functionalized oxide for different applications, such as nanocatalysts, biosensors and nanomedicine. Copyright © 2017 Elsevier B.V. All rights reserved.

Intranasal brain-targeted clonazepam polymeric micelles for immediate control of status epilepticus: in vitro optimization, ex vivo determination of cytotoxicity, in vivo biodistribution and pharmacodynamics studies.

PubMed

Nour, Samia A; Abdelmalak, Nevine S; Naguib, Marianne J; Rashed, Hassan M; Ibrahim, Ahmed B

2016-11-01

Clonazepam (CZ) is an anti-epileptic drug used mainly in status epilepticus (SE). The drug belongs to Class II according to BCS classification with very limited solubility and high permeability and it suffers from extensive first-pass metabolism. The aim of the present study was to develop CZ-loaded polymeric micelles (PM) for direct brain delivery allowing immediate control of SE. PM were prepared via thin film hydration (TFH) technique adopting a central composite face-centered design (CCFD). The seventeen developed formulae were evaluated in terms of entrapment efficiency (EE), particle size (PS), polydispersity index (PDI), zeta potential (ZP), and in vitro release. For evaluating the in vivo behavior of the optimized formula, both biodistrbution using 99m Tc-radiolabeled CZ and pharmacodynamics studies were done in addition to ex vivo cytotoxicty. At a drug:Pluronic® P123:Pluronic® L121 ratio of 1:20:20 (PM7), a high EE, ZP, Q8h, and a low PDI was achieved. The biodistribution studies revealed that the optimized formula had significantly higher drug targeting efficiency (DTE = 242.3%), drug targeting index (DTI = 144.25), and nose-to-brain direct transport percentage (DTP = 99.30%) and a significant prolongation of protection from seizures in comparison to the intranasally administered solution with minor histopathological changes. The declared results reveal the ability of the developed PM to be a strong potential candidate for the emergency treatment of SE.

Evaluating health of paddy rice field ecosystem with remote sensing and GIS in Lower Yangtze River Plain, China

NASA Astrophysics Data System (ADS)

Li, Jingjing; Qin, Zhihao; Li, Wenjuan; Lin, Lu

2008-10-01

A paddy rice ecosystem is a farming system composed of paddy, animals, microbes and other environmental factors in specific time and space, with particular temporal and spatial dynamics. Since paddy rice is a main grain crop to feed above half of population in China, the performance of paddy rice ecosystem is highly concerned to yield level of paddy and food supply safety in China. Therefore, monitoring the performance of paddy rice ecosystem is very important to obtain the required information for evaluation of ecosystem health. In the study we intend to develop an approach to monitor the ecosystem performance spatially and dynamically in a regional scale using MODIS remote sensing data and GIS spatial mapping. On the basis of key factors governing the paddy rice ecosystem, we accordingly develop the following three indicators for the evaluation: Crop growing index (CGI), environmental Index (EI), and pests-diseases index (PDI). Then, we integrated the three indicators into a model with different weight coefficients to calculate Comprehensive ecosystem health index (CEHI) to evaluate the performance and functioning of paddy rice ecosystem in a regional scale. CGI indicates the health status of paddy rice calculated from the normalizing enhanced vegetation Index (EVI) retrieved from MODIS data. EI is estimated from temperature Index (TI) and precipitation Index (PI) indicating heat and water stress on the rice field. PDI reflects the damage brought by pests and diseases, which can be estimated using the information obtained from governmental websites. Applying the approach to Lower Yangtze River Plain, we monitor and evaluate the performance of paddy rice ecosystem in various stages of rice growing period in 2006. The results indicated that the performance of the ecosystem was generally very encouraging. During booting stage and heading and blooming stage, the health level was the highest in Anhui province, which is the main paddy rice producer in the region. During stage of yellow ripeness, Jiangsu province had the lowest level of performance. Yield level of paddy rice in 2006 confirms that the applicability of the proposed approach for a rapid evaluation and monitoring of agricultural ecosystem performance in Lower Yangtze River Plain. As a result, the new approach could supply scientific basis for relevant departments taking policies and measures to make sure stable development of paddy yield.

Evaluating Teachers' Professional Development Initiatives: Towards an Extended Evaluative Framework

ERIC Educational Resources Information Center

Merchie, Emmelien; Tuytens, Melissa; Devos, Geert; Vanderlinde, Ruben

2018-01-01

Evaluating teachers' professional development initiatives (PDI) is one of the main challenges for the teacher professionalisation field. Although different studies have focused on the effectiveness of PDI, the obtained effects and evaluative methods have been found to be widely divergent. By means of a narrative review, this study provides an…

Design and formulation of nano-sized spray dried efavirenz-part I: influence of formulation parameters

NASA Astrophysics Data System (ADS)

Katata, Lebogang; Tshweu, Lesego; Naidoo, Saloshnee; Kalombo, Lonji; Swai, Hulda

2012-11-01

Efavirenz (EFV) is one of the first-line antiretroviral drugs recommended by the World Health Organisation for treating HIV. It is a hydrophobic drug that suffers from low aqueous solubility (4 μg/mL), which leads to a limited oral absorption and low bioavailability. In order to improve its oral bioavailability, nano-sized polymeric delivery systems are suggested. Spray dried polycaprolactone-efavirenz (PCL-EFV) nanoparticles were prepared by the double emulsion method. The Taguchi method, a statistical design with an L8 orthogonal array, was implemented to optimise the formulation parameters of PCL-EFV nanoparticles. The types of sugar (lactose or trehalose), surfactant concentration and solvent (dichloromethane and ethyl acetate) were chosen as significant parameters affecting the particle size and polydispersity index (PDI). Small nanoparticles with an average particle size of less than 254 ± 0.95 nm in the case of ethyl acetate as organic solvent were obtained as compared to more than 360 ± 19.96 nm for dichloromethane. In this study, the type of solvent and sugar were the most influencing parameters of the particle size and PDI. Taguchi method proved to be a quick, valuable tool in optimising the particle size and PDI of PCL-EFV nanoparticles. The optimised experimental values for the nanoparticle size and PDI were 217 ± 2.48 nm and 0.093 ± 0.02.

Enrichment desired quality chitosan fraction and advance yield by sequential static and static-dynamic supercritical CO2.

PubMed

Hsieh, Yi-Yin; Chin, Hui Yen; Tsai, Min-Lang

2015-11-20

This study aimed to establish the sequential static and static-dynamic supercritical carbon dioxide (SDCO2) fractionation conditions to obtain a higher yield and desired chitosan with lower polydispersity index (PDI) and higher degree of deacetylation (DD). The yield increased with increasing DD of used chitosan and amount of cosolvent. The yield of acetic acid cosolvent was higher than those of malic and citric acid cosolvents. SDCO2, compared to static supercritical carbon dioxide, has higher yield. The yield of extracted chitosan was 5.82-14.70% by SDCO2/acetic acid, which increases with increasing pressure. The DD of fractionated chitosan increased from 66.1% to 70.81-85.33%, while the PDI decreased from 3.97 to 1.69-3.16. The molecular weight changed from 622kDa to 412-649kDa, which increased as density of supercritical carbon dioxide increases. Hence, higher DD and lower PDI extracted chitosan can be obtained through controlling the temperature and pressure of SDCO2. Copyright © 2015 Elsevier Ltd. All rights reserved.

Optimization of processing parameters for the preparation of phytosterol microemulsions by the solvent displacement method.

PubMed

Leong, Wai Fun; Che Man, Yaakob B; Lai, Oi Ming; Long, Kamariah; Misran, Misni; Tan, Chin Ping

2009-09-23

The purpose of this study was to optimize the parameters involved in the production of water-soluble phytosterol microemulsions for use in the food industry. In this study, response surface methodology (RSM) was employed to model and optimize four of the processing parameters, namely, the number of cycles of high-pressure homogenization (1-9 cycles), the pressure used for high-pressure homogenization (100-500 bar), the evaporation temperature (30-70 degrees C), and the concentration ratio of microemulsions (1-5). All responses-particle size (PS), polydispersity index (PDI), and percent ethanol residual (%ER)-were well fit by a reduced cubic model obtained by multiple regression after manual elimination. The coefficient of determination (R(2)) and absolute average deviation (AAD) value for PS, PDI, and %ER were 0.9628 and 0.5398%, 0.9953 and 0.7077%, and 0.9989 and 1.0457%, respectively. The optimized processing parameters were 4.88 (approximately 5) homogenization cycles, homogenization pressure of 400 bar, evaporation temperature of 44.5 degrees C, and concentration ratio of microemulsions of 2.34 cycles (approximately 2 cycles) of high-pressure homogenization. The corresponding responses for the optimized preparation condition were a minimal particle size of 328 nm, minimal polydispersity index of 0.159, and <0.1% of ethanol residual. The chi-square test verified the model, whereby the experimental values of PS, PDI, and %ER agreed with the predicted values at a 0.05 level of significance.

BIOMARKERS S100B AND NSE PREDICT OUTCOME IN HYPOTHERMIA-TREATED ENCEPHALOPATHIC NEWBORNS

PubMed Central

Massaro, An N.; Chang, Taeun; Baumgart, Stephen; McCarter, Robert; Nelson, Karin B.; Glass, Penny

2014-01-01

Objective To evaluate if serum S100B protein and neuron specific enolase (NSE) measured during therapeutic hypothermia are predictive of neurodevelopmental outcome at 15 months in children with neonatal encephalopathy (NE). Design Prospective longitudinal cohort study Setting A level IV neonatal intensive care unit in a free-standing children’s hospital. Patients Term newborns with moderate to severe NE referred for therapeutic hypothermia during the study period. Interventions Serum NSE and S100B were measured at 0, 12, 24 and 72 hrs of hypothermia. Measurements and Main Reseults Of the 83 infants were enrolled, fifteen (18%) died in the newborn period. Survivors were evaluated by the Bayley Scales of Infant Development (BSID-II) at 15 months of age. Outcomes were assessed in 49/68 (72%) survivors at a mean age of 15.2±2.7 months. Neurodevelopmental outcome was classified by BSID-II Mental (MDI) and Psychomotor (PDI) Developmental Index scores, reflecting cognitive and motor outcomes respectively. Four-level outcome classifications were defined a priori: normal= MDI/PDI within 1SD (>85), mild= MDI/PDI <1SD (70–85), moderate/severe= MDI/PDI <2SD (<70), or died. Elevated serum S100B and NSE levels measured during hypothermia were associated with increasing outcome severity after controlling for baseline and soceioeconomic characteristics in ordinal regression models. Adjusted odds ratios for cognitive outcome were: S100B 2.5 (95% CI 1.3–4.8) and NSE 2.1 (1.2–3.6); for motor outcome: S100B 2.6 (1.2–5.6) and NSE 2.1 (1.2–3.6). Conclusions Serum S100B and NSE levels in babies with NE are associated with neurodevelopmental outcome at 15 months. These putative biomarkers of brain injury may help direct care during therapeutic hypothermia. PMID:24777302

Relationship of Intraoperative Cerebral Oxygen Saturation to Neurodevelopmental Outcome and Brain MRI at One Year of Age in Infants Undergoing Biventricular Repair

PubMed Central

Kussman, Barry D.; Wypij, David; Laussen, Peter C.; Soul, Janet S.; Bellinger, David C.; DiNardo, James A.; Robertson, Richard; Pigula, Frank A.; Jonas, Richard A.; Newburger, Jane W.

2010-01-01

Background Near-infrared spectroscopy (NIRS) monitoring of cerebral oxygen saturation (rSO2) has become routine in many centers, but no studies have reported the relationship of intraoperative NIRS to long-term neurodevelopmental outcomes after cardiac surgery. Methods and Results Of 104 infants undergoing biventricular repair without aortic arch reconstruction, 89 (86%) returned for neurodevelopmental testing at age 1 year. The primary NIRS variable was the integrated rSO2 (area under the curve) for rSO2 ≤ 45%; secondary variables were the average and minimum rSO2 by perfusion phase and at specific time points. Psychomotor (PDI) and Mental Development Indexes of the Bayley Scales, head circumference, neurologic examination, and abnormalities on brain MRI did not differ between subjects according to a threshold level for rSO2 of 45%. Lower PDI scores were modestly associated with lower average (r=0.23; P=0.03) and minimum rSO2 (r=0.22; P=0.04) during the 60 minute period following cardiopulmonary bypass (CPB), but not with other perfusion phases. Hemosiderin foci on brain MRI were associated with lower average rSO2 from post-induction to 60 minutes post-CPB (71±10 vs. 78±6%; P=0.01), and lower average rSO2 during the rewarming phase (72±12 vs. 83±9%; P=0.003) and during the 60 minute period following CPB (65±11 vs. 75±10%; P=0.009). In regression analyses adjusting for age ≤ 30 days, PDI score (P=0.02) and brain hemosiderin (P=0.04) remained significantly associated with rSO2 during the 60 minute period following CPB. Conclusions Perioperative periods of diminished cerebral oxygen delivery, as indicated by rSO2, are associated with one-year PDI and brain MRI abnormalities among infants undergoing reparative heart surgery. Clinical Trial Registration Information http://clinicaltrials.gov/ct2/show/NCT00006183 PMID:20606124

Characterization and stability studies of a novel liposomal cyclosporin A prepared using the supercritical fluid method: comparison with the modified conventional Bangham method

PubMed Central

Karn, Pankaj Ranjan; Cho, Wonkyung; Park, Hee-Jun; Park, Jeong-Sook; Hwang, Sung-Joo

2013-01-01

A novel method to prepare cyclosporin A encapsulated liposomes was introduced using supercritical fluid of carbon dioxide (SCF-CO2) as an antisolvent. To investigate the strength of the newly developed SCF-CO2 method compared with the modified conventional Bangham method, particle size, zeta potential, and polydispersity index (PDI) of both liposomal formulations were characterized and compared. In addition, entrapment efficiency (EE) and drug loading (DL) characteristics were analyzed by reversed-phase high-performance liquid chromatography. Significantly larger particle size and PDI were revealed from the conventional method, while EE (%) and DL (%) did not exhibit any significant differences. The SCF-CO2 liposomes were found to be relatively smaller, multilamellar, and spherical with a smoother surface as determined by transmission electron microscopy. SCF-CO2 liposomes showed no significant differences in their particle size and PDI after more than 3 months, whereas conventional liposomes exhibited significant changes in their particle size. The initial yield (%), EE (%), and DL (%) of SCF-CO2 liposomes and conventional liposomes were 90.98 ± 2.94, 92.20 ± 1.36, 20.99 ± 0.84 and 90.72 ± 2.83, 90.24 ± 1.37, 20.47 ± 0.94, respectively, which changed after 14 weeks to 86.65 ± 0.30, 87.63 ± 0.72, 18.98 ± 0.22 and 75.04 ± 8.80, 84.59 ± 5.13, 15.94 ± 2.80, respectively. Therefore, the newly developed SCF-CO2 method could be a better alternative compared with the conventional method and may provide a promising approach for large-scale production of liposomes. PMID:23378759

Application of calculated NMR parameters, aromaticity indices and wavefunction properties for evaluation of corrosion inhibition efficiency of pyrazine inhibitors

NASA Astrophysics Data System (ADS)

Behzadi, Hadi; Manzetti, Sergio; Dargahi, Maryam; Roonasi, Payman; Khalilnia, Zahra

2018-01-01

In light of the importance of developing novel corrosion inhibitors, a series of quantum chemical calculations were carried out to evaluate 15N chemical shielding CS tensors as well as aromaticity indexes including NICS, HOMA, FLU, and PDI of three pyrazine derivatives, 2-methylpyrazine (MP), 2-aminopyrazine (AP) and 2-amino-5-bromopyrazine (ABP). The NICS parameters have been shown in previous studies to be paramount to the prediction of anti-corrosion properties, and have been combined here with HOMA, FLU and PDI and detailed wavefunction analysis to determine the effects from bromination and methylation on pyrazine. The results show that the electron density around the nitrogens, represented by CS tensors, can be good indicators of anti-corrosion efficiency. Additionally, the NICS, FLU and PDI, as aromaticity indicators of molecule, are well correlated with experimental corrosion inhibition efficiencies of the studied inhibitors. Bader sampling and detailed wavefunction analysis shows that the major effects from bromination on the pyrazine derivatives affect the Laplacian of the electron density of the ring, delocalizing the aromatic electrons of the carbon atoms into lone pairs and increasing polarization of the Laplacian values. This feature is well agreement with empirical studies, which show that ABP is the most efficient anti-corrosion compound followed by AP and MP, a property which can be attributed and predicted by derivation of the Laplacian of the electron density of the ring nuclei. This study shows the importance of devising DFT methods for development of new corrosion inhibitors, and the strength of electronic and nuclear analysis, and depicts most importantly how corrosion inhibitors composed of aromatic moieties may be modified to increase anti-corrosive properties.

Duloxetine loaded-microemulsion system to improve behavioral activities by upregulating serotonin and norepinephrine in brain for the treatment of depression.

PubMed

Sindhu, Pardeep; Kumar, Shobhit; Iqbal, Babar; Ali, Javed; Baboota, Sanjula

2018-04-01

Duloxetine is a well-known antidepressant molecule which is used in the treatment of depression but due to poor solubility it suffers with the drawback of low oral bioavailability. The objective of present work was to formulate and characterize duloxetine loaded microemulsion to enhance the oral bioavailability. Prepared microemulsion was studied for droplet size, zeta potential, refractive index, polydispersity index (PDI), percentage transmittance, viscosity and in vitro release study. Optimized microemulsion (D1) showed spherical droplets with mean diameter of 35.40 ± 3.11 nm, PDI of 0.170 and zeta potential values of -25.8 mV. Formulation showed good transmittance (greater than 99%), viscosity (0.205 Pa s) and refractive index (1.43 ± 0.01). Increased duloxetine release was obtained with microemulsion in comparison to drug suspension. Behavioral tests like mobility test, tail suspension test and forced swimming test performed in depressed and treated rats with duloxetine microemulsion significantly improved the behavioral activities in comparison to duloxetine suspension. Pharmacokinetic studies showed that microemulsion exhibited 1.8 times increment in bioavailability in comparison to duloxetine suspension. Copyright © 2018 Elsevier Ltd. All rights reserved.

Development and characterization of voriconazole loaded nanoparticles for parenteral delivery.

PubMed

Füredi, Petra; Kovács, Kristóf; Ludányi, Krisztina; Antal, István; Klebovich, Imre

2016-08-20

Human serum albumin (HSA) has attracted the most attention in the last decades as a new nanocarrier system of active pharmaceutical ingredients (API) due to its biocompatibility and high binding capacity to hydrophobic drugs. Voriconazole (VCZ), an antifungal agent with low water solubility, was selected to produce albumin based nanoparticles using nanoparticle albumin-bound technology (nab™-technology). Aim of our study was to study the development process of VCZ-loaded nanoparticles for parenteral drug delivery, such as homogenizing pressure, homogenizing cycle number and drug loading capacity. The main characters of nanoparticles such as particle size distribution and polydispersity index (PDI) were determined by dynamic light scattering. Six homogenization cycles at 1800bar were ensured the acceptable PDI value (lower than 0.3) of the VCZ content nanoparticles. Optimized formulation process produced 81.2±1nm average particle size which meets the requirements of intravenous administration. Furthermore, the encapsulated concentration of VCZ was 69.7±4.2% and the water solubility was over 2 times greater than the API itself which were determined by the developed HPLC method. The in vivo release behavior can be predicted from our applied in vitro dissolution study. Almost 50% of VCZ was liberated from the nanoparticles in the first 60min. Copyright © 2016 Elsevier B.V. All rights reserved.

PreImplantation factor (PIF) protects cultured embryos against oxidative stress: relevance for recurrent pregnancy loss (RPL) therapy.

PubMed

Goodale, Lindsay F; Hayrabedran, Soren; Todorova, Krassimira; Roussev, Roumen; Ramu, Sivakumar; Stamatkin, Christopher; Coulam, Carolyn B; Barnea, Eytan R; Gilbert, Robert O

2017-05-16

Recurrent pregnancy loss (RPL) affects 2-3% of couples. Despite a detailed work-up, the etiology is frequently undefined, leading to non-targeted therapy. Viable embryos and placentae express PreImplantation Factor (PIF). Maternal circulating PIF regulates systemic immunity and reduces circulating natural killer cells cytotoxicity in RPL patients. PIF promotes singly cultured embryos' development while anti-PIF antibody abrogates it. RPL serum induced embryo toxicity is negated by PIF. We report that PIF rescues delayed embryo development caused by <3 kDa RPL serum fraction likely by reducing reactive oxygen species (ROS). We reveal that protein disulfide isomerase/thioredoxin (PDI/TRX) is a prime PIF target in the embryo, rendering it an important ROS scavenger. The 16F16-PDI/TRX inhibitor drastically reduced blastocyst development while exogenous PIF increased >2 fold the number of embryos reaching the blastocyst stage. Mechanistically, PDI-inhibitor preferentially binds covalently to oxidized PDI over its reduced form where PIF avidly binds. PIF by targeting PDI/TRX at a distinct site limits the inhibitor's pro-oxidative effects. The >3kDa RPL serum increased embryo demise by three-fold, an effect negated by PIF. However, embryo toxicity was not associated with the presence of putative anti-PIF antibodies. Collectively, PIF protects cultured embryos both against ROS, and higher molecular weight toxins. Using PIF for optimizing in vitro fertilization embryos development and reducing RPL is warranted.

Reduction of the 3,4,9,10-perylenediimides and the formation of eletrodeposited films based on their radical anions

NASA Astrophysics Data System (ADS)

Zhu, Yuan-Yuan; Gu, Shuang-Xi

2014-09-01

The reduction of the two 3,4,9,10-perylene diimide (PDI) derivatives in the mixture of hydrazine hydrate and N,N-dimethylformamide was investigated by the UV-vis absorption spectra, fluorescence spectra (FL) and electron spin resonance spectroscopy (ESR). The time dependence of the PDI content, as well as the structure of PDI aggregates were also investigated and discussed. Combining the electro-migration behavior of PDI-· with the molecular self-assembly properties, the films of two PDI derivatives (PDI-32 and PDI-123) were successfully fabricated via anode electro-deposition (AED). The difference of aggregation state between the two PDI films was studied by UV-vis absorption spectra, XRD and SEM. Based on these, the formation mechanism of PDI films was also deduced.

The patient dignity inventory: a novel way of measuring dignity-related distress in palliative care.

PubMed

Chochinov, Harvey Max; Hassard, Thomas; McClement, Susan; Hack, Thomas; Kristjanson, Linda J; Harlos, Mike; Sinclair, Shane; Murray, Alison

2008-12-01

Quality palliative care depends on a deep understanding of distress facing patients nearing death. Yet, many aspects of psychosocial, existential and spiritual distress are often overlooked. The aim of this study was to test a novel psychometric--the Patient Dignity Inventory (PDI)--designed to measure various sources of dignity-related distress among patients nearing the end of life. Using standard instrument development techniques, this study examined the face validity, internal consistency, test-retest reliability, factor structure and concurrent validity of the PDI. The 25-items of the PDI derive from a model of dignity in the terminally ill. To establish its basic psychometric properties, the PDI was administered to 253 patients receiving palliative care, along with other measures addressing issues identified within the Dignity Model in the Terminally Ill. Cronbach's coefficient alpha for the PDI was 0.93; the test-retest reliability was r = 0.85. Factor analysis resulted in a five-factor solution; factor labels include Symptom Distress, Existential Distress, Dependency, Peace of Mind, and Social Support, accounting for 58% of the overall variance. Evidence for concurrent validity was reported by way of significant associations between PDI factors and concurrent measures of distress. The PDI is a valid and reliable new instrument, which could assist clinicians to routinely detect end-of-life dignity-related distress. Identifying these sources of distress is a critical step toward understanding human suffering and should help clinicians deliver quality, dignity-conserving end-of-life care.

Fluorescent supramolecular micelles for imaging-guided cancer therapy

NASA Astrophysics Data System (ADS)

Sun, Mengmeng; Yin, Wenyan; Dong, Xinghua; Yang, Wantai; Zhao, Yuliang; Yin, Meizhen

2016-02-01

A novel smart fluorescent drug delivery system composed of a perylene diimide (PDI) core and block copolymer poly(d,l-lactide)-b-poly(ethyl ethylene phosphate) is developed and named as PDI-star-(PLA-b-PEEP)8. The biodegradable PDI-star-(PLA-b-PEEP)8 is a unimolecular micelle and can self-assemble into supramolecular micelles, called as fluorescent supramolecular micelles (FSMs), in aqueous media. An insoluble drug camptothecin (CPT) can be effectively loaded into the FSMs and exhibits pH-responsive release. Moreover, the FSMs with good biocompatibility can also be employed as a remarkable fluorescent probe for cell labelling because the maximum emission of PDI is beneficial for bio-imaging. The flow cytometry and confocal laser scanning microscopy analysis demonstrate that the micelles are easily endocytosed by cancer cells. In vitro and in vivo tumor growth-inhibitory studies reveal a better therapeutic effect of FSMs after CPT encapsulation when compared with the free CPT drug. The multifunctional FSM nanomedicine platform as a nanovehicle has great potential for fluorescence imaging-guided cancer therapy.A novel smart fluorescent drug delivery system composed of a perylene diimide (PDI) core and block copolymer poly(d,l-lactide)-b-poly(ethyl ethylene phosphate) is developed and named as PDI-star-(PLA-b-PEEP)8. The biodegradable PDI-star-(PLA-b-PEEP)8 is a unimolecular micelle and can self-assemble into supramolecular micelles, called as fluorescent supramolecular micelles (FSMs), in aqueous media. An insoluble drug camptothecin (CPT) can be effectively loaded into the FSMs and exhibits pH-responsive release. Moreover, the FSMs with good biocompatibility can also be employed as a remarkable fluorescent probe for cell labelling because the maximum emission of PDI is beneficial for bio-imaging. The flow cytometry and confocal laser scanning microscopy analysis demonstrate that the micelles are easily endocytosed by cancer cells. In vitro and in vivo tumor growth-inhibitory studies reveal a better therapeutic effect of FSMs after CPT encapsulation when compared with the free CPT drug. The multifunctional FSM nanomedicine platform as a nanovehicle has great potential for fluorescence imaging-guided cancer therapy. Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nr00450d

Cerebral blood flow velocity and neurodevelopmental outcome in infants undergoing surgery for congenital heart disease.

PubMed

Cheng, Henry H; Wypij, David; Laussen, Peter C; Bellinger, David C; Stopp, Christian D; Soul, Janet S; Newburger, Jane W; Kussman, Barry D

2014-07-01

Cerebral blood flow velocity (CBFV) measured by transcranial Doppler sonography has provided information on cerebral perfusion in patients undergoing infant heart surgery, but no studies have reported a relationship to early postoperative and long-term neurodevelopmental outcomes. CBFV was measured in infants undergoing biventricular repair without aortic arch reconstruction as part of a trial of hemodilution during cardiopulmonary bypass (CPB); CBFV (Vm, mean; Vs, systolic; Vd, end-diastolic) in the middle cerebral artery and change in Vm (rVm) were measured intraoperatively and up to 18 hours post-CPB. Neurodevelopmental outcomes, measured at 1 year of age, included the psychomotor development index (PDI) and mental development index (MDI) of the Bayley Scales of Infant Development-II. CBFV was measured in 100 infants; 43 with D-transposition of the great arteries, 36 with tetralogy of Fallot, and 21 with ventricular septal defects. Lower Vm, Vs, Vd, and rVm at 18 hours post-CPB were independently related to longer intensive care unit duration of stay (p<0.05). In the 85 patients who returned for neurodevelopmental testing, lower Vm, Vs, Vd, and rVm at 18 hours post-CPB were independently associated with lower PDI (p<0.05) and MDI (p<0.05, except Vs: p=0.06) scores. Higher Vs and rVm at 18 hours post-CPB were independently associated with increased incidence of brain injury on magnetic resonance imaging in 39 patients. Postoperative CBFV after biventricular repair is related to early postoperative and neurodevelopmental outcomes at 1 year of age, possibly indicating that low CBFV is a marker of suboptimal postoperative hemodynamics and cerebral perfusion. Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Cerebral Blood Flow Velocity and Neurodevelopmental Outcome in Infants Undergoing Surgery for Congenital Heart Disease

PubMed Central

Cheng, Henry H.; Wypij, David; Laussen, Peter C.; Bellinger, David C.; Stopp, Christian D.; Soul, Janet S.; Newburger, Jane W.; Kussman, Barry D.

2014-01-01

Background Cerebral blood flow velocity (CBFV) measured by transcranial Doppler sonography has provided information on cerebral perfusion in patients undergoing infant heart surgery, but no studies have reported a relationship to early postoperative and long-term neurodevelopmental outcomes. Methods CBFV was measured in infants undergoing biventricular repair without aortic arch reconstruction as part of a trial of hemodilution during cardiopulmonary bypass (CPB). CBFV (Vm, mean; Vs, systolic; Vd, end-diastolic) in the middle cerebral artery and change in Vm (rVm) were measured intraoperatively and up to 18 hours post-CPB. Neurodevelopmental outcomes, measured at 1 year of age, included the Psychomotor Development Index (PDI) and Mental Development Index (MDI) of the Bayley Scales of Infant Development-II. Results CBFV was measured in 100 infants: 43 with D-transposition of the great arteries, 36 with tetralogy of Fallot, and 21 with ventricular septal defects. Lower Vm, Vs, Vd, and rVm at18 hours post-CPB were independently related to longer ICU duration of stay (P<0.05). In the 85 patients who returned for neurodevelopmental testing, lower Vm, Vs, Vd and rVm at 18 hours post-CPB were independently associated with lower PDI (P<0.05) and MDI (P<0.05, except Vs: P=0.06) scores. Higher Vs and rVm at 18 hours post-CPB were independently associated with increased incidence of brain injury on MRI in 39 patients. Conclusions Postoperative CBFV after biventricular repair is related to early postoperative and neurodevelopmental outcomes at 1 year of age, possibly indicating that low CBFV is a marker of suboptimal postoperative hemodynamics and cerebral perfusion. PMID:24820395

Effect of the Molecular Configuration of Perylene Diimide Acceptors on Charge Transfer and Device Performance

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

Qu, Jianfei; Mu, Zhao; Lai, Hanjian

Three perylene diimides (PDI)-based small molecules, T2-SePDI2, T3B-SePDI3, and T4B-SePDI4, with different molecular configurations are synthesized. Due to a large steric hindrance, the molecular configuration of T3B-SePDI3 is the most distorted, followed by T4BSePDI4, while T2-SePDI2 shows the smallest steric hindrance. Inverted bulk heterojunction solar cells based on T3B-SePDI3 and PBDB-T show the highest power conversion efficiency (PCE) of 5.82% with an open-circuit voltage of 0.98 V, a high short-circuit current density of 10.52 mA/cm2, and a fill factor of 56.31%. The PCEs of the T2-SePDI2- and T4B-SePDI4- based devices are 4.10% and 5.10%, respectively. Furthermore, the results demonstrate thatmore » the molecular configuration of the PDI-based small molecule acceptor is critical and that increasing the steric hindrance is helpful in suppressing aggregation and improving device performance.« less

Effect of the Molecular Configuration of Perylene Diimide Acceptors on Charge Transfer and Device Performance

DOE PAGES

Qu, Jianfei; Mu, Zhao; Lai, Hanjian; ...

2018-01-25

Three perylene diimides (PDI)-based small molecules, T2-SePDI2, T3B-SePDI3, and T4B-SePDI4, with different molecular configurations are synthesized. Due to a large steric hindrance, the molecular configuration of T3B-SePDI3 is the most distorted, followed by T4BSePDI4, while T2-SePDI2 shows the smallest steric hindrance. Inverted bulk heterojunction solar cells based on T3B-SePDI3 and PBDB-T show the highest power conversion efficiency (PCE) of 5.82% with an open-circuit voltage of 0.98 V, a high short-circuit current density of 10.52 mA/cm2, and a fill factor of 56.31%. The PCEs of the T2-SePDI2- and T4B-SePDI4- based devices are 4.10% and 5.10%, respectively. Furthermore, the results demonstrate thatmore » the molecular configuration of the PDI-based small molecule acceptor is critical and that increasing the steric hindrance is helpful in suppressing aggregation and improving device performance.« less

Rich micronutrient fortification of locally produced infant food does not improve mental and motor development of Zambian infants: a randomised controlled trial

PubMed Central

Manno, Daniela; Kowa, Priscilla K.; Bwalya, Hellen K.; Siame, Joshua; Grantham-McGregor, Sally; Baisley, Kathy; De Stavola, Bianca L.; Jaffar, Shabbar; Filteau, Suzanne

2013-01-01

It is uncertain whether multiple micronutrients benefit the mental and psychomotor development of young children in developing countries. We conducted a randomised double-blind controlled trial to evaluate the effect of a richly micronutrient-fortified v. a basal fortified porridge on mental and psychomotor development in Zambian infants. Infants (n 743) were randomised at age 6 months to receive either the richly fortified or the basal fortified infant food and were followed up until 18 months of age. All the infants were evaluated monthly for achievement of a series of developmental milestones. The Bayley scales of infant development II were administered to a subsample of 502 infants at 6, 12 and 18 months. Rich micronutrient fortification had no significant benefit on the following: (a) number of developmental milestones achieved (rate ratio at 12 months = 1·00; 95 % CI 0·96, 1·05; P=0·81, adjusted for sex, socio-economic status and maternal education, with similar results at 15 and 18 months); (b) ages of walking unsupported (hazard ratio (HR) 1·04; 95 % CI 0·88, 1·24; P=0·63, adjusted for the above covariates) and of speaking three or four clear words (HR 1·01; 95 % CI 0·84, 1·20; P=0·94, adjusted for the above covariates); (c) mental development index (MDI) and psychomotor development index (PDI) of the Bayley scales (scores difference adjusted for baseline scores, age at the assessment, sex, socio-economic status, maternal education, language, age and HIV status: MDI 0·3 (95 % CI −0·5, 1·1), P=0·43; PDI −0·1 (95 % CI −0·9, 0·7), P=0·78). In conclusion, the results do not support the hypothesis that rich micronutrient fortification improves Zambian infants’ mental and motor development. PMID:21733297

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

Ma, Ying, E-mail: yingma@imr.ac.cn; Shenyang National Laboratory for Materials Science, Institute of Metal Research, Chinese Academy of Science; An, Boxing

By using an electron donor–acceptor molecule that consists of a perylenediimide (PDI) core bonded with two ferrocene (Fc) units, well-defined nanorods, nanowires and microwires of PDI-Fc were formed through simply adjusting the initial concentration of PDI-Fc in dichloromethane or CH{sub 2}Cl{sub 2}. Moreover, the two-ended devices based on individual microwire were fabricated. Highly reproducible and sensitive photo response characteristics were demonstrated in the microwire through controlling the white light on and off with different light intensities. The assembly strategy via complementary donors and acceptors is of significance for constructing photoconductive systems and developing novel functional devices. - Graphical abstract: Themore » two-ended devices based on individual microwire were fabricated. Highly reproducible and sensitive photo response characteristics were observed by controlling the white light on and off with different light intensities. - Highlights: • An electron donor–acceptor molecule (PDI-Fc) was synthesized. • Well-defined nanorods, nanowires and microwires of PDI-Fc were formed. • The two-ended devices based on individual microwire were fabricated. • Highly reproducible and sensitive photo response characteristics were observed.« less

The Impact of Changes in Psoriasis Area and Severity Index by Body Region on Quality of Life in Patients with Psoriasis.

PubMed

Sojević Timotijević, Zorica; Majcan, Predrag; Trajković, Goran; Relić, Milijana; Novaković, Tatjana; Mirković, Momčilo; Djurić, Sladjana; Nikolić, Simon; Lazić, Bratislav; Janković, Slavenka

2017-10-01

Psoriasis severity varies by body region, with each affected region having a different impact on patient quality of life (QoL). The aim of this study was to assess the impact of changes in the Psoriasis Area and Severity Index (PASI) scores by body region on QoL in patients with psoriasis after treatment. A total of 100 patients with psoriasis were recruited to the study. All patients completed the generic EuroQol-5D instrument and two specific QoL measures, Dermatology Life Quality Index (DLQI) and Psoriasis Disability Index (PDI) at the beginning of the study, and 50 patients successfully completed the same questionnaires four weeks after the end of the treatment. Clinical severity was assessed using PASI total score and PASI body region (head, trunk, arms, and legs) scores. QoL improved after treatment, and PASI improvements on visible body regions (head, legs, and arms) showed significant correlation with the most sub-areas of the Visual Analog Scale (EQ VAS), DLQI, and PDI. Multiple linear regression analysis revealed that PASI improvement (particularly on the head), sex, age, and disease duration were predictors of QoL score changes for most domains of the three instruments. Improvement of psoriasis in visible body regions has an appreciable influence on QoL improvement, and may positively affect treatment success in patients with psoriasis.

Protein-disulfide Isomerase Regulates the Thyroid Hormone Receptor-mediated Gene Expression via Redox Factor-1 through Thiol Reduction-Oxidation*

PubMed Central

Hashimoto, Shoko; Imaoka, Susumu

2013-01-01

Protein-disulfide isomerase (PDI) is a dithiol/disulfide oxidoreductase that regulates the redox state of proteins. We previously found that overexpression of PDI in rat pituitary tumor (GH3) cells suppresses 3,3′,5-triiodothyronine (T3)-stimulated growth hormone (GH) expression, suggesting the contribution of PDI to the T3-mediated gene expression via thyroid hormone receptor (TR). In the present study, we have clarified the mechanism of regulation by which TR function is regulated by PDI. Overexpression of wild-type but not redox-inactive mutant PDI suppressed the T3-induced GH expression, suggesting that the redox activity of PDI contributes to the suppression of GH. We considered that PDI regulates the redox state of the TR and focused on redox factor-1 (Ref-1) as a mediator of the redox regulation of TR by PDI. Interaction between Ref-1 and TRβ1 was detected. Overexpression of wild-type but not C64S Ref-1 facilitated the GH expression, suggesting that redox activity of Cys-64 in Ref-1 is involved in the TR-mediated gene expression. Moreover, PDI interacted with Ref-1 and changed the redox state of Ref-1, suggesting that PDI controls the redox state of Ref-1. Our studies suggested that Ref-1 contributes to TR-mediated gene expression and that the redox state of Ref-1 is regulated by PDI. Redox regulation of PDI via Ref-1 is a new aspect of PDI function. PMID:23148211

Structural Changes in Self-Catalyzed Adsorption of Carbon Monoxide on 1,4-Phenylene Diisocyanide Modified Au(111)

DOE PAGES

Kestell, John; Boscoboinik, J. Anibal; Cheng, Lanxia; ...

2015-07-23

The self-accelerated adsorption of CO on 1,4-phenylene diisocyanide (PDI)-derived oligomers on Au(111) is explored by reflection–absorption infrared spectroscopy and scanning tunneling microscopy. PDI incorporates gold adatoms from the Au(111) surface to form one-dimensional —(Au–PDI) n— chains that can also connect between gold nanoparticles on mica to form a conductive pathway between them. CO adsorption occurs in two stages; it first adsorbs adjacent to the oligomers that move to optimize CO adsorption. Further CO exposure induces PDI decoordination to form Au–PDI adatom complexes thereby causing the conductivity of a PDI-linked gold nanoparticle array on mica to decrease to act as amore » chemically drive molecular switch. This simple system enables the adsorption process to be explored in detail. DFT calculations reveal that both the —(Au–PDI) n— oligomer chain and the Au–PDI adatom complex are stabilized by coadsorbed CO. A kinetic “foot-in-the-door” model is proposed in which fluctuations in PDI coordination allow CO to diffuse into the gap between gold adatoms to prevent the PDI from reattaching, thereby allowing additional CO to adsorb, to provide kinetic model for allosteric CO adsorption on PDI-covered gold.« less

Methods of measuring Protein Disulfide Isomerase activity: a critical overview

NASA Astrophysics Data System (ADS)

Watanabe, Monica; Laurindo, Francisco; Fernandes, Denise

2014-09-01

Protein disulfide isomerase is an essential redox chaperone from the endoplasmic reticulum (ER) and is responsible for correct disulfide bond formation in nascent proteins. PDI is also found in other cellular locations in the cell, particularly the cell surface. Overall, PDI contributes to ER and global cell redox homeostasis and signaling. The knowledge about PDI structure and function progressed substantially based on in vitro studies using recombinant PDI and chimeric proteins. In these experimental scenarios, PDI reductase and chaperone activities are readily approachable. In contrast, assays to measure PDI isomerase activity, the hallmark of PDI family, are more complex. Assessment of PDI roles in cells and tissues mainly relies on gain- or loss-of-function studies. However, there is limited information regarding correlation of experimental readouts with the distinct types of PDI activities. In this mini-review, we evaluate the main methods described for measuring the different kinds of PDI activity: thiol reductase, thiol oxidase, thiol isomerase and chaperone. We emphasize the need to use appropriate controls and the role of critical interferents (e.g., detergent, presence of reducing agents). We also discuss the translation of results from in vitro studies with purified recombinant PDI to cellular and tissue samples, with critical comments on the interpretation of results.

Arabidopsis protein disulfide isomerase-8 is a type I endoplasmic reticulum transmembrane protein with thiol-disulfide oxidase activity.

PubMed

Yuen, Christen Y L; Shek, Roger; Kang, Byung-Ho; Matsumoto, Kristie; Cho, Eun Ju; Christopher, David A

2016-08-22

In eukaryotes, classical protein disulfide isomerases (PDIs) facilitate the oxidative folding of nascent secretory proteins in the endoplasmic reticulum by catalyzing the formation, breakage, and rearrangement of disulfide bonds. Terrestrial plants encode six structurally distinct subfamilies of PDIs. The novel PDI-B subfamily is unique to terrestrial plants, and in Arabidopsis is represented by a single member, PDI8. Unlike classical PDIs, which lack transmembrane domains (TMDs), PDI8 is unique in that it has a C-terminal TMD and a single N-terminal thioredoxin domain (instead of two). No PDI8 isoforms have been experimentally characterized to date. Here we describe the characterization of the membrane orientation, expression, sub-cellular localization, and biochemical function of this novel member of the PDI family. Histochemical staining of plants harboring a PDI8 promoter:β-glucuronidase (GUS) fusion revealed that the PDI8 promoter is highly active in young, expanding leaves, the guard cells of cotyledons, and in the vasculature of several organs, including roots, leaves, cotyledons, and flowers. Immunoelectron microscopy studies using a PDI8-specific antibody on root and shoot apical cells revealed that PDI8 localizes to the endoplasmic reticulum (ER). Transient expression of two PDI8 fusions to green fluorescent protein (spGFP-PDI8 and PDI8-GFP-KKED) in leaf mesophyll protoplasts also resulted in labeling of the ER. Protease-protection immunoblot analysis indicated that PDI8 is a type I membrane protein, with its catalytic domain facing the ER lumen. The lumenal portion of PDI8 was able to functionally complement the loss of the prokaryotic protein foldase, disulfide oxidase (DsbA), as demonstrated by the reconstitution of periplasmic alkaline phosphatase in Escherichia coli. The results indicate that PDI8 is a type I transmembrane protein with its catalytic domain facing the lumen of the ER and functions in the oxidation of cysteines to produce disulfide bonds. It likely plays a role in folding newly-synthesized secretory proteins as they translocate across the ER membrane into the lumen. These foundational results open the door to identifying the substrates of PDI8 to enable a more thorough understanding of its function in plants.

Analysis of the fluctuations of a laser beam due to thermal turbulence

NASA Astrophysics Data System (ADS)

Ndlovu, Sphumelele C.; Chetty, Naven

2014-07-01

A laser beam propagating in air and passing through a point diffraction interferometer (PDI) produces stable interferograms that can be used to extract wavefront data such as major atmospheric characteristics: turbulence strength, inner scale and outer scale of the refractive index. These parameters need to be taken into consideration when developing defense laser weapons since they can be affected by thermal fluctuations that are due to the changes in temperature in close proximity to the propagating beam and results in phase shifts that can be used to calculate the temperature which causes wavefront perturbations on a propagating beam.

Intranasal delivery of paroxetine nanoemulsion via the olfactory region for the management of depression: formulation, behavioural and biochemical estimation

NASA Astrophysics Data System (ADS)

Pandey, Yogendra Raj; Kumar, Shobhit; Gupta, Bijay Kumar; Ali, Javed; Baboota, Sanjula

2016-01-01

Paroxetine is a selective serotonin reuptake inhibitor (SSRI) and is used for the treatment of depression and anxiety problems, but suffers from the drawback of poor oral bioavailability (less than 50%) due to its extensive first pass metabolism. The objective of the present study was to develop a paroxetine loaded nanoemulsion (o/w type) for direct nose-to-brain delivery. Nanoemulsions were prepared by the spontaneous emulsification technique using Capmul MCM, Solutol HS 15 and propylene glycol as oil phase, surfactant and co-surfactant, respectively, for delivery of drug directly to the brain through the nasal route for better management of depression. Formulations were studied for droplet size, polydispersity index (PDI), percentage transmittance, refractive index, viscosity, zeta potential, surface morphology and in vitro permeation study. TEM images of optimized formulation showed spherical droplets with a mean diameter of 58.47 ± 3.02 nm, PDI of 0.339 ± 0.007 and zeta potential values of -33 mV. The formulation showed good results for transmittance (100.60 ± 0.577%), refractive index (1.412 ± 0.003) and viscosity (40.85 ± 6.40 cP). Permeation studies revealed a 2.57-fold enhancement in permeation as compared to the paroxetine suspension. Behavioural studies such as the forced swimming test and locomotor activity test were done on Wistar rats to study the antidepressant effect of the optimized formulation. Treatment of depressed rats with paroxetine nanoemulsion (administered intranasally) significantly improved the behavioural activities in comparison to paroxetine suspension (orally administered). Biochemical estimation results revealed that the prepared nanoemulsion was effective in enhancing the depressed levels of glutathione and decreasing the elevated levels of TBARS.

The flexibility and dynamics of protein disulfide isomerase

PubMed Central

Wells, Stephen A.; Emilio Jimenez‐Roldan, J.; Bhattacharyya, Moitrayee; Vishweshwara, Saraswathi; Freedman, Robert B.

2016-01-01

ABSTRACT We have studied the mobility of the multidomain folding catalyst, protein disulfide isomerase (PDI), by a coarse‐graining approach based on flexibility. We analyze our simulations of yeast PDI (yPDI) using measures of backbone movement, relative positions and orientations of domains, and distances between functional sites. We find that there is interdomain flexibility at every interdomain junction but these show very different characteristics. The extent of interdomain flexibility is such that yPDI's two active sites can approach much more closely than is found in crystal structures—and indeed hinge motion to bring these sites into proximity is the lowest energy normal mode of motion of the protein. The flexibility predicted for yPDI (based on one structure) includes the other known conformation of yPDI and is consistent with (i) the mobility observed experimentally for mammalian PDI and (ii) molecular dynamics. We also observe intradomain flexibility and clear differences between the domains in their propensity for internal motion. Our results suggest that PDI flexibility enables it to interact with many different partner molecules of widely different sizes and shapes, and highlights considerable similarities of yPDI and mammalian PDI. Proteins 2016; 84:1776–1785. © 2016 Wiley Periodicals, Inc. PMID:27616289

Recommended Approaches for Pharmacokinetic Natural Product-Drug Interaction Research: a NaPDI Center Commentary.

PubMed

Paine, Mary F; Shen, Danny D; McCune, Jeannine S

2018-05-07

Sales of botanical dietary supplements and other purported medicinal natural products (NPs) have escalated over the past ~25 years, increasing the potential for NPs to precipitate clinically significant pharmacokinetic interactions with United States Food and Drug Administration (FDA)-approved medications (NP-drug interactions or NPDIs). Published NPDI studies to date often lack consistency in design, implementation, and documentation, which present difficulties in assessing the clinical significance of the results. Common hurdles include large variability in the admixture composition of phytoconstituents between and within batches of a given NP, limited knowledge on the pharmacokinetics of precipitant NP constituents, and use of animal and/or in vitro models which, in some cases, are not mechanistically appropriate for extrapolation to humans. The National Center for Complementary and Integrative Health has created a Center of Excellence for Natural Product-Drug Interaction (NaPDI Center) to address these unmet research needs. The NaPDI Center has two overarching goals: 1) develop Recommended Approaches to guide researchers in the proper conduct of NPDI studies, which will evolve over time concurrent with emerging technologies and new research data; and 2) apply the Recommended Approaches in evaluating four model NPs as precipitants of NPDIs with clinically relevant object drugs. The major objectives of this commentary are to 1) explain the rationale for creating the NaPDI Center; 2) describe the Decision Trees developed by the NaPDI Center to enhance the planning, rigor, and consistency of NPDI studies; and 3) provide a framework for communicating results to the multidisciplinary scientists interested in the NaPDI Center&rsquo's Interaction Projects. The American Society for Pharmacology and Experimental Therapeutics.

Dual-domain lateral shearing interferometer

DOEpatents

Naulleau, Patrick P.; Goldberg, Kenneth Alan

2004-03-16

The phase-shifting point diffraction interferometer (PS/PDI) was developed to address the problem of at-wavelength metrology of extreme ultraviolet (EUV) optical systems. Although extremely accurate, the fact that the PS/PDI is limited to use with coherent EUV sources, such as undulator radiation, is a drawback for its widespread use. An alternative to the PS/PDI, with relaxed coherence requirements, is lateral shearing interferometry (LSI). The use of a cross-grating, carrier-frequency configuration to characterize a large-field 4.times.-reduction EUV lithography optic is demonstrated. The results obtained are directly compared with PS/PDI measurements. A defocused implementation of the lateral shearing interferometer in which an image-plane filter allows both phase-shifting and Fourier wavefront recovery. The two wavefront recovery methods can be combined in a dual-domain technique providing suppression of noise added by self-interference of high-frequency components in the test-optic wavefront.

Sex-specific differences in effect of prenatal exposure to dioxin-like compounds on neurodevelopment in Japanese children: Sapporo cohort study.

PubMed

Nakajima, Sonomi; Saijo, Yasuaki; Miyashita, Chihiro; Ikeno, Tamiko; Sasaki, Seiko; Kajiwara, Junboku; Kishi, Reiko

2017-11-01

Consistent reports are not available on the effects of dioxin-like polychlorinated biphenyls (PCBs) and polychlorinated dibenzo-p-dioxins (PCDD)/ polychlorinated dibenzofurans (PCDF) (dioxin-like compounds [DLCs]) on child neurodevelopment. Further, the effect of background-level exposure to individual DLC isomers is not known. We carried out the Sapporo cohort study to evaluate the effect of prenatal exposure to each DLC isomer on child neurodevelopment at 6 and 18 months of age, and assessed sex-specific differences in these effects. The levels of all and each individual DLC isomers were estimated in maternal peripheral blood. Neurodevelopment was evaluated using the Bayley Scales of Infant Development-2nd Edition for 6-month-old infants (n = 190) and 18-month-old children (n = 121). In male children, levels of 10 DLC isomers were significantly negatively associated with the Psychomotor Developmental Index (PDI) at 6 months of age after adjustment for potential confounding variables. However, at 18 months of age, these associations were absent. In female children, the level of only one DLC isomer was significantly negatively associated with PDI at 6 months of age. However, in contrast to the male children, the levels of six DLC isomers in 18-month-old female children were significantly positively associated with the Mental Developmental Index. These findings indicate that adverse neurodevelopmental effects of prenatal background-level exposure to DLCs may be stronger in male children. Copyright © 2017 Elsevier Inc. All rights reserved.

Perylene Diimide Based Fluorescent Dyes for Selective Sensing of Nitroaromatic Compounds: Selective Sensing in Aqueous Medium Across Wide pH Range.

PubMed

Hariharan, P S; Pitchaimani, J; Madhu, Vedichi; Anthony, Savarimuthu Philip

2016-03-01

Water soluble perylenediimide based fluorophore salt, N,N'-bis(ethelenetrimethyl ammoniumiodide)-perylene-3,4,9,10-tetracarboxylicbisimide (PDI-1), has been used for selective fluorescence sensing of picric acid (PA) and 4-nitroaniline (4-NA) in organic as well as aqueous medium across wide pH range (1.0 to 10.0). PDI-1 showed strong fluorescence in dimethylformamide (DMF) (Φf = 0.26 (DMF) and moderate fluorescence in water. Addition of picric acid (PA) and 4-nitroaniline (4-NA) into PDI-1 in DMF/aqueous solution selectively quenches the fluorescence. The concentration dependent studies showed decrease of fluorescence linearly with increase of PA and 4-NA concentration. The interference studies demonstrate high selectivity for PA and 4-NA. Interestingly, PDI-1 showed selective fluorescence sensing of PA and 4-NA across wide pH range (1.0 to 10.0). Selective fluorescence sensing of PA and 4-NA has also been observed with trifluoroacetate (PDI-2), sulfate (PDI-3) salt of PDI-1 as well as octyl chain substituted PDI (PDI-4) without amine functionality. These studies suggest that PA and 4-NA might be having preferential interaction with PDI aromatic core and quenches the fluorescence. Thus PDI based dyes have been used for selective fluorescent sensing of explosive NACs for the first time to the best our knowledge.

Permeability-diffusivity modeling vs. fractional anisotropy on white matter integrity assessment and application in schizophrenia.

PubMed

Kochunov, P; Chiappelli, J; Hong, L E

2013-01-01

Diffusion tensor imaging (DTI) assumes a single pool of anisotropically diffusing water to calculate fractional anisotropy (FA) and is commonly used to ascertain white matter (WM) deficits in schizophrenia. At higher b-values, diffusion-signal decay becomes bi-exponential, suggesting the presence of two, unrestricted and restricted, water pools. Theoretical work suggests that semi-permeable cellular membrane rather than the presence of two physical compartments is the cause. The permeability-diffusivity (PD) parameters measured from bi-exponential modeling may offer advantages, over traditional DTI-FA, in identifying WM deficits in schizophrenia. Imaging was performed in N = 26/26 patients/controls (age = 20-61 years, average age = 40.5 ± 12.6). Imaging consisted of fifteen b-shells: b = 250-3800 s/mm(2) with 30 directions/shell, covering seven slices of mid-sagittal corpus callosum (CC) at 1.7 × 1.7 × 4.6 mm. 64-direction DTI was also collected. Permeability-diffusivity-index (PDI), the ratio of restricted to unrestricted apparent diffusion coefficients, and the fraction of unrestricted compartment (Mu) were calculated for CC and cingulate gray matter (GM). FA values for CC were calculated using tract-based-spatial-statistics. Patients had significantly reduced PDI in CC (p ≅ 10(- 4)) and cingulate GM (p = 0.002), while differences in CC FA were modest (p ≅ .03). There was no group-related difference in Mu. Additional theoretical-modeling analysis suggested that reduced PDI in patients may be caused by reduced cross-membrane water molecule exchanges. PDI measurements for cerebral WM and GM yielded more robust patient-control differences than DTI-FA. Theoretical work offers an explanation that patient-control PDI differences should implicate abnormal active membrane permeability. This would implicate abnormal activities in ion-channels that use water as substrate for ion exchange, in cerebral tissues of schizophrenia patients.

Optimization and design of ibuprofen-loaded nanostructured lipid carriers using a hybrid-design approach for ocular drug delivery

NASA Astrophysics Data System (ADS)

Rathod, Vishal

The objective of the present project was to develop the Ibuprofen-loaded Nanostructured Lipid Carrier (IBU-NLCs) for topical ocular delivery based on substantial pre-formulation screening of the components and understanding the interplay between the formulation and process variables. The BCS Class II drug: Ibuprofen was selected as the model drug for the current study. IBU-NLCs were prepared by melt emulsification and ultrasonication technique. Extensive pre-formulation studies were performed to screen the lipid components (solid and liquid) based on drug's solubility and affinity as well as components compatibility. The results from DSC & XRD assisted in selecting the most suitable ratio to be utilized for future studies. DynasanRTM 114 was selected as the solid lipid & MiglyolRTM 840 was selected as the liquid lipid based on preliminary lipid screening. The ratio of 6:4 was predicted to be the best based on its crystallinity index and the thermal events. As there are many variables involved for further optimization of the formulation, a single design approach is not always adequate. A hybrid-design approach was applied by employing the Plackett Burman design (PBD) for preliminary screening of 7 critical variables, followed by Box-Behnken design (BBD), a sub-type of response surface methodology (RSM) design using 2 relatively significant variables from the former design and incorporating Surfactant/Co-surfactant ratio as the third variable. Comparatively, KolliphorRTM HS15 demonstrated lower Mean Particle Size (PS) & Polydispersity Index (PDI) and KolliphorRTM P188 resulted in Zeta Potential (ZP) < -20 mV during the surfactant screening & stability studies. Hence, Surfactant/Cosurfactant ratio was employed as the third variable to understand its synergistic effect on the response variables. We selected PS, PDI, and ZP as critical response variables in the PBD since they significantly influence the stability & performance of NLCs. Formulations prepared using BBD were further characterized and evaluated concerning PS, PDI, ZP and Entrapment Efficiency (EE) to identify the multi-factor interactions between selected formulation variables. In vitro release studies were performed using Spectra/por dialysis membrane on Franz diffusion cell and Phosphate Saline buffer (7.4 pH) as the medium. Samples for assay, EE, Loading Capacity (LC), Solubility studies & in-vitro release were filtered using Amicon 50K and analyzed via UPLC system (Waters) at a detection wavelength of 220 nm. Significant variables were selected through PBD, and the third variable was incorporated based on surfactant screening & stability studies for the next design. Assay of the BBD based formulations was found to be within 95-104% of the theoretically calculated values. Further studies were investigated for PS, PDI, ZP & EE. PS was found to be in the range of 103-194 nm with PDI ranging from 0.118 to 0.265. The ZP and EE were observed to be in the range of -22.2 to -11 mV & 90 to 98.7 % respectively. Drug release of 30% was observed from the optimized formulation in the first 6 hr of in-vitro studies, and the drug release showed a sustained release of ibuprofen thereafter over several hours. These values also confirm that the production method, and all other selected variables, effectively promoted the incorporation of ibuprofen in NLC. Quality by Design (QbD) approach was successfully implemented in developing a robust ophthalmic formulation with superior physicochemical and morphometric properties. NLCs as the nanocarrier demonstrated promising perspective for topical delivery of poorly water-soluble drugs.

Protein disulfide isomerases in the endoplasmic reticulum promote anchorage-independent growth of breast cancer cells.

PubMed

Wise, Randi; Duhachek-Muggy, Sara; Qi, Yue; Zolkiewski, Michal; Zolkiewska, Anna

2016-06-01

Metastatic breast cancer cells are exposed to stress of detachment from the extracellular matrix (ECM). Cultured breast cancer cells that survive this stress and are capable of anchorage-independent proliferation form mammospheres. The purpose of this study was to explore a link between mammosphere growth, ECM gene expression, and the protein quality control system in the endoplasmic reticulum (ER). We compared the mRNA and protein levels of ER folding factors in SUM159PT and MCF10DCIS.com breast cancer cells grown as mammospheres versus adherent conditions. Publicly available gene expression data for mammospheres formed by primary breast cancer cells and for circulating tumor cells (CTCs) were analyzed to assess the status of ECM/ER folding factor genes in clinically relevant samples. Knock-down of selected protein disulfide isomerase (PDI) family members was performed to examine their roles in SUM159PT mammosphere growth. We found that cells grown as mammospheres had elevated expression of ECM genes and ER folding quality control genes. CTC gene expression data for an index patient indicated that upregulation of ECM and ER folding factor genes occurred at the time of acquired therapy resistance and disease progression. Knock-down of PDI, ERp44, or ERp57, three members of the PDI family with elevated protein levels in mammospheres, in SUM159PT cells partially inhibited the mammosphere growth. Thus, breast cancer cell survival and growth under detachment conditions require enhanced assistance of the ER protein folding machinery. Targeting ER folding factors, in particular members of the PDI family, may improve the therapeutic outcomes in metastatic breast cancer.

Botulinum toxin occipital nerve block for the treatment of severe occipital neuralgia: a case series.

PubMed

Kapural, Leonardo; Stillman, Mark; Kapural, Miranda; McIntyre, Patrick; Guirgius, Maged; Mekhail, Nagy

2007-12-01

Persistent occipital neuralgia can produce severe headaches that are difficult to control by conservative or surgical approaches. We retrospectively describe a series of six patients with severe occipital neuralgia who received conservative and interventional therapies, including oral antidepressants, membrane stabilizers, opioids, and traditional occipital nerve blocks without significant relief. This group then underwent occipital nerve blocks using the botulinum toxin type A (BoNT-A) BOTOX Type A (Allergan, Inc., Irvine, CA, U.S.A.) 50 U for each block (100 U if bilateral). Significant decreases in pain Visual Analog Scale (VAS) scores and improvement in Pain Disability Index (PDI) were observed at four weeks follow-up in five out of six patients following BoNT-A occipital nerve block. The mean VAS score changed from 8 +/- 1.8 (median score of 8.5) to 2 +/- 2.7 (median score of 1), while PDI improved from 51.5 +/- 17.6 (median 56) to 19.5 +/- 21 (median 17.5) and the duration of the pain relief increased to an average of 16.3 +/- 3.2 weeks (median 16) from an average of 1.9 +/- 0.5 weeks (median 2) compared to diagnostic 0.5% bupivacaine block. Following block resolution, the average pain scores and PDI returned to similar levels as before BoNT-A block. In conclusion, BoNT-A occipital nerve blocks provided a much longer duration of analgesia than diagnostic local anesthetics. The functional capacity improvement measured by PDI was profound enough in the majority of the patients to allow patients to resume their regular daily activities for a period of time.

Diphenylphenoxy-Thiophene-PDI Dimers as Acceptors for OPV Applications with Open Circuit Voltage Approaching 1 Volt.

PubMed

Stenta, Caterina; Molina, Desiré; Viterisi, Aurélien; Montero-Rama, María Pilar; Pla, Sara; Cambarau, Werther; Fernández-Lázaro, Fernando; Palomares, Emilio; Marsal, Lluis F; Sastre-Santos, Ángela

2018-03-30

Two new perylenediimides (PDIs) have been developed for use as electron acceptors in solution-processed bulk heterojunction solar cells. The compounds were designed to exhibit maximal solubility in organic solvents, and reduced aggregation in the solid state. In order to achieve this, diphenylphenoxy groups were used to functionalize a monomeric PDI core, and two PDI dimers were bridged with either one or two thiophene units. In photovoltaic devices prepared using PDI dimers and a monomer in conjunction with PTB7, it was found that the formation of crystalline domains in either the acceptor or donor was completely suppressed. Atomic force microscopy, X-ray diffraction, charge carrier mobility measurements and recombination kinetics studies all suggest that the lack of crystallinity in the active layer induces a significant drop in electron mobility. Significant surface recombination losses associated with a lack of segregation in the material were also identified as a significant loss mechanism. Finally, the monomeric PDI was found to have sub-optimum LUMO energy matching the cathode contact, thus limiting charge carrier extraction. Despite these setbacks, all PDIs produced high open circuit voltages, reaching almost 1 V in one particular case.

Expression of protein disulfide isomerase family members correlates with tumor progression and patient survival in ovarian cancer

PubMed Central

Samanta, Soma; Tamura, Shuzo; Dubeau, Louis; Mhawech-Fauceglia, Paulette; Miyagi, Yohei; Kato, Hisamori; Lieberman, Rich; Buckanovich, Ronald J.; Lin, Yvonne G.; Neamati, Nouri

2017-01-01

Objective Protein disulfide isomerase (PDI) is an oxidoreductase that is overexpressed in several cancers. PDI family members (PDIs) play a role in various diseases including cancer. Select PDIs were reported as useful markers in other cancers but their expression in ovarian cancer has not been thoroughly assessed. We sought to evaluate the expression of PDI, PDIA6, PDIR, ERp57, ERp72 and AGR3 in ovarian cancer patient samples and examine their prognostic significance. Methods TMA samples from 415 tissues collected from three cancer centers (UM, USC, and KCCRI) were used to assess the expression levels of PDI family proteins using IHC. Results We observed significant increases in PDI (p = 9.16E-36), PDIA6 (p = 5.51E-33), PDIR (p = 1.81E-12), ERp57 (p = 9.13E-07), ERp72 (p = 3.65E-22), and AGR3 (p = 4.56E-24) expression in ovarian cancers compared to normal tissues. Expression of PDI family members also increases during disease progression (p <0.001). All PDI family members are overexpressed in serous ovarian cancer (p<0.001). However, PDI, PDIA6, PDIR, ERp72 and AGR3 are more significantly overexpressed (p<0.001) than ERp57 (p<0.05) in clear cell ovarian carcinoma. Importantly, overexpression of PDI family members is associated with poor survival in ovarian cancer (p = 0.045 for PDI, p = 0.047 for PDIR, p = 0.037 for ERp57, p = 0.046 for ERp72, p = 0.040 for AGR3) with the exception of PDIA6 (p = 0.381). Conclusions Our findings demonstrate that select PDI family members (PDI, PDIR, ERp72, ERp57 and AGR3) are potential prognostic markers for ovarian cancer. PMID:29262583

Charge versus Energy Transfer Effects in High-Performance Perylene Diimide Photovoltaic Blend Films.

PubMed

Singh, Ranbir; Shivanna, Ravichandran; Iosifidis, Agathaggelos; Butt, Hans-Jürgen; Floudas, George; Narayan, K S; Keivanidis, Panagiotis E

2015-11-11

Perylene diimide (PDI)-based organic photovoltaic devices can potentially deliver high power conversion efficiency values provided the photon energy absorbed is utilized efficiently in charge transfer (CT) reactions instead of being consumed in nonradiative energy transfer (ET) steps. Hitherto, it remains unclear whether ET or CT primarily drives the photoluminescence (PL) quenching of the PDI excimer state in PDI-based blend films. Here, we affirm the key role of the thermally assisted PDI excimer diffusion and subsequent CT reaction in the process of PDI excimer PL deactivation. For our study we perform PL quenching experiments in the model PDI-based composite made of poly[4,8-bis(5-(2-ethylhexyl)thiophen-2-yl)benzo[1,2-b;4,5-b']dithiophene-2,6-diyl-alt-(4-(2-ethylhexanoyl)-thieno[3,4-b]thiophene)-2-6-diyl] (PBDTTT-CT) polymeric donor mixed with the N,N'-bis(1-ethylpropyl)-perylene-3,4,9,10-tetracarboxylic diimide (PDI) acceptor. Despite the strong spectral overlap between the PDI excimer PL emission and UV-vis absorption of PBDTTT-CT, two main observations indicate that no significant ET component operates in the overall PL quenching: the PL intensity of the PDI excimer (i) increases with decreasing temperature and (ii) remains unaffected even in the presence of 10 wt % content of the PBDTTT-CT quencher. Temperature-dependent wide-angle X-ray scattering experiments further indicate that nonradiative resonance ET is highly improbable due to the large size of PDI domains. The dominance of the CT over the ET process is verified by the high performance of devices with an optimum composition of 30:70 PBDTTT-CT:PDI. By adding 0.4 vol % of 1,8-diiodooctane we verify the plasticization of the polymer side chains that balances the charge transport properties of the PBDTTT-CT:PDI composite and results in additional improvement in the device efficiency. The temperature-dependent spectral width of the PDI excimer PL band suggests the presence of energetic disorder in the PDI excimer excited state manifold.

Dual-domain point diffraction interferometer

DOEpatents

Naulleau, Patrick P.; Goldberg, Kenneth Alan

2000-01-01

A hybrid spatial/temporal-domain point diffraction interferometer (referred to as the dual-domain PS/PDI) that is capable of suppressing the scattered-reference-light noise that hinders the conventional PS/PDI is provided. The dual-domain PS/PDI combines the separate noise-suppression capabilities of the widely-used phase-shifting and Fourier-transform fringe pattern analysis methods. The dual-domain PS/PDI relies on both a more restrictive implementation of the image plane PS/PDI mask and a new analysis method to be applied to the interferograms generated and recorded by the modified PS/PDI. The more restrictive PS/PDI mask guarantees the elimination of spatial-frequency crosstalk between the signal and the scattered-light noise arising from scattered-reference-light interfering with the test beam. The new dual-domain analysis method is then used to eliminate scattered-light noise arising from both the scattered-reference-light interfering with the test beam and the scattered-reference-light interfering with the "true" pinhole-diffracted reference light. The dual-domain analysis method has also been demonstrated to provide performance enhancement when using the non-optimized standard PS/PDI design. The dual-domain PS/PDI is essentially a three-tiered filtering system composed of lowpass spatial-filtering the test-beam electric field using the more restrictive PS/PDI mask, bandpass spatial-filtering the individual interferogram irradiance frames making up the phase-shifting series, and bandpass temporal-filtering the phase-shifting series as a whole.

Revisiting the mechanistic basis of the French Paradox: Red wine inhibits the activity of protein disulfide isomerase in vitro.

PubMed

Galinski, Christine N; Zwicker, Jeffrey I; Kennedy, Daniel R

2016-01-01

Although epidemiologic evidence points to cardioprotective activity of red wine, the mechanistic basis for antithrombotic activity has not been established. Quercetin and related flavonoids are present in high concentrations in red but not white wine. Quercetin-glycosides were recently shown to prevent thrombosis in animal models through the inhibition of extracellular protein disulfide isomerase (PDI). We evaluated whether red or white wine inhibited PDI activity in vitro. Quercetin levels in red and white wines were measured by HPLC analysis. Inhibition of PDI activity by red and white wines was assessed by an insulin reduction turbidity assay at various concentrations of wine. PDI inhibition was confirmed using a reduced peptide that contained a disulfide containing peptide as a substrate. The inhibition of PDI related thiol isomerases ERp5 and ERp57 was also assessed. We observed a dose-dependent decrease of PDI activity for a variety of red but not white wines. Red wine diluted to 3% final concentration resulted in over 80% inhibition of PDI activity by insulin reductase assay for all varieties tested. This inhibition was also observed in the peptide based assay. Red grape juice yielded similar results but ethanol alone did not affect PDI activity. Interestingly, red wine also inhibited the PDI related thiol isomerases ERp5 and ERp57, albeit to a lesser degree than PDI. PDI activity is inhibited by red wine and grape juice, identifying a potentially novel mechanism underlying the cardiovascular benefits attributed to wine consumption. Copyright © 2015 Elsevier Ltd. All rights reserved.

Revisiting the mechanistic basis of the French Paradox: red wine inhibits the activity of protein disulfide isomerase in vitro

PubMed Central

Galinski, Christine N.; Zwicker, Jeffrey I.; Kennedy, Daniel R.

2015-01-01

Introduction Although epidemiologic evidence points to cardioprotective activity of red wine, the mechanistic basis for antithrombotic activity has not been established. Quercetin and related flavonoids are present in high concentrations in red but not white wine. Quercetin-glycosides were recently shown to prevent thrombosis in animal models through the inhibition of extracellular protein disulfide isomerase (PDI). We evaluated whether red or white wine inhibited PDI activity in vitro. Methods Quercetin levels in red and white wines were measured by HPLC analysis. Inhibition of PDI activity by red and white wines was assessed by an insulin reduction turbidity assay at various concentrations of wine. PDI inhibition was confirmed using a reduced peptide that contained a disulfide containing peptide as a substrate. The inhibition of PDI related thiol isomerases ERp5 and ERp57 was also assessed. Results We observed a dose-dependent decrease of PDI activity for a variety of red but not white wines. Red wine diluted to 3% final concentration resulted in over 80% inhibition of PDI activity by insulin reductase assay for all varieties tested. This inhibition was also observed in the peptide based assay. Red grape juice yielded similar results but ethanol alone did not affect PDI activity. Interestingly, red wine also inhibited the PDI related thiol isomerases ERp5 and ERp57, albeit to a lesser degree than PDI. Conclusions PDI activity is inhibited by red wine and grape juice, identifying a potentially novel mechanism underlying the cardiovascular benefits attributed to wine consumption. PMID:26585763

Urinary 3-phenoxybenzoic acid (3-PBA) levels among pregnant women in Mexico City: Distribution and relationships with child neurodevelopment

PubMed Central

Watkins, Deborah J.; Fortenberry, Gamola Z.; Sánchez, Brisa N.; Barr, Dana Boyd; Panuwet, Parinya; Schnaas, Lourdes; Osorio-Valencia, Erika; Solano-González, Maritsa; Ettinger, Adrienne S.; Hernández-Ávila, Mauricio; Hu, Howard; Téllez-Rojo, Martha María; Meeker, John D.

2016-01-01

Background In recent years, pyrethroid pesticide use has increased in Mexico, the United States, and elsewhere, resulting in extensive human exposure. There is growing concern that pregnant women may be a particularly vulnerable population, as in utero fetal exposure during critical periods of development could adversely affect long-term neurobehavioral function. Methods We measured maternal urinary 3-phenoxybenzoic acid (3-PBA) concentrations during the third trimester of pregnancy as a measure of in utero pyrethroid exposure to the fetus among participants in an established Mexico City birth cohort (n=187). In a subset of mothers, we measured 3-PBA during the first, second, and third trimester (n=21) to assess variability across pregnancy. We examined associations between third trimester 3-PBA concentrations and children’s scores on the Mental Development Index (MDI) and Psychomotor Development Index (PDI) from the Bayley Scales for Infant Development (BSID-IIS) at 24 and 36 months of age. Results 3-PBA was detected in 46% of all urine samples, with similar detection rates and geometric mean concentrations across pregnancy among the 21 participants who provided repeat samples. Participants in the medium and high 3-PBA categories (≥LOD) had lower MDI scores at 24 months compared to those in the low 3-PBA category (

Investigation of the electronic ground states for a reduced pyridine(diimine) uranium series: evidence for a ligand tetraanion stabilized by a uranium dimer.

PubMed

Anderson, Nickolas H; Odoh, Samuel O; Williams, Ursula J; Lewis, Andrew J; Wagner, Gregory L; Lezama Pacheco, Juan; Kozimor, Stosh A; Gagliardi, Laura; Schelter, Eric J; Bart, Suzanne C

2015-04-15

The electronic structures of a series of highly reduced uranium complexes bearing the redox-active pyridine(diimine) ligand, (Mes)PDI(Me) ((Mes)PDI(Me) = 2,6-(2,4,6-Me3-C6H2-N═CMe)2C5H3N) have been investigated. The complexes, ((Mes)PDI(Me))UI3(THF) (1), ((Mes)PDI(Me))UI2(THF)2 (2), [((Mes)PDI(Me))UI]2 (3), and [((Mes)PDI(Me))U(THF)]2 (4), were examined using electronic and X-ray absorption spectroscopies, magnetometry, and computational analyses. Taken together, these studies suggest that all members of the series contain uranium(IV) centers with 5f (2) configurations and reduced ligand frameworks, specifically [(Mes)PDI(Me)](•/-), [(Mes)PDI(Me)](2-), [(Mes)PDI(Me)](3-) and [(Mes)PDI(Me)](4-), respectively. In the cases of 2, 3, and 4 no unpaired spin density was found on the ligands, indicating a singlet diradical ligand in monomeric 2 and ligand electron spin-pairing through dimerization in 3 and 4. Interaction energies, representing enthalpies of dimerization, of -116.0 and -144.4 kcal mol(-1) were calculated using DFT for the monomers of 3 and 4, respectively, showing there is a large stabilization gained by dimerization through uranium-arene bonds. Highlighted in these studies is compound 4, bearing a previously unobserved pyridine(diimine) tetraanion, that was uniquely stabilized by backbonding between uranium cations and the η(5)-pyridyl ring.

Spanish Version of the Patient Dignity Inventory: Translation and Validation in Patients With Advanced Cancer.

PubMed

Rullán, María; Carvajal, Ana; Núñez-Córdoba, Jorge M; Martínez, Marina; Carrasco, José Miguel; García, Irene; Arantzamendi, María; Belar, Alazne; Centeno, Carlos

2015-12-01

The Patient Dignity Inventory (PDI) is an instrument to measure sources of distress related to dignity at the end of life. To obtain a Spanish version of the PDI and measure psychometric aspects in patients with advanced cancer. A back-translation method was used to obtain the Spanish version. Inpatients and outpatients with advanced cancer were included. Patients completed the Spanish versions of the PDI (PDI-s), Edmonton Symptom Assessment System (ESAS), Hospital Anxiety and Depression Scale (HADS), and Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being (FACIT-Sp-12) instruments. The psychometric properties evaluated were internal consistency; concurrent validity between PDI-s/ESAS, PDI-s/HADS, and PDI-s/FACIT-Sp-12; discriminant validity, test-retest reliability, and factor analysis. The usefulness of the instrument also was tested. A Spanish version of the PDI was obtained. One hundred twenty-four patients completed the study. Cronbach's alpha coefficient for the PDI-s was 0.89. The PDI-s significantly correlated with the ESAS (rs = 0.669; P < 0.001), HADS (rs = 0.788; P < 0.001), and FACIT-Sp-12 (rs = -0.442; P = 0.008). The instrument distinguished outpatients from inpatients and between patients with differing Karnofsky Performance Status scores (rs = -0.328; P < 0.001). The test-retest method indicated excellent reproducibility (intraclass correlation coefficient = 0.931). Factor analysis showed three factors accounting for 79.4% of the variance. Factors were labeled psychological and existential distress, physical symptoms and dependency, and social support. Patients had no difficulties in understanding or completing the questionnaire (mean time to complete: 7.2 minutes). The Spanish version of the PDI showed adequate psychometric properties when tested with advanced cancer patients. This research provides a three-factor alternative in Spanish to the PDI. Copyright © 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Impact of molecular solvophobicity vs. solvophilicity on device performances of dimeric perylene diimide based solution-processed non-fullerene organic solar cells.

PubMed

Lu, Zhenhuan; Zhang, Xin; Zhan, Chuanlang; Jiang, Bo; Zhang, Xinliang; Chen, Lili; Yao, Jiannian

2013-07-21

Because of their outstanding molecular optoelectronic properties, perylene diimides (PDIs) are promising alternatives to the commonly used PCBM. However, the overly strong aggregation ability, poor solution-processability and compatibility of PDIs severely limit their photovoltaic applications. We turned to borrowing the amphiphile concept to improve these supramolecular properties. Practically, we fine-tuned the molecular solvophobicity with respect to the molecular solvophilicity, e.g. F(solvophob/solvophil), by changing the number of the weakly solvophobic 2-methoxyethoxyl (EG) groups in the bay-region of the thienyl-bridged dimeric PDI backbone, forming three PDI dimers of Bis-PDI-T (0 EG), Bis-PDI-T-EG (2 EG) and Bis-PDI-T-di-EG (4 EG) (Scheme 1). The photovoltaic properties using these dimers as the solution-processed non-fullerene electron-acceptor and P3HT as the electron-donor were investigated via the device configuration of ITO/PEDOT:PSS/P3HT:PDI dimer/Ca/Al. Bis-PDI-T exhibited overly strong aggregation ability and very poor solution-processability, which severely limited compatibility, giving a very poor power conversion efficiency (PCE) of 0.007%. When two EG groups were attached at the 1,1'-positions, the resulted Bis-PDI-T-EG showed dramatically reduced aggregation ability, improved solution-processability, compatibility and proper phase separation. Small sized phases (∼20 nm) dominated in the active layer and the best PCE was increased to 0.39%. When four solvophobic EG functions were introduced, affording Bis-PDI-T-di-EG with excellent supramolecular properties, particularly, the improvement of the phase separation with an increased phase size of 24 nm and the enhanced electron and hole mobilities, by 2-4 times, with respect to that of Bis-PDI-T-EG. The best PCE was further enhanced to 0.88%. After using 1-chloronaphthalene as the co-solvent of 1,2-dichlorobenzene to further improve the compatibility, the PCE was improved further up to 0.41% for Bis-PDI-T, 0.76% for Bis-PDI-T-EG and 1.54% for Bis-PDI-T-di-EG.

Atypical protein disulfide isomerases (PDI): Comparison of the molecular and catalytic properties of poplar PDI-A and PDI-M with PDI-L1A

PubMed Central

Selles, Benjamin; Zannini, Flavien; Couturier, Jérémy; Jacquot, Jean-Pierre

2017-01-01

Protein disulfide isomerases are overwhelmingly multi-modular redox catalysts able to perform the formation, reduction or isomerisation of disulfide bonds. We present here the biochemical characterization of three different poplar PDI isoforms. PDI-A is characterized by a single catalytic Trx module, the so-called a domain, whereas PDI-L1a and PDI-M display an a-b-b’-a’ and a°-a-b organisation respectively. Their activities have been tested in vitro using purified recombinant proteins and a series of model substrates as insulin, NADPH thioredoxin reductase, NADP malate dehydrogenase (NADP-MDH), peroxiredoxins or RNase A. We demonstrated that PDI-A exhibited none of the usually reported activities, although the cysteines of the WCKHC active site signature are able to form a disulfide with a redox midpoint potential of -170 mV at pH 7.0. The fact that it is able to bind a [Fe2S2] cluster upon Escherichia coli expression and anaerobic purification might indicate that it does not have a function in dithiol-disulfide exchange reactions. The two other proteins were able to catalyze oxidation or reduction reactions, PDI-L1a being more efficient in most cases, except that it was unable to activate the non-physiological substrate NADP-MDH, in contrast to PDI-M. To further evaluate the contribution of the catalytic domains of PDI-M, the dicysteinic motifs have been independently mutated in each a domain. The results indicated that the two a domains seem interconnected and that the a° module preferentially catalyzed oxidation reactions whereas the a module catalyzed reduction reactions, in line with the respective redox potentials of -170 mV and -190 mV at pH 7.0. Overall, these in vitro results illustrate that the number and position of a and b domains influence the redox properties and substrate recognition (both electron donors and acceptors) of PDI which contributes to understand why this protein family expanded along evolution. PMID:28362814

Functional roles and efficiencies of the thioredoxin boxes of calcium-binding proteins 1 and 2 in protein folding.

PubMed Central

Kramer, B; Ferrari, D M; Klappa, P; Pöhlmann, N; Söling, H D

2001-01-01

The rat luminal endoplasmic-recticulum calcium-binding proteins 1 and 2 (CaBP1 and CaBP2 respectively) are members of the protein disulphide-isomerase (PDI) family. They contain two and three thioredoxin boxes (Cys-Gly-His-Cys) respectively and, like PDI, may be involved in the folding of nascent proteins. We demonstrate here that CaBP1, similar to PDI and CaBP2, can complement the lethal phenotype of the disrupted Saccharomyces cerevisiae PDI gene, provided that the natural C-terminal Lys-Asp-Glu-Leu sequence is replaced by His-Asp-Glu-Leu. Both the in vitro RNase AIII-re-activation assays and in vivo pro-(carboxypeptidase Y) processing assays using CaBP1 and CaBP2 thioredoxin (trx)-box mutants revealed that, whereas the three trx boxes in CaBP2 seem to be functionally equivalent, the first trx box of CaBP1 is significantly more active than the second trx box. Furthermore, only about 65% re-activation of denatured reduced RNase AIII could be obtained with CaBP1 or CaBP2 compared with PDI, and the yield of PDI-catalysed reactions was significantly reduced in the presence of either CaBP1 or CaBP2. In contrast with PDI, neither CaBP1 nor CaBP2 could catalyse the renaturation of denatured glyceraldehyde-3-phosphate dehydrogenase (GAPDH), which is a redox-independent process, and neither protein had any effect on the PDI-catalysed refolding of GAPDH. Furthermore, although PDI can bind peptides via its b' domain, a property it shares with PDIp, the pancreas-specific PDI homologue, and although PDI can bind malfolded proteins such as 'scrambled' ribonuclease, no such interactions could be detected for CaBP2. We conclude that: (1) both CaBP2 and CaBP1 lack peptide-binding activity for GAPDH attributed to the C-terminal region of the a' domain of PDI; (2) CaBP2 lacks the general peptide-binding activity attributed to the b' domain of PDI; (3) interaction of CaBP2 with substrate (RNase AIII) is different from that of PDI and substrate; and (4) both CaBP2 and CaBP1 may promote oxidative folding by different kinetic pathways. PMID:11415439

Isolation of Mn(I) Compounds Featuring a Reduced Bis(imino)pyridine Chelate and Their Relevance to Electrocatalytic Hydrogen Production.

PubMed

Mukhopadhyay, Tufan K; MacLean, Nicholas L; Flores, Marco; Groy, Thomas L; Trovitch, Ryan J

2018-05-21

We report the preparation and electronic structure determination of chelate-reduced Mn(I) compounds that are relevant to electrocatalytic proton reduction mediated by [( Ph2PPr PDI)Mn(CO)][Br]. Reducing [( Ph2PPr PDI)Mn(CO)][Br] with excess Na-Hg afforded a neutral paramagnetic complex, ( Ph2PPr PDI)Mn(CO). This compound was found to feature a low spin Mn(I) center and a PDI radical anion as determined by magnetic susceptibility measurement (1.97 μ B ), EPR spectroscopy ( S = 1 / 2 ), and density functional theory calculations. When [( Ph2PPr PDI)Mn(CO)][Br] was reduced with K-Hg, Mn(I) complexes with highly activated CO ligands were obtained. Recrystallization of the reduced product from diethyl ether solution allowed for the isolation of dimeric [(κ 4 - Ph2PPr PDI)Mn(μ-η 1 ,η 1 ,η 2 -CO)K(Et 2 O)] 2 (ν CO = 1710 cm -1 , 1656 cm -1 ), while methyl tert-butyl ether treatment afforded dimeric [(κ 4 - Ph2PPr PDI)Mn(μ-η 1 ,η 1 -CO)K(MTBE) 2 ] 2 (ν CO = 1695 cm -1 , MTBE = methyl tert-butyl ether). Addition of 18-crown-6 to these products, or conducting the K-Hg reduction of [( Ph2PPr PDI)Mn(CO)][Br] in the presence of 18-crown-6, allowed for the isolation of a monomeric example, (κ 4 - Ph2PPr PDI)Mn(μ-η 1 ,η 2 -CO)K(18-crown-6) (ν CO = 1697 cm -1 ). All three complexes were found to be diamagnetic and were characterized thoroughly by multinuclear 1D and 2D NMR spectroscopy and single crystal X-ray diffraction. Detailed analysis of the metrical parameters and spectroscopic properties suggest that all three compounds possess a Mn(I) center that is supported by a PDI dianion. Importantly, (κ 4 - Ph2PPr PDI)Mn(μ-η 1 ,η 2 -CO)K(18-crown-6) was found to react instantaneously with either HBF 4 ·OEt 2 or HOTf to evolve H 2 and generate the corresponding Mn(I) complex, [( Ph2PPr PDI)Mn(CO)][BF 4 ] or [( Ph2PPr PDI)Mn(CO)][OTf], respectively. These products are spectroscopically and electrochemically similar to previously reported [( Ph2PPr PDI)Mn(CO)][Br]. It is believed that the mechanism of [( Ph2PPr PDI)Mn(CO)][Br]-mediated proton reduction involves intermediates that are related to the compounds described herein and that their ambient temperature isolation is aided by the redox active nature of Ph2PPr PDI.

INFLUENCE OF LIPOPHILIC AND HYDROPHILIC CO-MONOMERS ON THE HYDRODYNAMIC DIAMETER OF THERMOSENSITIVE NIPA DERIVATIVES FOR THERMALLY CONTROLLED DRUG DELIVERY.

PubMed

Musial, Witold; Gasztych, Monika; Kokol, Vanja; Mucha, Igor; Makanis, Aleksandra; Kolodziejczyk, Woiciech; Gola, Agnieszka

2017-01-01

For modem drug delivery, new drug carriers sensitive to various factors and with size in the range of micro- and nanometers are required. The aim of this work was to evaluate the influence of hydrophilic and hydrophobic co-monomers on the hydrodynamic diameter of three co-polymers of N-isopropylacrylamide (NIPA) nanogels synthesized at 70*C in the presence of potassium persulfate (KPS) as the initiator and N.N'-methylene bis-acrylamide (MBA) as the cross-linker. The first batch of nanoparticles was synthesized without co-monomer, whereas poly(ethylene glycol) methyl ether acrylate (PEG-MEA), and N-teii-butylacrylamide (NTB), were implemented as co-monomers for the second and third batch. Hydrodynamic diameter of nanoparticles was in the range 550-800 rn. The compositions of the synthesized co-polymer nanoparticles were con- firmed via IR and NMR analyses. The SFPP conditions resulted in hydrodynamic diameters ranging from approximately 550 to 800 nm at temperatures lower than the volume phase transition temperature (VPTT) and diameters ranging from 250 to 600 nm at temperatures above the VPTT, where the VPTT was between 26 and 41'C. The polydispersity index (PDI) showed a maximum or a minimum value at the VPTT, which was an important indicator of the volume phase transition. According to the PDI observation during thermal cycling, the addition of NTB into the polymeric chain resulted in maximal values of the PDI at the VPIT, similar to the case of nanoparticles without any additional co-monomers. In contrast, in the case of PEG-MEA, the PDI presented a minimal value. Dynamic light scattering (DLS) volume measurements, performed simultaneously with spectral methods, may lead to a fast evaluation of nanoparticles prepared by SFPP.

Death or Neurodevelopmental Impairment at 18 To 22 Months in a Randomized Trial of Early Dexamethasone to Prevent Death or Chronic Lung Disease in Extremely Low Birth Weight Infants

PubMed Central

Stark, Ann R.; Carlo, Waldemar A.; Vohr, Betty R; Papile, Lu Ann; Saha, Shampa; Bauer, Charles R.; Donovan, Edward F.; Oh, William; Shankaran, Seetha; Tyson, Jon E.; Wright, Linda L.; Poole, W. Kenneth; Das, Abhik; Stoll, Barbara J.; Fanaroff, Avroy A.; Korones, Sheldon B.; Ehrenkranz, Richard A.; Stevenson, David K.; Peralta-Carcelen, Myriam; Adams-Chapman, Ira; Wilson-Costello, Deanne E.; Bada, Henrietta S.; Heyne, Roy J.; Johnson, Yvette R.; Lee, Kimberly Gronsman; Steichen, Jean J.; Hintz, Susan R.

2014-01-01

Objective To evaluate the incidence of death or neurodevelopmental impairment (NDI) at 18 to 22 months corrected age in subjects enrolled in a trial of early dexamethasone treatment to prevent death or chronic lung disease in extremely low birth weight infants. Methods Evaluation of infants at 18 to 22 months corrected age included anthropomorphic measurements, a standard neurological examination, and the Bayley Scales of Infant Development-II, including the Mental Developmental Index (MDI) and the Psychomotor Developmental Index (PDI). NDI was defined as moderate or severe cerebral palsy, MDI or PDI less than 70, blindness, or hearing impairment. Results Death or NDI at 18 to 22 months corrected age was similar in the dexamethasone and placebo groups (65 vs 66 percent, p= 0.99 among those with known outcome). The proportion of survivors with NDI was also similar, as were mean values for weight, length, and head circumference and the proportion of infants with poor growth (50 vs 41 percent, p=0.42 for weight less than 10th percentile). Forty nine percent of infants in the placebo group received treatment with corticosteroid compared to 32% in the dexamethasone group (p=0.02). Conclusion The risk of death or NDI and rate of poor growth were high but similar in the dexamethasone and placebo groups. The lack of a discernible effect of early dexamethasone on neurodevelopmental outcome may be due to frequent clinical corticosteroid use in the placebo group. PMID:23992673

Important cellular targets for antimicrobial photodynamic therapy.

PubMed

Awad, Mariam M; Tovmasyan, Artak; Craik, James D; Batinic-Haberle, Ines; Benov, Ludmil T

2016-09-01

The persistent problem of antibiotic resistance has created a strong demand for new methods for therapy and disinfection. Photodynamic inactivation (PDI) of microbes has demonstrated promising results for eradication of antibiotic-resistant strains. PDI is based on the use of a photosensitive compound (photosensitizer, PS), which upon illumination with visible light generates reactive species capable of damaging and killing microorganisms. Since photogenerated reactive species are short lived, damage is limited to close proximity of the PS. It is reasonable to expect that the larger the number of damaged targets is and the greater their variety is, the higher the efficiency of PDI is and the lower the chances for development of resistance are. Exact molecular mechanisms and specific targets whose damage is essential for microbial inactivation have not been unequivocally established. Two main cellular components, DNA and plasma membrane, are regarded as the most important PDI targets. Using Zn porphyrin-based PSs and Escherichia coli as a model Gram-negative microorganism, we demonstrate that efficient photoinactivation of bacteria can be achieved without detectable DNA modification. Among the cellular components which are modified early during illumination and constitute key PDI targets are cytosolic enzymes, membrane-bound protein complexes, and the plasma membrane. As a result, membrane barrier function is lost, and energy and reducing equivalent production is disrupted, which in turn compromises cell defense mechanisms, thus augmenting the photoinduced oxidative injury. In conclusion, high PDI antimicrobial effectiveness does not necessarily require impairment of a specific critical cellular component and can be achieved by inducing damage to multiple cellular targets.

A Longitudinal Analysis of Prenatal Exposure to Methylmercury and Fatty Acids in the Seychelles

PubMed Central

Stokes-Riner, Abbie; Thurston, Sally W.; J.Myers, Gary; Duffy, Emeir M.; Wallace, Julie; Bonham, Maxine; Robson, Paula; Shamlaye, Conrad F.; Strain, J.J.; Watson, Gene

2011-01-01

Background Maternal fish consumption during pregnancy exposes the fetus simultaneously to methyl mercury (MeHg) and long chain polyunsaturated fatty acids (LCPUFA). Data from the Seychelles Child Development Nutrition Study (SCDNS) showed a negative association of MeHg with child development when children were 30 months of age, only when controlling for LCPUFA. Concomitantly, n-3 LCPUFA were found to have a significant positive association only at 9 months. These findings suggest that the effects of MeHg and LCPUFA may vary with age over the first few years of life. We address this by including outcomes at two ages and adjusting for the child's age at testing. Methods A longitudinal analysis utilizing linear mixed models was performed to assess the associations of maternal hair total mercury (THg, a biomarker for MeHg) and maternal LCPUFA with children's Bayley Scales of Infant Development Psychomotor Developmental Index (BSID-II PDI) at 9 and 30 months of age, and to determine whether these associations change over time. Data from 228 children were included. Results Maternal hair MeHg had a negative effect on BSID PDI, while maternal n-3 LCPUFA had a positive effect. These effects did not change significantly from 9 to 30 months in this analysis. Conclusions The longitudinal analysis provides increased power for estimating the relationships of prenatal MeHg and LCPUFA exposures during child development. Significant associations of these exposures in opposite directions confirm the importance of LCPUFA in development and the need to adjust for maternal nutrition when studying prenatal MeHg exposure. PMID:21145963

A longitudinal analysis of prenatal exposure to methylmercury and fatty acids in the Seychelles.

PubMed

Stokes-Riner, Abbie; Thurston, Sally W; Myers, Gary J; Duffy, Emeir M; Wallace, Julie; Bonham, Maxine; Robson, Paula; Shamlaye, Conrad F; Strain, J J; Watson, Gene; Davidson, Philip W

2011-01-01

Maternal fish consumption during pregnancy exposes the fetus simultaneously to methylmercury (MeHg) and long chain polyunsaturated fatty acids (LCPUFA). Data from the Seychelles Child Development Nutrition Study (SCDNS) showed a negative association of MeHg with child development when children were 30 months of age, only when controlling for LCPUFA. Concomitantly, n-3 LCPUFA were found to have a significant positive association only at 9 months. These findings suggest that the effects of MeHg and LCPUFA may vary with age over the first few years of life. We address this by including outcomes at two ages and adjusting for the child's age at testing. A longitudinal analysis utilizing linear mixed models was performed to assess the associations of maternal hair total mercury (THg, a biomarker for MeHg) and maternal LCPUFA with children's Bayley Scales of Infant Development Psychomotor Developmental Index (BSID-II PDI) at 9 and 30 months of age, and to determine whether these associations change over time. Data from 228 children were included. Maternal hair MeHg had a negative effect on BSID PDI, while maternal n-3 LCPUFA had a positive effect. These effects did not change significantly from 9 to 30 months in this analysis. The longitudinal analysis provides increased power for estimating the relationships of prenatal MeHg and LCPUFA exposures during child development. Significant associations of these exposures in opposite directions confirm the importance of LCPUFA in development and the need to adjust for maternal nutrition when studying prenatal MeHg exposure. Copyright © 2010 Elsevier B.V. All rights reserved.

Galectin-9 binds to O-glycans on protein disulfide isomerase.

PubMed

Schaefer, Katrin; Webb, Nicholas E; Pang, Mabel; Hernandez-Davies, Jenny E; Lee, Katharine P; Gonzalez, Pascual; Douglass, Martin V; Lee, Benhur; Baum, Linda G

2017-09-01

Changes in the T cell surface redox environment regulate critical cell functions, such as cell migration, viral entry and cytokine production. Cell surface protein disulfide isomerase (PDI) contributes to the regulation of T cell surface redox status. Cell surface PDI can be released into the extracellular milieu or can be internalized by T cells. We have found that galectin-9, a soluble lectin expressed by T cells, endothelial cells and dendritic cells, binds to and retains PDI on the cell surface. While endogenous galectin-9 is not required for basal cell surface PDI expression, exogenous galectin-9 mediated retention of cell surface PDI shifted the disulfide/thiol equilibrium on the T cell surface. O-glycans on PDI are required for galectin-9 binding, and PDI recognition appears to be specific for galectin-9, as galectin-1 and galectin-3 do not bind PDI. Galectin-9 is widely expressed by immune and endothelial cells in inflamed tissues, suggesting that T cells would be exposed to abundant galectin-9, in cis and in trans, in infectious or autoimmune conditions. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Ultrafast Photoinduced Symmetry-Breaking Charge Separation and Electron Sharing in Perylenediimide Molecular Triangles.

PubMed

Wu, Yilei; Young, Ryan M; Frasconi, Marco; Schneebeli, Severin T; Spenst, Peter; Gardner, Daniel M; Brown, Kristen E; Würthner, Frank; Stoddart, J Fraser; Wasielewski, Michael R

2015-10-21

We report on a visible-light-absorbing chiral molecular triangle composed of three covalently linked 1,6,7,12-tetra(phenoxy)perylene-3,4:9,10-bis(dicarboximide) (PDI) units. The rigid triangular architecture reduces the electronic coupling between the PDIs, so ultrafast symmetry-breaking charge separation is kinetically favored over intramolecular excimer formation, as revealed by femtosecond transient absorption spectroscopy. Photoexcitation of the PDI triangle dissolved in CH2Cl2 gives PDI(+•)-PDI(-•) in τCS = 12.0 ± 0.2 ps. Fast subsequent intramolecular electron/hole hopping can equilibrate the six possible energetically degenerate ion-pair states, as suggested by electron paramagnetic resonance/electron-nuclear double resonance spectroscopy, which shows that one-electron reduction of the PDI triangle results in complete electron sharing among the three PDIs. Charge recombination of PDI(+•)-PDI(-•) to the ground state occurs in τCR = 1.12 ± 0.01 ns with no evidence of triplet excited state formation.

Varying coefficient function models to explore interactions between maternal nutritional status and prenatal methylmercury toxicity in the Seychelles Child Development Nutrition Study

PubMed Central

Lynch, Miranda L.; Huang, Li-Shan; Cox, Christopher; Strain, J.J.; Myers, Gary J.; Bonham, Maxine P.; Shamlaye, Conrad F.; Stokes-Riner, Abbie; Wallace, Julie M.W.; Duffy, Emeir M.; Clarkson, Thomas W.; Davidson, Philip W.

2010-01-01

Maternal consumption of fish during the gestational period exposes the fetus to both nutrients, especially the long-chain polyunsaturated fatty acids (LCPUFAs), believed to be beneficial for fetal brain development, as well as to the neurotoxicant methylmercury (MeHg). We recently reported that nutrients present in fish may modify MeHg neurotoxicity. Understanding the apparent interaction of MeHg exposure and nutrients present in fish is complicated by the limitations of modeling methods. In this study we fit varying coefficient function models to data from the Seychelles Child Development Nutrition Study (SCDNS) cohort to assess the association of dietary nutrients and children’s development. This cohort of mother-child pairs in the Republic of Seychelles had fish consumption averaging 9 meals per week. Maternal nutritional status was assessed for five different nutritional components known to be present in fish (n-3 LCPUFA, n-6 LCPUFA, iron status, iodine status, and choline) and associated with children’s neurological development. We also included prenatal MeHg exposure (measured in maternal hair). We examined two child neurodevelopmental outcomes (Bayley Scales Infant Development-II (BSID-II) Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI)), each administered at 9 and at 30 months. The varying coefficient models allow the possible interactions between each nutritional component and MeHg to be modeled as a smoothly varying function of MeHg as an effect modifier. Iron, iodine, choline, and n-6 LCPUFA had little or no observable modulation at different MeHg exposures. In contrast the n-3 LCPUFA docosahexaenoic acid (DHA) had beneficial effects on the BSID-II PDI that were reduced or absent at higher MeHg exposures. This study presents a useful modeling method that can be brought to bear on questions involving interactions between covariates, and illustrates the continuing importance of viewing fish consumption during pregnancy as a case of multiple exposures to nutrients and to MeHg. The results encourage more emphasis on a holistic view of the risks and benefits of fish consumption as it relates to infant development. PMID:20961536

Varying coefficient function models to explore interactions between maternal nutritional status and prenatal methylmercury toxicity in the Seychelles Child Development Nutrition Study.

PubMed

Lynch, Miranda L; Huang, Li-Shan; Cox, Christopher; Strain, J J; Myers, Gary J; Bonham, Maxine P; Shamlaye, Conrad F; Stokes-Riner, Abbie; Wallace, Julie M W; Duffy, Emeir M; Clarkson, Thomas W; Davidson, Philip W

2011-01-01

Maternal consumption of fish during the gestational period exposes the fetus to both nutrients, especially the long-chain polyunsaturated fatty acids (LCPUFAs), believed to be beneficial for fetal brain development, as well as to the neurotoxicant methylmercury (MeHg). We recently reported that nutrients present in fish may modify MeHg neurotoxicity. Understanding the apparent interaction of MeHg exposure and nutrients present in fish is complicated by the limitations of modeling methods. In this study we fit varying coefficient function models to data from the Seychelles Child Development Nutrition Study (SCDNS) cohort to assess the association of dietary nutrients and children's development. This cohort of mother-child pairs in the Republic of Seychelles had fish consumption averaging 9 meals per week. Maternal nutritional status was assessed for five different nutritional components known to be present in fish (n-3 LCPUFA, n-6 LCPUFA, iron status, iodine status, and choline) and associated with children's neurological development. We also included prenatal MeHg exposure (measured in maternal hair). We examined two child neurodevelopmental outcomes (Bayley Scales Infant Development-II (BSID-II) Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI)), each administered at 9 and at 30 months. The varying coefficient models allow the possible interactions between each nutritional component and MeHg to be modeled as a smoothly varying function of MeHg as an effect modifier. Iron, iodine, choline, and n-6 LCPUFA had little or no observable modulation at different MeHg exposures. In contrast the n-3 LCPUFA docosahexaenoic acid (DHA) had beneficial effects on the BSID-II PDI that were reduced or absent at higher MeHg exposures. This study presents a useful modeling method that can be brought to bear on questions involving interactions between covariates, and illustrates the continuing importance of viewing fish consumption during pregnancy as a case of multiple exposures to nutrients and to MeHg. The results encourage more emphasis on a holistic view of the risks and benefits of fish consumption as it relates to infant development. Copyright © 2010 Elsevier Inc. All rights reserved.

Impact of active and stable psoriasis on health-related quality of life: the PSO-LIFE study.

PubMed

Daudén, E; Herrera, E; Puig, L; Sánchez-Carazo, J L; Toribio, J; Perulero, N

2013-10-01

The aim of this study was to assess the impact of psoriasis on health-related quality of life (HRQOL) using different questionnaires. Prospective observational study of patients with plaque psoriasis of at least 6 months' duration stratified by active and stable disease. The patients were evaluated at baseline, 7 days, and 12 weeks. At the 3 visits, the investigators recorded sociodemographic and clinical data and the patients completed the following HRQOL questionnaires: the Dermatology Life Quality Index (DLQI), the Psoriasis Disability Index (PDI), and psoriasis quality of life questionnaire (PSO-LIFE). In total, 304 patients (182 with active psoriasis and 122 with stable psoriasis) were evaluated. The mean (SD) age was 45.3 (14.5) years, and 56.3% of the group were men. At baseline, the mean (SD) psoriasis and area severity index (PASI) score was 17.0 (7.4) in patients with active disease and 5.6 (5.3) in those with stable disease; a reduction was seen in PASI scores during the evaluation period (P<.01). The mean (SD) score on the PSO-LIFE questionnaire increased significantly from 57.4 (20.4) to 72.2 (19.6) in patients with active psoriasis and from 76.4 (20.6) to 82.3 (18.3) in those with stable disease (P<0.01 in both groups). The difference in standardized mean scores between the 2 groups was 0.79 for the DLQI, 0.62 for the PDI, and 0.85 for the PSO-LIFE questionnaire. The impact of psoriasis on HRQOL as assessed by the PSO-LIFE questionnaire was greater in patients with lesions in visible areas than in those with less visible lesions (P<.01). Changes in PSO-LIFE and PASI scores were moderately and significantly correlated (r=-0.4). The impact of psoriasis on HRQOL is higher in patients with active disease. The PSO-LIFE questionnaire showed a greater tendency to discriminate between active and stable psoriasis than either the DLQI or the PDI. PSO-LIFE scores correlated significantly with lesion site and disease severity as measured by PASI. Copyright © 2012 Elsevier España, S.L. and AEDV. All rights reserved.

PDILT, a divergent testis-specific protein disulfide isomerase with a non-classical SXXC motif that engages in disulfide-dependent interactions in the endoplasmic reticulum.

PubMed

van Lith, Marcel; Hartigan, Nichola; Hatch, Jennifer; Benham, Adam M

2005-01-14

Protein disulfide isomerase (PDI) is the archetypal enzyme involved in the formation and reshuffling of disulfide bonds in the endoplasmic reticulum (ER). PDI achieves its redox function through two highly conserved thioredoxin domains, and PDI can also operate as an ER chaperone. The substrate specificities and the exact functions of most other PDI family proteins remain important unsolved questions in biology. Here, we characterize a new and striking member of the PDI family, which we have named protein disulfide isomerase-like protein of the testis (PDILT). PDILT is the first eukaryotic SXXC protein to be characterized in the ER. Our experiments have unveiled a novel, glycosylated PDI-like protein whose tissue-specific expression and unusual motifs have implications for the evolution, catalytic function, and substrate selection of thioredoxin family proteins. We show that PDILT is an ER resident glycoprotein that liaises with partner proteins in disulfide-dependent complexes within the testis. PDILT interacts with the oxidoreductase Ero1alpha, demonstrating that the N-terminal cysteine of the CXXC sequence is not required for binding of PDI family proteins to ER oxidoreductases. The expression of PDILT, in addition to PDI in the testis, suggests that PDILT performs a specialized chaperone function in testicular cells. PDILT is an unusual PDI relative that highlights the adaptability of chaperone and redox function in enzymes of the endoplasmic reticulum.

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

Liu Ke; Li Yanqiu; Wang Hai

Characterization of measurement accuracy of the phase-shifting point diffraction interferometer (PS/PDI) is usually performed by two-pinhole null test. In this procedure, the geometrical coma and detector tilt astigmatism systematic errors are almost one or two magnitude higher than the desired accuracy of PS/PDI. These errors must be accurately removed from the null test result to achieve high accuracy. Published calibration methods, which can remove the geometrical coma error successfully, have some limitations in calibrating the astigmatism error. In this paper, we propose a method to simultaneously calibrate the geometrical coma and detector tilt astigmatism errors in PS/PDI null test. Basedmore » on the measurement results obtained from two pinhole pairs in orthogonal directions, the method utilizes the orthogonal and rotational symmetry properties of Zernike polynomials over unit circle to calculate the systematic errors introduced in null test of PS/PDI. The experiment using PS/PDI operated at visible light is performed to verify the method. The results show that the method is effective in isolating the systematic errors of PS/PDI and the measurement accuracy of the calibrated PS/PDI is 0.0088{lambda} rms ({lambda}= 632.8 nm).« less

Multi-hazard risk assessment of coastal vulnerability from tropical cyclones - A GIS based approach for the Odisha coast.

PubMed

Sahoo, Bishnupriya; Bhaskaran, Prasad K

2018-01-15

The coastal region bordering the East coast of India is a thickly populated belt exposed to high risk and vulnerability from natural hazards such as tropical cyclones. Tropical cyclone frequencies that develop over the Bay of Bengal (average of 5-6 per year) region are much higher as compared to the Arabian Sea thereby posing a high risk factor associated with storm surge, inland inundation, wind gust, intense rainfall, etc. The Odisha State in the East coast of India experiences the highest number of cyclone strikes as compared to West Bengal, Andhra Pradesh, and Tamil Nadu. To express the destructive potential resulting from tropical cyclones the Power Dissipation Index (PDI) is a widely used metric globally. A recent study indicates that PDI for cyclones in the present decade have increased about six times as compared to the past. Hence there is a need to precisely ascertain the coastal vulnerability and risk factors associated with high intense cyclones expected in a changing climate. As such there are no comprehensive studies attempted so far on the determination of Coastal Vulnerability Index (CVI) for Odisha coast that is highly prone to cyclone strikes. With this motivation, the present study makes an attempt to investigate the physical, environmental, social, and economic impacts on coastal vulnerability associated with tropical cyclones for the Odisha coast. The study also investigates the futuristic projection of coastal vulnerability over this region expected in a changing climate scenario. Eight fair weather parameters along with storm surge height and onshore inundation were used to estimate the Physical Vulnerability Index (PVI). Thereafter, the PVI along with social, economic, and environmental vulnerability was used to determine the overall CVI using the GIS based approach. The authors believe that the comprehensive nature of this study is expected to benefit coastal zone management authorities. Copyright © 2017 Elsevier Ltd. All rights reserved.

White matter tract integrity and developmental outcome in newborn infants with hypoxic-ischemic encephalopathy treated with hypothermia.

PubMed

Massaro, An N; Evangelou, Iordanis; Fatemi, Ali; Vezina, Gilbert; Mccarter, Robert; Glass, Penny; Limperopoulos, Catherine

2015-05-01

To determine whether corpus callosum (CC) and corticospinal tract (CST) diffusion tensor imaging (DTI) measures relate to developmental outcome in encephalopathic newborn infants after therapeutic hypothermia. Encephalopathic newborn infants enrolled in a longitudinal study underwent DTI after hypothermia. Parametric maps were generated for fractional anisotropy, mean, radial, and axial diffusivity. CC and CST were segmented by DTI-based tractography. Multiple regression models were used to examine the association of DTI measures with Bayley-II Mental (MDI) and Psychomotor Developmental Index (PDI) at 15 months and 21 months of age. Fifty-two infants (males n=32, females n=20) underwent DTI at median age of 8 days. Two were excluded because of poor magnetic resonance imaging quality. Outcomes were assessed in 42/50 (84%) children at 15 months and 35/50 (70%) at 21 months. Lower CC and CST fractional anisotropy were associated with lower MDI and PDI respectively, even after controlling for gestational age, birth weight, sex, and socio-economic status. There was also a direct relationship between CC axial diffusivity and MDI, while CST radial diffusivity was inversely related to PDI. In encephalopathic newborn infants, impaired microstructural organization of the CC and CST predicts poorer cognitive and motor performance respectively. Tractography provides a reliable method for early assessment of perinatal brain injury. © 2014 Mac Keith Press.

Methotrexate loading in chitosan nanoparticles at a novel pH: Response surface modeling, optimization and characterization.

PubMed

Hashad, Rania A; Ishak, Rania A H; Geneidi, Ahmed S; Mansour, Samar

2016-10-01

The aim of this study was to assess the feasibility of employing a novel but critical formulation pH (6.2) to encapsulate an anionic model drug (methotrexate, MTX) into chitosan(Cs)-tripolyphosphate nanoparticles(NPs). A response surface methodology using a three-level full factorial design was applied studying the effects of two independent variables namely; Cs concentration and MTX concentration. The responses investigated were the entrapment efficiency (EE%), mean hydrodynamic particle size (PS), polydispersity index (PDI) and zeta potential (ZP). In order to simultaneously optimize the series of models obtained, the desirability function approach was applied with a goal to produce high percent of MTX encapsulated into highly charged Cs-TPP NPs of homogenous optimum PS. MTX-loaded CsNPs were successfully prepared at the novel pH applied. The suggested significant models were found quadratic for EE, PS and ZP responses, while 2-factor interaction model for PDI. The optimization overlay graph showed that the maximum global desirability, D=0.856, was reached when the conditions were set at high Cs and MTX concentration. Thus, the use of such optimized conditions, at this novel pH, achieved a maximum drug EE% (73.38%) into NPs characterized by optimum PS (232.6nm), small PDI value (0.195) and highly surface charged (+18.4mV). Copyright © 2016 Elsevier B.V. All rights reserved.

Remote Sensing of Agro-droughts in Guangdong Province of China Using MODIS Satellite Data.

PubMed

Gao, Maofang; Qin, Zhihao; Zhang, Hong'ou; Lu, Liping; Zhou, Xia; Yang, Xiuchun

2008-08-08

A practical approach was developed in the study for drought monitoring in Guangdong province of China on the basis of vegetation supply water index (VSWI) and precipitation distance index (PDI). A comprehensive index for assessment of agro-drought severity (SADI) was then established from the normalized VSWI and PDI. Using MODIS satellite images and precipitation data from ground-observed meteorological stations, we applied the approach to Guangdong for drought monitoring in 2006. The monitoring results showed that the drought severity on average was very low in the province during the main growing season from May to September in 2006. However, seasonal variation of the severity was also obvious in difference counties of the province. Higher severity of drought could be seen in the periods of late-June (In China each month is traditionally divided into 3 periods. Each is with 10 days and has different names. This division system is mainly with consideration of farming seasons hence has been widely used as the basis of drought monitoring periods in China. In order to keep this tradition, we define, for example, for June, the early-June as the period from 1 st to 10 th of June, the mid-June as the period from 11 th to 20 th , and the late-June as the period from 21 st to 30 th . So mid-August denotes the period from 11 th to 20 th of August, and early-July the period from 1 st to 10th of July, and so on.), early-July, mid-August and late-September. Regionally, Leizhou Peninsula in the west had the most serious drought before mid-May. Validation indicated that our monitoring results were generally consistent with the drought statistics data and the results from Chinese National Satellite Meteorological Center (CNSMC), which used only remote sensing data. This consistence confirmed the applicability of our approach for drought monitoring. Our better identification of drought severity in Leizhou Peninsula of western Guangdong than that of CNSMC might suggest that the approach developed in the study was able to provide a better alternative to increase the accuracy of drought monitoring for agricultural administration and farming.

Oxidative protein folding: from thiol-disulfide exchange reactions to the redox poise of the endoplasmic reticulum.

PubMed

Hudson, Devin A; Gannon, Shawn A; Thorpe, Colin

2015-03-01

This review examines oxidative protein folding within the mammalian endoplasmic reticulum (ER) from an enzymological perspective. In protein disulfide isomerase-first (PDI-first) pathways of oxidative protein folding, PDI is the immediate oxidant of reduced client proteins and then addresses disulfide mispairings in a second isomerization phase. In PDI-second pathways the initial oxidation is PDI-independent. Evidence for the rapid reduction of PDI by reduced glutathione is presented in the context of PDI-first pathways. Strategies and challenges are discussed for determination of the concentrations of reduced and oxidized glutathione and of the ratios of PDI(red):PDI(ox). The preponderance of evidence suggests that the mammalian ER is more reducing than first envisaged. The average redox state of major PDI-family members is largely to almost totally reduced. These observations are consistent with model studies showing that oxidative protein folding proceeds most efficiently at a reducing redox poise consistent with a stoichiometric insertion of disulfides into client proteins. After a discussion of the use of natively encoded fluorescent probes to report the glutathione redox poise of the ER, this review concludes with an elaboration of a complementary strategy to discontinuously survey the redox state of as many redox-active disulfides as can be identified by ratiometric LC-MS-MS methods. Consortia of oxidoreductases that are in redox equilibrium can then be identified and compared to the glutathione redox poise of the ER to gain a more detailed understanding of the factors that influence oxidative protein folding within the secretory compartment. Copyright © 2014 Elsevier Inc. All rights reserved.

Efficient and Stable Ternary Organic Solar Cells Based on Two Planar Nonfullerene Acceptors with Tunable Crystallinity and Phase Miscibility.

PubMed

Wang, Jialin; Peng, Jiajun; Liu, Xiaoyu; Liang, Ziqi

2017-06-21

Planar perylene diimides (PDIs), when used as nonfullerene acceptors for organic photovoltaics, are constrained by their large π-aggregation in solid state. To tackle this issue, another planar nonfullerene acceptor 3,9-bis(2-methylene-(3-(1,1-dicyanomethylene)-indanone)-5,5,11,11-tetrakis(4-hexylphenyl)-dithieno[2,3-d:2',3'-d']-s-indaceno[1,2-b:5,6-b']dithiophene (ITIC) with weak crystallinity and near-infrared light absorption is introduced into the PTB7-Th:PDI binary blend to fabricate efficient and stable ternary solar cells. We have finely tuned the PDI/ITIC weight ratio to investigate the influences of individual ITIC and PDI on the optical, electronic, and morphological properties of the PTB7-Th:ITIC:PDI ternary blend. Compared to the binary blend, complementary optical absorption is achieved in all ternary blends. More importantly, it is found that ITIC plays a critical role on largely suppressing the PDI aggregates in the PTB7-Th:PDI blend, while PDI aids to form an interpenetrating network morphology to facilitate charge transport in the PTB7-Th:ITIC blend. Consequently, when the PDI/ITIC ratio is 3:7 (w/w), the PTB7-Th:ITIC:PDI based inverted solar cells exhibit the highest power conversion efficiency of 8.64% due to their favorable out-of-plane π-π stacking, finest phase-separation morphology, and highest charge mobility. Remarkably, the optimal cells that are solution-processed in air show the promising efficiency of 7.09%, suggesting good ambient stability of such ternary solar cells.

Defective PDI release from platelets and endothelial cells impairs thrombus formation in Hermansky-Pudlak syndrome

PubMed Central

Sharda, Anish; Kim, Sarah H.; Jasuja, Reema; Gopal, Srila; Flaumenhaft, Robert; Furie, Barbara C.

2015-01-01

Protein disulfide isomerase (PDI), secreted from platelets and endothelial cells after injury, is required for thrombus formation. The effect of platelet and endothelial cell granule contents on PDI-mediated thrombus formation was studied by intravital microscopy using a mouse model of Hermansky-Pudlak syndrome in which platelet dense granules are absent. Platelet deposition and fibrin generation were nearly absent, and extracellular PDI was significantly reduced in HPS6−/− mice after vascular injury. HPS6−/− platelets displayed impaired PDI secretion and impaired exocytosis of α granules, lysosomes, and T granules due to decreased sensitivity to thrombin, but these defects could be corrected by addition of subthreshold amounts of adenosine 5′-diphosphate (ADP). Human Hermansky-Pudlak syndrome platelets demonstrated similar characteristics. Infusion of wild-type platelets rescued thrombus formation in HPS6−/− mice. Human umbilical vein endothelial cells in which the HPS6 gene was silenced displayed impaired PDI secretion and exocytosis of Weibel-Palade bodies. Defective thrombus formation in Hermansky-Pudlak syndrome, associated with impaired exocytosis of residual granules in endothelial cells and platelets, the latter due to deficiency of ADP, is characterized by a defect in T granule secretion, a deficiency in extracellular PDI secretion, and impaired fibrin generation and platelet aggregation. Hermansky-Pudlak syndrome is an example of a hereditary disease whereby impaired PDI secretion contributes to a bleeding phenotype. PMID:25593336

Protein disulfide isomerase acts as an injury response signal that enhances fibrin generation via tissue factor activation

PubMed Central

Reinhardt, Christoph; von Brühl, Marie-Luise; Manukyan, Davit; Grahl, Lenka; Lorenz, Michael; Altmann, Berid; Dlugai, Silke; Hess, Sonja; Konrad, Ildiko; Orschiedt, Lena; Mackman, Nigel; Ruddock, Lloyd; Massberg, Steffen; Engelmann, Bernd

2008-01-01

The activation of initiator protein tissue factor (TF) is likely to be a crucial step in the blood coagulation process, which leads to fibrin formation. The stimuli responsible for inducing TF activation are largely undefined. Here we show that the oxidoreductase protein disulfide isomerase (PDI) directly promotes TF-dependent fibrin production during thrombus formation in vivo. After endothelial denudation of mouse carotid arteries, PDI was released at the injury site from adherent platelets and disrupted vessel wall cells. Inhibition of PDI decreased TF-triggered fibrin formation in different in vivo murine models of thrombus formation, as determined by intravital fluorescence microscopy. PDI infusion increased — and, under conditions of decreased platelet adhesion, PDI inhibition reduced — fibrin generation at the injury site, indicating that PDI can directly initiate blood coagulation. In vitro, human platelet–secreted PDI contributed to the activation of cryptic TF on microvesicles (microparticles). Mass spectrometry analyses indicated that part of the extracellular cysteine 209 of TF was constitutively glutathionylated. Mixed disulfide formation contributed to maintaining TF in a state of low functionality. We propose that reduced PDI activates TF by isomerization of a mixed disulfide and a free thiol to an intramolecular disulfide. Our findings suggest that disulfide isomerases can act as injury response signals that trigger the activation of fibrin formation following vessel injury. PMID:18274674

Protein disulfide isomerase acts as an injury response signal that enhances fibrin generation via tissue factor activation.

PubMed

Reinhardt, Christoph; von Brühl, Marie-Luise; Manukyan, Davit; Grahl, Lenka; Lorenz, Michael; Altmann, Berid; Dlugai, Silke; Hess, Sonja; Konrad, Ildiko; Orschiedt, Lena; Mackman, Nigel; Ruddock, Lloyd; Massberg, Steffen; Engelmann, Bernd

2008-03-01

The activation of initiator protein tissue factor (TF) is likely to be a crucial step in the blood coagulation process, which leads to fibrin formation. The stimuli responsible for inducing TF activation are largely undefined. Here we show that the oxidoreductase protein disulfide isomerase (PDI) directly promotes TF-dependent fibrin production during thrombus formation in vivo. After endothelial denudation of mouse carotid arteries, PDI was released at the injury site from adherent platelets and disrupted vessel wall cells. Inhibition of PDI decreased TF-triggered fibrin formation in different in vivo murine models of thrombus formation, as determined by intravital fluorescence microscopy. PDI infusion increased - and, under conditions of decreased platelet adhesion, PDI inhibition reduced - fibrin generation at the injury site, indicating that PDI can directly initiate blood coagulation. In vitro, human platelet-secreted PDI contributed to the activation of cryptic TF on microvesicles (microparticles). Mass spectrometry analyses indicated that part of the extracellular cysteine 209 of TF was constitutively glutathionylated. Mixed disulfide formation contributed to maintaining TF in a state of low functionality. We propose that reduced PDI activates TF by isomerization of a mixed disulfide and a free thiol to an intramolecular disulfide. Our findings suggest that disulfide isomerases can act as injury response signals that trigger the activation of fibrin formation following vessel injury.

SOD1 aggregation in astrocytes following ischemia/reperfusion injury: a role of NO-mediated S-nitrosylation of protein disulfide isomerase (PDI).

PubMed

Chen, Xueping; Guan, Teng; Li, Chen; Shang, Huifang; Cui, Liying; Li, Xin-Min; Kong, Jiming

2012-10-12

Ubiquitinated-protein aggregates are implicated in cerebral ischemia/reperfusion injury. The very presence of these ubiquitinated-protein aggregates is abnormal and seems to be disease-related. However, it is not clear what leads to aggregate formation and whether the aggregations represent a reaction to aggregate-mediated neurodegeneration. To study the nitrosative stress-induced protein aggregation in cerebral ischemia/reperfusion injury, we used primary astrocyte cultures as a cell model, and systematically examined their iNOS expression and consequent NO generation following oxygen glucose deprivation and reperfusion. The expression of protein disulfide isomerase (PDI) and copper-zinc superoxide dismutase (SOD1) were also examined, and the biochemical interaction between PDI and SOD1 was determined by immunoprecipitation. In addition, the levels of S-nitrosylated PDI in cultured astrocytes after oxygen glucose deprivation and reperfusion treatment were measured using the biotin-switch assay. The formation of ubiquitinated-protein aggregates was detected by immunoblot and immunofluorescence staining. Our data showed that the up-regulation of iNOS expression after oxygen glucose deprivation and reperfusion treatment led to excessive NO generation. Up-regulation of PDI and SOD1 was also identified in cultured astrocytes following oxygen glucose deprivation and reperfusion, and these two proteins were found to bind to each other. Furthermore, the increased nitrosative stress due to ischemia/reperfusion injury was highly associated with NO-induced S-nitrosylation of PDI, and this S-nitrosylation of PDI was correlated with the formation of ubiquitinated-protein aggregates; the levels of S-nitrosylated PDI increased in parallel with the formation of aggregates. When NO generation was pharmacologically inhibited by iNOS specific inhibitor 1400W, S-nitrosylation of PDI was significantly blocked. In addition, the formation of ubiquitinated-protein aggregates in cultured astrocytes following oxygen glucose deprivation and reperfusion was also suppressed by 1400W. Interestingly, these aggregates were colocalized with SOD1, which was found to co-immunoprecipitate with PDI. NO-mediated S-nitrosylation of PDI may be involved in the formation of the SOD1-linked ubiquitinated-protein aggregates in cerebral ischemia/reperfusion injury.

Light-driven photosensitizer uptake increases Candida albicans photodynamic inactivation.

PubMed

Romano, Renan A; Pratavieira, Sebastião; Silva, Ana P da; Kurachi, Cristina; Guimarães, Francisco E G

2017-11-01

Photodynamic Inactivation (PDI) is based on the use of a photosensitizer (PS) and light that results mainly in the production of reactive oxygen species, aiming to produce microorganism cell death. PS incubation time and light dose are key protocol parameters that influence PDI response; the correct choice of them can increase the efficiency of inactivation. The results of this study show that a minor change in the PDI protocol, namely light-driven incubation leads to a higher photosensitizer and more uniform cell uptake inside the irradiated zone. Furthermore, as the uptake increases, the damage caused by PDI also increases. The proposed light-driven incubation prior to the inactivation illumination dose has advantages when compared to the traditional PDI treatments since it can be more selective and effective. Using a violet light as pre-illumination (light-driven incubation) source and a red-light system as PDI source, it was possible to demonstrate that when compared to the traditional protocol of dark incubation, the pre-illuminated cell culture showed an inactivation increase of 7 log units. These in vitro results performed in Candida albicans cells may result in the introduction of a new protocol for PDI. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Implications of altered maternal cytokine concentrations on infant outcomes in children with prenatal alcohol exposure.

PubMed

Sowell, K D; Uriu-Adams, J Y; Van de Water, J; Chambers, C D; Coles, C D; Kable, J A; Yevtushok, L; Zymak-Zakutnya, N; Wertelecki, W; Keen, C L

2018-05-01

Excessive alcohol consumption has been shown to increase serum plasma levels of numerous immune cytokines. Maternal immune activation and elevated cytokines have been implicated in certain neurological disorders (e.g., autism and schizophrenia) in the offspring. We investigated the hypothesis that elevated cytokines during pregnancy are a risk factor in women who gave birth to a child with Fetal Alcohol Spectrum Disorder (FASD) or a child with neurobehavioral impairment, regardless of prenatal alcohol exposure. Moderate to heavy alcohol-exposed (AE) (N = 149) and low or no alcohol-exposed (LNA) (N = 92) women were recruited into the study during mid pregnancy (mean of 19.8 ± 5.8 weeks' gestation) in two regions of Ukraine: Khmelnytsky and Rivne. Maternal blood samples were obtained at enrollment into the study at early to mid-pregnancy and during a third-trimester follow-up visit and analyzed for plasma cytokines. Children were examined at 6 and/or 12 months of age and were classified as having FASD if their mothers reported alcohol use and if they had at least one standardized score (Bayley Scales of Infant Development II Mental Development Index [MDI], or Psychomotor Development Index [PDI]) below 85 with the presence or absence of physical features of FASD. In multivariate analyses of maternal cytokine levels in relation to infant MDI and PDI scores in the entire sample, increases in the ratio of TNF-α/IL-10 and IL-6/IL-10 were negatively associated with PDI scores at 6 months (p = 0.020 and p = 0.036, respectively) and 12 months (p = 0.043 and p = 0.029, respectively), and with MDI scores at 12 months (p = 0.013 and p = 0.050, respectively). A reduction in the odds ratio of having an FASD child was observed with increasing levels of IL-1β, IL-2, IL-4, IL-6, and IL-10 in early to mid-pregnancy and IL-1β and IL-10 during late pregnancy. However, women that failed to increase IL-10 levels in the third trimester in order to maintain the balance of pro- and anti-inflammatory cytokines had an elevated risk of having an FASD child, specifically a significant increase in the odds ratio of FASD with every one-unit log increase in late pregnancy TNF-α/IL-10 levels (aOR: 1.654, CI: 1.096-2.495, p = 0.017). These data support the concept that disruptions in the balance between pro- and anti-inflammatory cytokines may contribute to neurobehavioral impairment and alter the risk of FASD. Copyright © 2017 Elsevier Inc. All rights reserved.

Protein disulfide isomerase-mediated apoptosis and proliferation of vascular smooth muscle cells induced by mechanical stress and advanced glycosylation end products result in diabetic mouse vein graft atherosclerosis.

PubMed

Ping, Suning; Liu, Shuying; Zhou, Yuhuan; Li, Ziqing; Li, Yuhuang; Liu, Kefeng; Bardeesi, Adham Sa; Wang, Linli; Chen, Jingbo; Deng, Lie; Wang, Jingjing; Wang, Hong; Chen, Dadi; Zhang, Zhengyu; Sheng, Puyi; Li, Chaohong

2017-05-25

Protein disulfide isomerase (PDI) involves cell survival and death. Whether PDI mediates mechanical stretch stress (SS) and/or advanced glycosylation end products (AGEs) -triggered simultaneous increases in proliferation and apoptosis of vascular smooth muscle cells (VSMCs) is unknown. Here, we hypothesized that different expression levels of PDI trigger completely opposite cell fates among the different VSMC subtypes. Mouse veins were grafted into carotid arteries of non-diabetic and diabetic mice for 8 weeks; the grafted veins underwent simultaneous increases in proliferation and apoptosis, which triggered vein graft arterializations in non-diabetic or atherosclerosis in diabetic mice. A higher rate of proliferation and apoptosis was seen in the diabetic group. SS and/or AGEs stimulated the quiescent cultured VSMCs, resulting in simultaneous increases in proliferation and apoptosis; they could induce increased PDI activation and expression. Both in vivo and in vitro, the proliferating VSMCs indicated weak co-expression of PDI and SM-α-actin while apoptotic or dead cells showed strong co-expression of both. Either SS or AGEs rapidly upregulated the expression of PDI, NOX1 and ROS, and their combination had synergistic effects. Inhibiting PDI simultaneously suppressed the proliferation and apoptosis of VSMCs, while inhibition of SM-α-actin with cytochalasin D led to increased apoptosis and cleaved caspases-3 but had no effect on proliferation. In conclusion, different expression levels of PDI in VSMCs induced by SS and/or AGEs triggered a simultaneous increase in proliferation and apoptosis, accelerated vein graft arterializations or atherosclerosis, leading us to propose PDI as a novel target for the treatment of vascular remodeling and diseases.

Protein disulfide isomerase-mediated apoptosis and proliferation of vascular smooth muscle cells induced by mechanical stress and advanced glycosylation end products result in diabetic mouse vein graft atherosclerosis

PubMed Central

Ping, Suning; Liu, Shuying; Zhou, Yuhuan; Li, Ziqing; Li, Yuhuang; Liu, Kefeng; Bardeesi, Adham SA; Wang, Linli; Chen, Jingbo; Deng, Lie; Wang, Jingjing; Wang, Hong; Chen, Dadi; Zhang, Zhengyu; Sheng, Puyi; Li, Chaohong

2017-01-01

Protein disulfide isomerase (PDI) involves cell survival and death. Whether PDI mediates mechanical stretch stress (SS) and/or advanced glycosylation end products (AGEs) -triggered simultaneous increases in proliferation and apoptosis of vascular smooth muscle cells (VSMCs) is unknown. Here, we hypothesized that different expression levels of PDI trigger completely opposite cell fates among the different VSMC subtypes. Mouse veins were grafted into carotid arteries of non-diabetic and diabetic mice for 8 weeks; the grafted veins underwent simultaneous increases in proliferation and apoptosis, which triggered vein graft arterializations in non-diabetic or atherosclerosis in diabetic mice. A higher rate of proliferation and apoptosis was seen in the diabetic group. SS and/or AGEs stimulated the quiescent cultured VSMCs, resulting in simultaneous increases in proliferation and apoptosis; they could induce increased PDI activation and expression. Both in vivo and in vitro, the proliferating VSMCs indicated weak co-expression of PDI and SM-α-actin while apoptotic or dead cells showed strong co-expression of both. Either SS or AGEs rapidly upregulated the expression of PDI, NOX1 and ROS, and their combination had synergistic effects. Inhibiting PDI simultaneously suppressed the proliferation and apoptosis of VSMCs, while inhibition of SM-α-actin with cytochalasin D led to increased apoptosis and cleaved caspases-3 but had no effect on proliferation. In conclusion, different expression levels of PDI in VSMCs induced by SS and/or AGEs triggered a simultaneous increase in proliferation and apoptosis, accelerated vein graft arterializations or atherosclerosis, leading us to propose PDI as a novel target for the treatment of vascular remodeling and diseases. PMID:28542133

Protein disulfide isomerase and Nox: new partners in redox signaling.

PubMed

Trevelin, Silvia Cellone; Lopes, Lucia Rossetti

2015-01-01

Reactive oxygen species (ROS) contribute to the pathogenesis of cardiovascular disease, including hypertension, atherosclerosis, cardiac hypertrophy, heart failure and restenosis. Thiol proteins and thiol oxidoreductases are key players in cell signaling, and their altered expression and/or activity has been associated with a disrupture in cardiac and vascular homeostasis. Protein disulfide isomerase (PDI) is a thiol oxidoreductase member of the thioredoxin family that has multiple roles in cellular function. Originally discovered in the endoplasmic reticulum (ER), PDI is essential for protein folding. However, it can also be found in the cytosol and closely associated with the surface of platelets, smooth muscle cells, neutrophils and endothelial cells. On the cell surface, PDI is imperative for platelet aggregation and transnitrosation, which are related to thrombosis and control of vascular tone by nitric oxide, respectively. Furthermore, PDI signaling contributes to redox-dependent events such as smooth muscle cell migration induced by PDGF and TNFα-dependent angiogenesis. Studies from our group have shown that intracellular PDI regulates the expression and activity of the NADPH oxidase family of proteins (Nox), which are enzymes dedicated to ROS generation. PDI acts as a new organizer of leukocyte Nox2 by redox dependently associating with p47phox and controlling its recruitment to the plasma membrane, an essential step for assembly of the active enzyme. Such multiple effects of PDI suggest that specific targeting of this oxidoreductase could represent a new approach in the treatment of vascular disease. In this review, we present a novel role for PDI as an adaptor protein involved in redox processes and Nox signaling and propose PDI as a potential therapeutic target in the treatment of atherosclerosis, thrombosis and hypertension.

Compact Conformations of Human Protein Disulfide Isomerase

PubMed Central

Cui, Lei; Ding, Xiang; Niu, Lili; Yang, Fuquan; Wang, Chao; Wang, Chih-chen; Lou, Jizhong

2014-01-01

Protein disulfide isomerase (PDI) composed of four thioredoxin-like domains a, b, b', and a', is a key enzyme catalyzing oxidative protein folding in the endoplasmic reticulum. Large scale molecular dynamics simulations starting from the crystal structures of human PDI (hPDI) in the oxidized and reduced states were performed. The results indicate that hPDI adopts more compact conformations in solution than in the crystal structures, which are stabilized primarily by inter-domain interactions, including the salt bridges between domains a and b' observed for the first time. A prominent feature of the compact conformations is that the two catalytic domains a and a' can locate close enough for intra-molecular electron transfer, which was confirmed by the characterization of an intermediate with a disulfide between the two domains. Mutations, which disrupt the inter-domain interactions, lead to decreased reductase activity of hPDI. Our molecular dynamics simulations and biochemical experiments reveal the intrinsic conformational dynamics of hPDI and its biological impact. PMID:25084354

PDI using nebulized indocyanine green for pneumonia treatment

NASA Astrophysics Data System (ADS)

Geralde, Mariana C.; Kassab, Giulia; Inada, Natalia M.; Kurachi, Cristina; Bagnato, Vanderlei S.

2018-02-01

Infectious pneumonia is a major cause of morbidity/mortality, mainly due to the increasing rate of microorganisms resistant to antibiotics. Photodynamic Inactivation (PDI) is emerging as a promising treatment option, which effects are based on oxidative stress, targeting several biomolecules and probably preventing potential resistant strains. In previous studies, the in vitro inactivation of Streptococcus pneumoniae using indocyanine green (ICG) and infrared (IR) light source (780 nm) was successful, and achieving satisfactory reduction of colony-forming units (CFU/mL). In the present study, a proof-of-principle protocol was designed to treat lung infections by PDI using extracorporeal irradiation with a 780 nm laser device and nebulized ICG as photosensitizer. Balb/c mice were infected with S. pneumoniae and PDI was performed two days after infection using 800 μM of nebulized ICG and extracorporeal irradiation. Our results indicate that IR-extracorporeal PDI using nebulized ICG may be considered a potential pneumonia treatment, and pulmonary decontamination with PDI may be used as a single therapy or as an adjuvant for antibiotics.

FAD oxidizes the ERO1-PDI electron transfer chain: The role of membrane integrity

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

Papp, Eszter; Nardai, Gabor; Mandl, Jozsef

2005-12-16

The molecular steps of the electron transfer in the endoplasmic reticulum from the secreted proteins during their oxidation are relatively unknown. We present here that flavine adenine dinucleotide (FAD) is a powerful oxidizer of the oxidoreductase system, Ero1 and PDI, besides the proteins of rat liver microsomes and HepG2 hepatoma cells. Inhibition of FAD transport hindered the action of FAD. Microsomal membrane integrity was mandatory for all FAD-related oxidation steps downstream of Ero1. The PDI inhibitor bacitracin could inhibit FAD-mediated oxidation of microsomal proteins and PDI, but did not hinder the FAD-driven oxidation of Ero1. Our data demonstrated that Ero1more » can utilize FAD as an electron acceptor and that FAD-driven protein oxidation goes through the Ero1-PDI pathway and requires the integrity of the endoplasmic reticulum membrane. Our findings prompt further studies to elucidate the membrane-dependent steps of PDI oxidation and the role of FAD in redox folding.« less

Synthesis and Characterization of Superhydrophobic, Self-cleaning NIR-reflective Silica Nanoparticles

NASA Astrophysics Data System (ADS)

Sriramulu, Deepa; Reed, Ella Louise; Annamalai, Meenakshi; Venkatesan, Thirumalai Venky; Valiyaveettil, Suresh

2016-11-01

Multifunctional coatings offer many advantages towards protecting various surfaces. Here we apply aggregation induced segregation of perylene diimide (PDI) to control the surface morphology and properties of silica nanoparticles. Differentially functionalized PDI was incorporated on the surface of silica nanoparticles through Si-O-Si bonds. The absorption and emission spectra of the resultant functionalised nanoparticles showed monomeric or excimeric peaks based on the amounts of perylene molecules present on the surface of silica nanoparticles. Contact angle measurements on thin films prepared from nanoparticles showed that unfunctionalised nanoparticles were superhydrophilic with a contact angle (CA) of 0°, whereas perylene functionalised silica particles were hydrophobic (CA > 130°) and nanoparticles functionalised with PDI and trimethoxy(octadecyl)silane (TMODS) in an equimolar ratio were superhydrophobic with static CA > 150° and sliding angle (SA) < 10°. In addition, the near infrared (NIR) reflectance properties of PDI incorporated silica nanoparticles can be used to protect various heat sensitive substrates. The concept developed in this paper offers a unique combination of super hydrophobicity, interesting optical properties and NIR reflectance in nanosilica, which could be used for interesting applications such as surface coatings with self-cleaning and NIR reflection properties.

Zirconium amine tris(phenolate): A more effective initiator for biomedical lactide.

PubMed

Jones, Matthew D; Wu, Xujun; Chaudhuri, Julian; Davidson, Matthew G; Ellis, Marianne J

2017-11-01

Here a zirconium amine tris(phenolate) is used as the initiator for the production of polylactide for biomedical applications, as a replacement for a tin initiator (usually tin octanoate). The ring opening polymerization (ROP) was carried out in the melt at 130°C. The zirconium-catalyzed PLA (PLA-Zr) required 30min, resulting in a polydispersity index (PDI) of 1.17, compared to 1h and PDI=1.77 for tin-catalyzed PLA (PLA-Sn). PLA-Zr and PLA-Sn supported osteosarcoma cell (MG63) culture to the same extent (cell number, morphology, extracellular matrix production and osteogenic function) until day 14 when the PLA-Zr showed increased cell number, overall extracellular matrix production and osteogenic function. To conclude, the reduction in reaction time, controllable microstructure and biologically benign nature of the zirconium amine tris(phenolate) initiator shows that it is a more effective initiator for ROP of polylactide for biomedical applications. Copyright © 2017 Elsevier B.V. All rights reserved.

hPDI: a database of experimental human protein-DNA interactions.

PubMed

Xie, Zhi; Hu, Shaohui; Blackshaw, Seth; Zhu, Heng; Qian, Jiang

2010-01-15

The human protein DNA Interactome (hPDI) database holds experimental protein-DNA interaction data for humans identified by protein microarray assays. The unique characteristics of hPDI are that it contains consensus DNA-binding sequences not only for nearly 500 human transcription factors but also for >500 unconventional DNA-binding proteins, which are completely uncharacterized previously. Users can browse, search and download a subset or the entire data via a web interface. This database is freely accessible for any academic purposes. http://bioinfo.wilmer.jhu.edu/PDI/.

Protein disulfide isomerase a multifunctional protein with multiple physiological roles

NASA Astrophysics Data System (ADS)

Ali Khan, Hyder; Mutus, Bulent

2014-08-01

Protein disulfide isomerase (PDI), is a member of the thioredoxin superfamily of redox proteins. PDI has three catalytic activities including, thiol-disulfide oxireductase, disulfide isomerase and redox-dependent chaperone. Originally, PDI was identified in the lumen of the endoplasmic reticulum and subsequently detected at additional locations, such as cell surfaces and the cytosol. This review will provide an overview of the recent advances in relating the structural features of PDI to its multiple catalytic roles as well as its physiological and pathophysiological functions related to redox regulation and protein folding.

Novel Roles of the Non-catalytic Elements of Yeast Protein-disulfide Isomerase in Its Interplay with Endoplasmic Reticulum Oxidoreductin 1*

PubMed Central

Niu, Yingbo; Zhang, Lihui; Yu, Jiaojiao; Wang, Chih-chen; Wang, Lei

2016-01-01

The formation of disulfide bonds in the endoplasmic reticulum (ER) of eukaryotic cells is catalyzed by the sulfhydryl oxidase, ER oxidoreductin 1 (Ero1), and protein-disulfide isomerase (PDI). PDI is oxidized by Ero1 to continuously introduce disulfides into substrates, and feedback regulates Ero1 activity by manipulating the regulatory disulfides of Ero1. In this study we find that yeast Ero1p is enzymatically active even with its regulatory disulfides intact, and further activation of Ero1p by reduction of the regulatory disulfides requires the reduction of non-catalytic Cys90-Cys97 disulfide in Pdi1p. The principal client-binding site in the Pdi1p b′ domain is necessary not only for the functional Ero1p-Pdi1p disulfide relay but also for the activation of Ero1p. We also demonstrate by complementary activation assays that the regulatory disulfides in Ero1p are much more stable than those in human Ero1α. These new findings on yeast Ero1p-Pdi1p interplay reveal significant differences from our previously identified mode of human Ero1α-PDI interplay and provide insights into the evolution of the eukaryotic oxidative protein folding pathway. PMID:26846856

In Vitro Toxicity of Silver Nanoparticles in Human Lung Epithelial Cells

DTIC Science & Technology

2009-03-01

software from the particle distributions measured and the polydispersity index (PdI) given is a measure of the size ranges present in the solution...Transmission Electron Microscopy Figure 22 shows the TEM primary particles size and distribution determined from measurement of over 100 particles from...nm uncoated. (B) Ag 80 nm uncoated. (C) Ag 10 nm coated. (D) Ag 80 nm coated Table 4 shows the TEM primary particles size and distribution

Protein Disulfide Isomerase Directly Interacts with β-Actin Cys374 and Regulates Cytoskeleton Reorganization*

PubMed Central

Sobierajska, Katarzyna; Skurzynski, Szymon; Stasiak, Marta; Kryczka, Jakub; Cierniewski, Czeslaw S.; Swiatkowska, Maria

2014-01-01

Recent studies support the role of cysteine oxidation in actin cytoskeleton reorganization during cell adhesion. The aim of this study was to explain whether protein disulfide isomerase (PDI) is responsible for the thiol-disulfide rearrangement in the β-actin molecule of adhering cells. First, we showed that PDI forms a disulfide-bonded complex with β-actin with a molecular mass of 110 kDa. Specific interaction of both proteins was demonstrated by a solid phase binding assay, surface plasmon resonance analysis, and immunoprecipitation experiments. Second, using confocal microscopy, we found that both proteins colocalized when spreading MEG-01 cells on fibronectin. Colocalization of PDI and β-actin could be abolished by the membrane-permeable sulfhydryl blocker, N-ethylmaleimide, by the RGD peptide, and by anti-αIIbβ3 antibodies. Consequently, down-regulation of PDI expression by antisense oligonucleotides impaired the spreading of cells and initiated reorganization of the cytoskeleton. Third, because of transfection experiments followed by immunoprecipitation and confocal analysis, we provided evidence that PDI binds to the β-actin Cys374 thiol. Formation of the β-actin-PDI complex was mediated by integrin-dependent signaling in response to the adhesion of cells to the extracellular matrix. Our data suggest that PDI is released from subcellular compartments to the cytosol and translocated toward the periphery of the cell, where it forms a disulfide bond with β-actin when MEG-01 cells adhere via the αIIbβ3 integrin to fibronectin. Thus, PDI appears to regulate cytoskeletal reorganization by the thiol-disulfide exchange in β-actin via a redox-dependent mechanism. PMID:24415753

Potential drug interactions and chemotoxicity in older patients with cancer receiving chemotherapy.

PubMed

Popa, Mihaela A; Wallace, Kristie J; Brunello, Antonella; Extermann, Martine; Balducci, Lodovico

2014-07-01

Increased risk of drug interactions due to polypharmacy and aging-related changes in physiology among older patients with cancer is further augmented during chemotherapy. No previous studies examined potential drug interactions (PDIs) from polypharmacy and their association with chemotherapy tolerance in older patients with cancer. This study is a retrospective medical chart review of 244 patients aged 70+ years who received chemotherapy for solid or hematological malignancies. PDI among all drugs, supplements, and herbals taken with the first chemotherapy cycle were screened for using the Drug Interaction Facts software, which classifies PDIs into five levels of clinical significance with level 1 being the highest. Descriptive and correlative statistics were used to describe rates of PDI. The association between PDI and severe chemotoxicity was tested with logistic regressions adjusted for baseline covariates. A total of 769 PDIs were identified in 75.4% patients. Of the 82 level 1 PDIs identified among these, 32 PDIs involved chemotherapeutics. A large proportion of the identified PDIs were of minor clinical significance. The risk of severe non-hematological toxicity almost doubled with each level 1 PDI (OR=1.94, 95% CI: 1.22-3.09), and tripled with each level 1 PDI involving chemotherapeutics (OR=3.08, 95% CI: 1.33-7.12). No association between PDI and hematological toxicity was found. In this convenience sample of older patients with cancer receiving chemotherapy we found notable rates of PDI and a substantial adjusted impact of PDI on risk of non-hematological toxicity. These findings warrant further research to optimize chemotherapy outcomes. Copyright © 2014 Elsevier Inc. All rights reserved.

EF24 prevents rotenone-induced estrogenic status alteration in breast cancer.

PubMed

Roy, Debarshi; Kabiraj, Parijat; Pal, Rituraj

2014-04-01

Protein disulfide isomerase (PDI), an important endoplasmic reticulum-resident oxidoreductase chaperone can bind to estrogens as well as intact with its receptor proteins [i.e. estrogen receptors (ER) α and β]. It has been postulated that PDI also acts as an intracellular 17β-estradiol (E2)-binding protein that transports and accumulates E2 in live cells. Drop in E2 level promotes dissociation of E2 from PDI and released in cytosol; the released E2 can augment estrogen receptor-mediated transcriptional activity and mitogenic action in cultured cells by modulating the ERβ/ERα ratio. In this study, we observed rotenone-induced damage to PDI leads to significant increase in ERβ/ERα ratio by down-regulating ERα and up-regulating ERβ. We demonstrated that nitrosative stress induced disruption of the cellular estrogenic status can be prevented through diphenyl difluoroketone (EF24, curcumin analog) intervention by protecting PDI from reactive oxygen species (ROS)-induced damage. Together, our study suggests that both PDI and EF24 can play a vital role in maintaining cellular estrogenic homeostasis. © 2013 International Federation for Cell Biology.

Post-Streptococcal Auto-Antibodies Inhibit Protein Disulfide Isomerase and Are Associated with Insulin Resistance

PubMed Central

Aran, Adi; Weiner, Karin; Lin, Ling; Finn, Laurel Ann; Greco, Mary Ann; Peppard, Paul; Young, Terry; Ofran, Yanay; Mignot, Emmanuel

2010-01-01

Post-streptococcal autoimmunity affects millions worldwide, targeting multiple organs including the heart, brain, and kidneys. To explore the post-streptococcal autoimmunity spectrum, we used western blot analyses, to screen 310 sera from healthy subjects with (33%) and without (67%) markers of recent streptococcal infections [anti-Streptolysin O (ASLO) or anti-DNAse B (ADB)]. A 58 KDa protein, reacting strongly with post-streptococcal sera, was identified as Protein Disulfide Isomerase (PDI), an abundant protein with pleiotropic metabolic, immunologic, and thrombotic effects. Anti-PDI autoantibodies, purified from human sera, targeted similar epitopes in Streptolysin O (SLO, P51-61) and PDI (P328-338). The correlation between post-streptococcal status and anti-human PDI auto-immunity was further confirmed in a total of 2987 samples (13.6% in 530 ASLO positive versus 5.6% in 2457 ASLO negative samples, p<0.0001). Finally, anti-PDI auto-antibodies inhibited PDI-mediated insulin degradation in vitro (n = 90, p<0.001), and correlated with higher serum insulin (14.1 iu/ml vs. 12.2 iu/ml, n = 1215, p = 0.039) and insulin resistance (Homeostatic Model Assessment (HOMA) 4.1 vs. 3.1, n = 1215, p = 0.004), in a population-based cohort. These results identify PDI as a major target of post-streptococcal autoimmunity, and establish a new link between infection, autoimmunity, and metabolic disturbances. PMID:20886095

Application of the central composite design to optimize the preparation of novel micelles of harmine.

PubMed

Bei, Yong-Yan; Zhou, Xiao-Feng; You, Ben-Gang; Yuan, Zhi-Qiang; Chen, Wei-Liang; Xia, Peng; Liu, Yang; Jin, Yong; Hu, Xiao-Juan; Zhu, Qiao-Ling; Zhang, Chun-Ge; Zhang, Xue-Nong; Zhang, Liang

2013-01-01

Lactose-palmitoyl-trimethyl-chitosan (Lac-TPCS), a novel amphipathic self-assembled polymer, was synthesized for administration of insoluble drugs to reduce their adverse effects. The central composite design was used to study the preparation technique of harmine (HM)-loaded self-assembled micelles based on Lac-TPCS (Lac-TPCS/HM). Three preparation methods and single factors were screened, including solvent type, HM amount, hydration volume, and temperature. The optimal preparation technique was identified after investigating the influence of two independent factors, namely, HM amount and hydration volume, on four indexes, ie, encapsulation efficiency (EE), drug-loading amount (LD), particle size, and polydispersity index (PDI). Analysis of variance showed a high coefficient of determination of 0.916 to 0.994, thus ensuring a satisfactory adjustment of the predicted prescription. The maximum predicted values of the optimal prescription were 91.62%, 14.20%, 183.3 nm, and 0.214 for EE, LD, size, and PDI, respectively, when HM amount was 1.8 mg and hydration volume was 9.6 mL. HM-loaded micelles were successfully characterized by Fourier-transform infrared spectroscopy, differential scanning calorimetry, X-ray diffraction, and a fluorescence-quenching experiment. Sustained release of Lac-TPCS/HM reached 65.3% in 72 hours at pH 7.4, while free HM released about 99.7% under the same conditions.

Neurodevelopment for the first three years following prenatal mobile phone use, radio frequency radiation and lead exposure.

PubMed

Choi, Kyung-Hwa; Ha, Mina; Ha, Eun-Hee; Park, Hyesook; Kim, Yangho; Hong, Yun-Chul; Lee, Ae-Kyoung; Hwa Kwon, Jong; Choi, Hyung-Do; Kim, Nam; Kim, Suejin; Park, Choonghee

2017-07-01

Studies examining prenatal exposure to mobile phone use and its effect on child neurodevelopment show different results, according to child's developmental stages. To examine neurodevelopment in children up to 36 months of age, following prenatal mobile phone use and radiofrequency radiation (RFR) exposure, in relation to prenatal lead exposure. We analyzed 1198 mother-child pairs from a prospective cohort study (the Mothers and Children's Environmental Health Study). Questionnaires were provided to pregnant women at ≤20 weeks of gestation to assess mobile phone call frequency and duration. A personal exposure meter (PEM) was used to measure RFR exposure for 24h in 210 pregnant women. Maternal blood lead level (BLL) was measured during pregnancy. Child neurodevelopment was assessed using the Korean version of the Bayley Scales of Infant Development-Revised at 6, 12, 24, and 36 months of age. Logistic regression analysis applied to groups classified by trajectory analysis showing neurodevelopmental patterns over time. The psychomotor development index (PDI) and the mental development index (MDI) at 6, 12, 24, and 36 months of age were not significantly associated with maternal mobile phone use during pregnancy. However, among children exposed to high maternal BLL in utero, there was a significantly increased risk of having a low PDI up to 36 months of age, in relation to an increasing average calling time (p-trend=0.008). There was also a risk of having decreasing MDI up to 36 months of age, in relation to an increasing average calling time or frequency during pregnancy (p-trend=0.05 and 0.007 for time and frequency, respectively). There was no significant association between child neurodevelopment and prenatal RFR exposure measured by PEM in all subjects or in groups stratified by maternal BLL during pregnancy. We found no association between prenatal exposure to RFR and child neurodevelopment during the first three years of life; however, a potential combined effect of prenatal exposure to lead and mobile phone use was suggested. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Comparison of two common aEEG classifications for the prediction of neurodevelopmental outcome in preterm infants.

PubMed

Bruns, Nora; Dransfeld, Frauke; Hüning, Britta; Hobrecht, Julia; Storbeck, Tobias; Weiss, Christel; Felderhoff-Müser, Ursula; Müller, Hanna

2017-02-01

Neurodevelopmental outcome after prematurity is crucial. The aim was to compare two amplitude-integrated EEG (aEEG) classifications (Hellström-Westas (HW), Burdjalov) for outcome prediction. We recruited 65 infants ≤32 weeks gestational age with aEEG recordings within the first 72 h of life and Bayley testing at 24 months corrected age or death. Statistical analyses were performed for each 24 h section to determine whether very immature/depressed or mature/developed patterns predict survival/neurological outcome and to find predictors for mental development index (MDI) and psychomotor development index (PDI) at 24 months corrected age. On day 2, deceased infants showed no cycling in 80% (HW, p = 0.0140) and 100% (Burdjalov, p = 0.0041). The Burdjalov total score significantly differed between groups on day 2 (p = 0.0284) and the adapted Burdjalov total score on day 2 (p = 0.0183) and day 3 (p = 0.0472). Cycling on day 3 (HW; p = 0.0059) and background on day 3 (HW; p = 0.0212) are independent predictors for MDI (p = 0.0016) whereas no independent predictor for PDI was found (multiple regression analyses). Cycling in both classifications is a valuable tool to assess chance of survival. The classification by HW is also associated with long-term mental outcome. What is Known: •Neurodevelopmental outcome after preterm birth remains one of the major concerns in neonatology. •aEEG is used to measure brain activity and brain maturation in preterm infants. What is New: •The two common aEEG classifications and scoring systems described by Hellström-Westas and Burdjalov are valuable tools to predict neurodevelopmental outcome when performed within the first 72 h of life. •Both aEEG classifications are useful to predict chance of survival. The classification by Hellström-Westas can also predict long-term outcome at corrected age of 2 years.

Reflections on the development and implementation of an early warning system for ecstasy and related drug markets in Australia.

PubMed

Kinner, Stuart A; Degenhardt, Louisa

2006-09-01

Regular and systematic monitoring of drug markets provides the basis for evidence-based policy. In Australia, trends in ecstasy and related drug (ERD) markets have been monitored in selected jurisdictions since 2000 and nationally since 2003, by the Party Drugs Initiative (PDI). The PDI maximises the validity of conclusions by triangulating information from (a) interviews with regular ecstasy users (REU), (b) interviews with key experts and (c) indicator data. There is currently no other system in Australia for monitoring these markets systematically; however, the value of the PDI has been constrained by the quality of available data. Difficulties in recruiting and interviewing appropriate consumers (REU) and key experts have been experienced, but largely overcome. Limitations of available indicator data from both health and law enforcement continue to present challenges and there remains considerable scope for enhancing existing routine data collection systems, to facilitate monitoring of ERD markets. With an expanding market for ecstasy and related drugs in Australia, and in the context of indicator data that continue to be limited in scope and detail, there is a strong argument for the continued collection of annual, comparable data from a sentinel group of REU, such as those recruited for the PDI.

Parametric Decay Instability and Dissipation of Low-frequency Alfvén Waves in Low-beta Turbulent Plasmas

NASA Astrophysics Data System (ADS)

Fu, Xiangrong; Li, Hui; Guo, Fan; Li, Xiaocan; Roytershteyn, Vadim

2018-03-01

Evolution of the parametric decay instability (PDI) of a circularly polarized Alfvén wave in a turbulent low-beta plasma background is investigated using 3D hybrid simulations. It is shown that the turbulence reduces the growth rate of PDI as compared to the linear theory predictions, but PDI can still exist. Interestingly, the damping rate of the ion acoustic mode (as the product of PDI) is also reduced as compared to the linear Vlasov predictions. Nonetheless, significant heating of ions in the direction parallel to the background magnetic field is observed due to resonant Landau damping of the ion acoustic waves. In low-beta turbulent plasmas, PDI can provide an important channel for energy dissipation of low-frequency Alfvén waves at a scale much larger than the ion kinetic scales, different from the traditional turbulence dissipation models.

Computational Study of Formic Acid Dehydrogenation Catalyzed by Al(III)-Bis(imino)pyridine.

PubMed

Lu, Qian-Qian; Yu, Hai-Zhu; Fu, Yao

2016-03-18

The mechanism of formic acid dehydrogenation catalyzed by the bis(imino)pyridine-ligated aluminum hydride complex (PDI(2-))Al(THF)H (PDI=bis(imino)pyridine) was studied by density functional theory calculations. The overall transformation is composed of two stages: catalyst activation and the catalytic cycle. The catalyst activation begins with O-H bond cleavage of HCOOH promoted by aluminum-ligand cooperation, followed by HCOOH-assisted Al-H bond cleavage, and protonation of the imine carbon atom of the bis(imino)pyridine ligand. The resultant doubly protonated complex ((H,H) PDI)Al(OOCH)3 is the active catalyst for formic acid dehydrogenation. Given this, the catalytic cycle includes β-hydride elimination of ((H,H) PDI)Al(OOCH)3 to produce CO2, and the formed ((H,H) PDI)Al(OOCH)2 H mediates HCOOH to release H2. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

National workshop on core competencies for success in the veterinary profession.

PubMed

Lloyd, James W; King, Lonnie J; Klausner, Jeffrey S; Harris, Donna

2003-01-01

A workshop was designed to (1) present results of the Core Competencies for Veterinary Medicine project conducted by Personnel Decisions International (PDI); (2) discuss and analyze the implications of the PDI study results for academia, private practice, and industry; (3) identify actionable items-discuss opportunities and barriers; and (4) develop appropriate recommendations-devise specific actions for implementation as next steps. In total, 25 veterinary colleges were represented at the workshop and a total of 110 attendees participated, a broad cross-section of the veterinary profession (both academic and non-academic). Through an orchestrated combination of general sessions and facilitated, small group discussions, prioritized recommendations for implementation and initial action plans for next steps were developed. Recommendations included publicizing results of the PDI study, reconsidering current admissions policies and processes, evaluating the applicant pool and current recruitment programs, developing structured mentoring programs, enhancing DVM/VMD training programs, coordinating the development of continuing education programs, and overcoming existing barriers to change. Next steps should involve collaborative efforts across all sectors of the veterinary profession to develop plans for implementing the workshop's recommendations. Leadership for follow-up might reasonably come from the Association of American Veterinary Medical Colleges (AAVMC), the American Veterinary Medical Association (AVMA), and the American Animal Hospital Association (AAHA), either individually or collectively, through the National Commission on Veterinary Economic Issues (NCVEI). Partnerships with industry are also possible and should be strongly considered.

Perylene Diimide as a Precise Graphene-like Superoxide Dismutase Mimetic

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

Jalilov, Almaz S.; Nilewski, Lizanne G.; Berka, Vladimir

Here we show that the active portion of a graphitic nanoparticle can be mimicked by a perylene diimide (PDI) to explain the otherwise elusive biological and electrocatalytic activity of the nanoparticle construct. Development of molecular analogues that mimic the antioxidant properties of oxidized graphenes, in this case the poly(ethylene glycolated) hydrophilic carbon clusters (PEG–HCCs), will afford important insights into the highly efficient activity of PEG–HCCs and their graphitic analogues. PEGylated perylene diimides (PEGn–PDI) serve as well-defined molecular analogues of PEG–HCCs and oxidized graphenes in general, and their antioxidant and superoxide dismutase-like (SOD-like) properties were studied. PEGn–PDIs have two reversible reductionmore » peaks, which are more positive than the oxidation peak of superoxide (O2•–). This is similar to the reduction peak of the HCCs. Thus, as with PEG–HCCs, PEGn–PDIs are also strong single-electron oxidants of O2•–. Furthermore, reduced PEGn–PDI, PEGn–PDI•–, in the presence of protons, was shown to reduce O2•– to H2O2 to complete the catalytic cycle in this SOD analogue. The kinetics of the conversion of O2•– to O2 and H2O2 by PEG8–PDI was measured using freeze-trap EPR experiments to provide a turnover number of 133 s–1; the similarity in kinetics further supports that PEG8–PDI is a true SOD mimetic. Finally, PDIs can be used as catalysts in the electrochemical oxygen reduction reaction in water, which proceeds by a two-electron process with the production of H2O2, mimicking graphene oxide nanoparticles that are otherwise difficult to study spectroscopically.« less

Δg: The new aromaticity index based on g-factor calculation applied for polycyclic benzene rings

NASA Astrophysics Data System (ADS)

Ucun, Fatih; Tokatlı, Ahmet

2015-02-01

In this work, the aromaticity of polycyclic benzene rings was evaluated by the calculation of g-factor for a hydrogen placed perpendicularly at geometrical center of related ring plane at a distance of 1.2 Å. The results have compared with the other commonly used aromatic indices, such as HOMA, NICSs, PDI, FLU, MCI, CTED and, generally been found to be in agreement with them. So, it was proposed that the calculation of the average g-factor as Δg could be applied to study the aromaticity of polycyclic benzene rings without any restriction in the number of benzene rings as a new magnetic-based aromaticity index.

Phase-shifting point diffraction interferometer focus-aid enhanced mask

DOEpatents

Naulleau, Patrick

2000-01-01

A phase-shifting point diffraction interferometer system (PS/PDI) employing a PS/PDI mask that includes a PDI focus aid is provided. The PDI focus aid mask includes a large or secondary reference pinhole that is slightly displaced from the true or primary reference pinhole. The secondary pinhole provides a larger capture tolerance for interferometrically performing fine focus. With the focus-aid enhanced mask, conventional methods such as the knife-edge test can be used to perform an initial (or rough) focus and the secondary (large) pinhole is used to perform interferometric fine focus. Once the system is well focused, high accuracy interferometry can be performed using the primary (small) pinhole.

The Feasibility of Thermophilic Caldimonas manganoxidans as a Platform for Efficient PHB Production.

PubMed

Hsiao, Li-Jung; Lin, Ji-Hong; Sankatumvong, Pantitra; Wu, Tzong-Ming; Li, Si-Yu

2016-11-01

Recently, poly(3-hydroxybutyrate) (PHB) has been found in a few thermophilic strains where several advantages can be gained from running fermentation at high temperatures. Caldimonas manganoxidans, a thermophilic gram-negative bacterium, was investigated for the feasibility as a PHB-producing strain. It is suggested that the best fermentation strategy for achieving the highest PHB concentration of 5.4 ± 1.1 g/L (from 20 g/L glucose) in 24 h is to use the fermentation conditions that are favored for the bacterial growth, yet temperature and pH should be chosen at conditions that are favored for the PHB content. Besides, the above fermentation conditions produce PHB that has a high molecular weight of 1274 kDa with a low polydispersity index (PDI) of 1.45, where the highest Mw of PHB of 1399 kDa (PDI of 1.32) is obtained in this study. To the best knowledge of authors, C. manganoxidans has the best PHB productivity among the thermophiles and is comparable to those common PHB-producing mesophiles.

Ero1-α and PDIs constitute a hierarchical electron transfer network of endoplasmic reticulum oxidoreductases

PubMed Central

Araki, Kazutaka; Iemura, Shun-ichiro; Kamiya, Yukiko; Ron, David; Kato, Koichi; Natsume, Tohru

2013-01-01

Ero1-α and endoplasmic reticulum (ER) oxidoreductases of the protein disulfide isomerase (PDI) family promote the efficient introduction of disulfide bonds into nascent polypeptides in the ER. However, the hierarchy of electron transfer among these oxidoreductases is poorly understood. In this paper, Ero1-α–associated oxidoreductases were identified by proteomic analysis and further confirmed by surface plasmon resonance. Ero1-α and PDI were found to constitute a regulatory hub, whereby PDI induced conformational flexibility in an Ero1-α shuttle cysteine (Cys99) facilitated intramolecular electron transfer to the active site. In isolation, Ero1-α also oxidized ERp46, ERp57, and P5; however, kinetic measurements and redox equilibrium analysis revealed that PDI preferentially oxidized other oxidoreductases. PDI accepted electrons from the other oxidoreductases via its a′ domain, bypassing the a domain, which serves as the electron acceptor from reduced glutathione. These observations provide an integrated picture of the hierarchy of cooperative redox interactions among ER oxidoreductases in mammalian cells. PMID:24043701

An evaluation of prescribing trends and patterns of claims within the Preferred Drugs Initiative in Ireland (2011-2016): an interrupted time-series study.

PubMed

McDowell, Ronald; Bennett, Kathleen; Moriarty, Frank; Clarke, Sarah; Barry, Michael; Fahey, Tom

2018-04-20

To examine the impact of the Preferred Drugs Initiative (PDI), an Irish health policy aimed at enhancing evidence-based cost-effective prescribing, on prescribing trends and the cost of prescription medicines across seven medication classes. Retrospective repeated cross-sectional study spanning the years 2011 - 2016. Health Service Executive Primary Care Reimbursement Service pharmacy claims data for General Medical Services (GMS) patients, approximately 40% of the Irish population. Adults aged ≥18 years between 2011 and 2016 are eligible for the GMS scheme. The percentage of PDI medications within each drug class per calendar quarter. Linear regression was used to model prescribing of the preferred drug within each medication group and to assess the impact of PDI guidelines and other relevant changes in prescribing practice. Savings in drug expenditure were estimated. Between 2011 and 2016, around a quarter (23.59%) of all medications were for single-agent drugs licensed in the seven drug classes. There was a small increase in the percentage of PDI drugs, increasing from 4.64% of all medications in 2011 to 4.76% in 2016 (P<0.001). The percentage of preferred drugs within each drug class was significantly higher immediately following publication of the guidelines for all classes except urology, with the largest increases noted for lansoprazole (1.21%, 95% CI: 0.84% to 1.57%, P<0.001) and venlafaxine (0.71%, 95% CI: 0.15% to 1.27%, P=0.02). Trends in prescribing of the preferred drugs between PDI guidelines and the end of 2016 varied between drug classes. Total cost savings between 2013 and 2016 were estimated to be €2.7 million. There has been a small increase in prescribing of PDI drugs in response to prescribing guidelines, with inconsistent changes observed across therapeutic classes. These findings are relevant where health services are seeking to develop more active prescribing interventions aimed at changing prescribing practice. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Molecular characterization and analysis of a novel protein disulfide isomerase-like protein of Eimeria tenella.

PubMed

Han, Hongyu; Dong, Hui; Zhu, Shunhai; Zhao, Qiping; Jiang, Lianlian; Wang, Yange; Li, Liujia; Wu, Youlin; Huang, Bing

2014-01-01

Protein disulfide isomerase (PDI) and PDI-like proteins are members of the thioredoxin superfamily. They contain thioredoxin-like domains and catalyze the physiological oxidation, reduction and isomerization of protein disulfide bonds, which are involved in cell function and development in prokaryotes and eukaryotes. In this study, EtPDIL, a novel PDI-like gene of Eimeria tenella, was cloned using rapid amplification of cDNA ends (RACE) according to the expressed sequence tag (EST). The EtPDIL cDNA contained 1129 nucleotides encoding 216 amino acids. The deduced EtPDIL protein belonged to thioredoxin-like superfamily and had a single predicted thioredoxin domain with a non-classical thioredoxin-like motif (SXXC). BLAST analysis showed that the EtPDIL protein was 55-59% identical to PDI-like proteins of other apicomplexan parasites. The transcript and protein levels of EtPDIL at different development stages were investigated by real-time quantitative PCR and western blot. The messenger RNA and protein levels of EtPDIL were higher in sporulated oocysts than in unsporulated oocysts, sporozoites or merozoites. Protein expression was barely detectable in unsporulated oocysts. Western blots showed that rabbit antiserum against recombinant EtPDIL recognized only a native 24 kDa protein from parasites. Immunolocalization with EtPDIL antibody showed that EtPDIL had a disperse distribution in the cytoplasm of whole sporozoites and merozoites. After sporozoites were incubated in complete medium, EtPDIL protein concentrated at the anterior of the sporozoites and appeared on the surface of parasites. Specific staining was more intense and mainly located on the parasite surface after merozoites released from mature schizonts invaded DF-1 cells. After development of parasites in DF-1 cells, staining intensified in trophozoites, immature schizonts and mature schizonts. Antibody inhibition of EtPDIL function reduced the ability of E. tenella to invade DF-1 cells. These results suggested that EtPDIL might be involved in sporulation in external environments and in host cell adhesion, invasion and development of E. tenella.

Frequency-dependent Alfvén-wave Propagation in the Solar Wind: Onset and Suppression of Parametric Decay Instability

NASA Astrophysics Data System (ADS)

Shoda, Munehito; Yokoyama, Takaaki; Suzuki, Takeru K.

2018-06-01

Using numerical simulations we investigate the onset and suppression of parametric decay instability (PDI) in the solar wind, focusing on the suppression effect by the wind acceleration and expansion. Wave propagation and dissipation from the coronal base to 1 au is solved numerically in a self-consistent manner; we take into account the feedback of wave energy and pressure in the background. Monochromatic waves with various injection frequencies, f 0, are injected to discuss the suppression of PDI, while broadband waves are applied to compare the numerical results with observation. We find that high-frequency ({f}0≳ {10}-3 {Hz}) Alfvén waves are subject to PDI. Meanwhile, the maximum growth rate of the PDI of low-frequency ({f}0≲ {10}-4 {Hz}) Alfvén waves becomes negative due to acceleration and expansion effects. Medium-frequency ({f}0≈ {10}-3.5 {Hz}) Alfvén waves have a positive growth rate but do not show the signature of PDI up to 1 au because the growth rate is too small. The medium-frequency waves experience neither PDI nor reflection so they propagate through the solar wind most efficiently. The solar wind is shown to possess a frequency-filtering mechanism with respect to Alfvén waves. The simulations with broadband waves indicate that the observed trend of the density fluctuation is well explained by the evolution of PDI while the observed cross-helicity evolution is in agreement with low-frequency wave propagation.

A preliminary study of Patient Dignity Inventory validation among patients hospitalized in an acute psychiatric ward

PubMed Central

Di Lorenzo, Rosaria; Cabri, Giulio; Carretti, Eleonora; Galli, Giacomo; Giambalvo, Nina; Rioli, Giulia; Saraceni, Serena; Spiga, Giulia; Del Giovane, Cinzia; Ferri, Paola

2017-01-01

Purpose To investigate the perception of dignity among patients hospitalized in a psychiatric setting using the Patient Dignity Inventory (PDI), which had been first validated in oncologic field among terminally ill patients. Patients and methods After having modified two items, we administered the Italian version of PDI to all patients hospitalized in a public psychiatric ward (Service of Psychiatric Diagnosis and Treatment of a northern Italian town), who provided their consent and completed it at discharge, from October 21, 2015 to May 31, 2016. We excluded minors and patients with moderate/severe dementia, with poor knowledge of Italian language, who completed PDI in previous hospitalizations and/or were hospitalized for <72 hours. We collected the demographic and clinical variables of our sample (n=135). We statistically analyzed PDI scores, performing Cronbach’s alpha coefficient and principal factor analysis, followed by orthogonal and oblique rotation. We concomitantly administered to our sample other scales (Hamilton Rating Scales for Depression and Anxiety, Global Assessment of Functioning and Health of the Nation Outcome Scales) to analyze the PDI concurrent validity. Results With a response rate of 93%, we obtained a mean PDI score of 48.27 (±19.59 SD) with excellent internal consistency (Cronbach’s alpha coefficient =0.93). The factorial analysis showed the following three factors with eigenvalue >1 (Kaiser’s criterion), which explained >80% of total variance with good internal consistency: 1) “Loss of self-identity and social role”, 2) “Anxiety and uncertainty for future” and 3) “Loss of personal autonomy”. The PDI and the three-factor scores were statistically significantly positively correlated with the Hamilton Scales for Depression and Anxiety but not with other scale scores. Conclusion Our preliminary research suggests that PDI can be a reliable tool to assess patients’ dignity perception in a psychiatric setting, until now little investigated, helping professionals to improve quality of care and patients to accept treatments. PMID:28182110

Optimal arrangement of magnetic coils for functional magnetic stimulation of the inspiratory muscles in dogs.

PubMed

Lin, Vernon Weh-Hau; Zhu, Ercheng; Sasse, Scott A; Sassoon, Catherine; Hsiao, Ian N

2005-12-01

In an attempt to maximize inspiratory pressure and volume, the optimal position of a single or of dual magnetic coils during functional magnetic stimulation (FMS) of the inspiratory muscles was evaluated in twenty-three dogs. Unilateral phrenic magnetic stimulation (UPMS) or bilateral phrenic magnetic stimulation (BPMS), posterior cervical magnetic stimulation (PCMS), anterior cervical magnetic stimulation (ACMS) as well as a combination of PCMS and ACMS were performed. Trans-diaphragmatic pressure (Pdi), flow, and lung volume changes with an open airway were measured. Transdiaphragmatic pressure was also measured with an occluded airway. Changes in inspiratory parameters during FMS were compared with 1) electrical stimulation of surgically exposed bilateral phrenic nerves (BPES) and 2) ventral root electrical stimulation at C5-C7 (VRES C5-C7). Relative to the Pdi generated by BPES of 36.3 +/- 4.5 cm H2O (Mean +/- SEM), occluded Pdi(s) produced by UPMS, BPMS, PCMS, ACMS, and a combined PCMS + ACMS were 51.7%, 61.5%, 22.4%, 100.3%, and 104.5% of the maximal Pdi, respectively. Pdi(s) produced by UPMS, BPMS, PCMS, ACMS, and combined ACMS + PCMS were 38.0%, 45.2%, 16.5%, 73.8%, and 76.8%, respectively, of the Pdi induced by VRES (C5-C7) (48.0 +/- 3.9 cm H2O). The maximal Pdi(s) generated during ACMS and combined PCMS + ACMS were higher than the maximal Pdi(s) generated during UPMS, BPMS, or PCMS (p < 0.05). ACMS alone induced 129.8% of the inspiratory flow (73.0 +/- 9.4 L/ min) and 77.5% of the volume (626 +/- 556 ml) induced by BPES. ACMS and combined PCMS + ACMS produce a greater inspiratory pressure than UPMS, BPMS or PCMS. ACMS can be used to generate sufficient inspiratory pressure, flow, and volume for activation of the inspiratory muscles.

Maternal nicotine exposure leads to decreased cardiac protein disulfide isomerase and impaired mitochondrial function in male rat offspring.

PubMed

Barra, Nicole G; Lisyansky, Maria; Vanduzer, Taylor A; Raha, Sandeep; Holloway, Alison C; Hardy, Daniel B

2017-12-01

Smoking throughout pregnancy can lead to complications during gestation, parturition and neonatal development. Thus, nicotine replacement therapies are a popular alternative thought to be safer than cigarettes. However, recent studies in rodents suggest that fetal and neonatal nicotine exposure alone results in cardiac dysfunction and high blood pressure. While it is well known that perinatal nicotine exposure causes increased congenital abnormalities, the mechanisms underlying longer-term deficits in cardiac function are not completely understood. Recently, our laboratory demonstrated that nicotine impairs placental protein disulfide isomerase (PDI) triggering an increase in endoplasmic reticulum stress, leading us to hypothesize that this may also occur in the heart. At 3 months of age, nicotine-exposed offspring had 45% decreased PDI levels in the absence of endoplasmic reticulum stress. Given the association of PDI and superoxide dismutase enzymes, we further observed that antioxidant superoxide dismutase-2 levels were reduced by 32% in these offspring concomitant with a 26-49% decrease in mitochondrial complex proteins (I, II, IV and V) and tissue inhibitor of metalloproteinase-4, a critical matrix metalloprotease for cardiac contractility and health. Collectively, this study suggests that perinatal nicotine exposure decreases PDI, which can promote oxidative damage and mitochondrial damage, associated with a premature decline in cardiac function. Copyright © 2017 John Wiley & Sons, Ltd.

Does maternal psychological distress affect neurodevelopmental outcomes of preterm infants at a gestational age of ≤32weeks.

PubMed

Bozkurt, Ozlem; Eras, Zeynep; Sari, Fatma Nur; Dizdar, Evrim Alyamac; Uras, Nurdan; Canpolat, Fuat Emre; Oguz, Serife Suna

2017-01-01

There is some evidence that maternal psychological status in the prenatal and postnatal periods is associated with infants' cognitive, behavioural, and emotional functions. The aim of this study was to examine the relationships of maternal depression and anxiety with neurodevelopmental outcomes of preterm infants with a gestational age of ≤32weeks, examined at a corrected age of 18 to 22months. Cross-sectional study. In total, 220 preterm infants with a gestational age of ≤32weeks who were born from January 2008 to September 2011 and admitted to the neonatal intensive care unit were prospectively examined. Neurodevelopmental evaluation was performed at a corrected age of 18 to 22months by a developmental paediatrician using the Bayley Scales of Infant Development II (BSID-II). The Beck Depression Inventory and Beck Anxiety Inventory were used to assess maternal depression and anxiety at the same visit as the neurodevelopmental evaluation. The depression scores of mothers of infants with a Mental Development Index (MDI) score of <70 were significantly higher than those of mothers of infants with an MDI score of >70 (16.3±12.8 vs 8.8±7.0, p<0.001). The depression scores of mothers of infants with neurodevelopmental impairment were also significantly higher than those without neurodevelopmental impairment (12.8±10.5 vs 8.8±7.3, p=0.003). There was no relationship between the presence of cerebral palsy or a Psychomotor Developmental Index (PDI) score of <70 and the mothers' depression scores. Multiple regression analysis revealed that maternal depression and the occurrence of more than two sepsis attacks were associated with an MDI score of <70, and grade III to IV intraventricular haemorrhage was associated with neurodevelopmental impairment and a PDI score of <70. Maternal depression is negatively associated with the neurodevelopment of preterm infants at a gestational age of ≤32weeks. Maternal psychological well-being should be taken into consideration during the long-term follow-up of preterm infants. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Sae regulator factor impairs the response to photodynamic inactivation mediated by Toluidine blue in Staphylococcus aureus.

PubMed

Gándara, Lautaro; Mamone, Leandro; Dotto, Cristian; Buzzola, Fernanda; Casas, Adriana

2016-12-01

Photodynamic inactivation (PDI) involves the combined use of light and a photosensitizer, which, in the presence of oxygen, originates cytotoxic species capable of inactivating bacteria. Since the emergence of multi-resistant bacterial strains is becoming an increasing public health concern, PDI becomes an attractive choice. The aim of this work was to study the differential susceptibility to Toluidine blue (TB) mediated PDI (TB-PDI) of S. aureus mutants (RN6390 and Newman backgrounds) for different key regulators of virulence factors related to some extent to oxidative stress. Complete bacteria eradication of planktonic cultures of RN6390 S. aureus photosensitized with 13μM TB was obtained upon illumination with a low light dose of 4.2J/cm 2 from a non-coherent light source. Similarly, complete cell death was achieved applying 1.3μM TB and 19J/cm 2 light dose, showing that higher light doses can lead to equal cell death employing low photosensitizer concentrations. Interestingly, RN6390 in planktonic culture responded significantly better to TB-PDI than the Newman strain. We showed that deficiencies in rsbU, mgrA (transcription factors related to stress response) or agr (quorum sensing system involved in copper resistance to oxidative stress) did not modify the response of planktonic S. aureus to PDI. On the other hand, the two component system sae impaired the response to TB-PDI through a mechanism not related to the Eap adhesin. More severe conditions were needed to inactivate S. aureus biofilms (0.5mM TB, 157J/cm 2 laser light). In mutant sae biofilms, strain dependant differential susceptibilities are not noticed. Copyright © 2016 Elsevier B.V. All rights reserved.

Dissipation of Alfven Waves at Fluid Scale through Parametric Decay Instabilities in Low-beta Turbulent Plasma

NASA Astrophysics Data System (ADS)

Fu, X.; Li, H.; Guo, F.; Li, X.; Roytershteyn, V.

2017-12-01

The solar wind is a turbulent magnetized plasma extending from the upper atmosphere of the sun to the edge of the heliosphere. It carries charged particles and magnetic fields originated from the Sun, which have great impact on the geomagnetic environment and human activities in space. In such a magnetized plasma, Alfven waves play a crucial role in carrying energy from the surface of the Sun, injecting into the solar wind and establishing power-law spectra through turbulent energy cascades. On the other hand, in compressible plasmas large amplitude Alfven waves are subject to a parametric decay instability (PDI) which converts an Alfven wave to another counter-propagating Alfven wave and an ion acoustic wave (slow mode). The counter-propagating Alfven wave provides an important ingredient for turbulent cascade, and the slow-mode wave provides a channel for solar wind heating in a spatial scale much larger than ion kinetic scales. Growth and saturation of PDI in quiet plasma have been intensively studied using linear theory and nonlinear simulations in the past. Here using 3D hybrid simulations, we show that PDI is still effective in turbulent low-beta plasmas, generating slow modes and causing ion heating. Selected events in WIND data are analyzed to identify slow modes in the solar wind and the role of PDI, and compared with our simulation results. We also investigate the validity of linear Vlasov theory regarding PDI growth and slow mode damping in turbulent plasmas. Since PDI favors low plasma beta, we expect to see more evidence of PDI in the solar wind close to the Sun, especially from the upcoming NASA's Parker Solar Probe mission which will provide unprecedented wave and plasma data as close as 8.5 solar radii from the Sun.

In vitro photodynamic inactivation effects of benzylidene cyclopentanone photosensitizers on clinical fluconazole-resistant Candida albicans.

PubMed

Zhou, Shaona; Sun, Zhiyuan; Ye, Zulin; Wang, Ying; Wang, Leili; Xing, Limei; Qiu, Haixia; Huang, Naiyan; Luo, Yanping; Zhao, Yuxia; Gu, Ying

2018-06-01

The incidence of Candida infections has increased for various reasons, including, the more frequent use of immunosuppresants or broad-spectrum antibiotics. Photodynamic inactivation (PDI) is a promising approach for treating localized Candida infections. The PDI efficacies of three benzylidene cyclopentanone-based (BCB) photosensitizers (PSs: P1, P2 and Y1) against three fluconazole-resistant C. albicans (cal-1, cal-2, and cal-3) and one control C. albicans (ATCC 90028), respectively, were evaluated using an established plate dilution method. The binding of PSs to C. albicans was determined by fluorescence spectroscopy. The mechanism of antifungal PDI was investigated using confocal laser scanning microscopy (CLSM) and transmission electron microscopy (TEM). Three BCB PSs all bound rapidly to C. albicans. After incubation with PSs for 30 min and irradiation with a 532 nm laser for 10 min (40 mW cm -2 , 24 J cm -2 ), the fungicidal activity was achieved as 7.5 μM for P1 and P2, and 25 μM for Y1. CLSM confirmed that P1 and Y1 were located in intracellular components, including mitochondria, while P2 bound to the protoplast exterior and failed to enter the cells. TEM revealed the damage of mitochondria ultrastructures after P1- or Y1-mediated PDI, consistenting with the CLSM results. However, most cells became edematous, enlarged or deformation after P2-mediated PDI. The three BCB PSs all have remarkable PDI effects on C. albicans. The best effect is obtained by P1, which has one cationic charge with a proper lipophilicity. The respective subcellular localization of the three PSs led to different PDI mechanisms. Copyright © 2018. Published by Elsevier B.V.

Experimental stroke protection induced by 4-hydroxybenzyl alcohol is cancelled by bacitracin.

PubMed

Descamps, Elodie; Petrault-Laprais, Maud; Maurois, Pierre; Pages, Nicole; Bac, Pierre; Bordet, Régis; Vamecq, Joseph

2009-06-01

Induction of protein disulfide isomerase (PDI) is validated as a main mechanism by which 4-hydroxybenzyl alcohol (4-HBA), an active principle of Gastrodia elata Blume, reduces cerebral infarct volumes in a murine model of focal brain ischemia/reperfusion. In contrast to its position isomers, i.e. 3-hydroxybenzyl alcohol (3-HBA) and 2-hydroxybenzyl alcohol (2-HBA), and to aliphatic diols (1,4-butanediol and 1,5-pentanediol), 4-HBA administered intravenously at 25 mg/kg protected mice, significantly reducing total, cortical and sub-cortical infarct volumes by 42, 28 and 55%, respectively. All compounds, 4-HBA included, were devoid of antioedematous properties. Only the stroke protective 4-HBA, but neither 3-HBA nor 2-HBA, was capable of significantly inducing PDI in intact mouse brains. Stroke protection was fully prevented by bacitracin (500 mg/kg), a known inhibitor of PDI, which, without affecting basal brain PDI levels, altered the ability of 4-HBA to induce significantly PDI in intact brains. Taken as a whole, our data indicate that stroke protection induced by 4-HBA involves PDI as a key player, making this protein a valuable target to control brain injury disorders. The fact that 4-HBA, at doses up to 200mg/kg, was devoid of neurotoxicity in the rotarod test is also a decisive element to promote the neuroprotective use of this plant compound.

Interaction of albumin with perylene-diimides with aromatic substituents

NASA Astrophysics Data System (ADS)

Farooqi, Mohammed; Penick, Mark; Burch, Jessica; Negrete, George; Brancaleon, Lorenzo

2015-03-01

Polyaromatic hydrocarbons (PAH) binding to proteins remains one of the fundamental aspects of research in biophysics. Ligand binding can regulate the function of proteins. Binding to small ligands remains a very important aspect in the study of the function of many proteins. Perylene diimide or PDI derivatives have attracted initial interest as industrial dyes and pigments. Recently, much attention has been focused on their strong π - π stacks resulting from the large PDI aromatic core. These PDI stacks have distinct optical properties, and provide informative models that mimic the light-harvesting system and initial charge separation and charge transfer in the photosynthetic system. The absorption property of PDI derivatives may be largely tuned from visible to near-infrared region by chemical modifications at the bay-positions. We are currently studying a new class of PDI derivatives with substituents made of the side chains of aromatic amino acids (Tyrosine, Tryptophan and Phenylalanine). We have looked at the fluorescence absorption and emission of these PDIs in water and other organic solvents. PDIs show evidence of dimerization and possible aggregation. We also present binding studies of these PDIs with Human Serum Albumin (HSA). The binding was studied using fluorescence emission quenching of the HSA Tryptophan residue. Stern-Volmer equation is used to derive the quenching constants. PDI binding to HSA also has an effect on the fluorescence emission of the PDIs themselves by red shifting the spectra. Funded by RCMI grant.

Demographic characteristics and health-related quality of life of patients with moderate-to-severe psoriasis: The VACAP study.

PubMed

Daudén, E; Pujol, R M; Sánchez-Carazo, J L; Toribio, J; Vanaclocha, F; Puig, L; Yébenes, M; Sabater, E; Casado, M A; Caloto, M T; Aragón, B

2013-11-01

Psoriasis is associated with a deterioration in the health-related quality of life (HRQoL) of affected patients. The aim of this study was to assess the HRQoL of patients with moderate-to-severe psoriasis. A prospective observational study (the VACAP Study) was carried out in 123 centers in Spain with 1217 patients. Patients were evaluated at baseline (visit 1 [V1]) and again four months later (visit 2 [V2]). The severity of psoriasis was determined using the following indices: (i) Psoriasis Area and Severity Index (PASI) (score range 0-72, higher score indicates more severe disease), (ii) the body surface area (BSA) affected, and (iii) the Physicians Global Assessment (PGA) (range 1-7, higher score indicates more severe disease). Four questionnaires were used for the assessment of the HRQoL: (i) the Short-Form 36 quality-of-life questionnaire (SF-36) (score range 0-100, higher score indicates better HRQoL); (ii) Euroqol (EQ-5D) (range from 1 to 3, lower score indicates better HRQoL); (iii) Dermatology Life Quality Index (DLQI) (ranges 0-30; from best to worst HRQoL); and (iv) Psoriasis Disability Index (PDI) (ranges 0-45; higher score indicates better HRQoL). The mean (SD) age of the patients was 45.11 (13.92) years at V1. The mean age at the onset of psoriasis was 26.08 (14.19) years. The majority of patients were female (61%) and were employed (68%). The mean PASI score was 13.24 (9.50) at V1 and 5.07 (6.03) at V2 (P<.001). Scores from the generic HRQoL questionnaires (EQ-5D, SF-36) showed significant improvement between visits in all dimensions measured (P<.001). The disease-specific questionnaires also revealed overall improvements in quality of life over time: the DLQI mean total score was 8.97 (7.28) at V1 and 4.76 (5.72) at V2 (P<.001), and the PDI mean total score was 9.24 (8.76) V1 and 4.88 (6.65) at V2 (P<.001). Multivariate analysis using PDI as the dependent variable showed that the principal factors related to HRQoL were severity of psoriasis as measured by PASI (P<.001), and gender (P=.048). The principal factor related to HRQoL in patients with psoriasis is the severity of the disease. Copyright © 2012 Elsevier España, S.L. and AEDV. All rights reserved.

Protein disulphide isomerase is required for signal peptide peptidase-mediated protein degradation

PubMed Central

Lee, Seong-Ok; Cho, Kwangmin; Cho, Sunglim; Kim, Ilkwon; Oh, Changhoon; Ahn, Kwangseog

2010-01-01

The human cytomegalovirus glycoprotein US2 induces dislocation of MHC class I heavy chains from the endoplasmic reticulum (ER) into the cytosol and targets them for proteasomal degradation. Signal peptide peptidase (SPP) has been shown to be integral for US2-induced dislocation of MHC class I heavy chains although its mechanism of action remains poorly understood. Here, we show that knockdown of protein disulphide isomerase (PDI) by RNA-mediated interference inhibited the degradation of MHC class I molecules catalysed by US2 but not by its functional homolog US11. Overexpression of the substrate-binding mutant of PDI, but not the catalytically inactive mutant, dominant-negatively inhibited US2-mediated dislocation of MHC class I molecules by preventing their release from US2. Furthermore, PDI associated with SPP independently of US2 and knockdown of PDI inhibited SPP-mediated degradation of CD3δ but not Derlin-1-dependent degradation of CFTR DeltaF508. Together, our data suggest that PDI is a component of the SPP-mediated ER-associated degradation machinery. PMID:19942855

Potential Role of Protein Disulfide Isomerase in Metabolic Syndrome-Derived Platelet Hyperactivity

PubMed Central

Gaspar, Renato Simões

2016-01-01

Metabolic Syndrome (MetS) has become a worldwide epidemic, alongside with a high socioeconomic cost, and its diagnostic criteria must include at least three out of the five features: visceral obesity, hypertension, dyslipidemia, insulin resistance, and high fasting glucose levels. MetS shows an increased oxidative stress associated with platelet hyperactivation, an essential component for thrombus formation and ischemic events in MetS patients. Platelet aggregation is governed by the peroxide tone and the activity of Protein Disulfide Isomerase (PDI) at the cell membrane. PDI redox active sites present active cysteine residues that can be susceptible to changes in plasma oxidative state, as observed in MetS. However, there is a lack of knowledge about the relationship between PDI and platelet hyperactivation under MetS and its metabolic features, in spite of PDI being a mediator of important pathways implicated in MetS-induced platelet hyperactivation, such as insulin resistance and nitric oxide dysfunction. Thus, the aim of this review is to analyze data available in the literature as an attempt to support a possible role for PDI in MetS-induced platelet hyperactivation. PMID:28053690

Potential Role of Protein Disulfide Isomerase in Metabolic Syndrome-Derived Platelet Hyperactivity.

PubMed

Gaspar, Renato Simões; Trostchansky, Andrés; Paes, Antonio Marcus de Andrade

2016-01-01

Metabolic Syndrome (MetS) has become a worldwide epidemic, alongside with a high socioeconomic cost, and its diagnostic criteria must include at least three out of the five features: visceral obesity, hypertension, dyslipidemia, insulin resistance, and high fasting glucose levels. MetS shows an increased oxidative stress associated with platelet hyperactivation, an essential component for thrombus formation and ischemic events in MetS patients. Platelet aggregation is governed by the peroxide tone and the activity of Protein Disulfide Isomerase (PDI) at the cell membrane. PDI redox active sites present active cysteine residues that can be susceptible to changes in plasma oxidative state, as observed in MetS. However, there is a lack of knowledge about the relationship between PDI and platelet hyperactivation under MetS and its metabolic features, in spite of PDI being a mediator of important pathways implicated in MetS-induced platelet hyperactivation, such as insulin resistance and nitric oxide dysfunction. Thus, the aim of this review is to analyze data available in the literature as an attempt to support a possible role for PDI in MetS-induced platelet hyperactivation.

Protein disulphide isomerase is required for signal peptide peptidase-mediated protein degradation.

PubMed

Lee, Seong-Ok; Cho, Kwangmin; Cho, Sunglim; Kim, Ilkwon; Oh, Changhoon; Ahn, Kwangseog

2010-01-20

The human cytomegalovirus glycoprotein US2 induces dislocation of MHC class I heavy chains from the endoplasmic reticulum (ER) into the cytosol and targets them for proteasomal degradation. Signal peptide peptidase (SPP) has been shown to be integral for US2-induced dislocation of MHC class I heavy chains although its mechanism of action remains poorly understood. Here, we show that knockdown of protein disulphide isomerase (PDI) by RNA-mediated interference inhibited the degradation of MHC class I molecules catalysed by US2 but not by its functional homolog US11. Overexpression of the substrate-binding mutant of PDI, but not the catalytically inactive mutant, dominant-negatively inhibited US2-mediated dislocation of MHC class I molecules by preventing their release from US2. Furthermore, PDI associated with SPP independently of US2 and knockdown of PDI inhibited SPP-mediated degradation of CD3delta but not Derlin-1-dependent degradation of CFTR DeltaF508. Together, our data suggest that PDI is a component of the SPP-mediated ER-associated degradation machinery.

A Developmentally Regulated Chaperone Complex for the Endoplasmic Reticulum of Male Haploid Germ Cells

PubMed Central

van Lith, Marcel; Karala, Anna-Riikka; Bown, Dave; Gatehouse, John A.; Ruddock, Lloyd W.; Saunders, Philippa T.K.

2007-01-01

Glycoprotein folding is mediated by lectin-like chaperones and protein disulfide isomerases (PDIs) in the endoplasmic reticulum. Calnexin and the PDI homologue ERp57 work together to help fold nascent polypeptides with glycans located toward the N-terminus of a protein, whereas PDI and BiP may engage proteins that lack glycans or have sugars toward the C-terminus. In this study, we show that the PDI homologue PDILT is expressed exclusively in postmeiotic male germ cells, in contrast to the ubiquitous expression of many other PDI family members in the testis. PDILT is induced during puberty and represents the first example of a PDI family member under developmental control. We find that PDILT is not active as an oxido-reductase, but interacts with the model peptide Δ-somatostatin and nonnative bovine pancreatic trypsin inhibitor in vitro, indicative of chaperone activity. In vivo, PDILT forms a tissue-specific chaperone complex with the calnexin homologue calmegin. The identification of a redox-inactive chaperone partnership defines a new system of testis-specific protein folding with implications for male fertility. PMID:17507649

Dye adsorbates BrPDI, BrGly, and BrAsp on anatase TiO2(001) for dye-sensitized solar cell applications

NASA Astrophysics Data System (ADS)

Çakır, D.; Gülseren, O.; Mete, E.; Ellialtıoǧlu, Ş.

2009-07-01

Using the first-principles plane-wave pseudopotential method within density functional theory, we systematically investigated the interaction of perylenediimide (PDI)-based dye compounds (BrPDI, BrGly, and BrAsp) with both unreconstructed (UR) and reconstructed (RC) anatase TiO2(001) surfaces. All dye molecules form strong chemical bonds with surface in the most favorable adsorption structures. In UR-BrGly, RC-BrGly, and RC-BrAsp cases, we have observed that highest occupied molecular orbital and lowest unoccupied molecular orbital levels of molecules appear within band gap and conduction-band region, respectively. Moreover, we have obtained a gap narrowing upon adsorption of BrPDI on the RC surface. Because of the reduction in effective band gap of surface-dye system and possibly achieving the visible-light activity, these results are valuable for photovoltaic and photocatalytic applications. We have also considered the effects of hydration of surface to the binding of BrPDI. It has been found that the binding energy drops significantly for the completely hydrated surfaces.

Personal dimensions of identity and empirical research in APA journals.

PubMed

Munley, Patrick H; Anderson, Mary Z; Baines, Tonita C; Borgman, Amy L; Briggs, Denise; Dolan, James P; Koyama, Miki

2002-11-01

This study reviewed 402 empirical research papers published during 1999 in 9 American Psychological Association journals from the perspective of the Personal Dimensions of Identity (PDI) model. Descriptions of participants were reviewed to determine whether researchers reported information concerning Dimensions A, B, and C of the PDI model. PDI A and B Dimensions of age, gender, education, and geographic location were reported with the highest frequency: 88.56%, 89.30%, 78.50%, and 73.88%, respectively, whereas race/ethnicity was reported with moderate frequency, 60.70%. The remaining PDI A Dimensions of language, physical disability, sexual orientation, and social class, and the remaining B Dimensions of citizenship status, employment status, income, marital status, military experience, occupation, and religion, were reported in relatively low percentages of studies.

Varying coefficient function models to explore interactions between maternal nutritional status and prenatal methylmercury toxicity in the Seychelles Child Development Nutrition Study

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

Lynch, Miranda L., E-mail: Miranda_Lynch@urmc.rochester.edu; Huang, Li-Shan; Cox, Christopher

Maternal consumption of fish during the gestational period exposes the fetus to both nutrients, especially the long-chain polyunsaturated fatty acids (LCPUFAs), believed to be beneficial for fetal brain development, as well as to the neurotoxicant methylmercury (MeHg). We recently reported that nutrients present in fish may modify MeHg neurotoxicity. Understanding the apparent interaction of MeHg exposure and nutrients present in fish is complicated by the limitations of modeling methods. In this study we fit varying coefficient function models to data from the Seychelles Child Development Nutrition Study (SCDNS) cohort to assess the association of dietary nutrients and children's development. Thismore » cohort of mother-child pairs in the Republic of Seychelles had fish consumption averaging 9 meals per week. Maternal nutritional status was assessed for five different nutritional components known to be present in fish (n-3 LCPUFA, n-6 LCPUFA, iron status, iodine status, and choline) and associated with children's neurological development. We also included prenatal MeHg exposure (measured in maternal hair). We examined two child neurodevelopmental outcomes (Bayley Scales Infant Development-II (BSID-II) Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI)), each administered at 9 and at 30 months. The varying coefficient models allow the possible interactions between each nutritional component and MeHg to be modeled as a smoothly varying function of MeHg as an effect modifier. Iron, iodine, choline, and n-6 LCPUFA had little or no observable modulation at different MeHg exposures. In contrast the n-3 LCPUFA docosahexaenoic acid (DHA) had beneficial effects on the BSID-II PDI that were reduced or absent at higher MeHg exposures. This study presents a useful modeling method that can be brought to bear on questions involving interactions between covariates, and illustrates the continuing importance of viewing fish consumption during pregnancy as a case of multiple exposures to nutrients and to MeHg. The results encourage more emphasis on a holistic view of the risks and benefits of fish consumption as it relates to infant development. - Research highlights: {yields}Varying coefficient models are tools for examining interactions in exposure settings Associations between MeHg and fish nutrients and developmental outcomes were examined. {yields} Interactions between MeHg exposure and fish-derived nutrients were modeled using VC. {yields} Models show beneficial association of DHA with outcomes were reduced as MeHg increases. {yields} VC models show other measured nutrients unmodulated by increasing MeHg exposure.« less

Poly-N-Isopropylacrylamide/acrylic Acid Copolymers for the Generation of Nanostructures at Mica Surfaces and as Hydrophobic Host Systems for the Porin MspA from Mycobacterium smegmatis.

PubMed

Gamage, Pubudu; Basel, Matthew T; Lovell, Kimberly; Pokhrel, Megh Raj; Battle, Deletria; Ito, Takashi; Pavlenok, Mikhail; Niederweis, Michael; Bossmann, Stefan H

2009-09-17

The work presented here aims at utilizing poly-N-isopropyl-acrylamide/acrylic acid copolymers to create nanostructured layers on mica surfaces by a simple spin-casting procedure. The average composition of the copolymers determined by elemental analysis correlates excellently with the feed composition indicating that the radical polymerization process is statistical. The resulting surfaces were characterized by Atomic Force Microscopy (magnetic AC-mode) at the copolymer/air interface. Postpolymerization modification of the acrylic acid functions with perfluoro-octyl-iodide decreased the tendency towards spontaneous formation of nanopores. Crosslinking of individual polymer chains permitted the generation of ultraflat layers, which hosted the mycobacterial channel protein MspA, without compromising its channel function. The comparison of copolymers of very similar chemical composition that have been prepared by living radical polymerization and classic radical polymerization indicated that differences in polydispersity played only a minor role when poly-N-isopropyl-acrylamide/acrylic acid copolymers were spincast, but a major role when copolymers featuring the strongly hydrophobic perfluoro-octyl-labels were used. The mean pore diameters were 23.8+/-4.4 nm for P[(NIPAM)(95.5)-co-(AA)(4.5)] (PDI (polydispersity index)=1.55) and 21.8+/-4.2 nm for P[(NIPAM)(95.3)-co-(AA)(4.7)] (PDI=1.25). The depth of the nanopores was approx. 4 nm. When depositing P[(NIPAM)(95)-co-(AA)(2.8)-AAC(8)F(17 2.2)] (PDI=1.29) on Mica, the resulting mean pore diameter was 35.8+/-7.1 nm, with a depth of only 2 nm.

Poly-N-Isopropylacrylamide/acrylic Acid Copolymers for the Generation of Nanostructures at Mica Surfaces and as Hydrophobic Host Systems for the Porin MspA from Mycobacterium smegmatis

PubMed Central

Gamage, Pubudu; Basel, Matthew T.; Lovell, Kimberly; Pokhrel, Megh Raj; Battle, Deletria; Ito, Takashi; Pavlenok, Mikhail; Niederweis, Michael

2009-01-01

The work presented here aims at utilizing poly-N-isopropyl-acrylamide/acrylic acid copolymers to create nanostructured layers on mica surfaces by a simple spin-casting procedure. The average composition of the copolymers determined by elemental analysis correlates excellently with the feed composition indicating that the radical polymerization process is statistical. The resulting surfaces were characterized by Atomic Force Microscopy (magnetic AC-mode) at the copolymer/air interface. Postpolymerization modification of the acrylic acid functions with perfluoro-octyl-iodide decreased the tendency towards spontaneous formation of nanopores. Crosslinking of individual polymer chains permitted the generation of ultraflat layers, which hosted the mycobacterial channel protein MspA, without compromising its channel function. The comparison of copolymers of very similar chemical composition that have been prepared by living radical polymerization and classic radical polymerization indicated that differences in polydispersity played only a minor role when poly-N-isopropyl-acrylamide/acrylic acid copolymers were spincast, but a major role when copolymers featuring the strongly hydrophobic perfluoro-octyl-labels were used. The mean pore diameters were 23.8±4.4 nm for P[(NIPAM)95.5-co-(AA)4.5] (PDI (polydispersity index)=1.55) and 21.8±4.2 nm for P[(NIPAM)95.3-co-(AA)4.7] (PDI=1.25). The depth of the nanopores was approx. 4 nm. When depositing P[(NIPAM)95-co-(AA)2.8-AAC8F17 2.2] (PDI=1.29) on Mica, the resulting mean pore diameter was 35.8±7.1 nm, with a depth of only 2 nm. PMID:20161351

Donor-acceptor cocrystal based on hexakis(alkoxy)triphenylene and perylenediimide derivatives with an ambipolar transporting property

NASA Astrophysics Data System (ADS)

Su, Yajun; Li, Yan; Liu, Jiangang; Xing, Rubo; Han, Yanchun

2015-01-01

An organic donor-acceptor cocrystal with an ambipolar transporting property was constructed based on N,N'-bis(1-ethylpropyl)-perylene-3,4,9,10-tetracarboxylic diimide (EP-PDI) and 2,3,6,7,10,11-hexakis-(hexyloxy)-triphenylene (H6TP). The cocrystal with an alternating stacking of H6TP and EP-PDI molecules was formed through both drop-casting and spin-coating processes, especially at the optimized ratios of H6TP/EP-PDI (2/1, 1/1). The formation of the cocrystal was driven by the strong π-π interaction and the weaker steric hindrance, resulting from the smaller side groups, between the donor and acceptor molecules. Field effect transistors (FETs) based on the H6TP/EP-PDI cocrystal exhibited relatively balanced hole/electron transport, with a hole mobility of 1.14 × 10-3 cm2 V-1 s-1 and an electron mobility of 1.40 × 10-3 cm2 V-1 s-1.An organic donor-acceptor cocrystal with an ambipolar transporting property was constructed based on N,N'-bis(1-ethylpropyl)-perylene-3,4,9,10-tetracarboxylic diimide (EP-PDI) and 2,3,6,7,10,11-hexakis-(hexyloxy)-triphenylene (H6TP). The cocrystal with an alternating stacking of H6TP and EP-PDI molecules was formed through both drop-casting and spin-coating processes, especially at the optimized ratios of H6TP/EP-PDI (2/1, 1/1). The formation of the cocrystal was driven by the strong π-π interaction and the weaker steric hindrance, resulting from the smaller side groups, between the donor and acceptor molecules. Field effect transistors (FETs) based on the H6TP/EP-PDI cocrystal exhibited relatively balanced hole/electron transport, with a hole mobility of 1.14 × 10-3 cm2 V-1 s-1 and an electron mobility of 1.40 × 10-3 cm2 V-1 s-1. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr05915h

Traditional living in the Amazon: Extended breastfeeding, fish consumption, mercury exposure and neurodevelopment.

PubMed

Marques, Rejane C; Abreu, Luciana; Bernardi, José V E; Dórea, José G

2016-07-01

Features of traditional living in the Amazon Basin (high fish consumption and long breastfeeding) are likely to expose children to Mercury (Hg). To study neurodevelopment in 690 children in relation to prolonged breastfeeding and mercury exposure. Three groups of breastfeeding children were formed: Group 1 (breastfed for 6 months), Group 2 (7-12 months) and Group 3 (extending up to 24 months). Neurodevelopment was assessed as age of walking, age of talking and the Bayley Scales of Infant Development-BSID. Mercury exposure was assessed from Thimerosal-containing vaccines and fish consumption from hair Hg (HHg). HHg increased in children and decreased in mothers at 24 months. Frequency of fish consumption was significantly correlated with maternal HHg at birth (Spearman's r = 0.8583; p = 0.0001); likewise, there was a significant correlation between duration of breastfeeding and children's HHg (Spearman's r = 0.15; p = 0.0018). Extended breastfeeding did not influence the Mental Development Index-MDI or Psychomotor Development Index-PDI, but maternal education and HHg (marker of fish consumption) interacted positively and significantly with both. Frequency of maternal fish consumption and education had a positive association with BSID scores; it is speculated that maternal education and nutrients in fish have an opposing effect on Hg exposure.

SU-F-T-229: A Novel Method for EPID-Based In-Vivo Exit Dose Verification for Intensity Modulated Radiotherapy

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

Wu, Z; Wang, J; Peng, J

Purpose: Electronic portal imaging device (EPID) can be used to acquire a two-dimensional exit dose distribution during treatment delivery, thus allowing the in-vivo verification of the dose delivery through a comparison of measured portal images to predicted portal dose images (PDI). The aim of this study was to present a novel method to easily and accurately predict PDI, and to establish an EPID-based in-vivo dose verification method during IMRT treatments. Methods: We developed a model to determine the predicted portal dose at the same plane of the EPID detector location. The Varian EPID (aS1000) positions at 150cm source-to-detector-distance (SDD), andmore » can be used to acquire in-vivo exit dose using Portal Dosimetry (PD) function. Our model was generated to make an equivalent water thickness represent the buildup plate of EPID. The exit dose at extend SDD plane with patient CT data in the beam can be calculated as the predicted PDI in the treatment planning system (TPS). After that, the PDI was converted to the fluence at SDD of 150cm using the inverse square law coded in MATLAB. Five head-and-neck and prostate IMRT patient plans contain 32 fields were investigated to evaluate the feasibility of this new method. The measured EPID image was compared with PDI using the gamma analysis. Results: The average results for cumulative dose comparison were 81.9% and 91.6% for 3%, 3mm and 4%, 4mm gamma criteria, respectively. Results indicate that the patient transit dosimetry predicted algorithm compares well with EPID measured PD doses for test situations. Conclusion: Our new method can be used as an easy and feasible tool for online EPID-based in-vivo dose delivery verification for IMRT treatments. It can be implemented for fast detecting those obvious treatment delivery errors for individual field and patient quality assurance.« less

Cell viability studies and operation in cellular culture medium of n-type organic field-effect transistors

NASA Astrophysics Data System (ADS)

Barra, M.; Viggiano, D.; Di Capua, R.; Di Girolamo, F.; Santoro, F.; Taglialatela, M.; Cassinese, A.

2012-02-01

The possibility of the fabrication of organic devices suitable to be applied in bio-sensing fields depends largely on the availability of organic compounds displaying robust electrical properties even in aqueous solutions and effective biocompatibility features. In this paper, we report about the good cellular biocompatibility and the electrical response stability in an ionic medium of n-type organic transistors based on the recently developed PDI-8CN2 oligomer. The biocompatibility has been tested by analyzing the adhesion and viability of two different cell lines, human epithelial HeLa cells and murine neuronal F11 cells, on PDI-8CN2 films grown by organic molecular beam deposition (OMBD) on SiO2 substrates. The effect of film thickness on cell attachment was also tested. Uncoated SiO2 substrates were used as control surfaces and sexithiophene (T6) as device testing control. Moreover, the possible toxicity of -CN groups of PDI-8CN2 was tested on HeLa cell cultures, using PDI-8 and T6 molecules as controls. Results showed that, although at high concentration these organic compounds are toxic in solution, if they are presented in form of film, cell lines can attach and grow on them. The electrical response stability of PDI-8CN2 transistors in a cellular culture medium characterized by high concentrations of ionic species has been also investigated. For this purpose, low-voltage operation devices with VGS ranging from -5 V to 5 V, able to strongly reduce the influence of Faradaic currents coming from the electrical operation in an highly ionic environment, have been fabricated on 35 nm thick SiO2 layers and electrically characterized. These results are useful to experimentally define the main critical issues to be further addressed for the fabrication of reliable bio-sensors based on organic transistors.

Endothelin-1 receptor antagonists regulate cell surface-associated protein disulfide isomerase in sickle cell disease.

PubMed

Prado, Gregory N; Romero, Jose R; Rivera, Alicia

2013-11-01

Increased endothelin-1 (ET-1) levels, disordered thiol protein status, and erythrocyte hydration status play important roles in sickle cell disease (SCD) through unresolved mechanisms. Protein disulfide isomerase (PDI) is an oxidoreductase that mediates thiol/disulfide interchange reactions. We provide evidence that PDI is present in human and mouse erythrocyte membranes and that selective blockade with monoclonal antibodies against PDI leads to reduced Gardos channel activity (1.6±0.03 to 0.56±0.02 mmol·10(13) cell(-1)·min(-1), P<0.001) and density of sickle erythrocytes (D50: 1.115±0.001 to 1.104±0.001 g/ml, P=0.012) with an IC50 of 4 ng/ml. We observed that erythrocyte associated-PDI activity was increased in the presence of ET-1 (3.1±0.2 to 5.6±0.4%, P<0.0001) through a mechanism that includes casein kinase II. Consistent with these results, in vivo treatment of BERK sickle transgenic mice with ET-1 receptor antagonists lowered circulating and erythrocyte associated-PDI activity (7.1±0.3 to 5.2±0.2%, P<0.0001) while improving hematological parameters and Gardos channel activity. Thus, our results suggest that PDI is a novel target in SCD that regulates erythrocyte volume and oxidative stress and may contribute to cellular adhesion and endothelial activation leading to vasoocclusion as observed in SCD.

Electron Acceptors Based on α-Substituted Perylene Diimide (PDI) for Organic Solar Cells

DOE PAGES

Zhao, Donglin; Wu, Qinghe; Cai, Zhengxu; ...

2016-02-20

The ortho-position functionalized perylene diimide derivatives (αPPID, αPBDT) were synthesized and used as the electron acceptors in nonfullerene organic photovoltaics. Due to the good planarity of ortho-position functionalized PDI, the αPPID and αPBDT show strong tendency to form aggregate because of their enhanced intermolecular pie-pie interaction. Moreover, they maintain the pure domains and the same packing order as in the pure film if they are blended with PBT7-TH and the SCLC measurement also shows the high electron mobility. The inverted OPVs employing αPDI-based compounds as acceptor and PBT7-TH as the donor give the highest PCE of 4.92 % for αPBDTmore » based device and 3.61 % for αPPID based device, which is 39 % and 4 % higher than that for their counterpart βPBDT and βPPID. The charge separation study shows the more efficient exciton dissociation at interfaces between PDI based compounds and PBT7-TH. In conclusion, the results suggest that compared to beta-substituted ones, alpha-substituted PDI derivatives are more promising electron acceptors for OPV.« less

Adsorption and oligomerization of 1,3-phenylene diisocyanide on Au(111)

DOE PAGES

Kestell, John; Walker, Joshua; Bai, Yun; ...

2016-04-18

The adsorption and self-assembly of 1,3-phenylene diisocyanide (1,3-PDI) are studied on Au(111) using reflection–adsorption infrared spectroscopy (RAIRS), scanning tunneling microscopy (STM), and temperature-programmed desorption (TPD) supplemented by density functional theory (DFT) calculations and the results compared with the structures formed from 1,4-PDI where it assembled to form –(Au–PDI)– oligomer chains that incorporate gold adatoms. The infrared spectra display a single isocyanide feature consistent with the isocyanide binding to gold adatoms, while DFT calculations confirm that isocyanide binding to gold adatoms is more energetically favorable than binding to the surface. STM images show that 1,3-PDI forms zigzag chains containing hairpin bendsmore » that cause the chains to double back on each other, consistent with the 120° angle between the isocyanide groups. Hexagonal structural motifs are also observed that are proposed to be due to the self-assembly of three isocyanides as well as small structures that are assigned to 1,3-PDI dimers. Furthermore, the results suggest that the formation of gold-containing oligomers from isocyanide-containing molecules is a general phenomenon.« less

UV and γ-ray resistance of poly(N-methylmaleimide-alt-isobutene) and poly(diisopropyl fumarate) as transparent polymer films

NASA Astrophysics Data System (ADS)

Imaizumi, Ryota; Furuta, Masakazu; Okamura, Haruyuki; Matsumoto, Akikazu

2017-09-01

UV and γ-ray resistance of transparent polymers obtained by radical polymerization of maleic and fumaric acid derivatives, i.e., an alternating copolymer of N-methylmaleimide and isobutene (PMI) and poly(diisopropyl fumarate) (PDiPF), was investigated. Transmittance in UV and visible regions of these polymers were examined after UV irradiation and compared with the results for poly(methyl methacrylate) (PMMA) and polycarbonate (PC) as conventional transparent polymers. The order of stability toward UV irradiation was PMMA≈PDiPF>PMI>>PC, deduced from changes in the transmittance of 380 nm light. Tensile mechanical properties, such as elastic modulus, maximum strength, and elongation values of PMI, PDiPF, and PMMA were also investigated after UV and γ-radiation. UV irradiation induced the side chain scission of PMI and PDiPF via Norrish I type reaction as well as crosslinking by combination between formed polymer radicals, leading to deterioration in their optical and mechanical properties. γ-radiation induced significant changes in molecular weight and mechanical properties of the polymers. In conclusion, PMI exhibited unchanged mechanical properties and PDiPF maintained its high transparency under various irradiation conditions.

75 FR 8080 - Proposed Collection; Comment Request; Investigating the Causes of Post Donation Information (PDI...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-23

... explore PDI donors' knowledge, attitudes, behaviors and beliefs (KABB) about the health history... regarding their knowledge, attitudes, behaviors and beliefs about the donor health history process. Even...

Dynamics and order-disorder transitions in bidisperse diblock copolymer blends

NASA Astrophysics Data System (ADS)

Wang, Yueqiang; Li, Xuan; Tang, Ping; Yang, Yuliang

2011-03-01

We employ the dynamic extension of self-consistent field theory (DSCFT) to study dynamics and order-disorder transitions (ODT) in AB diblock copolymer binary mixtures of two different monodisperse chain lengths by imitating the dynamic storage modulus G‧ corresponding to any given morphology in the oscillatory shear measurements. The different polydispersity index (PDI) is introduced by binary blending AB diblock copolymers with variations in chain lengths and chain number fractions. The simulation results show that the increase of polydispersity in the minority or symmetric block introduces a decrease in the segregation strength at the ODT, ( χN) ODT, whereas the increase of polydispersity in the majority block results in a decrease, then increase and final decrease again in ( χN) ODT. To the best of our knowledge, our DSCFT simulations, for the first time, predict an increase in ( χN) ODT with the PDI in the majority block, which produces the experimental results. The simulations by previous SCFT, which generally speaking, is capable of describing equilibrium morphologies, however, contradict the experimental data. The polydispersity acquired by properly tuning the chain lengths and number fractions of binary diblock copolymer blends should be a convenient and efficient way to control the microphase separation strength at the ODT.

Molecular Characterization and Analysis of a Novel Protein Disulfide Isomerase-Like Protein of Eimeria tenella

PubMed Central

Han, Hongyu; Dong, Hui; Zhu, Shunhai; Zhao, Qiping; Jiang, Lianlian; Wang, Yange; Li, Liujia; Wu, Youlin; Huang, Bing

2014-01-01

Protein disulfide isomerase (PDI) and PDI-like proteins are members of the thioredoxin superfamily. They contain thioredoxin-like domains and catalyze the physiological oxidation, reduction and isomerization of protein disulfide bonds, which are involved in cell function and development in prokaryotes and eukaryotes. In this study, EtPDIL, a novel PDI-like gene of Eimeria tenella, was cloned using rapid amplification of cDNA ends (RACE) according to the expressed sequence tag (EST). The EtPDIL cDNA contained 1129 nucleotides encoding 216 amino acids. The deduced EtPDIL protein belonged to thioredoxin-like superfamily and had a single predicted thioredoxin domain with a non-classical thioredoxin-like motif (SXXC). BLAST analysis showed that the EtPDIL protein was 55–59% identical to PDI-like proteins of other apicomplexan parasites. The transcript and protein levels of EtPDIL at different development stages were investigated by real-time quantitative PCR and western blot. The messenger RNA and protein levels of EtPDIL were higher in sporulated oocysts than in unsporulated oocysts, sporozoites or merozoites. Protein expression was barely detectable in unsporulated oocysts. Western blots showed that rabbit antiserum against recombinant EtPDIL recognized only a native 24 kDa protein from parasites. Immunolocalization with EtPDIL antibody showed that EtPDIL had a disperse distribution in the cytoplasm of whole sporozoites and merozoites. After sporozoites were incubated in complete medium, EtPDIL protein concentrated at the anterior of the sporozoites and appeared on the surface of parasites. Specific staining was more intense and mainly located on the parasite surface after merozoites released from mature schizonts invaded DF-1 cells. After development of parasites in DF-1 cells, staining intensified in trophozoites, immature schizonts and mature schizonts. Antibody inhibition of EtPDIL function reduced the ability of E. tenella to invade DF-1 cells. These results suggested that EtPDIL might be involved in sporulation in external environments and in host cell adhesion, invasion and development of E. tenella. PMID:24932912

Facile fabrication of organic/inorganic nanotube heterojunction arrays for enhanced photoelectrochemical water splitting

NASA Astrophysics Data System (ADS)

Chen, Yingzhi; Li, Aoxiang; Yue, Xiaoqi; Wang, Lu-Ning; Huang, Zheng-Hong; Kang, Feiyu; Volinsky, Alex A.

2016-07-01

Organic/inorganic heterojunction photoanodes are appealing for making concurrent use of the highly photoactive organic semiconductors, and the efficient dielectric screening provided by their inorganic counterparts. In the present work, organic/inorganic nanotube heterojunction arrays composed of TiO2 nanotube arrays and a semiconducting N,N-(dicyclohexyl) perylene-3,4,9,10-tetracarboxylic diimide (PDi) layer were fabricated for photoelectrochemical water splitting. In this arrayed architecture, a PDi layer with a tunable thickness was coated on anodic TiO2 nanotube arrays by physical vapor deposition, which is advantageous for the formation of a uniform layer and an adequate interface contact between PDi and TiO2. The obtained PDi/TiO2 junction exhibited broadened visible light absorption, and an effective interface for enhanced photogenerated electron-hole separation, which is supported by the reduced charge transfer resistance and prolonged excitation lifetime via impedance spectroscopy analysis and fluorescence emission decay investigations. Consequently, such a heterojunction photoanode was photoresponsive to a wide visible light region of 400-600 nm, and thus demonstrated a highly enhanced photocurrent density at 1.23 V vs. a reversible hydrogen electrode. Additionally, the durability of such a photoanode can be guaranteed after long-time illumination because of the geometrical restraint imposed by the PDi aggregates. These results pave the way to discover new organic/inorganic assemblies for high-performance photoelectric applications and device integration.Organic/inorganic heterojunction photoanodes are appealing for making concurrent use of the highly photoactive organic semiconductors, and the efficient dielectric screening provided by their inorganic counterparts. In the present work, organic/inorganic nanotube heterojunction arrays composed of TiO2 nanotube arrays and a semiconducting N,N-(dicyclohexyl) perylene-3,4,9,10-tetracarboxylic diimide (PDi) layer were fabricated for photoelectrochemical water splitting. In this arrayed architecture, a PDi layer with a tunable thickness was coated on anodic TiO2 nanotube arrays by physical vapor deposition, which is advantageous for the formation of a uniform layer and an adequate interface contact between PDi and TiO2. The obtained PDi/TiO2 junction exhibited broadened visible light absorption, and an effective interface for enhanced photogenerated electron-hole separation, which is supported by the reduced charge transfer resistance and prolonged excitation lifetime via impedance spectroscopy analysis and fluorescence emission decay investigations. Consequently, such a heterojunction photoanode was photoresponsive to a wide visible light region of 400-600 nm, and thus demonstrated a highly enhanced photocurrent density at 1.23 V vs. a reversible hydrogen electrode. Additionally, the durability of such a photoanode can be guaranteed after long-time illumination because of the geometrical restraint imposed by the PDi aggregates. These results pave the way to discover new organic/inorganic assemblies for high-performance photoelectric applications and device integration. Electronic supplementary information (ESI) available: Additional structural characterization. See DOI: 10.1039/c5nr07893h

Arabidopsis cotyledon chloroplast biogenesis factor CYO1 uses glutathione as an electron donor and interacts with PSI (A1 and A2) and PSII (CP43 and CP47) subunits.

PubMed

Muranaka, Atsuko; Watanabe, Shunsuke; Sakamoto, Atsushi; Shimada, Hiroshi

2012-08-15

CYO1 is required for thylakoid biogenesis in cotyledons of Arabidopsis thaliana. To elucidate the enzymatic characteristics of CYO1, we analyzed the protein disulfide isomerase (PDI) activity of CYO1 using dieosin glutathione disulfide (Di-E-GSSG) as a substrate. The reductase activity of CYO1 increased as a function of Di-E-GSSG, with an apparent K(m) of 824nM and K(cat) of 0.53min(-1). PDI catalyzes dithiol/disulfide interchange reactions, and the cysteine residues in PDI proteins are very important. To analyze the significance of the cysteine residues for the PDI activity of CYO1, we estimated the kinetic parameters of point-mutated CYO1 proteins. C117S, C124S, C135S, and C156S had higher values for K(m) than did wild-type CYO1. C158S had a similar K(m) but a higher K(cat), and C138S and C161S had similar K(m) values but lower K(cat) values than did wild-type CYO1. These results suggested that the cysteine residues at positions 138 and 161 were important for PDI activity. Low PDI activity of CYO1 was observed when NADPH or NADH was used as an electron donor. However, PDI activity was observed with CYO1 and glutathione, suggesting that glutathione may serve as a reducing agent for CYO1 in vivo. Based on analysis with the split-ubiquitin system, CYO1 interacted with the A1 and A2 subunits of PSI and the CP43 and CP47 subunits of PSII. Thus, CYO1 may accelerate the folding of cysteine residue--containing PSI and PSII subunits by repeatedly breaking and creating disulfide bonds. Copyright © 2012 Elsevier GmbH. All rights reserved.

Preparation of a solid self-microemulsifying drug delivery system by hot-melt extrusion.

PubMed

Silva, Luis Antonio D; Almeida, Susana L; Alonso, Ellen C P; Rocha, Priscila B R; Martins, Felipe T; Freitas, Luís A P; Taveira, Stephania F; Cunha-Filho, Marcilio S S; Marreto, Ricardo N

2018-04-25

Hot-melt extrusion (HME) has gained increasing attention in the pharmaceutical industry; however, its potential in the preparation of solid self-emulsifying drug delivery systems (S-SMEDDS) is still unexplored. This study sought to prepare enteric S-SMEDDS by HME and evaluate the effects of the process and formulation variables on S-SMEDDS properties via Box-Behnken design. Liquid SMEDDS were developed, and carvedilol was used as a class II model drug. Mean size, polydispersity index (PdI) and zeta potential of the resulting microemulsions were determined. The extrudates were then obtained by blending the lipid mixture and HPMCAS using a twin-screw hot-melt extruder. SEM, optical microscopy and PXRD were used to characterize the extrudates. In vitro microemulsion reconstitution and drug release were also studied. L-SMEDDS gave rise to microemulsions with low mean size, PdI and zeta potential (140.04 ± 7.22 nm, 0.219 ± 0.011 and -9.77 ± 0.86 mV). S-SMEDDS were successfully prepared by HME, and an HMPCAS matrix was able to avoid microemulsion reconstitution and retain drug release in pH 1.2 (12.97%-25.54%). Conversely, microemulsion reconstitution and drug release were gradual in pH 6.8 and complete for some formulations. Extrudates prepared at the lowest drug concentration and highest temperature and recirculation time promoted a complete and rapid drug release in pH 6.8 giving rise to small and uniform microemulsion droplets. Copyright © 2018 Elsevier B.V. All rights reserved.

Evaluation of critical formulation parameters in design and differentiation of self-microemulsifying drug delivery systems (SMEDDSs) for oral delivery of aciclovir.

PubMed

Janković, Jovana; Djekic, Ljiljana; Dobričić, Vladimir; Primorac, Marija

2016-01-30

The study investigated the influence of formulation parameters for design of self-microemulsifying drug delivery systems (SMEDDSs) comprising oil (medium chain triglycerides) (10%), surfactant (Labrasol(®), polysorbate 20, or Kolliphor(®) RH40), cosurfactant (Plurol(®) Oleique CC 497) (q.s. ad 100%), and cosolvent (glycerol or macrogol 400) (20% or 30%), and evaluate their potential as carriers for oral delivery of a poorly permeable antivirotic aciclovir (acyclovir). The drug loading capacity of the prepared formulations ranged from 0.18-31.66 mg/ml. Among a total of 60 formulations, three formulations meet the limits for average droplet size (Z-ave) and polydispersity index (PdI) that have been set for SMEDDSs (Z-ave≤100nm, PdI<0.250) upon spontaneous dispersion in 0.1M HCl and phosphate buffer pH 7.2. SMEDDSs with the highest aciclovir loading capacity (24.06 mg/ml and 21.12 mg/ml) provided the in vitro drug release rates of 0.325 mg cm(-2)min(-1) and 0.323 mg cm(-2)min(-1), respectively, and significantly enhanced drug permeability in the parallel artificial membrane permeability assay (PAMPA), in comparison with the pure drug substance. The results revealed that development of SMEDDSs with enhanced drug loading capacity and oral delivery potential, required optimization of hydrophilic ingredients, in terms of size of hydrophilic moiety of the surfactant, surfactant-to-cosurfactant mass ratio (Km), and log P of the cosolvent. Copyright © 2015 Elsevier B.V. All rights reserved.

Dynamic Regulation of Ero1α and Peroxiredoxin 4 Localization in the Secretory Pathway*

PubMed Central

Kakihana, Taichi; Araki, Kazutaka; Vavassori, Stefano; Iemura, Shun-ichiro; Cortini, Margherita; Fagioli, Claudio; Natsume, Tohru; Sitia, Roberto; Nagata, Kazuhiro

2013-01-01

In the early secretory compartment (ESC), a network of chaperones and enzymes assists oxidative folding of nascent proteins. Ero1 flavoproteins oxidize protein disulfide isomerase (PDI), generating H2O2 as a byproduct. Peroxiredoxin 4 (Prx4) can utilize luminal H2O2 to oxidize PDI, thus favoring oxidative folding while limiting oxidative stress. Interestingly, neither ER oxidase contains known ER retention signal(s), raising the question of how cells prevent their secretion. Here we show that the two proteins share similar intracellular localization mechanisms. Their secretion is prevented by sequential interactions with PDI and ERp44, two resident proteins of the ESC-bearing KDEL-like motifs. PDI binds preferentially Ero1α, whereas ERp44 equally retains Ero1α and Prx4. The different binding properties of Ero1α and Prx4 increase the robustness of ER redox homeostasis. PMID:23979138

The stability of N-[2-(4-o-fluorophenylpiperazin-1-yl)ethyl]-2,5-dimethyl-1 -phenylpyrrole-3,4-dicarboximide in aqueous-organic solutions.

PubMed

Zajac, Marianna; Sobczak, Agnieszka; Malinka, Wiesław; Redzicka, Aleksandra

2010-01-01

The first-order reaction of solvolysis of N-[2-(4-o-fluorophenylpiperazin-1-yl)ethyl]-2,5-dimethyl-1-phenylpyrrole-3,4-dicarboximide (PDI) was investigated as a function of pH at 333, 328, 323, 318 and 308 K in the pH range 1.11 - 12.78. The decomposition of PDI was followed by the HPLC method (Nucleosil 10-C8 column (250 x 4 mm I.D., dp = 10 microm), mobile phase: 0.018 mol/L ammonia acetate - acetonitrile (40: 60 v/v), UV detector: 240 nm, flow rate: 1 mL/min. Specific acid-base catalysis involves solvolysis of the undissociated molecules of PDI catalyzed by hydroxide ions and spontaneous solvolysis of the undissociated and monoprotonated forms of PDI under the influence of solvents. The thermodynamic parameters of the reactions--activation energy (E(a)), enthalpy (DH(#)), entropy (DS(#))--were calculated.

The effect of long chain polyunsaturated fatty acid supplementation on intelligence in low birth weight infant during lactation: A meta-analysis

PubMed Central

Song, Yuan; Liu, Ya; Pan, Yun; Yuan, Xiaofeng; Chang, Pengyu; Tian, Yuan; Cui, Weiwei

2018-01-01

Background Low birth weight infant (LBWIs) are prone to mental and behavioural problems. As an important constituent of the brain and retina, long chain polyunsaturated fatty acids are essential for foetal infant mental and visual development. The effect of lactation supplemented with long chain polyunsaturated fatty acids (LCPUFA) on the improvement of intelligence in low birth weight children requires further validation. Methods In this study, a comprehensive search of multiple databases was performed to identify studies focused the association between intelligence and long chain polyunsaturated fatty acid supplementation in LBWIs. Studies that compared the Bayley Scales of Infant Development (BSID) or the Wechsler Abbreviated Scale of Intelligence for Children (WISC) scores between LBWIs who were supplemented and controls that were not supplemented with LCPUFA during lactation were selected for inclusion in the meta-analysis. Results The main outcome was the mean difference in the mental development index (MDI) and psychomotor development index (PDI) of the BSID and the full scale intelligence quotient (FSIQ), verbal intelligence quotient (VIQ) and performance intelligence quotient (PIQ) of the WISC between LBWIs and controls. Our findings indicated that the mean BSID or WISC scores in LBWIs did not differ between the supplemented groups and controls. Conclusion This meta-analysis does not reveal that LCPUFA supplementation has a significant impact on the level of intelligence in LBWIs. PMID:29634752

Endothelin-1 receptor antagonists regulate cell surface-associated protein disulfide isomerase in sickle cell disease

PubMed Central

Prado, Gregory N.; Romero, Jose R.; Rivera, Alicia

2013-01-01

Increased endothelin-1 (ET-1) levels, disordered thiol protein status, and erythrocyte hydration status play important roles in sickle cell disease (SCD) through unresolved mechanisms. Protein disulfide isomerase (PDI) is an oxidoreductase that mediates thiol/disulfide interchange reactions. We provide evidence that PDI is present in human and mouse erythrocyte membranes and that selective blockade with monoclonal antibodies against PDI leads to reduced Gardos channel activity (1.6±0.03 to 0.56±0.02 mmol·1013 cell−1·min−1, P<0.001) and density of sickle erythrocytes (D50: 1.115±0.001 to 1.104±0.001 g/ml, P=0.012) with an IC50 of 4 ng/ml. We observed that erythrocyte associated-PDI activity was increased in the presence of ET-1 (3.1±0.2 to 5.6±0.4%, P<0.0001) through a mechanism that includes casein kinase II. Consistent with these results, in vivo treatment of BERK sickle transgenic mice with ET-1 receptor antagonists lowered circulating and erythrocyte associated-PDI activity (7.1±0.3 to 5.2±0.2%, P<0.0001) while improving hematological parameters and Gardos channel activity. Thus, our results suggest that PDI is a novel target in SCD that regulates erythrocyte volume and oxidative stress and may contribute to cellular adhesion and endothelial activation leading to vasoocclusion as observed in SCD.—Prado, G. N., Romero, J. R., Rivera, A. Endothelin-1 receptor antagonists regulate cell surface-associated protein disulfide isomerase in sickle cell disease. PMID:23913858

Curcumin uptake enhancement using low dose light illumination during incubation in Candida albicans

NASA Astrophysics Data System (ADS)

Romano, Renan A.; Pratavieira, Sebastião.; da Silva, Ana P.; Kurachi, Cristina; Bagnato, Vanderlei S.; Guimarães, Francisco E. G.

2017-07-01

A new PDI protocol is presented in this study. C. albicans cells pre-illuminated with a low dose light demonstrated an increase of curcumin uptake when compared to dark incubation, leading to a higher PDI efficacy.

A comparative analysis of aPDI effect of phenothiazinium dyes in presence of inorganic salt as potentiator

NASA Astrophysics Data System (ADS)

Ghaffari, Sahand; Kabas Sarp, Ayşe. Sena; Kemal Ruhi, Mustafa; Gülsoy, Murat

2018-02-01

Photodynamic therapy is a non-invasive therapeutic modality that has gained much attention in the last few decades. It involves administration of a photoactivatable substance, called photosensitizer (PS) into the body, and this substance, upon receiving light can generate reactive oxygen species (ROS), which could subsequently destroy nearby malignancies. The technique has been widely used for cancer treatment, but is also of significance to fight against infectious diseases. For the purpose of this study, Enterococcus faecalis, a bacterial strain common in oral cavities, gastrointestinal system, and wound infections, was selected and its antimicrobial photodynamic inactivation (aPDI) effect with the phenothiazinium dye Toluidine Blue Ortho (TBO) using a 635 nm diode laser was observed. To investigate the possibility of aPDI enhancement, potassium iodide (KI), an inorganic salt which has been proven to have antimicrobial use in dermatology, was used as a potentiating mediator, in order to give a comparative account of the aPDI effect. Laser power was set at 300 mW with irradiation times of 30, 60, and 180 s. Photosensitizer and inorganic potentiator concentration ranges were selected to be 100 μM(TBO) and 100 mM(KI) respectively. Noticeable potentiation of aPDI effect was observed, especially for 60 and 180 s irradiation groups.

Thiol-disulfide exchange between the PDI family of oxidoreductases negates the requirement for an oxidase or reductase for each enzyme

PubMed Central

Oka, Ojore B.V.; Yeoh, Hui Y.; Bulleid, Neil J.

2015-01-01

The formation of disulfides in proteins entering the secretory pathway is catalysed by the protein disulfide isomerase (PDI) family of enzymes. These enzymes catalyse the introduction, reduction and isomerization of disulfides. To function continuously they require an oxidase to reform the disulfide at their active site. To determine how each family member can be recycled to catalyse disulfide exchange, we have studied whether disulfides are transferred between individual PDI family members. We studied disulfide exchange either between purified proteins or by identifying mixed disulfide formation within cells grown in culture. We show that disulfide exchange occurs efficiently and reversibly between specific PDIs. These results have allowed us to define a hierarchy for members of the PDI family, in terms of ability to act as electron acceptors or donors during thiol-disulfide exchange reactions and indicate that there is no kinetic barrier to the exchange of disulfides between several PDI proteins. Such promiscuous disulfide exchange negates the necessity for each enzyme to be oxidized by Ero1 (ER oxidoreductin 1) or reduced by a reductive system. The lack of kinetic separation of the oxidative and reductive pathways in mammalian cells contrasts sharply with the equivalent systems for native disulfide formation within the bacterial periplasm. PMID:25989104

In vitro photoinactivation of bovine mastitis related pathogens.

PubMed

Sellera, Fábio Parra; Sabino, Caetano Padial; Ribeiro, Martha Simões; Gargano, Ronaldo Gomes; Benites, Nilson Roberti; Melville, Priscilla Anne; Pogliani, Fabio Celidonio

2016-03-01

Bovine mastitis is considered the most important disease of worldwide dairy industry. Treatment of this disease is based on the application intramammary antibiotic, which favors an increase in the number of resistant bacteria in the last decade. Photodynamic inactivation (PDI) has been investigated in different areas of Health Sciences, and has shown great potential for inactivating different pathogens, without any selection of resistant microorganisms. The objective of this study was to investigate the efficacy of PDI in the inactivation of pathogens associated with bovine mastitis. We tested the effectiveness of PDI against antibiotic resistant strains, isolated from bovine mastitis, from the following species: Staphylococcus aureus, Streptococcus agalactiae, Streptococcus dysgalactiae, Corynebacterium bovis, and the alga Prototheca zopfii. Nine experimental groups were evaluated: control, no treatment; light only, irradiation of a red light-emitting diode (λ=662 (20) nm) for 180 s; exposure to 50 μM methylene blue alone for 5 min; and PDI for 5, 10, 30, 60, 120 and 180 s. S. dysgalactiae, S. aureus, and C. bovis were inactivated after 30s of irradiation, whereas S. agalactiae was inactivated after 120 s and P. zopfii at 180 s of irradiation. These results show that PDI can be an interesting tool for inactivating pathogens for bovine mastitis. Copyright © 2015 Elsevier B.V. All rights reserved.

Transdiaphragmatic pressure in quadriplegic individuals ventilated by diaphragmatic pacemaker.

PubMed Central

Garrido-García, H.; Martín-Escribano, P.; Palomera-Frade, J.; Arroyo, O.; Alonso-Calderón, J. L.; Mazaira-Alvarez, J.

1996-01-01

BACKGROUND: Electrophrenic pacing can be used in the management of ventilatory failure in quadriplegic patients. A study was undertaken to determine the pattern of transdiaphragmatic pressure (PDI) during the conditioning phase of electrophrenic pacing to see if it had a possible role in optimising the process of conditioning. METHODS: The tidal volume (TV) and PDI were measured in a group of six quadriplegic patients commencing ventilation by low frequency pulse stimulation (7-10 Hz) and low respiratory rate stimulation (< 10 breaths/min). RESULTS: Tidal volume increased between baseline and month 1 (4.33 ml/kg, p < 0.001) and between months 1 and 2 (3.00 ml/kg, p < 0.05) and then stabilised. PDI was higher during bilateral diaphragmatic pacing (mean (SD) 1.73 (0.30) kPa) than with either left (1.15 (0.34) kPa) or right (0.86 (0.37) kPa) unilateral pacing. PDI varied throughout the observation period, probably by interaction between recovery of the diaphragmatic fibres and the pacing regimen. CONCLUSIONS: Patients with quadriplegia due to high spinal injury can be maintained with ventilation by continuous electrophrenic pacing. The control criteria used in this study for pacing were tidal volume and the patient's tolerance, and the PDI measurement did not contribute any additional information to help with managing the conditioning process. PMID:8733497

Does marital conflict predict infants' physiological regulation? A short-term prospective study.

PubMed

Porter, Christin L; Dyer, W Justin

2017-06-01

Prior research has linked marital conflict to children's internalizing/externalizing disorders, insecure attachment, and poor emotional regulation (e.g., Cummings & Davies, 2010; Cummings, Iannotti, & Zahn-Waxler, 1985). Although investigators have examined the impact of marital discord on older children (e.g., Crockenberg & Langrock, 2001), few have explored direct links in infancy (e.g., Cowan & Cowan, 1999). This study extends earlier work by examining linkages between marital functioning (conflict and harmony) and infants' cardiac vagal tone and developmental status across 2 time points using a cross-lag approach. Differential findings were found for boys and girls, with concurrent linkages between marital love and vagal tone at 6 months for boys and girls but only for boys at 12 months. In addition, marital conflict at 6 months predicted lower cardiac vagal tone in girls at 12 months but not boys. Finally, infants' developmental status at 6 months was found to predict marital conflict at 12 months. Higher scores on the Psychomotor Development Index (PDI) predicted greater marital conflict whereas higher scores on the Mental Development Index (MDI) predicted lower conflict. These findings are discussed in the context of the emotional security hypothesis and the spillover framework as well as differential susceptibilities to early developmental contexts. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Health state utilities and subjective well-being among psoriasis vulgaris patients in mainland China.

PubMed

Liu, Liu; Li, Shunping; Zhao, Yue; Zhang, Jianglin; Chen, Gang

2018-05-01

To investigate the validity of direct and indirect health state utility (HSU) and subjective well-being measures in psoriasis vulgaris patients. A convenience sampling framework was used to successively recruit patients with psoriasis vulgaris from the outpatient clinics of a tertiary hospital in Changsha, Central South China. Participants completed time trade-off (TTO), standard gamble (SG), the five-level EQ-5D (EQ-5D-5L), the WHO-5 well-being index, and the psoriasis disability index (PDI). The concurrent and known-groups validity of HSUs and well-being index in psoriasis patients were firstly studied. The agreements among HSUs and the relationship between HSU and well-being measures were further explored. A valid sample of 343 patients was analyzed. Mean HSU and well-being scores elicited from the EQ-5D-5L/TTO/SG and WHO-5 were 0.90/0.85/0.88 and 13.69, respectively. The Spearman correlation (concurrent validity) was the strongest between PDI and WHO-5 (r = 0.45), followed by with EQ-5D-5L (0.38), SG (r = 0.20), and the TTO (r = 0.18). The pairwise intraclass correlation coefficients among the three HSU measures were < 0.30. The known-groups validity was evident in all measures except for the SG. Exploratory factor analysis further suggests a complementary relationship between the EQ-5D-5L and WHO-5. There is a poor agreement between direct and indirect methods on measuring HSU with psoriasis vulgaris. Results from this study recommend that the EQ-5D-5L is the most preferred method to elicit HSU from psoriasis vulgaris patients in mainland China. It is important to further analyze the subjective well-being in addition to the HSU to fully understand the impact of psoriasis.

Human ER Oxidoreductin-1α (Ero1α) Undergoes Dual Regulation through Complementary Redox Interactions with Protein-Disulfide Isomerase.

PubMed

Kanemura, Shingo; Okumura, Masaki; Yutani, Katsuhide; Ramming, Thomas; Hikima, Takaaki; Appenzeller-Herzog, Christian; Akiyama, Shuji; Inaba, Kenji

2016-11-11

In the mammalian endoplasmic reticulum, oxidoreductin-1α (Ero1α) generates protein disulfide bonds and transfers them specifically to canonical protein-disulfide isomerase (PDI) to sustain oxidative protein folding. This oxidative process is coupled to the reduction of O 2 to H 2 O 2 on the bound flavin adenine dinucleotide cofactor. Because excessive thiol oxidation and H 2 O 2 generation cause cell death, Ero1α activity must be properly regulated. In addition to the four catalytic cysteines (Cys 94 , Cys 99 , Cys 104 , and Cys 131 ) that are located in the flexible active site region, the Cys 208 -Cys 241 pair located at the base of another flexible loop is necessary for Ero1α regulation, although the mechanistic basis is not fully understood. The present study revealed that the Cys 208 -Cys 241 disulfide was reduced by PDI and other PDI family members during PDI oxidation. Differential scanning calorimetry and small angle X-ray scattering showed that mutation of Cys 208 and Cys 241 did not grossly affect the thermal stability or overall shape of Ero1α, suggesting that redox regulation of this cysteine pair serves a functional role. Moreover, the flexible loop flanked by Cys 208 and Cys 241 provides a platform for functional interaction with PDI, which in turn enhances the oxidative activity of Ero1α through reduction of the Cys 208 -Cys 241 disulfide. We propose a mechanism of dual Ero1α regulation by dynamic redox interactions between PDI and the two Ero1α flexible loops that harbor the regulatory cysteines. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Correlation between antibodies to bisphenol A, its target enzyme protein disulfide isomerase and antibodies to neuron‐specific antigens

PubMed Central

Vojdani, Aristo

2016-01-01

Abstract Evidence continues to increase linking autoimmunity and other complex diseases to the chemicals commonly found in our environment. Bisphenol A (BPA) is a synthetic monomer used widely in many forms, from food containers to toys, medical products and many others. The potential for BPA to participate as a triggering agent for autoimmune diseases is likely due to its known immunological influences. The goal of this research was to determine if immune reactivity to BPA has any correlation with neurological antibodies. BPA binds to a target enzyme called protein disulfide isomerase (PDI). Myelin basic protein (MBP) and myelin oligodendrocyte glycoprotein (MOG) are neuronal antigens that are target sites for neuroinflammation and neuroautoimmunity. We determined the co‐occurrence of anti‐MBP and anti‐MOG antibodies with antibodies made against BPA bound to human serum albumin in 100 healthy human subjects. Correlation between BPA to PDI, BPA to MOG, BPA to MBP, PDI to MBP and PDI to MOG were all highly statistically significant (P < 0.0001). The outcome of our study suggests that immune reactivity to BPA‐human serum albumin and PDI has a high degree of statistical significance with substantial correlation with both MBP and MOG antibody levels. This suggests that BPA may be a trigger for the production of antibodies against PDI, MBP and MOG. Immune reactivity to BPA bound to human tissue proteins may be a contributing factor to neurological autoimmune disorders. Further research is needed to determine the exact relationship of these antibodies with neuroautoimmunities. Copyright © 2016 The Authors Journal of Applied Toxicology Published by John Wiley & Sons Ltd. PMID:27610592

Rejuvenating harm reduction projects for injection drug users: Ukraine's nationwide introduction of peer-driven interventions.

PubMed

Smyrnov, Pavlo; Broadhead, Robert S; Datsenko, Oleksandra; Matiyash, Oksana

2012-03-01

A peer-driven intervention (PDI) for injecting drug users (IDUs) was implemented in five Ukrainian city-sites to test-pilot its effectiveness in rejuvenating harm reduction (HR) projects that had become moribund. A PDI relies on drug users in a unique way to educate their peers in the community and recruit them for HIV prevention services. The goal of the PDI was to recruit in six month 500 IDUs who had never been respondents before to each of the five HR projects, especially stimulant- and women-injectors, and IDUs<25 years of age. We standardized the PDI's structure and operations across all five sites. All five PDIs were started in May 2007 using a carefully selected handful of "seed" IDU-recruiters who were trained to educate three peers who had never received HR services. We also accessed the database of all five projects and analysed the new respondents they recruited six-months prior to the start-up of the PDIs with the new recruits generated by the PDIs. Whilst the HR projects in the five city-sites recruited 72 new respondents on average during the six months prior to the PDIs' start-up, the PDIs recruited 455 new respondents on average in each city during their six months of operation, indicating that the PDI was 6.3 times more powerful as a recruitment mechanism. Compared to traditional outreach the PDIs resulted in significant increases in the recruitment of women- and young-injectors, and IDUs who injected a more diverse variety of drugs. The PDI can have a rejuvenating effect when added to HR projects that had become stagnate over time, resulting in an increase in the number and diversity of new IDU-respondents. Copyright © 2012 Elsevier B.V. All rights reserved.

Evaluation of gene expression SAP5, LIP9, and PLB2 of Candida albicans biofilms after photodynamic inactivation.

PubMed

Freire, Fernanda; de Barros, Patrícia Pimentel; da Silva Ávila, Damara; Brito, Graziella Nuernberg Back; Junqueira, Juliana Campos; Jorge, Antonio Olavo Cardoso

2015-07-01

With the increasing number of strains of Candida ssp. resistant to antifungal agents, the accomplishment of researches that evaluate the effects of new therapeutic methods, like photodynamic inactivation (PDI), becomes important and necessary. Thus, the objective of this study was to verify the effects of the PDI on Candida albicans biofilms, evaluating their effects on the expression of the gene hydrolytic enzymes aspartyl proteinase (SAP5), lipase (LIP9), and phospholipase (PLB2). Clinical strains of C. albicans (n = 9) isolated from patient bearers of the virus HIV and a pattern strain ATCC 18804 were used. The quantification of gene expression was related to the production of hydrolytic enzymes using the quantitative polymerase chain reaction (qPCR) assay. For PDI, we used laser-aluminum-gallium arsenide low power (red visible, 660 nm) as a light source and the methylene blue at 300 μM as a photosensitizer. We assessed two experimental groups for each strain: (a) PDI: sensitization with methylene blue and laser irradiation and (b) control: without sensitization with methylene blue and light absence. The PDI decreased gene expression in 60 % of samples for gene SAP5 and 50 % of the samples decreased expression of LIP9 and PLB2. When we compared the expression profile for of each gene between the treated and control group, a decrease in all gene expression was observed, however no statistically significant difference (Tukey's test/p = 0.12). It could be concluded that PDI (photosensitization with methylene blue followed by low-level laser irradiation) showed a slight reduction on the expression of hydrolytic enzymes of C. albicans, without statistical significance.

Are microbubbles free flowing tracers through the Myocardium? Comparison of indicator-dilution curves obtained from dye dilution and echo contrast using harmonic power Doppler imaging.

PubMed

Tiemann, K; Schlosser, T; Pohl, C; Bimmel, D; Wietasch, G; Hoeft, A; Likungu, J; Vahlhaus, C; Kuntz, S; Nanda, N C; Becher, H; Lüderitz, B

2000-01-01

Harmonic power Doppler imaging (H-PDI) has been introduced into the field of contrast echocardiography as a contrast-specific imaging modality. However, there has been considerable skepticism as to whether H-PDI would be quantifiable, because it depends on the destruction of microbubbles and has more complex signal processing than gray scale imaging. The aim of the present study was to evaluate the relationship between the concentration of microbubbles and the resulting H-PDI signals even under conditions where bubble destruction is most likely. Furthermore, we evaluated whether microbubbles of Levovist freely pass the microcirculation, which is a prerequisite for the assessment of myocardial blood flow. A strong positive correlation was found between the H-PDI signals and the amount of microbubbles up to the onset of acoustic shadowing (r = 0. 968, P<0.001). Time-intensity curves for H-PDI of air-filled microbubbles were compared with time-concentration curves of indocyanine green (ICG) in both a flow phantom and a working heart setup. The mean transit times (MTTs) through the myocardium of both agents were compared after a bolus injection into the left coronary artery. A close correlation was observed between 1/MTT and flow in both setups (r>0.98, P<0.0001). However, at high flow rates, the MTTs of the microbubbles were slightly, albeit not significantly, faster than those of indocyanine green. We conclude that microbubbles fulfill the prerequisites of free flowing tracers through the myocardium. Furthermore, H-PDI technology allows a reliable assessment of time-concentration curves of air-filled microbubbles up to the onset of acoustic shadowing.

Tropical Cyclone Activity in the North Atlantic Basin During the Weather Satellite Era, 1960-2014

NASA Technical Reports Server (NTRS)

Wilson, Robert M.

2016-01-01

This Technical Publication (TP) represents an extension of previous work concerning the tropical cyclone activity in the North Atlantic basin during the weather satellite era, 1960-2014, in particular, that of an article published in The Journal of the Alabama Academy of Science. With the launch of the TIROS-1 polar-orbiting satellite in April 1960, a new era of global weather observation and monitoring began. Prior to this, the conditions of the North Atlantic basin were determined only from ship reports, island reports, and long-range aircraft reconnaissance. Consequently, storms that formed far from land, away from shipping lanes, and beyond the reach of aircraft possibly could be missed altogether, thereby leading to an underestimate of the true number of tropical cyclones forming in the basin. Additionally, new analysis techniques have come into use which sometimes has led to the inclusion of one or more storms at the end of a nominal hurricane season that otherwise would not have been included. In this TP, examined are the yearly (or seasonal) and 10-year moving average (10-year moving average) values of the (1) first storm day (FSD), last storm day (LSD), and length of season (LOS); (2) frequencies of tropical cyclones (by class); (3) average peak 1-minute sustained wind speed () and average lowest pressure (); (4) average genesis location in terms of north latitudinal () and west longitudinal () positions; (5) sum and average power dissipation index (); (6) sum and average accumulated cyclone energy (); (7) sum and average number of storm days (); (8) sum of the number of hurricane days (NHD) and number of major hurricane days (NMHD); (9) net tropical cyclone activity index (NTCA); (10) largest individual storm (LIS) PWS, LP, PDI, ACE, NSD, NHD, NMHD; and (11) number of category 4 and 5 hurricanes (N4/5). Also examined are the December-May (D-M) and June-November (J-N) averages and 10-year moving average values of several climatic factors, including the (1) oceanic Nino index (); (2) Atlantic multi-decadal oscillation () index; (3) Atlantic meridional mode () index; (4) global land-ocean temperature index (); and (5) quasi-biennial oscillation () index. Lastly, the associational aspects (using both linear and nonparametric statistical tests) between selected tropical cyclone parameters and the climatic factors are examined based on their 10-year moving average trend values.

The Effect of Reduction Potential on the Generation of the Perylene Diimide Radical Anions

NASA Astrophysics Data System (ADS)

Zhao, Y. Z.; Li, K. X.; Ding, S. Y.; Zhu, M.; Ren, H. P.; Ma, Q.; Guo, Z.; Tian, S. P.; Zhang, H. Q.; Miao, Z. C.

2018-07-01

Perylene diimide derivatives (PDIs) with different substituents in the bay positions (Un-PDI, DFPDI and THBPDI) were chosen in this report to investigate the effect of potential on the reduction of PDIs through base (hydrazine, 1,2-ethanediamine and triethylamine)-driven keto-enol anion tautomerism. The reduction potentials (PDI/PDI•-) of these compounds determined via cyclic voltammetry are -0.51, ‒0.34, and -0.098 V for Un-PDI, DFPDI, and THBPDI, respectively. The reduction of Un-PDI, DFPDI and THBPDI by hydrazine can produce corresponding radical anions and dianions, but the volume of hydrazine added at which the radicals started to appear is different and depends on their reduction potential. The similar phenomenon was observed using 1,2-ethylenediamine and triethylamine. However, only the radical anion was obtained even in a large excess of 1,2-ethanediamine or triethylamine. Moreover, the reduction of these PDIs with different bases added in the same amount was investigated, and the correlation with their basicity was shown.

Donor-acceptor cocrystal based on hexakis(alkoxy)triphenylene and perylenediimide derivatives with an ambipolar transporting property.

PubMed

Su, Yajun; Li, Yan; Liu, Jiangang; Xing, Rubo; Han, Yanchun

2015-02-07

An organic donor-acceptor cocrystal with an ambipolar transporting property was constructed based on N,N'-bis(1-ethylpropyl)-perylene-3,4,9,10-tetracarboxylic diimide (EP-PDI) and 2,3,6,7,10,11-hexakis-(hexyloxy)-triphenylene (H6TP). The cocrystal with an alternating stacking of H6TP and EP-PDI molecules was formed through both drop-casting and spin-coating processes, especially at the optimized ratios of H6TP/EP-PDI (2/1, 1/1). The formation of the cocrystal was driven by the strong π-π interaction and the weaker steric hindrance, resulting from the smaller side groups, between the donor and acceptor molecules. Field effect transistors (FETs) based on the H6TP/EP-PDI cocrystal exhibited relatively balanced hole/electron transport, with a hole mobility of 1.14 × 10(-3) cm(2) V(-1) s(-1) and an electron mobility of 1.40 × 10(-3) cm(2) V(-1) s(-1).

Human Protein-disulfide Isomerase Is a Redox-regulated Chaperone Activated by Oxidation of Domain a′*

PubMed Central

Wang, Chao; Yu, Jiang; Huo, Lin; Wang, Lei; Feng, Wei; Wang, Chih-chen

2012-01-01

Protein-disulfide isomerase (PDI), with domains arranged as abb′xa′c, is a key enzyme and chaperone localized in the endoplasmic reticulum (ER) catalyzing oxidative folding and preventing misfolding/aggregation of proteins. It has been controversial whether the chaperone activity of PDI is redox-regulated, and the molecular basis is unclear. Here, we show that both the chaperone activity and the overall conformation of human PDI are redox-regulated. We further demonstrate that the conformational changes are triggered by the active site of domain a′, and the minimum redox-regulated cassette is located in b′xa′. The structure of the reduced bb′xa′ reveals for the first time that domain a′ packs tightly with both domain b′ and linker x to form one compact structural module. Oxidation of domain a′ releases the compact conformation and exposes the shielded hydrophobic areas to facilitate its high chaperone activity. Thus, the study unequivocally provides mechanistic insights into the redox-regulated chaperone activity of human PDI. PMID:22090031

Synergistic cooperation of PDI family members in peroxiredoxin 4-driven oxidative protein folding.

PubMed

Sato, Yoshimi; Kojima, Rieko; Okumura, Masaki; Hagiwara, Masatoshi; Masui, Shoji; Maegawa, Ken-ichi; Saiki, Masatoshi; Horibe, Tomohisa; Suzuki, Mamoru; Inaba, Kenji

2013-01-01

The mammalian endoplasmic reticulum (ER) harbors disulfide bond-generating enzymes, including Ero1α and peroxiredoxin 4 (Prx4), and nearly 20 members of the protein disulfide isomerase family (PDIs), which together constitute a suitable environment for oxidative protein folding. Here, we clarified the Prx4 preferential recognition of two PDI family proteins, P5 and ERp46, and the mode of interaction between Prx4 and P5 thioredoxin domain. Detailed analyses of oxidative folding catalyzed by the reconstituted Prx4-PDIs pathways demonstrated that, while P5 and ERp46 are dedicated to rapid, but promiscuous, disulfide introduction, PDI is an efficient proofreader of non-native disulfides. Remarkably, the Prx4-dependent formation of native disulfide bonds was accelerated when PDI was combined with ERp46 or P5, suggesting that PDIs work synergistically to increase the rate and fidelity of oxidative protein folding. Thus, the mammalian ER seems to contain highly systematized oxidative networks for the efficient production of large quantities of secretory proteins.

Combining Fullerenes and Zwitterions in non-Conjugated Polymer Interlayers to Raise Solar Cell Efficiency.

PubMed

Liu, Yao; Sheri, Madhu; Cole, Marcus D; Emrick, Todd; Russell, Thomas P

2018-06-12

Polymer zwitterions were synthesized by nucleophilic ring-opening of 3,3'-(but-2-ene-1,4-diyl)bis(1,2-oxathiolane 2,2-dioxide) (a bis-sultone) with functional perylene diimide (PDI) or fullerene monomers. Integration of these polymers into solar cell devices as cathode interlayers boosted efficiencies of fullerene-based organic photovoltaics (OPVs) from 2.75% to 10.74%, and of non-fullerene-based OPVs from 4.25% to 10.10%, demonstrating the versatility of these interlayer materials in OPVs. The fullerene-containing polymer zwitterion (C60-PZ) showed a higher interfacial dipole (∆) value and electron mobility than its PDI counterpart (PDI-PZ), affording solar cells with high efficiency. The power of PDI-PZ and C60-PZ to improve electron injection and extraction processes when positioned between metal electrodes and organic semiconductors highlights their promise to overcome energy barriers at the hard-soft materials interface of organic electronics. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Using X-ray spectroscopy of relativistic laser plasma interaction to reveal parametric decay instabilities: a modeling tool for astrophysics.

PubMed

Oks, E; Dalimier, E; Faenov, A Ya; Angelo, P; Pikuz, S A; Tubman, E; Butler, N M H; Dance, R J; Pikuz, T A; Skobelev, I Yu; Alkhimova, M A; Booth, N; Green, J; Gregory, C; Andreev, A; Zhidkov, A; Kodama, R; McKenna, P; Woolsey, N

2017-02-06

By analyzing profiles of experimental x-ray spectral lines of Si XIV and Al XIII, we found that both Langmuir and ion acoustic waves developed in plasmas produced via irradiation of thin Si foils by relativistic laser pulses (intensities ~10²¹ W/cm²). We prove that these waves are due to the parametric decay instability (PDI). This is the first time that the PDI-induced ion acoustic turbulence was discovered by the x-ray spectroscopy in laser-produced plasmas. These conclusions are also supported by PIC simulations. Our results can be used for laboratory modeling of physical processes in astrophysical objects and a better understanding of intense laser-plasma interactions.

Synthesis and electronic structure determination of N-alkyl-substituted bis(imino)pyridine iron imides exhibiting spin crossover behavior.

PubMed

Bowman, Amanda C; Milsmann, Carsten; Bill, Eckhard; Turner, Zoë R; Lobkovsky, Emil; DeBeer, Serena; Wieghardt, Karl; Chirik, Paul J

2011-11-02

Three new N-alkyl substituted bis(imino)pyridine iron imide complexes, ((iPr)PDI)FeNR ((iPr)PDI = 2,6-(2,6-(i)Pr(2)-C(6)H(3)-N═CMe)(2)C(5)H(3)N; R = 1-adamantyl ((1)Ad), cyclooctyl ((Cy)Oct), and 2-adamantyl ((2)Ad)) were synthesized by addition of the appropriate alkyl azide to the iron bis(dinitrogen) complex, ((iPr)PDI)Fe(N(2))(2). SQUID magnetic measurements on the isomeric iron imides, ((iPr)PDI)FeN(1)Ad and ((iPr)PDI)FeN(2)Ad, established spin crossover behavior with the latter example having a more complete spin transition in the experimentally accessible temperature range. X-ray diffraction on all three alkyl-substituted bis(imino)pyridine iron imides established essentially planar compounds with relatively short Fe-N(imide) bond lengths and two-electron reduction of the redox-active bis(imino)pyridine chelate. Zero- and applied-field Mössbauer spectroscopic measurements indicate diamagnetic ground states at cryogenic temperatures and established low isomer shifts consistent with highly covalent molecules. For ((iPr)PDI)FeN(2)Ad, Mössbauer spectroscopy also supports spin crossover behavior and allowed extraction of thermodynamic parameters for the S = 0 to S = 1 transition. X-ray absorption spectroscopy and computational studies were also performed to explore the electronic structure of the bis(imino)pyridine alkyl-substituted imides. An electronic structure description with a low spin ferric center (S = 1/2) antiferromagnetically coupled to an imidyl radical (S(imide) = 1/2) and a closed-shell, dianionic bis(imino)pyridine chelate (S(PDI) = 0) is favored for the S = 0 state. An iron-centered spin transition to an intermediate spin ferric ion (S(Fe) = 3/2) accounts for the S = 1 state observed at higher temperatures. Other possibilities based on the computational and experimental data are also evaluated and compared to the electronic structure of the bis(imino)pyridine iron N-aryl imide counterparts.

Note: Durability analysis of optical fiber hydrogen sensor based on Pd-Y alloy film.

PubMed

Huang, Peng-cheng; Chen, You-ping; Zhang, Gang; Song, Han; Liu, Yi

2016-02-01

The Pd-Y alloy sensing film has an excellent property for hydrogen detection, but just for one month, the sensing film's property decreases seriously. To study the failure of the sensing film, the XPS spectra analysis was used to explore the chemical content of the Pd-Y alloy film, and analysis results demonstrate that the yttrium was oxidized. The paper presented that such an oxidized process was the potential reason of the failure of the sensing film. By understanding the reason of the failure of the sensing film better, we could improve the manufacturing process to enhance the property of hydrogen sensor.

Post-discharge body weight and neurodevelopmental outcomes among very low birth weight infants in Taiwan: A nationwide cohort study.

PubMed

Hsu, Chung-Ting; Chen, Chao-Huei; Lin, Ming-Chih; Wang, Teh-Ming; Hsu, Ya-Chi

2018-01-01

Premature infants are at high risk for developmental delay and cognitive dysfunction. Besides medical conditions, growth restriction is regarded as an important risk factor for cognitive and neurodevelopmental dysfunction throughout childhood and adolescence and even into adulthood. In this study, we analyzed the relationship between post-discharge body weight and psychomotor development using a nationwide dataset. This was a nationwide cohort study conducted in Taiwan. Total of 1791 premature infants born between 2007 and 2011 with a birth weight of less than 1500 g were enrolled into this multi-center study. The data were obtained from the Taiwan Premature Infant Developmental Collaborative Study Group. The growth and neurodevelopmental evaluations were performed at corrected ages of 6, 12 and 24 months. Post-discharge failure to thrive was defined as a body weight below the 3rd percentile of the standard growth curve for Taiwanese children by the corrected age. The prevalence of failure to thrive was 15.8%, 16.9%, and 12.0% at corrected ages of 6, 12, and 24 months, respectively. At corrected ages of 24 months, 12.9% had low Mental Developmental Index (MDI) scores (MDI<70), 17.8% had low Psychomotor Developmental Index (PDI) scores (PDI<70), 12.7% had cerebral palsy, and 29.5% had neurodevelopmental impairment. Post-discharge failure to thrive was significantly associated with poor neurodevelopmental outcomes. After controlling for potential confounding factors (small for gestational age, extra-uterine growth retardation at discharge, cerebral palsy, gender, mild intraventricular hemorrhage, persistent pulmonary hypertension of newborn, respiratory distress syndrome, chronic lung disease, hemodynamic significant patent ductus arteriosus, necrotizing enterocolitis, surfactant use and indomethacin use), post-discharge failure to thrive remained a risk factor. This observational study observed the association between lower body weight at corrected age of 6, 12, and 24 months and poor neurodevelopmental outcomes among VLBW premature infants. There are many adverse factors which can influence the neurodevelopment in NICU care. More studies are needed to elucidate the causal relationship.

Post-discharge body weight and neurodevelopmental outcomes among very low birth weight infants in Taiwan: A nationwide cohort study

PubMed Central

Hsu, Chung-Ting; Chen, Chao-Huei; Wang, Teh-Ming; Hsu, Ya-Chi

2018-01-01

Background Premature infants are at high risk for developmental delay and cognitive dysfunction. Besides medical conditions, growth restriction is regarded as an important risk factor for cognitive and neurodevelopmental dysfunction throughout childhood and adolescence and even into adulthood. In this study, we analyzed the relationship between post-discharge body weight and psychomotor development using a nationwide dataset. Materials and methods This was a nationwide cohort study conducted in Taiwan. Total of 1791 premature infants born between 2007 and 2011 with a birth weight of less than 1500 g were enrolled into this multi-center study. The data were obtained from the Taiwan Premature Infant Developmental Collaborative Study Group. The growth and neurodevelopmental evaluations were performed at corrected ages of 6, 12 and 24 months. Post-discharge failure to thrive was defined as a body weight below the 3rd percentile of the standard growth curve for Taiwanese children by the corrected age. Results The prevalence of failure to thrive was 15.8%, 16.9%, and 12.0% at corrected ages of 6, 12, and 24 months, respectively. At corrected ages of 24 months, 12.9% had low Mental Developmental Index (MDI) scores (MDI<70), 17.8% had low Psychomotor Developmental Index (PDI) scores (PDI<70), 12.7% had cerebral palsy, and 29.5% had neurodevelopmental impairment. Post-discharge failure to thrive was significantly associated with poor neurodevelopmental outcomes. After controlling for potential confounding factors (small for gestational age, extra-uterine growth retardation at discharge, cerebral palsy, gender, mild intraventricular hemorrhage, persistent pulmonary hypertension of newborn, respiratory distress syndrome, chronic lung disease, hemodynamic significant patent ductus arteriosus, necrotizing enterocolitis, surfactant use and indomethacin use), post-discharge failure to thrive remained a risk factor. Conclusion This observational study observed the association between lower body weight at corrected age of 6, 12, and 24 months and poor neurodevelopmental outcomes among VLBW premature infants. There are many adverse factors which can influence the neurodevelopment in NICU care. More studies are needed to elucidate the causal relationship. PMID:29444139

Conserved Residues Lys57 and Lys401 of Protein Disulfide Isomerase Maintain an Active Site Conformation for Optimal Activity: Implications for Post-Translational Regulation

PubMed Central

Caba, Cody; Ali Khan, Hyder; Auld, Janeen; Ushioda, Ryo; Araki, Kazutaka; Nagata, Kazuhiro; Mutus, Bulent

2018-01-01

Despite its study since the 1960's, very little is known about the post-translational regulation of the multiple catalytic activities performed by protein disulfide isomerase (PDI), the primary protein folding catalyst of the cell. This work identifies a functional role for the highly conserved CxxC-flanking residues Lys57 and Lys401 of human PDI in vitro. Mutagenesis studies have revealed these residues as modulating the oxidoreductase activity of PDI in a pH-dependent manner. Non-conservative amino acid substitutions resulted in enzyme variants upwards of 7-fold less efficient. This attenuated activity was found to translate into a 2-fold reduction of the rate of electron shuttling between PDI and the intraluminal endoplasmic reticulum oxidase, ERO1α, suggesting a functional significance to oxidative protein folding. In light of this, the possibility of lysine acetylation at residues Lys57 and Lys401 was assessed by in vitro treatment using acetylsalicylic acid (aspirin). A total of 28 acetyllysine residues were identified, including acLys57 and acLys401. The kinetic behavior of the acetylated protein form nearly mimicked that obtained with a K57/401Q double substitution variant providing an indication that acetylation of the active site-flanking lysine residues can act to reversibly modulate PDI activity. PMID:29541639

Psychometric Properties of the Greek Version of the Patient Dignity Inventory in Advanced Cancer Patients.

PubMed

Parpa, Efi; Kostopoulou, Sotiria; Tsilika, Eleni; Galanos, Antonis; Katsaragakis, Stylianos; Mystakidou, Kyriaki

2017-09-01

The patient dignity inventory (PDI) is an instrument to measure dignity distressing aspects at the end of life. The aims of the present study were the translation of the PDI in Greek language as well as to measure its psychometric aspects in a palliative care unit. A back-translation method was obtained at the Greek version. One hundred twenty advanced cancer patients completed the Greek version of the PDI, the Greek hospital anxiety and depression scale, the Greek schedule of attitudes toward hastened death (SAHD-Gr), and the Greek 12-item short form health survey. Confirmatory factor analysis failed to fit to the original instrument's structure and exploratory factor analysis was conducted revealing five factors ("Psychological Distress," "Body Image and Role Identity," "Self-Esteem," "Physical Distress and Dependency," and "Social Support"). The psychometric analysis of the PDI-Gr demonstrated a good concurrent validity, and the instrument discriminated well between subgroups of patients regarding age differences. Cronbach α were between 0.71 and 0.9 showing a good internal consistency. The Greek version of the PDI showed good psychometric properties in advanced cancer patients, supported the usefulness of the instrument assessing the sense of dignity distressing aspects of the terminally ill cancer patients. Copyright © 2017 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Effects of Trx2p and Sec23p expression on stable production of hepatitis B surface antigen S domain in recombinant Saccharomyces cerevisiae.

PubMed

Park, Young-Kyoung; Jung, Sang-Min; Lim, Hyung-Kwon; Son, Young-Jin; Park, Yong-Cheol; Seo, Jin-Ho

2012-08-31

The S domain of hepatitis B virus surface antigen (sHBsAg) is the primary component for vaccine development against virus infection. For stable expression of sHBsAg in recombinant Saccharomyces cerevisiae, new accessory genes necessary for foreign protein expression were screened by DNA microarray. Among 600 genes of interest, genes coding for an activating protein of ATPase in Hsp90 (Aha1p), S. cerevisiae DnaJ (Scj1p), thioredoxin 2 (Trx2p) and a GTPase-activator specific for Sar1 (Sec23p) as well as Pdi1p were selected in transcriptome analysis, which are known to facilitate disulfide bond formation or induce protein transport in the secretion pathway. Individual and combinatorial expression of SEC23, TRX2 and PDI1 increased total sHBsAg concentration by 1.9-6.5-fold, relative to the control strain expressing sHBsAg only. Additionally, moderate expression of Kex2p protease able to cut off the signal peptide enhanced the portion of the authentic sHBsAg to total sHBsAg. Fed-batch fermentation of the S. cerevisiae 2805 strain coexpressing the sHBsAg, SEC23, PDI1 and KEX2 genes resulted in 70.6mg/L final sHBsAg concentration which was 5.6 times higher than that of the control. Transmission electron microscopic analysis of the yeast cells elucidated the effects of the accessory gene coexpression on the intracellular localization of sHBsAg. Like PDI1, coexpression of both SEC23 and/or TRX2 newly isolated in this study is expected to improve the target protein expression in S. cerevisiae. Copyright © 2012 Elsevier B.V. All rights reserved.

Measuring of temperatures of phase objects using a point-diffraction interferometer plate made with the thermocavitation process

NASA Astrophysics Data System (ADS)

Aguilar, Juan C.; Berriel-Valdos, L. R.; Aguilar, J. Felix; Mejia-Romero, S.

An optical system formed by four point-diffraction interferometers is used for measuring the refractive index distribution of a phase object. The phase of the object is assumed enough smooth to be computed in terms of the Radon Transform and it is processed with a tomographic iterative algorithm. Then, the associated refractive index distribution is calculated. To recovery the phase from the inteferograms we use the Kreis method, which is useful for interferograms having only few fringes. As an application of our technique, the temperature distribution of a candle flame is retrieved, this was made with the aid of the Gladstone-Dale equation. We also describe the process of manufacturing the point-diffraction interferometer (PDI) plates. These were made by means of the thermocavitation process. The obtained three dimensional distribution of temperature is presented.

Effect of surfactant concentration and solidification temperature on the characteristics and stability of nanostructured lipid carrier (NLC) prepared from rambutan (Nephelium lappaceum L.) kernel fat.

PubMed

Witayaudom, Pimchanok; Klinkesorn, Utai

2017-11-01

Nanostructured lipid carrier (NLC) was fabricated from rambutan (Nephelium lappaceum L.) kernel fat stabilized with Tween 80 in this present work. The influence of the Tween 80 concentration (0.025, 0.05, 0.1, 0.2, 0.5 and 1.0wt%) and solidification temperature (5 and 25°C) on the characteristics and stability of the NLC were investigated. The results showed that an increase in the Tween 80 concentration caused decreased zeta-potential (ζ-potential) and particle size (Z-average) with no significant effect on the polydispersity index (PDI). Lipid particles in the NLC at all Tween 80 concentrations had a tendency to grow and the PDI tended to increase due to Ostwald ripening upon storage over 28days. At least 0.2wt% Tween 80 concentrations could be used to stabilize 1wt% rambutan NLC. The solidification temperature affected the microstructure, melting behavior and stability of rambutan NLC. Pre-solidification at 5°C could create stable NLC with monodispersed-spherical lipid particles. Consequently, these stable NLC particles produced from rambutan kernel fat may serve as useful carriers for the delivery of bioactive lipophilic nutraceuticals. Copyright © 2017 Elsevier Inc. All rights reserved.

Preparation of nanodispersions by solvent displacement using the Venturi tube.

PubMed

García-Salazar, Gilberto; de la Luz Zambrano-Zaragoza, María; Quintanar-Guerrero, David

2018-05-02

The Venturi tube (VT) is an apparatus that produces turbulence which is taken advantage of to produce nanoparticles (NP) by solvent displacement. The objective of this study was to evaluate the potential of this device for preparing NP of poly-ε-caprolactone. Response Surface Methodology was used to determine the effect of the operating conditions and optimization. The NP produced by VT were characterized by Dynamic Light-Scattering to determine their particle size distribution (PS) and polydispersity index (PDI). Results showed that the Reynolds number (Re) has a strong effect on both PS and process yield (PY).The turbulence regime is key to the efficient formation of NP. The optimal conditions for obtaining NP were a polymer concentration of 1.6 w/v, a recirculation rate of 4.8 L/min, and a stabilizer concentration of 1.1 w/v. The predicted response of the PY was 99.7%, with a PS of 333 nm, and a PDI of 0.2. Maintaining the same preparation conditions will make it possible to obtain NP using other polymers with similar properties. Our results show that VT is a reproducible and versatile method for manufacturing NP, and so may be a feasible method for industrial-scale nanoprecipitation production. Copyright © 2018 Elsevier B.V. All rights reserved.

Thermal properties and nanodispersion behavior of synthesized β-sitosteryl acyl esters: a structure-activity relationship study.

PubMed

Panpipat, Worawan; Dong, Mingdong; Xu, Xuebing; Guo, Zheng

2013-10-01

The efficiency (dose response) of cholesterol-lowering effect of phytosterols in humans depends on their chemical forms (derived or non-derived) and formulation methods in a delivery system. With a series of synthesized β-sitosteryl fatty acid esters (C2:0-C18:0 and C18:1-C18:3), this work examined their thermal properties and applications in preparation of nanodispersion with β-sitosterol as a comparison. Inspection of the melting point (Tm) and the heat of fusion (ΔH) of β-sitosteryl fatty acid esters and the chain length and unsaturation degree of fatty acyl moiety revealed a pronounced structure-property relationship. The nanodispersions prepared with β-sitosterol and β-sitosteryl saturated fatty acid (SFA) esters displayed different particle size distribution patterns (polymodal vs bimodal), mean diameter (115 nm vs less than 100 nm), and polydispersity index (PDI) (0.50 vs 0.23-0.38). β-sitosteryl unsaturated fatty acid (USFA) esters showed a distinctly different dispersion behavior to form nanoemulsions, rather than nanodispersions, with more homogeneous particle size distribution (monomodal, mean diameter 27-63 nm and PDI 0.18-0.25). The nanodispersion of β-sitosteryl medium chain SFA ester (C14:0) demonstrated a best storage stability. Copyright © 2013 Elsevier Inc. All rights reserved.

THE EFFECT OF BODY AWARENESS THERAPY AND AEROBIC EXERCISES ON PAIN AND QUALITY OF LIFE IN THE PATIENTS WITH TENSION TYPE HEADACHE.

PubMed

Sertel, Meral; Bakar, Yeşim; Şimşek, Tülay Tarsuslu

2017-01-01

This study is to investigate the effect of Body Awareness Therapy (BAT) and Aerobic Exercises on pain and quality of life in patients with Tension-Type Headache (TTH). Sixty individuals with TTH diagnosis who referred Neurologist were incorporated into study. The individuals were randomly grouped into 3 as BAT (n=20), aerobic exercise (n=20) and control group (n=20). Pain severity of the individuals was evaluated by Visual Analog Scale (VAS) and pain diary, disability with ache; by Pain Disability Index (PDI) and Headache Impact Tests (HIT) and quality of life was evaluated by SF-36. Subsequent to first assessments, 3 sessions of 60 minutes per week throughout 6 weeks totally. When the groups were compared at the end of the study, a significant decrease was observed in VAS, PDI and HIT values in the individuals in the BAT and aerobic exercise groups. With the individuals in group BAT and aerobic exercise all parameters of quality of life were observed to be increased significantly. BAT and aerobic exercise programs to be applied on TTH patients were concluded to be important in decreasing the pain, in increasing the quality of life and in reducing pain-related daily constraints of the individuals.

Enhancement of dissolution and oral bioavailability of lacidipine via pluronic P123/F127 mixed polymeric micelles: formulation, optimization using central composite design and in vivo bioavailability study.

PubMed

Fares, Ahmed R; ElMeshad, Aliaa N; Kassem, Mohamed A A

2018-11-01

This study aims at preparing and optimizing lacidipine (LCDP) polymeric micelles using thin film hydration technique in order to overcome LCDP solubility-limited oral bioavailability. A two-factor three-level central composite face-centered design (CCFD) was employed to optimize the formulation variables to obtain LCDP polymeric micelles of high entrapment efficiency and small and uniform particle size (PS). Formulation variables were: Pluronic to drug ratio (A) and Pluronic P123 percentage (B). LCDP polymeric micelles were assessed for entrapment efficiency (EE%), PS and polydispersity index (PDI). The formula with the highest desirability (0.959) was chosen as the optimized formula. The values of the formulation variables (A and B) in the optimized polymeric micelles formula were 45% and 80%, respectively. Optimum LCDP polymeric micelles had entrapment efficiency of 99.23%, PS of 21.08 nm and PDI of 0.11. Optimum LCDP polymeric micelles formula was physically characterized using transmission electron microscopy. LCDP polymeric micelles showed saturation solubility approximately 450 times that of raw LCDP in addition to significantly enhanced dissolution rate. Bioavailability study of optimum LCDP polymeric micelles formula in rabbits revealed a 6.85-fold increase in LCDP bioavailability compared to LCDP oral suspension.

Prenatal Exposure to Dental Amalgam in the Seychelles Child Development Nutrition Study: Associations with Neurodevelopmental Outcomes at 9 and 30 Months

PubMed Central

Watson, Gene E.; Evans, Katie; Thurston, Sally W.; van Wijngaarden, Edwin; Wallace, Julie M. W.; McSorley, Emeir M.; Bonham, Maxine P.; Mulhern, Maria S.; McAfee, Alison J.; Davidson, Philip W.; Shamlaye, Conrad F.; Strain, J.J.; Love, Tanzy; Zareba, Grazyna; Myers, Gary J.

2012-01-01

Background Dental amalgam is approximately 50% metallic mercury and releases mercury vapor into the oral cavity, where it is inhaled and absorbed. Maternal amalgams expose the developing fetus to mercury vapor. Mercury vapor can be toxic, but uncertainty remains whether prenatal amalgam exposure is associated with neurodevelopmental consequences in offspring. Objective To determine if prenatal mercury vapor exposure from maternal dental amalgam is associated with adverse effects to cognition and development in children. Methods We prospectively determined dental amalgam status in a cohort of 300 pregnant women recruited in 2001 in the Republic of Seychelles to study the risks and benefits of fish consumption. The primary exposure measure was maternal amalgam surfaces present during gestation. Maternal occlusal points were a secondary measure. Outcomes were the child’s mental (MDI) and psychomotor (PDI) developmental indices of the Bayley Scales of Infant Development-II (BSID-II) administered at 9 and 30 months. Complete exposure, outcome, and covariate data were available on a subset of 242 mother-child pairs. Results The number of amalgam surfaces was not significantly (p>0.05) associated with either PDI or MDI scores. Similarly, secondary analysis with occlusal points showed no effect on the PDI or MDI scores for boys and girls combined. However, secondary analysis of the 9 month MDI was suggestive of an adverse association present only in girls. Conclusion We found no evidence of an association between our primary exposure metric, amalgam surfaces, and neurodevelopmental endpoints. Secondary analyses using occlusal points supported these findings, but suggested the possibility of an adverse association with the MDI for girls at 9 months. Given the continued widespread use of dental amalgam, we believe additional prospective studies to clarify this issue are a priority. PMID:23064204

Prenatal exposure to dental amalgam in the Seychelles Child Development Nutrition Study: associations with neurodevelopmental outcomes at 9 and 30 months.

PubMed

Watson, Gene E; Evans, Katie; Thurston, Sally W; van Wijngaarden, Edwin; Wallace, Julie M W; McSorley, Emeir M; Bonham, Maxine P; Mulhern, Maria S; McAfee, Alison J; Davidson, Philip W; Shamlaye, Conrad F; Strain, J J; Love, Tanzy; Zareba, Grazyna; Myers, Gary J

2012-12-01

Dental amalgam is approximately 50% metallic mercury and releases mercury vapor into the oral cavity, where it is inhaled and absorbed. Maternal amalgams expose the developing fetus to mercury vapor. Mercury vapor can be toxic, but uncertainty remains whether prenatal amalgam exposure is associated with neurodevelopmental consequences in offspring. To determine if prenatal mercury vapor exposure from maternal dental amalgam is associated with adverse effects to cognition and development in children. We prospectively determined dental amalgam status in a cohort of 300 pregnant women recruited in 2001 in the Republic of Seychelles to study the risks and benefits of fish consumption. The primary exposure measure was maternal amalgam surfaces present during gestation. Maternal occlusal points were a secondary measure. Outcomes were the child's mental (MDI) and psychomotor (PDI) developmental indices of the Bayley Scales of Infant Development-II (BSID-II) administered at 9 and 30 months. Complete exposure, outcome, and covariate data were available on a subset of 242 mother-child pairs. The number of amalgam surfaces was not significantly (p>0.05) associated with either PDI or MDI scores. Similarly, secondary analysis with occlusal points showed no effect on the PDI or MDI scores for boys and girls combined. However, secondary analysis of the 9-month MDI was suggestive of an adverse association present only in girls. We found no evidence of an association between our primary exposure metric, amalgam surfaces, and neurodevelopmental endpoints. Secondary analyses using occlusal points supported these findings, but suggested the possibility of an adverse association with the MDI for girls at 9 months. Given the continued widespread use of dental amalgam, we believe additional prospective studies to clarify this issue are a priority. Copyright © 2012 Elsevier Inc. All rights reserved.

Effectiveness of cervical spinal cord stimulation for the management of chronic pain.

PubMed

Deer, Timothy R; Skaribas, Ioannis M; Haider, Nameer; Salmon, John; Kim, Chong; Nelson, Christopher; Tracy, Jerry; Espinet, Anthony; Lininger, Todd E; Tiso, Robert; Archacki, Melinda A; Washburn, Stephanie N

2014-04-01

Scientific evidence supports spinal cord stimulation (SCS) as a cost-effective treatment option that, for many disease states, should be employed earlier in the treatment continuum. Reimbursement for SCS in the cervical spine has recently been challenged based on supposed lack of clinical literature. To refute this assumption, we analyzed data from an international registry to support the use of cervical SCS. The following outcomes were collected as part of an institutional review board-approved, prospective, multicenter, international registry: pain relief, Pain Disability Index (PDI) score, quality of life (QoL), and satisfaction at 3, 6, and 12 months post-implantation. Descriptive statistics are provided for all measures. Changes from baseline in PDI scores were analyzed using Tukey's pairwise comparisons. Thirty-eight patients underwent implantation of SCS leads in the cervical spine at 16 study sites in the United States and 3 international study sites. Direct patient report of percentage of pain relief was 54.2%, 60.2%, and 66.8% at 3, 6, and 12 months post-implantation, respectively. Pain relief was categorized as excellent/good by 61.6% of patients at 3 months, with similar results observed at 6 and 12 months. PDI scores were significantly reduced at all time points. At 3 months post-implantation, 92.4% of patients indicated they were very satisfied/satisfied with the SCS device. No patients indicated that they were dissatisfied. Overall QoL was reported as improved/greatly improved by 73.1% of patients at 3 months. Similar results for QoL and satisfaction were reported at 6 and 12 months. The results suggest that the use of SCS in the cervical spine is a medically effective method of pain management that satisfies and improves the QoL of most patients. The use of SCS can reduce the high cost of direct medical treatment of pain, as well as increasing the productivity of patients, and therefore should be reimbursed in appropriately selected patients. © 2013 International Neuromodulation Society.

Pulmonary decontamination for photodynamic inactivation with extracorporeal illumination

NASA Astrophysics Data System (ADS)

Geralde, Mariana C.; Leite, Ilaiáli S.; Inada, Natalia M.; Grecco, Clóvis; Medeiros, Alexandra I.; Kurachi, Cristina; Bagnato, Vanderlei S.

2014-03-01

Infectious pneumonia is a major cause of morbidity and mortality, despite advances in diagnostics and therapeutics in pulmonary infections. One of the major difficulties associated with the infection comes from the high rate of antibiotic resistant microorganisms, claiming for the use of alternative techniques with high efficiency and low cost. The photodynamic inactivation (PDI) is emerging as one of the great possibilities in this area, once its action is oxidative, not allowing microorganism develops resistance against the treatment. PDI for decontamination pulmonary has potential for treatment or creating better conditions for the action of antibiotics. In this study, we are developing a device to implement PDI for the treatment of lung diseases with extracorporeal illumination. To validate our theory, we performed measurements in liquid phantom to simulate light penetration in biological tissues at various fluency rates, the temperature was monitored in a body of hairless mice and the measurements of light transmittance in this same animal model. A diode laser emitting at 810 nm in continuous mode was used. Our results show 70% of leakage at 0.5 mm of thickness in phantom model. The mouse body temperature variation was 5.4 °C and was observed light transmittance through its chest. These results are suggesting the possible application of the extracorporeal illumination using infrared light source. Based on these findings, further studies about photodynamic inactivation will be performed in animal model using indocyanine green and bacteriochlorin as photosensitizers. The pulmonary infection will be induced with Streptococcus pneumoniae and Klebsiella pneumoniae.

A Simple Experiment to Show Photodynamic Inactivation of Bacteria on Surfaces

ERIC Educational Resources Information Center

Caminos, Daniel A.; Durantini, Edgardo N.

2007-01-01

New suitable approaches were investigated to visualize the photodynamic inactivation (PDI) of bacteria immobilized on agar surfaces. The PDI capacities of a cationic photosensitizer (5,10,15,20-tetra(4-N,N,N-trimethylammoniumphenyl)porphyrin) and an anionic photosensitizer (5,10,15,20-tetra(4-sulfonatophenyl)porphyrin) were analyzed on a typical…

75 FR 23265 - Submission for OMB Review; Comment Request; Investigating the Causes of Post Donation Information...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-03

... displays a current valid OMB control number. Proposed Collection: Title: Investigating the causes of post...; Comment Request; Investigating the Causes of Post Donation Information (PDI): Errors in the Donor... Post Donation Information (PDI). While this deferral risk may be at the next donation event, many...

Purchase decision involvement: Event management segments and related event behavior

Treesearch

Rodney B. Warnick; David C. Bojanic

2012-01-01

The goal of this research was to examine the relationships between different levels of event purchase decision involvement (PDI) segments and their respective event behaviors (e.g., expenditures, travel behavior, event consumption and satisfaction). The specific purpose was to answer two major research questions: 1) Can PDI identify different levels or segments of...

Synthesis and investigation of Pd(I) carbonyl complexes with heteroorganic ligands

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

Lamberov, A.A.; Polovnyak, V.K.; Akhmetov, N.S.

1987-09-10

Pd(I) carbonyl complexes are attracting attention because they have been shown to have catalytic properties in a series of organic syntheses. The stability and catalytic properties of these compounds are determined by the nature of the phosphine ligand and the bridge coordination of the carbonylgroup. Through the partial replacement of carbonyl and acido ligands by heteroorganic ligands in carbonyl halogenide and carbonyl acetate Pd(I) complexes, new stable Pd(I) complexes were obtained: (PdLX)/sub 2/CO, where L = PPh/sub 3/, X = OAc; L = AsPh/sub 3/, X = Cl, Br, OAc; L = SbPh/sub 3/, X = Cl Br, OAc; Lmore » = Ph/sub 2/PCH/sub 2/PPh/sub 2/, Ph/sub 2/AsCH/sub 2/AsPh/sub 2/, X = OAc. Atoms of the heteroorganic and acido ligands are equivalently coordinated to the palladium atoms. The carbonyl group in the complexes has bridge coordination to palladium atoms in the Pd(CO)Pd fragment; in complexes with bidentate heteroorganic ligands the covalent bond between palladium atoms is absent.« less

Hardness assurance for proton direct ionization-induced SEEs using a high-energy proton beam

DOE PAGES

Dodds, Nathaniel Anson; Schwank, James R.; Shaneyfelt, Marty R.; ...

2014-11-06

The low-energy proton energy spectra of all shielded space environments have the same shape. This shape is easily reproduced in the laboratory by degrading a high-energy proton beam, producing a high-fidelity test environment. We use this test environment to dramatically simplify rate prediction for proton direct ionization effects, allowing the work to be done at high-energy proton facilities, on encapsulated parts, without knowledge of the IC design, and with little or no computer simulations required. Proton direct ionization (PDI) is predicted to significantly contribute to the total error rate under the conditions investigated. Scaling effects are discussed using data frommore » 65-nm, 45-nm, and 32-nm SOI SRAMs. These data also show that grazing-angle protons will dominate the PDI-induced error rate due to their higher effective LET, so PDI hardness assurance methods must account for angular effects to be conservative. As a result, we show that this angular dependence can be exploited to quickly assess whether an IC is susceptible to PDI.« less

Perylene Diimide Based ``Nanofabric'' Thin Films for Organic Photovoltaic Cells

NASA Astrophysics Data System (ADS)

Carter, Austin; Park, June Hyoung; Min, Yong; Epstein, Arthur

2011-03-01

We report progress in using a perylene diimide (PDI) nanofabric as an effective electron accepting nanostructure for organic photovoltaics (OPV). A key challenge in OPV continues to be the recovery of electrons after charge separation due to the relatively poor mobility of C60 and related materials. A series of PDI compounds and complexes have been synthesized and used to fabricate nanofibers and thin films using solution and vacuum deposition techniques. Overlaping PDI-based nanofibers form a fast electron-transporting ``nanofabric'' that has been characterized (AFM, PL, UV-vis, etc.) and can be blended with electron donating materials. A solution-processible OPV configuration containing a nanofabric heterojunction (FHJ) of poly(3-hexylthiophene) and the PDI nanofabric was investigated. We observed a significant improvement in power-conversion efficiency due in part to expansion of the interfacial area and the presence of high mobility electron pathways to the LiF/Al electrode. This work is supported by the Wright Center for Photovoltaic Innovation and Commercialization, the Institute for Materials Research and the Center for Affordable Nanoengineering of Polymeric Biomedical Devices.

Study on the Curcumin dynamics and distribution through living biofilms

NASA Astrophysics Data System (ADS)

Carvalho, Mariana T.; Dovigo, Lívia N.; Rastelli, Alessandra N. S.; Bagnato, Vanderlei S.

2013-03-01

Human oral cavity is colonized by a wide range of microorganisms, often organized in biofilms. These biofilms are responsible for the pathogenesis of caries and most periodontal diseases. A possible alternative to reduce biofilms is the photodynamic inactivation (PDI). The success of the PDI depends on different factors. The time required by the PS to remain in contact with the target cells prior to illumination is determinant for the technique's efficacy. This study aimed to assess the interaction between the PS and the biofilm prior to the PDI. We used confocal microscopy and FLIM to evaluate the interaction between the PS and the biofilm's microorganism during the pre-irradiation time (PIT). The study of this dynamics can lead to the understanding of why only some PSs are effective and why is necessary a long PIT for some microorganisms. Our results showed that are differences for each PIT. These differences can be the determinate for the efficacy of the PDI. We observed that the microorganism needs time to concentrate and/or transport the PS within the biofilm. We presented preliminary results for biofilms of Candida albicans and Streptococcus mutans in the presence of Curcumin and compared it with the literature. We observed that the effectiveness of the PDI might be directly correlated to the position of the PS with the biofilm. Further analyses will be conducted in order to confirm the potential of FLIM to assess the PS dynamics within the biofilms.

Transdiaphragmatic pressure and neural respiratory drive measured during inspiratory muscle training in stable patients with chronic obstructive pulmonary disease.

PubMed

Wu, Weiliang; Zhang, Xianming; Lin, Lin; Ou, Yonger; Li, Xiaoying; Guan, Lili; Guo, Bingpeng; Zhou, Luqian; Chen, Rongchang

2017-01-01

Inspiratory muscle training (IMT) is a rehabilitation therapy for stable patients with COPD. However, its therapeutic effect remains undefined due to the unclear nature of diaphragmatic mobilization during IMT. Diaphragmatic mobilization, represented by transdiaphragmatic pressure (Pdi), and neural respiratory drive, expressed as the corrected root mean square (RMS) of the diaphragmatic electromyogram (EMGdi), both provide vital information to select the proper IMT device and loads in COPD, therefore contributing to the curative effect of IMT. Pdi and RMS of EMGdi (RMSdi%) were measured and compared during inspiratory resistive training and threshold load training in stable patients with COPD. Pdi and neural respiratory drive were measured continuously during inspiratory resistive training and threshold load training in 12 stable patients with COPD (forced expiratory volume in 1 s ± SD was 26.1%±10.2% predicted). Pdi was significantly higher during high-intensity threshold load training (91.46±17.24 cmH 2 O) than during inspiratory resistive training (27.24±6.13 cmH 2 O) in stable patients with COPD, with P <0.01 for each. Significant difference was also found in RMSdi% between high-intensity threshold load training and inspiratory resistive training (69.98%±16.78% vs 17.26%±14.65%, P <0.01). We concluded that threshold load training shows greater mobilization of Pdi and neural respiratory drive than inspiratory resistive training in stable patients with COPD.

Delayed diaphragm injury and diaphragm force production.

PubMed

Jiang, T X; Reid, W D; Road, J D

1998-03-01

The present study was designed to examine the effect of delayed diaphragm injury produced by inspiratory resistive loading (IRL) on diaphragm force production. On Day 1, three groups of anesthetized and intubated NZW rabbits (n = 7 in each group) were subjected to moderate IRL (Pao approximately 30 cm H2O), high IRL (Pao approximately 45 cm H2O), or no load for 1.5 h. On Day 3, the baseline twitch transdiaphragmatic pressure (Pdi) and Pdi at 10 to 80 Hz were measured during bilateral phrenic stimulation and these measurements were repeated after another IRL (high level) in all three groups. Diaphragm injury was assessed by the point-counting technique. Marked diaphragm injury was observed in the high-IRL group (p < 0.01), but no significant diaphragm injury was observed in the moderate-IRL or control groups. The baseline twitch Pdi was maintained in both IRL groups, whereas the baseline Pdi-frequency values in the high-IRL group were significantly reduced at most frequencies (p < 0.05). The decreases in twitch and Pdi at different frequencies were more pronounced after the IRL on Day 3 in the high-IRL group compared with controls. Moderate IRL did not decrease diaphragm force either before or after the high IRL on Day 3. We conclude that the diaphragm injury induced by high IRL has a significant impact on diaphragm force production and the attendant force loss produced by IRL is dependent on the intensity of inspiratory loading.

The nairovirus nairobi sheep disease virus/ganjam virus induces the translocation of protein disulphide isomerase-like oxidoreductases from the endoplasmic reticulum to the cell surface and the extracellular space.

PubMed

Lasecka, Lidia; Baron, Michael D

2014-01-01

Nairobi sheep disease virus (NSDV) of the genus Nairovirus causes a haemorrhagic gastroenteritis in sheep and goats with mortality up to 90%; the virus is found in East and Central Africa, and in India, where the virus is called Ganjam virus. NSDV is closely related to the human pathogen Crimean-Congo haemorrhagic fever virus, which also causes a haemorrhagic disease. As with other nairoviruses, replication of NSDV takes place in the cytoplasm and the new virus particles bud into the Golgi apparatus; however, the effect of viral replication on cellular compartments has not been studied extensively. We have found that the overall structure of the endoplasmic reticulum (ER), the ER-Golgi intermediate compartment and the Golgi were unaffected by infection with NSDV. However, we observed that NSDV infection led to the loss of protein disulphide isomerase (PDI), an oxidoreductase present in the lumen of the endoplasmic reticulum (ER) and which assists during protein folding, from the ER. Further investigation showed that NSDV-infected cells have high levels of PDI at their surface, and PDI is also secreted into the culture medium of infected cells. Another chaperone from the PDI family, ERp57, was found to be similarly affected. Analysis of infected cells and expression of individual viral glycoproteins indicated that the NSDV PreGn glycoprotein is involved in redistribution of these soluble ER oxidoreductases. It has been suggested that extracellular PDI can activate integrins and tissue factor, which are involved respectively in pro-inflammatory responses and disseminated intravascular coagulation, both of which manifest in many viral haemorrhagic fevers. The discovery of enhanced PDI secretion from NSDV-infected cells may be an important finding for understanding the mechanisms underlying the pathogenicity of haemorrhagic nairoviruses.

The Nairovirus Nairobi Sheep Disease Virus/Ganjam Virus Induces the Translocation of Protein Disulphide Isomerase-Like Oxidoreductases from the Endoplasmic Reticulum to the Cell Surface and the Extracellular Space

PubMed Central

Lasecka, Lidia; Baron, Michael D.

2014-01-01

Nairobi sheep disease virus (NSDV) of the genus Nairovirus causes a haemorrhagic gastroenteritis in sheep and goats with mortality up to 90%; the virus is found in East and Central Africa, and in India, where the virus is called Ganjam virus. NSDV is closely related to the human pathogen Crimean-Congo haemorrhagic fever virus, which also causes a haemorrhagic disease. As with other nairoviruses, replication of NSDV takes place in the cytoplasm and the new virus particles bud into the Golgi apparatus; however, the effect of viral replication on cellular compartments has not been studied extensively. We have found that the overall structure of the endoplasmic reticulum (ER), the ER-Golgi intermediate compartment and the Golgi were unaffected by infection with NSDV. However, we observed that NSDV infection led to the loss of protein disulphide isomerase (PDI), an oxidoreductase present in the lumen of the endoplasmic reticulum (ER) and which assists during protein folding, from the ER. Further investigation showed that NSDV-infected cells have high levels of PDI at their surface, and PDI is also secreted into the culture medium of infected cells. Another chaperone from the PDI family, ERp57, was found to be similarly affected. Analysis of infected cells and expression of individual viral glycoproteins indicated that the NSDV PreGn glycoprotein is involved in redistribution of these soluble ER oxidoreductases. It has been suggested that extracellular PDI can activate integrins and tissue factor, which are involved respectively in pro-inflammatory responses and disseminated intravascular coagulation, both of which manifest in many viral haemorrhagic fevers. The discovery of enhanced PDI secretion from NSDV-infected cells may be an important finding for understanding the mechanisms underlying the pathogenicity of haemorrhagic nairoviruses. PMID:24714576

New donor polymer with tetrafluorinated blocks for enhanced performance in perylenediimide-based solar cells

DOE PAGES

Timalsina, Amod; Hartnett, Patrick E.; Melkonyan, Ferdinand S.; ...

2017-02-09

The synthesis of a new tetrafluorinated semiconducting donor polymer, poly[(4,8-bis(5-(2-ethylhexyl)-4-fluorothiophene-2-yl)-benzo[1,2-b:4,5-b']dithiophene)-alt-(5,6-difluoro-4,7-(4-(2-ethylhexyl)-dithien-2-yl-2,1,3-benzothiadiazole)] (PBTZF4), and its photovoltaic performance in bulk heterojunction (BHJ) blends with the non-fullerene molecular acceptor [1,2:3,4]-bis-[N,N'-bis-1-pentylhexyl-perylenediimide-1,12-yl]-benzene (bPDI2P), are reported. PBTZF4:bPDI2P solar cells exhibit a high open circuit voltage (V oc) of 1.118 V, a short circuit current density (J sc) of 10.02 mA cm –2, and a fill factor (FF) of 49.5%, affording a power conversion efficiency (PCE) of 5.55%. Interestingly, a lower PCE of 3.68% is obtained with the difluorinated analogue, poly[(4,8-bis(5-(2-ethylhexyl)-thiophene-2-yl)-benzo[1,2-b:4,5-b']dithiophene)- alt-(5,6-difluoro-4,7-(4-(2-ethyl-hexyl)-dithien-2-yl-2,1,3-benzothiadiazole)] (PBTZF2). Both PBTZF4:bPDI2P and PBTZF2:bPDI2P cells benefit from complementary (donor/acceptor) light absorption and very low geminatemore » recombination, with bimolecular recombination being the dominant loss mechanism, as established by femtosecond transient absorption spectroscopy. DFT computation and physicochemical characterization data argue that the “additional” tetrafluorination planarizes the PBTZF4 backbone and enhances aggregation versusPBTZF2, affording superior charge carrier transport as assayed by field-effect mobility. In addition, fluorine-originated HOMO stabilization, –5.41 eV for PBTZF4 versus –5.33 eV for PBTZF2, and a superior blend microstructure afford a higher PBTZF4:bPDI2P solar cell PCE versusPBTZF2:bPDI2P.« less

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

Timalsina, Amod; Hartnett, Patrick E.; Melkonyan, Ferdinand S.

The synthesis of a new tetrafluorinated semiconducting donor polymer, poly[(4,8-bis(5-(2-ethylhexyl)-4-fluorothiophene-2-yl)-benzo[1,2-b:4,5-b']dithiophene)-alt-(5,6-difluoro-4,7-(4-(2-ethylhexyl)-dithien-2-yl-2,1,3-benzothiadiazole)] (PBTZF4), and its photovoltaic performance in bulk heterojunction (BHJ) blends with the non-fullerene molecular acceptor [1,2:3,4]-bis-[N,N'-bis-1-pentylhexyl-perylenediimide-1,12-yl]-benzene (bPDI2P), are reported. PBTZF4:bPDI2P solar cells exhibit a high open circuit voltage (V oc) of 1.118 V, a short circuit current density (J sc) of 10.02 mA cm –2, and a fill factor (FF) of 49.5%, affording a power conversion efficiency (PCE) of 5.55%. Interestingly, a lower PCE of 3.68% is obtained with the difluorinated analogue, poly[(4,8-bis(5-(2-ethylhexyl)-thiophene-2-yl)-benzo[1,2-b:4,5-b']dithiophene)- alt-(5,6-difluoro-4,7-(4-(2-ethyl-hexyl)-dithien-2-yl-2,1,3-benzothiadiazole)] (PBTZF2). Both PBTZF4:bPDI2P and PBTZF2:bPDI2P cells benefit from complementary (donor/acceptor) light absorption and very low geminatemore » recombination, with bimolecular recombination being the dominant loss mechanism, as established by femtosecond transient absorption spectroscopy. DFT computation and physicochemical characterization data argue that the “additional” tetrafluorination planarizes the PBTZF4 backbone and enhances aggregation versusPBTZF2, affording superior charge carrier transport as assayed by field-effect mobility. In addition, fluorine-originated HOMO stabilization, –5.41 eV for PBTZF4 versus –5.33 eV for PBTZF2, and a superior blend microstructure afford a higher PBTZF4:bPDI2P solar cell PCE versusPBTZF2:bPDI2P.« less

An allosteric disulfide bond is involved in enhanced activation of factor XI by protein disulfide isomerase.

PubMed

Zucker, M; Seligsohn, U; Yeheskel, A; Mor-Cohen, R

2016-11-01

Essentials Reduction of three disulfide bonds in factor (F) XI enhances chromogenic substrate cleavage. We measured FXI activity upon reduction and identified a bond involved in the enhanced activity. Reduction of FXI augments FIX cleavage, probably by faster conversion of FXI to FXIa. The Cys362-Cys482 disulfide bond is responsible for FXI enhanced activation upon its reduction. Background Reduction of factor (F) XI by protein disulfide isomerase (PDI) has been shown to enhance the ability of FXI to cleave its chromogenic substrate. Three disulfide bonds in FXI (Cys118-Cys147, Cys362-Cys482, and Cys321-Cys321) are involved in this augmented activation. Objectives To characterize the mechanisms by which PDI enhances FXI activity. Methods FXI activity was measured following PDI reduction. Thiols that were exposed in FXI after PDI reduction were labeled with 3-(N-maleimidopropionyl)-biocytin (MPB) and detected with avidin. The rate of conversion of FXI to activated FXI (FXIa) following thrombin activation was assessed with western blotting. FXI molecules harboring mutations that disrupt the three disulfide bonds (C147S, C321S, and C482S) were expressed in cells. The antigenicity of secreted FXI was measured with ELISA, and its activity was assessed by the use of a chromogenic substrate. The effect of disulfide bond reduction was analyzed by the use of molecular dynamics. Results Reduction of FXI by PDI enhanced cleavage of both its chromogenic substrate, S2366, and its physiologic substrate, FIX, and resulted in opening of the Cys362-Cys482 bond. The rate of conversion of FXI to FXIa was increased following its reduction by PDI. C482S-FXI showed enhanced activity as compared with both wild-type FXI and C321S-FXI. MD showed that disruption of the Cys362-Cys482 bond leads to a broader thrombin-binding site in FXI. Conclusions Reduction of FXI by PDI enhances its ability to cleave FIX, probably by causing faster conversion of FXI to FXIa. The Cys362-Cys482 disulfide bond is involved in enhancing FXI activation following its reduction, possibly by increasing thrombin accessibility to FXI. © 2016 International Society on Thrombosis and Haemostasis.

An Unsymmetric Ligand Framework for Noncoupled Homo- and Heterobimetallic Complexes.

PubMed

Haas, Ruth M; Hern, Zachary; Sproules, Stephen; Hess, Corinna R

2017-12-18

We introduce a new unsymmetric ligand, PDIpCy (PDI = pyridyldiimine; Cy = cyclam), that offers two distinct, noncoupled coordination sites. A series of homo- and heterobimetallic complexes, [Zn 2 (PDIpCy)(THF)(OTf) 4 ] (1; THF = tetrahydrofuran and OTf = triflate), [Ni 2 (PDIpCy)(THF)(OTf) 2 ](OTf) 2 (2), and [NiZn(PDIpCy)(THF)(OTf) 4 ] (3), are described. The one-electron-reduced compounds, [Zn 2 (PDIpCy)(OTF) 3 ] (4), [Ni 2 (PDIpCy)(OTf)](OTf) 2 (5), and [NiZn(PDIpCy)(OTf) 3 ] (6), were isolated, and their electronic structures were characterized. The reduced compounds are charge-separated species, with electron storage at either the PDI ligand (4) or at the PDI-bound metal ion (5 and 6).

The impact of nutritional status and longitudinal recovery of motor and cognitive milestones in internationally adopted children.

PubMed

Park, Hyun; Bothe, Denise; Holsinger, Eva; Kirchner, H Lester; Olness, Karen; Mandalakas, Anna

2011-01-01

Internationally adopted children often arrive from institutional settings where they have experienced medical, nutritional and psychosocial deprivation. This study uses a validated research assessment tool to prospectively assess the impact of baseline (immediately post adoption) nutritional status on fifty-eight children as measured by weight-for-age, height-for-age, weight-for-height and head circumference-for-age z scores, as a determinant of cognitive (MDI) and psychomotor development (PDI) scores longitudinally. A statistical model was developed to allow for different ages at time of initial assessment as well as variable intervals between follow up visits. The study results show that both acute and chronic measures of malnutrition significantly affect baseline developmental status as well as the rate of improvement in both MDI and PDI scores. This study contributes to the body of literature with its prospective nature, unique statistical model for longitudinal evaluation, and use of a validated assessment tool to assess outcomes.

Efficient in vitro photodynamic inactivation of Candida albicans by repetitive light doses

NASA Astrophysics Data System (ADS)

Torres-Hurtado, S. A.; Ramírez Ramírez, J.; Ramos-García, R.; Ramírez-San-Juan, J. C.; Spezzia-Mazzocco, T.

2018-02-01

The aim of this study was to compare the effectiveness of Rose Bengal (RB) and Methylene Blue (MB) as photosensitizers (PS) in Photodynamic Inactivation (PDI) on planktonic cultures of Candida albicans, a well-known opportunistic pathogen. RB and MB at concentrations ranging from 0.5 to 60 μM and fluences of 10, 30, 45 and 60 J/cm2 were tested. The light sources consist of an array of 12 led diodes with 30 mW of optical power each; 490-540 nm (green light) to activate RB and 600 -650 nm (red light) to activate MB. We first optimize the in vitro PDI technique using a single light dose and the optimum PS concentration. The novelty of our approach consist in reducing further the PS concentration than the optimum obtained with a single light exposure and using smaller light fluence doses by using repetitive light exposures (two to three times). MB and RB were tested for repetitive exposures at concentrations ranging from 0.1 to 10 μM, with fluences of 3 to 20 J/cm2, doses well below than those reported previously. All experiments were done in triplicate with the corresponding controls; cells without treatment, light control and dark toxicity control. RB-PDI and MB-PDI significantly reduced the number of CFU/mL when compared to the control groups. The results showed that RB was more effective than MB for C. albicans inactivation. Thus, we show that is possible to reduce significantly the amount of PS and light fluence requirements using repetitive light doses of PDI in vitro.

Analysis of the construct of dignity and content validity of the patient dignity inventory

PubMed Central

2011-01-01

Background Maintaining dignity, the quality of being worthy of esteem or respect, is considered as a goal of palliative care. The aim of this study was to analyse the construct of personal dignity and to assess the content validity of the Patient Dignity Inventory (PDI) in people with an advance directive in the Netherlands. Methods Data were collected within the framework of an advance directives cohort study. This cohort study is aiming to get a better insight into how decisions are made at the end of life with regard to advance directives in the Netherlands. One half of the cohort (n = 2404) received an open-ended question concerning factors relevant to dignity. Content labels were assigned to issues mentioned in the responses to the open-ended question. The other half of the cohort (n = 2537) received a written questionnaire including the PDI. The relevance and comprehensiveness of the PDI items were assessed with the COSMIN checklist ('COnsensus-based Standards for the selection of health status Measurement INstruments'). Results The majority of the PDI items were found to be relevant for the construct to be measured, the study population, and the purpose of the study but the items were not completely comprehensive. The responses to the open-ended question indicated that communication and care-related aspects were also important for dignity. Conclusions This study demonstrated that the PDI items were relevant for people with an advance directive in the Netherlands. The comprehensiveness of the items can be improved by including items concerning communication and care. PMID:21682924

Analysis of the construct of dignity and content validity of the patient dignity inventory.

PubMed

Albers, Gwenda; Pasman, H Roeline W; Rurup, Mette L; de Vet, Henrica C W; Onwuteaka-Philipsen, Bregje D

2011-06-19

Maintaining dignity, the quality of being worthy of esteem or respect, is considered as a goal of palliative care. The aim of this study was to analyse the construct of personal dignity and to assess the content validity of the Patient Dignity Inventory (PDI) in people with an advance directive in the Netherlands. Data were collected within the framework of an advance directives cohort study. This cohort study is aiming to get a better insight into how decisions are made at the end of life with regard to advance directives in the Netherlands. One half of the cohort (n = 2404) received an open-ended question concerning factors relevant to dignity. Content labels were assigned to issues mentioned in the responses to the open-ended question. The other half of the cohort (n = 2537) received a written questionnaire including the PDI. The relevance and comprehensiveness of the PDI items were assessed with the COSMIN checklist ('COnsensus-based Standards for the selection of health status Measurement INstruments'). The majority of the PDI items were found to be relevant for the construct to be measured, the study population, and the purpose of the study but the items were not completely comprehensive. The responses to the open-ended question indicated that communication and care-related aspects were also important for dignity. This study demonstrated that the PDI items were relevant for people with an advance directive in the Netherlands. The comprehensiveness of the items can be improved by including items concerning communication and care.

Photodynamic Inactivation of Mammalian Viruses and Bacteriophages

PubMed Central

Costa, Liliana; Faustino, Maria Amparo F.; Neves, Maria Graça P. M. S.; Cunha, Ângela; Almeida, Adelaide

2012-01-01

Photodynamic inactivation (PDI) has been used to inactivate microorganisms through the use of photosensitizers. The inactivation of mammalian viruses and bacteriophages by photosensitization has been applied with success since the first decades of the last century. Due to the fact that mammalian viruses are known to pose a threat to public health and that bacteriophages are frequently used as models of mammalian viruses, it is important to know and understand the mechanisms and photodynamic procedures involved in their photoinactivation. The aim of this review is to (i) summarize the main approaches developed until now for the photodynamic inactivation of bacteriophages and mammalian viruses and, (ii) discuss and compare the present state of the art of mammalian viruses PDI with phage photoinactivation, with special focus on the most relevant mechanisms, molecular targets and factors affecting the viral inactivation process. PMID:22852040

Different redox sensitivity of endoplasmic reticulum associated degradation clients suggests a novel role for disulphide bonds in secretory proteins.

PubMed

Medraño-Fernandez, Iria; Fagioli, Claudio; Mezghrani, Alexandre; Otsu, Mieko; Sitia, Roberto

2014-04-01

To maintain proteostasis in the endoplasmic reticulum (ER), terminally misfolded secretory proteins must be recognized, partially unfolded, and dislocated to the cytosol for proteasomal destruction, in a complex process called ER-associated degradation (ERAD). Dislocation implies reduction of inter-chain disulphide bonds. When in its reduced form, protein disulphide isomerase (PDI) can act not only as a reductase but also as an unfoldase, preparing substrates for dislocation. PDI oxidation by Ero1 favours substrate release and transport across the ER membrane. Here we addressed the redox dependency of ERAD and found that DTT stimulates the dislocation of proteins with DTT-resistant disulphide bonds (i.e., orphan Ig-μ chains) but stabilizes a ribophorin mutant (Ri332) devoid of them. DTT promotes the association of Ri332, but not of Ig-µ, with PDI. This discrepancy may suggest that disulphide bonds in cargo proteins can be utilized to oxidize PDI, hence facilitating substrate detachment and degradation also in the absence of Ero1. Accordingly, Ero1 silencing retards Ri332 degradation, but has little if any effect on Ig-µ. Thus, some disulphides can increase the stability and simultaneously favour quality control of secretory proteins.

Machine Learning and Network Analysis of Molecular Dynamics Trajectories Reveal Two Chains of Red/Ox-specific Residue Interactions in Human Protein Disulfide Isomerase.

PubMed

Karamzadeh, Razieh; Karimi-Jafari, Mohammad Hossein; Sharifi-Zarchi, Ali; Chitsaz, Hamidreza; Salekdeh, Ghasem Hosseini; Moosavi-Movahedi, Ali Akbar

2017-06-16

The human protein disulfide isomerase (hPDI), is an essential four-domain multifunctional enzyme. As a result of disulfide shuffling in its terminal domains, hPDI exists in two oxidation states with different conformational preferences which are important for substrate binding and functional activities. Here, we address the redox-dependent conformational dynamics of hPDI through molecular dynamics (MD) simulations. Collective domain motions are identified by the principal component analysis of MD trajectories and redox-dependent opening-closing structure variations are highlighted on projected free energy landscapes. Then, important structural features that exhibit considerable differences in dynamics of redox states are extracted by statistical machine learning methods. Mapping the structural variations to time series of residue interaction networks also provides a holistic representation of the dynamical redox differences. With emphasizing on persistent long-lasting interactions, an approach is proposed that compiled these time series networks to a single dynamic residue interaction network (DRIN). Differential comparison of DRIN in oxidized and reduced states reveals chains of residue interactions that represent potential allosteric paths between catalytic and ligand binding sites of hPDI.

Redox-regulated Export of the Major Histocompatibility Complex Class I-Peptide Complexes from the Endoplasmic Reticulum

PubMed Central

Lee, Sungwook; Park, Boyoun; Kang, Kwonyoon

2009-01-01

In contrast to the fairly well-characterized mechanism of assembly of MHC class I-peptide complexes, the disassembly mechanism by which peptide-loaded MHC class I molecules are released from the peptide-loading complex and exit the endoplasmic reticulum (ER) is poorly understood. Optimal peptide binding by MHC class I molecules is assumed to be sufficient for triggering exit of peptide-filled MHC class I molecules from the ER. We now show that protein disulfide isomerase (PDI) controls MHC class I disassembly by regulating dissociation of the tapasin-ERp57 disulfide conjugate. PDI acts as a peptide-dependent molecular switch; in the peptide-bound state, it binds to tapasin and ERp57 and induces dissociation of the tapasin-ERp57 conjugate. In the peptide-free state, PDI is incompetent to bind to tapasin or ERp57 and fails to dissociate the tapasin-ERp57 conjugates, resulting in ER retention of MHC class I molecules. Thus, our results indicate that even after optimal peptide loading, MHC class I disassembly does not occur by default but, rather, is a regulated process involving PDI-mediated interactions within the peptide-loading complex. PMID:19477919

Chemical and Morphological Control of Interfacial Self-Doping for Efficient Organic Electronics.

PubMed

Liu, Yao; Cole, Marcus D; Jiang, Yufeng; Kim, Paul Y; Nordlund, Dennis; Emrick, Todd; Russell, Thomas P

2018-04-01

Solution-based processing of materials for electrical doping of organic semiconductor interfaces is attractive for boosting the efficiency of organic electronic devices with multilayer structures. To simplify this process, self-doping perylene diimide (PDI)-based ionene polymers are synthesized, in which the semiconductor PDI components are embedded together with electrolyte dopants in the polymer backbone. Functionality contained within the PDI monomers suppresses their aggregation, affording self-doping interlayers with controllable thickness when processed from solution into organic photovoltaic devices (OPVs). Optimal results for interfacial self-doping lead to increased power conversion efficiencies (PCEs) of the fullerene-based OPVs, from 2.62% to 10.64%, and of the nonfullerene-based OPVs, from 3.34% to 10.59%. These PDI-ionene interlayers enable chemical and morphological control of interfacial doping and conductivity, demonstrating that the conductive channels are crucial for charge transport in doped organic semiconductor films. Using these novel interlayers with efficient doping and high conductivity, both fullerene- and nonfullerene-based OPVs are achieved with PCEs exceeding 9% over interlayer thicknesses ranging from ≈3 to 40 nm. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Charge Separation Mechanisms in Ordered Films of Self-Assembled Donor–Acceptor Dyad Ribbons

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

Logsdon, Jenna L.; Hartnett, Patrick E.; Nelson, Jordan N.

2017-04-21

Orthogonal attachment of polar and nonpolar side-chains to a zinc porphyrin-perylenediimide dyad (ZnP-PDI, 1a) is shown to result in self-assembly of ordered supramolecular ribbons in which the ZnP and PDI molecules form segregated π-stacked columns. Following photoexcitation of the ordered ribbons, ZnP+•-PDI–• radical ion pairs form in <200 fs and subsequently produce a 30 ± 3% yield of free charge carriers that live for about 100 μs. Elongating the side chains on ZnP and PDI in 1b enhances the order of the films, but does not result in an increase in free charge carrier yield. In addition, this yield ismore » independent of temperature, free energy of reaction, and the ZnP-PDI distance in the covalent dyad. These results suggest that the free charge carrier yield in this system is not limited by a bound charge transfer (CT) state or promoted by a vibronically hot CT state. Instead, it is likely that π-stacking of the segregated donors and acceptors within the ribbons results in delocalization of the charges following photoexcitation, allowing them to overcome Coulombic attraction and generate free charge carriers.« less

A helical perylene diimide-based acceptor for non-fullerene organic solar cells: synthesis, morphology and exciton dynamics

NASA Astrophysics Data System (ADS)

Chen, Li; Wu, Mingliang; Shao, Guangwei; Hu, Jiahua; He, Guiying; Bu, Tongle; Yi, Jian-Peng; Xia, Jianlong

2018-05-01

Helical perylene diimide-based (hPDI) acceptors have been established as one of the most promising candidates for non-fullerene organic solar cells (OSCs). In this work, we report a novel hPDI-based molecule, hPDI2-CN2, as an electron acceptor for OSCs. Combining the hPDI2-CN2 with a low-bandgap polymeric donor (PTB7-Th), the blending film morphology exhibited high sensitivity to various treatments (such as thermal annealing and addition of solvent additives), as evidenced by atomic force microscope studies. The power conversion efficiency (PCE) was improved from 1.42% (as-cast device) to 2.76% after thermal annealing, and a PCE of 3.25% was achieved by further addition of 1,8-diiodooctane (DIO). Femtosecond transient absorption (TA) spectroscopy studies revealed that the improved thin-film morphology was highly beneficial for the charge carrier transport and collection. And a combination of fast exciton diffusion rate and the lowest recombination rate contributed to the best performance of the DIO-treated device. This result further suggests that the molecular conformation needs to be taken into account in the design of perylene diimide-based acceptors for OSCs.

Multifunctional nanoparticulate polyelectrolyte complexes.

PubMed

Hartig, Sean M; Greene, Rachel R; DasGupta, Jayasri; Carlesso, Gianluca; Dikov, Mikhail M; Prokop, Ales; Davidson, Jeffrey M

2007-12-01

Water-soluble, biodegradable, polymeric, polyelectrolyte complex dispersions (PECs) have evolved because of the limitations, in terms of toxicity, of the currently available systems. These aqueous nanoparticulate architectures offer a significant advantage for products that may be used as drug delivery systems in humans. PECs are created by mixing oppositely charged polyions. Their hydrodynamic diameter, surface charge, and polydispersity are highly dependent on concentration, ionic strength, pH, and molecular parameters of the polymers that are used. In particular, the complexation between polyelectrolytes with significantly different molecular weights leads to the formation of water-insoluble aggregates. Several PEC characteristics are favorable for cellular uptake and colloidal stability, including hydrodynamic diameter less than 200 nm, surface charge of >30 mV or <-30 mV, spherical morphology, and polydispersity index (PDI) indicative of a homogeneous distribution. Maintenance of these properties is critical for a successful delivery vehicle. This review focuses on the development and potential applications of PECs as multi-functional, site-specific nanoparticulate drug/gene delivery and imaging devices.

A Simple Approach to Prepare Carboxycellulose Nanofibers from Untreated Biomass.

PubMed

Sharma, Priyanka R; Joshi, Ritika; Sharma, Sunil K; Hsiao, Benjamin S

2017-08-14

A simple approach was developed to prepare carboxycellulose nanofibers directly from untreated biomass using nitric acid or nitric acid-sodium nitrite mixtures. Experiments indicated that this approach greatly reduced the need for multichemicals, and offered significant benefits in lowering the consumption of water and electric energy, when compared with conventional multiple-step processes at bench scale (e.g., TEMPO oxidation). Additionally, the effluent produced by this approach could be efficaciously neutralized using base to produce nitrogen-rich salts as fertilizers. TEM measurements of resulting nanofibers from different biomasses, possessed dimensions in the range of 190-370 and 4-5 nm, having PDI = 0.29-0.38. These nanofibers exhibited lower crystallinity than untreated jute fibers as determined by TEM diffraction, WAXD and 13 C CPMAS NMR (e.g., WAXD crystallinity index was ∼35% for nanofibers vs 62% for jute). Nanofibers with low crystallinity were found to be effective for removal of heavy metal ions for drinking water purification.

Ciprofloxacin hydrochloride-loaded glyceryl monostearate nanoparticle: factorial design of Lutrol F68 and Phospholipon 90G.

PubMed

Shah, Malay; Agrawal, Yadvendra

2012-01-01

This investigation was undertaken to develop glyceryl monostearate (Geleol)-based solid lipid nanoparticles (SLNs) of a hydrophilic drug ciprofloxacin HCl. Hansen's solubility parameter study was carried out in screening of a suitable carrier and solvent system. Subsequently, SLNs were prepared by solvent diffusion evaporation method and investigated for particle size, polydispersity index (PDI), zeta potential (ZP), entrapment efficiency (EE) and drug release behaviour. Variations in SLN composition resulted in particle sizes between 170 and 810 nm and ZPs between 8 and 14 mV. The maximum EE was found to be 26.3% with particle size of 188.8 nm. SLN can sustain the release of drug for up to 15 h and it shows Higuchi matrix model as the best-fitted model. SLNs were stable without aggregation of particles under storage conditions. The results of this study provide the framework for further study involving the SLN formulation for hydrophilic drug molecule.

General Characteristics and Cytotoxic Effects of Nano-Poly (Butyl Cyanoacrylate) Containing Carboplatin on Ovarian Cancer Cells

PubMed Central

Kanaani, Leila; Far, Meysam Ebrahimi; Kazemi, S Maryam; Choupani, Edris; Tabrizi, Maral Mazloumi; Shahmabadi, Hasan Ebrahimi; Khiyavi, Azim Akbarzadeh

2017-01-01

The initial response to treatment and subsequent development of resistance to carboplatin are very important challenges. Use of nano drug delivery is a new method to replace standard chemotherapy. In this research, both non-PEGylated and PEGylated nanoparticles (NPs) were prepared by mini-emulsion polymerization of poly (butyl cyanoacrylate) (PBCA) NPs. Characteristics such as size, polydispersity index (PDI), zeta potential, drug release, and stability were examined. In addition, infrared spectroscopy was used for description of the produced NPs. Then, cytotoxicity effects of both formulations were studied on the A2780CIS ovarian cancer cell line with incubation for 24, 48, and 72h. Examination of characteristics of loaded carboplatin on the PBCA NPs under suitable laboratory conditions showed a positive effect of PEG on their properties. Cytotoxicity studies demonstrated greater toxicity with both formulations of nano-drugs than the free drug. The results indicated that PBCA NPs can be considered as suitable candidates for nano-drugs in chemotherapy. PMID:28240014

Peripheral Blood Leukocytes Interleukin-1 Beta (IL-1β) Cytokine Hyper-Reactivity in Chronic Periodontitis.

PubMed

Sakalauskiene, Jurgina; Giedrimiene, Dalia; Gleiznys, Darius; Gleiznys, Alvydas; Gleizniene, Rymante; Vitkauskiene, Astra

2016-11-12

BACKGROUND Levels of pro-inflammatory cytokine (IL-1β) released by peripheral blood leukocyte medium (PBLM), isolated from chronic periodontitis patients (P) before therapy and matched to controls, were determined in the presence or absence of non-opsonized Escherichia coli and Staphylococcus aureus. MATERIAL AND METHODS In this investigation, 26 patients with untreated, severe, generalized, chronic periodontitis and 26 healthy subjects (H) were enrolled. Periodontal status was assessed by measuring bleeding on probing (BOP), clinical attachment loss (CAL), probing pocket depth (PPD), and Ramfjord index (PDI). The levels of IL-1β (µg/ml) were assayed by a standard Immunoenzymetric Assay Diasource IL-1β ELISA kit in PBLM. RESULTS Our study showed that the values of IL-1β levels in PBLM of the P group (stimulated with non-opsonized E. coli and S. aureus) were significantly higher than in the analogous medium of H group subjects (P<0.001). All correlations between the cytokine levels of IL-1β in the samples of PBLM (stimulated with non-opsonized E. coli and S. aureus) and clinical parameters such as BOP, PPD, CAL, and PDI were significantly higher in the group of patients with periodontitis. CONCLUSIONS Levels of IL-1β secreted by leukocytes may help measure severe, generalized, chronic periodontitis, and can be predictive of future detrimental clinical sequelae associated with chronic periodontitis.

Different Sources of Dignity-Related Distress in Women Receiving Chemotherapy for Breast Cancer

PubMed Central

Shahhoseini, Somaye; Borhani, Fariba; Shoorideh, Foroozan Atashzadeh; Kavousi, Amir; Bagheri, Hossein; Almasi-Hashiani, Amir

2017-01-01

Background: Identification of different sources of dignity-related distress experienced by people nearing the end of life may help nurses to provide better care services. This study was conducted to determine sources of dignity-related distress from the perspective of women with breast cancer undergoing chemotherapy. Materials and Methods: In this cross sectional study, the participants comprised 207 women with breast cancer undergoing chemotherapy in chemotherapy clinics in hospitals of Tehran, Iran. The Cronbach’s coefficient alpha for the PDI was 0.76. Validity of PDI by confirmatory factor analysis shows that the comparative Fit Index of this instrument is 0.96 and so it is appropriate for application in different setting. Data were analyzed by Stata version 13. Results: Patients were mostly concerned about the distress caused by disease symptoms (mean; 2.4061, S.D.; 0.96), followed by existential distress (mean; 1.8784, S.D.; 0.75), peace of mind (mean; 1.871, S.D.; 0.77), dependence (mean; 1.8647, S.D.; 0.98), and social support (mean; 1.4097, S.D.; 0.99), respectively, in order of highest scores. Conclusion: Considering that the patients were mostly concerned about the distress caused by disease symptoms, followed by existential distress, peace of mind, dependency, and social support, it seems necessary to take further measures toward addressing these issues. PMID:29172264

Lumbar Sympathetic Plexus Block as a Treatment for Postamputation Pain: Methodology for a Randomized Controlled Trial.

PubMed

McCormick, Zachary L; Hendrix, Andrew; Dayanim, David; Clay, Bryan; Kirsling, Amy; Harden, Norman

2018-03-08

We present a technical protocol for rigorous assessment of patient-reported outcomes and psychophysical testing relevant to lumbar sympathetic blocks for the treatment of postamputation pain (PAP). This description is intended to inform future prospective investigation. Series of four participants from a blinded randomized sham-controlled trial. Tertiary, urban, academic pain medicine center. Four participants with a single lower limb amputation and associated chronic PAP. Participants were randomized to receive a lumbar sympathetic block with 0.25% bupivacaine or sham needle placement. Patient-rated outcome measures included the numerical rating scale (NRS) for pain, the McGill Pain Questionnaire-Short Form, Center for Epidemiological Studies Depression Scale, Pain and Anxiety Symptoms Scale-short version, and Pain Disability Index (PDI). Psychophysical and biometric testing was also performed, which included vibration sensation testing, pinprick sensation testing, brush sensation testing, Von Frey repeated weighted pinprick sensation, and thermal quantitative sensory testing. In the four described cases, treatment of PAP with a single lumbar sympathetic block but not sham intervention resulted in reduction of both residual limb pain and phantom limb pain as well as perceived disability on the PDI at three-month follow-up. An appropriately powered randomized controlled study using this methodology may not only aid in determining the possible clinical efficacy of lumbar sympathetic block in PAP, but could also improve our understanding of underlying pathophysiologic mechanisms of PAP.

Electronic Interactions of n-Doped Perylene Diimide Groups Appended to Polynorbornene Chains: Implications for Electron Transport in Organic Electronics.

PubMed

Nguyen, Minh T; Biberdorf, Joshua D; Holliday, Bradley J; Jones, Richard A

2017-11-01

A polymer consisting of a polynorbornene backbone with perylene diimide (PDI) pendant groups on each monomeric unit is synthesized via ring opening metathesis polymerization. The PDI pendant groups along the polymer backbone, studied by UV-vis absorption, fluorescence emission, and electron paramagnetic resonance spectroscopy in addition to electrochemical methods, show evidence of molecular aggregation and corresponding electronic coupling with neighboring groups, which forms pathways for efficient electron transport from one group to another in a specific reduced form. When n-doped, the title polymer shows redox conductivity of 5.4 × 10 -3 S cm -1 , comparable with crystalline PDI materials, and is therefore a promising material for use in organic electronics. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

[Parent-child interaction therapy (PCIT)].

PubMed

Briegel, Wolfgang

2016-11-01

Parent-child interaction therapy (PCIT), a manualized evidence-based intervention, was originally developed to treat disruptive behavior problems in children aged 2–6 years. It is also considered to be an evidence-based intervention for physical abuse among children. Moreover, PCIT has proved to be effective for attention deficit hyperactivity disorder, autism spectrum disorder, separation anxiety disorder, and depression. Thus, it could become the first evidence-based, transdiagnostic intervention method for 2–6-year-old children. PCIT is based on attachment theory as well as learning theory, combining aspects of play therapy and behavior therapy. It consists of two treatment phases: child-directed interaction (CDI) and parent-directed interaction (PDI). In both phases parents are taught special skills. When interacting with their child parents practice these skills and are live coached by the therapist. CDI aims at improving the parent-child relationship and is the basis for PDI. In CDI, parents learn to follow their child’s lead as long as the child shows appropriate behavior. In PDI, parents practice effectively taking the lead wherever necessary. On average, it takes about 15–20 sessions to complete PCIT, which can be terminated as soon as the parents demonstrate a mastery of the skills, when child disruptive behavior has been reduced to clearly normal levels, and when the parents have become confident in managing child behavior on their own.

Formulation development and optimization of a novel Cremophore EL-based nanoemulsion using ultrasound cavitation.

PubMed

Tang, Siah Ying; Manickam, Sivakumar; Wei, Tan Khang; Nashiru, Billa

2012-03-01

In the present study, response surface methodology (RSM) based on central composite design (CCD) was employed to investigate the influence of main emulsion composition variables, namely drug loading, oil content, emulsifier content as well as the effect of the ultrasonic operating parameters such as pre-mixing time, ultrasonic amplitude, and irradiation time on the properties of aspirin-loaded nanoemulsions. The two main emulsion properties studied as response variables were: mean droplet size and polydispersity index. The ultimate goal of the present work was to determine the optimum level of the six independent variables in which an optimal aspirin nanoemulsion with desirable properties could be produced. The response surface analysis results clearly showed that the variability of two responses could be depicted as a linear function of the content of main emulsion compositions and ultrasonic processing variables. In the present investigation, it is evidently shown that ultrasound cavitation is a powerful yet promising approach in the controlled production of aspirin nanoemulsions with smaller average droplet size in a range of 200-300 nm and with a polydispersity index (PDI) of about 0.30. This study proved that the use of low frequency ultrasound is of considerable importance in the controlled production of pharmaceutical nanoemulsions in the drug delivery system. Copyright © 2011 Elsevier B.V. All rights reserved.

[The new method monitoring crop water content based on NIR-Red spectrum feature space].

PubMed

Cheng, Xiao-juan; Xu, Xin-gang; Chen, Tian-en; Yang, Gui-jun; Li, Zhen-hai

2014-06-01

Moisture content is an important index of crop water stress condition, timely and effective monitoring of crop water content is of great significance for evaluating crop water deficit balance and guiding agriculture irrigation. The present paper was trying to build a new crop water index for winter wheat vegetation water content based on NIR-Red spectral space. Firstly, canopy spectrums of winter wheat with narrow-band were resampled according to relative spectral response function of HJ-CCD and ZY-3. Then, a new index (PWI) was set up to estimate vegetation water content of winter wheat by improveing PDI (perpendicular drought index) and PVI (perpendicular vegetation index) based on NIR-Red spectral feature space. The results showed that the relationship between PWI and VWC (vegetation water content) was stable based on simulation of wide-band multispectral data HJ-CCD and ZY-3 with R2 being 0.684 and 0.683, respectively. And then VWC was estimated by using PWI with the R2 and RMSE being 0.764 and 0.764, 3.837% and 3.840%, respectively. The results indicated that PWI has certain feasibility to estimate crop water content. At the same time, it provides a new method for monitoring crop water content using remote sensing data HJ-CCD and ZY-3.

Enhancement of photodynamic inactivation of Staphylococcus aureus biofilms by disruptive strategies.

PubMed

Gándara, Lautaro; Mamone, Leandro; Bohm, Gabriela Cervini; Buzzola, Fernanda; Casas, Adriana

2017-11-01

Photodynamic inactivation (PDI) has been used to inactivate microorganisms through the use of photosensitizers and visible light. On the one hand, near-infrared treatment (NIRT) has also bactericidal and dispersal effects on biofilms. In addition, dispersal biological tools such as enzymes have also been employed in antibiotic combination treatments. The aim of this work was to use alternative approaches to increase the PDI efficacy, employing combination therapies aimed at the partial disruption of the biofilms, thus potentially increasing photosensitizer or oxygen penetration and interaction with bacteria. To that end, we applied toluidine blue (TB)-PDI treatment to Staphylococcus aureus biofilms previously treated with NIRT or enzymes and investigated the outcome of the combined therapies. TB employed at 0.5 mM induced per se 2-log drop in S. aureus RN6390 biofilm viability. Each NIRT (980-nm laser) and PDI (635-nm laser) treatment induced a further reduction of 1-log of viable counts. The combination of successive 980- and 635-nm laser treatments on TB-treated biofilms induced additive effects, leading to a 4.5-log viable count decrease. Proteinase K treatment applied to S. aureus of the Newman strain induced an additive effect on PDI mortality, leading to an overall 4-log decrease in S. aureus viability. Confocal scanning laser microscopy after biofilm staining with a fluorescent viability test and scanning electron microscopy observations were correlated with colony counts. The NIRT dose employed (227 J/cm 2 ) led to an increase from 21 to 47 °C in the buffer temperature of the biofilm system, and this NIRT dose also induced 100% keratinocyte death. Further work is needed to establish conditions under which biofilm dispersal occurs at lower NIRT doses.

Policies and Procedures for Reviewing Medical Images From Portable Media: Survey of Radiology Departments

PubMed Central

Kalia, Vivek; Carrino, John A.; Macura, Katarzyna J.

2015-01-01

Purpose The purpose of this study was to survey current practices for portable media (CDs and DVDs) use for medical imaging in both academic and nonacademic radiology departments in the United States. Methods This survey was a stratified, nonrandom sample, 22-question electronic survey, using SurveyMonkey, of members of the Association of Administrators in Academic Radiology, the Association for Medical Imaging Management, and the University HealthSystem Consortium, conducted in November 2009. Questions were grouped by media production and media viewing practices. Results One hundred and two individual responses to the survey were received. Ninety-eight percent of respondents said that their institutions produced Digital Imaging and Communications in Medicine (DICOM)-compliant media, with only 2.0% uncertain. Only 22.2% of respondents claimed that their institutions produced Integrating the Healthcare Enterprise (IHE) Portable Data for Imaging (PDI)-compliant media, while 71.6% were uncertain. Rates of DICOM and IHE PDI compliance did not differ between academic and nonacademic centers. As for testing digital media produced at the institutions for DICOM and IHE PDI compliance, only 16.0% of respondents’ institutions routinely did so. Conclusions Three main problem areas regarding portable media became evident from this study: (1) access, (2) importability, and (3) viewing issues, and problems with any of the 3 can delay patient care. Noncompliance and a lack of knowledge about compliance were found to be major issues in the present study, more so for IHE PDI than for DICOM, and there is much room for improvement. Recommendations include that radiology practices should routinely generate only media compliant with DICOM and IHE PDI and should test for compliance. PMID:21211763

Marine Stratocumulus Properties from the FPDR - PDI as a Function of Aerosol during ORACLES

NASA Astrophysics Data System (ADS)

Small Griswold, J. D.; Heikkila, A.

2016-12-01

Aerosol-cloud interactions in the southeastern Atlantic (SEA) region were investigated during year 1 of the ObseRvations of Aerosols above CLouds and their intEractionS (ORACLES) field project in Aug-Sept 2016. This region is of interest due to seasonally persistent marine stratocumulus cloud decks that are an important component of the climate system due to their radiative and hydrologic impacts. The SEA deck is unique due to the interactions between these clouds and transported biomass burning aerosol during the July-October fire season. These biomass burning aerosol play multiple roles in modifying the cloud deck through interactions with radiation as absorbing aerosol and through modifications to cloud microphysical properties as cloud condensation nuclei. This work uses in situcloud data obtained with a Flight Probe Dual Range - Phase Doppler Interferometer (FPDR - PDI), standard aerosol instrumentation on board the NASA P-3, and reanalysis data to investigate Aerosol-Cloud Interactions (ACI). The FPDR - PDI provides unique cloud microphysical observations of individual cloud drop arrivals allowing for the computation of a variety of microphysical cloud properties including individual drop size, cloud drop number concentration, cloud drop size distributions, liquid water content, and cloud thickness. The FPDR - PDI measurement technique also provides droplet spacing and drop velocity information which is used to investigate turbulence and entrainment mixing processes. We use aerosol information such as average background aerosol amount (low, mid, high) and location relative to cloud (above or mixing) to sort FPDR - PDI cloud properties. To control for meteorological co-variances we further sort the data within aerosol categories by lower tropospheric stability, vertical velocity, and surface wind direction. We then determine general marine stratocumulus cloud characteristics under each of the various aerosol categories to investigate ACI in the SEA.

Small molecule modulator of protein disulfide isomerase attenuates mutant huntingtin toxicity and inhibits endoplasmic reticulum stress in a mouse model of Huntington's disease.

PubMed

Zhou, Xiao; Li, Gang; Kaplan, Anna; Gaschler, Michael M; Zhang, Xiaoyan; Hou, Zhipeng; Jiang, Mali; Zott, Roseann; Cremers, Serge; Stockwell, Brent R; Duan, Wenzhen

2018-05-01

Huntington's disease (HD) is caused by a cytosine-adenine-guanine (CAG) trinucleotide repeat expansion in the huntingtin (HTT) gene encoding an elongated polyglutamine tract within the N-terminal of the huntingtin protein (Htt) and leads to Htt misfolding, aberrant protein aggregation, and progressive appearance of disease symptoms. Chronic activation of endoplasmic reticulum (ER) stress by mutant Htt (mHtt) results in cellular dysfunction and ultimately cell death. Protein disulfide isomerase (PDI) is a chaperone protein located in the ER. Our previous studies demonstrated that mHtt caused PDI to accumulate at mitochondria-associated ER membranes and triggered cell death, and that modulating PDI activity using small molecules protected cells again mHtt toxicity in cell and brain slice models of HD. In this study, we demonstrated that PDI is upregulated in the HD human brain, in cell and mouse models. Chronic administration of a reversible, brain penetrable small molecule PDI modulator, LOC14 (20 mg/kg/day), significantly improved motor function, attenuated brain atrophy and extended survival in the N171-82Q HD mice. Moreover, LOC14 preserved medium spiny neuronal marker dopamine- and cyclic-AMP-regulated phosphoprotein of molecular weight 32 000 (DARPP32) levels in the striatum of HD mice. Mechanistic study revealed that LOC14 suppressed mHtt-induced ER stress, indicated by repressing the abnormally upregulated ER stress proteins in HD models. These findings suggest that LOC14 is promising to be further optimized for clinical trials of HD, and modulation of signaling pathways coping with ER stress may constitute an attractive approach to reduce mHtt toxicity and identify new therapeutic targets for treatment of HD.

Cyclic perylene diimide: Selective ligand for tetraplex DNA binding over double stranded DNA.

PubMed

Vasimalla, Suresh; Sato, Shinobu; Takenaka, Fuminori; Kurose, Yui; Takenaka, Shigeori

2017-12-15

Synthesized cyclic perylene diimide, cPDI, showed the binding constant of 6.3 × 10 6  M -1 with binding number of n = 2 with TA-core as a tetraplex DNA in 50 mM Tris-HCl buffer (pH = 7.4) containing 100 mM KCl using Schatchard analysis and showed a higher preference for tetraplex DNA than for double stranded DNA with over 10 3 times. CD spectra showed that TA-core induced its antiparallel conformation upon addition of cPDI in the absence or presence of K + or Na + ions. The cPDI inhibits the telomerase activity with IC 50 of 0.3 µM using TRAP assay which is potential anti-cancer drug with low side effect. Copyright © 2017 Elsevier Ltd. All rights reserved.

Exploring the development of novice unqualified graduate teachers' topic-specific PCK in teaching the particulate nature of matter in South Africa's classrooms

NASA Astrophysics Data System (ADS)

Pitjeng-Mosabala, Phihlo; Rollnick, Marissa

2018-05-01

This study investigates the development of Topic-Specific Pedagogical Content Knowledge (TSPCK) of 14 novice uncertified graduate science teachers during a Professional Development Intervention (PDI) on teaching particulate nature of matter. TSPCK was defined in terms of five knowledge components: learner prior knowledge, curricular saliency, representations, what is difficult to teach and conceptual teaching strategies. Data sources consisted of validated pre- and post-TSPCK and content knowledge (CK) tests, teacher-constructed Content Representations (CoRes) before and after teaching and, for four teachers, video-recorded lessons, and field notes together with teacher interviews. The purpose of this study was to investigate how the teachers develop TSPCK through the process. The results provide an insight into how initial construction of CoRes enabled the entire group to start thinking about how to teach the topic. For the four case-study teachers, evidence of TSPCK development was observed in their teaching. These teachers showed greater improvement in TSPCK and CK than those who taught only the prerequisite concepts of the topic. The findings show that it is possible for uncertified teachers to develop PCK in the practice context with appropriate PDI. Some improvement in PCK was also observed for the larger group who taught only prerequisite concepts.

Protein disulfide isomerase mediates glutathione depletion-induced cytotoxicity.

PubMed

Okada, Kazushi; Fukui, Masayuki; Zhu, Bao-Ting

2016-08-26

Glutathione depletion is a distinct cause underlying many forms of pathogenesis associated with oxidative stress and cytotoxicity. Earlier studies showed that glutamate-induced glutathione depletion in immortalized murine HT22 hippocampal neuronal cells leads to accumulation of reactive oxygen species (ROS) and ultimately cell death, but the precise mechanism underlying these processes is not clear. Here we show that during the induction of glutathione depletion, nitric oxide (NO) accumulation precedes ROS accumulation. While neuronal NO synthase (nNOS) in untreated HT22 cells exists mostly as a monomer, glutathione depletion results in increased formation of the dimer nNOS, accompanied by increases in the catalytic activity. We identified that nNOS dimerization is catalyzed by protein disulfide isomerase (PDI). Inhibition of PDI's isomerase activity effectively abrogates glutathione depletion-induced conversion of monomer nNOS into dimer nNOS, accumulation of NO and ROS, and cytotoxicity. Furthermore, we found that PDI is present in untreated cells in an inactive S-nitrosylated form, which becomes activated following glutathione depletion via S-denitrosylation. These results reveal a novel role for PDI in mediating glutathione depletion-induced oxidative cytotoxicity, as well as its role as a valuable therapeutic target for protection against oxidative cytotoxicity. Copyright © 2016. Published by Elsevier Inc.

Comparing the Personality Disorder Interview for DSM-IV (PDI-IV) and SCID-II borderline personality disorder scales: an item-response theory analysis.

PubMed

Huprich, Steven K; Paggeot, Amy V; Samuel, Douglas B

2015-01-01

One-hundred sixty-nine psychiatric outpatients and 171 undergraduate students were assessed with the Personality Disorder Interview-IV (PDI-IV; Widiger, Mangine, Corbitt, Ellis, & Thomas, 1995) and the Structured Clinical Interview for DSM-IV Axis II disorders (SCID-II; First, Gibbon, Spitzer, Williams, & Benjamin, 1997) for borderline personality disorder (BPD). Eighty individuals met PDI-IV BPD criteria, whereas 34 met SCID-II BPD criteria. Dimensional ratings of both measures were highly intercorrelated (rs = .78, .75), and item-level interrater reliability fell in the good to excellent range. An item-response theory analysis was performed to investigate whether properties of the items from each interview could help understand these differences. The limited agreement seemed to be explained by differences in the response options across the two interviews. We found that suicidal behavior was among the most discriminating criteria on both instruments, whereas dissociation and difficulty controlling anger had the 2 lowest alpha parameter values. Finally, those meeting BPD criteria on both interviews had higher levels of anxiety, depression, and more impairments in object relations than those meeting criteria on just the PDI-IV. These findings suggest that the choice of measure has a notable effect on the obtained diagnostic prevalence and the level of BPD severity that is detected.

Using diagnostic experiences in experience-based innovative design

NASA Astrophysics Data System (ADS)

Prabhakar, Sattiraju; Goel, Ashok K.

1992-03-01

Designing a novel class of devices requires innovation. Often, the design knowledge of these devices does not identify and address the constraints that are required for their performance in the real world operating environment. So any new design adapted from these devices tend to be similarly sketchy. In order to address this problem, we propose a case-based reasoning method called performance driven innovation (PDI). We model the design as a dynamic process, arrive at a design by adaptation from the known designs, generate failures for this design for some new constraints, and then use this failure knowledge to generate the required design knowledge for the new constraints. In this paper, we discuss two aspects of PDI: the representation of PDI cases and the translation of the failure knowledge into design knowledge for a constraint. Each case in PDI has two components: design and failure knowledge. Both of them are represented using a substance-behavior-function model. Failure knowledge has internal device failure behaviors and external environmental behaviors. The environmental behavior, for a constraint, interacting with the design behaviors, results in the failure internal behavior. The failure adaptation strategy generates functions, from the failure knowledge, which can be addressed using the routine design methods. These ideas are illustrated using a coffee-maker example.

Structural basis of redox-dependent substrate binding of protein disulfide isomerase

PubMed Central

Yagi-Utsumi, Maho; Satoh, Tadashi; Kato, Koichi

2015-01-01

Protein disulfide isomerase (PDI) is a multidomain enzyme, operating as an essential folding catalyst, in which the b′ and a′ domains provide substrate binding sites and undergo an open–closed domain rearrangement depending on the redox states of the a′ domain. Despite the long research history of this enzyme, three-dimensional structural data remain unavailable for its ligand-binding mode. Here we characterize PDI substrate recognition using α-synuclein (αSN) as the model ligand. Our nuclear magnetic resonance (NMR) data revealed that the substrate-binding domains of PDI captured the αSN segment Val37–Val40 only in the oxidized form. Furthermore, we determined the crystal structure of an oxidized form of the b′–a′ domains in complex with an undecapeptide corresponding to this segment. The peptide-binding mode observed in the crystal structure with NMR validation, was characterized by hydrophobic interactions on the b′ domain in an open conformation. Comparison with the previously reported crystal structure indicates that the a′ domain partially masks the binding surface of the b′ domain, causing steric hindrance against the peptide in the reduced form of the b′–a′ domains that exhibits a closed conformation. These findings provide a structural basis for the mechanism underlying the redox-dependent substrate binding of PDI. PMID:26350503

A primary care, multi-disciplinary disease management program for opioid-treated patients with chronic non-cancer pain and a high burden of psychiatric comorbidity.

PubMed

Chelminski, Paul R; Ives, Timothy J; Felix, Katherine M; Prakken, Steven D; Miller, Thomas M; Perhac, J Stephen; Malone, Robert M; Bryant, Mary E; DeWalt, Darren A; Pignone, Michael P

2005-01-13

Chronic non-cancer pain is a common problem that is often accompanied by psychiatric comorbidity and disability. The effectiveness of a multi-disciplinary pain management program was tested in a 3 month before and after trial. Providers in an academic general medicine clinic referred patients with chronic non-cancer pain for participation in a program that combined the skills of internists, clinical pharmacists, and a psychiatrist. Patients were either receiving opioids or being considered for opioid therapy. The intervention consisted of structured clinical assessments, monthly follow-up, pain contracts, medication titration, and psychiatric consultation. Pain, mood, and function were assessed at baseline and 3 months using the Brief Pain Inventory (BPI), the Center for Epidemiological Studies-Depression Scale scale (CESD) and the Pain Disability Index (PDI). Patients were monitored for substance misuse. Eighty-five patients were enrolled. Mean age was 51 years, 60% were male, 78% were Caucasian, and 93% were receiving opioids. Baseline average pain was 6.5 on an 11 point scale. The average CESD score was 24.0, and the mean PDI score was 47.0. Sixty-three patients (73%) completed 3 month follow-up. Fifteen withdrew from the program after identification of substance misuse. Among those completing 3 month follow-up, the average pain score improved to 5.5 (p = 0.003). The mean PDI score improved to 39.3 (p < 0.001). Mean CESD score was reduced to 18.0 (p < 0.001), and the proportion of depressed patients fell from 79% to 54% (p = 0.003). Substance misuse was identified in 27 patients (32%). A primary care disease management program improved pain, depression, and disability scores over three months in a cohort of opioid-treated patients with chronic non-cancer pain. Substance misuse and depression were common, and many patients who had substance misuse identified left the program when they were no longer prescribed opioids. Effective care of patients with chronic pain should include rigorous assessment and treatment of these comorbid disorders and intensive efforts to insure follow up.

A primary care, multi-disciplinary disease management program for opioid-treated patients with chronic non-cancer pain and a high burden of psychiatric comorbidity

PubMed Central

Chelminski, Paul R; Ives, Timothy J; Felix, Katherine M; Prakken, Steven D; Miller, Thomas M; Perhac, J Stephen; Malone, Robert M; Bryant, Mary E; DeWalt, Darren A; Pignone, Michael P

2005-01-01

Background Chronic non-cancer pain is a common problem that is often accompanied by psychiatric comorbidity and disability. The effectiveness of a multi-disciplinary pain management program was tested in a 3 month before and after trial. Methods Providers in an academic general medicine clinic referred patients with chronic non-cancer pain for participation in a program that combined the skills of internists, clinical pharmacists, and a psychiatrist. Patients were either receiving opioids or being considered for opioid therapy. The intervention consisted of structured clinical assessments, monthly follow-up, pain contracts, medication titration, and psychiatric consultation. Pain, mood, and function were assessed at baseline and 3 months using the Brief Pain Inventory (BPI), the Center for Epidemiological Studies-Depression Scale scale (CESD) and the Pain Disability Index (PDI). Patients were monitored for substance misuse. Results Eighty-five patients were enrolled. Mean age was 51 years, 60% were male, 78% were Caucasian, and 93% were receiving opioids. Baseline average pain was 6.5 on an 11 point scale. The average CESD score was 24.0, and the mean PDI score was 47.0. Sixty-three patients (73%) completed 3 month follow-up. Fifteen withdrew from the program after identification of substance misuse. Among those completing 3 month follow-up, the average pain score improved to 5.5 (p = 0.003). The mean PDI score improved to 39.3 (p < 0.001). Mean CESD score was reduced to 18.0 (p < 0.001), and the proportion of depressed patients fell from 79% to 54% (p = 0.003). Substance misuse was identified in 27 patients (32%). Conclusions A primary care disease management program improved pain, depression, and disability scores over three months in a cohort of opioid-treated patients with chronic non-cancer pain. Substance misuse and depression were common, and many patients who had substance misuse identified left the program when they were no longer prescribed opioids. Effective care of patients with chronic pain should include rigorous assessment and treatment of these comorbid disorders and intensive efforts to insure follow up. PMID:15649331

Crystal engineering of giant molecules based on perylene diimide conjugated polyhedral oligomeric silsesquioxane nano-atom

NASA Astrophysics Data System (ADS)

Ren, He

Molecular architectures and topologies are found contributing to the formation of supramolecular structures of giant molecules. Dr. Cheng's research group developed a diverse of giant molecules via precisely controlled chemistry synthetic routes. These giant molecules can be categorized into several different families, namely giant surfactants, giant shape amphiphiles and giant polyhedron. By analyzing the hierarchical structures of these carefully designed and precisely synthesized giant molecules, the structural factors which affect, or even dominates, in some cases, the formation of supramolecular structures are revealed in these intensive researches. The results will further contribute to the understanding of dependence of supramolecular structures on molecular designs as well as molecular topology, and providing a practical solution to the scaling up of microscopic molecular functionalities to macroscopic material properties. Molecular Nano Particles (MNPs), including fullerene (C60), POSS, Polyoxometalate (POM) and proteins etc., is defined and applied as a specific type of building blocks in the design and synthesis of giant molecules. The persistence in shape and symmetry is considered as one of the major properties of MNPs. This persistence will support the construction of giant molecules for further supramolecular structures' study by introducing specific shapes, or precisely located side groups which will facilitate self-assembling behaviors with pre-programmed secondary interactions. Dictating material physical properties by its chemical composition is an attractive yet currently failed approach in the study of materials. However, the pursuit of determining material properties by microscopic molecular level properties is never seized, and found its solution when the idea of crystal engineering is raised: should each atom in the material is located exactly where it is designed to be and is properly bonded, the property of the material is hence determined. In such "bottom-up" approach, the precise fabrication of 2 nm 100 nm nanostructures, is of great research interest. In this thesis, crystal engineering of giant molecules based on PDI conjugated POSS Nano-Atom (PDI-BPOSS) nano-atoms via self-assembly is performed and studied. Herein, three different giant molecules were synthesized: shape amphiphile, m-phenyl-(PDI-BPOSS)2 (S1) and tetrahedron, R-(PDI-BPOSS)4 (S2) and S-(PDI-BPOSS)4 (S3). Single crystals were grown for S1 and S2, X-ray diffraction (XRD), Scanning Electron Microscopy (SEM) and transmission electron microscopy (TEM) were performed, and crystal structures of these samples were determined, while hexagonal superlattice without crystal order can be observed for S3 to exhibit crystal-like morphology.

Characterization of onset of parametric decay instability of lower hybrid waves

NASA Astrophysics Data System (ADS)

Baek, S. G.; Bonoli, P. T.; Parker, R. R.; Shiraiwa, S.; Wallace, G. M.; Porkolab, M.; Takase, Y.; Brunner, D.; Faust, I. C.; Hubbard, A. E.; LaBombard, B. L.; Lau, C.

2014-02-01

The goal of the lower hybrid current drive (LHCD) program on Alcator C-Mod is to develop and optimize ITER-relevant steady-state plasmas by controlling the current density profile. Using a 4×16 waveguide array, over 1 MW of LH power at 4.6 GHz has been successfully coupled to the plasmas. However, current drive efficiency precipitously drops as the line averaged density (n¯e) increases above 1020m-3. Previous numerical work shows that the observed loss of current drive efficiency in high density plasmas stems from the interactions of LH waves with edge/scrape-off layer (SOL) plasmas [Wallace et al., Physics of Plasmas 19, 062505 (2012)]. Recent observations of parametric decay instability (PDI) suggest that non-linear effects should be also taken into account to fully characterize the parasitic loss mechanisms [Baek et al., Plasma Phys. Control Fusion 55, 052001 (2013)]. In particular, magnetic configuration dependent ion cyclotron PDIs are observed using the probes near n¯e≈1.2×1020m-3. In upper single null plasmas, ion cyclotron PDI is excited near the low field side separatrix with no apparent indications of pump depletion. The observed ion cyclotron PDI becomes weaker in inner wall limited plasmas, which exhibit enhanced current drive effects. In lower single null plasmas, the dominant ion cyclotron PDI is excited near the high field side (HFS) separatrix. In this case, the onset of PDI is correlated with the decrease in pump power, indicating that pump wave power propagates to the HFS and is absorbed locally near the HFS separatrix. Comparing the observed spectra with the homogeneous growth rate calculation indicates that the observed ion cyclotron instability is excited near the plasma periphery. The incident pump power density is high enough to overcome the collisional homogeneous threshold. For C-Mod plasma parameters, the growth rate of ion sound quasi-modes is found to be typically smaller by an order of magnitude than that of ion cyclotron quasi-modes. When considering the convective threshold near the plasma edge, convective growth due to parallel coupling rather than perpendicular coupling is likely to be responsible for the observed strength of the sidebands. To demonstrate the improved LHCD efficiency in high density plasmas, an additional launcher has been designed. In conjunction with the existing launcher, this new launcher will allow access to an ITER-like high single pass absorption regime, replicating the JLH(r) expected in ITER. The predictions from the time domain discharge scenarios, in which the two launchers are used, will be also presented.

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

Khezri, Khezrollah, E-mail: kh.khezri@ut.ac.ir; Roghani-Mamaqani, Hossein

Graphical abstract: Effect of mesoporous silica nanoparticles (MCM-41) on the activator generated by electron transfer for atom transfer radical polymerization (AGET ATRP) is investigated. Decrement of conversion and number average molecular weight and also increment of polydispersity index (PDI) values are three main results of addition of MCM-41 nanoparticles. Incorporation of MCM-41 nanoparticles in the polystyrene matrix can clearly increase thermal stability and decrease glass transition temperature of the nanocomposites. - Highlights: • Spherical morphology, hexagonal structure, and high surface area with regular pore diameters of the synthesized MCM-41 nanoparticles are examined. • AGET ATRP of styrene in the presencemore » of MCM-41 nanoparticles is performed. • Effect of MCM-41 nanoparticles addition on the polymerization rate, conversion and molecular weights of the products are discussed. • Improvement in thermal stability of the nanocomposites and decreasing T{sub g} values was also observed by incorporation of MCM-41 nanoparticles. - Abstract: Activator generated by electron transfer for atom transfer radical polymerization was employed to synthesize well-defined mesoporous silica nanoparticles/polystyrene composites. Inherent features of spherical mesoporous silica nanoparticles were evaluated by nitrogen adsorption/desorption isotherm, X-ray diffraction and scanning electron microscopy analysis techniques. Conversion and molecular weight evaluations were carried out using gas and size exclusion chromatography respectively. By the addition of only 3 wt% mesoporous silica nanoparticles, conversion decreases from 81 to 58%. Similarly, number average molecular weight decreases from 17,116 to 12,798 g mol{sup −1}. However, polydispersity index (PDI) values increases from 1.24 to 1.58. A peak around 4.1–4.2 ppm at proton nuclear magnetic resonance spectroscopy results clearly confirms the living nature of the polymerization. Thermogravimetric analysis shows that thermal stability of the nanocomposites increases by adding nanoparticles content. Decrease of glass transition temperature is also demonstrated by the addition of 3 wt% of silica nanoparticles according to the differential scanning calorimetry results.« less

Predictive value of early amplitude-integrated electroencephalography for later diagnosed cerebral white matter damage in preterm infants.

PubMed

Song, Juan; Zhu, Changlian; Xu, Falin; Guo, Jiajia; Zhang, Yanhua

2014-10-01

 The aim of the article is to assess the predictive value of amplitude-integrated electroencephalogram (aEEG) for cerebral white matter damage (WMD) in preterm infants. Patients and  Preterms ≤ 32 weeks' gestational age (GA) born between March 2012 and December 2012 were enrolled. The aEEG patterns within 72 hours were classified and recorded to predict their neurodevelopmental prognosis and the predictive results were used to compare with the results by cerebral ultrasound examination. Neurobehavioral disorder (neonatal behavioral neurological assessment score < 35, dyskinesia or dysgnosia) or death was thought as poor neurodevelopmental prognosis. Psychomotor development index (PDI) or mental development index (MDI) ≤ 79 was regarded as dyskinesia or dysgnosia, respectively.  Of the 63 preterms, 3.2% were born < 27 weeks' gestation and 96.8% at 27 to 32 weeks' gestation. The median GA was 29.3 weeks and the median birth weight was 1,030 g. On the basis of the aEEG results, normal, mildly abnormal, and severely abnormal cases were 10, 24, and 29; whereas determined by cerebral ultrasound, normal, mild, and severe cases were 17, 20, and 26, respectively. The aEEG degree showed significantly positive correlations with both WMD and poor neurodevelopmental prognosis (p < 0.01).  Abnormal aEEG of preterm infants within 72 hours after birth may imply WMD occurrence and poor neurodevelopmental prognosis. Georg Thieme Verlag KG Stuttgart · New York.

Observation of beat oscillation generation by coupled waves associated with parametric decay during radio frequency wave heating of a spherical tokamak plasma.

PubMed

Nagashima, Yoshihiko; Oosako, Takuya; Takase, Yuichi; Ejiri, Akira; Watanabe, Osamu; Kobayashi, Hiroaki; Adachi, Yuuki; Tojo, Hiroshi; Yamaguchi, Takashi; Kurashina, Hiroki; Yamada, Kotaro; An, Byung Il; Kasahara, Hiroshi; Shimpo, Fujio; Kumazawa, Ryuhei; Hayashi, Hiroyuki; Matsuzawa, Haduki; Hiratsuka, Junichi; Hanashima, Kentaro; Kakuda, Hidetoshi; Sakamoto, Takuya; Wakatsuki, Takuma

2010-06-18

We present an observation of beat oscillation generation by coupled modes associated with parametric decay instability (PDI) during radio frequency (rf) wave heating experiments on the Tokyo Spherical Tokamak-2. Nearly identical PDI spectra, which are characterized by the coexistence of the rf pump wave, the lower-sideband wave, and the low-frequency oscillation in the ion-cyclotron range of frequency, are observed at various locations in the edge plasma. A bispectral power analysis was used to experimentally discriminate beat oscillation from the resonant mode for the first time. The pump and lower-sideband waves have resonant mode components, while the low-frequency oscillation is exclusively excited by nonlinear coupling of the pump and lower-sideband waves. Newly discovered nonlocal transport channels in spectral space and in real space via PDI are described.

The cross-cultural generalizability of Axis-II constructs: an evaluation of two personality disorder assessment instruments in the People's Republic of China.

PubMed

Yang, J; McCrae, R R; Costa, P T; Yao, S; Dai, X; Cai, T; Gao, B

2000-01-01

We examined the reliability, cross-instrument validity, and factor structure of Chinese adaptations of the Personality Diagnostic Questionnaire (PDQ-4+; N = 1,926) and Personality Disorders Interview (PDI-IV; N = 525) in psychiatric patients. Comparisons with data from Western countries suggest that the psychometric properties of these two instruments are comparable across cultures. Low to modest agreement between the PDQ-4+ and PDI-IV was observed for both dimensional and categorical personality disorder evaluations. When the PDI-IV was used as the diagnostic standard, the PDQ-4+ showed higher sensitivity than specificity, and higher negative predictive power than positive predictive power. Factor analyses of both instruments replicated the four-factor structure O'Connor and Dyce (1998) found in Western samples. Results suggested that conceptions and measures of DSM-IV personality disorders are cross-culturally generalizable to Chinese psychiatric populations.

Assessing parental empathy: a role for empathy in child attachment.

PubMed

Stern, Jessica A; Borelli, Jessica L; Smiley, Patricia A

2015-01-01

Although empathy has been associated with helping behavior and relationship quality, little research has evaluated the role of parental empathy in the development of parent-child relationships. The current study (1) establishes preliminary validity of the Parental Affective and Cognitive Empathy Scale (PACES), a method for coding empathy from parents' narrative responses to the Parent Development Interview - Revised for School-Aged Children (PDI-R-SC), and (2) tests a theoretical model of empathy and attachment. Sixty caregivers and their children completed a battery of questionnaire and interview measures, including the PDI-R-SC and the Child Attachment Interview (CAI). Caregivers' interview narratives were scored for empathy using PACES. PACES showed good interrater reliability and good convergent validity with a self-report empathy measure. Parent empathy was positively related to child attachment security (using a continuous score for narrative coherence) and emotional openness on the CAI, as well as to child perceptions of parental warmth. Moreover, parent empathy mediated the relation between parents' self-reported attachment style and their children's attachment security. Implications for attachment theory and future directions for establishing scale validity are discussed.

Bias stress in PDI-CN2 and P3HT studied with Kelvin Probe Force Microscopy

NASA Astrophysics Data System (ADS)

Cao, Minxuan; Moscatello, Jason; Castaneda, Chloe; Xue, Binglan; Usluer, Ozlem; Briseno, Alejandro; Aidala, Katherine

We have developed a technique that uses scanning probe microscopy (SPM) to study the real-time injection and extraction of charge carriers in organic semiconductor devices. We investigate PDI-CN2 and P3HT in a back gate field effect transistor geometry with gold electrodes. By positioning the SPM tip at an individual location and using Kelvin probe microscopy to record the potential over time, we can record how the charge carriers respond to changing the gate voltage while the source and drain electrodes are grounded. We see relatively fast screening when carriers are injected into the film. The screening is slower when carriers must escape from traps to exit the film. By incrementally stepping the gate voltage, we can probe different trap depths. By repeating the measurement, we observe the development of longer lived trap states, shown by the longer time recorded to fully screen the gate voltage. This work is supported by NSF Grant DMR-0955348, and the Center for Heirarchical Manufacturing at the University of Massachusetts, Amherst (NSF CMMI-1025020).

A universal aptameric biosensor: Multiplexed detection of small analytes via aggregated perylene-based broad-spectrum quencher.

PubMed

Hu, Rong; Zhang, Xi; Xu, Qiang; Lu, Dan-Qing; Yang, Yun-Hui; Xu, Quan-Qing; Ruan, Qiong; Mo, Liu-Ting; Zhang, Xiao-Bing

2017-06-15

A universal aptameric system based on the taking advantage of double-stranded DNA/perylene diimide (dsDNA/PDI) as the signal probe was developed for multiplexed detection of small molecules. Aptamers are single-stranded DNA or RNA oligonucleotides which are selected in vitro by a process known as systematic evolution of ligands by exponential enrichment. In this work, we synthesized a new kind of PDI and reported this aggregated PDI could quench the double-stranded DNA (dsDNA)-labeled fluorophores with a high quenching efficiency. The quenching efficiencies on the fluorescence of FAM, TAMRA and Cy5 could reach to 98.3%±0.9%, 97.2%±0.6% and 98.1%±1.1%, respectively. This broad-spectrum quencher was then adopted to construct a multicolor biosensor via a label-free approach. A structure-switching-triggered enzymatic recycling amplification was employed for signal amplification. High quenching efficiency combined with autocatalytic target recycling amplification afforded the biosensor with high sensitivity towards small analytes. For other targets, changing the corresponding aptamer can achieve the goal. The quencher did not interfere with the catalytic activity of nuclease. The biosensor could be manipulated with similar sensitivity no matter in pre-addition or post-addition manner. Moreover, simultaneous and multiplexed analysis of several small molecules in homogeneous solution was achieved, demonstrating its potential application in the rapid screening of multiple biotargets. Copyright © 2017 Elsevier B.V. All rights reserved.

Influence of conditioning temperature on the performance, nutrient utilisation and digestive tract development of broilers fed on maize- and wheat-based diets.

PubMed

Abdollahi, M R; Ravindran, V; Wester, T J; Ravindran, G; Thomas, D V

2010-10-01

1. The influence of conditioning temperature on the performance, nutrient utilisation and digestive tract development of broilers fed on maize- and wheat-based diets was examined up to 21 d of age. The experimental design was a 2 × 3 factorial arrangement of treatments evaluating two grain types (maize and wheat) and three conditioning temperatures (60°C, 75°C and 90°C). Broiler starter diets, each based on one grain (maize or wheat), were formulated and pelleted at the three temperatures. 2. Increasing conditioning temperature decreased the body-weight gain and feed intake in wheat-based diets, but birds fed on maize-based diets conditioned at 60°C and 90°C had higher body-weight gain and feed intake than those fed on the diet conditioned at 75°C. Increasing conditioning temperature increased feed per body-weight gain in both grain-type diets but improved pellet durability index (PDI) only in wheat-based diets; PDI was unaffected in maize-based diets. 3. In wheat-based diets, increasing conditioning temperature decreased the ileal digestibility of nitrogen and starch. Ileal nitrogen digestibility of maize-based diets conditioned at 60°C and 90°C was higher than at 75°C. Starch digestibility was unaffected by conditioning temperature in maize-based diets. No effect of conditioning temperature was found for apparent metabolisable energy (AME). Increasing conditioning temperature decreased digestible protein and AME intakes in wheat-based diets but, in maize-based diets, birds fed on the diet conditioned at 75°C had lower digestible protein and AME intakes compared to those fed on diets conditioned at 60°C and 90°C. 4. Small intestine was longer in birds fed on diets conditioned at 75°C and 90°C compared with those fed on diets conditioned at 60°C. 5. Overall, the data suggest that while the effects of conditioning temperature on body-weight gain and feed intake of broilers to 21 d of age differed depending on the grain type, feed per body-weight gain was adversely affected by higher conditioning temperatures.

The dehydrogenase region of the NADPH oxidase component Nox2 acts as a protein disulfide isomerase (PDI) resembling PDIA3 with a role in the binding of the activator protein p67phox

PubMed Central

Bechor, Edna; Dahan, Iris; Fradin, Tanya; Berdichevsky, Yevgeny; Zahavi, Anat; Federman Gross, Aya; Rafalowski, Meirav; Pick, Edgar

2015-01-01

The superoxide (O·−2)-generating NADPH oxidase of phagocytes consists of a membrane component, cytochrome b558 (a heterodimer of Nox2 and p22phox), and four cytosolic components, p47phox, p67phox, p40phox, and Rac. The catalytic component, responsible for O·−2 generation, is Nox2. It is activated by the interaction of the dehydrogenase region (DHR) of Nox2 with the cytosolic components, principally with p67phox. Using a peptide-protein binding assay, we found that Nox2 peptides containing a 369CysGlyCys371 triad (CGC) bound p67phox with high affinity, dependent upon the establishment of a disulfide bond between the two cysteines. Serially truncated recombinant Nox2 DHR proteins bound p67phox only when they comprised the CGC triad. CGC resembles the catalytic motif (CGHC) of protein disulfide isomerases (PDIs). This led to the hypothesis that Nox2 establishes disulfide bonds with p67phox via a thiol-dilsulfide exchange reaction and, thus, functions as a PDI. Evidence for this was provided by the following: (1) Recombinant Nox2 protein, which contained the CGC triad, exhibited PDI-like disulfide reductase activity; (2) Truncation of Nox2 C-terminal to the CGC triad or mutating C369 and C371 to R, resulted in loss of PDI activity; (3) Comparison of the sequence of the DHR of Nox2 with PDI family members revealed three small regions of homology with PDIA3; (4) Two monoclonal anti-Nox2 antibodies, with epitopes corresponding to regions of Nox2/PDIA3 homology, reacted with PDIA3 but not with PDIA1; (5) A polyclonal anti-PDIA3 (but not an anti-PDIA1) antibody reacted with Nox2; (6) p67phox, in which all cysteines were mutated to serines, lost its ability to bind to a Nox2 peptide containing the CGC triad and had an impaired capacity to support oxidase activity in vitro. We propose a model of oxidase assembly in which binding of p67phox to Nox2 via disulfide bonds, by virtue of the intrinsic PDI activity of Nox2, stabilizes the primary interaction between the two components. PMID:25699251

The dehydrogenase region of the NADPH oxidase component Nox2 acts as a protein disulfide isomerase (PDI) resembling PDIA3 with a role in the binding of the activator protein p67phox

NASA Astrophysics Data System (ADS)

Bechor, Edna; Dahan, Iris; Fradin, Tanya; Berdichevsky, Yevgeny; Zahavi, Anat; Rafalowski, Meirav; Federman-Gross, Aya; Pick, Edgar

2015-02-01

The superoxide (O2.-)-generating NADPH oxidase of phagocytes consists of a membrane component, cytochrome b558 (a heterodimer of Nox2 and p22phox), and four cytosolic components, p47phox, p67phox, p40phox, and Rac. The catalytic component, responsible for O2.- generation, is Nox2. It is activated by the interaction of the dehydrogenase region (DHR) of Nox2 with the cytosolic components, principally with p67phox. Using a peptide-protein binding assay, we found that Nox2 peptides containing a 369CysGlyCys371 triad (CGC) bound p67phox with high affinity, dependent upon the establishment of a disulfide bond between the two cysteines. Serially truncated recombinant Nox2 DHR proteins bound p67phox only when they comprised the CGC triad. CGC resembles the catalytic motif (CGHC) of protein disulfide isomerases (PDIs). This led to the hypothesis that Nox2 establishes disulfide bonds with p67phox via a thiol-dilsulfide exchange reaction and, thus, functions as a PDI. Evidence for this was provided by the following: 1. Recombinant Nox2 protein, which contained the CGC triad, exhibited PDI-like disulfide reductase activity; 2. Truncation of Nox2 C-terminal to the CGC triad or mutating C369 and C371 to R, resulted in loss of PDI activity; 3. Comparison of the sequence of the DHR of Nox2 with PDI family members revealed three small regions of homology with PDIA3; 4. Two monoclonal anti-Nox2 antibodies, with epitopes corresponding to regions of Nox2/PDIA3 homology, reacted with PDIA3 but not with PDIA1; 5. A polyclonal anti-PDIA3 (but not an anti-PDIA1) antibody reacted with Nox2; 6. p67phox, in which all cysteines were mutated to serines, lost its ability to bind to a Nox2 peptide containing the CGC triad and had an impaired capacity to support oxidase activity in vitro. We propose a model of oxidase assembly in which binding of p67phox to Nox2 via disulfide bonds, by virtue of the intrinsic PDI activity of Nox2, stabilizes the primary interaction between the two components.

Natural lipids in nanostructured lipid carriers and its cytotoxicity

NASA Astrophysics Data System (ADS)

Lima, Paula A.; Rampazo, Caroline A. D.; Costa, Amanda F.; Rodrigues, Tiago; Watashi, Carolina M.; Durán, Nelson

2017-06-01

Nanostructured lipid carriers (NLCs) are active carrier systems which modulate the sustained release of actives and protect unstable compounds against degradation. NLCs can also protect skin from sun light, due to its particulates nature, which gives them intrinsic scattering properties. In this work, we present the preparation of NLCs using natural lipids and its cytotoxicity profile. It was used a vegetal butter with melting point (m.p.) ~32-40°C, an animal wax (m.p. 35-40°C) and a vegetal oil (boiling point ~120-150°C). NLCs were prepared by hot high pressure homogenization method and particles were characterized by average size (Zave), polydispersity index (PDI) and zeta potential (PZ) (Fig.1). The thermal behavior of the NLCs was studied using Differential Scanning Calorimetry (DSC). All the formulations were followed up for 60 days in order to evaluate their stability. NLCs exhibited a Zave around 150-200 nm, PDI less than 0.2 and PZ varying from -25 to -40 mV. The m.p. for the lyophilized NLCs was about 40-56°C. Cytotoxicity of the formulations were evaluated for human keratinocytes (HaCaT) and melanocytes (Melan-A) in the exponential growth phase. Cell viability was used as indicator of cytotoxicity and determined after 4 days of culture by MTT assay. It was found that the NLC formulations were not toxic against HaCaT and Melan-A cells. Results showed that the NLCs produced are potential carriers for nanocosmetics and sunscreen products.

The use of surfactants to enhance the solubility and stability of the water-insoluble anticancer drug SN38 into liquid crystalline phase nanoparticles.

PubMed

Ranneh, Abdul-Hackam; Iwao, Yasunori; Noguchi, Shuji; Oka, Toshihiko; Itai, Shigeru

2016-12-30

Cubosomes were used to increase the aqueous solubility of the water insoluble anticancer drug SN38. The results showed that the use of a common cubosome formulation consisting of phytantriol (PHYT) as the matrix amphiphile (PHYT-cubosome) led to a 6-fold increase in the solubility of SN38. However, mean hydrodynamic diameter (D H ) and polydispersity index (PDI) of these PHYT-cubosome particles were 345±49nm and 0.37±0.05, respectively, making them unsuitable for intravenous applications. Several additives were investigated to increase the solubility of SN38 and reduce the D H and PDI values of the resulting particles. Charged additives such as didodecyldimethyl ammonium bromide (DDAB) and sodium dodecyl sulfate (SDS) led to improvements in the physiochemical properties of the cubosomes. Notably, the PHYT-DDAB and PHT-SDS cubosomes led to 15- and 14-fold increases in the aqueous solubility of SN38, respectively. Moreover, the SN38 loaded into the PHYT-DDAB and PHYT-SDS cubosomes was found to be highly stable, with very little hydrolysis to its inactive acid form. In summary, the addition of DDAB and SDS to PHYT-cubosome nanoparticle drug delivery systems not only led to considerable improvements in their physiochemical properties, but also enhanced the aqueous solubility of SN38 and increased its chemical stability. Copyright © 2016 Elsevier B.V. All rights reserved.

Post-Traumatic Stress Symptoms and Burnout Among Medical Rescue Workers 4 Years After the Great East Japan Earthquake: A Longitudinal Study.

PubMed

Kawashima, Yuzuru; Nishi, Daisuke; Noguchi, Hiroko; Usuki, Masato; Yamashita, Akihiro; Koido, Yuichi; Okubo, Yoshiro; Matsuoka, Yutaka J

2016-12-01

This study aimed to evaluate factors associated with post-traumatic stress disorder (PTSD) symptoms and burnout 4 years after the Great East Japan Earthquake among medical rescue workers in Disaster Medical Assistance Teams (DMATs). We examined participants' background characteristics, prior health condition, rescue work experiences, and the Peritraumatic Distress Inventory (PDI) score at 1 month after the earthquake. Current psychological condition was assessed by the Impact of Event Scale-Revised and Maslach Burnout Inventory administered 4 years after the earthquake. By applying univariate and multivariate linear regression analyses, we assessed the relative value of the PDI and other baseline variables for PTSD symptoms and burnout at 4 years after the earthquake. We obtained baseline data from 254 participants during April 2 to 22, 2011. Of the 254 participants, 188 (74.0%) completed the follow-up assessment. PDI score 1 month after the earthquake was associated with symptoms of PTSD (β=0.35, P<.01) and burnout (β=0.21, P<.01). Stress before deployment was a related factor for burnout 4 years after the earthquake in these medical rescue workers (β=2.61, P<.04). It seems important for DMAT headquarters to establish a routine system for assessing the PDI of medical rescue workers after deployment and screen those workers who have high stress prior to deployment (Disaster Med Public Health Preparedness. 2016;10:848-853).

Photodynamic inactivation of Escherichia coli - Correlation of singlet oxygen kinetics and phototoxicity.

PubMed

Müller, Alexander; Preuß, Annegret; Röder, Beate

2018-01-01

Photodynamic inactivation (PDI) of bacteria may play a major role in facing the challenge of the ever expanding antibiotic resistances. Here we report about the direct correlation of singlet oxygen luminescence kinetics and phototoxicity in E. coli cell suspension under PDI using the widely applied cationic photosensitizer TMPyP. Through direct access to the microenvironment, the time resolved investigation of singlet oxygen luminescence plays a key role in understanding the photosensitization mechanism and inactivation pathway. Using the homemade set-up for highly sensitive time resolved singlet oxygen luminescence detection, we show that the cationic TMPyP is localized predominantly outside the bacterial cells but in their immediate vicinity prior to photodynamic inactivation. Throughout following light exposure, a clear change in singlet oxygen kinetics indicates a redistribution of photosensitizer molecules to at least one additional microenvironment. We found the signal kinetics mirrored in cell viability measurements of equally treated samples from same overnight cultures conducted in parallel: A significant drop in cell viability of the illuminated samples and stationary viability of dark controls. Thus, for the system investigated in this work - a Gram-negative model bacteria and a well-known PS for its PDI - singlet oxygen kinetics correlates with phototoxicity. This finding suggests that it is well possible to evaluate PDI efficiency directly via time resolved singlet oxygen detection. Copyright © 2017 Elsevier B.V. All rights reserved.

Photodynamic inactivation of Acanthamoeba polyphaga with curcuminoids: an in vitro study

NASA Astrophysics Data System (ADS)

Corrêa, Thaila Q.; Geralde, Mariana C.; Carvalho, Mariana T.; Bagnato, Vanderlei S.; Kurachi, Cristina; de Souza, Clovis W. O.

2016-03-01

Acanthamoeba polyphaga are free-living amoebae that can be considered potentially pathogenic organisms by cause serious human infections, including keratitis and granulomatous amoebic encephalitis that usually results in death. Photodynamic inactivation (PDI) has been used for the biological control of microorganisms and can be promise in the control of Acanthamoeba infections. This study evaluated the in vitro effectiveness of PDI in A. polyphaga using curcuminoids salt as photosensitizer (PS) besides observing morphological changes caused by this PS in this organism, in confocal microscopy. A. polyphaga trophozoites were grown at 37°C in PYG medium for 48 to 72 hours. After, the trophozoites were incubated with PS solution during one hour and the samples were irradiated using light-emitting diodes at 460 nm at light doses 30 and 50 J/cm2. The results revealed reduction of 27.7%, 61.4% and 82.5% at 30 J/cm2 and 75.2%, 85.0% and 95.9% at 50 J/cm2, respectively, at curcuminoid salt concentrations of 500, 1000 and 1500 μg/mL. Through fluorescence images, it was possible to visualize the curcuminoid salt's uptake by the trophozoites. The PS showed toxicity to amoebae, in the dark, but the irradiation in PDI contributed to amoebae death effect. These data suggest that PDI may be an application of therapeutic intervention against Acanthamoeba infections, since it was effective in the inactivation of these amoebae.

Thermal Gradient During Vacuum-Deposition Dramatically Enhances Charge Transport in Organic Semiconductors: Toward High-Performance N-Type Organic Field-Effect Transistors.

PubMed

Kim, Joo-Hyun; Han, Singu; Jeong, Heejeong; Jang, Hayeong; Baek, Seolhee; Hu, Junbeom; Lee, Myungkyun; Choi, Byungwoo; Lee, Hwa Sung

2017-03-22

A thermal gradient distribution was applied to a substrate during the growth of a vacuum-deposited n-type organic semiconductor (OSC) film prepared from N,N'-bis(2-ethylhexyl)-1,7-dicyanoperylene-3,4:9,10-bis(dicarboxyimide) (PDI-CN2), and the electrical performances of the films deployed in organic field-effect transistors (OFETs) were characterized. The temperature gradient at the surface was controlled by tilting the substrate, which varied the temperature one-dimensionally between the heated bottom substrate and the cooled upper substrate. The vacuum-deposited OSC molecules diffused and rearranged on the surface according to the substrate temperature gradient, producing directional crystalline and grain structures in the PDI-CN2 film. The morphological and crystalline structures of the PDI-CN2 thin films grown under a vertical temperature gradient were dramatically enhanced, comparing with the structures obtained from either uniformly heated films or films prepared under a horizontally applied temperature gradient. The field effect mobilities of the PDI-CN2-FETs prepared using the vertically applied temperature gradient were as high as 0.59 cm 2 V -1 s -1 , more than a factor of 2 higher than the mobility of 0.25 cm 2 V -1 s -1 submitted to conventional thermal annealing and the mobility of 0.29 cm 2 V -1 s -1 from the horizontally applied temperature gradient.

Endoplasmic reticulum-dependent redox reactions control endoplasmic reticulum-associated degradation and pathogen entry.

PubMed

Walczak, Christopher P; Bernardi, Kaleena M; Tsai, Billy

2012-04-15

Protein misfolding within the endoplasmic reticulum (ER) is managed by an ER quality control system that retro-translocates aberrant proteins into the cytosol for proteasomal destruction. This process, known as ER-associated degradation, utilizes the action of ER redox enzymes to accommodate the disulfide-bonded nature of misfolded proteins. Strikingly, various pathogenic viruses and toxins co-opt these redox components to reach the cytosol during entry. These redox factors thus regulate critical cellular homeostasis and host-pathogen interactions. Recent studies identify specific members of the protein disulfide isomerase (PDI) family, which use their chaperone and catalytic activities, in engaging both misfolded ER proteins and pathogens. The precise molecular mechanism by which a dedicated PDI family member disrupts the disulfide bonds in the misfolded ER proteins and pathogens, as well as how they act to unfold these substrates to promote their ER-to-cytosol membrane transport, remain poorly characterized. How PDI family members distinguish folded versus misfolded ER substrates remains enigmatic. What physical characteristics surrounding a substrate's disulfide bond instruct PDI that it is mispaired or native? For the pathogens, as their disulfide bonds normally serve a critical role in providing physical support, what conformational changes experienced in the host enable their disulfide bonds to be disrupted? A combination of more rigorous biochemical and high-resolution structural studies should begin to address these questions.

Protein disulfide isomerases: Redox connections in and out of the endoplasmic reticulum.

PubMed

Soares Moretti, Ana Iochabel; Martins Laurindo, Francisco Rafael

2017-03-01

Protein disulfide isomerases are thiol oxidoreductase chaperones from thioredoxin superfamily. As redox folding catalysts from the endoplasmic reticulum (ER), their roles in ER-related redox homeostasis and signaling are well-studied. PDIA1 exerts thiol oxidation/reduction and isomerization, plus chaperone effects. Also, substantial evidence indicates that PDIs regulate thiol-disulfide switches in other cell locations such as cell surface and possibly cytosol. Subcellular PDI translocation routes remain unclear and seem Golgi-independent. The list of signaling and structural proteins reportedly regulated by PDIs keeps growing, via thiol switches involving oxidation, reduction and isomerization, S-(de)nytrosylation, (de)glutathyonylation and protein oligomerization. PDIA1 is required for agonist-triggered Nox NADPH oxidase activation and cell migration in vascular cells and macrophages, while PDIA1-dependent cytoskeletal regulation appears a converging pathway. Extracellularly, PDIs crucially regulate thiol redox signaling of thrombosis/platelet activation, e.g., integrins, and PDIA1 supports expansive caliber remodeling during injury repair via matrix/cytoskeletal organization. Some proteins display regulatory PDI-like motifs. PDI effects are orchestrated by expression levels or post-translational modifications. PDI is redox-sensitive, although probably not a mass-effect redox sensor due to kinetic constraints. Rather, the "all-in-one" organization of its peculiar redox/chaperone properties likely provide PDIs with precision and versatility in redox signaling, making them promising therapeutic targets. Copyright © 2016. Published by Elsevier Inc.

Rigidifying Nonplanar Perylene Diimides by Ring Fusion Toward Geometry-Tunable Acceptors for High-Performance Fullerene-Free Solar Cells.

PubMed

Zhong, Hongliang; Wu, Chen-Hao; Li, Chang-Zhi; Carpenter, Joshua; Chueh, Chu-Chen; Chen, Jung-Yao; Ade, Harald; Jen, Alex K-Y

2016-02-03

Rigid fused perylene diimide (PDI) dimers bridged with heterocycles exhibit superior photovoltaic performance compared to their unfused semiflexible analogues. Changing the chalcogen atoms in the aromatic bridges gradually increases the twist angles between the two PDI planes, leading to a varied morphology in which the one bridged by thiophene achieves a balance and shows the best efficiency of 6.72%. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Photodynamic inactivation requires innovative approach concerning numerous bacterial isolates and multicomponent sensitizing agents.

PubMed

Nakonieczna, Joanna; Grinholc, Mariusz

2012-12-01

It is known that Staphylococcus aureus is susceptible to photodynamic inactivation in general, but the significant variation among particular strains in the response to the treatment exists. However, factors that determine the observed phenomenon remain unclear. This study was aimed to explore the PDI effect of two sensitizers (protoporphyrin diarginate and toluidine blue O) against clinical as well as reference strains of S. aureus. Obtained results indicate that the same isolate could be characterized as highly resistant or highly sensitive to PDI according to a sensitizer used. Moreover, the same sensitizing agent could be successfully used for total eradication of some isolates and could be non-effective in the case of other strains. Additionally, changing the photosensitizer, we are able to reverse the PDI "resistant" phenotype into "sensitive" one. Thus, one could conclude that photoinactivation involving several sensitizing agents and several isolates of the same bacterial species should be undertaken to make antimicrobial photodynamic inactivation reliable. Copyright © 2012 Elsevier B.V. All rights reserved.

Highly Efficient White Organic Light Emitting Diodes Using New Blue Fluorescence Emitter.

PubMed

Kim, Seungho; Kim, Beomjin; Lee, Jaehyun; Yu, Young-Jun; Park, Jongwook

2015-07-01

Two different emitting compounds, 1-[1,1';3',1"]Terphenyl-5'-yl-6-(10-[1,1';3',1"]terpheny-5'-yl- anthracen-9-yl)-pyrene (TP-AP-TP) and Poly-phenylene vinylene derivative (PDY 132) were used to white OLED device. By incorporating adjacent blue and yellow emitting layers in a multi-layered structure, highly efficient white emission has been attained. The device was fabricated with a hybrid configuration structure: ITO/PEDOT (40 nm)/PDY-132 (8-50 nm)/ NPB (10 nm)/TP-AP-TP (30 nm)/Alq3 (20 nm)/LiF (1 nm)/Al (200 nm). After fixing TP-AP-TP thickness of 30 nm by evaporation, PDY-132 thickness varied with 8, 15, 35, and 50 nm by spin coating in device. The luminance efficiency of the white devices at 10 mA/cm2 were 2.93 cd/A-6.55 cd/A. One of white devices showed 6.55 cd/A and white color of (0.290, 0.331).

A recyclable palladium-catalyzed synthesis of 2-methylene-2,3-dihydrobenzofuran-3-ols by cycloisomerization of 2-(1-hydroxyprop-2-ynyl)phenols in ionic liquids.

PubMed

Mancuso, Raffaella; Gabriele, Bartolo

2013-09-04

A recyclable palladium-catalyzed synthesis of 2-methylene-2,3-dihydrobenzofuran-3-ols 2 by heterocyclization of 2-(1-hydroxyprop-2-ynyl)phenols 1 in an ionic liquid medium (BmimBF4) is presented. The process takes place under relatively mild conditions (100 °C, 5 h) in the presence of catalytic amounts (2 mol %) of PdI2 in conjunction with KI (5 equiv with respect to PdI2) and an organic base, such as morpholine (1 equiv with respect to 1), to give 2 in high yields (70%-86%). The PdI2-KI catalytic system could be recycled up to six times without appreciable loss of activity. Moreover, products 2 could be easily converted in a one-pot fashion into 2-hydroxymethylbenzofurans 3 (52%-71%, based on 1) and 2-methoxymethylbenzofurans 4 (52%-80%, based on 1) by acid-catalyzed allylic isomerization or allylic nucleophilic substitution.

Fine-Tuning the Quasi-3D Geometry: Enabling Efficient Nonfullerene Organic Solar Cells Based on Perylene Diimides.

PubMed

Liu, Zhitian; Zhang, Linhua; Shao, Ming; Wu, Yao; Zeng, Di; Cai, Xiang; Duan, Jiashun; Zhang, Xiaolu; Gao, Xiang

2018-01-10

The geometries of acceptors based on perylene diimides (PDIs) are important for improving the phase separation and charge transport in organic solar cells. To fine-tune the geometry, biphenyl, spiro-bifluorene, and benzene were used as the core moiety to construct quasi-three-dimensional nonfullerene acceptors based on PDI building blocks. The molecular geometries, energy levels, optical properties, photovoltaic properties, and exciton kinetics were systematically studied. The structure-performance relationship was discussed as well. Owing to the finest phase separation, the highest charge mobility and smallest nongeminate recombination, the power conversion efficiency of nonfullerene solar cells using PDI derivatives with biphenyl core (BP-PDI 4 ) as acceptor reached 7.3% when high-performance wide band gap donor material poly[(2,6-(4,8-bis(5-(2-ethylhexyl)thiophen-2-yl)-benzo[1,2-b:4,5-b']dithiophene))-alt-(5,5-(1',3'-di-2-thienyl-5',7'-bis(2-ethylhexyl)benzo[1',2'-c:4',5'-c']dithiophene-4,8-dione))] was blended.

The Parametric Decay Instability of Alfvén Waves in Turbulent Plasmas and the Applications in the Solar Wind

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

Shi, Mijie; Xiao, Chijie; Wang, Xiaogang

2017-06-10

We perform three-dimensional ideal magnetohydrodynamic (MHD) simulations to study the parametric decay instability (PDI) of Alfvén waves in turbulent plasmas and explore its possible applications in the solar wind. We find that, over a broad range of parameters in background turbulence amplitudes, the PDI of an Alfvén wave with various amplitudes can still occur, though its growth rate in turbulent plasmas tends to be lower than both the theoretical linear theory prediction and that in the non-turbulent situations. Spatial–temporal FFT analyses of density fluctuations produced by the PDI match well with the dispersion relation of the slow MHD waves. Thismore » result may provide an explanation of the generation mechanism of slow waves in the solar wind observed at 1 au. It further highlights the need to explore the effects of density variations in modifying the turbulence properties as well as in heating the solar wind plasmas.« less

Characterization of onset of parametric decay instability of lower hybrid waves

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

Baek, S. G.; Bonoli, P. T.; Parker, R. R.

2014-02-12

The goal of the lower hybrid current drive (LHCD) program on Alcator C-Mod is to develop and optimize ITER-relevant steady-state plasmas by controlling the current density profile. Using a 4×16 waveguide array, over 1 MW of LH power at 4.6 GHz has been successfully coupled to the plasmas. However, current drive efficiency precipitously drops as the line averaged density (nÐœ„{sub e}) increases above 10{sup 20}m{sup −3}. Previous numerical work shows that the observed loss of current drive efficiency in high density plasmas stems from the interactions of LH waves with edge/scrape-off layer (SOL) plasmas [Wallace et al., Physics of Plasmasmore » 19, 062505 (2012)]. Recent observations of parametric decay instability (PDI) suggest that non-linear effects should be also taken into account to fully characterize the parasitic loss mechanisms [Baek et al., Plasma Phys. Control Fusion 55, 052001 (2013)]. In particular, magnetic configuration dependent ion cyclotron PDIs are observed using the probes near nÐœ„{sub e}≈1.2×10{sup 20}m{sup −3}. In upper single null plasmas, ion cyclotron PDI is excited near the low field side separatrix with no apparent indications of pump depletion. The observed ion cyclotron PDI becomes weaker in inner wall limited plasmas, which exhibit enhanced current drive effects. In lower single null plasmas, the dominant ion cyclotron PDI is excited near the high field side (HFS) separatrix. In this case, the onset of PDI is correlated with the decrease in pump power, indicating that pump wave power propagates to the HFS and is absorbed locally near the HFS separatrix. Comparing the observed spectra with the homogeneous growth rate calculation indicates that the observed ion cyclotron instability is excited near the plasma periphery. The incident pump power density is high enough to overcome the collisional homogeneous threshold. For C-Mod plasma parameters, the growth rate of ion sound quasi-modes is found to be typically smaller by an order of magnitude than that of ion cyclotron quasi-modes. When considering the convective threshold near the plasma edge, convective growth due to parallel coupling rather than perpendicular coupling is likely to be responsible for the observed strength of the sidebands. To demonstrate the improved LHCD efficiency in high density plasmas, an additional launcher has been designed. In conjunction with the existing launcher, this new launcher will allow access to an ITER-like high single pass absorption regime, replicating the J{sub LH}(r) expected in ITER. The predictions from the time domain discharge scenarios, in which the two launchers are used, will be also presented.« less

Liquid crystalline perylene diimide outperforming nonliquid crystalline counterpart: higher power conversion efficiencies (PCEs) in bulk heterojunction (BHJ) cells and higher electron mobility in space charge limited current (SCLC) devices.

PubMed

Zhang, Youdi; Wang, Helin; Xiao, Yi; Wang, Ligang; Shi, Dequan; Cheng, Chuanhui

2013-11-13

In this work, we propose the application of liquid crystalline acceptors as a potential means to improve the performances of bulk heterojunction (BHJ) organic solar cells. LC-1, a structurally-simple perylene diimide (PDI), has been adopted as a model for thorough investigation. It exhibits a broad temperature range of liquid crystalline (LC) phase from 41 °C to 158 °C, and its LC properties have been characterized by differental scanning calorimetry (DSC), polarization optical microscopy (POM), and X-ray diffraction (XRD). The BHJ devices, using P3HT:LC-1 (1:2) as an organic photovoltaic active layer undergoing thermal annealing at 120 °C, shows an optimized efficiency of 0.94 %. By contrast, the devices based on PDI-1, a nonliquid crystalline PDI counterpart, only obtain a much lower efficiency of 0.22%. Atomic force microscopy (AFM) images confirm that the active layers composed of P3HT:LC-1 have smooth and ordered morphology. In space charge limited current (SCLC) devices fabricated via a spin-coating technique, LC-1 shows the intrinsic electron mobility of 2.85 × 10(-4) cm(2)/(V s) (at 0.3 MV/cm) which is almost 5 times that of PDI-1 (5.83 × 10(-5) cm(2)/(V s)) under the same conditions for thermal annealing at 120 °C.

Attaching NorA efflux pump inhibitors to methylene blue enhances antimicrobial photodynamic inactivation of Escherichia coli and Acinetobacter baumannii in vitro and in vivo.

PubMed

Rineh, Ardeshir; Bremner, John B; Hamblin, Michael R; Ball, Anthony R; Tegos, George P; Kelso, Michael J

2018-02-24

Resistance of bacteria to antibiotics is a public health concern worldwide due to the increasing failure of standard antibiotic therapies. Antimicrobial photodynamic inactivation (aPDI) is a promising non-antibiotic alternative for treating localized bacterial infections that uses non-toxic photosensitizers and harmless visible light to produce reactive oxygen species and kill microbes. Phenothiazinium photosensitizers like methylene blue (MB) and toluidine blue O are hydrophobic cations that are naturally expelled from bacterial cells by multidrug efflux pumps, which reduces their effectiveness. We recently reported the discovery of a NorA efflux pump inhibitor-methylene blue (EPI-MB) hybrid compound INF55-(Ac)en-MB that shows enhanced photodynamic inactivation of the Gram-positive bacterium methicillin-resistant Staphylococcus aureus (MRSA) relative to MB, both in vitro and in vivo. Here, we report the surprising observation that INF55-(Ac)en-MB and two related hybrids bearing the NorA efflux pump inhibitors INF55 and INF271 also show enhanced aPDI activity in vitro (relative to MB) against the Gram-negative bacteria Escherichia coli and Acinetobacter baumannii, despite neither species expressing the NorA pump. Two of the hybrids showed superior effects to MB in murine aPDI infection models. The findings motivate wider exploration of aPDI with EPI-MB hybrids against Gram-negative pathogens and more detailed studies into the molecular mechanisms underpinning their activity. Copyright © 2018 Elsevier Ltd. All rights reserved.

Investigation on principle of polarization-difference imaging in turbid conditions

NASA Astrophysics Data System (ADS)

Ren, Wei; Guan, Jinge

2018-04-01

We investigate the principle of polarization-difference imaging (PDI) of objects in optically scattering environments. The work is performed by both Marius's law and Mueller-Stokes formalism, and is further demonstrated by simulation. The results show that the object image is obtained based on the difference in polarization direction between the scatter noise and the target signal, and imaging performance is closely related to the choice of polarization analyzer axis. In addition, this study illustrates the potential of Stoke vector for promoting application of PDI system in the real world scene.

Three-factor response surface optimization of nano-emulsion formation using a microfluidizer.

PubMed

Sadeghpour Galooyak, Saeed; Dabir, Bahram

2015-05-01

Emulsification of sunflower oil in water by microfluidization was studied. Response surface methodology (RSM) and the central composite design (CCD) were applied to determine the effects of certain process parameters on performance of the apparatus for optimization of nano-emulsion fabrication. Influence of pressure, oil content and number of passes on the disruption of emulsions was studied. Quadratic multiple regression models were chosen for two available responses, namely Sauter mean diameter (SMD) and Polydispersity index (PdI). Analysis of variance (ANOVA) showed a high coefficient of determination (R(2)) value for both responses, confirming adjustment of the models with experimental data. The SMD and the PdI decreased as the pressure of emulsification increased from 408 to 762.3 bar for the oil content of 5 vol% and from 408 to 854.4 bar for the oil content of 13 vol%, and thereafter, increasing the pressure up to 952 bar led to increasing the both responses. The results implied that laminar elongational flow is the alternative disruption mechanism in addition to inertia in turbulence flow, especially at low treatment pressures. Both of responses improved with increase in number of passes from 2 to 4 cycles. The oil content depicted low effect on responses; however, interaction of this parameter with other regressors pointed remarkable impact. Also, the effect of pressure on Kolmogorov micro-scale was studied. The results implied that Kolmogorov equation did not take into account the over-processing and was applicable only for disruption of droplets in the inertial turbulent flow.

PEGylated non-ionic surfactant vesicles as drug delivery systems for Gambogenic acid.

PubMed

Lin, Tongyuan; Fang, Qingying; Peng, Daiyin; Huang, Xia; Zhu, Tingting; Luo, Qing; Zhou, Kai; Chen, Weidong

2013-01-01

Gambogenic acid (GNA), a popular Chinese traditional medicine, has its limitations of coming into use due to its low aqueous solubility and poor bioavailability. In this study, therefore, the PEGylated non-ionic surfactant vesicles drug delivery systems were prepared from biocompatible non-ionic surfactant of Span60, cholesterol and dicetyl phosphate (DCP) by the improved ethanol injection method, and were modified with a polyethylene glycol monostearate15 (PEG15-SA). PEG15-SA, as a biocompatible, non-toxic and non-immunogenic hydrophilic segment, was grafted onto the surface of colloidal niosomes carries to reduce the uptake by the reticuloendothelial system (RES), prolonging the circulation time and attaining higher entrapment efficiency. To our knowledge, this work is the first to report that PEG15-SA was applied to coating of niosomes for encapsulation of GNA. The optimized PEG-GNA-NISVs (P-GNA-NISVs) were characterized in terms of mean vesicles size, polydispersity index (PDI), Zeta potential and entrapment efficiency of the P-GNA-NISVs. The results showed that the mean diameter, PDI, Zeta potential, and the entrapment efficiency of the P-GNA-NISVs were 70.1 nm, 0.166, -44.3 mV and 87.74%, respectively. Furthermore, the release studies of GNA from PEGylated niosomes in vitro and the pharmacokinetics in vivo exhibited a prolonged release profile as studied over 24 h. In conclusion, the result suggests that P-GNA-NISVs prepared in this way not only have higher encapsulation capacity, more colloidal stability but also offer an approach that the PEGylated niosomes is a promising carrier for anticancer GNA.

Microcurrent transcutaneous electric nerve stimulation in painful diabetic neuropathy: a randomized placebo-controlled study.

PubMed

Gossrau, Gudrun; Wähner, Michael; Kuschke, Marion; Konrad, Birgit; Reichmann, Heinz; Wiedemann, Bärbel; Sabatowski, Rainer

2011-06-01

Diabetes is a common health care problem in western countries. Painful diabetic neuropathy (PDN) might be one of the consequences of long ongoing diabetes; it is estimated that approximately 20% of European diabetic patients suffer from PDN. Transcutaneous electrical nerve stimulation (TENS) is often used as additional pain treatment. However, recent studies show inconsistent results. We aimed to assess the effect of micro-TENS in reducing neuropathic pain in patients with PDN in a placebo-controlled, single-blinded, and randomized design. DESIGN/SETTING/PATIENTS/OUTCOME MEASURES: 22 diabetic patients have been treated with a micro-TENS therapy and 19 patients have been treated with a placebo therapy. Treatment duration was 4 weeks with three therapeutical settings per week. Standardized questionnaires (Pain Disability Index [PDI], neuropathic pain score [NPS], Center for Epidemiologic Studies Depression Scale [CES-D]) were used to assess pain intensity, pain disability, as well as quality of life at baseline at the end of the treatment period and 4 weeks after treatment termination. Patients with a minimum of 30% reduction in NPS were defined as therapy responders. After 4 weeks of treatment, 6/21 patients in the verum group vs 10/19 patients in the placebo group responded to therapy. The median PDI score after 4 weeks of treatment showed a reduction of 23% in the verum vs 25% in the placebo group. The differences did not reach statistical significance. The pain reduction with the applied transcutaneous electrotherapy regimen is not superior to a placebo treatment. Wiley Periodicals, Inc.

Influence of apple pomace inclusion on the process of animal feed pelleting.

PubMed

Maslovarić, Marijana D; Vukmirović, Đuro; Pezo, Lato; Čolović, Radmilo; Jovanović, Rade; Spasevski, Nedeljka; Tolimir, Nataša

2017-08-01

Apple pomace (AP) is the main by-product of apple juice production. Large amounts of this material disposed into landfills can cause serious environmental problems. One of the solutions is to utilise AP as animal feed. The aim of this study was to investigate the impact of dried AP inclusion into model mixtures made from conventional feedstuffs on pellet quality and pellet press performance. Three model mixtures, with different ratios of maize, sunflower meal and AP, were pelleted. Response surface methodology (RSM) was applied when designing the experiment. The simultaneous and interactive effects of apple pomace share (APS) in the mixtures, die thickness (DT) of the pellet press and initial moisture content of the mixtures (M), on pellet quality and production parameters were investigated. Principal component analysis (PCA) and standard score (SS) analysis were applied for comprehensive analysis of the experimental data. The increase in APS led to an improvement of pellet quality parameters: pellet durability index (PDI), hardness (H) and proportion of fines in pellets. The increase in DT and M resulted in pellet quality improvement. The increase in DT and APS resulted in higher energy consumption of the pellet press. APS was the most influential variable for PDI and H calculation, while APS and DT were the most influential variables in the calculation of pellet press energy consumption. PCA showed that the first two principal components could be considered sufficient for data representation. In conclusion, addition of dried AP to feed model mixtures significantly improved the quality of the pellets.

Long-Term Neurodevelopmental Outcome after Doxapram for Apnea of Prematurity.

PubMed

Ten Hove, Christine H; Vliegenthart, Roseanne J; Te Pas, Arjan B; Brouwer, Emma; Rijken, Monique; van Wassenaer-Leemhuis, Aleid G; van Kaam, Anton H; Onland, Wes

2016-01-01

Doxapram has been advocated as a treatment for persistent apnea of prematurity (AOP). To evaluate the effect of doxapram on long-term neurodevelopmental outcome in preterm infants as its safety still needs to be established. From a retrospective cohort of preterm infants with a gestational age (GA) <30 weeks and/or a birth weight <1,250 g, born between 2000 and 2010, infants treated with doxapram (n = 142) and a nontreated control group were selected (n = 284). Patient characteristics and clinical and neurodevelopmental outcome data at 24 months' corrected age were collected. Neurodevelopmental delay (ND) was defined as having a Mental or Psychomotor Developmental Index (MDI/PDI) <-1 standard deviation (SD), cerebral palsy, or a hearing or visual impairment. Odds ratios (OR) were calculated using multiple logistic regression analyses adjusting for potential confounders. Infants treated with doxapram had a lower GA compared to controls. The number of infants with a MDI or PDI <-1 SD was not different between the groups. The risk of the combined outcome death or ND was significantly lower in the doxapram group after adjusting for confounding factors (OR = 0.54, 95% CI: 0.37, 0.78). Doxapram-treated infants had a higher risk of bronchopulmonary dysplasia and patent ductus arteriosus, but a lower risk of spontaneous intestinal perforation. All other morbidities were not different between the groups. This study suggests that doxapram is not associated with an increased risk of ND. These findings need to be confirmed or refuted by a large, well-designed, placebo-controlled randomized trial. © 2016 The Author(s) Published by S. Karger AG, Basel.

Correlation of Salivary pH, Incidence of Dental Caries and Periodontal Status in Diabetes Mellitus Patients: A Cross-sectional Study.

PubMed

Seethalakshmi, C; Reddy, R C Jagat; Asifa, Nisha; Prabhu, S

2016-03-01

Diabetes mellitus is a chronic disease affecting many parts of the body. A number of oral diseases have been associated with diabetes mellitus with an increased risk of dental caries and periodontal disease. The aim of the study was to evaluate the salivary pH and incidence of dental caries and periodontal status in diabetes mellitus compared to that of the normal subjects. The study population consisted of 40 patients divided into 2 groups with group I comprising of 20 known diabetes mellitus patients and group II comprising of 20 non diabetic subjects as control group. The pH of the saliva was determined using a digital pH meter. Dental caries and periodontal status were assessed by DMFT and PDI indices respectively. There was a decrease in the mean salivary pH of 6.51 in the study group, compared to the normal mean salivary pH of 7.88 in the control group. The mean DMFT index was higher in the study group (8.10) when compared to that of control group (1.15). The mean PDI score was also higher in the study group (4.0) as compared to that of the control group (0.45). The results of the present study concluded that there was a significant relationship between the diabetes mellitus and increased incidence of dental caries and periodontitis and there was also a significant reduction in the salivary pH in diabetes mellitus patients, compared to that of non diabetic subjects.

Adjustment to chronic pain in back pain patients classified according to the motivational stages of chronic pain management.

PubMed

Zenker, Stefanie; Petraschka, Michael; Schenk, Michael; Reisshauer, Anett; Newie, Tanja; Hermanns, Kai; Wernecke, Klaus-Dieter; Spies, Claudia

2006-06-01

According to Prochaska's transtheoretical model, the Freiburg Questionnaire stages of chronic pain management (FQ-STAPM) were used to classify chronic back patients into 4 distinct motivational stages. The FQ-STAMP was completed by 163 chronic back pain patients. Pain chronicity was measured by the Mainz Pain Staging System; pain intensity was measured by the numeric rating scale. Healthcare system expenses were considered as number of consulted physicians, number of stays in hospital, and number of rehabilitation programs. As psychometric tests, the lower pain disability index (PDI), the Hospital Anxiety and Depression Scale (HADS), and a quality of life score (SF36) were used. Patients were in the following motivational stages: precontemplation in 30%, preparation in 19%, action in 30%, maintenance in 21%. The intensity of pain in the precontemplation stage patients was significantly higher compared to patients in the maintenance stage. A lower pain chronicity was related to a significantly higher motivation. Moreover, there was a significant increase in healthcare system expenses by the lesser motivated patients. Patients in the maintenance stage used significantly less opioids than patients in the precontemplation stage. The higher motivated patients had a significantly lower PDI, a significantly lower HADS, and a significantly higher quality of life compared to less motivated patients. The study indicates that the FQ-STAPM might be a useful tool to classify chronic back pain patients and to work out a strategy together with the patient relevant to the outcome of pain management among chronic back pain patients.

Correlation of Salivary pH, Incidence of Dental Caries and Periodontal Status in Diabetes Mellitus Patients: A Cross-sectional Study

PubMed Central

Reddy, R.C. Jagat; Asifa, Nisha; Prabhu, S.

2016-01-01

Introduction Diabetes mellitus is a chronic disease affecting many parts of the body. A number of oral diseases have been associated with diabetes mellitus with an increased risk of dental caries and periodontal disease. Aim The aim of the study was to evaluate the salivary pH and incidence of dental caries and periodontal status in diabetes mellitus compared to that of the normal subjects. Materials and Methods The study population consisted of 40 patients divided into 2 groups with group I comprising of 20 known diabetes mellitus patients and group II comprising of 20 non diabetic subjects as control group. The pH of the saliva was determined using a digital pH meter. Dental caries and periodontal status were assessed by DMFT and PDI indices respectively. Results There was a decrease in the mean salivary pH of 6.51 in the study group, compared to the normal mean salivary pH of 7.88 in the control group. The mean DMFT index was higher in the study group (8.10) when compared to that of control group (1.15). The mean PDI score was also higher in the study group (4.0) as compared to that of the control group (0.45). Conclusion The results of the present study concluded that there was a significant relationship between the diabetes mellitus and increased incidence of dental caries and periodontitis and there was also a significant reduction in the salivary pH in diabetes mellitus patients, compared to that of non diabetic subjects. PMID:27134992

Encountering epidemic effects of leaf spot disease (Alternaria brassicae) on Aloe vera by fungal biocontrol agents in agrifields-An ecofriendly approach.

PubMed

Ghosh, Swapan Kumar; Banerjee, Subhankar; Pal, Sujoy; Chakraborty, Niloy

2018-01-01

Aloe vera (L.) Burm.f. is a highly important and extensively cultivated medicinal plant and that is also extensively used in the cosmetic industry. It has been frequently reported to suffer from Alternaria leaf spot disease in various parts of the world. Various fungicides used to combat this disease, have deleterious effects on the environment and on pharmacologically important constituents of Aloe vera. To avoid the harmful effects of fungicides an ecofriendly approach has been adopted here. A weekly survey was conducted during 2013-2015 in and around North 24 Parganas (West Bengal) to obtain the percentage of disease index (PDI). For biological control of the disease, screening of the antagonistic efficacy of biocontrol agents was carried out through the in vitro dual-culture-plate method and scanning electron microscopy (SEM) was used to study the mechanism. The in vitro effects of fungicides on the radial growth of the pathogen were evaluated through the poison food method and were compared with potent antagonistic fungi. Field application of potent antagonistic fungi was conducted through the dip-and-spray method. The results showed that, the PDI peaked during the hot and humid conditions of May to September (76.57%-98.57%) but decreased during the winter, December-January (35.71-46.66%). Trichoderma asperellum exerted the greatest inhibition of the radial growth of A. brassicae acting through non volatile (70.39%) and volatile metabolites (72.17%). A SEM study confirmed the hyperparasitic nature of T. asperellum through hyphal coiling-T. asperellum was similar to 2% blitox-50 (73.92%) and better than 2% bavistin (59.77%) (in vitro). In agricultural field trials (2013-15), Trichoderma application restricted the disease to the smallest area (PDI 24.00-29.33%) in comparison to untreated plots (73.33%). In conclusion, saplings treated with the dip method (108 spores / mL) and sprayed 4 times with a spore suspension of biocontrol agents such as T. asperellum, T. viride and T. harzianum, standardized at a rate of 2.5 L / plot (36 sq ft) (108 spores/ mL) are suggested for the ecofriendly management of this epidemic leaf spot disease of Aloe vera in agricultural fields.

Encountering epidemic effects of leaf spot disease (Alternaria brassicae) on Aloe vera by fungal biocontrol agents in agrifields—An ecofriendly approach

PubMed Central

Banerjee, Subhankar; Pal, Sujoy; Chakraborty, Niloy

2018-01-01

Aloe vera (L.) Burm.f. is a highly important and extensively cultivated medicinal plant and that is also extensively used in the cosmetic industry. It has been frequently reported to suffer from Alternaria leaf spot disease in various parts of the world. Various fungicides used to combat this disease, have deleterious effects on the environment and on pharmacologically important constituents of Aloe vera. To avoid the harmful effects of fungicides an ecofriendly approach has been adopted here. A weekly survey was conducted during 2013–2015 in and around North 24 Parganas (West Bengal) to obtain the percentage of disease index (PDI). For biological control of the disease, screening of the antagonistic efficacy of biocontrol agents was carried out through the in vitro dual-culture-plate method and scanning electron microscopy (SEM) was used to study the mechanism. The in vitro effects of fungicides on the radial growth of the pathogen were evaluated through the poison food method and were compared with potent antagonistic fungi. Field application of potent antagonistic fungi was conducted through the dip-and-spray method. The results showed that, the PDI peaked during the hot and humid conditions of May to September (76.57%–98.57%) but decreased during the winter, December-January (35.71–46.66%). Trichoderma asperellum exerted the greatest inhibition of the radial growth of A. brassicae acting through non volatile (70.39%) and volatile metabolites (72.17%). A SEM study confirmed the hyperparasitic nature of T. asperellum through hyphal coiling-T. asperellum was similar to 2% blitox-50 (73.92%) and better than 2% bavistin (59.77%) (in vitro). In agricultural field trials (2013–15), Trichoderma application restricted the disease to the smallest area (PDI 24.00–29.33%) in comparison to untreated plots (73.33%). In conclusion, saplings treated with the dip method (108 spores / mL) and sprayed 4 times with a spore suspension of biocontrol agents such as T. asperellum, T. viride and T. harzianum, standardized at a rate of 2.5 L / plot (36 sq ft) (108 spores/ mL) are suggested for the ecofriendly management of this epidemic leaf spot disease of Aloe vera in agricultural fields. PMID:29579070

The role of protein disulfide isomerase in the post-ligation phase of β3 integrin-dependent cell adhesion.

PubMed

Leader, Avi; Mor-Cohen, Ronit; Ram, Ron; Sheptovitsky, Vera; Seligsohn, Uri; Rosenberg, Nurit; Lahav, Judith

2015-12-01

Protein disulfide isomerase (PDI) catalyzes disulfide bond exchange. It is crucial for integrin-mediated platelet adhesion and aggregation and disulfide bond exchange is necessary for αIIbβ3 and αvβ3 activation. However, the role of disulfide bond exchange and PDI in the post-ligation phase of αIIbβ3 and αvβ3 mediated cell adhesion has yet to be determined. To investigate a possible such role, we expressed wild type (WT) human αIIb and either WT human β3, or β3 harboring single or double cysteine to serine substitutions disrupting Cys473-Cys503 or Cys523-Cys544 bonds, in baby hamster kidney (BHK) cells, leading to expression of both human αIIbβ3 and a chimeric hamster/human αvβ3. Adhesion to fibrinogen-coated wells was studied in the presence or absence of bacitracin, a PDI inhibitor, with and without an αvβ3 blocker. Flow cytometry showed WT and mutant αIIbβ3 expression in BHK cells and indicated that mutated αIIbβ3 receptors were constitutively active while WT αIIbβ3 was inactive. Both αIIbβ3 and αvβ3 integrins, WT and mutants, mediated adhesion to fibrinogen as shown by reduced but still substantial adhesion following treatment with the αvβ3 blocker. Mutated αIIbβ3 integrins disrupted in the Cys523-Cys544 bond still depended on PDI for adhesion as shown by the inhibitory effect of bacitracin in the presence of the αvβ3 blocker. Mutated integrins disrupted in the Cys473-Cys503 bond showed a similar trend. PDI-mediated disulfide bond exchange plays a pivotal role in the post-ligation phase of αIIbβ3-mediated adhesion to fibrinogen, while this step in αvβ3-mediated adhesion is independent of disulfide exchange. Copyright © 2015 Elsevier Ltd. All rights reserved.

Neurodevelopmental outcome of infants with meconium aspiration syndrome: report of a study and literature review.

PubMed

Beligere, N; Rao, R

2008-12-01

There is a paucity of information on long-term outcome of infants who have suffered from meconium aspiration syndrome (MAS) in the neonatal period. We analyzed long-term developmental outcome data of 35 infants who were admitted to the neonatal intensive care unit (NICU) at the University of Illinois Hospital at Chicago (UICMC) with a diagnosis of MAS, and we reviewed the literature pertinent to the subject. The objective of the study was to assess the neurodevelopment status of MAS infants and compare the possible effects of different variables that are known to affect the later developmental outcome. The variables included mode of delivery, APGAR score, cord pH, mode of treatment, and neurological findings during the course of NICU. The infants were enrolled in the developmental follow-up program (DFUP) after discharge from the nursery for assessment of long-term developmental status and neurodevelopmental outcome. In order to assess the impact of the treatment on long-term outcome and compare our findings with previously published reports, we also reviewed the previously published literature on neurodevelopment outcome of infants treated for MAS (with different modalities) during the last three decades. Total of 35 infants with a diagnosis of MAS admitted to the NICU at UICMC were followed in the DFUP clinic for 3 years during January 1999 to September 2001. The medical records of these infants were reviewed for the mode of delivery, APGAR score, birth weight (BW), gestational age, mode of treatment during the neonatal period, and neurodevelopment status. 19/35 (54%) infants were delivered vaginally, 16/35 (46%) by cesarean section (C-section). All were treated in the delivery room using the standard resuscitation protocol. Following initial resuscitation, all except three required intubation and ventilation for varying duration. One infant required inhaled nitric oxide therapy, and two required extracorporeal membrane oxygenation treatment. Subsequent to discharge, the infants were evaluated in the clinic at 2 months of age, and then every 4 months up to 3 years. The developmental assessment of mental development index (MDI), psychomotor development index (PDI), and behavior rating scale (BRS) were obtained using the Bayley II infant motor scale, and neurodevelopment evaluation was performed using the Amiel-Tison technique. Speech evaluation was performed in infants >18 months using the Rossetti Infant-Toddler language scale. Infants were considered normal when MDI and PDI scores were >85 to 110; mildly delayed when scores were >70 to 84; and severely delayed if the scores were <69. In addition, neurological evaluation also confirmed the disability. The report is based on the final analysis of 29 infants. Data of six infants were not included in the final analysis because of incomplete information. The mean BW of the infants was 3269+/-671 g; mean gestational age was 39.5+/-3.1 weeks. The median APGAR score at 1' was 4, and at 5' was 6. Out of 29, 11 (38%) infants were normal. Out of 29, 2 infants (7%) had cerebral palsy (CP) and 4 (14%) had severe delay at 12 months of age. Out of 29, 2 who were neurologically disabled had PDI <69. Out of 29, 12 (41%) had mild delay in speech. No statistical difference in neurodevelopment was found in infants born vaginally or by C-section. Our findings show poor outcome (CP and global delay) in 21% of infants who suffered MAS, even though the majority of the infants (26/29) responded to conventional ventilator support alone. No difference was found in the outcome of infants between NSVD vs C-section delivery. These findings suggest that infants with the diagnosis of MAS manifest later neurodevelopmental delays, even if they respond well to conventional treatment. This abstract was presented at the Society for Pediatric Research Annual Meeting, 2000.

Pronounced Effects of a Triazine Core on Photovoltaic Performance-Efficient Organic Solar Cells Enabled by a PDI Trimer-Based Small Molecular Acceptor.

PubMed

Duan, Yuwei; Xu, Xiaopeng; Yan, He; Wu, Wenlin; Li, Zuojia; Peng, Qiang

2017-02-01

A novel-small molecular acceptor with electron-deficient 1,3,5-triazine as the core and perylene diimides as the arms is developed as the acceptor material for efficient bulk heterojunction organic solar cells with an efficiency of 9.15%. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Relationship between overweight-obesity and periodontal disease in Mexico.

PubMed

Zermeño-Ibarra, Jorge A; Delgado-Pastrana, Soledad; Patiño-Marín, Nuria; Loyola-Rodríguez, Juan P

2010-01-01

The aim of this study was to examine the association between overweight-obesity and periodontal disease in subjects who attended the clinic of Periodontics, Faculty of Dentistry, San Luis de Potosi, México. This was cross-sectional study involving 88 subjects--60 without overweight-obesity and 28 with overweight-obesity. The following clinical parameters were evaluated: dental bacterial plaque, index of calculus, gingivitis, probing depth and periodontal disease index (PDI). When comparing the group of subjects with overweight-obesity to the control, there were statistically significant differences in the variables calculus (p = 0.0015), gingivitis (p = 0.0050) and periodontal disease (p = 0.0154). Regarding the logistic regression analysis, the dependent variable was subjects with and without overweight-obesity and the independent variables were sex, age and periodontal disease. We found statistically significant differences (p = 0.0162) with OR = 3.16 in periodontal disease. Periodontal disease showed statistically significant differences in the group of subjects with overweight-obesity. The oral health of subjects with overweight-obesity should be supervised and checked in order to prevent oral alterations.

Effects of discontinuing coffee intake on iron deficient Guatemalan toddlers' cognitive development and sleep.

PubMed

Engle, P L; VasDias, T; Howard, I; Romero-Abal, M E; Quan de Serrano, J; Bulux, J; Solomons, N W; Dewey, K G

1999-01-01

Coffee is commonly given daily to toddlers in Guatemala. Possible negative effects of coffee ingestion on cognitive development and sleep patterns were assessed in 132 children 12-24 months of age who had received coffee for > 2 months and were iron deficient on at least one indicator. Children were stratified by initial hemoglobin (A= anemic, Hgb < 10.5 g/dl; NA = 'non-anemic', Hgb > or = 10.5 g/dl) and were randomly assigned to an experimental group (S = substitute consisting of sugar and coloring), and a control group (C = continuation of coffee) (42 C-NA; 53 S-NA; 18 C-A; and 19 S-A). Anemic children were provided Fe supplements for 2-3 months. Compliance was assessed every 2 weeks. After 5 months, testers masked to treatment group and anemia evaluated children with the Bayley Scales of Infant Development II in a central location. Scores were the Mental Development Index (MDI), the Psychomotor Development Index (PDI), and scales from the Behavior Rating Scale (BRS). The child's sleep in the previous 24 h was assessed with a set of standardized sleep questions to the care giver on the first visit and every 2 weeks thereafter. No significant effects of treatment on test scores or BRS ratings were found. In the 24 h period reported on at the final visit, children in the Substitute group slept more during the night and overall (night plus naps) than children in the Coffee group, a difference not found at the first visit. No differences were found in sleep difficulty or number of times waking at night. Women's reported coffee intake per day during pregnancy was associated with lower BRS ratings, even after controlling for SES and child age. The effects of postnatal coffee ingestion in Guatemala were seen for sleep duration, but not for cognitive development. Prenatal coffee ingestion was negatively associated with Behavior Rating Scales and should be investigated further.

Substrate dependent structure of adsorbed aryl isocyanides studied by sum frequency generation (SFG) spectroscopy.

PubMed

Ito, Mikio; Noguchi, Hidenori; Ikeda, Katsuyoshi; Uosaki, Kohei

2010-04-07

Effects of metal substrate on the bonding nature of isocyanide group of two aryl isocyanides, 1,4-phenylene diisocyanide (PDI) and 4-methylphenyl isocyanide (MPI), and tilt angle of MPI were examined by measuring sum frequency generation (SFG) spectra of the self-assembled monolayers (SAMs) of these molecules on Au, Pt, Ag, and Pd surfaces. The SFG peaks due to "metal bonded" and "free"-NC groups were resolved by comparing the SFG spectra of PDI with IR spectra obtained by DFT calculations and previous results of vibrational spectroscopy. Based on the peak positions of the "metal bonded"-NC, it is clarified that while PDI and MPI were adsorbed at top sites on Au, Ag, and Pt surfaces, they adsorbed at bridge sites on the Pd surface. The tilt angles of MPI were determined from the intensity ratio between the SFG peaks of C-H symmetric and asymmetric stretching vibrational modes of the CH(3) group. The tilt angles of the MPI SAMs were in the order of Pt < Pd < Ag < Au, reflecting the bonding nature between the -NC group and the substrate atoms.

17β-Estradiol Alters Oxidative Stress Response Protein Expression and Oxidative Damage in the Uterus

PubMed Central

Yuan, Lisi; Dietrich, Alicia K.; Nardulli, Ann M.

2014-01-01

The steroid hormone 17β-estradiol (E2) has profound effects on the uterus. However, with the E2-induced increase in uterine cell proliferation and metabolism comes increased production of reactive oxygen species (ROS). We examined the expression of an interactive network of oxidative stress response proteins including thioredoxin (Trx), Cu/Zn superoxide dismutase (SOD1), apurinic endonuclease (Ape1), and protein disulfide isomerase (PDI). We demonstrated that treatment of ovariectomized C57BL/6J female mice with E2 increased the mRNA and protein levels of Trx, but decreased SOD1 and Ape1 mRNA and protein expression. In contrast, E2 treatment increased PDI protein levels but had no effect on PDI transcript levels.Interestingly, E2 treatment also increased two markers of cellular damage, lipid peroxidation and protein carbonylation. Our studies suggest that the decreased expression of SOD1 and Ape1 caused by E2 treatment may in the long term result in disruption of ROS regulation and play a role in endometrial carcinogenesis. PMID:24103313

A Comprehensive Tutorial on In Vitro Characterization of New Photosensitizers for Photodynamic Antitumor Therapy and Photodynamic Inactivation of Microorganisms

PubMed Central

Maisch, Tim; Berneburg, Mark; Plaetzer, Kristjan

2013-01-01

In vitro research performed on eukaryotic or prokaryotic cell cultures usually represents the initial step for characterization of a novel photosensitizer (PS) intended for application in photodynamic therapy (PDT) of cancer or photodynamic inactivation (PDI) of microorganisms. Although many experimental steps of PS testing make use of the wide spectrum of methods readily employed in cell biology, special aspects of working with photoactive substances, such as the autofluorescence of the PS molecule or the requirement of light protection, need to be considered when performing in vitro experiments in PDT/PDI. This tutorial represents a comprehensive collection of operative instructions, by which, based on photochemical and photophysical properties of a PS, its uptake into cells, the intracellular localization and photodynamic action in both tumor cells and microorganisms novel photoactive molecules may be characterized for their suitability for PDT/PDI. Furthermore, it shall stimulate the efforts to expand the convincing benefits of photodynamic therapy and photodynamic inactivation within both established and new fields of applications and motivate scientists of all disciplines to get involved in photodynamic research. PMID:23762860

Photodynamic inactivation of antibiotic-resistant bacteria and biofilms by hematoporphyrin monomethyl ether.

PubMed

Liu, Chengcheng; Hu, Min; Ma, Dandan; Lei, Jin'e; Xu, Jiru

2016-02-01

The worldwide increase in bacterial antibiotic resistance has led to a search for alternative antibacterial therapies. A promising approach to killing antibiotic-resistant bacteria is photodynamic antimicrobial chemotherapy, which uses light in combination with a photosensitizer to induce a phototoxic reaction. We evaluated the photodynamic inactivation (PDI) efficiency of hematoporphyrin monomethyl ether (HMME) on antibiotic-resistant bacteria and biofilms. HMME exhibited no significant dark toxicity and provided dose-dependent inactivation of antibiotic-resistant bacteria and biofilms. After incubation with 100-μM HMME and irradiation with 72-J cm(-2) white light, 4.19-7.59 log10 reductions in survival were achieved in planktonic suspension. Antibiotic-resistant strains were as susceptible to PDI in biofilms as in planktonic suspensions, but the inactivation of bacterial cells in biofilms was attenuated. In addition, gram-positive bacterial strains and biofilms were more susceptible than gram-negative strains and biofilms to the PDI effect of HMME. Thus, HMME is a promising photosensitizer for the treatment of infectious diseases caused by antibiotic-resistant bacteria, especially gram-positive bacteria.

Cryogenic Temperature-dependent Refractive Index Measurements of N-BK7, BaLKN3, and SF15 for NOTES PDI

NASA Technical Reports Server (NTRS)

Frey, Bradley J.; Leviton, Douglas F.; Madison, Timothy J.

2007-01-01

In order to enable high quality lens designs using N-BK7, BaLKN3, and SF15 at cryogenic temperatures, we have measured the absolute refractive index of prisms of these three materials using the Cryogenic, High-Accuracy Refraction Measuring System (CHARMS) at NASA's Goddard Space Flight Center, as a function of both wavelength and temperature. For N-BK7, we report absolute refractive index and thermo-optic coefficient (dn/dT) at temperatures ranging from 50 to 300 K at wavelengths from 0.45 to 2.7 micrometers; for BaLKN3 we cover temperatures ranging from 40 to 300 K and wavelengths from 0.4 to 2.6 micrometers; for SF15 we cover temperatures ranging from 50 to 300 K and wavelengths from 0.45 to 2.6 micrometers. We compare our measurements with others in the literature and provide temperature-dependent Sellmeier coefficients based on our data to allow accurate interpolation of index to other wavelengths and temperatures. While we generally find good agreement (plus or minus 2 x 10(exp -4) for N-BK7, less than 1 x 10(exp -4) for the other materials) at room temperature between our measured values and those provided by the vendor, there is some variation between the datasheets provided with the prisms we measured and the catalog values published by the vendor. This underlines the importance of measuring the absolute refractive index of the material when precise knowledge of the refractive index is required.

Association of Impaired Linear Growth and Worse Neurodevelopmental Outcome in Infants with Single Ventricle Physiology: A Report from the Pediatric Heart Network Infant Single Ventricle Trial

PubMed Central

Ravishankar, Chitra; Zak, Victor; Williams, Ismee A.; Bellinger, David C.; Gaynor, J. William; Ghanayem, Nancy S.; Krawczeski, Catherine D.; Licht, Daniel J.; Mahony, Lynn; Newburger, Jane W.; Pemberton, Victoria L.; Williams, Richard V.; Sananes, Renee; Cook, Amanda L.; Atz, Teresa; Khaikin, Svetlana; Hsu, Daphne T.

2012-01-01

Objectives To describe neurodevelopmental outcomes in infants with single ventricle (SV) physiology and determine factors associated with worse outcomes. Study design Neurodevelopmental outcomes for infants with SV enrolled in a multicenter drug trial were assessed at 14 months of age using the Bayley Scales of Infant Development-II. Multivariable regression analysis was used to identify factors associated with worse outcomes. Results Neurodevelopmental testing was performed at 14±1 months in 170/185 subjects in the trial. Hypoplastic left heart syndrome was present in 59% and 75% had undergone the Norwood operation. Mean psychomotor (PDI) and mental developmental indices (MDI) were 80±18 and 96±14 respectively (normal 100±15, P<0.001 for each). Group-based trajectory analysis provided a two-group model (high” and “low”) for height z-score trajectory and brain type natriuretic peptide (BNP) trajectory. The predicted PDI scores were 15 points higher in the “high” height z-score trajectory compared with the “low” cluster (P<.001). A higher number of serious adverse events during the trial was associated with lower PDI scores (P=.02). The predicted MDI scores were 13–17 points lower in “low height trajectory- high BNP trajectory” group compared with the other three groups (P<.001). MDI scores were also lower in subjects who required extracorporeal membrane oxygenation during the neonatal hospitalization (P=.01) or supplemental oxygen at discharge (P=.01). Conclusions Neurodevelopmental outcome at 14 months of age is impaired in infants with SV physiology. Low height trajectory and high BNP trajectory were associated with worse neurodevelopmental outcomes. Efforts to improve nutritional status alone may not improve neurodevelopmental outcomes. PMID:22939929

Delusion proneness and emotion appraisal in individuals with high psychosis vulnerability.

PubMed

Szily, Erika; Kéri, Szabolcs

2013-01-01

Evidence suggests that emotional processes play an important role in the development of delusions. The aim of the present study was to investigate emotion appraisal in individuals with high and low psychosis proneness. We compared 30 individuals who experienced a transient psychotic episode followed by a complete remission with 30 healthy control volunteers. The participants received the Peters et al. Delusion Inventory (PDI) and the Scherer's Emotion Appraisal Questionnaire. We also assessed the IQ and the severity of depressive and anxiety symptoms. Results revealed that individuals with high psychosis proneness displayed increased PDI scores and more pronounced anxiety compared with individuals with low psychosis proneness. There was a specific pattern of emotion appraisal in individuals with high psychosis proneness. In the case of fear, they achieved higher scores for external causality and immorality, and lower scores for coping ability and self-esteem compared with individuals with low proneness. The PDI scores were weakly related to external causality (r = 0.41) and self-esteem (r = -0.37). In the case of sadness and joy, no emotion appraisal differences were found between participants with low and high proneness. These results suggest that individuals who had a history of psychotic breakdown and therefore exhibit high psychosis proneness display an altered appraisal of fear, emphasizing external circumstances, feeling less power to cope and experience low self-esteem. Patients remitted from a transient psychotic episode still exhibit milder forms of delusion proneness. Emotion appraisal for fear is related to delusion proneness. Clinicians should pay a special attention to self-esteem and attribution biases in psychosis-prone individuals. Copyright © 2011 John Wiley & Sons, Ltd.

Mechanisms to Explain the Elemental Composition of the Initial Aragonite Shell of Larval Oysters

NASA Astrophysics Data System (ADS)

Haley, Brian A.; Hales, Burke; Brunner, Elizabeth L.; Kovalchik, Kevin; Waldbusser, George G.

2018-04-01

Calcifying organisms face increasing stress from the changing carbonate chemistry of an acidifying ocean, particularly bivalve larvae that live in upwelling regions of the world, such as the coastal and estuarine waters of Oregon (USA). Arguably the first and most significant developmental hurdle faced by larval oysters is formation of their initial prodissoconch I (PDI) shell, upon which further ontological development depends. We measured the minor metal compositions (Sr/Ca, Mg/Ca) of this aragonitic PDI shell and of post-PDI larval Crassostrea gigas shell, as well as the water they were reared in, over ˜20 days for a May and an August cohort in 2011, during which time there was no period of carbonate under-saturation. After testing various methods, we successfully isolated the shell from organic tissue using a 5% active chlorine bleach solution. Elemental compositions (Sr, Mg, C, N) of the shells post-treatment showed that shell Sr/Ca ranged from 1.55 to 1.82 mmol/mol; Mg/Ca from 0.60 to 1.11 mmol/mol, similar to the few comparable published data for larval oyster aragonite compositions. We compare these data in light of possible biomineralization mechanisms: an amorphous calcium carbonate (ACC) path, an intercellular path, and a direct-from-seawater path to shell formation via biologically induced inorganic precipitation of aragonite. The last option provides a mechanistic explanation for: (1) the accelerated precipitation rates of biogenic calcification in the absence of a calcifying fluid; (2) consistently elevated precipitation rates at varying ambient-water saturation states; and (3) the high Ca-selectivity of the early larval calcification despite rapid precipitation rates.

Acceptor Percolation Determines How Electron-Accepting Additives Modify Transport of Ambipolar Polymer Organic Field-Effect Transistors.

PubMed

Ford, Michael J; Wang, Ming; Bustillo, Karen C; Yuan, Jianyu; Nguyen, Thuc-Quyen; Bazan, Guillermo C

2018-06-18

Organic field-effect transistors (OFETs) that utilize ambipolar polymer semiconductors can benefit from the ability of both electron and hole conduction, which is necessary for complementary circuits. However, simultaneous hole and electron transport in organic field-effect transistors result in poor ON/OFF ratios, limiting potential applications. Solution processing methods have been developed to control charge transport properties and transform ambipolar conduction to hole-only conduction. The electron-acceptor phenyl-C61-butyric acid methyl ester (PC 61 BM), when mixed in solution with an ambipolar semiconducting polymer, can reduce electron conduction. Unipolar p-type OFETs with high, well-defined ON/OFF ratios and without detrimental effects on hole conduction are achieved for a wide range of blend compositions, from 95:5 to 5:95 wt % semiconductor polymer:PC 61 BM. When introducing the alternative acceptor N, N'-bis(1-ethylpropyl)-3,4:9,10-perylenediimide (PDI), high ON/OFF ratios are achieved for 95:5 wt % semiconductor polymer:PDI; however, electron conduction increases for 50:50 and 5:95 wt % semiconductor polymer:PDI. As described within, we show that electron conduction is practically eliminated when additive domains do not percolate across the OFET channel, that is, electrons are "morphologically trapped". Morphologies were characterized by optical, electron, and atomic force microscopy as well as X-ray scattering techniques. PC 61 BM was substituted with an endohedral Lu 3 N fullerene, which enhanced contrast in electron microscopy and allowed for more detailed insight into the blend morphologies. Blends with alternative, nonfullerene acceptors further emphasize the importance of morphology and acceptor percolation, providing insights for such blends that control ambipolar transport and ON/OFF ratios.

Progress toward development of photodynamic vaccination against infectious/malignant diseases and photodynamic mosquitocides

NASA Astrophysics Data System (ADS)

Chang, Kwang Poo; Kolli, Bala K.; Fan, Chia-Kwung; Ng, Dennis K. P.; Wong, Clarence T. T.; Manna, Laura; Corso, Raffaele; Shih, Neng-Yao; Elliott, Robert; Jiang, X. P.; Shiao, Shin-Hong; Fu, Guo-Liang

2018-02-01

Photodynamic therapy (PDT) uses photosensitizers (PS) that are excited with light to generate ROS in the presence of oxygen for treating various diseases. PS also has the potential use as photodynamic insecticides (PDI) and for light-inactivation of Leishmania for photodynamic vaccination (PDV). PDT-inactivated Leishmania are non-viable, but remain immunologically competent as whole-cell vaccines against leishmaniasis, and as a universal carrier for delivery of add-on vaccines against other infectious and malignant diseases. We have screened novel PS, including Zn- and Si-phthalocyanines (PC) for differential PDT activities against Leishmania, insect and mammalian cells in vitro to assess their PDI and PDV potential. Here, Zn-PC were conjugated with various functional groups. The conjugates were examined for uptake by cells as a prerequisite for their susceptibility to light-inactivation. PDT sensitivity was found to vary with cell types and PS used. PDI potential of several PS was demonstrated by their mosquito larvicidal PDT activities in vitro. PDT-inactivated Leishmania were stored frozen for PDV in several ongoing studies: [1] Open label trial with 20 sick dogs for immunotherapy of canine leishmaniasis after chemotherapy in Naples, Italy. Clinical follow-up for >3 years indicate that the PDV prolongs their survival; [2] PDV of murine models with a human lung cancer vaccine showed dramatic tumor suppression; [3] Open label trial of multiple PDV via compassionate access to 4 advanced cancer patients showed no clinically adverse effects. Two subjects remain alive. Genetic modifications of Leishmania are underway to further enhance their safety and efficacy for PDV by installation of activable mechanisms for self-destruction and spontaneous light-emission.

Curcumin-encapsulated polymeric micelles suppress the development of colon cancer in vitro and in vivo.

PubMed

Yang, Xi; Li, Zhaojun; Wang, Ning; Li, Ling; Song, Linjiang; He, Tao; Sun, Lu; Wang, Zhihan; Wu, Qinjie; Luo, Na; Yi, Cheng; Gong, Changyang

2015-05-18

To develop injectable formulation and improve the stability of curcumin (Cur), Cur was encapsulated into monomethyl poly (ethylene glycol)-poly (ε-caprolactone)-poly (trimethylene carbonate) (MPEG-P(CL-co-TMC)) micelles through a single-step solid dispersion method. The obtained Cur micelles had a small particle size of 27.6 ± 0.7 nm with polydisperse index (PDI) of 0.11 ± 0.05, drug loading of 14.07 ± 0.94%, and encapsulation efficiency of 96.08 ± 3.23%. Both free Cur and Cur micelles efficiently suppressed growth of CT26 colon carcinoma cells in vitro. The results of in vitro anticancer studies confirmed that apoptosis induction and cellular uptake on CT26 cells had completely increased in Cur micelles compared with free Cur. Besides, Cur micelles were more effective in suppressing the tumor growth of subcutaneous CT26 colon in vivo, and the mechanisms included the inhibition of tumor proliferation and angiogenesis and increased apoptosis of tumor cells. Furthermore, few side effects were found in Cur micelles. Overall, our findings suggested that Cur micelles could be a stabilized aqueous formulation for intravenous application with improved antitumor activity, which may be a potential treatment strategy for colon cancer in the future.

Preparation of a novel lipid-core micelle using a low-energy emulsification method.

PubMed

Fritz, Hans F; Ortiz, Andrea C; Velaga, Sitaram P; Morales, Javier O

2018-04-16

High-energy methods for the manufacturing of nanomedicines are widely used; however, interest in low-energy methods is increasing due to their simplicity, better control over the process, and energy-saving characteristics during upscaling. Here, we developed a novel lipid-core micelle (LCM) as a nanocarrier to encapsulate a poorly water-soluble drug, nifedipine (NFD), by hot-melt emulsification, a low-energy method. LCMs are self-assembling colloidal particles composed of a hydrophobic core and a hydrophilic shell. Hybrid materials, such as Gelucire 44/14, are thus excellent candidates for their preparation. We characterized the obtained nanocarriers for their colloidal properties, drug loading and encapsulation efficiency, liquid state, stability, and drug release. The low-energy method hot-melt emulsification was successfully adapted for the manufacturing of small and narrowly dispersed LCMs. The obtained LCMs had a small average size of ~ 11 nm and a narrow polydispersity index (PDI) of 0.228. These nanocarriers were able to increase the amount of NFD dispersible in water more than 700-fold. Due to their sustained drug release profile and the PEGylation of Gelucire 44/14, these nanocarriers represent an excellent starting point for the development of drug delivery systems designed for long circulation times and passive targeting.

Sequential two-photon double ionization of noble gases by circularly polarized XUV radiation

NASA Astrophysics Data System (ADS)

Gryzlova, E. V.; Grum-Grzhimailo, A. N.; Kuzmina, E. I.; Strakhova, S. I.

2014-10-01

Photoelectron angular distributions (PADs) and angular correlations between two emitted electrons in sequential two-photon double ionization (2PDI) of atoms by circularly polarized radiation are studied theoretically. In particular, the sequential 2PDI of the valence n{{p}6} shell in noble gas atoms (neon, argon, krypton) is analyzed, accounting for the first-order corrections to the dipole approximation. Due to different selection rules in ionization transitions, the circular polarization of photons causes some new features of the cross sections, PADs and angular correlation functions in comparison with the case of linearly polarized photons.

The Paleolimnological Record of the North Atlantic Oscillation: Magnetic Properties and Diatom Counts from Hemlock and Conesus Lakes, Western New York State

NASA Astrophysics Data System (ADS)

Chaisson, W. P.; Arnold, M. R.; Cottrell, R. D.

2002-05-01

Between 1900 and 1930 CE when the NAO index showed large amplitude positive excursions, but the AO index varied at very small amplitudes, drought conditions frequently prevailed in western New York state according the Palmer Drought Index (PDI). Since 1970, when both the NAO and the AO indices show large and progressively increasing positive excursions, the PDI has been generally positive, indicating moisture surpluses in the region. Magnetic properties, including coercivity of remanence, have been measured and the diatoms have been enumerated in sediments from two gravity cores collected from Hemlock and Conesus Lakes. The sediments date from ~1875 CE in the Hemlock core and ~1923 CE in the Conesus core. Variations in magnetic grain-size are interpreted from the coercivity of remanence, with lower coercivity of remanence associated with large grain size. The primary productivity of lakes is interpreted from the Lake Trophic Status Index (LTSI), which is calculated based on known ecologies of several diatom species. In both lakes we find that larger magnetic grain size is associated with greater productivity in the lakes. In the Hemlock core, through the interval corresponding to 1913-1943 coercivity of remanence values declined to 281-259 Oersteds, from late 19th century values that were >350 Oersteds. The bottom of the Conesus core (1923-1938 CE) has the lowest coercivity of remanance values in the record (309-317 Oersteds). LTSI values in the Hemlock samples increase as remanence of coercivity values decline between 1888 and 1920 CE. This reflects an increase in the abundance of the mesoeutrophic Tabellaria fenestrata during this interval. In the Conesus samples the agreement between coercivity of remanence and LTSI is quite close. The range of variation in both LTSI and magnetic grain size is smaller in Conesus than in Hemlock Lake. The diatom assemblage is also quite different in Conesus, dominated by eutrophic Aulacosiera granulata, which are rare or absent at Hemlock Lake. The Hemlock basin is much steeper than than that of Conesus and its water level fluctuates more extremely because it is the reservoir for the city of Rochester. Hemlock Lake is oligotrophic and its drainage basin is heavily forested and lightly populated. Conesus Lake is eutrophic, its shores lined with cottages and the basin is heavily agricultural. In spite of these differences in both natural conditions and anthropogenic factors, the LTSI and magnetic measurements of the two lakes share variance, ostensibly forced by regional climate change. Initial results suggest that the shared component of variance in these proxy indicators can predict variations in regional drought intensity. Regional drought intensity, in turn, seems associated with an uncoupling of AO and NAO variation.

Clinical research on intelligence seven needle therapy treated infants with brain damage syndrome.

PubMed

Liu, Zhen-Huan; Li, Ye-Rong; Lu, Yong-Lin; Chen, Jie-Kui

2016-06-01

To assess whether the intelligence seven needle therapy administered in infants with perinatal brain damage syndrome (BDS) as early intervention would improve patients' neural development. A randomized controlled trial was conducted. Sixty-four infants with BDS were randomly assigned to two groups: the comprehensive group and the control group. Both groups received routine early intervention; in addition, the comprehensive group received intelligence seven needle therapy. Before and after treatment, the Bayley Scale of Infant Development (BSID), Gesell Developmental Schedules, Gross Motor Function Measure (GMFM), transcranial doppler ultrasound (TCD), and cranial imaging examination were tested for contrast. After treatment, the comprehensive group showed significant difference in the Mental Development Index (MDI) scores of BSID compared with the control group (P<0.05), however, no significant discrepancy in psychomotor development index (PDI,P>0.05) was observed. The children's development quotients (DQ) of the comprehensive group exhibited a significant superiority in improving the social adaptation DQ of Gesell Developmental Schedules compared with the control group (P<0.01), as well as GMFM and linguistic and social intercourse (P<0.05). Again, no discrepancy in the fine movement DQ was found (P>0.05). The total scores of GMFM in the comprehensive group were higher than those in the control group (P<0.05). Comparing the two groups, the comprehensive group showed a significantly greater recovery rate than the control group on TCD after treatment (P<0.05). After 6-month follow-up, some recovery in both groups, specifically on broadening of brain outside space by cranial imaging examination were observed. The comprehensive group demonstrated a significantly greater recovery rate than the control group (P<0.05). The developmental level of intelligence, motion function, linguistic competence and social intercourse can be promoted for infants with perinatal BDS by treating with the intelligence seven needle therapy. This approach can improve the brain blood supply and promote the growth of frontal and parietal lobes.

Polymorphisms in ATP-binding cassette transporters associated with maternal methylmercury disposition and infant neurodevelopment in mother-infant pairs in the Seychelles Child Development Study

PubMed Central

Engström, Karin; Love, Tanzy M; Watson, Gene E; Zareba, Grazyna; Yeates, Alison; Wahlberg, Karin; Alhamdow, Ayman; Thurston, Sally W; Mulhern, Maria; McSorley, Emeir M; Strain, JJ; Davidson, Philip W; Shamlaye, Conrad F; Myers, GJ; Rand, Matthew D; van Wijngaarden, Edwin; Broberg, Karin

2016-01-01

Background ATP-binding cassette (ABC) transporters have been associated with methylmercury (MeHg) toxicity in experimental animal models. Aims To evaluate the association of single nucleotide polymorphisms (SNPs) in maternal ABC transporter genes with 1) maternal hair MeHg concentrations during pregnancy and 2) child neurodevelopmental outcomes. Materials and methods Nutrition Cohort 2 (NC2) is an observational mother-child cohort recruited in the Republic of Seychelles from 2008–2011. Total mercury (Hg) was measured in maternal hair growing during pregnancy as a biomarker for prenatal MeHg exposure (N=1313) (mean 3.9 ppm). Infants completed developmental assessments by Bayley Scales of Infant Development II (BSID-II) at 20 months of age (N=1331). Genotyping for fifteen SNPs in ABCC1, ABCC2 and ABCB1 was performed for the mothers. Results Seven of fifteen ABC SNPs (ABCC1 rs11075290, rs212093, and rs215088; ABCC2 rs717620; ABCB1 rs10276499, rs1202169, and rs2032582) were associated with concentrations of maternal hair Hg (p<0.001 to 0.013). One SNP (ABCC1 rs11075290) was also significantly associated with neurodevelopment; children born to mothers with rs11075290 CC genotype (mean hair Hg 3.6 ppm) scored on average 2 points lower on the Mental Development Index (MDI) and 3 points lower on the Psychomotor Development Index (PDI) than children born to mothers with TT genotype (mean hair Hg 4.7 ppm) while children with the CT genotype (mean hair Hg 4.0 ppm) had intermediate BSID scores. Discussion Genetic variation in ABC transporter genes was associated with maternal hair Hg concentrations. The implications for MeHg dose in the developing child and neurodevelopmental outcomes need to be further investigated. PMID:27262785

Polymorphisms in ATP-binding cassette transporters associated with maternal methylmercury disposition and infant neurodevelopment in mother-infant pairs in the Seychelles Child Development Study.

PubMed

Engström, Karin; Love, Tanzy M; Watson, Gene E; Zareba, Grazyna; Yeates, Alison; Wahlberg, Karin; Alhamdow, Ayman; Thurston, Sally W; Mulhern, Maria; McSorley, Emeir M; Strain, J J; Davidson, Philip W; Shamlaye, Conrad F; Myers, G J; Rand, Matthew D; van Wijngaarden, Edwin; Broberg, Karin

2016-09-01

ATP-binding cassette (ABC) transporters have been associated with methylmercury (MeHg) toxicity in experimental animal models. To evaluate the association of single nucleotide polymorphisms (SNPs) in maternal ABC transporter genes with 1) maternal hair MeHg concentrations during pregnancy and 2) child neurodevelopmental outcomes. Nutrition Cohort 2 (NC2) is an observational mother-child cohort recruited in the Republic of Seychelles from 2008-2011. Total mercury (Hg) was measured in maternal hair growing during pregnancy as a biomarker for prenatal MeHg exposure (N=1313) (mean 3.9ppm). Infants completed developmental assessments by Bayley Scales of Infant Development II (BSID-II) at 20months of age (N=1331). Genotyping for fifteen SNPs in ABCC1, ABCC2 and ABCB1 was performed for the mothers. Seven of fifteen ABC SNPs (ABCC1 rs11075290, rs212093, and rs215088; ABCC2 rs717620; ABCB1 rs10276499, rs1202169, and rs2032582) were associated with concentrations of maternal hair Hg (p<0.001 to 0.013). One SNP (ABCC1 rs11075290) was also significantly associated with neurodevelopment; children born to mothers with rs11075290 CC genotype (mean hair Hg 3.6ppm) scored on average 2 points lower on the Mental Development Index (MDI) and 3 points lower on the Psychomotor Development Index (PDI) than children born to mothers with TT genotype (mean hair Hg 4.7ppm) while children with the CT genotype (mean hair Hg 4.0ppm) had intermediate BSID scores. Genetic variation in ABC transporter genes was associated with maternal hair Hg concentrations. The implications for MeHg dose in the developing child and neurodevelopmental outcomes need to be further investigated. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Improving the water solubility and antimicrobial activity of silymarin by nanoencapsulation.

PubMed

Lee, Ji-Soo; Hong, Da Young; Kim, Eun Suh; Lee, Hyeon Gyu

2017-06-01

The aims of this study were to improve the water solubility and antimicrobial activity of milk thistle silymarin by nanoencapsulation and to assess the functions of silymarin nanoparticle-containing film as an antimicrobial food-packaging agent. Silymarin nanoparticles were prepared using water-soluble chitosan (WCS) and poly-γ-glutamic acid (γ-PGA). As the WCS and silymarin concentrations increased, particle size and polydispersity index (PDI) significantly increased. Nanoencapsulation significantly improved the water solubility of silymarin 7.7-fold. Antimicrobial activity of silymarin was effectively improved when silymarin was entrapped within the nanocapsule compared to when it was not entrapped. Films incorporating silymarin nanoparticles had better antimicrobial activity than films incorporating free silymarin. The results suggest that silymarin nanoparticles have applications in antimicrobial food additives and food packing. Copyright © 2017 Elsevier B.V. All rights reserved.

Influence of milling time on fineness of Centella Asiatica particle size produced using planetary ball mill

NASA Astrophysics Data System (ADS)

Borhan, M. Z.; Ahmad, R.; Rusop, M.; Abdullah, S.

2012-11-01

Centella Asiatica (C. Asiatica)contains asiaticoside as bioactive constituent which can be potentially used in skin healing process. Unfortunately, the normal powders are difficult to be absorbed by the body effectively. In order to improve the value of use, nano C. Asiatica powder was prepared. The influence of milling time was carried out at 0.5, 2, 4, 6, 8 hours and 10 hours. The effect of ball milling at different times was characterized using particles size analysis and FTIR Spectroscopy. The fineness of ground product was evaluated by recording the z-Average (nm), undersize distribution and polydispersity index (PdI). The results show that the smallest size particles by mean is 233 nm while FTIR spectra shows that there is no changing in the major component in the C. Asiatica powders with milling time.

Coordination Polymerization of Renewable 3-Methylenecyclopentene with Rare-Earth-Metal Precursors.

PubMed

Liu, Bo; Li, Shihui; Wang, Meiyan; Cui, Dongmei

2017-04-10

Coordination polymerization of renewable 3-methylenecyclopentene has been investigated for the first time using rare-earth metal-based precursors bearing various bulky ligands. All the prepared complexes catalyze controllable polymerization of 3-methylenecyclopentene into high molecular weight polymers, of which the NPN- and NSN-tridentate non-Cp ligated lutetium-based catalytic systems exhibited extremely high activities up to 11 520 kg/(mol Lu ⋅h) in a dilute toluene solution (3.2 g/100 mL) at room temperature. The resultant polymers have pure 1,4-regioregularity (>99 %) and tailorable number average molecular weights (1-20×10 4 ) with narrow molecular weight distributions (polydispersity index (PDI)=1.45-1.79). DFT simulations were employed to study the polymerization mechanism and stereoregularity control. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Extreme ultraviolet interferometry

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

Goldberg, Kenneth A.

EUV lithography is a promising and viable candidate for circuit fabrication with 0.1-micron critical dimension and smaller. In order to achieve diffraction-limited performance, all-reflective multilayer-coated lithographic imaging systems operating near 13-nm wavelength and 0.1 NA have system wavefront tolerances of 0.27 nm, or 0.02 waves RMS. Owing to the highly-sensitive resonant reflective properties of multilayer mirrors and extraordinarily tight tolerances set forth for their fabrication, EUV optical systems require at-wavelength EUV interferometry for final alignment and qualification. This dissertation discusses the development and successful implementation of high-accuracy EUV interferometric techniques. Proof-of-principle experiments with a prototype EUV point-diffraction interferometer for themore » measurement of Fresnel zoneplate lenses first demonstrated sub-wavelength EUV interferometric capability. These experiments spurred the development of the superior phase-shifting point-diffraction interferometer (PS/PDI), which has been implemented for the testing of an all-reflective lithographic-quality EUV optical system. Both systems rely on pinhole diffraction to produce spherical reference wavefronts in a common-path geometry. Extensive experiments demonstrate EUV wavefront-measuring precision beyond 0.02 waves RMS. EUV imaging experiments provide verification of the high-accuracy of the point-diffraction principle, and demonstrate the utility of the measurements in successfully predicting imaging performance. Complementary to the experimental research, several areas of theoretical investigation related to the novel PS/PDI system are presented. First-principles electromagnetic field simulations of pinhole diffraction are conducted to ascertain the upper limits of measurement accuracy and to guide selection of the pinhole diameter. Investigations of the relative merits of different PS/PDI configurations accompany a general study of the most significant sources of systematic measurement errors. To overcome a variety of experimental difficulties, several new methods in interferogram analysis and phase-retrieval were developed: the Fourier-Transform Method of Phase-Shift Determination, which uses Fourier-domain analysis to improve the accuracy of phase-shifting interferometry; the Fourier-Transform Guided Unwrap Method, which was developed to overcome difficulties associated with a high density of mid-spatial-frequency blemishes and which uses a low-spatial-frequency approximation to the measured wavefront to guide the phase unwrapping in the presence of noise; and, finally, an expedient method of Gram-Schmidt orthogonalization which facilitates polynomial basis transformations in wave-front surface fitting procedures.« less

Autoinducer-2 Quorum Sensing Contributes to Regulation of Microcin PDI in Escherichia coli

PubMed Central

Lu, Shao-Yeh; Zhao, Zhe; Avillan, Johannetsy J.; Liu, Jinxin; Call, Douglas R.

2017-01-01

The Escherichia coli quorum sensing (QS) signal molecule, autoinducer-2 (AI-2), reaches its maximum concentration during mid-to-late growth phase after which it quickly degrades during stationary phase. This pattern of AI-2 concentration coincides with the up- then down-regulation of a recently described microcin PDI (mccPDI) effector protein (McpM). To determine if there is a functional relationship between these systems, a prototypical mccPDI-expressing strain of E. coli 25 was used to generate ΔluxS, ΔlsrACDBFG (Δlsr), and ΔlsrR mutant strains that are deficient in AI-2 production, transportation, and AI-2 transport regulation, respectively. Trans-complementation, RT-qPCR, and western blot assays were used to detect changes of microcin expression and synthesis under co-culture and monoculture conditions. Compared to the wild-type strain, the AI-2-deficient strain (ΔluxS) and -uptake negative strain (Δlsr) were >1,000-fold less inhibitory to susceptible bacteria (P < 0.05). With in trans complementation of luxS, the AI-2 deficient mutant reduced the susceptible E. coli population by 4-log, which was within 1-log of the wild-type phenotype. RT-qPCR and western blot results for the AI-2 deficient E. coli 25 showed a 5-fold reduction in mcpM transcription with an average 2-h delay in McpM synthesis. Furthermore, overexpression of sRNA micC and micF (both involved in porin protein regulation) was correlated with mcpM regulation, consistent with a possible link between QS and mcpM regulation. This is the direct first evidence that microcin regulation can be linked to quorum sensing in a Gram-negative bacterium. PMID:29312248

Potassium Iodide Potentiates Broad-Spectrum Antimicrobial Photodynamic Inactivation Using Photofrin.

PubMed

Huang, Liyi; Szewczyk, Grzegorz; Sarna, Tadeusz; Hamblin, Michael R

2017-04-14

It is known that noncationic porphyrins such as Photofrin (PF) are effective in mediating antimicrobial photodynamic inactivation (aPDI) of Gram-positive bacteria or fungi. However, the aPDI activity of PF against Gram-negative bacteria is accepted to be extremely low. Here we report that the nontoxic inorganic salt potassium iodide (KI) at a concentration of 100 mM when added to microbial cells (10 8 /mL) + PF (10 μM hematoporphyrin equivalent) + 415 nm light (10 J/cm 2 ) can eradicate (>6 log killing) five different Gram-negative species (Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Proteus mirabilis, and Acinetobacter baumannii), whereas no killing was obtained without KI. The mechanism of action appears to be the generation of microbicidal molecular iodine (I 2 /I 3 - ) as shown by comparable bacterial killing when cells were added to the mixture after completion of illumination and light-dependent generation of iodine as detected by the formation of the starch complex. Gram-positive methicillin-resistant Staphylococcus aureus is much more sensitive to aPDI (200-500 nM PF), and in this case potentiation by KI may be mediated mainly by short-lived iodine reactive species. The fungal yeast Candida albicans displayed intermediate sensitivity to PF-aPDI, and killing was also potentiated by KI. The reaction mechanism occurs via singlet oxygen ( 1 O 2 ). KI quenched 1 O 2 luminescence (1270 nm) at a rate constant of 9.2 × 10 5 M -1 s -1 . Oxygen consumption was increased when PF was illuminated in the presence of KI. Hydrogen peroxide but not superoxide was generated from illuminated PF in the presence of KI. Sodium azide completely inhibited the killing of E. coli with PF/blue light + KI.

Cooperative Protein Folding by Two Protein Thiol Disulfide Oxidoreductases and ERO1 in Soybean1[OPEN

PubMed Central

Okuda, Aya; Masuda, Taro; Koishihara, Katsunori; Mita, Ryuta; Iwasaki, Kensuke; Hara, Kumiko; Naruo, Yurika; Hirose, Akiho; Tsuchi, Yuichiro

2016-01-01

Most proteins produced in the endoplasmic reticulum (ER) of eukaryotic cells fold via disulfide formation (oxidative folding). Oxidative folding is catalyzed by protein disulfide isomerase (PDI) and PDI-related ER protein thiol disulfide oxidoreductases (ER oxidoreductases). In yeast and mammals, ER oxidoreductin-1s (Ero1s) supply oxidizing equivalent to the active centers of PDI. In this study, we expressed recombinant soybean Ero1 (GmERO1a) and found that GmERO1a oxidized multiple soybean ER oxidoreductases, in contrast to mammalian Ero1s having a high specificity for PDI. One of these ER oxidoreductases, GmPDIM, associated in vivo and in vitro with GmPDIL-2, was unable to be oxidized by GmERO1a. We therefore pursued the possible cooperative oxidative folding by GmPDIM, GmERO1a, and GmPDIL-2 in vitro and found that GmPDIL-2 synergistically accelerated oxidative refolding. In this process, GmERO1a preferentially oxidized the active center in the a′ domain among the a, a′, and b domains of GmPDIM. A disulfide bond introduced into the active center of the a′ domain of GmPDIM was shown to be transferred to the active center of the a domain of GmPDIM and the a domain of GmPDIM directly oxidized the active centers of both the a or a′ domain of GmPDIL-2. Therefore, we propose that the relay of an oxidizing equivalent from one ER oxidoreductase to another may play an essential role in cooperative oxidative folding by multiple ER oxidoreductases in plants. PMID:26645455

The Paradox of Pelvic Exenteration: The Interaction of Clinical and Psychological Variables.

PubMed

Arnaboldi, Paola; Santoro, Luigi; Mazzocco, Ketti; Oliveri, Serena; Maggioni, Angelo; Pravettoni, Gabriella

2015-10-01

To text the feasibility of a psychological intervention package administered to 49 pelvic exenteration candidates, aimed at evaluating the preoperative prevalence of psychological distress and assessing the presence of any correlation between preoperative psychological distress and clinical variables such as pain and hospitalization length. Patients were referred to the psychology unit from the very beginning of their clinical pathway and were administered the Psychological Distress Inventory (PDI) and the Mini-Mental Adjustment to Cancer (Mini-MAC) questionnaire at prehospital admission. Patients presenting with a significant level of distress received nonstandardized psychological support. Statistical analyses were performed to detect the presence of any correlation between psychological variables at prehospital admission and clinical outcomes. The 40% of patients had significant levels of distress at prehospital admission (PDI ≥ 30). As regards Mini-MAC, the mean value of fighting spirit attitude and fatalism was higher in our sample than in the normative sample of the Mini-MAC validation study in the Italian cancer population. Their anxious preoccupation attitude was lower. There were no correlations between clinical and psychological variables: level of postsurgery pain was higher (3.7) in the subgroup of patients with presurgery PDI < 30 compared with those with PDI ≥ 30 (3.5). However, this difference was not statistically significant (P = 1.00). Considering hospitalization length, the above described trend was similar. Although highly distressed, pelvic exenteration candidates show an adaptive range of coping mechanisms. This calls for a greater effort in studying the complexity of their psychoemotional status to provide them with the best multidisciplinary care. Extensive study of the real effectiveness of psychological intervention is warranted: randomized clinical trials could help in detecting the presence of any correlation between clinical and psychological variables in a multidisciplinary approach.

Purification and biochemical characterization of native ERp29 from rat liver

PubMed Central

2004-01-01

ERp29 is a recently characterized resident of the ER (endoplasmic reticulum) lumen that has broad biological significance, being expressed ubiquitously and abundantly in animal cells. As an apparent housekeeper, ERp29 is thought to be a general folding assistant for secretory proteins and to probably function as a PDI (protein disulphide isomerase)-like molecular chaperone. In the present paper, we report the first purification to homogeneity and direct functional analysis of native ERp29, which has led to the unexpected finding that ERp29 lacks PDI-like folding activities. ERp29 was purified 4800-fold in non-denaturing conditions exploiting an unusual affinity for heparin. Two additional biochemical hallmarks that will assist the classification of ERp29 homologues were identified, namely the idiosyncratic behaviours of ERp29 on size-exclusion chromatography (Mrmonomeric mass). In contrast with PDI and parallel-purified co-residents (calreticulin, ERp60), native ERp29 lacked classical chaperone, disulphide reductase and isomerase, and calcium-binding activities. In the chaperone assays, ERp29 neither protected substrate proteins against thermal aggregation nor interacted stably with chemically denatured proteins as detected by cross-linking. ERp29 also did not exhibit helper activity toward calreticulin (chaperone) or PDI and ERp60 (disulphide reductase). By refuting long-standing predictions about chaperone activity, these results expose ERp29 as a functionally distinct member of the ER machinery and prompt a revised hypothesis that ERp29 acts as a non-classical folding assistant. The native preparation and biochemical hallmarks established here provide a useful foundation for ongoing efforts to resolve the functional orphan status of ERp29. PMID:15500441

NIR-labeled perfluoropolyether nanoemulsions for drug delivery and imaging

PubMed Central

O’Hanlon, Claire E.; Amede, Konjit G.; O’Hear, Meredith R.; Janjic, Jelena M.

2012-01-01

Theranostic nanoparticle development recently took center stage in the field of drug delivery nanoreagent design. Theranostic nanoparticles combine therapeutic delivery systems (liposomes, micelles, nanoemulsions, etc.) with imaging reagents (MRI, optical, PET, CT). This combination allows for non-invasive in vivo monitoring of therapeutic nanoparticles in diseased organs and tissues. Here, we report a novel perfluoropolyether (PFPE) nanoemulsion with a water-insoluble lipophilic drug. The formulation enables non-invasive monitoring of nanoemulsion biodistribution using two imaging modalities, 19F MRI and near-infrared (NIR) optical imaging. The nanoemulsion is composed of PFPE-tyramide as a 19F MRI tracer, hydrocarbon oil, surfactants, and a NIR dye. Preparation utilizes a combination of self-assembly and high energy emulsification methods, resulting in droplets with average diameter 180 nm and low polydispersity index (PDI less than 0.2). A model nonsteroidal anti-inflammatory drug (NSAID), celecoxib, was incorporated into the formulation at 0.2 mg/mL. The reported nanoemulsion’s properties, including small particle size, visibility under 19F NMR and NIR fluorescence spectroscopy, and the ability to carry drugs make it an attractive potential theranostic agent for cancer imaging and treatment. PMID:22675234

Nanoencapsulation of water-soluble drug, lamivudine, using a double emulsion spray-drying technique for improving HIV treatment

NASA Astrophysics Data System (ADS)

Tshweu, Lesego; Katata, Lebogang; Kalombo, Lonji; Swai, Hulda

2013-11-01

Current treatments available for human immunodeficiency virus, namely antiretrovirals, do not completely eradicate the virus from the body, leading to life-time commitment. Many antiretrovirals suffer drawbacks from toxicity and unpleasant side effects, causing patience non-compliance. To minimize challenges associated with the antiretrovirals, biodegradable nanoparticles used as drug delivery systems hold tremendous potential to enhance patience compliance. The main objective of this work was to load lamivudine (LAM) into poly(epsilon-caprolactone) (PCL) nanoparticles. LAM is a hydrophilic drug with low plasma half-life of 5-7 h and several unpleasant side effects. LAM was nanoencapsulated into PCL polymer via the double emulsion spray-drying method. Formulation parameters such as the effect of solvent, excipient and drug concentration were optimized for the synthesis of the nanoparticles. Spherical nanoparticles with an average size of 215 ± 3 nm and polydispersity index (PDI) of 0.227 ± 0.01 were obtained, when ethyl acetate and lactose were used in the preparation. However, dichloromethane presented sizes larger than 454 ± 11 nm with PDI of more than 0.4 ± 0.05, irrespective of whether lactose or trehalose was used in the preparation. Some of the nanoparticles prepared with trehalose resulted in crystal formation. UV spectroscopy showed encapsulation efficiency ranging from 68 ± 4 to 78 ± 4 % for LAM depending on the starting drug concentration. Fourier transform infrared spectroscopy and X-ray diffraction confirmed the possibility of preparing amorphous PCL nanoparticles containing LAM. Drug release extended for 4 days in pH 1.3, pH 4.5 and pH 6.8. These results indicated that LAM-loaded PCL nanoparticles show promise for controlled delivery.

Evaluation of the effects of polymeric chitosan/tripolyphosphate and solid lipid nanoparticles on germination of Zea mays, Brassica rapa and Pisum sativum.

PubMed

Nakasato, Daniele Y; Pereira, Anderson E S; Oliveira, Jhones L; Oliveira, Halley C; Fraceto, Leonardo F

2017-08-01

Although the potential toxicity of many metallic and carbon nanoparticles to plants has been reported, few studies have evaluated the phytotoxic effects of polymeric and solid lipid nanoparticles. The present work described the preparation and characterization of chitosan/tripolyphosphate (CS/TPP) nanoparticles and solid lipid nanoparticles (SLN) and evaluated the effects of different concentrations of these nanoparticles on germination of Zea mays, Brassica rapa, and Pisum sativum. CS/TPP nanoparticles presented an average size of 233.6±12.1nm, polydispersity index (PDI) of 0.30±0.02, and zeta potential of +21.4±1.7mV. SLN showed an average size of 323.25±41.4nm, PDI of 0.23±0.103, and zeta potential of -13.25±3.2mV. Nanotracking analysis enabled determination of concentrations of 1.33×10 10 (CS/TPP) and 3.64×10 12 (SLN) nanoparticles per mL. At high concentrations, CS/TPP nanoparticles caused complete inhibition of germination, and thus negatively affected the initial growth of all tested species. Differently, SLN presented no phytotoxic effects. The different size and composition and the opposite charges of SLN and CS/TPP nanoparticles could be associated with the differential phytotoxicity of these nanomaterials. The present study reports the phytotoxic potential of polymeric CS/TPP nanoparticles towards plants, indicating that further investigation is needed on the effects of such formulations intended for future use in agricultural systems, in order to avoid damage to the environment. Copyright © 2017 Elsevier Inc. All rights reserved.

Nano-transfersomal formulations for transdermal delivery of asenapine maleate: in vitro and in vivo performance evaluations.

PubMed

Shreya, A B; Managuli, Renuka S; Menon, Jyothsna; Kondapalli, Lavanya; Hegde, Aswathi R; Avadhani, Kiran; Shetty, Pallavi K; Amirthalingam, Muthukumar; Kalthur, Guruprasad; Mutalik, Srinivas

2016-09-01

Asenapine maleate (ASPM) is an antipsychotic drug for the treatment of schizophrenia and bipolar disorder. Extensive metabolism makes the oral route inconvenient for ASPM. The objective of this study is to increase ASPM bioavailability via transdermal route by improving the skin permeation using combined strategy of chemical and nano-carrier (transfersomal) based approaches. Transfersomes were prepared by the thin film hydration method using soy-phosphatidylcholine (SPC) and sodium deoxycholate (SDC). Transfersomes were characterized for particle size, polydispersity index (PDI), zeta potential (ZP), entrapment efficiency, surface morphology, and in vitro skin permeation studies. Various chemical enhancers were screened for skin permeation enhancement of ASPM. Optimized transfersomes were incorporated into a gel base containing suitable chemical enhancer for efficient transdermal delivery. In vivo pharmacokinetic study was performed in rats to assess bioavailability by transdermal route against oral administration. Optimized transfersomes with drug:SPC:SDC weight ratio of 5:75:10 were spherical with an average size of 126.0 nm, PDI of 0.232, ZP of -43.7 mV, and entrapment efficiency of 54.96%. Ethanol (20% v/v) showed greater skin permeation enhancement. The cumulative amount of ASPM permeated after 24 h (Q24) by individual effect of ethanol and transfersome, and in combination was found to be 160.0, 132.9, and 309.3 μg, respectively, indicating beneficial synergistic effect of combined approach. In vivo pharmacokinetic study revealed significant (p < 0.05) increase in bioavailability upon transdermal application compared with oral route. Dual strategy of permeation enhancement was successful in increasing the transdermal permeation and bioavailability of ASPM.

Design of cationic nanostructured heterolipid matrices for ocular delivery of methazolamide

PubMed Central

Youshia, John; Kamel, Amany O; El Shamy, Abdelhameed; Mansour, Samar

2012-01-01

Solid lipid nanoparticles (SLNs) formulated from one type of lipid (homolipid) suffer from low drug encapsulation and drug bursting due to crystallization of the lipid into the more ordered β modification, which leads to decreased drug entrapment and faster drug release. This study assessed the feasibility of using nanostructured lipid matrices (NLMs) for ocular delivery of methazolamide-(MZA) adopting heterolipids composed of novel mixtures of Compritol ® and cetostearyl alcohol (CSA), and stabilized by Tween 80®. The systems were prepared using the modified high shear homogenization followed by ultrasonication method, which avoids the use of organic solvents. A 32 full factorial design was constructed to study the influence of two independent variables, namely the ratio of CSA:Compritol and the concentration of Tween 80, each in three levels. The dependent variables were the entrapment efficiency percentages (EE%), mean particle size (PS), polydispersity index (PDI), and zeta potential (ZP). In vivo intraocular pressure (IOP) lowering activity for the selected formulae was compared to that of MZA solution. The results showed that increasing the ratio of CSA to Compritol increased the EE% and PS, while increasing the concentration of Tween 80, decreased PS with no significant effect on EE%. The ZP values of all formulae were positive, and greater than 30 mV. The best formula, composed of 4% CSA, 2% Compritol, 0.15% stearylamine, and 2% Tween 80, with EE% of 25.62%, PS of 207.1 nm, PDI of 0.243, and ZP of 41.50 mV, showed in vitro sustained release properties for 8 hours and lowered the intraocular pressure by 8.3 mmHg within 3 hours, with this drop in pressure lasting for 12 hours. PMID:22679362

Near-infrared mediated quantum dots and paclitaxel co-loaded nanostructured lipid carriers for cancer theragnostic.

PubMed

Olerile, Livesey David; Liu, Yongjun; Zhang, Bo; Wang, Tianqi; Mu, Shengjun; Zhang, Jing; Selotlegeng, Lesego; Zhang, Na

2017-02-01

Timing is an important factor in cancer management. Theragnostic systems have benefit of improving patients' life-quality by expediting therapeutic decisions. The objective of this study was to explore the potential of co-loaded [quantum dots (CdTe/CdS/ZnS) and paclitaxel] NLC (nanostructured lipid carriers) as a parenteral multifunctional delivery system. The co-loaded NLC was prepared by emulsion-evaporation and low temperature-solidification method utilising glyceryl monostearate, oleic acid, and soya phosphatidylcholine as lipid matrix. In characterising the co-loaded NLC, physicochemical properties of particle size, polydispersity index (PDI), zeta potential (ZP), morphology, encapsulation efficacy (EE) and drug loading (DL) were investigated. Moreover, in-vitro paclitaxel release profile, cytotoxicity, histopathological, in-vivo anti-tumour efficacy, and in-vivo and ex-vivo fluorescence optical imaging abilities of the co-loaded NLC were assessed. The mean particle size, PDI and ZP were reported to be 115.93±1.61nm, 0.17±0.04 and -0.22±0.03mV, respectively. The particles were spheroid-like in shape with relatively smooth surface. A higher EE (80.70±2.11%) and DL (4.68±0.04%) were recorded. The coloaded NLC exhibited a biphasic pattern of drug release. IC 50 value was found to be 1.05±0.58μM. The tumour growth inhibition rate of 77.85% was registered. The in-vivo and ex-vivo imaging results indicated capability of the co-loaded NLC to specifically target and detect the H22 tumour. Tissues showed no significant cytoarchitectural differences. We can satisfactorily conclude that co-loaded NLC formulation can be qualified as a splendid parenteral drug delivery system foundation for cancer theragnostic. Copyright © 2016 Elsevier B.V. All rights reserved.

Uptake mechanism of furosemide-loaded pegylated nanoparticles by cochlear cell lines.

PubMed

Youm, Ibrahima; Youan, Bi-Botti C

2013-10-01

This study tests the hypothesis that pegylated nanoparticles (NPs) could be taken up by the cochlear cells [House Ear Institute-organ of Corti 1 (HEI-OC1) and Stria vascularis K-1 (SVK-1)], through endocytic pathways. Furthermore, the in vitro drug release and the cytotoxicity of Furosemide (FUR)-loaded NPs on these two cochlear cells are investigated. FUR-loaded pegylated NPs are prepared by the emulsion-solvent diffusion method without surfactant. The NPs are characterized for particle mean diameter, polydispersity index (PDI), morphology, percent drug encapsulation efficiency (EE%), and FUR release kinetics. The methyl tetrazolium salt (MTS) and lactate dehydrogenase (LDH) bioassays are used to evaluate in vitro, the cytotoxicity of FUR-loaded NPs and native FUR. The NPs uptake is investigated using confocal microscopy, microplate reader/fluorimetry, and flow cytometry. Spherical NPs with a mean diameter range of 133-210 nm and PDI values varying from 0.037 to 0.41 are produced. The FUR EE% is 86% and the drug is released from the NPs according to the zero-order and Higuchi models. After treatment with blank NPs, the percentage of cell viability and cell death are 95.96% and 8.95%, in HEI-OC1 cells, respectively. The NPs are internalized by HEI-OC1 cells through a clathrin-dependent pathway. In addition, results show that NPs can be taken up via clathrin and cytoskeleton mediated pathways in SVK-1 cells. The internalization of the pegylated NPs can enhance the drug toxicity by necrosis in a dose-dependent and sustained release manner. The formulated NPs provide a promising template for a targeted drug delivery system to the inner ear. Copyright © 2013 Elsevier B.V. All rights reserved.

Physiotherapy triage assessment of patients referred for orthopaedic consultation - Long-term follow-up of health-related quality of life, pain-related disability and sick leave.

PubMed

Samsson, Karin S; Larsson, Maria E H

2015-02-01

The literature indicates that physiotherapy triage assessment can be efficient for patients referred for orthopaedic consultation, however long-term follow up of patient reported outcome measures are not available. To report a long-term evaluation of patient-reported health-related quality of life, pain-related disability, and sick leave after a physiotherapy triage assessment of patients referred for orthopaedic consultation compared with standard practice. Patients referred for orthopaedic consultation (n = 208) were randomised to physiotherapy triage assessment or standard practice. The randomised cohort was analysed on an intention-to-treat (ITT) basis. The patient reported outcome measures EuroQol VAS (self-reported health-state), EuroQol 5D-3L (EQ-5D) and Pain Disability Index (PDI) were assessed at baseline and after 3, 6 and 12 months. EQ VAS was analysed using a repeated measure ANOVA. PDI and EQ-5D were analysed using a marginal logistic regression model. Sick leave was analysed for the 12 months following consultation using a Mann-Whitney U-test. The patients rated a significantly better health-state at 3 after physiotherapy triage assessment [mean difference -5.7 (95% CI -11.1; -0.2); p = 0.04]. There were no other statistically significant differences in perceived health-related quality of life or pain related disability between the groups at any of the follow-ups, or sick leave. This study reports that the long-term follow up of the patient related outcome measures health-related quality of life, pain-related disability and sick leave after physiotherapy triage assessment did not differ from standard practice, indicating the possible benefits of implementation of this model of care. Copyright © 2014 Elsevier Ltd. All rights reserved.

Enhancing the Solubility and Oral Bioavailability of Poorly Water-Soluble Drugs Using Monoolein Cubosomes.

PubMed

Ali, Md Ashraf; Kataoka, Noriko; Ranneh, Abdul-Hackam; Iwao, Yasunori; Noguchi, Shuji; Oka, Toshihiko; Itai, Shigeru

2017-01-01

Monoolein cubosomes containing either spironolactone (SPI) or nifedipine (NI) were prepared using a high-pressure homogenization technique and characterized in terms of their solubility and oral bioavailability. The mean particle size, polydispersity index (PDI), zeta potential, solubility and encapsulation efficiency (EE) values of the SPI- and NI-loaded cubosomes were determined to be 90.4 nm, 0.187, -13.4 mV, 163 µg/mL and 90.2%, and 91.3 nm, 0.168, -12.8 mV, 189 µg/mL and 93.0%, respectively, which were almost identical to those of the blank cubosome. Small-angle X-ray scattering analyses confirmed that the SPI-loaded, NI-loaded and blank cubosomes existed in the cubic space group Im3̄m. The lattice parameters of the SPI- and NI-loaded cubosomes were 147.6 and 151.6 Å, respectively, making them almost identical to that of blank cubosome (151.0 Å). The in vitro release profiles of the SPI- and NI-loaded cubosomes showed that they released less than 5% of the drugs into various media over 12-48 h, indicating that most of the drug remained encapsulated within the cubic phase of their lipid bilayer. Furthermore, the in vivo pharmacokinetic results suggested that these cubosomes led to a considerable increase in the systemic oral bioavailability of the drugs compared with pure dispersions of the same materials. Notably, the stability results indicated that the mean particle size and PDI values of these cubosomes were stable for at least 4 weeks. Taken together, these results demonstrate that monoolein cubosomes represent promising drug carriers for enhancing the solubility and oral bioavailability of poorly water-soluble drugs.

Photo-Double Ionization: Threshold Law and Low-Energy Behavior

NASA Technical Reports Server (NTRS)

Bhatia, A. K.; Temkin, A.

2007-01-01

The threshold law for photoejection of two electrons from atoms (PDI) is derived from a modification of the Coulomb-dipole (C-D) theory. The C-D theory applies to two-electron ejection from negative ions (photo-double detachment:PDD). The modification consists of correctly accounting for the fact that in PDI that the two escaping electrons see a Coulomb field, asymptotically no matter what their relative distances from the residual ion are. We find in the contralinear spherically symmetric model that the analytic threshold law Q(E), i.e. the yield of residual ions, to be Q Integral of (E) varies as E + (C(sub w) E(sup gamma W)) +CE(sup 5/4) sin [1/2 ln E + phi]/ln(E). The first and third terms are beyond the Wannier law. Our threshold law can only be rigorously justified for residual energies <= 10(exp -3) eV. Nevertheless in the present experimental range (0.1 - 4 eV), the form, even without the second term, can be fitted to experimental results of PDI for He, Li, and Be, in contrast to the Wannier law which has a larger deviation from the data for Li and Be.

Regulation of interleukin-4 signaling by extracellular reduction of intramolecular disulfides

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

Curbo, Sophie; Gaudin, Raphael; Carlsten, Mattias

2009-12-25

Interleukin-4 (IL-4) contains three structurally important intramolecular disulfides that are required for the bioactivity of the cytokine. We show that the cell surface of HeLa cells and endotoxin-activated monocytes can reduce IL-4 intramolecular disulfides in the extracellular space and inhibit binding of IL-4 to the IL-4R{alpha} receptor. IL-4 disulfides were in vitro reduced by thioredoxin 1 (Trx1) and protein disulfide isomerase (PDI). Reduction of IL-4 disulfides by the cell surface of HeLa cells was inhibited by auranofin, an inhibitor of thioredoxin reductase that is an electron donor to both Trx1 and PDI. Both Trx1 and PDI have been shown tomore » be located at the cell surface and our data suggests that these enzymes are involved in catalyzing reduction of IL-4 disulfides. The pro-drug N-acetylcysteine (NAC) that promotes T-helper type 1 responses was also shown to mediate the reduction of IL-4 disulfides. Our data provides evidence for a novel redox dependent pathway for regulation of cytokine activity by extracellular reduction of intramolecular disulfides at the cell surface by members of the thioredoxin enzyme family.« less

Thioredoxin-interacting protein regulates protein disulfide isomerases and endoplasmic reticulum stress.

PubMed

Lee, Samuel; Min Kim, Soo; Dotimas, James; Li, Letitia; Feener, Edward P; Baldus, Stephan; Myers, Ronald B; Chutkow, William A; Patwari, Parth; Yoshioka, Jun; Lee, Richard T

2014-06-01

The endoplasmic reticulum (ER) is responsible for protein folding, modification, and trafficking. Accumulation of unfolded or misfolded proteins represents the condition of ER stress and triggers the unfolded protein response (UPR), a key mechanism linking supply of excess nutrients to insulin resistance and type 2 diabetes in obesity. The ER harbors proteins that participate in protein folding including protein disulfide isomerases (PDIs). Changes in PDI activity are associated with protein misfolding and ER stress. Here, we show that thioredoxin-interacting protein (Txnip), a member of the arrestin protein superfamily and one of the most strongly induced proteins in diabetic patients, regulates PDI activity and UPR signaling. We found that Txnip binds to PDIs and increases their enzymatic activity. Genetic deletion of Txnip in cells and mice led to increased protein ubiquitination and splicing of the UPR regulated transcription factor X-box-binding protein 1 (Xbp1s) at baseline as well as under ER stress. Our results reveal Txnip as a novel direct regulator of PDI activity and a feedback mechanism of UPR signaling to decrease ER stress. © 2014 Brigham and Women's Hospital. Published under the terms of the CC BY 4.0 license.

BODIPY-Based Donor-Acceptor Pi-Conjugated Alternating Copolymers

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

Popere, Bhooshan C.; Della Pelle, Andrea M.; Thayumanavan, S.

2011-06-28

Four novel π-conjugated copolymers incorporating 4,4-difluoro-4-borata-3a-azonia-4a-aza-s-indacene (BODIPY) core as the “donor” and quinoxaline (Qx), 2,1,3-benzothiadiazole (BzT), N,N'-di(2'-ethyl)hexyl-3,4,7,8-naphthalenetetracarboxylic diimide (NDI), and N,N'-di(2'-ethyl)hexyl-3,4,9,10-perylene tetracarboxylic diimide (PDI) as acceptors were designed and synthesized via Sonogashira polymerization. The polymers were characterized by ¹H NMR spectroscopy, gel permeation chromatography (GPC), UV–vis absorption spectroscopy, and cyclic voltammetry. Density functional theory (DFT) calculations were performed on polymer repeat units, and the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) energy levels were estimated from the optimized geometry using B3LYP functional and 6-311g(d,p) basis set. Copolymers with Qx and BzT possessed HOMO and LUMOmore » energy levels comparable to those of BODIPY homopolymer, while PDI stabilized both HOMO and LUMO levels. Semiconductor behavior of these polymers was estimated in organic thin-film transistors (OTFT). While the homopolymer, Qx, and BzT-based copolymers showed only p-type semiconductor behavior, copolymers with PDI and NDI showed only n-type behavior.« less

Bond-rearrangement and ionization mechanisms in the photo-double-ionization of simple hydrocarbons (C 2H 4, C 2H 3F, and 1,1-C 2H 2F 2) near and above threshold

DOE PAGES

Gaire, B.; Gatton, A. S.; Wiegandt, F.; ...

2016-09-14

We have investigated bond-rearrangement driven by photo-double-ionization (PDI) near and above the double ionization threshold in a sequence of carbon-carbon double bonded hydrocarbon molecules: ethylene, fluoroethylene, and 1,1-difluoroethylene. We employ the kinematically complete cold target recoil ion momentum spectroscopy (COLTRIMS) method to resolve all photo-double-ionization events leading to two-ionic fragments. We observe changes in the branching ratios of different dissociative ionization channels depending on the presence of none, one, or two fluorine atoms. The role of the fluorine atom in the bond-rearrangement channels is intriguing as evident by the re-ordering of the threshold energies of the PDI in the fluorinatedmore » molecules. These effects offer a compelling argument that the electronegativity of the fluorine (or the polarity of the molecule) strongly influences the potential energy surfaces of the molcules and drives bond-rearrangement during the dissociation process. The energy sharing and the relative angle between the 3D-momentum vectors of the two electrons provide clear evidence of direct and indirect PDI processes.« less

Maternal and Cord Blood Manganese Concentrations and Early Childhood Neurodevelopment among Residents near a Mining-Impacted Superfund Site.

PubMed

Claus Henn, Birgit; Bellinger, David C; Hopkins, Marianne R; Coull, Brent A; Ettinger, Adrienne S; Jim, Rebecca; Hatley, Earl; Christiani, David C; Wright, Robert O

2017-06-28

Environmental manganese exposure has been associated with adverse neurodevelopmental outcomes among school-aged children; yet, few studies have evaluated prenatal exposure. Our study examines associations between prenatal manganese concentrations and placental transfer of manganese with neurodevelopment in 224 2-y-old children residing near the Tar Creek Superfund Site. We collected maternal and cord blood at delivery, measured manganese using inductively coupled plasma mass spectrometry, and assessed neurodevelopment using the Bayley Scales of Infant Development-II. Associations between manganese and mental (MDI) and psychomotor (PDI) development indices were estimated in multivariable models. Placental transfer, approximated by cord/maternal manganese ratio, cord/total manganese ratio (total=maternal+cord), and by joint classification according to high or low (above or below median) maternal and cord manganese, was evaluated as a predictor of neurodevelopment. Median levels [interquartile ranges (IQR)] of manganese in maternal and cord blood, respectively, were 24.0 (19.5-29.7) and 43.1 (33.5-52.1) μg/L. Adjusting for lead, arsenic, and other potential confounders, an IQR increase in maternal manganese was associated with -3.0 (95% CI: -5.3, -0.7) points on MDI and -2.3 (95% CI: -4.1, -0.4) points on PDI. Cord manganese concentrations were not associated with neurodevelopment scores. Cord/maternal and cord/total manganese ratios were positively associated with MDI [cord/maternal: β=2.6 (95% Cl: −0.04, 5.3); cord/total: β=22.0 (95% Cl: 3.2, 40.7)] and PDI (cord/maternal: β=1.7 (95% Cl: −0.5, 3.9); cord/total: β=15.6 (95% Cl: 0.3, 20.9)). Compared to mother-child pairs with low maternal and cord manganese, associations with neurodevelopment scores were negative for pairs with either high maternal, high cord, or high maternal and cord manganese. Maternal blood manganese concentrations were negatively associated with early childhood neurodevelopment scores in our study. Findings highlight the importance of understanding maternal exposures during pregnancy and factors influencing placental transfer. https://doi.org/10.1289/EHP925.

One-pot synthesis of monodisperse CoFe2O4@Ag core-shell nanoparticles and their characterization.

PubMed

Hara, Shuta; Aisu, Jumpei; Kato, Masahiro; Aono, Takashige; Sugawa, Kosuke; Takase, Kouichi; Otsuki, Joe; Shimizu, Shigeru; Ikake, Hiroki

2018-06-08

In recent years, monodispersed magnetic nanoparticles with a core/shell structure are expected for their wide applications including magnetic fluid, recoverable catalysts, and biological analysis. However, their synthesis method needs numerous processes such as solvent substitution, exchange of protective agents, and centrifugation. A simple and rapid method for the synthesis of monodispersed core-shell nanoparticles makes it possible to accelerate their further applications. This paper describes a simple and rapid one-pot synthesis of core (CoFe 2 O 4 )-shell (Ag) nanoparticles with high monodispersity. The synthesized nanoparticles showed plasmonic light absorption owing to the Ag shell. Moreover, the magnetic property of the nanoparticles had a soft magnetic behavior at room temperature and a hard magnetic behavior at 5 K. In addition, the nanoparticles showed high monodispersity with a low polydispersity index (PDI) value of 0.083 in hexane.

[Exploration of one-step preparation of Ganoderma lucidum multicomponent microemulsion].

PubMed

He, Jun-Jie; Chen, Yan; Du, Meng; Cao, Wei; Yuan, Ling; Zheng, Li-Yan

2013-03-01

To explore one-step method for the preparation of Ganoderma lucidum multicomponent microemulsion, according to the dissolution characteristics of triterpenes and polysaccharides in Ganoderma lucidum, formulation of the microemulsion was optimized. The optimal blank microemulsion was used as a solvent to sonicate the Ganoderma lucidum powder to prepare the multicomponent microemulsion, besides, its physicochemical properties were compared with the microemulsion made by conventional method. The results showed that the multicomponent microemulsion was characterized as (43.32 +/- 6.82) nm in size, 0.173 +/- 0.025 in polydispersity index (PDI) and -(3.98 +/- 0.82) mV in zeta potential. The contents of Ganoderma lucidum triterpenes and polysaccharides were (5.95 +/- 0.32) and (7.58 +/- 0.44) mg x mL(-1), respectively. Sonicating Ganoderma lucidum powder by blank microemulsion could prepare the multicomponent microemulsion. Compared with the conventional method, this method is simple and low cost, which is suitable for industrial production.

One-pot synthesis of monodisperse CoFe2O4@Ag core-shell nanoparticles and their characterization

NASA Astrophysics Data System (ADS)

Hara, Shuta; Aisu, Jumpei; Kato, Masahiro; Aono, Takashige; Sugawa, Kosuke; Takase, Kouichi; Otsuki, Joe; Shimizu, Shigeru; Ikake, Hiroki

2018-06-01

In recent years, monodispersed magnetic nanoparticles with a core/shell structure are expected for their wide applications including magnetic fluid, recoverable catalysts, and biological analysis. However, their synthesis method needs numerous processes such as solvent substitution, exchange of protective agents, and centrifugation. A simple and rapid method for the synthesis of monodispersed core-shell nanoparticles makes it possible to accelerate their further applications. This paper describes a simple and rapid one-pot synthesis of core (CoFe2O4)-shell (Ag) nanoparticles with high monodispersity. The synthesized nanoparticles showed plasmonic light absorption owing to the Ag shell. Moreover, the magnetic property of the nanoparticles had a soft magnetic behavior at room temperature and a hard magnetic behavior at 5 K. In addition, the nanoparticles showed high monodispersity with a low polydispersity index (PDI) value of 0.083 in hexane.

Maternal polymorphisms in glutathione-related genes are associated with maternal mercury concentrations and early child neurodevelopment in a population with a fish-rich diet.

PubMed

Wahlberg, Karin; Love, Tanzy M; Pineda, Daniela; Engström, Karin; Watson, Gene E; Thurston, Sally W; Yeates, Alison J; Mulhern, Maria S; McSorley, Emeir M; Strain, J J; Smith, Tristram H; Davidson, Philip W; Shamlaye, Conrad F; Myers, G J; Rand, Matthew D; van Wijngaarden, Edwin; Broberg, Karin

2018-06-01

Glutathione (GSH) pathways play a key role the metabolism and elimination of the neurotoxicant methylmercury (MeHg). We hypothesized that maternal genetic variation linked to GSH pathways could influence MeHg concentrations in pregnant mothers and children and thereby also affect early life development. The GCLM (rs41303970, C/T), GCLC (rs761142, T/G) and GSTP1 (rs1695, A/G) polymorphisms were genotyped in 1449 mothers in a prospective study of the Seychellois population with a diet rich in fish. Genotypes were analyzed in association with maternal hair and blood Hg, fetal blood Hg (cord blood Hg), as well as children's mental (MDI) and motor development (PDI; MDI and PDI assessed by Bayley Scales of Infant Development at 20 months). We also examined whether genotypes modified the association between Hg exposure and developmental outcomes. GCLC rs761142 TT homozygotes showed statistically higher mean maternal hair Hg (4.12 ppm) than G carriers (AG 3.73 and GG 3.52 ppm) (p = 0.037). For the combination of GCLC rs761142 and GCLM rs41303970, double homozygotes TT + CC showed higher hair Hg (4.40 ppm) than G + T carriers (3.44 ppm; p = 0.018). No associations were observed between GSTP1 rs1695 and maternal hair Hg or between any genotypes and maternal blood Hg or cord blood Hg. The maternal GSTP1 rs1695 rare allele (G) was associated with a lower MDI among children (β = -1.48, p = 0.048). We also observed some interactions: increasing Hg in maternal and cord blood was associated with lower PDI among GCLC rs761142 TT carriers; and increasing Hg in hair was associated with lower MDI among GSTP1 rs1695 GG carriers. Maternal genetic variation in genes involved in GSH synthesis is statistically associated with Hg concentrations in maternal hair, but not in maternal or fetal blood. We observed interactions that suggest maternal GSH genetics may modify associations between MeHg exposure and neurodevelopmental outcomes. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Effect of prenatal exposure to maternal cortisol and psychological distress on infant development in Bengaluru, southern India: a prospective cohort study.

PubMed

Nath, Anita; Murthy, Gudlavalleti Venkata Satyanarayana; Babu, Giridhara R; Di Renzo, Gian Carlo

2017-07-17

The mental health status of a pregnant woman and its consequent impact on foetal well being is not given much importance compared to the risk imposed by obstetric complications and medical conditions. Maternal psychological distress is a major public health problem and needs timely detection and intervention to prevent any adverse pregnancy outcome. There is ample evidence from literature that justifies the association of prenatal maternal mental stress and elevated cortisol with delayed infant motor and cognitive development; evidence from India being rather limited. The study aim is to prospectively assess the association of maternal psychological distress and cortisol level with motor and cognitive development of the infant. A sample of 2612 eligible pregnant women who have been registered for antenatal care at selected public sector hospitals in Bengaluru will be recruited after obtaining written informed consent. They will be assessed for the presence of maternal psychological distress in the form of depression and anxiety using appropriate scales and saliva samples will be collected for cortisol estimation during early, mid and late pregnancy. Follow up visits after delivery will be done on day 10, 3 months, 8 months and 12 months. The Bayley Scales of Infant and Toddler Development [BSID] (Third edition) will be used to measure both motor and mental milestones in terms of Psychomotor Development Index (PDI) and Mental Development Index (MDI). Logistic regression model will be used to determine the association between the exposure variables and outcomes which will be reported as Odd's Ratio (OR) and 95% confidence intervals (CI). Our study findings could add to the growing evidence that maternal psychological distress during pregnancy adversely influences growth and development in the offspring and subsequent development of the child. While maternal anxiety and depression can be measured by using self reporting instruments, estimation of maternal endogenous cortisol levels could serve as a biomarker of prenatal psychological stress. Findings from this study could be used to focus upon the burden of mental health problems during pregnancy and to consider steps to scale up prenatal mental health services in health care settings.

"Application of Box-Behnken design for optimization and development of quetiapine fumarate loaded chitosan nanoparticles for brain delivery via intranasal route* ".

PubMed

Shah, Brijesh; Khunt, Dignesh; Misra, Manju; Padh, Harish

2016-08-01

The objective of the present investigation was to optimize and develop quetiapine fumarate (QF) loaded chitosan nanoparticles (QF-NP) by ionic gelation method using Box-Behnken design. Three independent variables viz., X1-Concentration of chitosan, X2-Concentration of sodium tripolyphosphate and X3-Volume of sodium tripolyphosphate were taken to investigate their effect on dependent variables (Y1-Size, Y2-PDI and Y3-%EE). Optimized formula of QF-NP was selected from the design space which was further evaluated for physicochemical, morphological, solid state characterization, nasal diffusion and in-vivo distribution for brain targeting following non-invasive intranasal administration. The average particle size, PDI, %EE and nasal diffusion were found to be 131.08±7.45nm, 0.252±0.064, 89.93±3.85% and 65.24±5.26% respectively. Neither toxicity nor structural damage on nasal mucosa was observed upon histopathological examination. Significantly higher brain/blood ratio and 2 folds higher nasal bioavailability in brain with QF-NP in comparison to drug solution following intranasal administration revealed preferential nose to brain transport bypassing blood-brain barrier and prolonged retention of QF at site of action suggesting superiority of chitosan as permeability enhancer. Overall, the above finding shows promising results in the area of developing non-invasive intranasal route as an alternative to oral route for brain delivery. Copyright © 2016 Elsevier B.V. All rights reserved.

[Nasal submicron emulsion of Scutellariae Radix extract preparation technology research based on phase transfer of solute technology].

PubMed

Shi, Ya-jun; Shi, Jun-hui; Chen, Shi-bin; Yang, Ming

2015-07-01

Based on the demand of nasal drug delivery high drug loadings, using the unique phase transfer of solute, integrating the phospholipid complex preparation and submicron emulsion molding process of Scutellariae Radix extract, the study obtained the preparation of the high drug loadings submicron emulsion of Scutellariae Radix extract. In the study of drug solution dispersion method, the uniformity of drug dispersed as the evaluation index, the traditional mixing method, grinding, homogenate and solute phase transfer technology were investigated, and the solute phase transfer technology was adopted in the last. With the adoption of new technology, the drug loading capacity reached 1.33% (phospholipid complex was 4%). The drug loading capacity was improved significantly. The transfer of solute method and timing were studied as follows,join the oil phase when the volume of phospholipid complex anhydrous ethanol solution remaining 30%, the solute phase transfer was completed with the continued recycling of anhydrous ethanol. After drug dissolved away to oil phase, the preparation technology of colostrum was determined with the evaluation index of emulsion droplet form. The particle size of submicron emulsion, PDI and stability parameters were used as evaluation index, orthogonal methodology were adopted to optimize the submicron emulsion ingredient and main influential factors of high pressure homogenization technology. The optimized preparation technology of Scutellariae Radix extract nasal submicron emulsion is practical and stable.

The effect of metabolic alkalosis on the ventilatory response in healthy subjects.

PubMed

Oppersma, E; Doorduin, J; van der Hoeven, J G; Veltink, P H; van Hees, H W H; Heunks, L M A

2018-02-01

Patients with acute respiratory failure may develop respiratory acidosis. Metabolic compensation by bicarbonate production or retention results in posthypercapnic alkalosis with an increased arterial bicarbonate concentration. The hypothesis of this study was that elevated plasma bicarbonate levels decrease respiratory drive and minute ventilation. In an intervention study in 10 healthy subjects the ventilatory response using a hypercapnic ventilatory response (HCVR) test was assessed, before and after administration of high dose sodium bicarbonate. Total dose of sodiumbicarbonate was 1000 ml 8.4% in 3 days. Plasma bicarbonate increased from 25.2 ± 2.2 to 29.2 ± 1.9 mmol/L. With increasing inspiratory CO 2 pressure during the HCVR test, RR, V t , Pdi, EAdi and V E increased. The clinical ratio ΔV E /ΔP et CO 2 remained unchanged, but Pdi, EAdi and V E were significantly lower after bicarbonate administration for similar levels of inspired CO 2 . This study demonstrates that in healthy subjects metabolic alkalosis decreases the neural respiratory drive and minute ventilation, as a response to inspiratory CO 2 . Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Non-linear modeling of RF in fusion grade plasmas

NASA Astrophysics Data System (ADS)

Austin, Travis; Smithe, David; Hakim, Ammar; Jenkins, Thomas

2011-10-01

We are seeking to model nonlinear effects, particularly parametric decay instability in the vicinity of the edge plasma and RF launchers, which is thought to be a potential parasitic loss mechanism. We will use time-domain approaches which treat the full spectrum of modes. Two approaches are being tested for feasibility, a non-linear delta-f particle approach, and a higher order many-fluid closure approach. Our particle approach builds on extensive previous work demonstrating the ability to model IBW waves (one of the PDI daughter waves) with a linear delta-f particle model. Here we report on the performance of such simulations when the linear constraint is relaxed, and in particular on the ability of the low-noise loading scheme, specially developed for RF and ion-time scale physics, to operate and maintain low noise in the non-linear regime. Similarly, a novel high-order closure of the fluid equations is necessary to model the IBW and higher harmonics. We will report on the benchmarking of the fluid closure, and its ability to model the anticipated pump and daughter waves in a PDI scenario. This research supported by US DOE Grant # DE-SC0006242.

Development and evaluation of triclosan loaded poly-ɛ-caprolactone nanoparticulate system for the treatment of periodontal infections

NASA Astrophysics Data System (ADS)

Aminu, Nafiu; Baboota, Sanjula; Pramod, K.; Singh, Manisha; Dang, Shweta; Ansari, Shahid H.; Sahni, Jasjeet K.; Ali, Javed

2013-11-01

Periodontal disease affects tooth-supporting structures and nanoparticles (NPs) have been a promising approach for its treatment. The purpose of the study was to develop triclosan-loaded poly-ɛ-caprolactone (PCL) NPs for the treatment of periodontal infections. Solvent displacement method was used to prepare NPs following Box-Behnken design. The NPs were evaluated with respect to particle size, polydispersity index, surface morphology, zeta potential, thermal properties, in vitro drug release, and cell viability assay. The optimized NPs were in the size range of 180-230 nm with a mean size of 205.61 ± 10.4 nm. Entrapment efficiency (EE) of 91.02 ± 2.4 % was obtained with a drug loading of 21.71 ± 1.3 %. About 97 % of drug was released in vitro after 3 h. NPs demonstrated almost 100 % cell viability in L929 cell lines. Shelf life of the nanoparticles was 17.07 months. PCL affected particle size whereas triclosan affected loading and EE. The optimized NPs were spherical with smooth surface and exhibited biphasic in vitro release pattern. NPs had optimum zeta potential and PDI and were stable on storage. Absence of cytotoxicity of NPs to L929 cells indicated its safety. Triclosan-loaded PCL nanoparticles could thus serve as a novel colloidal drug delivery system against periodontal infections.

Gender and nurturance in families of children with neurodevelopmental conditions.

PubMed

Shapiro, Danielle N; Dixon-Thomas, Pamela; Warschausky, Seth

2014-05-01

This study tested the hypothesis that gender differences in parent-reported nurturance of children would be attenuated in families of children with neurodevelopmental conditions (NDCs). In this cross-sectional study, participants included 49 (29 male) children diagnosed with an NDC and 60 (30 male) typically developing (TD) children. Children in the NDC group had a diagnosis of cerebral palsy (CP; n = 41) or spina bifida (SB; n = 8). Parental nurturance was measured using the nurturance subscale of the Parenting Dimensions Inventory (PDI; Power, 1991). Data were analyzed using a 2 × 2 (gender × diagnosis) analysis of covariance (ANCOVA) with child age as the covariate. As a simple main effect, parents reported more nurturing behavior toward TD girls than TD boys. However, girls with an NDC received less nurturance, thereby eliminating the gender difference in parental nurturance in the NDC sample. This pattern was reflected in the larger ANCOVA as a 2-way interaction between diagnosis and gender. Group differences in other PDI subscales were not statistically significant. This pattern of results suggests that the parents of girls with NDCs may be less nurturing toward them, thereby attenuating gender differences observed in families with TD children. Findings highlight the need for more research on the gendered dynamics in families with a child with an NDC to develop systemic models of family functioning and targeted parenting interventions for this group. (c) 2014 APA, all rights reserved.

No change in developmental outcome with incubator covers and nesting for very preterm infants in a randomised controlled trial.

PubMed

Maguire, C M; Walther, F J; van Zwieten, P H T; Le Cessie, S; Wit, J M; Veen, S

2009-03-01

To investigate in a randomised controlled trial the effect of basic elements of developmental care (incubator covers and positioning aids) on growth and neurodevelopment in infants born at < 32 weeks. Infants were randomised within 48 h of birth to a developmental care (DC) or standard care (C) group. Outcome measures at 1 and 2 years corrected age were growth, standardised neurological examinations, and mental (MDI) and psychomotor (PDI) development (Dutch version of the Bayley Scales of Infant Development II). 192 infants were recruited (DC = 98; C = 94). Thirteen infants (DC = 7, C = 6) were excluded because they were admitted for <5 days or died within the first 5 days. In total, 179 infants met the inclusion criteria. In-hospital mortality was 12/91 (13.2%) in the DC group and 8/88 (9.1%) in the C group. Assessments were carried out on 147 children (DC = 74, C = 73) at 1 year and 142 children (DC = 72, C = 70) at 2 years. No significant difference in growth, neurological outcomes or MDI was found. A positive trend in PDI at 1 year (p = 0.05) did not continue once the children reached 2 years. There was no difference found when neurological and developmental scores were combined. Basic developmental care has no positive effect on neurological and mental development or growth at 1 and 2 years of age in infants born at <32 weeks. A positive effect on psychomotor development at 1 year did not continue at 2 years of age.

The influence of oscillations on product selectivity during the palladium-catalysed phenylacetylene oxidative carbonylation reaction.

PubMed

Novakovic, Katarina; Grosjean, Christophe; Scott, Stephen K; Whiting, Andrew; Willis, Mark J; Wright, Allen R

2008-02-07

This paper reports on the influence of oscillations on product selectivity as well as the dynamics of product formation during the palladium-catalysed phenylacetylene oxidative carbonylation reaction in a catalytic system (PdI2, KI, Air, NaOAc in methanol). The occurrence of the pH oscillations is related to PdI2 granularity and the initial pH drop after phenylacetylene addition. To achieve pH and reaction exotherm oscillations regulation of the amount of PdI2 is required, ensuring that the initial pH does not fall significantly below 1 after phenylacetylene addition. Experiments in both oscillatory and non-oscillatory pH regimes were performed in an HEL SIMULAR reaction calorimeter with the concentration-time profiles measured using a GC-MS. It is demonstrated that when operating in an oscillatory pH regime product formation may be suppressed until oscillations occur after which there is a steep increase in the formation of Z-2-phenyl-but-2-enedioic acid dimethyl ester. When operating in non-oscillatory pH mode the products are formed steadily over time with the main products being Z-2-phenyl-but-2-enedioic acid dimethyl ester, 2-phenyl-acrylic acid methyl ester and E-3-phenyl-acrylic acid methyl ester.

Photo-Double Ionization: Threshold Law and Low-Energy Behavior

NASA Technical Reports Server (NTRS)

Bhatia, Anand

2008-01-01

The threshold law for photoejection of two electrons from atoms (PDI) is derived from a modification of the Coulomb-dipole (C-D) theory. The C-D theory applies to two-electron ejection from negative ions (photo-double detachment:PDD). The modification consists of correctly accounting for the fact that in PDI that the two escaping electrons see a Coulomb field, asymptotically no matter what their relative distances from the residual ion are. We find in the contralinear spherically symmetric model that the analytic threshold law Q(E),i. e. the yield of residual ions, to be Qf(E)approaches E + CwE(sup gamma(w)) + CE(sup 5/4)sin[1/2 ln(E + theta)]/ln(E). The first and third terms are beyond the Wannier law. Our threshold law can only be rigorously justified for residual energies less than or equal to 10(exp -3) eV. Nevertheless in the present experimental range (0.1 - 4 eV), the form, even without the second term, can be fitted to experimental results of PDI for He, Li, and Be, in contrast to the Wannier law which has a larger deviation from the data for Li and Be, for both of which the data show signs of modulation.

A PDI-catalyzed thiol-disulfide switch regulates the production of hydrogen peroxide by human Ero1.

PubMed

Ramming, Thomas; Okumura, Masaki; Kanemura, Shingo; Baday, Sefer; Birk, Julia; Moes, Suzette; Spiess, Martin; Jenö, Paul; Bernèche, Simon; Inaba, Kenji; Appenzeller-Herzog, Christian

2015-06-01

Oxidative folding in the endoplasmic reticulum (ER) involves ER oxidoreductin 1 (Ero1)-mediated disulfide formation in protein disulfide isomerase (PDI). In this process, Ero1 consumes oxygen (O2) and releases hydrogen peroxide (H2O2), but none of the published Ero1 crystal structures reveal any potential pathway for entry and exit of these reactants. We report that additional mutation of the Cys(208)-Cys(241) disulfide in hyperactive Ero1α (Ero1α-C104A/C131A) potentiates H2O2 production, ER oxidation, and cell toxicity. This disulfide clamps two helices that seal the flavin cofactor where O2 is reduced to H2O2. Through its carboxyterminal active site, PDI unlocks this seal by forming a Cys(208)/Cys(241)-dependent mixed-disulfide complex with Ero1α. The H2O2-detoxifying glutathione peroxidase 8 also binds to the Cys(208)/Cys(241) loop region. Supported by O2 diffusion simulations, these data describe the first enzymatically controlled O2 access into a flavoprotein active site, provide molecular-level understanding of Ero1α regulation and H2O2 production/detoxification, and establish the deleterious consequences of constitutive Ero1 activity. Copyright © 2015 Elsevier Inc. All rights reserved.

Curcumin and Curcuma longa L. extract ameliorate lipid accumulation through the regulation of the endoplasmic reticulum redox and ER stress.

PubMed

Lee, Hwa-Young; Kim, Seung-Wook; Lee, Geum-Hwa; Choi, Min-Kyung; Chung, Han-Wool; Lee, Yong-Chul; Kim, Hyung-Ryong; Kwon, Ho Jeong; Chae, Han-Jung

2017-07-26

For this study, we examined the effects of curcumin against acute and chronic stress, paying specific attention to ROS. We also aimed to clarify the differences between acute and chronic stress conditions. We investigated the effects of curcumin against acute stress (once/1 day CCl 4 treatment) and chronic-stress (every other day/4week CCl 4 treatment). Compared with acute stress, in which the antioxidant system functioned properly and aspartate transaminase (AST) and ROS production increased, chronic stress increased AST, alanine aminotransferase (ALT), hepatic enzymes, and ROS more significantly, and the antioxidant system became impaired. We also found that ER-originated ROS accumulated in the chronic model, another difference between the two conditions. ER stress was induced consistently, and oxidative intra-ER protein folding status, representatively PDI, was impaired, especially in chronic stress. The PDI-associated client protein hepatic apoB accumulated with the PDI-binding status in chronic stress, and curcumin recovered the altered ER folding status, regulating ER stress and the resultant hepatic dyslipidemia. Throughout this study, curcumin and curcumin-rich Curcuma longa L. extract promoted recovery from CCl 4 -induced hepatic toxicity in both stress conditions. For both stress-associated hepatic dyslipidemia, curcumin and Curcuma longa L. extract might be recommendable to recover liver activity.

Attaching the NorA Efflux Pump Inhibitor INF55 to Methylene Blue Enhances Antimicrobial Photodynamic Inactivation of Methicillin-Resistant Staphylococcus aureus in Vitro and in Vivo.

PubMed

Rineh, Ardeshir; Dolla, Naveen K; Ball, Anthony R; Magana, Maria; Bremner, John B; Hamblin, Michael R; Tegos, George P; Kelso, Michael J

2017-10-13

Antimicrobial photodynamic inactivation (aPDI) uses photosensitizers (PSs) and harmless visible light to generate reactive oxygen species (ROS) and kill microbes. Multidrug efflux systems can moderate the phototoxic effects of PSs by expelling the compounds from cells. We hypothesized that increasing intracellular concentrations of PSs by inhibiting efflux with a covalently attached efflux pump inhibitor (EPI) would enhance bacterial cell phototoxicity and reduce exposure of neighboring host cells to damaging ROS. In this study, we tested the hypothesis by linking NorA EPIs to methylene blue (MB) and examining the photoantimicrobial activity of the EPI-MB hybrids against the human pathogen methicillin-resistant Staphylococcus aureus (MRSA). Photochemical/photophysical and in vitro microbiological evaluation of 16 hybrids carrying four different NorA EPIs attached to MB via four linker types identified INF55-(Ac)en-MB 12 as a lead. Compound 12 showed increased uptake into S. aureus cells and enhanced aPDI activity and wound healing effects (relative to MB) in a murine model of an abrasion wound infected by MRSA. The study supports a new approach for treating localized multidrug-resistant MRSA infections and paves the way for wider exploration of the EPI-PS hybrid strategy in aPDI.

Enhancement of soft X-ray reflectivity and interface stability in nitridated Pd/Y multilayer mirrors.

PubMed

Xu, Dechao; Huang, Qiushi; Wang, Yiwen; Li, Pin; Wen, Mingwu; Jonnard, Philippe; Giglia, Angelo; Kozhevnikov, Igor V; Wang, Kun; Zhang, Zhong; Wang, Zhanshan

2015-12-28

Pd/Y multilayer mirrors operating in the soft X-ray region are characterized by a high theoretical reflectance, reaching 65% at normal incidence in the 8-12 nm wavelength range. However, a severe intermixing of neighboring Pd and Y layers results in an almost total disappearance of the interfaces inside the multilayer structures fabricated by direct current magnetron sputtering and thus a dramatic reflectivity decrease. Based on grazing incidence X-ray reflectometry and X-ray photoelectron spectroscopy, we demonstrate that the stability of the interfaces in Pd/Y multilayer structures can be essentially improved by adding a small amount of nitrogen (4-8%) to the working gas (Ar). High resolution transmission electron microscopy shows that the interlayer width is only 0.9 nm and 0.6 nm for Y(N)-on-Pd(N) and Pd(N)-on-Y(N) interfaces, respectively. A well-defined crystalline texture of YN (200) is observed on the electron diffraction pattern. As a result, the measured reflectance of the Pd(N)/Y(N) multilayer achieves 30% at λ = 9.3 nm. The peak reflectivity value is limited by the remaining interlayers and the formation of the YN compound inside the yttrium layers, resulting in an increased absorption.

Analysis of photogem (hematoporphyrin derivative) and blood interaction

NASA Astrophysics Data System (ADS)

Corrêa, Thaila Quatrini; Pratavieira, Sebastião.; Bagnato, Vanderlei Salvador

2017-07-01

Sepsis is a potentially fatal condition that occurs when an infectious agent, such as bacteria, gets in a person's bloodstream. The infection affects the immune system, which then triggers a reaction that can cause uncontrolled inflammation in the body1 . All blood components may present the contamination. Once inoculated bacteria in a blood component, it can proliferate rapidly reaching high levels within few hours and, in a short period, it may lead to several basal changes in the individual and even death2 . Studies have shown an increase in the incidence of sepsis over the years, and it is mainly due to the growing resistance of microorganisms to antibiotics since these drugs are still sold and used improperly3 . The photodynamic inactivation (PDI) has been one of the most promising alternatives for microbiological control and other diseases. Its principle of action is based on a photosensitizer (PS) activated by light at the correct wavelength to oxidize organic substrates, resulting in cytotoxic effects4,5. The technique is being applied to a large variety of microorganisms and decontaminating blood. Some studies have investigated the action of PDI in blood6-9, and even then, there is a need to understand better what happens when we apply PS and light in blood in an attempt to eliminate the microorganisms. Photogem is a hematoporphyrin derivative that has been used with success in many clinical cases such as skin cancer and inactivation of bacteria10,11. Previous studies have shown that PDI using Photogem as a photosensitizing molecule is a good alternative for blood decontamination12,13. In the previous studies were observed hemolysis when red blood cells (RBCs) were submitted to PS concentration and light dose tested. This study has been conducted to further understand through absorption spectroscopy and fluorescence confocal microscope the PS-blood interaction. This is important because the PDI damage needs to be restricted to the bacteria and the blood functions should be preserved.

Phylogenetic reconstruction by cross-species chromosome painting and G-banding in four species of Phyllostomini tribe (Chiroptera, Phyllostomidae) in the Brazilian Amazon: an independent evidence for monophyly.

PubMed

Ribas, Talita Fernanda Augusto; Rodrigues, Luis Reginaldo Ribeiro; Nagamachi, Cleusa Yoshiko; Gomes, Anderson José Baia; Rissino, Jorge das Dores; O'Brien, Patricia Caroline Mary; Yang, Fengtang; Ferguson-Smith, Malcolm Andrew; Pieczarka, Julio Cesar

2015-01-01

The subfamily Phyllostominae comprises taxa with a variety of feeding strategies. From the cytogenetic point of view, Phyllostominae shows different rates of chromosomal evolution between genera, with Phyllostomus hastatus probably retaining the ancestral karyotype for the subfamily. Since chromosomal rearrangements occur rarely in the genome and have great value as phylogenetic markers and in taxonomic characterization, we analyzed three species: Lophostoma silvicola (LSI), Phyllostomus discolor (PDI) and Tonatia saurophila (TSA), representing the tribe Phyllostomini, collected in the Amazon region, by classic and molecular cytogenetic techniques in order to reconstruct the phylogenetic relationships within this tribe. LSA has a karyotype of 2n=34 and FN=60, PDI has 2n=32 and FN=60 and TSA has 2n=16 and FN=20. Comparative analysis using G-banding and chromosome painting show that the karyotypic complement of TSA is highly rearranged relative to LSI and PHA, while LSI, PHA and PDI have similar karyotypes, differing by only three chromosome pairs. Nearly all chromosomes of PDI and PHA were conserved in toto, except for chromosome 15 that was changed by a pericentric inversion. A strongly supported phylogeny (bootstrap=100 and Bremer=10 steps), confirms the monophyly of Phyllostomini. In agreement with molecular topologies, TSA was in the basal position, while PHA and LSI formed sister taxa. A few ancestral syntenies are conserved without rearrangements and most associations are autapomorphic traits for Tonatia or plesiomorphic for the three genera analyzed here. The karyotype of TSA is highly derived in relation to that of other phyllostomid bats, differing from the supposed ancestral karyotype of Phyllostomidae by multiple rearrangements. Phylogenies based on chromosomal data are independent evidence for the monophyly of tribe Phyllostomini as determined by molecular topologies and provide additional support for the paraphyly of the genus Tonatia by the exclusion of the genus Lophostoma.

Protein disulfide isomerase regulates renal AT1 receptor function and blood pressure in rats.

PubMed

Wang, Xitao; Asghar, Mohammad

2017-08-01

The role and mechanism of renal protein disulfide isomerase (PDI) in blood pressure regulation has not been tested before. Here, we test this possibility in Sprague-Dawley rats. Rats were treated with PDI inhibitor bacitracin (100 mg·kg -1 ip·day -1 for 14 days), and then blood pressure and renal angiotensin II type 1 (AT 1 ) receptor function were determined in anesthetized rats. Renal AT 1 receptor function was determined as the ability of candesartan (an AT 1 receptor blocker) to increase diuresis and natriuresis. A second set of vehicle- and bacitracin-treated rats was used to determine biochemical parameters. Systolic blood pressure as well as diastolic blood pressure increased in bacitracin-treated compared with vehicle-treated rats. Compared with vehicle, bacitracin-treated rats showed increased diuresis and natriuresis in response to candesartan (10-µg iv bolus dose) suggesting higher AT 1 receptor function in these rats. These were associated with higher renin activities in the plasma and renal tissues. Furthermore, urinary 8-isoprostane and kidney injury molecule-1 levels were higher and urinary antioxidant capacity was lower in bacitracin-treated rats. Renal protein carbonyl and nitrotyrosine levels also were higher in bacitracin- compared with vehicle-treated rats, suggesting oxidative stress burden in bacitracin-treated rats. Moreover, PDI activity decreased and its protein levels increased in renal tissues of bacitracin-treated rats. Also, nuclear levels of Nrf2 transcription factor, which regulates redox homeostasis, were decreased in bacitracin-treated rats. Furthermore, tissue levels of Keap1, an Nrf2 inhibitory molecule, and tyrosine 216-phosphorylated GSK3β protein, an Nrf2 nuclear export protein, were increased in bacitracin-treated rats. These results suggest that renal PDI by regulating Keap1-Nrf2 pathway acts as an antioxidant, maintaining redox balance, renal AT 1 receptor function, and blood pressure in rats. Copyright © 2017 the American Physiological Society.

Phylogenetic Reconstruction by Cross-Species Chromosome Painting and G-Banding in Four Species of Phyllostomini Tribe (Chiroptera, Phyllostomidae) in the Brazilian Amazon: An Independent Evidence for Monophyly

PubMed Central

Ribas, Talita Fernanda Augusto; Rodrigues, Luis Reginaldo Ribeiro; Nagamachi, Cleusa Yoshiko; Gomes, Anderson José Baia; Rissino, Jorge das Dores; O'Brien, Patricia Caroline Mary; Yang, Fengtang; Ferguson-Smith, Malcolm Andrew; Pieczarka, Julio Cesar

2015-01-01

The subfamily Phyllostominae comprises taxa with a variety of feeding strategies. From the cytogenetic point of view, Phyllostominae shows different rates of chromosomal evolution between genera, with Phyllostomus hastatus probably retaining the ancestral karyotype for the subfamily. Since chromosomal rearrangements occur rarely in the genome and have great value as phylogenetic markers and in taxonomic characterization, we analyzed three species: Lophostoma silvicola (LSI), Phyllostomus discolor (PDI) and Tonatia saurophila (TSA), representing the tribe Phyllostomini, collected in the Amazon region, by classic and molecular cytogenetic techniques in order to reconstruct the phylogenetic relationships within this tribe. LSA has a karyotype of 2n=34 and FN=60, PDI has 2n=32 and FN=60 and TSA has 2n=16 and FN=20. Comparative analysis using G-banding and chromosome painting show that the karyotypic complement of TSA is highly rearranged relative to LSI and PHA, while LSI, PHA and PDI have similar karyotypes, differing by only three chromosome pairs. Nearly all chromosomes of PDI and PHA were conserved in toto, except for chromosome 15 that was changed by a pericentric inversion. A strongly supported phylogeny (bootstrap=100 and Bremer=10 steps), confirms the monophyly of Phyllostomini. In agreement with molecular topologies, TSA was in the basal position, while PHA and LSI formed sister taxa. A few ancestral syntenies are conserved without rearrangements and most associations are autapomorphic traits for Tonatia or plesiomorphic for the three genera analyzed here. The karyotype of TSA is highly derived in relation to that of other phyllostomid bats, differing from the supposed ancestral karyotype of Phyllostomidae by multiple rearrangements. Phylogenies based on chromosomal data are independent evidence for the monophyly of tribe Phyllostomini as determined by molecular topologies and provide additional support for the paraphyly of the genus Tonatia by the exclusion of the genus Lophostoma. PMID:25806812

In Silico Identification of Protein Disulfide Isomerase Gene Families in the De Novo Assembled Transcriptomes of Four Different Species of the Genus Conus.

PubMed

Figueroa-Montiel, Andrea; Ramos, Marco A; Mares, Rosa E; Dueñas, Salvador; Pimienta, Genaro; Ortiz, Ernesto; Possani, Lourival D; Licea-Navarro, Alexei F

2016-01-01

Small peptides isolated from the venom of the marine snails belonging to the genus Conus have been largely studied because of their therapeutic value. These peptides can be classified in two groups. The largest one is composed by peptides rich in disulfide bonds, and referred to as conotoxins. Despite the importance of conotoxins given their pharmacology value, little is known about the protein disulfide isomerase (PDI) enzymes that are required to catalyze their correct folding. To discover the PDIs that may participate in the folding and structural maturation of conotoxins, the transcriptomes of the venom duct of four different species of Conus from the peninsula of Baja California (Mexico) were assembled. Complementary DNA (cDNA) libraries were constructed for each species and sequenced using a Genome Analyzer Illumina platform. The raw RNA-seq data was converted into transcript sequences using Trinity, a de novo assembler that allows the grouping of reads into contigs without a reference genome. An N50 value of 605 was established as a reference for future assemblies of Conus transcriptomes using this software. Transdecoder was used to extract likely coding sequences from Trinity transcripts, and PDI-specific sequence motif "APWCGHCK" was used to capture potential PDIs. An in silico analysis was performed to characterize the group of PDI protein sequences encoded by the duct-transcriptome of each species. The computational approach entailed a structural homology characterization, based on the presence of functional Thioredoxin-like domains. Four different PDI families were characterized, which are constituted by a total of 41 different gene sequences. The sequences had an average of 65% identity with other PDIs. Using MODELLER 9.14, the homology-based three-dimensional structure prediction of a subset of the sequences reported, showed the expected thioredoxin fold which was confirmed by a "simulated annealing" method.

PDSS configuration control plan and procedures

NASA Technical Reports Server (NTRS)

1983-01-01

The payload development support system (PDSS) configuration control plan and procedures are presented. These plans and procedures establish the process for maintaining configuration control of the PDSS system, especially the Spacelab experiment interface device's (SEID) RAU, HRM, and PDI interface simulations and the PDSS ECOS DEP Services simulation. The plans and procedures as specified are designed to provide a simplified but complete configuration control process. The intent is to require a minimum amount of paperwork but provide total traceability of PDSS during experiment test activities.

Parametric decay instability near the upper hybrid resonance in magnetically confined fusion plasmas

NASA Astrophysics Data System (ADS)

Hansen, S. K.; Nielsen, S. K.; Salewski, M.; Stejner, M.; Stober, J.; the ASDEX Upgrade Team

2017-10-01

In this paper we investigate parametric decay of an electromagnetic pump wave into two electrostatic daughter waves, particularly an X-mode pump wave decaying into a warm upper hybrid wave (a limit of an electron Bernstein wave) and a warm lower hybrid wave. We describe the general theory of the above parametric decay instability (PDI), unifying earlier treatments, and show that it may occur in underdense and weakly overdense plasmas. The PDI theory is used to explain anomalous sidebands observed in collective Thomson scattering (CTS) spectra at the ASDEX Upgrade tokamak. The theory may also account for similar observations during CTS experiments in stellarators, as well as in some 1st harmonic electron cyclotron resonance and O-X-B heating experiments.

Systematic Approach for the Formulation and Optimization of Solid Lipid Nanoparticles of Efavirenz by High Pressure Homogenization Using Design of Experiments for Brain Targeting and Enhanced Bioavailability

PubMed Central

Gupta, Shweta; Kesarla, Rajesh; Chotai, Narendra; Misra, Ambikanandan

2017-01-01

The nonnucleoside reverse transcriptase inhibitors, used for the treatment of HIV infections, are reported to have low bioavailability pertaining to high first-pass metabolism, high protein binding, and enzymatic metabolism. They also show low permeability across blood brain barrier. The CNS is reported to be the most important HIV reservoir site. In the present study, solid lipid nanoparticles of efavirenz were prepared with the objective of providing increased permeability and protection of drug due to biocompatible lipidic content and nanoscale size and thus developing formulation having potential for enhanced bioavailability and brain targeting. Solid lipid nanoparticles were prepared by high pressure homogenization technique using a systematic approach of design of experiments (DoE) and evaluated for particle size, polydispersity index, zeta potential, and entrapment efficiency. Particles of average size 108.5 nm having PDI of 0.172 with 64.9% entrapment efficiency were produced. Zeta potential was found to be −21.2 mV and the formulation was found stable. The in-vivo pharmacokinetic studies revealed increased concentration of the drug in brain, as desired, when administered through intranasal route indicating its potential for an attempt towards complete eradication of HIV and cure of HIV-infected patients. PMID:28243600

Improved pharmacokinetics and antihyperlipidemic efficacy of rosuvastatin-loaded nanostructured lipid carriers.

PubMed

Rizwanullah, Md; Amin, Saima; Ahmad, Javed

2017-01-01

In the present study, rosuvastatin calcium-loaded nanostructured lipid carriers were developed and optimized for improved efficacy. The ROS-Ca-loaded NLC was prepared using melt emulsification ultrasonication technique and optimized by Box-Behnken statistical design. The optimized NLC composed of glyceryl monostearate (solid lipid) and capmul MCM EP (liquid lipid) as lipid phase (3% w/v), poloxamer 188 (1%) and tween 80 (1%) as surfactant. The mean particle size, polydispersity index (PDI), zeta potential (ζ) and entrapment efficiency (%) of optimized NLC formulation was observed to be 150.3 ± 4.67 nm, 0.175 ± 0.022, -32.9 ± 1.36 mV and 84.95 ± 5.63%, respectively. NLC formulation showed better in vitro release in simulated intestinal fluid (pH 6.8) than API suspension. Confocal laser scanning showed deeper permeation of formulation across rat intestine compared to rhodamine B dye solution. Pharmacokinetic study on female albino Wistar rats showed 5.4-fold increase in relative bioavailability with NLC compared to API suspension. Optimized NLC formulation also showed significant (p < 0.01) lipid lowering effect in hyperlipidemic rats. Therefore, NLC represents a great potential for improved efficacy of ROS-Ca after oral administration.

Enhanced Ungual Permeation of Terbinafine HCl Delivered Through Liposome-Loaded Nail Lacquer Formulation Optimized by QbD Approach.

PubMed

Shah, Viral H; Jobanputra, Amee

2018-01-01

The present investigation focused on developing, optimizing, and evaluating a novel liposome-loaded nail lacquer formulation for increasing the transungual permeation flux of terbinafine HCl for efficient treatment of onychomycosis. A three-factor, three-level, Box-Behnken design was employed for optimizing process and formulation parameters of liposomal formulation. Liposomes were formulated by thin film hydration technique followed by sonication. Drug to lipid ratio, sonication amplitude, and sonication time were screened as independent variables while particle size, PDI, entrapment efficiency, and zeta potential were selected as quality attributes for liposomal formulation. Multiple regression analysis was employed to construct a second-order quadratic polynomial equation and contour plots. Design space (overlay plot) was generated to optimize a liposomal system, with software-suggested levels of independent variables that could be transformed to desired responses. The optimized liposome formulation was characterized and dispersed in nail lacquer which was further evaluated for different parameters. Results depicted that the optimized terbinafine HCl-loaded liposome formulation exhibited particle size of 182 nm, PDI of 0.175, zeta potential of -26.8 mV, and entrapment efficiency of 80%. Transungual permeability flux of terbinafine HCl through liposome-dispersed nail lacquer formulation was observed to be significantly higher in comparison to nail lacquer with a permeation enhancer. The developed formulation was also observed to be as efficient as pure drug dispersion in its antifungal activity. Thus, it was concluded that the developed formulation can serve as an efficient tool for enhancing the permeability of terbinafine HCl across human nail plate thereby improving its therapeutic efficiency.

Marker-based linkage map of Andean common bean (Phaseolus vulgaris L.) and mapping of QTLs underlying popping ability traits

PubMed Central

2012-01-01

Background Nuña bean is a type of ancient common bean (Phaseolus vulgaris L.) native to the Andean region of South America, whose seeds possess the unusual property of popping. The nutritional features of popped seeds make them a healthy low fat and high protein snack. However, flowering of nuña bean only takes place under short-day photoperiod conditions, which means a difficulty to extend production to areas where such conditions do not prevail. Therefore, breeding programs of adaptation traits will facilitate the diversification of the bean crops and the development of new varieties with enhanced healthy properties. Although the popping trait has been profusely studied in maize (popcorn), little is known about the biology and genetic basis of the popping ability in common bean. To obtain insights into the genetics of popping ability related traits of nuña bean, a comprehensive quantitative trait loci (QTL) analysis was performed to detect single-locus and epistatic QTLs responsible for the phenotypic variance observed in these traits. Results A mapping population of 185 recombinant inbred lines (RILs) derived from a cross between two Andean common bean genotypes was evaluated for three popping related traits, popping dimension index (PDI), expansion coefficient (EC), and percentage of unpopped seeds (PUS), in five different environmental conditions. The genetic map constructed included 193 loci across 12 linkage groups (LGs), covering a genetic distance of 822.1 cM, with an average of 4.3 cM per marker. Individual and multi-environment QTL analyses detected a total of nineteen single-locus QTLs, highlighting among them the co-localized QTLs for the three popping ability traits placed on LGs 3, 5, 6, and 7, which together explained 24.9, 14.5, and 25.3% of the phenotypic variance for PDI, EC, and PUS, respectively. Interestingly, epistatic interactions among QTLs have been detected, which could have a key role in the genetic control of popping. Conclusions The QTLs here reported constitute useful tools for marker assisted selection breeding programs aimed at improving nuña bean cultivars, as well as for extending our knowledge of the genetic determinants and genotype x environment interaction involved in the popping ability traits of this bean crop. PMID:22873566

Imputation method for lifetime exposure assessment in air pollution epidemiologic studies

PubMed Central

2013-01-01

Background Environmental epidemiology, when focused on the life course of exposure to a specific pollutant, requires historical exposure estimates that are difficult to obtain for the full time period due to gaps in the historical record, especially in earlier years. We show that these gaps can be filled by applying multiple imputation methods to a formal risk equation that incorporates lifetime exposure. We also address challenges that arise, including choice of imputation method, potential bias in regression coefficients, and uncertainty in age-at-exposure sensitivities. Methods During time periods when parameters needed in the risk equation are missing for an individual, the parameters are filled by an imputation model using group level information or interpolation. A random component is added to match the variance found in the estimates for study subjects not needing imputation. The process is repeated to obtain multiple data sets, whose regressions against health data can be combined statistically to develop confidence limits using Rubin’s rules to account for the uncertainty introduced by the imputations. To test for possible recall bias between cases and controls, which can occur when historical residence location is obtained by interview, and which can lead to misclassification of imputed exposure by disease status, we introduce an “incompleteness index,” equal to the percentage of dose imputed (PDI) for a subject. “Effective doses” can be computed using different functional dependencies of relative risk on age of exposure, allowing intercomparison of different risk models. To illustrate our approach, we quantify lifetime exposure (dose) from traffic air pollution in an established case–control study on Long Island, New York, where considerable in-migration occurred over a period of many decades. Results The major result is the described approach to imputation. The illustrative example revealed potential recall bias, suggesting that regressions against health data should be done as a function of PDI to check for consistency of results. The 1% of study subjects who lived for long durations near heavily trafficked intersections, had very high cumulative exposures. Thus, imputation methods must be designed to reproduce non-standard distributions. Conclusions Our approach meets a number of methodological challenges to extending historical exposure reconstruction over a lifetime and shows promise for environmental epidemiology. Application to assessment of breast cancer risks will be reported in a subsequent manuscript. PMID:23919666

Neutralizing Monoclonal Antibodies against Ricin’s Enzymatic Subunit Interfere with Protein Disulfide Isomerase-Mediated Reduction of Ricin Holotoxin In Vitro

PubMed Central

O’Hara, Joanne M.; Mantis, Nicholas J.

2013-01-01

The penultimate event in the intoxication of mammalian cells by ricin toxin is the reduction, in the endoplasmic reticulum (ER), of the intermolecular disulfide bond that links ricin’s enzymatic (RTA) and binding (RTB) subunits. In this report we adapted an in vitro protein disulfide isomerase (PDI)-mediated reduction assay to test the hypothesis that the RTA-specific neutralizing monoclonal antibody (mAb) IB2 interferes with the liberation of RTA from RTB. IB2 recognizes an epitope located near the interface between RTA and RTB and, like a number of other RTA-specific neutralizing mAbs, is proposed to neutralize ricin intracellularly. In this study, we found that IB2 virtually eliminated the reduction of ricin holotoxin into RTA and RTB in vitro. Surprisingly, three other neutralizing mAbs (GD12, R70 and SyH7) that bind epitopes at considerable distance from ricin’s disulfide bond were as effective (or nearly as effective) as IB2 in interfering with PDI-mediated liberation of RTA from RTB. By contrast, two non-neutralizing RTA-specific mAbs, FGA12 and SB1, did not affect PDI-mediated reduction of ricin. These data reveal a possible mechanism by which RTA-specific antibodies may neutralize ricin intracellularly, provided they are capable of trafficking in association with ricin from the cell surface to the ER. PMID:23774033

Optimization of ciprofloxacin complex loaded PLGA nanoparticles for pulmonary treatment of cystic fibrosis infections: Design of experiments approach.

PubMed

Günday Türeli, Nazende; Türeli, Akif Emre; Schneider, Marc

2016-12-30

Design of Experiments (DoE) is a powerful tool for systematic evaluation of process parameters' effect on nanoparticle (NP) quality with minimum number of experiments. DoE was employed for optimization of ciprofloxacin loaded PLGA NPs for pulmonary delivery against Pseudomonas aeruginosa infections in cystic fibrosis (CF) lungs. Since the biofilm produced by bacteria was shown to be a complicated 3D barrier with heterogeneous meshes ranging from 100nm to 500nm, nanoformulations small enough to travel through those channels were assigned as target quality. Nanoprecipitation was realized utilizing MicroJet Reactor (MJR) technology based on impinging jets principle. Effect of MJR parameters flow rate, temperature and gas pressure on particle size and PDI was investigated using Box-Behnken design. The relationship between process parameters and particle quality was demonstrated by constructed fit functions (R 2 =0.9934 p<0.0001 and R 2 =0.9983 p<0.0001, for particle size and PDI, respectively). Prepared nanoformulations varied between 145.2 and 979.8nm with PDI ranging from 0.050 to 1.00 and showed encapsulation efficiencies >65%. Response surface plots provided experimental data-based understanding of MJR parameters' effect, thus NP quality. Presented work enables ciprofloxacin loaded PLGA nanoparticle preparations with pre-defined quality to fulfill the requirements of local drug delivery under CF disease conditions. Copyright © 2016 Elsevier B.V. All rights reserved.

Effect of Energy Alignment, Electron Mobility, and Film Morphology of Perylene Diimide Based Polymers as Electron Transport Layer on the Performance of Perovskite Solar Cells.

PubMed

Guo, Qiang; Xu, Yingxue; Xiao, Bo; Zhang, Bing; Zhou, Erjun; Wang, Fuzhi; Bai, Yiming; Hayat, Tasawar; Alsaedi, Ahmed; Tan, Zhan'ao

2017-03-29

For organic-inorganic perovskite solar cells (PerSCs), the electron transport layer (ETL) plays a crucial role in efficient electron extraction and transport for high performance PerSCs. Fullerene and its derivatives are commonly used as ETL for p-i-n structured PerSCs. However, these spherical small molecules are easy to aggregate with high annealing temperature and thus induce morphology stability problems. N-type conjugated polymers are promising candidates to overcome these problems due to the tunable energy levels, controllable aggregation behaviors, and good film formation abilities. Herein, a series of perylene diimide (PDI) based polymers (PX-PDIs), which contain different copolymeried units (X), including vinylene (V), thiophene (T), selenophene (Se), dibenzosilole (DBS), and cyclopentadithiophene (CPDT), are introduced as ETL for p-i-n structured PerSCs. The effect of energy alignment, electron mobility, and film morphology of these ETLs on the photovoltaic performance of the PerSCs are fully investigated. Among the PX-PDIs, PV-PDI demonstrates the deeper LUMO energy level, the highly delocalized LUMO electron density, and a better planar structure, making it the best electron transport material for PerSCs. The planar heterojunction PerSC with PV-PDI as ETL achieves a power conversion efficiency (PCE) of 10.14%, among the best values for non-fullerene based PerSCs.

Photodynamic inactivation assisted by localized surface plasmon resonance of silver nanoparticles: In vitro evaluation on Escherichia coli and Streptococcus mutans.

PubMed

Ribeiro, Martha S; de Melo, Luciana S A; Farooq, Sajid; Baptista, Alessandra; Kato, Ilka T; Núñez, Silvia C; de Araujo, Renato E

2018-06-01

Localized surface plasmon resonance (LSPR) of gold nanoparticles has been reported to increase the antimicrobial effect of the photodynamic therapy. Although silver nanoparticles (AgNPs) are an efficient growth inhibitor of microorganisms, no studies exploring LSPR of AgNPs to enhance the photodynamic inactivation (PDI) have been related. In this work, we described the LSPR phenomenon of AgNP sand investigated its interaction with riboflavin, a natural photosensitizer. We evaluated the use of AgNPs coated with pectin (p-AgNP) in riboflavin (Rb)-mediated PDI of Escherichia coli (Gram- bacteria) and Streptococcus mutans (Gram + bacteria) using a blue light-emitting diode (λ = 455 ± 20 nm) of optical power 200 mW. Irradiance was 90 mW/cm 2 and radiant exposure varied according to the time exposure. Uptake of Rb and p-AgNP by the cells was evaluated by measuring the supernatant absorption spectra of the samples. We observed that LSPR of p-AgNPs was able to enhance the riboflavin photodynamic action on S. mutans but not on E. coli, probably due to the lower uptake of Rb by E. coli. Taken together, our results provide insights to explore the use of the LPRS promoted by silver nanostructures to optimize antimicrobial PDI protocols. Copyright © 2018 Elsevier B.V. All rights reserved.

Organophosphate Pesticide Exposure and Neurodevelopment in Young Mexican-American Children

PubMed Central

Eskenazi, Brenda; Marks, Amy R.; Bradman, Asa; Harley, Kim; Barr, Dana B.; Johnson, Caroline; Morga, Norma; Jewell, Nicholas P.

2007-01-01

Background Organophosphate (OP) pesticides are widely used in agriculture and homes. Animal studies suggest that even moderate doses are neurodevelopmental toxicants, but there are few studies in humans. Objectives We investigated the relationship of prenatal and child OP urinary metabolite levels with children’s neurodevelopment. Methods Participating children were from a longitudinal birth cohort of primarily Latino farm-worker families in California. We measured six nonspecific dialkylphosphate (DAP) metabolites in maternal and child urine as well as metabolites specific to malathion (MDA) and chlorpyrifos (TCPy) in maternal urine. We examined their association with children’s performance at 6 (n = 396), 12 (n = 395), and 24 (n = 372) months of age on the Bayley Scales of Infant Development [Mental Development (MDI) and Psychomotor Development (PDI) Indices] and mother’s report on the Child Behavior Checklist (CBCL) (n = 356). Results Generally, pregnancy DAP levels were negatively associated with MDI, but child measures were positively associated. At 24 months of age, these associations reached statistical significance [per 10-fold increase in prenatal DAPs: β = −3.5 points; 95% confidence interval (CI), −6.6 to −0.5; child DAPs: β = 2.4 points; 95% CI, 0.5 to 4.2]. Neither prenatal nor child DAPs were associated with PDI or CBCL attention problems, but both prenatal and postnatal DAPs were associated with risk of pervasive developmental disorder [per 10-fold increase in prenatal DAPs: odds ratio (OR) = 2.3, p = 0.05; child DAPs OR = 1.7, p = 0.04]. MDA and TCPy were not associated with any outcome. Conclusions We report adverse associations of prenatal DAPs with mental development and pervasive developmental problems at 24 months of age. Results should be interpreted with caution given the observed positive relationship with postnatal DAPs. PMID:17520070

Compressibility effects on dynamic stall of airfoils undergoing rapid transient pitching motion

NASA Technical Reports Server (NTRS)

Chandrasekhara, M. S.; Platzer, M. F.

1992-01-01

The research was carried out in the Compressible Dynamic Stall Facility, CDSF, at the Fluid Mechanics Laboratory (FML) of NASA Ames Research Center. The facility can produce realistic nondimensional pitch rates experienced by fighter aircraft, which on model scale could be as high as 3600/sec. Nonintrusive optical techniques were used for the measurements. The highlight of the effort was the development of a new real time interferometry method known as Point Diffraction Interferometry - PDI, for use in unsteady separated flows. This can yield instantaneous flow density information (and hence pressure distributions in isentropic flows) over the airfoil. A key finding is that the dynamic stall vortex forms just as the airfoil leading edge separation bubble opens-up. A major result is the observation and quantification of multiple shocks over the airfoil near the leading edge. A quantitative analysis of the PDI images shows that pitching airfoils produce larger suction peaks than steady airfoils at the same Mach number prior to stall. The peak suction level reached just before stall develops is the same at all unsteady rates and decreases with increase in Mach number. The suction is lost once the dynamic stall vortex or vortical structure begins to convect. Based on the knowledge gained from this preliminary analysis of the data, efforts to control dynamic stall were initiated. The focus of this work was to arrive at a dynamically changing leading edge shape that produces only 'acceptable' airfoil pressure distributions over a large angle of attack range.

Inactivation of pathogenic bacteria in food matrices: high pressure processing, photodynamic inactivation and pressure-assisted photodynamic inactivation

NASA Astrophysics Data System (ADS)

Cunha, A.; Couceiro, J.; Bonifácio, D.; Martins, C.; Almeida, A.; Neves, M. G. P. M. S.; Faustino, M. A. F.; Saraiva, J. A.

2017-09-01

Traditional food processing methods frequently depend on the application of high temperature. However, heat may cause undesirable changes in food properties and often has a negative impact on nutritional value and organoleptic characteristics. Therefore, reducing the microbial load without compromising the desirable properties of food products is still a technological challenge. High-pressure processing (HPP) can be classified as a cold pasteurization technique, since it is a non-thermal food preservation method that uses hydrostatic pressure to inactivate spoilage microorganisms. At the same time, it increases shelf life and retains the original features of food. Photodynamic inactivation (PDI) is also regarded as promising approach for the decontamination of food matrices. In this case, the inactivation of bacterial cells is achieved by the cytotoxic effects of reactive oxygens species (ROS) produced from the combined interaction of a photosensitizer molecule, light and oxygen. This short review examines some recent developments on the application of HPP and PDI with food-grade photosensitizers for the inactivation of listeriae, taken as a food pathogen model. The results of a proof-of-concept trial of the use of high-pressure as a coadjutant to increase the efficiency of photodynamic inactivation of bacterial endospores is also addressed.

Photodynamic inactivation of pathogenic species Pseudomonas aeruginosa and Candida albicans with lutetium (III) acetate phthalocyanines and specific light irradiation.

PubMed

Mantareva, Vanya; Kussovski, Vesselin; Durmuş, Mahmut; Borisova, Ekaterina; Angelov, Ivan

2016-11-01

Photodynamic inactivation (PDI) is a light-associated therapeutic approach suitable for treatment of local acute infections. The method is based on specific light-activated compound which by specific irradiation and in the presence of molecular oxygen produced molecular singlet oxygen and other reactive oxygen species, all toxic for pathogenic microbial cells. The study presents photodynamic impact of two recently synthesized water-soluble cationic lutetium (III) acetate phthalocyanines (LuPc-5 and LuPc-6) towards two pathogenic strains, namely, the Gram-negative bacterium Pseudomonas aeruginosa and a fungus Candida albicans. The photodynamic effect was evaluated for the cells in suspensions and organized in 48-h developed biofilms. The relatively high levels of uptakes of LuPc-5 and LuPc-6 were determined for fungal cells compared to bacterial cells. The penetration depths and distribution of both LuPcs into microbial biofilms were investigated by means of confocal fluorescence microscopy. The photoinactivation efficiency was studied for a wide concentration range (0.85-30 μM) of LuPc-5 and LuPc-6 at a light dose of 50 J cm -2 from red light-emitting diode (LED; 665 nm). The PDI study on microbial biofilms showed incomplete photoinactivation (<3 logs) for the used gentle drug-light protocol.

Development of a DNA-liposome complex for gene delivery applications.

PubMed

Rasoulianboroujeni, M; Kupgan, G; Moghadam, F; Tahriri, M; Boughdachi, A; Khoshkenar, P; Ambrose, J J; Kiaie, N; Vashaee, D; Ramsey, J D; Tayebi, L

2017-06-01

The association structures formed by cationic liposomes and DNA (Deoxyribonucleic acid)-liposome have been effectively utilized as gene carriers in transfection assays. In this research study, cationic liposomes were prepared using a modified lipid film hydration method consisting of a lyophilization step for gene delivery applications. The obtained results demonstrated that the mean particle size had no significant change while the polydispersity (PDI) increased after lyophilization. The mean particle size slightly reduced after lyophilization (520±12nm to 464±25nm) while the PDI increased after lyophilization (0.094±0.017 to 0.220±0.004). In addition. The mean particle size of vesicles increases when DNA is incorporated to the liposomes (673±27nm). According to the Scanning Electron Microscopy (SEM) and transmission electron microscopy (TEM) images, the spherical shape of liposomes confirmed their successful preservation and reconstitution from the powder. It was found that liposomal formulation has enhanced transfection considerably compared to the naked DNA as negative control. Finally, liposomal formulation in this research had a better function than Lipofectamine® 2000 as a commercialized product because the cellular activity (cellular protein) was higher in the prepared lipoplex than Lipofectamine® 2000. Copyright © 2017 Elsevier B.V. All rights reserved.

Denudational slope processes on weathered basalt in northern California: 130 ka history of soil development, periods of slope stability and colluviation, and climate change

NASA Astrophysics Data System (ADS)

McDonald, Eric; Harrison, Bruce; Baldwin, John; Page, William; Rood, Dylan

2017-04-01

The geomorphic history of hillslope evolution is controlled by multiple types of denudational processes. Detailed analysis of hillslope soil-stratigraphy provides a means to identify the timing of periods of slope stability and non-stability, evidence of the types of denudational processes, and possible links to climatic drivers. Moreover, the degree of soil formation and the presence of buried or truncated soils provide evidence of the relative age of alternating periods of colluviation and stability. We use evaluation of soil stratigraphy, for a small forested hillslope (<500 m of slope length) located in the Cascades of northern California, to elucidate both the timing and processes controlling 130 ka of hillslope evolution. The soils and slope colluvium are derived from highly weathered basalt. Stratigraphic interpretation is reinforced with soil profile development index (PDI) derived age estimates, tephrochronology, luminescence ages on colluvium, and He3 nuclide exposure dates. Soils formed along hilltop ridges are well developed and reflect deep (>2-3 m) in-situ weathering of the basalt bedrock. PDI age estimates and He3 exposure dates indicate that these hilltop soils had been in place for 100-130 ka, implying a long period of relative surface stability. At about 40-30 ka, soil stratigraphy indicates the onset of 3 distinct cycles of denudation of the hilltop and slopes. Evidence for changes in stability and onset of soil erosion is the presence of several buried soils formed in colluvium downslope of the hilltop. These buried soils have formed in sediment derived from erosion of the hilltop soils (i.e. soil parent material of previously weathered soil matrix and basalt cobbles). The oldest buried soil indicates that slope stability was re-established between 32-23 ka, with stability and soil formation lasting to about 10 ka. Soil-stratigraphy indicates that two additional intervals of downslope transport of sediment between 6-10 ka, and 2-5 ka. Soil properties indicate that the primary method of downslope transport is largely due to tree throw and faunal burrowing. Onset of slope instability at 40-30 ka appears to be related to changes in vegetation with establishment of a pine dominated forest (increase in tree throw) and/or onset of local faulting. By comparison, slope stability from 30-10 ka appears to be a related to the formation of a shrub dominated steppe and a decrease in tree throw. The two periods of slope erosion after 10 ka appear related to regional periods of pronounced channel incision. Results indicate that soil stratigraphy can provide a key record of slope evolution and related paleoenvironmental changes.

First Principles Optical Absorption Spectra of Organic Molecules Adsorbed on Titania Nanoparticles

NASA Astrophysics Data System (ADS)

Baishya, Kopinjol; Ogut, Serdar; Mete, Ersen; Gulseren, Oguz; Ellialtioglu, Sinasi

2012-02-01

We present results from first principles computations on passivated rutile TiO2 nanoparticles in both free-standing and dye-sensitized configurations to investigate the size dependence of their optical absorption spectra. The computations are performed using time-dependent density functional theory (TDDFT) as well as GW-Bethe-Salpeter-Equation (GWBSE) methods and compared with each other. We interpret the first principles spectra for free-standing TiO2 nanoparticles within the framework of the classical Mie-Gans theory using the bulk dielectric function of TiO2. We investigate the effects of the titania support on the absorption spectra of a particular set of perylene-diimide (PDI) derived dye molecules, namely brominated PDI (Br2C24H8N2O4) and its glycine and aspartine derivatives.

Specificity in substrate binding by protein folding catalysts: tyrosine and tryptophan residues are the recognition motifs for the binding of peptides to the pancreas-specific protein disulfide isomerase PDIp.

PubMed Central

Ruddock, L. W.; Freedman, R. B.; Klappa, P.

2000-01-01

Using a cross-linking approach, we recently demonstrated that radiolabeled peptides or misfolded proteins specifically interact in vitro with two luminal proteins in crude extracts from pancreas microsomes. The proteins were the folding catalysts protein disulfide isomerase (PDI) and PDIp, a glycosylated, PDI-related protein, expressed exclusively in the pancreas. In this study, we explore the specificity of these proteins in binding peptides and related ligands and show that tyrosine and tryptophan residues in peptides are the recognition motifs for their binding by PDIp. This peptide-binding specificity may reflect the selectivity of PDIp in binding regions of unfolded polypeptide during catalysis of protein folding. PMID:10794419

Pain exposure physical therapy (PEPT) compared to conventional treatment in complex regional pain syndrome type 1: a randomised controlled trial

PubMed Central

Barnhoorn, Karlijn J; van de Meent, Henk; van Dongen, Robert T M; Klomp, Frank P; Groenewoud, Hans; Samwel, Han; Nijhuis-van der Sanden, Maria W G; Frölke, Jan Paul M; Staal, J Bart

2015-01-01

Objective To compare the effectiveness of pain exposure physical therapy (PEPT) with conventional treatment in patients with complex regional pain syndrome type 1 (CRPS-1) in a randomised controlled trial with a blinded assessor. Setting The study was conducted at a level 1 trauma centre in the Netherlands. Participants 56 adult patients with CRPS-1 participated. Three patients were lost to follow-up. Interventions Patients received either PEPT in a maximum of five treatment sessions, or conventional treatment following the Dutch multidisciplinary guideline. Measurements Outcomes were assessed at baseline and at 3, 6 and 9 months after randomisation. The primary outcome measure was the Impairment level Sum Score—Restricted Version (ISS-RV), consisting of visual analogue scale for pain (VAS-pain), McGill Pain Questionnaire, active range of motion (AROM) and skin temperature. Secondary outcome measures included Pain Disability Index (PDI); muscle strength; Short Form 36 (SF-36); disability of arm, shoulder and hand; Lower Limb Tasks Questionnaire (LLTQ); 10 m walk test; timed up-and-go test (TUG) and EuroQol-5D. Results The intention-to-treat analysis showed a clinically relevant decrease in ISS-RV (6.7 points for PEPT and 6.2 points for conventional treatment), but the between-group difference was not significant (0.96, 95% CI −1.56 to 3.48). Participants allocated to PEPT experienced a greater improvement in AROM (between-group difference 0.51, 95% CI 0.07 to 0.94; p=0.02). The per protocol analysis showed larger and significant between-group effects on ISS-RV, VAS-pain, AROM, PDI, SF-36, LLTQ and TUG. Conclusions We cannot conclude that PEPT is superior to conventional treatment for patients with CRPS-1. Further high-quality research on the effects of PEPT is warranted given the potential effects as indicated by the per protocol analysis. Trial registration numbers NCT00817128 and NTR 2090. PMID:26628523

Effects of processing, particle size and moisturizing of sorghum-based feeds on pellet quality and broiler production.

PubMed

da Silva, Patrícia Garcia; Oliveira, Luana Martins Schaly; de Oliveira, Nayanne Rodrigues; de Moura Júnior, Fábio Ataides; Silva, Maura Regina Sousa; Cordeiro, Deibity Alves; Minafra, Cibele Silva; Dos Santos, Fabiana Ramos

2018-01-01

This study aimed to assess the effect of pelleted and expanded sorghum-based feeds prepared with different moisture levels and particle size of ingredients on metabolizable energy, ileal digestibility of amino acids and broiler performance. The experiment was performed with 720 male broiler chicks of the Cobb strain, with treatments of six replications, with 15 birds each; they were arranged in a completely randomized design and 2×2×2 factorial scheme (pelleted or expanded feed processing, 0.8% or 1.6% moisture addition in the mixer, and particle size of 650 or 850 microns). Higher pellet quality (pellets, % and pellet durability index [PDI]) was obtained in expanded diets and inclusion of 1.6% moisture. The particle size of 850 microns increased the PDI of final diet. All studied treatments had no significant effect on weight gain and broiler carcass and cut yields. Lower feed conversion occurred for birds fed pelleted feed at 42 d. The highest apparent metabolizable energy (AME) and apparent metabolizable energy corrected to zero nitrogen balance (AMEn) values of feed in the initial rearing phase (10 to 13 days) were observed in birds fed pelleted feed or for feed prepared with 1.6% moisture. The highest ileal digestibility coefficients of amino acids were obtained with the consumption of pelleted feed prepared with a particle size of 650 microns and 1.6% moisture. Pelleted feed prepared with a milling particle size of 650 microns and 1.6% moisture provided increased ileal digestibility of amino acids and AMEn in the starter period. However, the expanded feed improved pellet quality and feed conversion of broilers at 42 days of age. We conclude that factors such as moisture, particle size and processing affect the pellet quality, and therefore should be considered when attempting to optimize broiler performance.

Effects of processing, particle size and moisturizing of sorghum-based feeds on pellet quality and broiler production

PubMed Central

2018-01-01

Objective This study aimed to assess the effect of pelleted and expanded sorghum-based feeds prepared with different moisture levels and particle size of ingredients on metabolizable energy, ileal digestibility of amino acids and broiler performance. Methods The experiment was performed with 720 male broiler chicks of the Cobb strain, with treatments of six replications, with 15 birds each; they were arranged in a completely randomized design and 2×2×2 factorial scheme (pelleted or expanded feed processing, 0.8% or 1.6% moisture addition in the mixer, and particle size of 650 or 850 microns). Results Higher pellet quality (pellets, % and pellet durability index [PDI]) was obtained in expanded diets and inclusion of 1.6% moisture. The particle size of 850 microns increased the PDI of final diet. All studied treatments had no significant effect on weight gain and broiler carcass and cut yields. Lower feed conversion occurred for birds fed pelleted feed at 42 d. The highest apparent metabolizable energy (AME) and apparent metabolizable energy corrected to zero nitrogen balance (AMEn) values of feed in the initial rearing phase (10 to 13 days) were observed in birds fed pelleted feed or for feed prepared with 1.6% moisture. The highest ileal digestibility coefficients of amino acids were obtained with the consumption of pelleted feed prepared with a particle size of 650 microns and 1.6% moisture. Conclusion Pelleted feed prepared with a milling particle size of 650 microns and 1.6% moisture provided increased ileal digestibility of amino acids and AMEn in the starter period. However, the expanded feed improved pellet quality and feed conversion of broilers at 42 days of age. We conclude that factors such as moisture, particle size and processing affect the pellet quality, and therefore should be considered when attempting to optimize broiler performance. PMID:28920405

Formulation and statistical optimization of self-microemulsifying drug delivery system of eprosartan mesylate for improvement of oral bioavailability.

PubMed

Dangre, Pankaj; Gilhotra, Ritu; Dhole, Shashikant

2016-10-01

The present investigation is aimed to design a statistically optimized self-microemulsifying drug delivery system (SMEDDS) of eprosartan mesylate (EM). Preliminary screening was carried out to find a suitable combination of various excipients for the formulation. A 3(2) full factorial design was employed to determine the effect of various independent variables on dependent (response) variables. The independent variables studied in the present work were concentration of oil (X 1) and the ratio of S mix (X 2), whereas the dependent variables were emulsification time (s), globule size (nm), polydispersity index (pdi), and zeta potential (mV), and the multiple linear regression analysis (MLRA) was employed to understand the influence of independent variables on dependent variables. Furthermore, a numerical optimization technique using the desirability function was used to develop a new optimized formulation with desired values of dependent variables. The optimized SMEDDS formulation of eprosartan mesylate (EMF-O) by the above method exhibited emulsification time, 118.45 ± 1.64 s; globule size, 196.81 ± 1.29 nm; zeta potential, -9.34 ± 1.2 mV, and polydispersity index, 0.354 ± 0.02. For the in vitro dissolution study, the optimized formulation (EMF-O) and pure drug were separately entrapped in the dialysis bag, and the study indicated higher release of the drug from EMF-O. In vivo pharmacokinetic studies in Wistar rats using PK solver software revealed 2.1-fold increment in oral bioavailability of EM from EMF-O, when compared with plain suspension of pure drug.

Development and stability evaluation of olive oil nanoemulsion using sucrose monoester laurate

NASA Astrophysics Data System (ADS)

Eid, Ahmad M. M.; Baie, Saringat Haji; Arafat, Osama

2012-11-01

Nanoemulsion is a type of emulsion that consists of fine oil-in-water dispersions, with the droplets covering the size range of 20-200 nm. It can be achieved through emulsification process. One of the processes is through low energy emulsification method. Olive oil was chosen in this study due to its efficiency in treating skin problem. Olive oil nanophase gel (NPG) formulations were performed through various ratios of olive oil, sucrose laurate and glycerin. The particle sizes and stability of the prepared olive oil nanophase gel were evaluated and the optimal formulation was then selected for the development of olive oil nanoemulsion. This study proved that the composition of oil and surfactant play an important roles in influencing the nanophase gel droplet size. Nanophase gels containing olive oil in the concentration of 50 and 60 % show good stability at 4 °C and room temperature while it was less stable at 40 °C. Olive oil nanophase gels in the concentration of 50 % and 60 % with sucrose laurate 25 % in each formulation were good candidates to prepare nanoemulsion because they have the suitable droplets size and Polydispersing Index (PDI) when compared to other formulations. A mixture of NPG 50 % and water in the ratio of 40:60 and NPG 60 % and water in the ratio of 33.3:66.7 were used to produce nanoemulsions containing 20 % of oil with negative values of zeta potential (>60) which indicate the good stability of the nanoemulsions.

Control of unsteady separated flow associated with the dynamic stall of airfoils

NASA Technical Reports Server (NTRS)

Wilder, Michael C.

1992-01-01

The two principal objectives of this research were to achieve an improved understanding of the mechanisms involved in the onset and development of dynamic stall under compressible flow conditions, and to investigate the feasibility of employing adaptive airfoil geometry as an active flow control device in the dynamic stall engine. Presented here are the results of a quantitative (PDI) study of the compressibility effects on dynamic stall over the transiently pitching airfoil, as well as a discussion of a preliminary technique developed to measure the deformation produced by the adaptive geometry control device, and bench test results obtained using an airfoil equipped with the device.

Chlorogenic acid stabilized nanostructured lipid carriers (NLC) of atorvastatin: formulation, design and in vivo evaluation.

PubMed

Khan, Saba; Baboota, Sanjula; Ali, Javed; Narang, R S; Narang, Jasjeet K

2016-01-01

The present work was aimed at developing an optimized oral nanostructured lipid carrier (NLC) formulation of poorly soluble atorvastatin Ca (AT Ca) and assessing its in vitro release, oral bioavailability and pharmacodynamic activity. In this study, chlorogenic acid, a novel excipient having synergistic cholesterol lowering activity was utilized and explored in NLC formulation development. The drug-loaded NLC formulations were prepared using a high pressure homogenization technique and optimized by the Box-Behnken statistical design using the Design-Expert software. The optimized NLC formulation was composed of oleic acid and stearic acid as lipid phase (0.9% w/v), poloxamer 188 as surfactant (1% w/v) and chlorogenic acid (0.05% w/v). The mean particle size, polydispersity index (PDI) and % drug entrapment efficiency of optimized NLC were 203.56 ± 8.57 nm, 0.27 ± 0.028 and 83.66 ± 5.69, respectively. In vitro release studies showed that the release of drug from optimized NLC formulations were markedly enhanced as compared to solid lipid nanoparticles (SLN) and drug suspension. The plasma concentration time profile of AT Ca in rats showed 3.08- and 4.89-fold increase in relative bioavailability of developed NLC with respect to marketed preparation (ATORVA® tablet) and drug suspension, respectively. Pharmacodynamic study suggested highly significant (**p < 0.01) reduction in the cholesterol and triglyceride values by NLC in comparison with ATORVA® tablet. Therefore, the results of in vivo studies demonstrated promising prospects for successful oral delivery of AT Ca by means of its chlorogenic acid integrated NLC.

Effect of drying conditions on crystallinity of amylose nanoparticles prepared by nanoprecipitation.

PubMed

Yan, Xiaoxia; Chang, Yanjiao; Wang, Qian; Fu, Youjia; Zhou, Jiang

2017-04-01

In this study, amylose nanoparticles prepared by nanoprecipitation were dried at different conditions. The crystalline structure, crystallinity, re-dispersibility and morphological characteristic of the amylose nanoparticles after drying were investigated. X-ray diffraction analysis revealed that the V-type crystalline structure of the amylose nanoparticles formed in the drying process instead of the precipitation process, and drying condition significantly affects the crystallinity. The temperature cycles drying at 4°C and 40°C considerably increased crystallinity of the amylose nanoparticles, 24h (4/40°C, 12h/12h) drying under 11% relative humidity could give rise to a crystallinity up to 50.05%. The applied drying procedures had no obvious effect on the appearance of the amylose nanoparticles. The Z average-size (d. nm) and polydispersity index (PDI) obtained from dynamic light scattering analysis suggested that the drying processes caused some aggregates, but the dried amylose nanoparticles could be well dispersed in water. Copyright © 2017 Elsevier B.V. All rights reserved.

Encapsulation and release studies of strawberry polyphenols in biodegradable chitosan nanoformulation.

PubMed

Pulicharla, Rama; Marques, Caroline; Das, Ratul Kumar; Rouissi, Tarek; Brar, Satinder Kaur

2016-07-01

Polyphenols (negative groups) of strawberry extract interacts with positively protonated amino groups of chitosan which helps in maximum encapsulation. This approach can improve the bioavailability and sustained release of phytochemicals having lower bioavailability. The optimum mass ratio of chitosan-tripolyphosphate and polyphenols (PPs) loading was investigated to be 3:1 and 0.5mg/ml of strawberry extract, respectively. Prepared nanoformulation were characterized by UV-vis spectroscopy, Fourier transform infrared spectroscopy and scanning electron microscopy. The formed particles size ranged between 300 and 600nm and polydispersity index (PDI) of≈0.5. The optimized formulation showed encapsulation efficiency of 58.09% at 36.47% of polyphenols loading. Initial burst and continuous release of PPs was observed at pH 7.4 of in vitro release studies. PPs release profile at this pH was found to be non-Fickian analomous diffusion and the release was followed first order kinetics. And at pH 1.4, diffusion-controlled Fickian release of PPs was observed. Copyright © 2016 Elsevier B.V. All rights reserved.

The study of size and stability of n-butylcyanoacrylate nanocapsule suspensions encapsulating green grass fragrance

NASA Astrophysics Data System (ADS)

Zhu, G. Y.; Lin, C. T.; Chen, J. M.; Lei, D. M.; Zhu, G. X.

2018-01-01

Green grass fragrance has been widely used in many fields. However, fragrances are volatile compounds that do not last long. In order to prolong its odor, nanocapsules encapsulated green grass fragrance were prepared. The paper deals with the preparation of green grass fragrance nanocapsules by emulsion polymerization. N-butylcyanoacrylate (BCA) with excellent biocompatibility and biodegradability was used as encapsulant. The nanocapsule suspension systems were characterized and its stability was investigated. The physicochemical properties of polymeric nanocapsules (average diameter and polydispersity) were evaluated as a function of time to assess the system stability. The result showed that the system (containing 0.8% of green grass fragrance, with a polydispersity index (PDI) near 0.1 and an average diameter in the range of 20-30 nm) was an ideal state and relatively stable. Besides, the distinction of stability of three nanocapsule suspensions with different green grass fragrance content was also obvious from scanning electron microscopy (SEM).

Development of High Speed Imaging and Analysis Techniques Compressible Dynamics Stall

NASA Technical Reports Server (NTRS)

Chandrasekhara, M. S.; Carr, L. W.; Wilder, M. C.; Davis, Sanford S. (Technical Monitor)

1996-01-01

Dynamic stall has limited the flight envelope of helicopters for many years. The problem has been studied in the laboratory as well as in flight, but most research, even in the laboratory, has been restricted to surface measurement techniques such as pressure transducers or skin friction gauges, except at low speed. From this research, it became apparent that flow visualization tests performed at Mach numbers representing actual flight conditions were needed if the complex physics associated with dynamic stall was to be properly understood. However, visualization of the flow field during compressible conditions required carefully aligned and meticulously reconstructed holographic interferometry. As part of a long-range effort focused on exposing of the physics of compressible dynamic stall, a research wind tunnel was developed at NASA Ames Research Center which permits visual access to the full flow field surrounding an oscillating airfoil during compressible dynamic stall. Initially, a stroboscopic schlieren technique was used for visualization of the stall process, but the primary research tool has been point diffraction interferometry(PDI), a technique carefully optimized for use in th is project. A review of the process of development of PDI will be presented in the full paper. One of the most valuable aspects of PDI is the fact that interferograms are produced in real time on a continuous basis. The use of a rapidly-pulsed laser makes this practical; a discussion of this approach will be presented in the full paper. This rapid pulsing(up to 40,000 pulses/sec) produces interferograms of the rapidly developing dynamic stall field in sufficient resolution(both in space and time) that the fluid physics of the compressible dynamic stall flowfield can be quantitatively determined, including the gradients of pressure in space and time. This permits analysis of the influence of the effect of pitch rate, Mach number, Reynolds number, amplitude of oscillation, and other parameters on the dynamic stall process. When interferograms can be captured in real time, the potential for real-time mapping of a developing unsteady flow such as dynamic stall becomes a possibility. This has been achieved in the present case through the use of a high-speed drum camera combined with electronic circuitry which has resulted in a series of interferograms obtained during a single cycle of dynamic stall; images obtained at the rate of 20 KHz will be presented as a part of the formal presentation. Interferometry has been available for a long time; however, most of its use has been limited to visualization. The present research has focused on use of interferograms for quantitative mapping of the flow over oscillating airfoils. Instantaneous pressure distributions can now be obtained semi-automatically, making practical the analysis of the thousands of interferograms that are produced in this research. A review of the techniques that have been developed as part of this research effort will be presented in the final paper.

Pixel-wise deblurring imaging system based on active vision for structural health monitoring at a speed of 100 km/h

NASA Astrophysics Data System (ADS)

Hayakawa, Tomohiko; Moko, Yushi; Morishita, Kenta; Ishikawa, Masatoshi

2018-04-01

In this paper, we propose a pixel-wise deblurring imaging (PDI) system based on active vision for compensation of the blur caused by high-speed one-dimensional motion between a camera and a target. The optical axis is controlled by back-and-forth motion of a galvanometer mirror to compensate the motion. High-spatial-resolution image captured by our system in high-speed motion is useful for efficient and precise visual inspection, such as visually judging abnormal parts of a tunnel surface to prevent accidents; hence, we applied the PDI system for structural health monitoring. By mounting the system onto a vehicle in a tunnel, we confirmed significant improvement in image quality for submillimeter black-and-white stripes and real tunnel-surface cracks at a speed of 100 km/h.

Immunization with Leishmania donovani protein disulfide isomerase DNA construct induces Th1 and Th17 dependent immune response and protection against experimental visceral leishmaniasis in Balb/c mice.

PubMed

Amit, Ajay; Vijayamahantesh; Dikhit, Manas R; Singh, Ashish Kumar; Kumar, Vikash; Suman, Shashi S; Singh, Ashu; Kumar, Akhilesh; Thakur, Ajit Kumar; Das, Vidyanand Ravi; Das, Pradeep; Bimal, Sanjiva

2017-02-01

In the present study, the efficacy of Leishmania donovani protein disulfide isomerase (LdPDI) as a DNA vaccine was evaluated in BALB/C mice. Mice immunized with the LdPDI-DNA construct were found to be the most immuno-reactive, as the construct induced higher T-cell proliferation. The increased T-cell proliferation was associated with a substantial rise in Th1 and Th17+ CD4 cell response and triggered a higher proportion of CD8+ T cells for the release of interferon-gamma along with a reduced splenic parasite load on Days20 and 60 post challenge (PC). Furthermore, the vaccine construct triggered increased interferon (IFN)-γ, interleukin(IL)-17A, and IL-22 release accompanied by decreased extracellular signal-regulated kinases (ERK) 1/2 signaling and increased mitogen-activated protein kinase (MAPK) signaling coinciding with an increase in the amount of nitrite and reactive oxygen species (ROS)in vaccinating the splenocyts. We summarize from our data that the PDI-DNA construct of Leishmania donovani has the potential to elicit protective immunity through the pro-inflammatory cytokines of CD8+ and CD4+(Th1 and Th17) following an intervention in the downstream signaling event of ERK1/2 (probably through p38MAPK signaling). Therefore, the study suggests a new control against visceral leishmaniasis in the future. Copyright © 2016 Elsevier Ltd. All rights reserved.

Is early adulthood a critical developmental stage for psychosis proneness? A survey of delusional ideation in normal subjects.

PubMed

Verdoux, H; van Os, J; Maurice-Tison, S; Gay, B; Salamon, R; Bourgeois, M

1998-02-09

It has been hypothesized that late adolescence and early adulthood might be a brain developmental stage favoring the clinical expression of psychotic symptoms in psychiatric or neurological diseases. The aim of the present survey was to examine the relationship between age and delusional ideation in a sample of subjects with no psychiatric disorder. The survey was carried out with the Aquitaine Sentinel Network of general practitioners. Consecutive practice attenders were invited to complete the PDI-21 (Peters Delusional Inventory 21 items), a self-report questionnaire designed to measure delusional ideation in the normal population. The study concerned 444 patients who had no lifetime history of psychiatric disorder and who completed the PDI-21. A principal component analysis of the PDI-21 items was performed in order to identify delusional dimensions. An age-related decrease in the likelihood to report delusional ideas was found, younger subjects scoring higher on most dimensions of delusional ideation, such as 'persecution', 'thought disturbance', 'grandiosity' and 'paranormal beliefs'. 'Religiosity' was the only dimension positively associated with age. The results suggest that there may be a physiological neurodevelopmental stage favouring the expression of psychosis proneness in normal subjects, and support the hypothesis that the association between age and positive psychotic symptoms in functional and organic psychoses may be linked to the interaction between normal brain maturational processes and cerebral abnormalities involved in the aetiology of functional and organic psychoses.

Neutralizing monoclonal antibodies against ricin's enzymatic subunit interfere with protein disulfide isomerase-mediated reduction of ricin holotoxin in vitro.

PubMed

O'Hara, Joanne M; Mantis, Nicholas J

2013-09-30

The penultimate event in the intoxication of mammalian cells by ricin toxin is the reduction, in the endoplasmic reticulum (ER), of the intermolecular disulfide bond that links ricin's enzymatic (RTA) and binding (RTB) subunits. In this report we adapted an in vitro protein disulfide isomerase (PDI)-mediated reduction assay to test the hypothesis that the RTA-specific neutralizing monoclonal antibody (mAb) IB2 interferes with the liberation of RTA from RTB. IB2 recognizes an epitope located near the interface between RTA and RTB and, like a number of other RTA-specific neutralizing mAbs, is proposed to neutralize ricin intracellularly. In this study, we found that IB2 virtually eliminated the reduction of ricin holotoxin into RTA and RTB in vitro. Surprisingly, three other neutralizing mAbs (GD12, R70 and SyH7) that bind epitopes at considerable distance from ricin's disulfide bond were as effective (or nearly as effective) as IB2 in interfering with PDI-mediated liberation of RTA from RTB. By contrast, two non-neutralizing RTA-specific mAbs, FGA12 and SB1, did not affect PDI-mediated reduction of ricin. These data reveal a possible mechanism by which RTA-specific antibodies may neutralize ricin intracellularly, provided they are capable of trafficking in association with ricin from the cell surface to the ER. Copyright © 2013 Elsevier B.V. All rights reserved.

Concern over radiation exposure and psychological distress among rescue workers following the Great East Japan Earthquake.

PubMed

Matsuoka, Yutaka; Nishi, Daisuke; Nakaya, Naoki; Sone, Toshimasa; Noguchi, Hiroko; Hamazaki, Kei; Hamazaki, Tomohito; Koido, Yuichi

2012-05-15

On March 11, 2011, the Great East Japan Earthquake and tsunami that followed caused severe damage along Japans northeastern coastline and to the Fukushima Daiichi nuclear power plant. To date, there are few reports specifically examining psychological distress in rescue workers in Japan. Moreover, it is unclear to what extent concern over radiation exposure has caused psychological distress to such workers deployed in the disaster area. One month after the disaster, 424 of 1816 (24%) disaster medical assistance team workers deployed to the disaster area were assessed. Concern over radiation exposure was evaluated by a single self-reported question. General psychological distress was assessed with the Kessler 6 scale (K6), depressive symptoms with the Center for Epidemiologic Studies Depression Scale (CES-D), fear and sense of helplessness with the Peritraumatic Distress Inventory (PDI), and posttraumatic stress symptoms with the Impact of Event Scale-Revised (IES-R). Radiation exposure was a concern for 39 (9.2%) respondents. Concern over radiation exposure was significantly associated with higher scores on the K6, CES-D, PDI, and IES-R. After controlling for age, occupation, disaster operation experience, duration of time spent watching earthquake news, and past history of psychiatric illness, these associations remained significant in men, but did not remain significant in women for the CES-D and PDI scores. The findings suggest that concern over radiation exposure was strongly associated with psychological distress. Reliable, accurate information on radiation exposure might reduce deployment-related distress in disaster rescue workers.

Development and evaluation of ultra-small nanostructured lipid carriers: novel topical delivery system for athlete's foot.

PubMed

Singh, Samipta; Singh, Mahendra; Tripathi, Chandra Bhushan; Arya, Malti; Saraf, Shubhini A

2016-02-01

Athlete's foot is a fungal infection of the foot which causes dry, itchy, flaky condition of the skin caused by Trichophyton species. In this study, the potential of ultra-small nanostructured lipid carrier (usNLC)-based topical gel of miconazole nitrate for the treatment of athlete's foot was evaluated. Nanostructure lipid carriers (NLCs) prepared by melt emulsification and sonication technique were characterized for particle size, drug entrapment, zeta potential and drug release. The optimized usNLC revealed particle size 53.79 nm, entrapment efficiency 86.77%, zeta potential -12.9 mV and polydispersity index (PDI) of 0.27. The drug release studies of usNLC showed initial fast release followed by sustained release with 91.99% drug released in 24 h. Optimized usNLCs were incorporated into carbopol-934 gel and evaluated for pH (6.8), viscosity (36,400 mPa s) and texture analysis. Antifungal activity against Trichophyton mentagrophytes exhibited wider zone of inhibition, 6.6 ± 1.5 mm for optimized usNLC3 gel viz-à-viz marketed gel formulation (3.7 ± 1.2 mm). Hen's egg test-chorioallantoic membrane (HET-CAM) irritation test confirmed optimized usNLC gel to be non-irritant to chorioallantoic membrane. Improved dermal delivery of miconazole by usNLC gel could be achieved for treatment of athlete's foot.

Microbial synthesis of Flower-shaped gold nanoparticles.

PubMed

Singh, Priyanka; Kim, Yeon Ju; Wang, Chao; Mathiyalagan, Ramya; Yang, Deok Chun

2016-09-01

The shape of nanoparticles has been recognized as an important attribute that determines their applicability in various fields. The flower shape (F-shape) has been considered and is being focused on, because of its enhanced properties when compared to the properties of the spherical shape. The present study proposed the microbial synthesis of F-shaped gold nanoparticles within 48 h using the Bhargavaea indica DC1 strain. The F-shaped gold nanoparticles were synthesized extracellularly by the reduction of auric acid in the culture supernatant of B. indica DC1. The shape, size, purity, and crystalline nature of F-shaped gold nanoparticles were revealed by various instrumental techniques including UV-Vis, FE-TEM, EDX, elemental mapping, XRD, and DLS. The UV-Vis absorbance showed a maximum peak at 536 nm. FE-TEM revealed the F-shaped structure of nanoparticles. The EDX peak obtained at 2.3 keV indicated the purity. The peaks obtained on XRD analysis corresponded to the crystalline nature of the gold nanoparticles. In addition, the results of elemental mapping indicated the maximum distribution of gold elements in the nanoproduct obtained. Particle size analysis revealed that the average diameter of the F-shaped gold nanoparticles was 106 nm, with a polydispersity index (PDI) of 0.178. Thus, the methodology developed for the synthesis of F-shaped gold nanoparticles is completely green and economical.

Liquid crystal point diffraction interferometer. Ph.D. Thesis - Arizona Univ., 1995

NASA Technical Reports Server (NTRS)

Mercer, Carolyn R.

1995-01-01

A new instrument, the liquid crystal point diffraction-interferometer (LCPDI), has been developed for the measurement of phase objects. This instrument maintains the compact, robust design of Linnik's point diffraction interferometer (PDI) and adds to it phase stepping capability for quantitative interferogram analysis. The result is a compact, simple to align, environmentally insensitive interferometer capable of accurately measuring optical wavefronts with very high data density and with automated data reduction. This dissertation describes the theory of both the PDI and liquid crystal phase control. The design considerations for the LCPDI are presented, including manufacturing considerations. The operation and performance of the LCPDI are discussed, including sections regarding alignment, calibration, and amplitude modulation effects. The LCPDI is then demonstrated using two phase objects: defocus difference wavefront, and a temperature distribution across a heated chamber filled with silicone oil. The measured results are compared to theoretical or independently measured results and show excellent agreement. A computer simulation of the LCPDI was performed to verify the source of observed periodic phase measurement error. The error stems from intensity variations caused by dye molecules rotating within the liquid crystal layer. Methods are discussed for reducing this error. Algorithms are presented which reduce this error; they are also useful for any phase-stepping interferometer that has unwanted intensity fluctuations, such as those caused by unregulated lasers.

Gentamicin Sulfate PEG-PLGA/PLGA-H Nanoparticles: Screening Design and Antimicrobial Effect Evaluation toward Clinic Bacterial Isolates

PubMed Central

Dorati, Rossella; DeTrizio, Antonella; Spalla, Melissa; Migliavacca, Roberta; Pagani, Laura; Pisani, Silvia; Chiesa, Enrica; Modena, Tiziana; Genta, Ida

2018-01-01

Nanotechnology is a promising approach both for restoring or enhancing activity of old and conventional antimicrobial agents and for treating intracellular infections by providing intracellular targeting and sustained release of drug inside infected cells. The present paper introduces a formulation study of gentamicin loaded biodegradable nanoparticles (Nps). Solid-oil-in water technique was studied for gentamicin sulfate nanoencapsulation using uncapped Polylactide-co-glycolide (PLGA-H) and Polylactide-co-glycolide-co-Polyethylenglycol (PLGA-PEG) blends. Screening design was applied to optimize: drug payload, Nps size and size distribution, stability and resuspendability after freeze-drying. PLGA-PEG concentration resulted most significant factor influencing particles size and drug content (DC): 8 w/w% DC and 200 nm Nps were obtained. Stirring rate resulted most influencing factor for size distribution (PDI): 700 rpm permitted to obtain homogeneous Nps dispersion (PDI = 1). Further experimental parameters investigated, by 23 screening design, were: polymer blend composition (PLGA-PEG and PLGA-H), Polyvinylalcohol (PVA) and methanol concentrations into aqueous phase. Drug content was increased to 10.5 w/w%. Nanoparticle lyophilization was studied adding cryoprotectants, polyvinypirrolidone K17 and K32, and sodiumcarboxymetylcellulose. Freeze-drying protocol was optimized by a mixture design. A freeze-dried Nps powder free resuspendable with stable Nps size and payload, was developed. The powder was tested on clinic bacterial isolates demonstrating that after encapsulation, gentamicin sulfate kept its activity. PMID:29329209

Wavefront measurements of phase plates combining a point-diffraction interferometer and a Hartmann-Shack sensor.

PubMed

Bueno, Juan M; Acosta, Eva; Schwarz, Christina; Artal, Pablo

2010-01-20

A dual setup composed of a point diffraction interferometer (PDI) and a Hartmann-Shack (HS) wavefront sensor was built to compare the estimates of wavefront aberrations provided by the two different and complementary techniques when applied to different phase plates. Results show that under the same experimental and fitting conditions both techniques provide similar information concerning the wavefront aberration map. When taking into account all Zernike terms up to 6th order, the maximum difference in root-mean-square wavefront error was 0.08 microm, and this reduced up to 0.03 microm when excluding lower-order terms. The effects of the pupil size and the order of the Zernike expansion used to reconstruct the wavefront were evaluated. The combination of the two techniques can accurately measure complicated phase profiles, combining the robustness of the HS and the higher resolution and dynamic range of the PDI.

Tracing the spatiotemporally resolved inactivation of optically arranged bacteria by photofunctional microparticles at the single-cell level (Conference Presentation)

NASA Astrophysics Data System (ADS)

Barroso Peña, Alvaro; Grüner, Malte; Forbes, Taylor; Denz, Cornelia; Strassert, Cristian A.

2016-09-01

Antimicrobial Photodynamic Inactivation (PDI) represents an attractive alternative in the treatment of infections by antibiotic-resistant pathogenic bacteria. In PDI a photosensitizer (PS) is administered to the site of the biological target in order to generate cytotoxic singlet oxygen which reacts with the biological membrane upon application of harmless visible light. Established methods for testing the photoinduced cytotoxicity of PSs rely on the observation of the whole bacterial ensemble providing only a population-averaged information about the overall produced toxicity. However, for a deeper understanding of the processes that take place in PDI, new methods are required that provide simultaneous regulation of the ROS production, monitoring the subsequent damage induced in the bacteria cells, and full control of the distance between the bacteria and the center of the singlet oxygen production. Herein we present a novel method that enables the quantitative spatio-time-resolved analysis at the single cell level of the photoinduced damage produced by transparent microspheres functionalized with PSs. For this purpose, a methodology was introduced to monitor phototriggered changes with spatiotemporal resolution employing holographic optical tweezers and functional fluorescence microscopy. The defined distance between the photoactive particles and individual bacteria can be fixed under the microscope before the photosensitization process, and the photoinduced damage is monitored by tracing the fluorescence turn-on of a suitable marker. Our methodology constitutes a new tool for the in vitro design and analysis of photosensitizers, as it enables a quantitative response evaluation of living systems towards oxidative stress.

Quaternized Zn(II) phthalocyanines for photodynamic strategy against resistant periodontal bacteria.

PubMed

Kussovski, Vesselin; Mantareva, Vanya; Durmuş, Mahmut; Angelov, Ivan

2018-04-25

Photodynamic inactivation (PDI) has been featured as an effective strategy in the treatment of acute drug-resistant infections. The efficiency of PDI was evaluated against three periodontal pathogenic bacteria that were tested as drug-resistant strains. In vitro studies were performed with four water-soluble cationic Zn(II) phthalocyanines (ZnPc1-4) and irradiation of a specific light source (light-emitting diode, 665 nm) with three doses (15, 36 and 60 J/cm2). The well detectable fluorescence of ZnPcs allowed the cellular imaging, which suggested relatively high uptakes of ZnPcs into bacterial species. Complete photoinactivation was achieved with all studied ZnPc1-4 for Enterococcus faecalis (E. faecalis) at a light dose of 15 J/cm2. The photodynamic response was high for Prevotella intermedia (P. intermedia) after the application of 6 μM of ZnPc1 and a light dose of 36 J/cm2 and for 6 μM of ZnPc2 at 60 J/cm2. P. intermedia was inactivated with ZnPc3 (4 log) and ZnPc4 (2 log) with irradiation at an optimal dose of 60 J/cm2. Similar photoinactivation results (2 log) were achieved for Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans) treated with 6 μM ZnPc1 and ZnPc2 at a light dose of 60 J/cm2. The study suggested that PDI with quaternized Zn(II) phthalocyanines and specific light irradiation appears to be a very useful antimicrobial strategy for effective inactivation of drug-resistant periodontal pathogens.

Concern over radiation exposure and psychological distress among rescue workers following the Great East Japan Earthquake

PubMed Central

2012-01-01

Background On March 11, 2011, the Great East Japan Earthquake and tsunami that followed caused severe damage along Japans northeastern coastline and to the Fukushima Daiichi nuclear power plant. To date, there are few reports specifically examining psychological distress in rescue workers in Japan. Moreover, it is unclear to what extent concern over radiation exposure has caused psychological distress to such workers deployed in the disaster area. Methods One month after the disaster, 424 of 1816 (24%) disaster medical assistance team workers deployed to the disaster area were assessed. Concern over radiation exposure was evaluated by a single self-reported question. General psychological distress was assessed with the Kessler 6 scale (K6), depressive symptoms with the Center for Epidemiologic Studies Depression Scale (CES-D), fear and sense of helplessness with the Peritraumatic Distress Inventory (PDI), and posttraumatic stress symptoms with the Impact of Event Scale-Revised (IES-R). Results Radiation exposure was a concern for 39 (9.2%) respondents. Concern over radiation exposure was significantly associated with higher scores on the K6, CES-D, PDI, and IES-R. After controlling for age, occupation, disaster operation experience, duration of time spent watching earthquake news, and past history of psychiatric illness, these associations remained significant in men, but did not remain significant in women for the CES-D and PDI scores. Conclusion The findings suggest that concern over radiation exposure was strongly associated with psychological distress. Reliable, accurate information on radiation exposure might reduce deployment-related distress in disaster rescue workers. PMID:22455604

Photoinduced electron transfer from rylenediimide radical anions and dianions to Re(bpy)(CO) 3 using red and near-infrared light

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

La Porte, Nathan T.; Martinez, Jose F.; Hedström, Svante

A major goal of artificial photosynthesis research is photosensitizing highly reducing metal centers using as much as possible of the solar spectrum reaching Earth's surface. The radical anions and dianions of rylenediimide (RDI) dyes, which absorb at wavelengths as long as 950 nm, are powerful photoreductants with excited state oxidation potentials that rival or exceed those of organometallic chromophores. These dyes have been previously incorporated into all-organic donor–acceptor systems, but have not yet been shown to reduce organometallic centers. This study describes a set of dyads in which perylenediimide (PDI) or naphthalenediimide (NDI) chromophores are attached to Re(bpy)(CO) 3 throughmore » either the bipyridine ligand or more directly to the Re center via a pyridine ligand. The chromophores are reduced with a mild reducing agent, after which excitation with long-wavelength red or near-infrared light leads to reduction of the Re complex. The kinetics of electron transfer from the photoexcited anions to the Re complex are monitored using transient visible/near-IR and mid-IR spectroscopy, complemented by theoretical spectroscopic assignments. The photo-driven charge shift from the reduced PDI or NDI to the complex occurs in picoseconds regardless of whether PDI or NDI is attached to the bipyridine or to the Re center, but back electron transfer is found to be three orders of magnitude slower with the chromophore attached to the Re center. These results will inform the design of future catalytic systems that incorporate RDI anions as chromophores.« less

Photoinduced electron transfer from rylenediimide radical anions and dianions to Re(bpy)(CO) 3 using red and near-infrared light

DOE PAGES

La Porte, Nathan T.; Martinez, Jose F.; Hedström, Svante; ...

2017-02-28

A major goal of artificial photosynthesis research is photosensitizing highly reducing metal centers using as much as possible of the solar spectrum reaching Earth's surface. The radical anions and dianions of rylenediimide (RDI) dyes, which absorb at wavelengths as long as 950 nm, are powerful photoreductants with excited state oxidation potentials that rival or exceed those of organometallic chromophores. These dyes have been previously incorporated into all-organic donor–acceptor systems, but have not yet been shown to reduce organometallic centers. This study describes a set of dyads in which perylenediimide (PDI) or naphthalenediimide (NDI) chromophores are attached to Re(bpy)(CO) 3 throughmore » either the bipyridine ligand or more directly to the Re center via a pyridine ligand. The chromophores are reduced with a mild reducing agent, after which excitation with long-wavelength red or near-infrared light leads to reduction of the Re complex. The kinetics of electron transfer from the photoexcited anions to the Re complex are monitored using transient visible/near-IR and mid-IR spectroscopy, complemented by theoretical spectroscopic assignments. The photo-driven charge shift from the reduced PDI or NDI to the complex occurs in picoseconds regardless of whether PDI or NDI is attached to the bipyridine or to the Re center, but back electron transfer is found to be three orders of magnitude slower with the chromophore attached to the Re center. These results will inform the design of future catalytic systems that incorporate RDI anions as chromophores.« less

Concentration-dependent photophysical switching in mixed self-assembled monolayers of pentacene and perylenediimide on gold nanoclusters.

PubMed

Kato, Daiki; Sakai, Hayato; Araki, Yasuyuki; Wada, Takehiko; Tkachenko, Nikolai V; Hasobe, Taku

2018-03-28

Photophysical control and switching on organic-inorganic hybrid interfaces are of great interest in diverse fundamental and applicative research areas. 6,13-Bis(triisopropylsilylethynyl)pentacene (TP) is well-known to exhibit efficient singlet fission (SF) for generation of high-yield triplet excited states in aggregated forms, whereas perylenediimide (PDI) ensembles show the characteristic excimer formation. Additionally, a combination of pentacene (electron donor: D) and PDI (electron acceptor: A) is expected to undergo an efficient photoinduced electron transfer (PET), and absorption of two chromophores combined covers the entire visible region. Therefore, the concentration-dependent mixed self-assembled monolayers (SAMs) composed of two chromophores enable us to control and switch the photophysical processes on a surface. In this work, a series of mixed SAMs composed of TP and PDI units on gold nanoclusters (GNCs) were newly synthesized by changing the relative molecular concentration ratios. Structural control of mixed SAMs on a gold surface based on the concentration ratios was successfully achieved. Time-resolved femtosecond and nanosecond transient absorption measurements clearly demonstrate photophysical control and switching of the above competitive reactions such as SF, electron transfer (ET) and excimer formation. The maximum quantum yields of triplet states (ΦT = ∼170%) and electron transfer (ΦET = ∼95%) were quantitatively evaluated by changing the concentration ratios. The rate constants of SF and excimer processes are largely dependent on the concentration ratios, whereas the rate constants of ET processes approximately remain constant. These findings are also discussed based on the statistical framework of the assembly of chromophores on the gold surface.

Characterization of one-dimensional molecular chains of 4,4'-biphenyl diisocyanide on Au(111) by scanning tunneling microscopy

DOE PAGES

Zhou, Jing; Li, Yan; Zahl, Percy; ...

2015-03-14

The morphology and electronic structure of vapor deposited 4,4'-biphenyldiisocyanide (BPDI) on a Au(111) surface were investigated using variable-temperature scanning tunneling microscopy (STM). When deposited at room temperature, BPDI molecules form one-dimensional molecular chains similar to that recently observed for the structurally related 1,4-phenyl diisocyanide (PDI). Compared to PDI, the longer periodicity for the BPDI molecular chains is consistent with the addition of a second phenyl ring and supports a structural model in which the BPDI molecules lie parallel to the surface and interconnected by Au-adatoms. The molecular chains are mostly aligned along the [110] direction of the Au(111) substrate, butmore » exhibit frequent changes in angle that are consistent with directions between fcc and hcp three-fold hollow sites. Dispersion-corrected density functional theory calculations for one-dimensional chains of BPDI molecules bound end-to-end via their isocyanide groups to Au-adatoms reproduce the observed periodicity of the chains and show that this morphology is energetically favored over upright binding with one free –NC group. The spatially resolved conductance (dI/dV) map for BPDI on Au(111) exhibits a feature centered at -0.67 eV below the Fermi level which are delocalized along the chain with maxima at the Au-adatom and biphenyl positions. This occupied resonant feature is close to that previously observed for the PDI in both photoemission and conductance measurements and is attributed to an occupied interfacial state resulting from BPDI-Au interactions« less

Imidazoacridinone Derivatives as Efficient Sensitizers in Photoantimicrobial Chemotherapy

PubMed Central

Taraszkiewicz, Aleksandra; Grinholc, Mariusz; Bielawski, Krzysztof P.; Kawiak, Anna

2013-01-01

The objective of this study was to investigate a new potential photosensitizer (PS) in the photodynamic inactivation (PDI) of microorganisms in vitro (11 reference strains and 13 clinical isolates, representing common Gram-positive and Gram-negative human pathogens), with special emphasis on Candida albicans. We studied the light-induced cytotoxicity of the imidazoacridinone derivative C1330 toward fungal cells grown in planktonic form. We examined the influence of various parameters (time of incubation, PDI quencher effect, and C1330 accumulation in C. albicans cells) on the efficacy of light-dependent cytotoxicity. Additionally, we checked for the potential cyto- and phototoxic activity of C1330 against human dermal keratinocytes. In our research, we used a broadband incoherent blue light source (380 to 470 nm) with an output power of 100 mW/cm2. In vitro studies showed that the C1330 action against C. albicans was a light-dependent process. C1330 was an efficient photosensitizer in the photodynamic inactivation of C. albicans, which reduced the growth of planktonic cells by 6.1 log10 units. Efficient accumulation of PS in the nucleus and vacuoles was observed after 30 min of incubation, which correlated with the highest photokilling efficacy. Significant changes in intracellular structure were observed upon illumination of C1330-incubated C. albicans cells. In the case of the human HaCaT cell line, approximately 40% of cells survived the treatment, which indicates the potential benefit of further study of the application of C1330 in photoantimicrobial chemotherapy. These data suggest that PDI may be a viable approach for the treatment of localized C. albicans infections. PMID:23563951

Formulation and optimization of pH sensitive drug releasing O/W emulsions using Albizia lebbeck L. seed polysaccharide.

PubMed

Varma, Chekuri Ashok Kumar; Jayaram Kumar, K

2018-04-30

Smart polymers, one of the class of polymers with extensive growth in the last few decades due to their wide applications in drug targeting and controlled delivery systems. With this in mind, the aim of the present study is to design and formulate smart releasing o/w emulsion by using Albizia lebbeck L. seed polysaccharide (ALPS). For this purpose, the physicochemical and drug release characteristics like emulsion capacity (EC), emulsion stability (ES), viscosity, microscopy, zeta potential, polydispersity index (PDI) and in-vitro drug release were performed. The EC and ES values were found to increase with an increased concentration of ALPS. The emulsion formulations were statistically designed by using 3 2 full factorial design. All the emulsions showed a shear-thinning behavior. The zeta potential and polydispersity index were found to be in the range of -35.83 mV to -19.00 mV and 0.232-1.000 respectively. Further, the percent cumulative drug release of the emulsions at 8 h was found to be in the range of 30.19-82.65%. The drug release profile exhibited zero order release kinetics. In conclusion, the ALPS can be used as a natural emulsifier and smart polymer for the preparation of pH sensitive emulsions in drug delivery systems. Copyright © 2018 Elsevier B.V. All rights reserved.

Enhanced Solubility and Dissolution Rate of Lacidipine Nanosuspension: Formulation Via Antisolvent Sonoprecipitation Technique and Optimization Using Box-Behnken Design.

PubMed

Kassem, Mohamed A A; ElMeshad, Aliaa N; Fares, Ahmed R

2017-05-01

Lacidipine (LCDP) is a highly lipophilic calcium channel blocker of poor aqueous solubility leading to poor oral absorption. This study aims to prepare and optimize LCDP nanosuspensions using antisolvent sonoprecipitation technique to enhance the solubility and dissolution of LCDP. A three-factor, three-level Box-Behnken design was employed to optimize the formulation variables to obtain LCDP nanosuspension of small and uniform particle size. Formulation variables were as follows: stabilizer to drug ratio (A), sodium deoxycholate percentage (B), and sonication time (C). LCDP nanosuspensions were assessed for particle size, zeta potential, and polydispersity index. The formula with the highest desirability (0.969) was chosen as the optimized formula. The values of the formulation variables (A, B, and C) in the optimized nanosuspension were 1.5, 100%, and 8 min, respectively. Optimal LCDP nanosuspension had particle size (PS) of 273.21 nm, zeta potential (ZP) of -32.68 mV and polydispersity index (PDI) of 0.098. LCDP nanosuspension was characterized using x-ray powder diffraction, differential scanning calorimetry, and transmission electron microscopy. LCDP nanosuspension showed saturation solubility 70 times that of raw LCDP in addition to significantly enhanced dissolution rate due to particle size reduction and decreased crystallinity. These results suggest that the optimized LCDP nanosuspension could be promising to improve oral absorption of LCDP.

Inflammatory mediators leading to protein misfolding and uncompetitive/fast off-rate drug therapy for neurodegenerative disorders.

PubMed

Lipton, Stuart A; Gu, Zezong; Nakamura, Tomohiro

2007-01-01

Inflammatory mediators, including free radicals such as nitric oxide (NO) and reactive oxygen species (ROS), can contribute to neurodegenerative diseases in part by triggering protein misfolding. In this chapter, we will discuss a newly discovered pathway for this phenomenon and possible novel treatments. Excitotoxicity, defined as overstimulation of glutamate receptors, has been implicated in a final common pathway contributing to neuronal injury and death in a wide range of acute and chronic neurological disorders, ranging from Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), multiple sclerosis, and Alzheimer's disease (AD) to stroke and trauma. Excitotoxic cell death is due, at least in part, to excessive activation of N-methyl-d-aspartate (NMDA)-type glutamate receptors, leading to excessive Ca(2+) influx through the receptor's associated ion channel and subsequent free radical production, including NO and ROS. These free radicals can trigger a variety of injurious pathways, but newly discovered evidence suggests that some proteins are S-nitrosylated (transfer of NO to a critical thiol group), and this reaction can mimic the effect of rare genetic mutations. This posttranslational modification can contribute to protein misfolding, triggering neurodegenerative diseases. One such molecule affected is protein disulfide isomerase (PDI), an enzyme responsible for normal protein folding in the endoplasmic reticulum (ER). We found that when PDI is S-nitrosylation (forming SNO-PDI), the function of the enzyme is compromised, leading to misfolded proteins and contributing to neuronal cell injury and loss. Moreover, SNO-PDI occurs at pathological levels in several human diseases, including AD and PD. This discovery thus links protein misfolding to excitotoxicity and free radical formation in a number of neurodegenerative disorders. Another molecule whose S-nitrosylation can lead to abnormal protein accumulation is the E3 ubiquitin ligase, parkin, which contributes to the pathogenesis of PD. One way to ameliorate excessive NO production and hence abnormal S-nitrosylations would be to inhibit NMDA receptors. In fact, blockade of excessive NMDA receptor activity can in large measure protect neurons from this type of injury and death. However, inhibition of the NMDA receptor by high-affinity antagonists also blocks the receptor's normal function in synaptic transmission and leads to unacceptable side effects. For this reason, many NMDA receptor antagonists have disappointingly failed in advanced clinical trials. Our group was the first to demonstrate that gentle blockade of NMDA receptors by memantine, via a mechanism of uncompetitive open-channel block with a rapid "off-rate," can prevent this type of damage in a clinically efficacious manner without substantial side effects. For these Uncompetitive/Fast Off-rate therapeutics, we use the term "UFO drugs" because like Unidentified Flying Objects, they leave very quickly as soon as their job is finished. As a result, memantine blocks excessive NMDA receptor activity without disrupting normal activity. Memantine does this by preferentially entering the receptor-associated ion channel when it is excessively open, and, most importantly, when its off-rate from the channel is relatively fast so that it does not accumulate to interfere with normal synaptic transmission. Hence, memantine is clinically well tolerated, has been used in Europe for PD for many years, and recently passed multiple phase III trials for dementia, leading to its approval by the FDA and European Union for moderate-to-severe AD. Clinical studies of memantine for additional neurological disorders, including other dementias, neuropathic pain, and glaucoma, are underway. We have also developed a series of second-generation drugs that display greater neuroprotective properties than memantine. These second-generation drugs take advantage of the fact that the NMDA receptor has other modulatory sites, including critical thiol groups that are S-nitrosylated. In this case, in contrast to PDI or parkin, S-nitrosylation proves to be neuroprotective by decreasing excessive NMDA receptor activity. Targeted S-nitrosylation of the NMDA receptor can be achieved by coupling NO to memantine, yielding second-generation "UFO drugs" known as NitroMemantines.

Antipsoriatic and Anti-inflammatory Studies of Berberis aristata Extract Loaded Nanovesicular Gels

PubMed Central

Nimisha; Rizvi, Dilshad Ali; Fatima, Zeeshan; Neema; Kaur, Chanchal Deep

2017-01-01

Objective: Novel nanovesicular gel of Berberis aristata extract was developed and evaluated for its anti-inflammatory and antipsoriatic activity. Materials and Methods: Transferosomes were prepared using soya phosphatidylcholine and edge activators (Tween 80, Span 80, and sodium deoxycholate) by a modified lipid film hydration technique using rotary evaporator and evaluated for various parameters. The quantification and standardization of extract have been carried out using its alkaloid content as berberine as biomarker. Topical application of imiquimod (IMQ) (immune modifier) on the shaved back of mice developed psoriasis-like inflammation followed by histopathological study of inflamed skin. Results: The size of transferosomes was in the range of 265–345 nm whereas polydispersity index ranges from 0.10 to 0.63, and for zeta potential, it was from −19.3 to −43.3 mV. Transferosomes were further added to Carbopol 934P for gel formation and subsequently evaluated for their physicochemical properties. Their efficacy against inflammation, IMQ-induced psoriasis, and skin sensitivity was compared with conventional formulation (commercial formulation-Angle Gloss, Phytolab Pvt. Ltd.). Percent inhibition of edema by transferosomal gel (55.76%) was more as compared to conventional gel of extract (33.5%) found out by Carrageenan-induced paw edema method. Primary irritation index was found to be <0.4 inferring its safe use for topical formulation. Conclusion: Histopathological report showed that, in psoriasis-induced animal treated with topical application of extract loaded transferosomal gel showed a marked reduction in thickness of epidermis, length of rete ridges as compared to conventional gel formulation. It can be inferred that B. aristata extract loaded transferosomal gel can function as potential anti-inflammatory and antipsoriatic formulation. SUMMARY The objective of the present research work was to prepare Berberis aristata extracts (roots, ethanolic 70%v/v) loaded transferosomal gel, to perform in vitro characterization and in vivo evaluation of their efficacy against inflammation as well as imiquimod (IMQ)-induced psoriasis in animalsThe remarkable enhancement in the in vitro release efficiency of B. aristata extract loaded transferosomal gel resulted in improved anti-inflammatory activity. The prepared novel formulation of B. aristata has also shown its efficacy against IMQ-induced psoriasis. Abbreviations used: SPC: Soyaphosphatidylcholine, PDI: Polydispersity index, IMQ: Imiquimod, EA: Edge activator, BE: Berberine, TEM: Transmission electron microscopy, PBS: Phosphate buffered saline, H and E: Hematoxylin and eosin, ZP: Zeta potential, EE: Entrapment efficiency. PMID:29142419

Synthesis of high molecular weight PEO using non-metal initiators

DOEpatents

Yang, Jin; Sivanandan, Kulandaivelu; Pistorino, Jonathan; Eitouni, Hany Basam

2015-05-19

A new synthetic method to prepare high molecular weight poly(ethylene oxide) with a very narrow molecular weight distribution (PDI<1.5) is described. The method involves a metal free initiator system, thus avoiding dangerous, flammable organometallic compounds.

Diabetes and Age-Related Differences in Vascular Function of Renal Artery: Possible Involvement of Endoplasmic Reticulum Stress.

PubMed

Matsumoto, Takayuki; Watanabe, Shun; Ando, Makoto; Yamada, Kosuke; Iguchi, Maika; Taguchi, Kumiko; Kobayashi, Tsuneo

2016-02-01

To study the time-course relationship between vascular functions and endoplasmic reticulum (ER) stress in type 2 diabetes, we investigated vascular function and associated protein expression, including cyclo-oxygenase (COX), ER stress, and apoptotic markers, in renal arteries (RA) from type 2 diabetic Otsuka Long-Evans Tokushima fatty (OLETF) rats at the young adult (4 months old) and aged (18 months old) stages. In the RA of aged OLETF (vs. young OLETF), we found: (1) Increased contractions induced by uridine adenosine tetraphosphate (Up4A) and phenylephrine, (2) decreased relaxation and increased contraction induced by acetylcholine (ACh) at lower and higher concentrations, respectively, and (3) increased expression of COX-1 and C/EBP-homologous protein (CHOP, a pro-apoptotic protein). In aged rats, the expression of COX-1, COX-2, PDI (an ER protein disulfide isomerase), Bax (a proapoptotic marker), and CHOP were increased in RA from OLETF rats (vs. age-matched control Long-Evans Tokushima Otsuka [LETO] rats). Up-regulation of PDI and Bax were seen in the RA from young OLETF (vs. young LETO) rats. No age-related alterations were apparent in the above changes in RA from LETO rats, excluding ACh-induced contraction. Short-term treatment with the ER stress inhibitor tauroursodeoxycholic acid (TUDCA, 100 mg/kg per day, intraperitoneally for 1 week) to OLETF rats at the chronic stage of the disease (12 months old) could suppress renal arterial contractions induced by Up4A and ACh. These results suggest that a long-term duration of disease may be important for the development of vascular dysfunction rather than aging per se. The early regulation of ER stress may be important against the development of diabetes-associated vascular dysfunction.

Development and Evaluation of Amphotericin B Loaded Iron Oxide Nanoparticles for Targeted Drug Delivery to Systemic Fungal Infections

NASA Astrophysics Data System (ADS)

Balabathula, Pavan

A targeted nanotheronostic drug delivery system to diagnose and treat life threatening invasive fungal infections (IFIs) such as cryptococcal meningitis was designed, developed, characterized, and evaluated. To address the development processes, first, iron oxide nanoparticles (IONP) (34-40 nm) coated with bovine serum albumin (BSA), loaded and targeted with amphotericin B (AMB) (AMB-IONP) was formulated by applying a layer by layer approach. Several designs (A, B, C, D, & E) of AMB-IONP were developed and their physicochemical properties such as drug loading with HPLC method, particle size, poly dispersity index (PDI), and zeta-potential using dynamic light scattering (DLS) technique, morphology with transmission electronic microscopy (TEM), and in vitro drug release profile with dialysis method were evaluated. Second, uptake (with fluorescence microscopy and flow cytometry) and killing efficacy (with susceptibility testing) of AMB-IONP in fungal clinical isolates of Candida species were evaluated and compared with standard drug AMB deoxycholate (AMB-D) data. Third, the cellular uptake mechanisms with endocytosis inhibitors and intracellular trafficking using TEM for design D were evaluated in selected isolates. Fourth, a stable lyophilized AMB-IONP formulation was developed and was suitable for clinical trials. A validated isocratic HPLC method was developed and validated for the quantitative determination of AMB. Design D was determined to be the lead formulation with drug loading of 13.6+/-6.9 of AMB/mg of IONP. The size, zeta-potential, and PDI for all formulation designs were found to be in an optimum range for a nanomedicine with ≤36 nm, ˜ -20 mV, and ≤0.2, respectively. The TEM images confirmed that the nanoparticles were monodispersed and spherical in shape. The drug release profile indicated a burst release up to 3 hours for designs A and B, followed by a sustained drug release profile up to 72 hours. Designs C and D (with and without glutaraldehyde) also had a sustained drug release profile up to 72 hours. The major mechanisms of drug release from these formulations were determined to be Fickian and non-Fickian diffusion with first order and Higuchi kinetic models as best fit. The cellular uptake profile for design D exhibited a time dependent uptake with maximum uptake at 0.5 and 4 hours for C. albicans and C. glabrata, respectively. All designs exhibited improved efficacy over AMB-D in the susceptibility testing conducted on clinical isolates of Candida. Design D was found to have an enhanced killing ability and was 16-25 fold more efficacious than AMB-D. An in vitro cellular association study found the uptake mechanism was energy dependent. An endocytosis inhibitor evaluation determined the major particle uptake pathway for C. albicans was lipid-raft mediated endocytosis, whereas for C. glabrata, it was clathrin-, caveolar-, and lipid-raft-mediated endocytosis. TEM and confocal images provided evidence the AMB-IONP were localized at or near the cell wall and membrane wall and inside the cytoplasm, nucleus and endolysosomal vesicles for tested isolates. The lyophilized formulation of AMB-IONP was successfully prepared using an appropriate amount (1:16 to the weight of IONP) of the lyoprotectant, sucrose. A short term stability study of both formulations (lyophilized and aqueous dispersion) at 5°C and 25°C for up to two months showed the lyophilized form was stable. In conclusion, a targeted nanotheronostic drug delivery system (AMB-IONP) was successfully designed, developed, characterized and evaluated as a potential drug product for IFIs treatment.

Production and characterization of cosmetic nanoemulsions containing Opuntia ficus-indica (L.) mill extract as moisturizing agent.

PubMed

Ribeiro, Renato Cesar de Azevedo; Barreto, Stella Maria de Andrade Gomes; Ostrosky, Elissa Aarantes; da Rocha-Filho, Pedro Alves; Veríssimo, Lourena Mafra; Ferrari, Márcio

2015-02-02

This study aimed to produce and characterize an oil in water (O/W) nanoemulsion containing Opuntia ficus-indica (L.) Mill hydroglycolic extract, as well as evaluate its preliminary and accelerated thermal stability and moisturizing efficacy. The formulations containing 0.5% of xanthan gum (FX) and 0.5% of xanthan gum and 1% of Opuntia ficus-indica MILL extract (FXE) were white, homogeneus and fluid in aspect. Both formulations were stable during preliminary and accelerated stability tests. FX and FXE presented a pH compatible to skin pH (4.5-6.0); droplet size varying from 92.2 to 233.6 nm; a polydispersion index (PDI) around 0.200 and a zeta potential from -26.71 to -47.01 mV. FXE was able to increase the water content of the stratum corneum for 5 h after application on the forearm. The O/W nanoemulsions containing 1% of Opuntia ficus-indica (L.) Mill extract presented suitable stability for at least for 60 days. Besides, this formulation was able to increase the water content of stratum corneum, showing its moisturizing efficacy.

Nanoliposomal carriers for improvement the bioavailability of high - valued phenolic compounds of pistachio green hull extract.

PubMed

Rafiee, Zahra; Barzegar, Mohsen; Sahari, Mohammad Ali; Maherani, Behnoush

2017-04-01

In present study, nanoliposomes were prepared by thin hydration method with different concentrations of phenolic compounds (500, 750 and 1000ppm) of pure extract and lecithin (1, 2 and 3%w/w) and characterized by considering the particle size, polydispersity index (PDI), zeta potential, encapsulation efficiency (EE) and morphology. The results showed that nanoliposome (90.39-103.78nm) had negative surface charge varied from -51.5±0.9 to -40.2±0.2mV with a narrow size distribution (PDI≈0.069-0.123). Nanoliposomes composed of 1% lecithin with 1000ppm of phenolic compounds had the highest EE (52.93%). The FTIR analysis indicated the formation of hydrogen bonds between the polar zone of phospholipid and the OH groups of phenolic compounds. Phenolic compounds also increased phase transition temperature (Tc) of nanoliposomes (2.01-7.24°C). Moreover, nanoliposomes had considerable stability during storage. Consequently, liposome is an efficient carrier for protection and improving PGHE biofunctional actives in foodstuffs. Copyright © 2016 Elsevier Ltd. All rights reserved.

Facile control of silica nanoparticles using a novel solvent varying method for the fabrication of artificial opal photonic crystals

NASA Astrophysics Data System (ADS)

Gao, Weihong; Rigout, Muriel; Owens, Huw

2016-12-01

In this work, the Stöber process was applied to produce uniform silica nanoparticles (SNPs) in the meso-scale size range. The novel aspect of this work was to control the produced silica particle size by only varying the volume of the solvent ethanol used, whilst fixing the other reaction conditions. Using this one-step Stöber-based solvent varying (SV) method, seven batches of SNPs with target diameters ranging from 70 to 400 nm were repeatedly reproduced, and the size distribution in terms of the polydispersity index (PDI) was well maintained (within 0.1). An exponential equation was used to fit the relationship between the particle diameter and ethanol volume. This equation allows the prediction of the amount of ethanol required in order to produce particles of any target diameter within this size range. In addition, it was found that the reaction was completed in approximately 2 h for all batches regardless of the volume of ethanol. Structurally coloured artificial opal photonic crystals (PCs) were fabricated from the prepared SNPs by self-assembly under gravity sedimentation.

Production of Nanoemulsions from Palm-Based Tocotrienol Rich Fraction by Microfluidization.

PubMed

Goh, Pik Seah; Ng, Mei Han; Choo, Yuen May; Amru, Nasrulhaq Boyce; Chuah, Cheng Hock

2015-11-05

In the present study, tocotrienol rich fraction (TRF) nanoemulsions were produced as an alternative approach to improve solubility and absorption of tocotrienols. In the present study, droplet size obtained after 10 cycles of homogenization with increasing pressure was found to decrease from 120 to 65.1 nm. Nanoemulsions stabilized with Tween series alone or emulsifier blend Brij 35:Span 80 (0.6:0.4 w/w) homogenized at 25,000 psi and 10 cycles, produced droplet size less than 100 nm and a narrow size distribution with a polydispersity index (PDI) value lower than 0.2. However blend of Tween series with Span 80 produced nanoemulsions with droplet size larger than 200 nm. This work has also demonstrated the amount of tocols losses in TRF nanoemulsion stabilized Tweens alone or emulsifier blend Brij 35:Span 80 (0.6:0.4 w/w) ranged between 3%-25%. This can be attributed to the interfacial film formed surrounding the droplets exhibited different level of oxidative stability against heat and free radicals created during high pressure emulsification.

Preparation and Optimization OF Palm-Based Lipid Nanoparticles Loaded with Griseofulvin.

PubMed

Huei Lim, Wen; Jean Tan, Yann; Sin Lee, Choy; Meng Er, Hui; Fung Wong, Shew

2017-01-01

Palm-based lipid nanoparticle formulation loaded with griseofulvin was prepared by solvent-free hot homogenization method. The griseofulvin loaded lipid nanoparticles were prepared via stages of optimisation, by altering the high pressure homogenisation (HPH) parameters, screening on palm-based lipids and Tween series surfactants and selection of lipid to surfactant ratios. A HPLC method has been validated for the drug loading capacity study. The optimum HPH parameter was determined to be 1500 bar with 5 cycles and among the palm-based lipid materials; Lipid C (triglycerides) was selected for the preparation of lipid nanoparticles. Tween 80 was chosen from the Tween series surfactants for its highest saturated solubility of griseofulvin at 53.1 ± 2.16 µg/mL. The optimum formulation of the griseofulvin loaded lipid nanoparticles demonstrated nano-range of particle size (179.8 nm) with intermediate distribution index (PDI) of 0.306, zeta potential of -27.9 mV and drug loading of 0.77%. The formulation was stable upon storage for 1 month at room temperature (25 ° C) and 45 ° C with consistent drug loading capacity.

[Self-hypnosis training for in-hospital chronic pain patients : A retrolective observational study].

PubMed

Keil, Peter C; Lindenberg, Nicole; Lassen, Christoph L; Graf, Bernhard M; Meier, Jens; Wiese, Christoph H

2018-06-01

Hypnosis is probably one of the oldest therapies known to man. In the last decades modern hypnosis has mainly been used by psychotherapists; however, hypnosis is becoming increasingly more important as a therapeutic method in medicine. Hypnosis can be used for a variety of medical indications. In the literature there is much evidence for the effectiveness of hypnosis. The aim of the present investigation was to demonstrate the effectiveness of hypnosis in inpatient treatment of chronic pain patients and to present a self-hypnosis program, which can be easily integrated into pain therapy. From October 2012 to April 2013 all inpatient chronic pain patients were included (group 1: non-hypnosis group, group 2: hypnosis group). Concerning group 2 a standardized protocol for hypnotherapy was integrated in addition to the standardized pain management program. The main goal of hypnotherapy was to integrate a self-hypnosis training so that further implementation in a domestic setting could be guaranteed. By means of standardized test procedures, e. g. Patient Health Questionnaire (PHQ-9), Pain Disability Index (PDI), Generalized Anxiety Disorder (GAD-7) and Numerical Rating Scales (NRS) for pain and general well-being, data were evaluated before and after the pain therapy. The prestandardized and poststandardized test procedures of 30 chronic pain patients were evaluated (17 patients without hypnosis, 13 patients with hypnosis). The main diagnosis according to ICD-10 was "chronic pain disorder" (F45.41) with a MPSS stage III in all patients. The PDI was significantly improved in the hypnosis group (p = 0.019). The other items all showed a trend towards improvement in the hypnosis group (exception GAD-7) but without statistical significance (p > 0.05). In a small patient collective, the present investigation was able to show that the integration of modern hypnotherapy into the treatment of chronic pain patients in an inpatient setting can be another useful therapeutic aspect. In particular, the instructions for learning independently seem to be useful due to the limited in-patient time. More research needs to be carried out to support our initial findings.

Colon-specific delivery of curcumin by exploiting Eudragit-decorated chitosan nanoparticles in vitro and in vivo

NASA Astrophysics Data System (ADS)

Khatik, Renuka; Mishra, Ramakant; Verma, Ashwni; Dwivedi, Pankaj; Kumar, Vivek; Gupta, Varsha; Paliwal, Sarvesh Kumar; Mishra, Prabhat Ranjan; Dwivedi, Anil Kumar

2013-09-01

The aim of present investigation was to prepare chitosan (CS) nanoparticles (NPs) and to study the targeting ability of Eudragit S 100 (ES)-coated chitosan nanoparticles (ES-CS-NPs) in comparison with CS-NPs; both loaded with curcumin (CU); to colon, when administered orally, by restricting the size of formulation up to few nanometers and exploiting the pH sensitivity of ES. The CU-loaded CS-NPs (CS-NPs-CU) have been prepared by ionic gelation method. The coating of ES on CS-NPs-CU (ES-CS-NPs-CU) was performed by oil-in-oil solvent evaporation method using coat:core ratio (2:1). The cross-linking of CS with tri poly phosphate during the preparation of CS-NPs has been confirmed by FTIR. CS-NPs-CU and ES-CS-NPs-CU were evaluated for particle size, their size distribution, percentage drug entrapment, and in vitro drug release study. CS-NPs-CU has an average size 173 ± 4.5 nm and poly dispersity index (PDI) 0.16, whereas ES-CS-NPs-CU shows average size 236 ± 3.2 nm and PDI 0.22. Surface morphology of prepared NPs was confirmed by scanning electron microscopy and transmission electron microscopy. The release profile reveals that the ES coating on the ES-CS-NPs-CU protects the release of CU in upper gastrointestinal tract while maximum release of CU occurred in simulated colonic fluids of pH 6.8. There was no major difference in cell viability between ES-CS-NPs-CU and CS-NPs-CU when they were exposed to Caco-2 cells at all equivalent concentrations. The in vivo uptake studies revealed preferential uptake of ES-CS-NPs-CU in the colon. The significantly higher ( P < 0.01) AUC0-∞ has been observed in case of ES-CS-NPs-CU as compared to CU and CS-NPs-CU representing that ES-CS-NPs-CU was more bioavailable. These results demonstrated that ES-CS-NPs-CU may be useful as potential delivery system for treatment of colon cancer.

Engineering of a novel adjuvant based on lipid-polymer hybrid nanoparticles: A quality-by-design approach.

PubMed

Rose, Fabrice; Wern, Jeanette Erbo; Ingvarsson, Pall Thor; van de Weert, Marco; Andersen, Peter; Follmann, Frank; Foged, Camilla

2015-07-28

The purpose of this study was to design a novel and versatile adjuvant intended for mucosal vaccination based on biodegradable poly(DL-lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) modified with the cationic surfactant dimethyldioctadecylammonium (DDA) bromide and the immunopotentiator trehalose-6,6'-dibehenate (TDB) (CAF01) to tailor humoral and cellular immunity characterized by antibodies and Th1/Th17 responses. Such responses are important for the protection against diseases caused by intracellular bacteria such as Chlamydia trachomatis and Mycobacterium tuberculosis. The hybrid NPs were engineered using an oil-in-water single emulsion method and a quality-by-design approach was adopted to define the optimal operating space (OOS). Four critical process parameters (CPPs) were identified, including the acetone concentration in the water phase, the stabilizer [polyvinylalcohol (PVA)] concentration, the lipid-to-total solid ratio, and the total concentration. The CPPs were linked to critical quality attributes consisting of the particle size, polydispersity index (PDI), zeta-potential, thermotropic phase behavior, yield and stability. A central composite face-centered design was performed followed by multiple linear regression analysis. The size, PDI, enthalpy of the phase transition and yield were successfully modeled, whereas the models for the zeta-potential and the stability were poor. Cryo-transmission electron microscopy revealed that the main structural effect on the nanoparticle architecture is caused by the use of PVA, and two different morphologies were identified: i) A PLGA core coated with one or several concentric lipid bilayers, and ii) a PLGA nanoshell encapsulating lipid membrane structures. The optimal formulation, identified from the OOS, was evaluated in vivo. The hybrid NPs induced antibody and Th1/Th17 immune responses that were similar in quality and magnitude to the response induced by DDA/TDB liposomes, showing that the adjuvant properties of DDA/TDB are maintained in the PLGA hybrid matrix. This study demonstrates the complexity of formulation design for the engineering of a hybrid lipid-polymer nanoparticle adjuvant. Copyright © 2015 Elsevier B.V. All rights reserved.

Chitosan-coated diacerein nanosuspensions as a platform for enhancing bioavailability and lowering side effects: preparation, characterization, and ex vivo/in vivo evaluation

PubMed Central

Allam, Ahmed N; Hamdallah, Sherif I; Abdallah, Ossama Y

2017-01-01

Nanodrug delivery systems have been widely reviewed for their use in several drug formulations to improve bioavailability, sustain effect, and decrease side effects of many candidate drugs. The objective of this study was to evaluate the potential of chitosan (CS)-coated nanosuspensions to enhance bioavailability and reduce the diarrheal side effect of diacerein (DCN) after oral administration. DCN nanosuspensions (DNS) were prepared by sonoprecipitation technique using different stabilizers at three different concentrations. The selected DNS with optimum particle size (PS), polydispersity index (PDI), and Zeta potential (ZP) was coated with three different concentrations of CS-coated DNS (CS-DNS) and screened. In vitro dissolution was performed for the selected lyophilized formulae and compared with DCN powder in addition to the assessment of drug crystallinity via scanning electron microscopy, X-ray powder diffraction, and differential scanning calorimetry. Ex vivo drug permeability using noneverted rat intestine, intraluminal content, and mucoadhesion evaluation was studied for nominated formulae in comparison to DCN suspension. Moreover, in vivo study, pharmacokinetic parameters, and evaluation of diarrheal potential were conducted after oral administration of selected formulae. Polyvinyl pyrrolidone (PVP)-stabilized DNS showed a significant increase (P≤0.05) in PS and PDI as the stabilizer concentration increased. PVP-stabilized DNS with the lowest CS concentration was protected from aggregation by lyophilization with mannitol. A remarked enhancement in dissolution parameters was observed in the nanocrystals’ formulae. Morphological examination and X-ray diffraction confirmed drug crystallinity. The intermediate permeation parameters of CS-DNS-F10, lowest rhein-to-DCN ratio in intraluminal content along with the highest percentage of mucoadhesive, could serve as a sustaining profile of coated formula. CS-DNS-F10 showed a significantly higher Cmax of 0.74±0.15 µg/mL at a delayed Tmax of 3.60±0.55 hours with a relative bioavailability of 172.1% compared to DCN suspension. CS-coated nanosuspensions could serve as promising revenue to enhance bioavailability and reduce the diarrheal side effect of DCN after oral administration. PMID:28740381

Chitosan-coated diacerein nanosuspensions as a platform for enhancing bioavailability and lowering side effects: preparation, characterization, and ex vivo/in vivo evaluation.

PubMed

Allam, Ahmed N; Hamdallah, Sherif I; Abdallah, Ossama Y

2017-01-01

Nanodrug delivery systems have been widely reviewed for their use in several drug formulations to improve bioavailability, sustain effect, and decrease side effects of many candidate drugs. The objective of this study was to evaluate the potential of chitosan (CS)-coated nanosuspensions to enhance bioavailability and reduce the diarrheal side effect of diacerein (DCN) after oral administration. DCN nanosuspensions (DNS) were prepared by sonoprecipitation technique using different stabilizers at three different concentrations. The selected DNS with optimum particle size (PS), polydispersity index (PDI), and Zeta potential (ZP) was coated with three different concentrations of CS-coated DNS (CS-DNS) and screened. In vitro dissolution was performed for the selected lyophilized formulae and compared with DCN powder in addition to the assessment of drug crystallinity via scanning electron microscopy, X-ray powder diffraction, and differential scanning calorimetry. Ex vivo drug permeability using noneverted rat intestine, intraluminal content, and mucoadhesion evaluation was studied for nominated formulae in comparison to DCN suspension. Moreover, in vivo study, pharmacokinetic parameters, and evaluation of diarrheal potential were conducted after oral administration of selected formulae. Polyvinyl pyrrolidone (PVP)-stabilized DNS showed a significant increase ( P ≤0.05) in PS and PDI as the stabilizer concentration increased. PVP-stabilized DNS with the lowest CS concentration was protected from aggregation by lyophilization with mannitol. A remarked enhancement in dissolution parameters was observed in the nanocrystals' formulae. Morphological examination and X-ray diffraction confirmed drug crystallinity. The intermediate permeation parameters of CS-DNS-F10, lowest rhein-to-DCN ratio in intraluminal content along with the highest percentage of mucoadhesive, could serve as a sustaining profile of coated formula. CS-DNS-F10 showed a significantly higher C max of 0.74±0.15 µg/mL at a delayed T max of 3.60±0.55 hours with a relative bioavailability of 172.1% compared to DCN suspension. CS-coated nanosuspensions could serve as promising revenue to enhance bioavailability and reduce the diarrheal side effect of DCN after oral administration.

Processing diets containing corn distillers' dried grains with solubles in growing broiler chickens: effects on performance, pellet quality, ileal amino acids digestibility, and intestinal microbiota.

PubMed

Kim, J S; Hosseindoust, A R; Shim, Y H; Lee, S H; Choi, Y H; Kim, M J; Oh, S M; Ham, H B; Kumar, A; Chae, B J

2018-04-03

The present study investigated the effects of feed form and distillers' dried grains with solubles (DDGS) on growth performance, nutrient digestibility, and intestine microbiota in broilers. A total of 720 broilers (Ross 308; average BW 541 ± 6 g) was randomly allotted to 6 treatments on the basis of BW. There were 6 replicates in each treatment with 20 birds per replicate. Birds were fed 3 different feed forms (mash, simple pellet, and expanded pellet) and DDGS (0 or 20% of diet) in a 3 × 2 factorial arrangement. Simple pellet (SP) and expanded pellet (EP) fed birds showed an increase in BW gain (P < 0.05). The interaction between feed processing and DDGS level was observed on pellet hardness (P < 0.01). The lowest (P < 0.01) pellet durability index (PDI) and hardness were observed in the diet with DDGS. Values for PDI and hardness were higher for EP compared with SP (P < 0.01). Simple pellet decreased ileal digestibility of CP compared to mash feed. The inclusion of DDGS decreased the digestibility of CP, and tended to decrease digestibility of DM (P = 0.056) and gross energy (P = 0.069). Expanded pellet feeding decreased (P < 0.05) the ileal digestibility of isoleucine, lysine, methionine, phenylalanine, threonine, cysteine, and glutamine compared with mash diet. Processed feed increased (P < 0.01) pH in the gizzard and duodenum; however, processing decreased pH in ileum. The addition of DDGS to the diet reduced pH in the duodenum. The population of Lactobacillus spp. was lower in the duodenum of birds fed the EP diet compared to the mash diet. Processed feed increased the colonization of Clostridium spp. in the gizzard. These results indicated that SP and EP in broiler diet had a potential to improve BW gain, but EP compromised amino acid digestibility. In addition, DDGS supplementation (20%) decreased pellet quality and CP digestibility in broiler chickens; however, the growth performance and feed intake were not affected.

The design of naproxen solid lipid nanoparticles to target skin layers.

PubMed

Akbari, Jafar; Saeedi, Majid; Morteza-Semnani, Katayoun; Rostamkalaei, Seyyed Sohrab; Asadi, Masoumeh; Asare-Addo, Kofi; Nokhodchi, Ali

2016-09-01

The aim of the current investigation was to produce naproxen solid lipid nanoparticles (Nap-SLNs) by the ultrasonication method to improve its skin permeation and also to investigate the influence of Hydrophilic-lipophilic balance (HLB) changes on nanoparticles properties. The properties of obtained SLNs loaded with naproxen were characterized by photon correlation spectroscopy (PCS), transmission electron microscopy (TEM) and differential scanning calorimetry (DSC). FT-IR was also used to investigate any interaction between naproxen and the excipients used at the molecular level during the preparation of the SLNs. The performance of the formulations was investigated in terms of skin permeation and also the retention of the drug by the skin. It was found that generally, with increasing the lipid concentration, the average particle size and polydispersity index (PDI) of SLNs increased from 94.257±4.852nm to 143.90±2.685nm and from 0.293±0.037 to 0.525±0.038 respectively. The results also showed that a reduction in the HLB resulted in an increase in the PDI, particle size, zeta potential and entrapment efficiency (EE%). DSC showed that the naproxen encapsulated in the SLNs was in its amorphous form. The peaks of prominent functional groups of naproxen were found in the FT-IR spectra of naproxen-SLN, which confirmed the entrapment of naproxen in the lipid matrix. FT-IR results also ruled out any chemical interaction between drug and the chemicals used in the preparation of SLNs. The amount of naproxen detected in the receptor chamber at all the sampling times for the reference formulation (naproxen solution containing all surfactants at pH 7.4) was higher than that of the Nap-SLN8 formulation. Nap-SLN8 showed an increase in the concentration of naproxen in the skin layer with less systemic absorption. This indicates that most of the drug in Nap-SLN8 remains in the skin which can reduce the side effect of systemic absorption of the drug and increases the concentration of the drug at the site of the action. Copyright © 2016 Elsevier B.V. All rights reserved.

Application of quality by design approach for intranasal delivery of rivastigmine loaded solid lipid nanoparticles: Effect on formulation and characterization parameters.

PubMed

Shah, Brijesh; Khunt, Dignesh; Bhatt, Himanshu; Misra, Manju; Padh, Harish

2015-10-12

In the present investigation, Quality by Design (QbD) approach was applied on the development and optimization of solid lipid nanoparticle (SLN) formulation of hydrophilic drug rivastigmine (RHT). RHT SLN were formulated by homogenization and ultrasonication method using Compritol 888 ATO, tween-80 and poloxamer-188 as lipid, surfactant and stabilizer respectively. The effect of independent variables (X1 - drug: lipid ratio, X2 - surfactant concentration and X3 - homogenization time) on quality attributes of SLN i.e. dependent variables (Y1 - size, Y2 - PDI and Y3 - %entrapment efficiency (%EE)) were investigated using 3(3) factorial design. Multiple linear regression analysis and ANOVA were employed to indentify and estimate the main effect, 2FI, quadratic and cubic effect. Optimized RHT SLN formula was derived from an overlay plot on which further effect of probe sonication was evaluated. Final RHT SLN showed narrow size distribution (PDI- 0.132±0.016) with particle size of 82.5±4.07 nm and %EE of 66.84±2.49. DSC and XRD study showed incorporation of RHT into imperfect crystal lattice of Compritol 888 ATO. In comparison to RHT solution, RHT SLN showed higher in-vitro and ex-vivo diffusion. The diffusion followed Higuchi model indicating drug diffusion from the lipid matrix due to erosion. Histopathology study showed intact nasal mucosa with RHT SLN indicating safety of RHT SLN for intranasal administration. Copyright © 2015 Elsevier B.V. All rights reserved.

[Preparation of ASODN-protamine-HSA-PLGA nanoparticles and initial evaluation of their nucleus targeting property in vitro].

PubMed

Zhang, Yi; Yuan, Li; Yan, Xiao-ling; Gong, Tao; Liu, Jie; Zhang, Zhi-rong; Sun, Xun

2009-05-01

To develop a novel non-viral gene delivery system-SODN-Protamine-HSA-PLGA (ASODN-P/H-PLGA-NP) and investigate its nucleus targeting potential in vitro. ASODN-P/H-PLGA-NP was prepared by mixing the protamine sulfate and HSA. Then the PLGA nanoparticles were prepared using double-emulsion evaporation technique, followed by addition of ASODN to the prepared P/H complex. The morphology of ASODN-P/H-PLGA-NP was observed by transmission electron microscopy. The diameter, PDI, and surface charge of ASODN-P/H-PLGA-NP were measured by photo correlation spectroscopy (PCS). The encapsulation efficiency of ASODN was determined by double step method. The cytotoxicity of ASODN-P/H-PLGA-NP was investigated by MTT assays. The ability to enter the squamouse carcinoma: Hep-2 cell line and its nucleus targeting property were observed by confocal laser scanning microscope. The average diameter, PDI, zeta potential, and encapsulation efficiency of ASODN-P/H-PLGA-NP were 128 nm, 0.234, -23.3 mV, and 78.45%, respectively. ASODN-P/H-PLGA-NP could protect the ASODN from the shear force in the ultrasound process during preparation. ASODN-P/H-PLGA-NP couldenter Hep-2 cells and have certain level of nucleus targeting property. ASODN-P/H-PLGA-NP can be prepared easily with small particle sizes and low cytotoxicity, which might be employed as a good non-viral vector for applications in ASODN delivery to nucleus.

Photodynamic inactivation using curcuminoids and Photogem on caenorhabditis elegans

NASA Astrophysics Data System (ADS)

Albuquerque, Yulli R.; Pratavieira, Sebastião.; Bagnato, Vanderlei S.; Inada, Natalia M.; Souza, Larissa M.; Afonso, Ana; de Souza, Clovis W. O.; Oliveira, Kleber T.; Anibal, Fernanda F.

2018-02-01

Resistance to various anthelmintic drugs is reported in many animals and can become a severe problem for human and animal health. In this study, Photogem® and three curcuminoids compounds (curcumin, demethoxycurcumin, bisdemethoxycurcumin) were used as photosensitizers in the photodynamic inactivation (PDI) in the helminth model Caenorhabditis elegans to investigate the ability of this procedure to worm life cycle. Initially, the presence and location of the photosensitizers in the worm's body were verified by fluorescence confocal microscopy. Curcumin was deposited in the digestive tract and Photogem® along the body of the animal in the incubation time of 12 hours with the photosensitizer. Subsequently, a PDI procedure using a LED device was performed to illuminate the worms treated with the photosensitizers. The worms were observed by optical microscopy until 48 hours after the PDI to verify the changes in motility, the presence of eggs and larvae and the number of live worms. Curcuminoids tested separately and in combination and two light doses of 30 J/m2 no changes were observed in the life cycle of the worm at concentrations of 2 mM and 1 mM. However, in treatment with Photogem® and a light dose of 100 J/m2 a reduction in motility and reproduction of the worm with 0.2 mg/mL was observed after 6 hours of exposure, in addition to the death of most worms at concentrations of 6, 4, and 2 mg/mL. We suggest, therefore, that photodynamic inactivation with Photogem® may present an anthelmintic effect against C. elegans, but there is a need for studies on helminths with parasitic activity.

Tissue Factor Coagulant Activity is Regulated by the Plasma Membrane Microenvironment.

PubMed

Yu, Yuanjie; Böing, Anita N; Hau, Chi M; Hajji, Najat; Ruf, Wolfram; Sturk, Auguste; Nieuwland, Rienk

2018-06-01

 Tissue factor (TF) can be present in a non-coagulant and coagulant form. Whether the coagulant activity is affected by the plasma membrane microenvironment is unexplored.  This article studies the presence and coagulant activity of human TF in plasma membrane micro-domains.  Plasma membranes were isolated from human MIA PaCa2 cells, MDA-MB-231 cells and human vascular smooth muscle cells by Percoll gradient ultracentrifugation after cell disruption. Plasma membranes were fractionated by OptiPrep gradient ultracentrifugation, and the presence of TF, flotillin, caveolin, clathrin, protein disulphide isomerase (PDI), TF pathway inhibitor (TFPI) and phosphatidylserine (PS) were determined.  Plasma membranes contain two detergent-resistant membrane (DRM) compartments differing in density and biochemical composition. High-density DRMs (DRM-H) have a density ( ρ ) of 1.15 to 1.20 g/mL and contain clathrin, whereas low-density DRMs (DRM-L) have a density between 1.09 and 1.13 g/mL and do not contain clathrin. Both DRMs contain TF, flotillin and caveolin. PDI is detectable in DRM-H, TFPI is not detectable in either DMR-H or DRM-L and PS is detectable in DRM-L. The DRM-H-associated TF (> 95% of the TF antigen) lacks detectable coagulant activity, whereas the DRM-L-associated TF triggers coagulation. This coagulant activity is inhibited by lactadherin and thus PS-dependent, but seemed insensitive to 16F16, an inhibitor of PDI.  Non-coagulant and coagulant TF are present within different types of DRMs in the plasma membrane, and the composition of these DRMs may affect the TF coagulant activity. Schattauer GmbH Stuttgart.

An additional function of the rough endoplasmic reticulum protein complex prolyl 3-hydroxylase 1·cartilage-associated protein·cyclophilin B: the CXXXC motif reveals disulfide isomerase activity in vitro.

PubMed

Ishikawa, Yoshihiro; Bächinger, Hans Peter

2013-11-01

Collagen biosynthesis occurs in the rough endoplasmic reticulum, and many molecular chaperones and folding enzymes are involved in this process. The folding mechanism of type I procollagen has been well characterized, and protein disulfide isomerase (PDI) has been suggested as a key player in the formation of the correct disulfide bonds in the noncollagenous carboxyl-terminal and amino-terminal propeptides. Prolyl 3-hydroxylase 1 (P3H1) forms a hetero-trimeric complex with cartilage-associated protein and cyclophilin B (CypB). This complex is a multifunctional complex acting as a prolyl 3-hydroxylase, a peptidyl prolyl cis-trans isomerase, and a molecular chaperone. Two major domains are predicted from the primary sequence of P3H1: an amino-terminal domain and a carboxyl-terminal domain corresponding to the 2-oxoglutarate- and iron-dependent dioxygenase domains similar to the α-subunit of prolyl 4-hydroxylase and lysyl hydroxylases. The amino-terminal domain contains four CXXXC sequence repeats. The primary sequence of cartilage-associated protein is homologous to the amino-terminal domain of P3H1 and also contains four CXXXC sequence repeats. However, the function of the CXXXC sequence repeats is not known. Several publications have reported that short peptides containing a CXC or a CXXC sequence show oxido-reductase activity similar to PDI in vitro. We hypothesize that CXXXC motifs have oxido-reductase activity similar to the CXXC motif in PDI. We have tested the enzyme activities on model substrates in vitro using a GCRALCG peptide and the P3H1 complex. Our results suggest that this complex could function as a disulfide isomerase in the rough endoplasmic reticulum.

Comparison Between Chronic Migraine and Temporomandibular Disorders in Pain-Related Disability and Fear-Avoidance Behaviors.

PubMed

Gil-Martínez, Alfonso; Navarro-Fernández, Gonzalo; Mangas-Guijarro, María Ángeles; Lara-Lara, Manuel; López-López, Almudena; Fernández-Carnero, Josué; La Touche, Roy

2017-11-01

To compare patients with chronic migraine (CM) and chronic temporomandibular disorders (TMD) on disability, pain, and fear avoidance factors and to associate these variables within groups. Descriptive, cross-sectional study. A neurology department and a temporomandibular disorders consult in a tertiary care center. A total of 50 patients with CM and 51 patients with chronic TMD, classified by international criteria classifications. The variables evaluated included pain intensity (visual analog scale [VAS]), neck disability (NDI), craniofacial pain and disability (CF-PDI), headache impact (HIT-6), pain catastrophizing (PCS), and kinesiophobia (TSK-11). Statistically significant differences were found between the CM group and the chronic TMD group in CF-PDI (P < 0.001), PCS (P = 0.03), and HIT-6 (P < 0.001); however, there were no differences between the CM group and the VAS, NDI, and TSK-11 groups (P > 0.05). For the chronic TMD group, the combination of NDI and TSK-11 was a significant covariate model of CF-PDI (adjusted R2 = 0.34). In the CM group, the regression model showed that NDI was a significant predictive factor for HIT-6 (adjusted R2 = 0.19). Differences between the CM group and the chronic TMD group were found in craniofacial pain and disability, pain catastrophizing, and headache impact, but they were similar for pain intensity, neck disability, and kinesiophobia. Neck disability and kinesiophobia were covariates of craniofacial pain and disability (34% of variance) for chronic TMD. In the CM group, neck disability was a predictive factor for headache impact (19.3% of variance). © 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Folic acid Targeted Polymeric Micelles Based on Tocopherol Succinate- Pulluan as an Effective Carrier for Epirubicin: Preparation, Characterization and In-vitro Cytotoxicity Assessment.

PubMed

Hassanzadeh, Farshid; Mehdifar, Mozhdeh; Varshosaz, Jaleh; Khodarahmi, Ghadam Ali; Rostami, Mahboubeh

2018-02-14

Chemotherapy still encounters a serious drawback, the lack of selectivity of anticancer drugs toward neoplastic cells, thus, the normal cells are affected by the cytotoxic action of the drugs. This causes a narrow therapeutic index in most anticancer drugs. We describe the preparation of pullulan-tocopherol succinate-folic acid (Pu-TS-FA) micelles for the first time to targeted delivery of Epirubicin (EPI) to Hela and MCF-7 cell lines. We confirmed the structure of conjugate using spectroscopic methods. The degree of substitution for both folic acid and tocopherol succinate was calculated using 1HNMR. We prepared the micelles via direct dissolution method. All the physicochemical properties of micelles including size, zeta potential, polydispersity index (PDI), critical micelle concentration (CMC), entrapment efficiency (EE %) and release efficiency (RE24%) were determined. The morphology of particles was studied using transmission electron microscopy (TEM), and the in-vitro cell cytotoxicity of EPI loaded micelles was studied using MTT assay on MCF-7 and Hela cell lines. The optimized micelles showed the particle size of 149.5 nm, the zeta potential of -6.49 mV, a polydispersity index of 0.259 ± 0.07, LE% of 88 %, and RE24% of 63 ± 2.45 % with a relatively low CMC 194.87 µg/ml. TEM showed the relatively uniform spherical structure for particles and in vitro MTT assay showed that EPI loaded micelles were more toxic on Hela cell line than MCF7 as expected. Since the Pu-TS-FA micelle could improve the anticancer activity of epirubicin and would be a promising candidate for EPI treatment of cancers. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Cumulative environmental risk in substance abusing women: early intervention, parenting stress, child abuse potential and child development☆

PubMed Central

Schuler, Maureen E.; Black, Maureen M.; Kettinger, Laurie; Harrington, Donna

2011-01-01

Objective To assess the relationship between cumulative environmental risks and early intervention, parenting attitudes, potential for child abuse and child development in substance abusing mothers. Method We studied 161 substance-abusing women, from a randomized longitudinal study of a home based early intervention, who had custody of their children through 18 months. The intervention group received weekly home visits in the first 6 months and biweekly visits from 6 to 18 months. Parenting stress and child abuse potential were assessed at 6 and 18 months postpartum. Children’s mental and motor development (Bayley MDI and PDI) and language development (REEL) were assessed at 6, 12, and 18 months postpartum. Ten maternal risk factors were assessed: maternal depression, domestic violence, nondomestic violence, family size, incarceration, no significant other in home, negative life events, psychiatric problems, homelessness, and severity of drug use. Level of risk was recoded into four categories (2 or less, 3, 4, and 5 or more), which had adequate cell sizes for repeated measures analysis. Data analysis Repeated measures analyses were run to examine how level of risk and group (intervention or control) were related to parenting stress, child abuse potential, and children’s mental, motor and language development over time. Results Parenting stress and child abuse potential were higher for women with five risks or more compared with women who had four or fewer risks; children’s mental, motor, and language development were not related to level of risk. Children in the intervention group had significantly higher scores on the PDI at 6 and 18 months (107.4 vs. 103.6 and 101.1 vs. 97.2) and had marginally better scores on the MDI at 6 and 12 months (107.7 vs. 104.2 and 103.6 vs. 100.1), compared to the control group. Conclusion Compared to drug-abusing women with fewer than five risks, women with five or more risks found parenting more stressful and indicated greater inclination towards abusive and neglectful behavior, placing their infants at increased risk for poor parenting, abuse and neglect. Early home-based intervention in high-risk families may be beneficial to infant development. PMID:14550327

EL:?:40

EPA Pesticide Factsheets

2015-09-10

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Promoting Inclusive Schooling Practices through Practitioner Directed Inquiry.

ERIC Educational Resources Information Center

Salisbury, Christine L.; Wilson, Linda L.; Palombaro, Mary M.

1998-01-01

A study investigated use of practitioner directed inquiry (PDI) by 45 different practitioners who designed, implemented, and evaluated solutions to educational issues affecting the inclusion of students with disabilities. Results indicate positive changes in attitudes and knowledge about inclusive practices and students with disabilities,…

Component analysis and initial validity of the exercise fear avoidance scale.

PubMed

Wingo, Brooks C; Baskin, Monica; Ard, Jamy D; Evans, Retta; Roy, Jane; Vogtle, Laura; Grimley, Diane; Snyder, Scott

2013-01-01

To develop the Exercise Fear Avoidance Scale (EFAS) to measure fear of exercise-induced discomfort. We conducted principal component analysis to determine component structure and Cronbach's alpha to assess internal consistency of the EFAS. Relationships between EFAS scores, BMI, physical activity, and pain were analyzed using multivariate regression. The best fit was a 3-component structure: weight-specific fears, cardiorespiratory fears, and musculoskeletal fears. Cronbach's alpha for the EFAS was α=.86. EFAS scores significantly predicted BMI, physical activity, and PDI scores. Psychometric properties of this scale suggest it may be useful for tailoring exercise prescriptions to address fear of exercise-related discomfort.

Phase unwrapping with a virtual Hartmann-Shack wavefront sensor.

PubMed

Akondi, Vyas; Falldorf, Claas; Marcos, Susana; Vohnsen, Brian

2015-10-05

The use of a spatial light modulator for implementing a digital phase-shifting (PS) point diffraction interferometer (PDI) allows tunability in fringe spacing and in achieving PS without the need for mechanically moving parts. However, a small amount of detector or scatter noise could affect the accuracy of wavefront sensing. Here, a novel method of wavefront reconstruction incorporating a virtual Hartmann-Shack (HS) wavefront sensor is proposed that allows easy tuning of several wavefront sensor parameters. The proposed method was tested and compared with a Fourier unwrapping method implemented on a digital PS PDI. The rewrapping of the Fourier reconstructed wavefronts resulted in phase maps that matched well the original wrapped phase and the performance was found to be more stable and accurate than conventional methods. Through simulation studies, the superiority of the proposed virtual HS phase unwrapping method is shown in comparison with the Fourier unwrapping method in the presence of noise. Further, combining the two methods could improve accuracy when the signal-to-noise ratio is sufficiently high.

Subclinical delusional ideation and a self-reference bias in everyday reasoning.

PubMed

Galbraith, Niall; Manktelow, Ken; Morris, Neil

2008-02-01

Previous studies (e.g. Moller & Husby, 2000; Blackwood et al., 2004) have revealed that delusional thinking is accompanied by an exaggerated focus upon the self and upon stimuli that are perceived to be related to the self. The objective was to examine whether those high in subclinical delusional ideation exhibit a heightened tendency for self-reference. Using a mixed design, healthy individuals, classified into high- and low-scoring groups on the Peters et al. Delusions Inventory (Peters, Day, & Garety, 1996), were compared on everyday reasoning tasks across three experiments. High-PDI scorers, in contrast to the low-PDI group, rated self-referent objections to everyday arguments as stronger than other-referent objections and formulated more self-referent assertion-based objections to everyday arguments. The findings support the notion that subclinical delusional ideation is linked to a self-reference bias, which is evident in the sort of everyday thinking that people engage in when forming or evaluating their beliefs and which may contribute to delusion formation.

Optimization of high purity chitin and chitosan production from Illex argentinus pens by a combination of enzymatic and chemical processes.

PubMed

Vázquez, José Antonio; Noriega, Diana; Ramos, Patricia; Valcarcel, Jesus; Novoa-Carballal, Ramon; Pastrana, Lorenzo; Reis, Rui L; Pérez-Martín, Ricardo I

2017-10-15

The present report illustrates the optimisation of the experimental conditions for the chemical and enzymatic production of chitin and chitosan from Illex argentinus pen by-products. Optima conditions for chitin isolation were established at 0.82M NaOH/36.4°C, 57.5°C/pH=9.29, 59.6°C/pH=9.30 and 49.6°C/pH=5.91 for chemical, alcalase, esperase and neutrase deproteinization, respectively. Chitin samples were subsequently deacetylated by alkaline treatment reaching the highest degrees of deacetylation (DD>93%) at 61.0-63.7% of NaOH and 14.9-16.4h of hydrolysis depending on the type of process previously performed to the squid pens. Molecular weight (as number average molecular weight, Mn) of chitosan produced in the experimental designs ranged from 143kDa (PDI 2.37) to 339kDa (PDI 2.38). Copyright © 2017 Elsevier Ltd. All rights reserved.

Photodynamic inactivation of the models Mycobacterium phlei and Mycobacterium smegmatis in vitro

NASA Astrophysics Data System (ADS)

Bruce-Micah, R.; Gamm, U.; Hüttenberger, D.; Cullum, J.; Foth, H.-J.

2009-07-01

Photodynamic inactivation (PDI) of bacterial strains presents an attractive potential alternative to antibiotic therapies. Success is dependent on the effective accumulation in bacterial cells of photochemical substances called photosensitizers, which are usually porphyrins or their derivatives. The kinetics of porphyrin synthesis after treatment with the precursor ALA and the accumulation of the Chlorin e6 and the following illumination were studied. The goal was to estimate effectivity of the destructive power of these PS in vitro in respect of the physiological states of Mycobacteria. So the present results examine the cell destruction by PDI using ALA-induced Porphyrins and Chlorin e6 accumulated in Mycobacterium phlei and Mycobacterium smegmatis, which serve as models for the important pathogens Mycobacterium tuberculosis, Mycobacterium leprae and Mycobacterium bovis. We could show that both Mycobacterium after ALA and Chlorin e6 application were killed by illumination with light of about 662 nm. A reduction of about 97% could be reached by using a lightdose of 70 mW/cm2.

S-nitrosylation of the thioredoxin-like domains of protein disulfide isomerase and its role in neurodegenerative conditions.

NASA Astrophysics Data System (ADS)

Conway, Myra; Harris, Matthew

2015-04-01

Correct protein folding and inhibition of protein aggregation is facilitated by a cellular ‘quality control system’ that engages a network of protein interactions including molecular chaperones and the ubiquitin proteasome system. Key chaperones involved in these regulatory mechanisms are the protein disulphide isomerases (PDI) and their homologues, predominantly expressed in the endoplasmic reticulum of most tissues. Redox changes that disrupt ER homeostasis can lead to modification of these enzymes or chaperones with the loss of their proposed neuroprotective role resulting in an increase in protein misfolding. Misfolded protein aggregates have been observed in several disease states and are considered to play a pivotal role in the pathogenesis of neurodegenerative conditions such as Alzheimer’s disease, Parkinson’s disease, and Amyotrophic Lateral sclerosis. This review will focus on the importance of the thioredoxin-like -CGHC- active site of PDI and how our understanding of this structural motif will play a key role in unravelling the pathogenic mechanisms that underpin these neurodegenerative conditions.

Inverted methoxypyridinium phthalocyanines for PDI of pathogenic bacteria.

PubMed

Lourenço, Leandro M O; Sousa, Andreina; Gomes, Maria C; Faustino, Maria A F; Almeida, Adelaide; Silva, Artur M S; Neves, Maria G P M S; Cavaleiro, José A S; Cunha, Ângela; Tomé, João P C

2015-10-01

Phthalocyanines (Pc) are photoactive molecules that can absorb and emit light in a large range of the UV-Vis spectrum with recognized potential for medical applications. Considering the biomedical applications an important limitation of these compounds is their low solubility in water. The use of suitable pyridinium groups on Pc is a good strategy to solve this drawback and to make them more effective to photoinactivate Gram-negative bacteria via a photodynamic inactivation (PDI) approach. Herein, an easy synthetic access to obtain inverted tetra- and octa-methoxypyridinium phthalocyanines (compounds 5 and 6) and also their efficiency to photoinactivate a recombinant bioluminescent strain of Escherichia coli is described. The obtained results were compared with the ones obtained when more conventional thiopyridinium phthalocyanines (compounds 7 and 8) were used. This innovative study comparing thiopyridinium and inverted methoxypyridinium moieties on cationic Pc is reported for the first time taking into account the efficiency of singlet oxygen ((1)O2) generation, water solubility and uptake properties.

Preparation of gentiooligosaccharides using Trichoderma viride β-glucosidase.

PubMed

Wang, Fei; Wu, Jing; Chen, Sheng

2018-05-15

The recombinant plasmid pPIC9K-bgl1 containing β-glucosidase bgl1 from Trichoderma viride was constructed by overlapping PCR and integrated into Pichia pastoris KM71. In order to assist the formation of disulfide bonds and thus improve protein folding efficiency, protein disulfide isomerase pdi was co-expressed in the P. pastoris KM71/pPIC9K-bgl1/pPICZ-A-pdi strain, and fermentation in flasks resulted in enzyme activity of 143 U/ml. The enzyme activity of β-glucosidase reached 1402 U/ml following optimisation of fermentation conditions in a 3.6 l bioreactor. With 80% glucose as substrate, gentiooligosaccharides were synthesised by β-glucosidase-based reverse hydrolysis. A yield of 130 g/l was achieved with a conversion rate of 16.25%. With 20% glucose and 40% cellobiose as substrates, gentiooligosaccharides were synthesised by transglycosylation with a yield of 116 g/l and a conversion rate of 19.4%. Copyright © 2017 Elsevier Ltd. All rights reserved.

Redox Regulation in Amyotrophic Lateral Sclerosis

PubMed Central

Parakh, Sonam; Spencer, Damian M.; Halloran, Mark A.; Soo, Kai Y.; Atkin, Julie D.

2013-01-01

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that results from the death of upper and lower motor neurons. Due to a lack of effective treatment, it is imperative to understand the underlying mechanisms and processes involved in disease progression. Regulations in cellular reduction/oxidation (redox) processes are being increasingly implicated in disease. Here we discuss the possible involvement of redox dysregulation in the pathophysiology of ALS, either as a cause of cellular abnormalities or a consequence. We focus on its possible role in oxidative stress, protein misfolding, glutamate excitotoxicity, lipid peroxidation and cholesterol esterification, mitochondrial dysfunction, impaired axonal transport and neurofilament aggregation, autophagic stress, and endoplasmic reticulum (ER) stress. We also speculate that an ER chaperone protein disulphide isomerase (PDI) could play a key role in this dysregulation. PDI is essential for normal protein folding by oxidation and reduction of disulphide bonds, and hence any disruption to this process may have consequences for motor neurons. Addressing the mechanism underlying redox regulation and dysregulation may therefore help to unravel the molecular mechanism involved in ALS. PMID:23533690

Culture and Happiness.

PubMed

Ye, Dezhu; Ng, Yew-Kwang; Lian, Yujun

Culture is an important factor affecting happiness. This paper examines the predictive power of cultural factors on the cross-country differences in happiness and explores how different dimensions of cultural indices differ in their effects on happiness. Our empirical results show that the global leadership and organizational behavior effectiveness nine culture indices are all significantly related with happiness. Out of these nine indices, power distance (PDI) and gender egalitarianism (GEI) play the most important and stable role in determining subjective well-being (SWB). We further examine the relative importance of the various variables in contributing to the R-squared of the regression. The results show that PDI is the most important, accounting for 50 % of the contributions to R-squared of all variables, or equalling the combined contributions of income, population density and four other traditional variables. The contribution of GEI is 37.1 %, also well surpassing other variables. Our results remain robust even taking account of the different data for culture and SWB.

Influence of Nanostructure on the Exciton Dynamics of Multichromophore Donor–Acceptor Block Copolymers

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

Xia, Jianlong; Busby, Erik; Sanders, Samuel N.

Here, we explore the synthesis and photophysics of nanostructured block copolymers that mimic light-harvesting complexes. We find that the combination of a polar and electron-rich boron dipyrromethene (BODIPY) block with a nonpolar electron-poor perylene diimide (PDI) block yields a polymer that self-assembles into ordered “nanoworms”. Numerical simulations are used to determine optimal compositions to achieve robust self-assembly. Photoluminescence spectroscopy is used to probe the rich exciton dynamics in these systems. Using controls, such as homopolymers and random copolymers, we analyze the mechanisms of the photoluminescence from these polymers. With this understanding it allows us to probe in detail the photophysicsmore » of the block copolymers, including the effects of their self-assembly into nanostructures on their excited-state properties. Similar to natural systems, ordered nanostructures result in properties that are starkly different than the properties of free polymers in solution, such as enhanced rates of electronic energy transfer and elimination of excitonic emission from disordered PDI trap states.« less

Influence of Nanostructure on the Exciton Dynamics of Multichromophore Donor–Acceptor Block Copolymers

DOE PAGES

Xia, Jianlong; Busby, Erik; Sanders, Samuel N.; ...

2017-03-27

Here, we explore the synthesis and photophysics of nanostructured block copolymers that mimic light-harvesting complexes. We find that the combination of a polar and electron-rich boron dipyrromethene (BODIPY) block with a nonpolar electron-poor perylene diimide (PDI) block yields a polymer that self-assembles into ordered “nanoworms”. Numerical simulations are used to determine optimal compositions to achieve robust self-assembly. Photoluminescence spectroscopy is used to probe the rich exciton dynamics in these systems. Using controls, such as homopolymers and random copolymers, we analyze the mechanisms of the photoluminescence from these polymers. With this understanding it allows us to probe in detail the photophysicsmore » of the block copolymers, including the effects of their self-assembly into nanostructures on their excited-state properties. Similar to natural systems, ordered nanostructures result in properties that are starkly different than the properties of free polymers in solution, such as enhanced rates of electronic energy transfer and elimination of excitonic emission from disordered PDI trap states.« less

Production of polycaprolactone nanoparticles with low polydispersity index in a tubular recirculating system by using a multifactorial design of experiments

NASA Astrophysics Data System (ADS)

Colmenares Roldán, Gabriel Jaime; Agudelo Gomez, Liliana María; Carlos Cornelio, Jesús Antonio; Rodriguez, Luis Fernando; Pinal, Rodolfo; Hoyos Palacio, Lina Marcela

2018-03-01

Encapsulation and controlled release of substances using polymeric nanoparticles require that these have a high reproducibility, homogeneity, and control over their properties (diameter and polydispersity), especially when they are to be used in medical, pharmaceutical, or nutritional applications among others. In conventional production systems, it is tough to ensure these characteristics; hence, the cost increases when we try to control these properties. This paper shows a comparison between a recirculating system and the standard nanoprecipitation technique for producing polymeric nanoparticles. In previous investigations, we evaluate the effect of recirculating flow and the ratio between the organic and aqueous phase. For this paper, we evaluated the effect of polymer and surfactant concentrations using a multifactorial design of experiments on the recirculating system and on the standard nanoprecipitation system. The response of the design was the average diameter of the nanoparticles and polydispersity index. Finally, we found that the polymer and surfactant concentrations could change the average diameter and polydispersity index of the nanoparticles obtained. On the other hand, it was found that the effect of the polymer concentration was stronger than the surfactant concentration to reduce the average diameter of the nanoparticles. The results of the present study show that the proposed recirculation system presents a high potential to produce polymer nanoparticles with good morphological characteristics, particle size distributions in the nano range, and with a low polydispersity. The average mean size of nanoparticles of polycaprolactone for the design using the recirculating system was of 61 to 140 nm and the values of polydispersity index PDI for this design were between 0.097 and 0.22, while for the design using the standard nanoprecipitation technique, the obtained diameters were 74 to 176 nm and the polydispersity was between 0.26 and 0.41.

Antenatal Dexamethasone Exposure in Preterm Infants Is Associated with Allergic Diseases and the Mental Development Index in Children.

PubMed

Tseng, Wan-Ning; Chen, Chih-Cheng; Yu, Hong-Ren; Huang, Li-Tung; Kuo, Ho-Chang

2016-12-03

Background: Antenatal steroid administration may benefit fetal lung maturity in preterm infants. Although some studies have shown that this treatment may increase asthma in childhood, the correlation between antenatal dexamethasone exposure and allergic diseases remains unclear. The purpose of this study is to investigate the association between antenatal dexamethasone and T cell expression in childhood allergic diseases. Methods: We recruited a cohort of preterm infants born at Kaohsiung Chang Gung Memorial Hospital between 2007 and 2010 with a gestational age of less than 35 weeks and body weight at birth of less than 1500 g. The status of antenatal exposure to steroids and allergic diseases were surveyed using a modified ISAAC questionnaire for subjects aged 2-5 years old. We analyzed Th1/Th2/Th17 expression of mRNA, cytokines (using the Magpix ® my-system), and mental development index (MDI). Results: Among the 40 patients that were followed, the data showed that the antenatal dexamethasone exposure group ( N = 24) had a significantly higher incidence of allergic diseases (75.0% vs. 18.8%, p < 0.0001) when compared to the non-dexamethasone exposure group ( N = 16), especially with regard to asthma (41.7% vs. 0.0%, p = 0.003) and allergic rhinitis (58.3% vs. 18.8%, p = 0.013), but not atopic dermatitis. No statistical difference was observed in the mRNA expression levels of total white blood cell count between the dexamethasone exposure and non-exposure groups ( p > 0.05). However, the asthma group had higher IL-5 levels ( p = 0.009), and the MDI was shown to be significantly higher in the dexamethasone exposure group (90.38 ± 3.31 vs. 79.94 ± 3.58, p = 0.043) while no significant difference was found between the PDI of the two groups. Conclusions: Exposure to antenatal dexamethasone in preterm infants will increase their susceptibility to allergic diseases, particularly asthma and allergic rhinitis. Preterm infants' exposure to antenatal dexamethasone also results in higher MDI scores. Such increases in allergic diseases may be related to increased IL-5 and IL-10 levels.

Neurodevelopmental outcomes of infants with very low birth weights are associated with the severity of their extra-uterine growth retardation.

PubMed

Chien, Han-Chun; Chen, Chao-Huei; Wang, Teh-Ming; Hsu, Ya-Chi; Lin, Ming-Chih

2018-04-01

For infants with very low birth weights (VLBW), their neurodevelopmental outcomes are thought to be associated with extra-uterine growth retardation (EUGR). In this study, based on a single institute, we analyzed the association between different levels or severity of EUGR of VLBW infants and their neurodevelopmental outcomes later at a corrected age of 24 months. This is a hospital-based retrospective cohort study. The severity of EUGR was classified into three categories according to the z-score of discharge weight: z < -2.0, <-2.5, and <-3.0. The outcomes were assessed using the Bayley Scales of Infant Development-II (BSID-II) at a corrected age of 24 months. We then estimated the association of EUGR with low mental developmental index (MDI) or low psychomotor developmental index (PDI). Multiple logistic regression and stratified analyses were used to adjust for the possible confounding factors. In total, 224 VLBW infants were enrolled in this study from 1997 to 2006. In the univariate analysis, EUGR for weight at discharge from hospital was associated with MDI <85 at the corrected age of 24 months, and this association was related to the severity of EUGR (z < -2.5, OR: 1.92 (1.04-3.53); z < -3.0, OR: 2.83 (1.26-6.36)). In addition, the relationship was not confounded by gender nor small for gestational age. The stratified analysis against hemodynamic significant patent ductus arteriosus also revealed that EUGR was an independent predictor for neurodevelopmental outcomes. In VLBW preterm infants, EUGR was significantly associated with low MDI scores assessed at a corrected age of 24 months. Early evaluation and recognition of EUGR should be emphasized when caring for preterm infants. Copyright © 2017. Published by Elsevier B.V.

Design Expert® supported optimization and predictive analysis of selegiline nanoemulsion via the olfactory region with enhanced behavioural performance in Parkinson’s disease

NASA Astrophysics Data System (ADS)

Kumar, Shobhit; Ali, Javed; Baboota, Sanjula

2016-10-01

Selegiline is a monoamine oxidase B (MAO-B) inhibitor and is used in the treatment of Parkinson’s disease. The main problem associated with its oral administration is its low oral bioavailability (10%) due to its poor aqueous solubility and extensive first pass metabolism. The aim of the present research work was to develop a nanoemulsion loaded with selegiline for direct nose-to-brain delivery for the better management of Parkinson’s disease. A quality by design (QbD) approach was used in a statistical multivariate method for the preparation and optimization of nanoemulsion. In this study, four independent variables were chosen, in which two were compositions and two were process variables, while droplet size, transmittance, zeta potential and drug release were selected as response variables. The optimized formulation was assessed for efficacy in Parkinson’s disease using behavioural studies, namely forced swimming, locomotor, catalepsy, muscle coordination, akinesia and bradykinesia or pole test in Wistar rats. The observed droplet size, polydispersity index (PDI), refractive index, transmittance, zeta potential and viscosity of selegiline nanoemulsion were found to be 61.43 ± 4.10 nm, 0.203 ± 0.005, 1.30 ± 0.01, 99.80 ± 0.04%, -34 mV and 31.85 ± 0.24 mPas respectively. Surface characterization studies demonstrated a spherical shape of nanoemulsion which showed 3.7 times enhancement in drug permeation as compared to drug suspension. The results of behaviour studies showed that treatment of haloperidol induced Parkinson’s disease in rats with selegiline nanoemulsion (administered intranasally) showed significant improvement in behavioural activities in comparison to orally administered drug. These findings demonstrate that nanoemulsion could be a promising new drug delivery carrier for intranasal delivery of selegiline in the treatment of Parkinson’s disease.