Glucose 6-Phosphate Dehydrogenase Deficiency Increases Redox Stress and Moderately Accelerates the Development of Heart Failure

PubMed Central

Hecker, Peter A.; Lionetti, Vincenzo; Ribeiro, Rogerio F.; Rastogi, Sharad; Brown, Bethany H.; O’Connell, Kelly A.; Cox, James W.; Shekar, Kadambari C.; Gamble, Dionna; Sabbah, Hani N.; Leopold, Jane A.; Gupte, Sachin A.; Recchia, Fabio A.; Stanley, William C.

2013-01-01

Background Glucose 6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme deficiency in the world. In failing hearts, G6PD is upregulated and generates NADPH that is used by the glutathione pathway to remove reactive oxygen species (ROS), but also as a substrate by ROS-generating enzymes. Therefore, G6PD deficiency might prevent heart failure by decreasing NADPH and ROS production. Methods and Results This hypothesis was evaluated in a mouse model of human G6PD deficiency (G6PDX mice, ~40% normal activity). Myocardial infarction with 3 months followup resulted in LV dilation and dysfunction in both WT and G6PDX mice, but significantly greater end diastolic volume and wall thinning in G6PDX mice. Similarly, pressure overload induced by transverse aortic constriction (TAC) for 6 weeks caused greater LV dilation in G6PDX mice than WT. We further stressed TAC mice by feeding a high fructose diet to increase flux through G6PD and ROS production, and again observed worse LV remodeling and a lower ejection fraction in G6PDX than WT mice. Tissue content of lipid peroxidation products was increased in G6PDX mice in response to infarction and aconitase activity was decreased with TAC, suggesting that G6PD deficiency increases myocardial oxidative stress and subsequent damage. Conclusions Contrary to our hypothesis, G6PD deficiency increased redox stress in response to infarction or pressure overload. However, we found only a modest acceleration of LV remodeling, suggesting that, in individuals with G6PD deficiency and concurrent hypertension or myocardial infarction, the risk for developing heart failure is higher, but limited by compensatory mechanisms. PMID:23170010

Social Learning as Approach for Teacher Professional Development; How Well Does It Suit Them?

ERIC Educational Resources Information Center

Meijs, Celeste; Prinsen, Fleur R.; de Laat, Maarten F.

2016-01-01

Learning from others has been reported as a productive approach for teacher Professional Development (PD) and is seen as a valuable addition to formal PD. Specific insights into whether social learning suits teachers is still lacking. Therefore, the aim of the current study was to develop and apply an instrument to assess social learning…

Interaction effect of psychological distress and asthma control on productivity loss?

PubMed

Moullec, Grégory; FitzGerald, J Mark; Rousseau, Roxanne; Chen, Wenjia; Sadatsafavi, Mohsen

2015-06-01

Little is known about the potential synergistic effect of comorbid psychological distress (PD) and uncontrolled asthma (UA) on productivity loss. We estimated the productivity loss associated with the combination of these two potentially preventable conditions in employed adults with asthma. A population-based random sample of 300 adults with asthma in British Columbia, Canada, was prospectively recruited between Dec 2010 and Aug 2012. PD and productivity loss due to absenteeism and presenteeism was measured using validated instruments, and asthma control was ascertained using 2010 Global Initiative for Asthma management strategy. We used two-part regression models to study the contribution of UA and PD to productivity loss. Compared with reference group (controlled asthma (CA)+noPD), those with UA+noPD had CAD$286 (95%CI $276-297) weekly productivity loss, and those with CA+PD had CAD$465 ($445-485). Those with UA+PD had CAD$449 (437-462) in productivity loss. There was no significant interaction effect of PD with asthma control levels on productivity loss (p=0.22). In patients without PD, uncontrolled asthma was associated with a higher productivity loss than controlled asthma, but this was not the case in patients with PD. This finding can be explained by the fact that the contribution of PD to productivity loss is so large that there is no room for synergy with asthma control. Future studies should assess the impact of interventions that modify PD in patients with asthma. Copyright ©ERS 2015.

Batch, design optimization, and DNA sequencing study for continuous 1,3-propanediol production from waste glycerol by a soil-based inoculum.

PubMed

Kanjilal, Baishali; Noshadi, Iman; Bautista, Eddy J; Srivastava, Ranjan; Parnas, Richard S

2015-03-01

1,3-propanediol (1,3-PD) was produced with a robust fermentation process using waste glycerol feedstock from biodiesel production and a soil-based bacterial inoculum. An iterative inoculation method was developed to achieve independence from soil and selectively breed bacterial populations capable of glycerol metabolism to 1,3-PD. The inoculum showed high resistance to impurities in the feedstock. 1,3-PD selectivity and yield in batch fermentations was optimized by appropriate nutrient compositions and pH control. The batch yield of 1,3-PD was maximized to ~0.7 mol/mol for industrial glycerol which was higher than that for pure glycerin. 16S rDNA sequencing results show a systematic selective enrichment of 1,3-PD producing bacteria with iterative inoculation and subsequent process control. A statistical design of experiments was carried out on industrial glycerol batches to optimize conditions, which were used to run two continuous flow stirred-tank reactor (CSTR) experiments over a period of >500 h each. A detailed analysis of steady states at three dilution rates is presented. Enhanced specific 1,3-PD productivity was observed with faster dilution rates due to lower levels of solvent degeneration. 1,3-PD productivity, specific productivity, and yield of 1.1 g/l hr, 1.5 g/g hr, and 0.6 mol/mol of glycerol were obtained at a dilution rate of 0.1 h(-1)which is bettered only by pure strains in pure glycerin feeds.

Population Pharmacokinetic and Pharmacodynamic Modeling of Lusutrombopag, a Newly Developed Oral Thrombopoietin Receptor Agonist, in Healthy Subjects.

PubMed

Katsube, Takayuki; Ishibashi, Toru; Kano, Takeshi; Wajima, Toshihiro

2016-11-01

The aim of this study was to develop a population pharmacokinetic (PK)/pharmacodynamic (PD) model for describing plasma lusutrombopag concentrations and platelet response following oral lusutrombopag dosing and for evaluating covariates in the PK/PD profiles. A population PK/PD model was developed using a total of 2539 plasma lusutrombopag concentration data and 1408 platelet count data from 78 healthy adult subjects following oral single and multiple (14-day once-daily) dosing. Covariates in PK and PK/PD models were explored for subject age, body weight, sex, and ethnicity. A three-compartment model with first-order rate and lag time for absorption was selected as a PK model. A three-transit and one-platelet compartment model with a sigmoid E max model for drug effect and feedback of platelet production was selected as the PD model. The PK and PK/PD models well described the plasma lusutrombopag concentrations and the platelet response, respectively. Body weight was a significant covariate in PK. The bioavailability of non-Japanese subjects (White and Black/African American subjects) was 13 % lower than that of Japanese subjects, while the simulated platelet response profiles using the PK/PD model were similar between Japanese and non-Japanese subjects. There were no significant covariates of the tested background data including age, sex, and ethnicity (Japanese or non-Japanese) for the PD sensitivity. A population PK/PD model was developed for lusutrombopag and shown to provide good prediction for the PK/PD profiles. The model could be used as a basic PK/PD model in the drug development of lusutrombopag.

Protective effects of Fc-fused PD-L1 on two different animal models of colitis.

PubMed

Song, Mi-Young; Hong, Chun-Pyo; Park, Seong Jeong; Kim, Jung-Hwan; Yang, Bo-Gie; Park, Yunji; Kim, Sae Won; Kim, Kwang Soon; Lee, Ji Yeung; Lee, Seung-Woo; Jang, Myoung Ho; Sung, Young-Chul

2015-02-01

Programmed death-ligand 1 (PD-L1) has been shown to negatively regulate immune responses via its interaction with PD-1 receptor. In this study, we investigated the effects of PD-L1-Fc treatment on intestinal inflammation using two murine models of inflammatory colitis induced by dextran sulfate sodium (DSS) and T-cell transfer. The anti-colitis effect of adenovirus expressing Fc-conjugated PD-L1 (Ad/PD-L1-Fc) and recombinant PD-L1-Fc protein was evaluated in DSS-treated wild-type and Rag-1 knockout (KO) mice. We examined differentiation of T-helper cells, frequency of innate immune cells, and cytokine production by dendritic cells (DCs) in the colon from DSS-treated mice after PD-L1-Fc administration. In Rag-1 KO mice reconstituted with CD4 CD45RB(high) T cells, we assessed the treatment effect of PD-L1-Fc protein on the development of colitis. Administration of Ad/PD-L1-Fc significantly ameliorated DSS-induced colitis, which was accompanied by diminished frequency of interleukin (IL)-17A-producing CD4 T cells and increased interferon-γ-producing CD4 T cells in the colon of DSS-fed mice. The anti-colitic effect of PD-L1-Fc treatment was also observed in DSS-treated Rag-1 KO mice, indicating lymphoid cell independency. PD-L1-Fc modulated cytokine production by colonic DCs and the effect was dependent on PD-1 expression. Furthermore, PD-L1-Fc protein could significantly reduce the severity of colitis in CD4 CD45RB(high) T-cell-transferred Rag-1 KO mice. Based on the protective effect of PD-L1-Fc against DSS-induced and T-cell-induced colitis, our results suggest that PD-1-mediated inhibitory signals have a crucial role in limiting the development of colonic inflammation. This implicates that PD-L1-Fc may provide a novel therapeutic approach to treat inflammatory bowel disease. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Fatal autoimmune hepatitis induced by concurrent loss of naturally arising regulatory T cells and PD-1-mediated signaling.

PubMed

Kido, Masahiro; Watanabe, Norihiko; Okazaki, Taku; Akamatsu, Takuji; Tanaka, Junya; Saga, Kazuyuki; Nishio, Akiyoshi; Honjo, Tasuku; Chiba, Tsutomu

2008-10-01

Because of the lack of animal models developing spontaneous autoimmune hepatitis (AIH), the molecular mechanisms involved in the development of AIH are still unclear. This study aims to examine the regulatory roles of naturally arising CD4(+)CD25(+) regulatory T (Treg) cells and programmed cell death 1 (PD-1)-mediated signaling in the development of AIH. To induce a concurrent loss of Treg cells and PD-1-mediated signaling, neonatal thymectomy (NTx), which severely reduces the number of Treg cells, was performed on PD-1(-/-) mice. After the NTx, we performed histologic examination, assessed autoantibody production and infiltrating cells in the liver, and conducted adoptive transfer experiments. In contrast to NTx mice and PD-1(-/-) mice, NTx-PD-1(-/-) mice produced antinuclear antibodies and developed fatal hepatitis characterized by a CD4(+) and CD8(+) T-cell infiltration invading the parenchyma with massive lobular necrosis. Induction of AIH in NTx-PD-1(-/-) mice was suppressed by transfer of Treg cells, even derived from PD-1(-/-) mice. Transfer of total but not CD4(+) T-cell-depleted splenocytes from NTx-PD-1(-/-) mice into RAG2(-/-) mice induced the development of severe hepatitis. In contrast, the transfer of CD8(+) T-cell-depleted splenocytes triggered only mononuclear infiltrates without massive necrosis of the parenchyma. NTx-PD-1(-/-) mice are the first mouse model of spontaneous fatal AIH. The concurrent loss of Treg cells and PD-1-mediated signaling can induce the development of fatal AIH. Autoreactive CD4(+) T cells are essential for induction of AIH, whereas CD8(+) T cells play an important role in progression to fatal hepatic damage.

Subthalamic nucleus stimulation and spontaneous language production in Parkinson's disease: A double laterality problem.

PubMed

Batens, Katja; De Letter, Miet; Raedt, Robrecht; Duyck, Wouter; Vanhoutte, Sarah; Van Roost, Dirk; Santens, Patrick

2015-08-01

Asymmetric degeneration of dopaminergic neurons, are characteristic for Parkinson's disease (PD). Despite the lateralized representation of language, the correlation of asymmetric degeneration of nigrostriatal networks in PD with language performance has scarcely been examined. The laterality of dopamine depletion influences language deficits in PD and thus modulates the effects of subthalamic nucleus (STN) stimulation on language production. The spontaneous language production of patients with predominant dopamine depletion of the left (PD-left) and right (PD-right) hemisphere was compared in four stimulation conditions. PD-right made comparatively more verb inflection errors than PD-left. Bilateral STN stimulation improves spontaneous language production only for PD-left. The laterality of dopamine depletion influences spontaneous language production and the effect of STN stimulation on linguistic functions. However, it is probably only one of the many variables influencing the effect of STN stimulation on language production. Copyright © 2015 Elsevier Inc. All rights reserved.

Use of Aryl Chlorides as Electrophiles in Pd-Catalyzed Alkene Difunctionalization Reactions

PubMed Central

Rosen, Brandon R.; Ney, Joshua E.; Wolfe, John P.

2010-01-01

The development of conditions that allow use of inexpensive aryl chlorides as electrophiles in Pd-catalyzed alkene carboamination and carboetherification reactions is described. A catalyst composed of Pd(OAc)2 and S-Phos minimizes N-arylation of the substrate and prevents formation of mixtures of regioisomeric products. A number of heterocycles, including pyrrolidines, isoxazolidines, tetrahydrofurans, and pyrazolidines, are efficiently generated with this method. PMID:20297834

Distinguishing Models of Professional Development: The Case of an Adaptive Model's Impact on Teachers' Knowledge, Instruction, and Student Achievement

ERIC Educational Resources Information Center

Koellner, Karen; Jacobs, Jennifer

2015-01-01

We posit that professional development (PD) models fall on a continuum from highly adaptive to highly specified, and that these constructs provide a productive way to characterize and distinguish among models. The study reported here examines the impact of an adaptive mathematics PD model on teachers' knowledge and instructional practices as well…

Characterization of the Xylella fastidiosa PD1311 gene mutant and its suppression of Pierce's disease on grapevines.

PubMed

Hao, Lingyun; Johnson, Kameka; Cursino, Luciana; Mowery, Patricia; Burr, Thomas J

2017-06-01

Xylella fastidiosa causes Pierce's disease (PD) on grapevines, leading to significant economic losses in grape and wine production. To further our understanding of X. fastidiosa virulence on grapevines, we examined the PD1311 gene, which encodes a putative acyl-coenzyme A (acyl-CoA) synthetase, and is highly conserved across Xylella species. It was determined that PD1311 is required for virulence, as the deletion mutant, ΔPD1311, was unable to cause disease on grapevines. The ΔPD1311 strain was impaired in behaviours known to be associated with PD development, including motility, aggregation and biofilm formation. ΔPD1311 also expressed enhanced sensitivity to H 2 O 2 and polymyxin B, and showed reduced survival in grapevine sap, when compared with wild-type X. fastidiosa Temecula 1 (TM1). Following inoculation, ΔPD1311 could not be detected in grape shoots, which may be related to its altered growth and sensitivity phenotypes. Inoculation with ΔPD1311 2 weeks prior to TM1 prevented the development of PD in a significant fraction of vines and eliminated detectable levels of TM1. In contrast, vines inoculated simultaneously with TM1 and ΔPD1311 developed disease at the same level as TM1 alone. In these vines, TM1 populations were distributed similarly to populations in TM1-only inoculated plants. These findings suggest that, through an indirect mechanism, pretreatment of vines with ΔPD1311 suppresses pathogen population and disease. © 2016 BSPP AND JOHN WILEY & SONS LTD.

Statistical Optimization of 1,3-Propanediol (1,3-PD) Production from Crude Glycerol by Considering Four Objectives: 1,3-PD Concentration, Yield, Selectivity, and Productivity.

PubMed

Supaporn, Pansuwan; Yeom, Sung Ho

2018-04-30

This study investigated the biological conversion of crude glycerol generated from a commercial biodiesel production plant as a by-product to 1,3-propanediol (1,3-PD). Statistical analysis was employed to derive a statistical model for the individual and interactive effects of glycerol, (NH 4 ) 2 SO 4 , trace elements, pH, and cultivation time on the four objectives: 1,3-PD concentration, yield, selectivity, and productivity. Optimum conditions for each objective with its maximum value were predicted by statistical optimization, and experiments under the optimum conditions verified the predictions. In addition, by systematic analysis of the values of four objectives, optimum conditions for 1,3-PD concentration (49.8 g/L initial glycerol, 4.0 g/L of (NH 4 ) 2 SO 4 , 2.0 mL/L of trace element, pH 7.5, and 11.2 h of cultivation time) were determined to be the global optimum culture conditions for 1,3-PD production. Under these conditions, we could achieve high 1,3-PD yield (47.4%), 1,3-PD selectivity (88.8%), and 1,3-PD productivity (2.1/g/L/h) as well as high 1,3-PD concentration (23.6 g/L).

The Role of Oxidative Stress in Parkinson’s Disease

PubMed Central

Dias, Vera; Junn, Eunsung; Mouradian, M. Maral

2014-01-01

Oxidative stress plays an important role in the degeneration of dopaminergic neurons in Parkinson’s disease (PD). Disruptions in the physiologic maintenance of the redox potential in neurons interfere with several biological processes, ultimately leading to cell death. Evidence has been developed for oxidative and nitrative damage to key cellular components in the PD substantia nigra. A number of sources and mechanisms for the generation of reactive oxygen species (ROS) are recognized including the metabolism of dopamine itself, mitochondrial dysfunction, iron, neuroinflammatory cells, calcium, and aging. PD causing gene products including DJ-1, PINK1, parkin, alpha-synuclein and LRRK2 also impact in complex ways mitochondrial function leading to exacerbation of ROS generation and susceptibility to oxidative stress. Additionally, cellular homeostatic processes including the ubiquitin-proteasome system and mitophagy are impacted by oxidative stress. It is apparent that the interplay between these various mechanisms contributes to neurodegeneration in PD as a feed forward scenario where primary insults lead to oxidative stress, which damages key cellular pathogenetic proteins that in turn cause more ROS production. Animal models of PD have yielded some insights into the molecular pathways of neuronal degeneration and highlighted previously unknown mechanisms by which oxidative stress contributes to PD. However, therapeutic attempts to target the general state of oxidative stress in clinical trials have failed to demonstrate an impact on disease progression. Recent knowledge gained about the specific mechanisms related to PD gene products that modulate ROS production and the response of neurons to stress may provide targeted new approaches towards neuroprotection. PMID:24252804

Theoretical study on the gas-phase reaction mechanism between palladium monoxide and methane.

PubMed

Yang, Hua-Qing; Hu, Chang-Wei; Gao, Chao; Yang, Meng-Yao; Li, Fang-Ming; Li, Cai-Qin; Li, Xiang-Yuan

2011-12-01

The gas-phase reaction mechanism between palladium monoxide and methane has been theoretically investigated on the singlet and triplet state potential energy surfaces (PESs) at the CCSD(T)/AVTZ//B3LYP/6-311+G(2d, 2p), SDD level. The major reaction channel leads to the products PdCH(2) + H(2)O, whereas the minor channel results in the products Pd + CH(3)OH, CH(2)OPd + H(2), and PdOH + CH(3). The minimum energy reaction pathway for the formation of main products (PdCH(2) + H(2)O), involving one spin inversion, prefers to start at the triplet state PES and afterward proceed along the singlet state PES, where both CH(3)PdOH and CH(3)Pd(O)H are the critical intermediates. Furthermore, the rate-determining step is RS-CH(3) PdOH → RS-2-TS1cb → RS-CH(2)Pd(H)OH with the rate constant of k = 1.48 × 10(12) exp(-93,930/RT). For the first C-H bond cleavage, both the activation strain ΔE(≠)(strain) and the stabilizing interaction ΔE(≠)(int) affect the activation energy ΔE(≠), with ΔE(≠)(int) in favor of the direct oxidative insertion. On the other hand, in the PdCH(2) + H(2) O reaction, the main products are Pd + CH(3)OH, and CH(3)PdOH is the energetically preferred intermediate. In the CH(2)OPd + H(2) reaction, the main products are Pd + CH(3)OH with the energetically preferred intermediate H(2)PdOCH(2). In the Pd + CH(3)OH reaction, the main products are CH(2)OPd + H(2), and H(2)PdOCH(2) is the energetically predominant intermediate. The intermediates, PdCH(2), H(2) PdCO, and t-HPdCHO are energetically preferred in the PdC + H(2), PdCO + H(2), and H(2)Pd + CO reactions, respectively. Besides, PdO toward methane activation exhibits higher reaction efficiency than the atom Pd and its first-row congener NiO. Copyright © 2011 Wiley Periodicals, Inc.

The role of economies of scale in the cost of dialysis across the world: a macroeconomic perspective.

PubMed

Karopadi, Akash Nayak; Mason, Giacomo; Rettore, Enrico; Ronco, Claudio

2014-04-01

The treatment of chronic kidney disease through dialysis is a considerable expense in most health systems. The two chief methods of providing dialysis, haemodialysis (HD) and peritoneal dialysis (PD) have significant differences in cost composition and factors of production. The aim of this article is to identify and quantify the macroeconomic variables that influence the relative cost of such modalities across different countries. From previously published literature, we extracted the estimates of HD/PD cost ratios in a total of 46 countries. We conducted a multivariate regression analysis using the estimated HD/PD cost ratio in each country, with several country level indicators as explanatory variables. We found a strong statistical effect of the following variables on the HD/PD cost ratio: country's level of development, economies of scale and percentage of private health-care expenditure. The statistical effects on HD/PD ratio by local manufacturing and relaxed import regulation of PD equipment were calculated and were found to be very significant. it is possible for a country to still reap the benefits of economies of scale in provision of PD, even in the absence of a large enough market to make local production of PD equipment feasible in that country.

Household organophosphorus pesticide use and Parkinson's disease.

PubMed

Narayan, Shilpa; Liew, Zeyan; Paul, Kimberly; Lee, Pei-Chen; Sinsheimer, Janet S; Bronstein, Jeff M; Ritz, Beate

2013-10-01

Household pesticide use is widespread in the USA. Since the 1970s, organophosphorus chemicals (OPs) have been common active ingredients in these products. Parkinson's disease (PD) has been linked to pesticide exposures but little is known about the contributions of chronic exposures to household pesticides. Here we investigate whether long-term use of household pesticides, especially those containing OPs, increases the odds of PD. In a population-based case-control study, we assessed frequency of household pesticide use for 357 cases and 807 controls, relying on the California Department of Pesticide Regulation product label database to identify ingredients in reported household pesticide products and the Pesticide Action Network pesticide database of chemical ingredients. Using logistic regression we estimated the effects of household pesticide use. Frequent use of any household pesticide increased the odds of PD by 47% [odds ratio (OR)=1.47, (95% confidence interval (CI): 1.13, 1.92)]; frequent use of products containing OPs increased the odds of PD more strongly by 71% [OR=1.71, (95% CI: 1.21, 2.41)] and frequent organothiophosphate use almost doubled the odds of PD. Sensitivity analyses showed that estimated effects were independent of other pesticide exposures (ambient and occupational) and the largest odds ratios were estimated for frequent OP users who were carriers of the 192QQ paraoxonase genetic variant related to slower detoxification of OPs. We provide evidence that household use of OP pesticides is associated with an increased risk of developing PD.

Household organophosphorus pesticide use and Parkinson’s disease

PubMed Central

Narayan, Shilpa; Liew, Zeyan; Paul, Kimberly; Lee, Pei-Chen; Sinsheimer, Janet S; Bronstein, Jeff M; Ritz, Beate

2013-01-01

Background Household pesticide use is widespread in the USA. Since the 1970s, organophosphorus chemicals (OPs) have been common active ingredients in these products. Parkinson’s disease (PD) has been linked to pesticide exposures but little is known about the contributions of chronic exposures to household pesticides. Here we investigate whether long-term use of household pesticides, especially those containing OPs, increases the odds of PD. Methods In a population-based case-control study, we assessed frequency of household pesticide use for 357 cases and 807 controls, relying on the California Department of Pesticide Regulation product label database to identify ingredients in reported household pesticide products and the Pesticide Action Network pesticide database of chemical ingredients. Using logistic regression we estimated the effects of household pesticide use. Results Frequent use of any household pesticide increased the odds of PD by 47% [odds ratio (OR) = 1.47, (95% confidence interval (CI): 1.13, 1.92)]; frequent use of products containing OPs increased the odds of PD more strongly by 71% [OR = 1.71, (95% CI: 1.21, 2.41)] and frequent organothiophosphate use almost doubled the odds of PD. Sensitivity analyses showed that estimated effects were independent of other pesticide exposures (ambient and occupational) and the largest odds ratios were estimated for frequent OP users who were carriers of the 192QQ paraoxonase genetic variant related to slower detoxification of OPs. Conclusions We provide evidence that household use of OP pesticides is associated with an increased risk of developing PD. PMID:24057998

Accumulation of advanced glycation end products and beta 2-microglobulin in fibrotic thickening of the peritoneum in long-term peritoneal dialysis patients.

PubMed

Nakamoto, Hirotaka; Hamada, Chieko; Shimaoka, Tetsutaro; Sekiguchi, Yoshimi; Io, Hiroaki; Kaneko, Kayo; Horikoshi, Satoshi; Tomino, Yasuhiko

2014-03-01

Characteristics of pathological alterations in long-term peritoneal dialysis (PD) are thickening of submesothelial compact (SMC) zone, small-vessel vasculopathy, and loss of mesothelial cells. Bioincompatible PD fluid plays crucial roles in peritoneal injury. Encapsulating peritoneal sclerosis (EPS), a rare and serious complication, occurred in patients on long-term PD or frequent peritonitis episodes, and ~50 % of EPS developed after PD cessation. We hypothesized that PD-related peritoneal injury factors induced by bioincompatible PD fluid accumulated in the peritoneum and might induce EPS. We therefore examined the accumulation of advanced glycation end products (AGE) and beta 2-microglobulin (β2M) in peritoneum and evaluated the relationship between their accumulation, clinical parameters, and outcome after PD cessation. Forty-five parietal peritoneal specimens were obtained from 28 PD patients, 14 uremic patients, and three patients with normal kidney function. The peritoneal equilibration test was used for peritoneal function. AGE- and β2M-expressing areas were found in vascular walls, perivascular areas, and the deep layer of the SMC in short-term PD patients and extended over the entire SMC in long-term patients. Peritonitis and prolonged PD treatment aggravated peritoneal thickening and the proportion of AGE-expressing areas. The proportion of β2M-expressing areas was increased in long-term PD patients. Thickening of the SMC and the proportions of AGE- and β2M-expressing areas were not related to ascites or EPS after PD withdrawal. It appears that the increased proportion of AGE and β2M deposition induced by long-term exposure of PD fluid may be a marker of peritoneal injury.

The Cladistic Basis for the Phylogenetic Diversity (PD) Measure Links Evolutionary Features to Environmental Gradients and Supports Broad Applications of Microbial Ecology’s “Phylogenetic Beta Diversity” Framework

PubMed Central

Faith, Daniel P.; Lozupone, Catherine A.; Nipperess, David; Knight, Rob

2009-01-01

The PD measure of phylogenetic diversity interprets branch lengths cladistically to make inferences about feature diversity. PD calculations extend conventional species-level ecological indices to the features level. The “phylogenetic beta diversity” framework developed by microbial ecologists calculates PD-dissimilarities between community localities. Interpretation of these PD-dissimilarities at the feature level explains the framework’s success in producing ordinations revealing environmental gradients. An example gradients space using PD-dissimilarities illustrates how evolutionary features form unimodal response patterns to gradients. This features model supports new application of existing species-level methods that are robust to unimodal responses, plus novel applications relating to climate change, commercial products discovery, and community assembly. PMID:20087461

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

Kojima, S.; Yokosawa, M.; Matsuyama, M.

To study the practical application of a tritium separation process using Self-Developing Gas Chromatography (SDGC) using a Pd-Pt alloy, intermediate scale-up experiments (22 mm ID x 2 m length column) and the development of a computational simulation method have been conducted. In addition, intermediate scale production of Pd-Pt powder has been developed for the scale-up experiments.The following results were obtained: (1) a 50-fold scale-up from 3 mm to 22 mm causes no significant impact on the SDGC process; (2) the Pd-Pt alloy powder is applicable to a large size SDGC process; and (3) the simulation enables preparation of a conceptualmore » design of a SDGC process for tritium separation.« less

Pd-catalyzed one-pot synthesis of polysubstituted acrylamidines from isocyanides, diazo compounds, and imines.

PubMed

Yan, Xu; Liao, Jinxi; Lu, Yongzhi; Liu, Jinsong; Zeng, Youlin; Cai, Qian

2013-05-17

A novel and efficient Pd-catalyzed one-pot reaction of ethyl diazoacetate, isocyanides, and imines for the synthesis of acrylamidines was developed. The multicomponent reaction may have occurred through an unpredicted ring-opening process of the ketenimine-imine [2 + 2] intermediate to form the acrylamidine products.

DFT study of hydrogen production from formic acid decomposition on Pd-Au alloy nanoclusters

NASA Astrophysics Data System (ADS)

Liu, D.; Gao, Z. Y.; Wang, X. C.; Zeng, J.; Li, Y. M.

2017-12-01

Recently, it has been reported that the hydrogen production rate of formic acid decomposition can be significantly increased using Pd-Au binary alloy nano-catalysts [Wang et al. J. Mater. Chem. A 1 (2013) 12721-12725]. To explain the reaction mechanism of this alloy catalysis method, formic acid decomposition reactions on pure Pd and Pd-Au alloy nanoclusters are studied via density functional theory simulations. The simulation results indicate that the addition of inert element Au would not influence formic acid decomposition on Pd surface sites of Pd-Au alloy nanoclusters. On the other hand, the existence of Au surface sites brings relative weak hydrogen atom adsorption. On Pd-Au alloy nanoclusters, the dissociated hydrogen atoms from formic acid are easier to combine as hydrogen molecules than that on pure Pd clusters. Via the synergetic effect between Pd and Au, both formic acid decomposition and hydrogen production are events with large probability, which eventually results in high hydrogen production rate.

Product review on the Anti-PD-L1 antibody atezolizumab.

PubMed

Shah, Neil J; Kelly, William J; Liu, Stephen V; Choquette, Karin; Spira, Alexander

2018-02-01

Immunotherapy as a therapeutic strategy has seized the narrative throughout clinical oncology over the past few years. Once considered a niche treatment for rare cancers, immunotherapy has quickly emerged as the standard of care for many common cancer types. The remarkable rise is largely due to the development of novel checkpoint inhibitors, specifically, antibodies targeting PD-1 and PD-L1. Offering promising efficacy with a favorable toxicity profile, these agents have been approved for use in several malignancies and are under investigation for many more. One of the more appealing features is the chance for meaningful, durable response - uncharacteristic for most cancer therapies. Atezolizumab is a humanized IgG1 monoclonal antibody that targets PD-L1. Atezolizumab has been approved for use in the treatment of advanced non-small cell lung cancer (NSCLC) and bladder cancer and has shown promising activity in several other types of cancer. Here, we provide a product review for atezolizumab.

Natural products from marine organisms with neuroprotective activity in the experimental models of Alzheimer's disease, Parkinson's disease and ischemic brain stroke: their molecular targets and action mechanisms.

PubMed

Choi, Dong-Young; Choi, Hyukjae

2015-02-01

Continuous increases in the incidence of neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), and brain stroke demand the urgent development of therapeutics. Marine organisms are well-known producers of natural products with diverse structures and pharmacological activities. Therefore, researchers have endeavored to identify marine natural products with neuroprotective effects. In this regard, this review summarizes therapeutic targets for AD, PD, and ischemic brain stroke and marine natural products with pharmacological activities on the targets according to taxonomies of marine organisms. Furthermore, several marine natural products on the clinical trials for the treatment of neurological disorders are discussed.

The relationship between glucocerebrosidase mutations and Parkinson disease.

PubMed

Migdalska-Richards, Anna; Schapira, Anthony H V

2016-10-01

Parkinson disease (PD) is the second most common neurodegenerative disorder after Alzheimer disease, whereas Gaucher disease (GD) is the most frequent lysosomal storage disorder caused by homozygous mutations in the glucocerebrosidase (GBA1) gene. Increased risk of developing PD has been observed in both GD patients and carriers. It has been estimated that GBA1 mutations confer a 20- to 30-fold increased risk for the development of PD, and that at least 7-10% of PD patients have a GBA1 mutation. To date, mutations in the GBA1 gene constitute numerically the most important risk factor for PD. The type of PD associated with GBA1 mutations (PD-GBA1) is almost identical to idiopathic PD, except for a slightly younger age of onset and a tendency to more cognitive impairment. Importantly, the pathology of PD-GBA1 is identical to idiopathic PD, with nigral dopamine cell loss, Lewy bodies, and neurites containing alpha-synuclein. The mechanism by which GBA1 mutations increase the risk for PD is still unknown. However, given that clinical manifestation and pathological findings in PD-GBA1 patients are almost identical to those in idiopathic PD individuals, it is likely that, as in idiopathic PD, alpha-synuclein accumulation, mitochondrial dysfunction, autophagic impairment, oxidative and endoplasmic reticulum stress may contribute to the development and progression of PD-GBA1. Here, we review the GBA1 gene, its role in GD, and its link with PD. The impact of glucocerebrosidase 1 (GBA1) mutations on functioning of endoplasmic reticulum (ER), lysosomes, and mitochondria. GBA1 mutations resulting in production of misfolded glucocerebrosidase (GCase) significantly affect the ER functioning. Misfolded GCase trapped in the ER leads to both an increase in the ubiquitin-proteasome system (UPS) and the ER stress. The presence of ER stress triggers the unfolded protein response (UPR) and/or endoplasmic reticulum-associated degradation (ERAD). The prolonged activation of UPR and ERAD subsequently leads to increased apoptosis. The presence of misfolded GCase in the lysosomes together with a reduction in wild-type GCase levels lead to a retardation of alpha-synuclein degradation via chaperone-mediated autophagy (CMA), which subsequently results in alpha-synuclein accumulation and aggregation. Impaired lysosomal functioning also causes a decrease in the clearance of autophagosomes, and so their accumulation. GBA1 mutations perturb normal mitochondria functioning by increasing generation of free radical species (ROS) and decreasing adenosine triphosphate (ATP) production, oxygen consumption, and membrane potential. GBA1 mutations also lead to accumulation of dysfunctional and fragmented mitochondria. This article is part of a special issue on Parkinson disease. © 2016 International Society for Neurochemistry.

Bimetallic Nanocatalysts in Mesoporous Silica for Hydrogen Production from Coal-Derived Fuels

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

Kuila, Debasish; Ilias, Shamsuddin

2013-02-13

In steam reforming reactions (SRRs) of alkanes and alcohols to produce H 2, noble metals such as platinum (Pt) and palladium (Pd) are extensively used as catalyst. These metals are expensive; so, to reduce noble-metal loading, bi-metallic nanocatalysts containing non-noble metals in MCM-41 (Mobil Composition of Material No. 41, a mesoporous material) as a support material with high-surface area were synthesized using one-pot hydrothermal procedure with a surfactant such as cetyltrimethylammonium bromide (CTAB) as a template. Bi-metallic nanocatalysts of Pd-Ni and Pd-Co with varying metal loadings in MCM-41 were characterized by x-ray diffraction (XRD), N 2 adsorption, and Transmission electronmore » microscopy (TEM) techniques. The BET surface area of MCM-41 (~1000 m 2/g) containing metal nanoparticles decreases with the increase in metal loading. The FTIR studies confirm strong interaction between Si-O-M (M = Pd, Ni, Co) units and successful inclusion of metal into the mesoporous silica matrix. The catalyst activities were examined in steam reforming of methanol (SRM) reactions to produce hydrogen. Reference tests using catalysts containing individual metals (Pd, Ni and Co) were also performed to investigate the effect of the bimetallic system on the catalytic behavior in the SRM reactions. The bimetallic system remarkably improves the hydrogen selectivity, methanol conversion and stability of the catalyst. The results are consistent with a synergistic behavior for the Pd-Ni-bimetallic system. The performance, durability and thermal stability of the Pd-Ni/MCM-41 and Pd-Co/MCM-41 suggest that these materials may be promising catalysts for hydrogen production from biofuels. A part of this work for synthesis and characterization of Pd-Ni-MCM-41 and its activity for SRM reactions has been published (“Development of Mesoporous Silica Encapsulated Pd-Ni Nanocatalyst for Hydrogen Production” in “Production and Purification of Ultraclean Transportation Fuels”; Hu, Y., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2011.)« less

Glucose 6-phosphate dehydrogenase deficiency enhances germ cell apoptosis and causes defective embryogenesis in Caenorhabditis elegans.

PubMed

Yang, H-C; Chen, T-L; Wu, Y-H; Cheng, K-P; Lin, Y-H; Cheng, M-L; Ho, H-Y; Lo, S J; Chiu, D T-Y

2013-05-02

Glucose 6-phosphate dehydrogenase (G6PD) deficiency, known as favism, is classically manifested by hemolytic anemia in human. More recently, it has been shown that mild G6PD deficiency moderately affects cardiac function, whereas severe G6PD deficiency leads to embryonic lethality in mice. How G6PD deficiency affects organisms has not been fully elucidated due to the lack of a suitable animal model. In this study, G6PD-deficient Caenorhabditis elegans was established by RNA interference (RNAi) knockdown to delineate the role of G6PD in animal physiology. Upon G6PD RNAi knockdown, G6PD activity was significantly hampered in C. elegans in parallel with increased oxidative stress and DNA oxidative damage. Phenotypically, G6PD-knockdown enhanced germ cell apoptosis (2-fold increase), reduced egg production (65% of mock), and hatching (10% of mock). To determine whether oxidative stress is associated with G6PD knockdown-induced reproduction defects, C. elegans was challenged with a short-term hydrogen peroxide (H2O2). The early phase egg production of both mock and G6PD-knockdown C. elegans were significantly affected by H2O2. However, H2O2-induced germ cell apoptosis was more dramatic in mock than that in G6PD-deficient C. elegans. To investigate the signaling pathways involved in defective oogenesis and embryogenesis caused by G6PD knockdown, mutants of p53 and mitogen-activated protein kinase (MAPK) pathways were examined. Despite the upregulation of CEP-1 (p53), cep-1 mutation did not affect egg production and hatching in G6PD-deficient C. elegans. Neither pmk-1 nor mek-1 mutation significantly affected egg production, whereas sek-1 mutation further decreased egg production in G6PD-deficient C. elegans. Intriguingly, loss of function of sek-1 or mek-1 dramatically rescued defective hatching (8.3- and 9.6-fold increase, respectively) induced by G6PD knockdown. Taken together, these findings show that G6PD knockdown reduces egg production and hatching in C. elegans, which are possibly associated with enhanced oxidative stress and altered MAPK pathways, respectively.

Artistic productivity and creative thinking in Parkinson's disease.

PubMed

Canesi, M; Rusconi, M L; Isaias, I U; Pezzoli, G

2012-03-01

Creative drive and enhanced artistic-like production may emerge in patients with Parkinson's disease (PD) during dopaminergic therapy. However, it has not been described to date whether this artistic-like production results from dopaminergic drugs triggering innate skills or it could be considered as a repeated behavior possibly associated with impulse control disorders (ICDs). We investigated creative drive in a cohort of cognitively preserved patients with PD by means of the Torrance Test of Creative Thinking (TTCT). We also investigated a putative association between creative drive and ICDs in 36 PD patients with (PD-c) or without (PD-nc) increased artistic-like production and 36 healthy controls (HC). We considered artistic-like productivity to be enhanced if patients reported working on any form of art more than 2h per day after the introduction of dopaminergic treatment. The TTCT, the Barratt Impulsiveness Scale (BIS-11A), the Minnesota Impulsive Disorders Interview (MIDI), and the Punding Rating Scale were applied. Mean TTCT score of PD-c was found to be similar to HC (169.4±51.6 vs. 170.2±69.7, respectively), and both PD-c and HC had significantly higher TTCT scores than patients with PD-nc (125.4±46.1 P<0.05). TTCT did not correlate with any demographic or clinical data in both PD subgroups. No correlation was found between TTCT, BIS-11A, and MIDI. Our study suggests that newly acquired artistic-like production in patients with PD is not associated with impulsivity or ICDs. Artistic-like production might represent the emerging of innate skills in a subset of predisposed patients with PD on dopaminergic therapy. © 2011 The Author(s). European Journal of Neurology © 2011 EFNS.

Development of sensory innervation in rat tibia: co-localization of CGRP and substance P with growth-associated protein 43 (GAP-43)

PubMed Central

Gajda, Mariusz; Litwin, Jan A; Cichocki, Tadeusz; Timmermans, Jean-Pierre; Adriaensen, Dirk

2005-01-01

The development of sensory innervation in long bones was investigated in rat tibia in fetuses on gestational days (GD) 16–21 and in neonates and juvenile individuals on postnatal days (PD) 1–28. A double immunostaining method was applied to study the co-localization of the neuronal growth marker growth-associated protein 43 (GAP-43) and the pan-neuronal marker protein gene product 9.5 (PGP 9.5) as well as that of two sensory fibre-associated neuropeptides, calcitonin gene-related peptide (CGRP) and substance P (SP). The earliest, not yet chemically coded, nerve fibres were observed on GD17 in the perichondrium of the proximal epiphysis. Further development of the innervation was characterized by the successive appearance of nerve fibres in the perichondrium/periosteum of the shaft (GD19), the bone marrow cavity and intercondylar eminence (GD21), the metaphyses (PD1), the cartilage canals penetrating into the epiphyses (PD7), and finally in the secondary ossification centres (PD10) and epiphyseal bone marrow (PD14). Maturation of the fibres, manifested by their immunoreactivity for CGRP and SP, was visible on GD21 in the epiphyseal perichondrium, the periosteum of the shaft and the bone marrow, on PD1 in the intercondylar eminence and the metaphyses, on PD7 in the cartilage canals, on PD10 in the secondary ossification centres and on PD14 in the epiphyseal bone marrow. The temporal and topographic pattern of nerve fibre appearance corresponds with the development of regions characterized by active mineralization and bone remodelling, suggesting a possible involvement of the sensory innervation in these processes. PMID:16050900

Attenuation of the programmed cell death-1 pathway increases the M1 polarization of macrophages induced by zymosan

PubMed Central

Chen, W; Wang, J; Jia, L; Liu, J; Tian, Y

2016-01-01

Programmed cell death-1 (PD-1) is a member of the CD28 superfamily that delivers negative signals on interaction with its 2 ligands, PD-L1 and PD-L2. We assessed the contribution of the PD-1 pathway to regulating the polarization of macrophages that promote inflammation induced by zymosan. We found that PD-1−/− mice developed robust peritonitis with more abundant infiltration of M1 macrophages, accompanied by higher levels of pro-inflammation factors, especially monocyte chemotactic protein-1 (MCP-1) compared with wild-type controls ex vivo and in vitro. Our results indicated that PD-1 deficiency promotes M1 rather than M2 polarization of macrophages by enhancing the expression of p-STAT1/p-NF-κB p65 and downregulating p-STAT6. We found that PD-1 engagement followed by zymosan stimulation might primarily attenuate the phosphorylation of tyrosine residue in PD-1 receptor/ligand and the recruitment of SHP-2 to PD-1 receptor/ligand, leading to the reduction of M1 type cytokine production. PMID:26913605

Influence of PD-L1 cross-linking on cell death in PD-L1-expressing cell lines and bovine lymphocytes

PubMed Central

Ikebuchi, Ryoyo; Konnai, Satoru; Okagawa, Tomohiro; Yokoyama, Kazumasa; Nakajima, Chie; Suzuki, Yasuhiko; Murata, Shiro; Ohashi, Kazuhiko

2014-01-01

Programmed death-ligand 1 (PD-L1) blockade is accepted as a novel strategy for the reactivation of exhausted T cells that express programmed death-1 (PD-1). However, the mechanism of PD-L1-mediated inhibitory signalling after PD-L1 cross-linking by anti-PD-L1 monoclonal antibody (mAb) or PD-1–immunogloblin fusion protein (PD-1-Ig) is still unknown, although it may induce cell death of PD-L1+ cells required for regular immune reactions. In this study, PD-1-Ig or anti-PD-L1 mAb treatment was tested in cell lines that expressed PD-L1 and bovine lymphocytes to investigate whether the treatment induces immune reactivation or PD-L1-mediated cell death. PD-L1 cross-linking by PD-1-Ig or anti-PD-L1 mAb primarily increased the number of dead cells in PD-L1high cells, but not in PD-L1low cells; these cells were prepared from Cos-7 cells in which bovine PD-L1 expression was induced by transfection. The PD-L1-mediated cell death also occurred in Cos-7 and HeLa cells transfected with vectors only encoding the extracellular region of PD-L1. In bovine lymphocytes, the anti-PD-L1 mAb treatment up-regulated interferon-γ (IFN-γ) production, whereas PD-1-Ig treatment decreased this cytokine production and cell proliferation. The IFN-γ production in B-cell-depleted peripheral blood mononuclear cells was not reduced by PD-1-Ig treatment and the percentages of dead cells in PD-L1+ B cells were increased by PD-1-Ig treatment, indicating that PD-1-Ig-induced immunosuppression in bovine lymphocytes could be caused by PD-L1-mediated B-cell death. This study provides novel information for the understanding of signalling through PD-L1. PMID:24405267

Glucose 6-phosphate dehydrogenase deficiency enhances germ cell apoptosis and causes defective embryogenesis in Caenorhabditis elegans

PubMed Central

Yang, H-C; Chen, T-L; Wu, Y-H; Cheng, K-P; Lin, Y-H; Cheng, M-L; Ho, H-Y; Lo, S J; Chiu, D T-Y

2013-01-01

Glucose 6-phosphate dehydrogenase (G6PD) deficiency, known as favism, is classically manifested by hemolytic anemia in human. More recently, it has been shown that mild G6PD deficiency moderately affects cardiac function, whereas severe G6PD deficiency leads to embryonic lethality in mice. How G6PD deficiency affects organisms has not been fully elucidated due to the lack of a suitable animal model. In this study, G6PD-deficient Caenorhabditis elegans was established by RNA interference (RNAi) knockdown to delineate the role of G6PD in animal physiology. Upon G6PD RNAi knockdown, G6PD activity was significantly hampered in C. elegans in parallel with increased oxidative stress and DNA oxidative damage. Phenotypically, G6PD-knockdown enhanced germ cell apoptosis (2-fold increase), reduced egg production (65% of mock), and hatching (10% of mock). To determine whether oxidative stress is associated with G6PD knockdown-induced reproduction defects, C. elegans was challenged with a short-term hydrogen peroxide (H2O2). The early phase egg production of both mock and G6PD-knockdown C. elegans were significantly affected by H2O2. However, H2O2-induced germ cell apoptosis was more dramatic in mock than that in G6PD-deficient C. elegans. To investigate the signaling pathways involved in defective oogenesis and embryogenesis caused by G6PD knockdown, mutants of p53 and mitogen-activated protein kinase (MAPK) pathways were examined. Despite the upregulation of CEP-1 (p53), cep-1 mutation did not affect egg production and hatching in G6PD-deficient C. elegans. Neither pmk-1 nor mek-1 mutation significantly affected egg production, whereas sek-1 mutation further decreased egg production in G6PD-deficient C. elegans. Intriguingly, loss of function of sek-1 or mek-1 dramatically rescued defective hatching (8.3- and 9.6-fold increase, respectively) induced by G6PD knockdown. Taken together, these findings show that G6PD knockdown reduces egg production and hatching in C. elegans, which are possibly associated with enhanced oxidative stress and altered MAPK pathways, respectively. PMID:23640458

Stable and Efficient CuO Based Photocathode through Oxygen-Rich Composition and Au-Pd Nanostructure Incorporation for Solar-Hydrogen Production.

PubMed

Masudy-Panah, Saeid; Siavash Moakhar, Roozbeh; Chua, Chin Sheng; Kushwaha, Ajay; Dalapati, Goutam Kumar

2017-08-23

Enhancing stability against photocorrosion and improving photocurrent response are the main challenges toward the development of cupric oxide (CuO) based photocathodes for solar-driven hydrogen production. In this paper, stable and efficient CuO-photocathodes have been developed using in situ materials engineering and through gold-palladium (Au-Pd) nanoparticles deposition on the CuO surface. The CuO photocathode exhibits a photocurrent generation of ∼3 mA/cm 2 at 0 V v/s RHE. Time-of-flight secondary ion mass spectrometry (TOF-SIMS) analysis and X-ray spectroscopy (XPS) confirm the formation of oxygen-rich (O-rich) CuO film which demonstrates a highly stable photocathode with retained photocurrent of ∼90% for 20 min. The influence of chemical composition on the photocathode performance and stability has been discussed in detail. In addition, O-rich CuO photocathodes deposited with Au-Pd nanostructures have shown enhanced photoelectrochemical performance. Linear scan voltammetry characteristic shows ∼25% enhancement in photocurrent after Au-Pd deposition and reaches ∼4 mA/cm 2 at "0" V v/s RHE. Hydrogen evolution rate significantly depends on the elemental composition of CuO and metal nanostructure. The present work has demonstrated a stable photocathode with high photocurrent for visible-light-driven water splitting and hydrogen production.

Enhanced photocatalytic H2 production of Mn0.5Cd0.5S solid solution through loading transition metal sulfides XS (X = Mo, Cu, Pd) cocatalysts

NASA Astrophysics Data System (ADS)

Zhai, Huishan; Liu, Xiaolei; Wang, Peng; Huang, Baibiao; Zhang, Qianqian

2018-02-01

Development of highly efficient cocatalyst is important towards photocatalytic H2 production. Herein, a series of transition metal sulfides XS (X = Mo, Cu, Pd) as cocatalysts have been successfully grown on Mn0.5Cd0.5S photocatalyst through photo-reduction or in-situ deposition method, respectively. Among them, the maximum production of H2 obtained from MoS2/Mn0.5Cd0.5S, CuxS/Mn0.5Cd0.5S (1 ≤ x ≤ 2) and PdS/Mn0.5Cd0.5S samples were 197, 347 and 614 μmol/h, which were around 6.5, 11.5 and 20.3 times than pristine Mn0.5Cd0.5S. MoS2/Mn0.5Cd0.5S heterostructure can facilitate electron transfer from Mn0.5Cd0.5S to MoS2 and MoS2 as active site for H2 production, p-n junction constructed between Mn0.5Cd0.5S and CuxS can efficiently separate the photo-generated carriers and PdS as a hole acceptor can accelerate the consume of photo-generated holes to enhance the photocatalytic H2 production. The effective charge transfer was further proved by the weaker PL intensity and stronger photocurrent density relative to that of Mn0.5Cd0.5S alone. This work demonstrated that transition metal sulfides XS (X = Mo, Cu, Pd) are efficient cocatalysts to improve the H2 production performance of Mn0.5Cd0.5S photocatalyst.

Pd-Catalyzed Asymmetric β-Hydride Elimination En Route to Chiral Allenes

PubMed Central

Crouch, Ian T.; Neff, Robynne K.; Frantz, Doug E.

2013-01-01

We wish to report our preliminary results on the discovery and development of a catalytic, asymmetric β-hydride elimination from vinyl Pd(II)-complexes derived from enol triflates to access chiral allenes. To achieve this, we developed a class of chiral phosphite ligands that demonstrate high enantioselectivity, allow access of either allene enantiomer, and are readily synthesized. The methodology is demonstrated on over 20 substrates and application to the formal asymmetric total synthesis of the natural product, (+)-epibatidine, is also provided. PMID:23488914

Curcumin: a potential neuroprotective agent in Parkinson's disease.

PubMed

Mythri, R B; Bharath, M M Srinivas

2012-01-01

Parkinson's disease (PD) is an age-associated neurodegenerative disease clinically characterized as a movement disorder. The motor symptoms in PD arise due to selective degeneration of dopaminergic neurons in the substantia nigra of the ventral midbrain thereby depleting the dopamine levels in the striatum. Most of the current pharmacotherapeutic approaches in PD are aimed at replenishing the striatal dopamine. Although these drugs provide symptomatic relief during early PD, many patients develop motor complications with long-term treatment. Further, PD medications do not effectively tackle tremor, postural instability and cognitive deficits. Most importantly, most of these drugs do not exhibit neuroprotective effects in patients. Consequently, novel therapies involving natural antioxidants and plant products/molecules with neuroprotective properties are being exploited for adjunctive therapy. Curcumin is a polyphenol and an active component of turmeric (Curcuma longa), a dietary spice used in Indian cuisine and medicine. Curcumin exhibits antioxidant, anti-inflammatory and anti-cancer properties, crosses the blood-brain barrier and is neuroprotective in neurological disorders. Several studies in different experimental models of PD strongly support the clinical application of curcumin in PD. The current review explores the therapeutic potential of curcumin in PD.

The Relationship Between Speech Production and Speech Perception Deficits in Parkinson's Disease.

PubMed

De Keyser, Kim; Santens, Patrick; Bockstael, Annelies; Botteldooren, Dick; Talsma, Durk; De Vos, Stefanie; Van Cauwenberghe, Mieke; Verheugen, Femke; Corthals, Paul; De Letter, Miet

2016-10-01

This study investigated the possible relationship between hypokinetic speech production and speech intensity perception in patients with Parkinson's disease (PD). Participants included 14 patients with idiopathic PD and 14 matched healthy controls (HCs) with normal hearing and cognition. First, speech production was objectified through a standardized speech intelligibility assessment, acoustic analysis, and speech intensity measurements. Second, an overall estimation task and an intensity estimation task were addressed to evaluate overall speech perception and speech intensity perception, respectively. Finally, correlation analysis was performed between the speech characteristics of the overall estimation task and the corresponding acoustic analysis. The interaction between speech production and speech intensity perception was investigated by an intensity imitation task. Acoustic analysis and speech intensity measurements demonstrated significant differences in speech production between patients with PD and the HCs. A different pattern in the auditory perception of speech and speech intensity was found in the PD group. Auditory perceptual deficits may influence speech production in patients with PD. The present results suggest a disturbed auditory perception related to an automatic monitoring deficit in PD.

"Biocompatible" Neutral pH Low-GDP Peritoneal Dialysis Solutions: Much Ado About Nothing?

PubMed

Misra, Paraish S; Nessim, Sharon J; Perl, Jeffrey

2017-03-01

Adverse outcomes in peritoneal dialysis (PD), including PD related infections, the loss of residual kidney function (RKF), and longitudinal, deleterious changes in peritoneal membrane function continue to limit the long-term success of PD therapy. The observation that these deleterious changes occur upon exposure to conventional glucose-based PD solutions fuels the search for a more biocompatible PD solution. The development of a novel PD solution with a neutral pH, and lower in glucose degradation products (GDPs) compared to its conventional predecessors has been labeled a "biocompatible" solution. While considerable evidence in support of these novel solutions' biocompatibility has emerged from cell culture and animal studies, the clinical benefits as compared to conventional PD solutions are less clear. Neutral pH low GDP (NpHLGDP) PD solutions appear to be effective in reducing infusion pain, but their effects on other clinical endpoints including peritoneal membrane function, preservation of RKF, PD-related infections, and technique and patient survival are less clear. The literature is limited by studies characterized by relatively few patients, short follow-up time, heterogeneity with regards to the novel PD solution type under study, and the different patient populations under study. Nonetheless, the search for a more biocompatible PD solution continues with emerging data on promising non glucose-based solutions. © 2017 Wiley Periodicals, Inc.

Is there an occupational status gradient in the development of periodontal disease in Japanese workers? A 5-year prospective cohort study.

PubMed

Irie, Koichiro; Yamazaki, Toru; Yoshii, Saori; Takeyama, Hideo; Shimazaki, Yoshihiro

2017-02-01

Development of periodontal disease (PD) may be affected by socioeconomic status. This study examined the relationship between occupational status and PD in a 5-year prospective cohort of Japanese workers. In total, 19,633 participants had initial examinations at the Aichi Health Promotion Foundation, of whom 8210 participants aged 20 years or older did not have PD. Follow-up examinations were conducted for 3757 participants, accounting for 45.8% of baseline participants. Ultimately, 3390 participants were analyzed according to the criterion of job classification at baseline, which was based on the International Standard Classification of Occupations, 1987. Oral examinations were performed using the Community Periodontal Index (CPI). The CPI scores were coded as follows: healthy (score of 0); bleeding after probing (1); dental calculus (2); shallow pockets (3); and deep pockets (4). Participants with one or more sextants with a score >2 were diagnosed with PD. Poisson regression analysis was performed to adjust for age and other potential confounders. Overall, 31.6% of men and 23.8% of women had developed PD (CPI scores of 3 or 4). The adjusted relative risk (RR) for PD (CPI scores of 3 or 4) in men was not significant. On the other hand, the adjusted RRs for PD (CPI score of 4) in men were 2.52-, 2.39-, and 2.74-fold higher for skilled workers, sales persons, and drivers, respectively, than for professionals. In contrast, we found no gradient in women. We found a gradient related to the risk of developing PD according to occupational status among men in a Japanese worker population. Copyright © 2016 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Impairment of work productivity in panic disorder patients.

PubMed

Lee Park, Yu; Kim, Won; Chae, Jeong-Ho; Seo Oh, Kang; Frick, Kevin D; Woo, Jong-Min

2014-03-01

Panic disorder (PD) has a critical impact on productivity at the workplace. This study aimed to identify the lost productivity time (LPT) for patients with PD. It also assessed change in LPT for patients with PD after 12 weeks of treatment with Selective Serotonin Reuptake Inhibitors (SSRIs), compared with healthy controls. Working patients diagnosed with PD without other major medical or psychiatric illness were enrolled at outpatient psychiatric clinics (N=108). Age and sex-matched healthy controls were recruited through advertisement (N=108). Health and productivity, PD symptoms, and depressive symptoms were assessed using the Korean version of the World Health Organization's Health and Work Performance Questionnaire (HPQ), the Panic Disorder Severity Scale (PDSS), and the Hamilton Rating Scales for Depression (HAM-D), respectively at baseline, week 4, and week 12. At baseline, the PD group showed significantly higher LPT compared to the control group (103.02 vs. 47.28h in the past 4 weeks). After 12 weeks of treatment, the PD group displayed significant clinical improvement as well as improved productivity with a marked reduction in LPT. Among the patients who completed the treatment, LPT due to PD was reduced from 104.38 to 55.15h in the past 4 weeks. There may be selection bias due to case-control study design. These data suggest that, after the treatment, there was significant improvement in clinical symptoms, and that productivity loss due to PD was almost entirely recovered to the level of healthy controls after 12 weeks of psychiatric outpatient treatment. Copyright © 2013 Elsevier B.V. All rights reserved.

One- and two-photon photosensitized singlet oxygen production: characterization of aromatic ketones as sensitizer standards.

PubMed

Arnbjerg, Jacob; Paterson, Martin J; Nielsen, Christian B; Jørgensen, Mikkel; Christiansen, Ove; Ogilby, Peter R

2007-07-05

Singlet molecular oxygen, O2(a1Deltag), can be efficiently produced in a photosensitized process using either one- or two-photon irradiation. The aromatic ketone 1-phenalenone (PN) is an established one-photon singlet oxygen sensitizer with many desirable attributes for use as a standard. In the present work, photophysical properties of two other aromatic ketones, pyrene-1,6-dione (PD) and benzo[cd]pyren-5-one (BP), are reported and compared to those of PN. Both PD and BP sensitize the production of singlet oxygen with near unit quantum efficiency in a nonpolar (toluene) and a polar (acetonitrile) solvent. With their more extensive pi networks, the one-photon absorption spectra for PD and BP extend out to longer wavelengths than that for PN, thus providing increased flexibility for sensitizer excitation over the range approximately 300-520 nm. Moreover, PD and BP have much larger two-photon absorption cross sections than PN over the range 655-840 nm which, in turn, results in amounts of singlet oxygen that are readily detected in optical experiments. One- and two-photon absorption spectra of PD and BP obtained using high-level calculations model the salient features of the experimental data well. In particular, the ramifications of molecular symmetry are clearly reflected in both the experimental and calculated spectra. The use of PD and BP as standards for both the one- and two-photon photosensitized production of singlet oxygen is expected to facilitate the development of new sensitizers for application in singlet-oxygen-based imaging experiments.

Inflammatory mechanisms and oxidative stress in Peyronie's disease: therapeutic "rationale" and related emerging treatment strategies.

PubMed

Paulis, Gianni; Brancato, Tommaso

2012-02-01

Peyronie's disease (PD) is a connective tissue disorder characterized by a fibrous plaque involving the tunica albuginea of the penis. The inelastic fibrous plaque leads to a penile curvature. Several Authors have suggested an immunological genesis of this disease, others have linked PD with Dupuytren's contracture. Signs of this disease are curvature, penile pain, penile deformity, difficulty with coitus, shortening, hinging, narrowing and erectile dysfunction. The natural history of PD and the clinical course can develop from spontaneous resolution of symptoms to progressive penile deformity and impotence. Surgical treatment is indicated when patients fail the conservative medical treatment and however, only in case of disease stabilization with a condition of impossibility of penetration. The medical treatment is indicated in the development stage of PD for at least one year after diagnosis and whenever in case of penile pain. Current non-surgical therapy includes vitamin-E, verapamil, para-aminobenzoate, propoleum, colchicine, carnitine, tamoxifen, interferons, collagenase, hyaluronidase, cortisone, pentoxifylline, superoxide dismutase, iontophoresis, radiation, extracorporeal shock wave therapy (ESWT) and the penile extender. The etiology of this fibrotic disease is not widely known, although in recent years pathophysiological knowledge has evolved and new studies propose the penile trauma as cause of the disease. The penile trauma results in a delamination of the tunica albuginea with a consequent small hematoma, then the process evolves as an inflammation with accumulation of inflammatory cells and production of reactive oxygen species (ROS). In the course of the inflammation, Peyronie's disease occurs due to the activation of nuclear factor kappa-B, that induces the production of inducible nitric oxide synthase (iNOS), with an increase of nitric oxide, leading to increased production of peroxynitrite anion. All these processes result in the proliferation of fibroblasts and myo-fibroblasts and excessive production of collagen between the layers of the tunica albuginea (penile plaque). Referring to the current knowledge of inflammatory and oxidative mechanisms of PD, a possible therapeutic strategy is then analyzed. © 2012 Bentham Science Publishers

Synergistic Catalysis between Pd and Fe in Gas Phase Hydrodeoxygenation of m-Cresol

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

Hong, Yongchun; Zhang, He; Sun, Junming

2014-10-31

In this work, a series of Pd/Fe2O3 catalysts were synthesized, characterized, and evaluated for the hydrodeoxygenation (HDO) of m-cresol. It was found that the addition of Pd remarkably promotes the catalytic activity of Fe while the product distributions resemble that of monometallic Fe catalyst, showing high selectivity towards the production of toluene (C-O cleavage without saturation of aromatic ring and C-C cleavage). Reduced catalysts featured with Pd patches on the top of reduced Fe nanoparticle surface, and the interaction between Pd and Fe was further confirmed using X-ray photoelectron spectroscopy (XPS), scanning transmission electron microscopy (STEM) and X-ray absorption nearmore » edge fine structure (XANES). A possible mechanism, including Pd assisted H2 dissociation and Pd facilitated stabilization of metallic Fe surface as well as Pd enhanced product desorption, is proposed to be responsible for the high activity and HDO selectivity in Pd-Fe catalysts. The synergic catalysis derived from Pd-Fe interaction found in this work was proved to be applicable to other precious metal promoted Fe catalysts, providing a promising strategy for future design of highly active and selective HDO catalysts.« less

PD-1+ CD8+ T cells are exhausted in tumours and functional in draining lymph nodes of colorectal cancer patients

PubMed Central

Wu, X; Zhang, H; Xing, Q; Cui, J; Li, J; Li, Y; Tan, Y; Wang, S

2014-01-01

Background: The blockade of PD-1–PD-L1 pathway is emerging as an effective therapeutic strategy for several advanced cancers. But the immune regulatory role of PD-1–PD-L1 pathway is not clear in colorectal cancer (CRC) patients. This study aims to evaluate the role of PD-1–PD-L1 pathway in CD8+ T-cell functions in tumour-draining lymph nodes (TDLNs) and tumours of CRC patients. Methods: PD-1 expression on CD8+ T cells was examined by flow cytometry, and PD-L1 expression in TDLNs and tumour tissues were examined by immunohistochemistry. Production of IFN-γ, IL-2 and expression of granzyme B, perforin in CD8+ T cells were detected by intracellular staining. Results: PD-1 expression is markedly upregulated on CD8+ T cells in TDLNs and tumours compared with that in peripheral blood. PD-1-expressing CD8+ T cells are competent for production of cytokine (IL-2 and IFN-γ) and perforin in the tumour-free lymph nodes (TFLNs), but exhibit exhausted phenotypes in tumours. In addition, PD-L1 is highly expressed in tumours rather than TFLNs, which is closely correlated with the impairment of IFN-γ production of tumour-infiltrating PD-1+ CD8+ T cells. Conclusions: Our findings suggest a suppressive effect of PD-1 on CD8+ T-cell function in tumours, but not in TFLNs. PMID:25093496

Development of small-molecule immune checkpoint inhibitors of PD-1/PD-L1 as a new therapeutic strategy for tumour immunotherapy.

PubMed

Li, Kui; Tian, Hongqi

2018-02-20

Cancer immunotherapy has been increasingly utilised to treat advanced malignancies. The signalling network of immune checkpoints has attracted considerable attention. Immune checkpoint inhibitors are revolutionising the treatment options and expectations for patients with cancer. The reported clinical success of targeting the T-cell immune checkpoint receptors PD-1/PD-L1 has demonstrated the importance of immune modulation. Indeed, antibodies binding to PD-1 or PD-L1 have shown remarkable efficacy. However, antibody drugs have many disadvantages, such as their production cost, stability, and immunogenicity and, therefore, small-molecule inhibitors of PD-1 and its ligand PD-L1 are being introduced. Small-molecule inhibitors could offer inherent advantages in terms of pharmacokinetics and druggability, thereby providing additional methods for cancer treatment and achieving better therapeutic effects. In this review, we first discuss how PD-1/PD-L1-targeting inhibitors modulate the relationship between immune cells and tumour cells in tumour immunotherapy. Second, we discuss how the immunomodulatory potential of these inhibitors can be exploited via rational combinations with immunotherapy and targeted therapy. Third, this review is the first to summarise the current clinical and preclinical evidence regarding small-molecule inhibitors of the PD-1/PD-L1 immune checkpoint, considering features and responses related to the tumours and to the host immune system.

Kinetic and mechanistic study of bimetallic Pt-Pd/Al 2O 3 catalysts for CO and C 3H 6 oxidation

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

Hazlett, Melanie J.; Moses-Debusk, Melanie; Parks, III, James E.

2016-09-21

Low temperature combustion (LTC) diesel engines are being developed to meet increased fuel economy demands. However, some LTC engines emit higher levels of CO and hydrocarbons and therefore diesel oxidation catalyst (DOC) efficiency will be critical. Here, CO and propylene oxidation were studied, as representative LTC exhaust components, over model bimetallic Pt-Pd/γ-Al 2O 3 catalysts. During CO oxidation tests, monometallic Pt suffered the most extensive inhibition which was correlated to a greater extent of dicarbonyl species formation. Pd and Pd-rich bimetallics were inhibited by carbonate formation at higher temperatures. The 1:1 and 3:1 Pt:Pd bimetallic catalysts did not form themore » dicarbonyl species to the same extent as the monometallic Pt sample, and therefore did not suffer from the same level of inhibition. Similarly they also did not form carbonates to as large an extent as the Pd-rich samples and were therefore not as inhibited from this intermediate surface species at higher temperature. The Pd-rich samples were relatively poor propylene oxidation catalysts; and partial oxidation product accumulation deactivated these catalysts. Byproducts observed include acetone, ethylene, acetaldehyde, acetic acid, formaldehyde and CO. For CO and propylene co-oxidation, the onset of propylene oxidation was not observed until complete CO oxidation was achieved, and the bimetallics showed higher activity. In conclusion, this was again related to less extensive poisoning, less dicarbonyl species formation and less overall partial oxidation product accumulation.« less

Structure-guided development of a high-affinity human Programmed Cell Death-1: Implications for tumor immunotherapy

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

Lázár-Molnár, Eszter; Scandiuzzi, Lisa; Basu, Indranil

Programmed Cell Death-1 (PD-1) is an inhibitory immune receptor, which plays critical roles in T cell co-inhibition and exhaustion upon binding to its ligands PD-L1 and PD-L2. We report the crystal structure of the human PD-1 ectodomain and the mapping of the PD-1 binding interface. Mutagenesis studies confirmed the crystallographic interface, and resulted in mutant PD-1 receptors with altered affinity and ligand-specificity. In particular, a high-affinity mutant PD-1 (HA PD-1) exhibited 45 and 30-fold increase in binding to PD-L1 and PD-L2, respectively, due to slower dissociation rates. This mutant (A132L) was used to engineer a soluble chimeric Ig fusion proteinmore » for cell-based and in vivo studies. HA PD-1 Ig showed enhanced binding to human dendritic cells, and increased T cell proliferation and cytokine production in a mixed lymphocyte reaction (MLR) assay. Moreover, in an experimental model of murine Lewis lung carcinoma, HA PD-1 Ig treatment synergized with radiation therapy to decrease local and metastatic tumor burden, as well as in the establishment of immunological memory responses. Our studies highlight the value of structural considerations in guiding the design of a high-affinity chimeric PD-1 Ig fusion protein with robust immune modulatory properties, and underscore the power of combination therapies to selectively manipulate the PD-1 pathway for tumor immunotherapy.« less

Entropy bound of horizons for accelerating, rotating and charged Plebanski–Demianski black hole

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

Debnath, Ujjal, E-mail: ujjaldebnath@yahoo.com

We first review the accelerating, rotating and charged Plebanski–Demianski (PD) black hole, which includes the Kerr–Newman rotating black hole and the Taub-NUT spacetime. The main feature of this black hole is that it has 4 horizons like event horizon, Cauchy horizon and two accelerating horizons. In the non-extremal case, the surface area, entropy, surface gravity, temperature, angular velocity, Komar energy and irreducible mass on the event horizon and Cauchy horizon are presented for PD black hole. The entropy product, temperature product, Komar energy product and irreducible mass product have been found for event horizon and Cauchy horizon. Also their sumsmore » are found for both horizons. All these relations are dependent on the mass of the PD black hole and other parameters. So all the products are not universal for PD black hole. The entropy and area bounds for two horizons have been investigated. Also we found the Christodoulou–Ruffini mass for extremal PD black hole. Finally, using first law of thermodynamics, we also found the Smarr relation for PD black hole.« less

Green diesel production via catalytic hydrogenation/decarboxylation of triglycerides and fatty acids of vegetable oil and brown grease

NASA Astrophysics Data System (ADS)

Sari, Elvan

Increase in the petroleum prices, projected increases in the world's energy demand and environmental awareness have shifted the research interest to the alternative fuel technologies. In particular, green diesel, vegetable oil/animal fat/waste oil and grease derived hydrocarbons in diesel boiling range, has become an attractive alternative to biodiesel---a mixture of fatty acid methyl esters, particularly due to its superior fuel properties that are similar to petroleum diesel. Hence, green diesel can be used as a drop-in fuel in the current diesel engines. The current technology for production of green diesel-hydrodeoxygenation of triglycerides and fatty acids over conventional hydrotreating catalysts suffers from fast catalyst deactivation in the absence of hydrogen combined with high temperatures and high fatty acid content in the feedstock. Additionally, excess hydrogen requirement for hydrodeoxygenation technique leads to high production costs. This thesis proposes a new technology-selective decarboxylation of brown grease, which is a mixture of fats and oils collected from waste water trap and rich in fatty acids, over a supported noble metal catalyst that overcomes the green diesel production challenges. In contrast to other feedstocks used for liquid biofuel production, brown grease is inexpensive and non-food competing feedstock, therefore the process finds solution to waste management issues, reduces the renewable fuel production cost and does not add to the global food shortage problems. Special catalyst formulations were developed to have a high activity and stability in the absence of hydrogen in the fatty acid decarboxylation process. The study shows how catalyst innovations can lead to a new technology that overcomes the process challenges. First, the effect of reaction parameters on the activity and the selectivity of brown grease decarboxylation with minimum hydrogen consumption over an activated carbon supported palladium catalyst were investigated. A 90% conversion of brown grease in a semi-batch mode was obtained in 7 hours. In contrast, in a batch reaction the conversion was roughly 40% in the same reaction time. However, by pre-treating the "as received" brown grease with H 2, the conversion in a batch reactor was increased 1.4--fold; and when the H2 to BG ratio was increased to 3/1 (mol/mol), the conversion was further improved. Therefore, such a two-step processing with selective hydrogenation prior to the decarboxylation of BG improves the product selectivity. The commercial 5% Pd/C catalyst was highly active for the decarboxylation of brown grease to green diesel at 300 °C and 1.5 MPa. Second, a class of Pd catalyst supported on a silica-activated carbon nanocomposite for free fatty acid decarboxylation was developed, and displayed excellent activity and operation stability selectively for the green diesel hydrocarbons formation in the absence of hydrogen under mild reaction conditions. The decarboxylation activities of different amount of silica containing catalysts were investigated in a batch reactor under inert gas. Among them, the formulation with the fewer oxygen surface groups (Pd/Si--C--4) was the most active catalyst for the decarboxylation of an unsaturated fatty acid. The high activity of the Pd/Si--C--4 catalyst is attributed to its accessible and well-distributed metallic Pd nanoparticles inside hybrid mesopores as well as to its low acidity, weak surface interactions and inertness. Thus, Pd supported on carbon modified with silica may be regarded as a prospective decarboxylation catalyst for the removal of oxygen from vegetable oil/animal fat without the need of additional hydrogen. Third, in order to design a suitable catalyst for conversion of brown grease to green diesel, a systematic study of the model compounds--oleic acid was conducted on various catalysts in super-critical water to understand the reaction pathways in the absence of hydrogen. A Si--C support was more effective than activated carbon itself for both decarboxylation of oleic acid and hydrogenation of alkenes. In an additional effort to reduce Pd amount in the catalyst, Pd2Co/C catalysts with various Pd content were prepared and the catalytic activity study showed that 0.5 wt% Pd2Co/C catalyst performs even better than a 5 wt% Pd/C catalyst. Pd and Co alloys were very well dispersed and formed fine clusters, which led to a higher active metal surface area and hence favored the decarboxylation of oleic acid. This study showed that an alloy of Pd on carbon with a significantly low Pd content is much more active and selective to diesel hydrocarbons production from an unsaturated fatty acid in super-critical water and may be regarded as a prospective feasible decarboxylation catalyst for the removal of oxygen from vegetable oil/animal fat without the need of additional hydrogen.

Formation of palladium(0) nanoparticles at microbial surfaces.

PubMed

Bunge, Michael; Søbjerg, Lina S; Rotaru, Amelia-Elena; Gauthier, Delphine; Lindhardt, Anders T; Hause, Gerd; Finster, Kai; Kingshott, Peter; Skrydstrup, Troels; Meyer, Rikke L

2010-10-01

The increasing demand and limited natural resources for industrially important platinum-group metal (PGM) catalysts render the recovery from secondary sources such as industrial waste economically interesting. In the process of palladium (Pd) recovery, microorganisms have revealed a strong potential. Hitherto, bacteria with the property of dissimilatory metal reduction have been in focus, although the biochemical reactions linking enzymatic Pd(II) reduction and Pd(0) deposition have not yet been identified. In this study we investigated Pd(II) reduction with formate as the electron donor in the presence of Gram-negative bacteria with no documented capacity for reducing metals for energy production: Cupriavidus necator, Pseudomonas putida, and Paracoccus denitrificans. Only large and close-packed Pd(0) aggregates were formed in cell-free buffer solutions. Pd(II) reduction in the presence of bacteria resulted in smaller, well-suspended Pd(0) particles that were associated with the cells (called "bioPd(0)" in the following). Nanosize Pd(0) particles (3-30 nm) were only observed in the presence of bacteria, and particles in this size range were located in the periplasmic space. Pd(0) nanoparticles were still deposited on autoclaved cells of C. necator that had no hydrogenase activity, suggesting a hydrogenase-independent formation mechanism. The catalytic properties of Pd(0) and bioPd(0) were determined by the amount of hydrogen released in a reaction with hypophosphite. Generally, bioPd(0) demonstrated a lower level of activity than the Pd(0) control, possibly due to the inaccessibility of the Pd(0) fraction embedded in the cell envelope. Our results demonstrate the suitability of bacterial cells for the recovery of Pd(0), and formation and immobilization of Pd(0) nanoparticles inside the cell envelope. However, procedures to make periplasmic Pd(0) catalytically accessible need to be developed for future nanobiotechnological applications.

Gingival Tissue Inflammation Promotes Increased Matrix Metalloproteinase-12 Production by CD200Rlow Monocyte-Derived Cells in Periodontitis.

PubMed

Björnfot Holmström, Sofia; Clark, Reuben; Zwicker, Stephanie; Bureik, Daniela; Kvedaraite, Egle; Bernasconi, Eric; Nguyen Hoang, Anh Thu; Johannsen, Gunnar; Marsland, Benjamin J; Boström, Elisabeth A; Svensson, Mattias

2017-12-15

Irreversible tissue recession in chronic inflammatory diseases is associated with dysregulated immune activation and production of tissue degradative enzymes. In this study, we identified elevated levels of matrix metalloproteinase (MMP)-12 in gingival tissue of patients with the chronic inflammatory disease periodontitis (PD). The source of MMP12 was cells of monocyte origin as determined by the expression of CD14, CD68, and CD64. These MMP12-producing cells showed reduced surface levels of the coinhibitory molecule CD200R. Similarly, establishing a multicellular three-dimensional model of human oral mucosa with induced inflammation promoted MMP12 production and reduced CD200R surface expression by monocyte-derived cells. MMP12 production by monocyte-derived cells was induced by CSF2 rather than the cyclooxygenase-2 pathway, and treatment of monocyte-derived cells with a CD200R ligand reduced CSF2-induced MMP12 production. Further, MMP12-mediated degradation of the extracellular matrix proteins tropoelastin and fibronectin in the tissue model coincided with a loss of Ki-67, a protein strictly associated with cell proliferation. Reduced amounts of tropoelastin were confirmed in gingival tissue from PD patients. Thus, this novel association of the CD200/CD200R pathway with MMP12 production by monocyte-derived cells may play a key role in PD progression and will be important to take into consideration in the development of future strategies to diagnose, treat, and prevent PD. Copyright © 2017 by The American Association of Immunologists, Inc.

Production of platelet-derived endothelial cell growth factor by normal and transformed human cells in culture.

PubMed Central

Usuki, K; Heldin, N E; Miyazono, K; Ishikawa, F; Takaku, F; Westermark, B; Heldin, C H

1989-01-01

Platelet-derived endothelial cell growth factor (PD-ECGF) is a 45-kDa endothelial cell mitogen which has angiogenic properties in vivo. We report here that human foreskin fibroblasts, a human squamous cell carcinoma cell line, and 2 out of the 3 human thyroid carcinoma cell lines investigated produce PD-ECGF, whereas 21 other cell lines examined do not. The positive cell lines contained a 1.8-kilobase PD-ECGF mRNA, and a 45-kDa protein could be demonstrated in lysates of the cell lines by immunoblotting and immunoprecipitation using a specific antiserum against PD-ECGF. Furthermore, the cell lysates contained mitogenic activity for endothelial cells that was neutralized by the PD-ECGF antiserum. PD-ECGF was found to be secreted only slowly from the producer cells, consistent with the previous finding that the primary translation product lacks a signal sequence. The restricted expression and intracellular sequestration of PD-ECGF imply a strictly controlled function in endothelial cell proliferation and angiogenesis. Aberrant production of PD-ECGF may play a role in tumor angiogenesis. Images PMID:2678104

Nix restores mitophagy and mitochondrial function to protect against PINK1/Parkin-related Parkinson's disease.

PubMed

Koentjoro, Brianada; Park, Jin-Sung; Sue, Carolyn M

2017-03-10

Therapeutic targets are needed to develop neuroprotective treatments for Parkinson's disease (PD). Mitophagy, the selective autophagic elimination of dysfunctional mitochondria, is essential for the maintenance of mitochondrial integrity and is predominantly regulated by the PINK1/Parkin-mediated pathway. Loss of function mutations in Parkin and PINK1 cause an accumulation of dysfunctional mitochondria, leading to nigral neurodegeneration and early-onset PD with a high penetrance rate. We previously identified an asymptomatic homozygous Parkin mutation carrier who had not developed PD by her eighth decade despite the loss of functional Parkin. Here we discover a putative mechanism that protects her against PD. In contrast to Parkin-related PD patient-derived cells, the asymptomatic carrier cells show preserved mitochondrial function and mitophagy which is mediated by mitochondrial receptor Nip3-like protein X (Nix). Nix-mediated mitophagy was not affected by PINK1 knockdown. Both genetic and pharmacological induction of Nix restores mitophagy in PINK1- and Parkin-related PD patient cell lines, confirming its ability to induce mitophagy in the absence of PINK1/Parkin-mediated pathway. Moreover, Nix over-expression improves mitochondrial ATP production in these patient cells. Our results demonstrate that Nix can serve as an alternative mediator of mitophagy to maintain mitochondrial turnover, identifying Nix as a promising target for neuroprotective treatment in PINK1/Parkin-related PD.

A three-electrode column for Pd-catalytic oxidation of TCE in groundwater with automatic pH-regulation and resistance to reduced sulfur compound foiling.

PubMed

Yuan, Songhu; Chen, Mingjie; Mao, Xuhui; Alshawabkeh, Akram N

2013-01-01

A hybrid electrolysis and Pd-catalytic oxidation process is evaluated for degradation of trichloroethylene (TCE) in groundwater. A three-electrode, one anode and two cathodes, column is employed to automatically develop a low pH condition in the Pd vicinity and a neutral effluent. Simulated groundwater containing up to 5 mM bicarbonate can be acidified to below pH 4 in the Pd vicinity using a total of 60 mA with 20 mA passing through the third electrode. By packing 2 g of Pd/Al(2)O(3) pellets in the developed acidic region, the column efficiency for TCE oxidation in simulated groundwater (5.3 mg/L TCE) increases from 44 to 59 and 68% with increasing Fe(II) concentration from 0 to 5 and 10 mg/L, respectively. Different from Pd-catalytic hydrodechlorination under reducing conditions, this hybrid electrolysis and Pd-catalytic oxidation process is advantageous in controlling the fouling caused by reduced sulfur compounds (RSCs) because the in situ generated reactive oxidizing species, i.e., O(2), H(2)O(2) and OH, can oxidize RSCs to some extent. In particular, sulfite at concentrations less than 1 mM even greatly increases TCE oxidation by the production of SO(4)(•-), a strong oxidizing radical, and more OH. Copyright © 2012 Elsevier Ltd. All rights reserved.

Mild Deoxygenation of Aromatic Ketones and Aldehydes over Pd/C Using Polymethylhydrosiloxane as the Reducing Agent**

PubMed Central

Volkov, Alexey; Gustafson, Karl P J; Tai, Cheuk-Wai; Verho, Oscar; Bäckvall, Jan-E; Adolfsson, Hans

2015-01-01

Herein, a practical and mild method for the deoxygenation of a wide range of benzylic aldehydes and ketones is described, which utilizes heterogeneous Pd/C as the catalyst together with the green hydride source, polymethylhydrosiloxane. The developed catalytic protocol is scalable and robust, as exemplified by the deoxygenation of ethyl vanillin, which was performed on a 30 mmol scale in an open-to-air setup using only 0.085 mol % Pd/C catalyst to furnish the corresponding deoxygenated product in 93 % yield within 3 hours at room temperature. Furthermore, the Pd/C catalyst was shown to be recyclable up to 6 times without any observable decrease in efficiency and it exhibited low metal leaching under the reaction conditions. PMID:25728614

Children's perception of their synthetically corrected speech production.

PubMed

Strömbergsson, Sofia; Wengelin, Asa; House, David

2014-06-01

We explore children's perception of their own speech - in its online form, in its recorded form, and in synthetically modified forms. Children with phonological disorder (PD) and children with typical speech and language development (TD) performed tasks of evaluating accuracy of the different types of speech stimuli, either immediately after having produced the utterance or after a delay. In addition, they performed a task designed to assess their ability to detect synthetic modification. Both groups showed high performance in tasks involving evaluation of other children's speech, whereas in tasks of evaluating one's own speech, the children with PD were less accurate than their TD peers. The children with PD were less sensitive to misproductions in immediate conjunction with their production of an utterance, and more accurate after a delay. Within-category modification often passed undetected, indicating a satisfactory quality of the generated speech. Potential clinical benefits of using corrective re-synthesis are discussed.

Increased percentages of PD-1 on CD4+ T cells is associated with higher INF-γ production and altered IL-17 production in patients with systemic lupus erythematosus.

PubMed

Dolff, S; Quandt, D; Feldkamp, T; Jun, C; Mitchell, A; Hua, F; Specker, C; Kribben, A; Witzke, O; Wilde, B

2014-01-01

Programmed death (PD)-1 is a cell death receptor that, upon stimulation, leads to apoptosis. Previous studies have shown alteration of PD-1 expression on T cells and PD-1 genes in patients with systemic lupus erythematosus (SLE). The aim of this study was to assess the expression of this receptor on effector T cells in patients with SLE. In this study we enrolled 32 SLE patients and 31 healthy controls. T cells from peripheral blood were analysed by flow cytometry for the expression of PD-1. Interferon (IFN)-γ and interleukin (IL)-17-producing cells were investigated for the expression of this co-stimulatory marker. Percentages of CD4(+) T cells expressing PD-1 were significantly increased in patients with SLE compared to healthy controls. The percentage of PD-1 expression was correlated with the production of INF-γ (r = 0.83, p < 0.0001). We also investigated the production of IL-17 by PD-1(+) CD3(+) T cells. Inactive patients (3.2 ± 1.2% vs. 5.9 ± 3.5%, p = 0.002) and patients without lupus nephritis (LN) (3.2 ± 1.5% vs. 5.9 ± 3.5%, p = 0.005) showed lower levels of IL-17 compared to healthy controls. We have demonstrated increased expression of PD-1 on CD4(+) T cells in SLE patients and an association between PD-1 expression on CD4(+) T cells and IFN-γ expression on CD3(+) T cells. We have also shown that there is an altered subset of PD-1(+) T cells in inactive patients and patients without LN producing lower amounts of IL-17.

Metabolic engineering for the production of 1,3-propanediol

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

Cameron, D.C.; Tong, I.T., Skraly, F.A.

1993-12-31

Metabolic engineering involves the use of recombinant DNA techniques for the modification of intermediary metabolic pathways. Microorganisms have recently been engineered to produce compounds such as indigo, ethanol, fatty acids and polyhydroxyalkanoates. As a model system for research in metabolic engineering, the authors have constructed a strain of the bacterium Escherichia coli, that is able to produce 1,3-propanediol (1,3-PD) from glycerol. This strain contains the genes for the glycerol deydratase and the 1,3-PD oxidoreductase from Klebsiella pneumoniae. The authors have also investigated genetic and environmental strategies for improving the yield and productivity of 1,3-PD by the engineered organism. In additionmore » to being a useful model system, 1,3-PD production is of current practical interest. First 1,3-PD (also known as trimethylene glycol) and 1,4-butanediol, the more readily available diols. Second, the volume of feedstock (glycerol) is expected to grow, as it is a by-product of the production of polyglycoside surfactants and biodiesel fluids.« less

Language Deficits as a Preclinical Window into Parkinson's Disease: Evidence from Asymptomatic Parkin and Dardarin Mutation Carriers.

PubMed

García, Adolfo M; Sedeño, Lucas; Trujillo, Natalia; Bocanegra, Yamile; Gomez, Diana; Pineda, David; Villegas, Andrés; Muñoz, Edinson; Arias, William; Ibáñez, Agustín

2017-02-01

The worldwide spread of Parkinson's disease (PD) calls for sensitive and specific measures enabling its early (or, ideally, preclinical) detection. Here, we use language measures revealing deficits in PD to explore whether similar disturbances are present in asymptomatic individuals at risk for the disease. We administered executive, semantic, verb-production, and syntactic tasks to sporadic PD patients, genetic PD patients with PARK2 (parkin) or LRRK2 (dardarin) mutation, asymptomatic first-degree relatives of the latter with similar mutations, and socio-demographically matched controls. Moreover, to detect sui generis language disturbances, we ran analysis of covariance tests using executive functions as covariate. The two clinical groups showed impairments in all measures, most of which survived covariation with executive functions. However, the key finding concerned asymptomatic mutation carriers. While these subjects showed intact executive, semantic, and action-verb production skills, they evinced deficits in a syntactic test with minimal working memory load. We propose that this sui generis disturbance may constitute a prodromal sign anticipating eventual development of PD. Moreover, our results suggest that mutations on specific genes (PARK2 and LRRK2) compromising basal ganglia functioning may be subtly related to language-processing mechanisms. (JINS, 2017, 23, 150-158).

Structure sensitivity in the kinetics and the dynamics of CO oxidation over stepped Pd(335) studied by the molecular beam infrared chemiluminescence technique: Determination of working sites during the steady-state reaction

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

Uetsuka, H.; Watanabe, K.; Kimpara, H.

Kinetics and dynamics of CO oxidation have been studied on a stepped Pd(335) surface at a steady-state condition and compared with those on flat Pd(111). The infrared (IR) chemiluminescence technique was applied to determine where the active catalytic sites are on the Pd(335) surface. Since the vibrational energy state of the product CO{sub 2} is sensitive to the structures of the reaction sites on Pd surfaces, information about the working reaction sites during the steady-state CO oxidation can be obtained from the IR emission spectra of the product CO{sub 2}. The production rate of CO{sub 2} was higher on Pd(335)more » than on Pd(111), indicating that the steps on the surface enhance the catalytic activity for Co oxidation under the steady-state condition. However, the rate data do not necessarily show the real active sites for the CO + O recombination reaction. At a surface temperature of 850 K, the vibrational Boltzmann temperature (T{sub v}) of the product CO{sub 2} on Pd(335) was quite different from (much lower than) that on Pd(111), although the Pd(335) surface has four-atom wide (111) terraces. The lower T{sub v} value on Pd(335) was similar to that on Pd(110)(1 x 1), indicating that a relatively linear activated CO{sub 2} complex was formed. Therefore, during the steady-state CO oxidation on Pd(335), the reaction does not take place on the (111) terrace sites, but mostly on the step sites at 850 K. On the contrary, as the CO coverage increased at a lower surface temperature and at a high CO/O{sub 2} ratio, the T{sub v} values on Pd(335) tend to approach those on Pd(111), indicating that the contribution of the active sites on the steps is decreased and the working reaction sites shift to the (111) terrace sites.« less

Biogenic nanopalladium production by self-immobilized granular biomass: application for contaminant remediation.

PubMed

Suja, E; Nancharaiah, Y V; Venugopalan, V P

2014-11-15

Microbial granules cultivated in an aerobic bubble column sequencing batch reactor were used for reduction of Pd(II) and formation of biomass associated Pd(0) nanoparticles (Bio-Pd) for reductive transformation of organic and inorganic contaminants. Addition of Pd(II) to microbial granules incubated under fermentative conditions resulted in rapid formation of Bio-Pd. The reduction of soluble Pd(II) to biomass associated Pd(0) was predominantly mediated by H2 produced through fermentation. X-ray diffraction and scanning electron microscope analysis revealed that the produced Pd nanoparticles were associated with the microbial granules. The catalytic activity of Bio-Pd was determined using p-nitrophenol and Cr(VI) as model compounds. Reductive transformation of p-nitrophenol by Bio-Pd was ∼20 times higher in comparison to microbial granules without Pd. Complete reduction of up to 0.25 mM of Cr(VI) by Bio-Pd was achieved in 24 h. Bio-Pd synthesis using self-immobilized microbial granules is advantageous and obviates the need for nanoparticle encapsulation or use of barrier membranes for retaining Bio-Pd in practical applications. In short, microbial granules offer a dual purpose system for Bio-Pd production and retention, wherein in situ generated H2 serves as electron donor powering biotransformations. Copyright © 2014 Elsevier Ltd. All rights reserved.

Fumagillin Prodrug Nanotherapy Suppresses Macrophage Inflammatory Response via Endothelial Nitric Oxide

PubMed Central

2015-01-01

Antiangiogenesis has been extensively explored for the treatment of a variety of cancers and certain inflammatory processes. Fumagillin, a mycotoxin produced by Aspergillus fumigatus that binds methionine aminopeptidase 2 (MetAP-2), is a potent antiangiogenic agent. Native fumagillin, however, is poorly soluble and extremely unstable. We have developed a lipase-labile fumagillin prodrug (Fum-PD) that eliminated the photoinstability of the compound. Using αvβ3-integrin-targeted perfluorocarbon nanocarriers to deliver Fum-PD specifically to angiogenic vessels, we effectively suppressed clinical disease in an experimental model of rheumatoid arthritis (RA). The exact mechanism by which Fum-PD-loaded targeted nanoparticles suppressed inflammation in experimental RA, however, remained unexplained. We herein present evidence that Fum-PD nanotherapy indirectly suppresses inflammation in experimental RA through the local production of endothelial nitric oxide (NO). Fum-PD-induced NO activates AMP-activated protein kinase (AMPK), which subsequently modulates macrophage inflammatory response. In vivo, NO-induced AMPK activation inhibits mammalian target of rapamycin (mTOR) activity and enhances autophagic flux, as evidenced by p62 depletion and increased autolysosome formation. Autophagy in turn mediates the degradation of IkappaB kinase (IKK), suppressing the NF-κB p65 signaling pathway and inflammatory cytokine release. Inhibition of NO production by NG-nitro-l-arginine methyl ester (l-NAME), a nitric oxide synthase inhibitor, reverses the suppression of NF-κB-mediated inflammatory response induced by Fum-PD nanotherapy. These unexpected results uncover an activity of Fum-PD nanotherapy that may be further explored in the treatment of angiogenesis-dependent diseases. PMID:24941020

Catalytic hydrodechlorination of trichloroethylene in water with supported CMC-stabilized palladium nanoparticles.

PubMed

Zhang, Man; Bacik, Deborah B; Roberts, Christopher B; Zhao, Dongye

2013-07-01

In this work, we developed and tested a new class of supported Pd catalysts by immobilizing CMC (carboxymethyl cellulose) stabilized Pd nanoparticles onto alumina support. The alumina supported Pd nanoparticles were able to facilitate rapid and complete hydrodechlorination of TCE (trichloroethylene) without intermediate by-products detected. With a Pd mass loading of 0.33 wt% of the alumina mass, the observed pseudo first order reaction rate constant, k(obs), for the catalyst was increased from 28 to 109 L/min/g when CMC concentration was raised from 0.005 to 0.15 wt%. The activity increase was in accord with an increase of the Pd dispersion (measured via CO chemisorption) from 30.4% to 45.1%. Compared to the commercial alumina supported Pd, which has a lower Pd dispersion of 21%, our CMC-stabilized Pd nanoparticles offered more than 7 times greater activity. Pre-calcination treatment of the supported catalyst resulted in minor drop in activity, yet greatly reduced bleeding (<6%) of the Pd nanoparticles from the support during multiple cycles of applications. The presence of DOM (dissolved organic matter) at up to 10 mg/L as TOC had negligible effect on the catalytic activity. The alumina supported CMC-stabilized Pd nanoparticles may serve as a class of more effective catalysts for water treatment uses. Copyright © 2013 Elsevier Ltd. All rights reserved.

Time Course of Lexicalization during Sentence Production in Parkinson's Disease: Eye-Tracking While Speaking

ERIC Educational Resources Information Center

Lee, Jiyeon

2017-01-01

Purpose: Growing evidence suggests that sentence formulation is affected in Parkinson's disease (PD); however, how speakers with PD coordinate sentence planning and speaking remains unclear. Within 2 competing models of sentence production, this study examined whether speakers with PD show advanced buffering of words to minimize disfluencies and…

Perianal Dermatitis, Its Incidence, and Patterns of Topical Therapies in a Level IV Neonatal Intensive Care Unit.

PubMed

Malik, Anuj; Witsberger, Emily; Cottrell, Lesley; Kiefer, Autumn; Yossuck, Panitan

2018-04-01

 To define the incidence of perianal dermatitis (PD) and determine the usage pattern and cost efficacy of diaper products among neonates admitted to a level IV neonatal intensive care unit (NICU) including those with a diagnosis of neonatal abstinence syndrome (NAS).  A retrospective cohort study to evaluate neonates with PD based on number of orders for Aquaphor, Bagbalm, Desitin, Flanders, or Nystatin. Various demographic and clinical parameters were recorded. Usage patterns of these five products were analyzed, and their costs estimated. Subgroup analysis was performed among infants with NAS.  Of 1,241 admissions, 56.2% had at least one diaper product ordered during their NICU stay, while 52.6% had multiple products ordered. Only 23.0% of all neonates had appropriate documentation of PD. The most common product ordered first was Aquaphor (64.3%), followed by Desitin (19.2%). Note that 86% term NAS infants had PD compared with 28% term non-NAS infants. The estimated product cost was $14,139 over 2 years, averaging $20 per patient.  Over half of NICU neonates were exposed to one or more diaper products, usually without documented PD diagnosis. Term NAS infants had three times higher incidence of PD than term non-NAS infants. The cost of diaper product use was significant, and possibly underestimated due to lack of documentation. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Photothermal Catalyst Engineering: Hydrogenation of Gaseous CO2 with High Activity and Tailored Selectivity

PubMed Central

Jia, Jia; Wang, Hong; Lu, Zhuole; O'Brien, Paul G.; Ghoussoub, Mireille; Duchesne, Paul; Zheng, Ziqi; Li, Peicheng; Qiao, Qiao; Wang, Lu; Gu, Alan; Jelle, Abdinoor A.; Dong, Yuchan; Wang, Qiang; Ghuman, Kulbir Kaur; Wood, Thomas; Qian, Chenxi; Shao, Yue; Qiu, Chenyue; Ye, Miaomiao; Zhu, Yimei; Lu, Zheng‐Hong; Zhang, Peng; Helmy, Amr S.; Singh, Chandra Veer; Kherani, Nazir P.; Perovic, Doug D.

2017-01-01

Abstract This study has designed and implemented a library of hetero‐nanostructured catalysts, denoted as Pd@Nb2O5, comprised of size‐controlled Pd nanocrystals interfaced with Nb2O5 nanorods. This study also demonstrates that the catalytic activity and selectivity of CO2 reduction to CO and CH4 products can be systematically tailored by varying the size of the Pd nanocrystals supported on the Nb2O5 nanorods. Using large Pd nanocrystals, this study achieves CO and CH4 production rates as high as 0.75 and 0.11 mol h−1 gPd −1, respectively. By contrast, using small Pd nanocrystals, a CO production rate surpassing 18.8 mol h−1 gPd −1 is observed with 99.5% CO selectivity. These performance metrics establish a new milestone in the champion league of catalytic nanomaterials that can enable solar‐powered gas‐phase heterogeneous CO2 reduction. The remarkable control over the catalytic performance of Pd@Nb2O5 is demonstrated to stem from a combination of photothermal, electronic and size effects, which is rationally tunable through nanochemistry. PMID:29051865

Expression of PD-L1 on Canine Tumor Cells and Enhancement of IFN-γ Production from Tumor-Infiltrating Cells by PD-L1 Blockade

PubMed Central

Maekawa, Naoya; Konnai, Satoru; Ikebuchi, Ryoyo; Okagawa, Tomohiro; Adachi, Mami; Takagi, Satoshi; Kagawa, Yumiko; Nakajima, Chie; Suzuki, Yasuhiko; Murata, Shiro; Ohashi, Kazuhiko

2014-01-01

Programmed death 1 (PD-1), an immunoinhibitory receptor, and programmed death ligand 1 (PD-L1), its ligand, together induce the “exhausted” status in antigen-specific lymphocytes and are thus involved in the immune evasion of tumor cells. In this study, canine PD-1 and PD-L1 were molecularly characterized, and their potential as therapeutic targets for canine tumors was discussed. The canine PD-1 and PD-L1 genes were conserved among canine breeds. Based on the sequence information obtained, the recombinant canine PD-1 and PD-L1 proteins were constructed; they were confirmed to bind each other. Antibovine PD-L1 monoclonal antibody effectively blocked the binding of recombinant PD-1 with PD-L1–expressing cells in a dose-dependent manner. Canine melanoma, mastocytoma, renal cell carcinoma, and other types of tumors examined expressed PD-L1, whereas some did not. Interestingly, anti-PD-L1 antibody treatment enhanced IFN-γ production from tumor-infiltrating cells. These results showed that the canine PD-1/PD-L1 pathway is also associated with T-cell exhaustion in canine tumors and that its blockade with antibody could be a new therapeutic strategy for canine tumors. Further investigations are needed to confirm the ability of anti-PD-L1 antibody to reactivate canine antitumor immunity in vivo, and its therapeutic potential has to be further discussed. PMID:24915569

Changes in artistic style and behaviour in Parkinson's disease: dopamine and creativity.

PubMed

Kulisevsky, Jaime; Pagonabarraga, Javier; Martinez-Corral, Mercè

2009-05-01

We present a PD patient in whom dopamine agonists awoke a hidden creativity that led to a gradual increase in painting productivity evolving to a disruptive impulsive behaviour that shared many features with punding. A dramatic change in painting style related to a more emotional experience during the process of creation developed after treatment onset. This case suggests that changes in creativity in PD seem to be related to dopaminergic imbalance in the limbic system.

Impact of glucose-6-phosphate dehydrogenase deficiency on the pathophysiology of cardiovascular disease

PubMed Central

Hecker, Peter A.; Leopold, Jane A.; Gupte, Sachin A.; Recchia, Fabio A.

2013-01-01

Glucose-6-phosphate dehydrogenase (G6PD) catalyzes the rate-determining step in the pentose phosphate pathway and produces NADPH to fuel glutathione recycling. G6PD deficiency is the most common enzyme deficiency in humans and affects over 400 million people worldwide; however, its impact on cardiovascular disease is poorly understood. The glutathione pathway is paramount to antioxidant defense, and G6PD-deficient cells do not cope well with oxidative damage. Limited clinical evidence indicates that G6PD deficiency may be associated with hypertension. However, there are also data to support a protective role of G6PD deficiency in decreasing the risk of heart disease and cardiovascular-associated deaths, perhaps through a decrease in cholesterol synthesis. Studies in G6PD-deficient (G6PDX) mice are mixed and provide evidence for both protective and deleterious effects. G6PD deficiency may provide a protective effect through decreasing cholesterol synthesis, superoxide production, and reductive stress. However, recent studies indicate that G6PDX mice are moderately more susceptible to ventricular dilation in response to myocardial infarction or pressure overload-induced heart failure. Furthermore, G6PDX hearts do not recover as well as nondeficient mice when faced with ischemia-reperfusion injury, and G6PDX mice are susceptible to the development of age-associated cardiac hypertrophy. Overall, the limited available data indicate a complex interplay in which adverse effects of G6PD deficiency may outweigh potential protective effects in the face of cardiac stress. Definitive clinical studies in large populations are needed to determine the effects of G6PD deficiency on the development of cardiovascular disease and subsequent outcomes. PMID:23241320

A Paleolithic-type diet results in iodine deficiency: a 2-year randomized trial in postmenopausal obese women.

PubMed

Manousou, S; Stål, M; Larsson, C; Mellberg, C; Lindahl, B; Eggertsen, R; Hulthén, L; Olsson, T; Ryberg, M; Sandberg, S; Nyström, H F

2018-01-01

Different diets are used for weight loss. A Paleolithic-type diet (PD) has beneficial metabolic effects, but two of the largest iodine sources, table salt and dairy products, are excluded. The objectives of this study were to compare 24-h urinary iodine concentration (24-UIC) in subjects on PD with 24-UIC in subjects on a diet according to the Nordic Nutrition Recommendations (NNR) and to study if PD results in a higher risk of developing iodine deficiency (ID), than NNR diet. A 2-year prospective randomized trial in a tertiary referral center where healthy postmenopausal overweight or obese women were randomized to either PD (n=35) or NNR diet (n=35). Dietary iodine intake, 24-UIC, 24-h urinary iodine excretion (24-UIE), free thyroxin (FT4), free triiodothyronine (FT3) and thyrotropin (TSH) were measured at baseline, 6 and 24 months. Completeness of urine sampling was monitored by para-aminobenzoic acid and salt intake by urinary sodium. At baseline, median 24-UIC (71.0 μg/l) and 24-UIE (134.0 μg/d) were similar in the PD and NNR groups. After 6 months, 24-UIC had decreased to 36.0 μg/l (P=0.001) and 24-UIE to 77.0 μg/d (P=0.001) in the PD group; in the NNR group, levels were unaltered. FT4, TSH and FT3 were similar in both groups, except for FT3 at 6 months being lower in PD than in NNR group. A PD results in a higher risk of developing ID, than a diet according to the NNR. Therefore, we suggest iodine supplementation should be considered when on a PD.

Carbon nanotube supported PdAg nanoparticles for electrocatalytic oxidation of glycerol in anion exchange membrane fuel cells

DOE PAGES

Benipal, Neeva; Qi, Ji; Dalian Univ. of Technology, Dalian; ...

2017-03-10

Electro-oxidation of alcohol is the key reaction occurring at the anode of a direct alcohol fuel cell (DAFC), in which both reaction kinetics (rate) and selectivity (to deep oxidation products) need improvement to obtain higher power density and fuel utilization for a more efficient DAFC. We recently found that a PdAg bimetallic nanoparticle catalyst is more efficient than Pd for alcohol oxidation: Pd can facilitate deprotonation of alcohol in a base electrolyte, while Ag can promote intermediate aldehyde oxidation and cleavage of C-single bondC bond of C 3 species to C 2 species. Furthermore, a combination of the two activemore » sites (Pd and Ag) with two different functions, can simultaneously improve the reaction rates and deeper oxidation products of alcohols. In this continuing work, Pd, Ag mono, and bimetallic nanoparticles supported on carbon nanotubes (Ag/CNT, Pd/CNT, Pd 1Ag 1/CNT, and Pd 1Ag 3/CNT) were prepared using an aqueous-phase reduction method; they served as working catalysts for studying electrocatalytic oxidation of glycerol in an anion-exchange membrane-based direct glycerol fuel cell. Combined XRD, TEM, and HAADF-STEM analyses performed to fully characterize as-prepared catalysts suggested that they have small particle sizes: 2.0 nm for Pd/CNT, 2.3 nm for PdAg/CNT, 2.4 nm for PdAg 3/CNT, and 13.9 nm for Ag/CNT. XPS further shows that alloying with Ag results in more metal state Pd presented on the surface, and this may be related to their higher direct glycerol fuel cell (DGFC) performances. Single DGFC performance and product analysis results show that PdAg bimetallic nanoparticles can not only improve the glycerol reaction rate so that higher power output can be achieved, but also facilitate deep oxidation of glycerol so that a higher faradaic efficiency and fuel utilization can be achieved along with optimal reaction conditions (increased base-to-fuel ratio). Half-cell electrocatalytic activity measurement and single fuel cell product analysis of different glycerol oxidation intermediates, including C 3: glycerate, tartronate, mesoxalate, and lactate; C 2: glycolate and oxalate, over PdAg/CNT catalyst was further conducted and produced deeper insight into the synergistic effects and reaction pathways of bimetallic PdAg catalysts in glycerol electrocatalytic oxidation.« less

Exercise-Induced Neuroprotection of the Nigrostriatal Dopamine System in Parkinson's Disease

PubMed Central

Hou, Lijuan; Chen, Wei; Liu, Xiaoli; Qiao, Decai; Zhou, Fu-Ming

2017-01-01

Epidemiological studies indicate that physical activity and exercise may reduce the risk of developing Parkinson's disease (PD), and clinical observations suggest that physical exercise can reduce the motor symptoms in PD patients. In experimental animals, a profound observation is that exercise of appropriate timing, duration, and intensity can reduce toxin-induced lesion of the nigrostriatal dopamine (DA) system in animal PD models, although negative results have also been reported, potentially due to inappropriate timing and intensity of the exercise regimen. Exercise may also minimize DA denervation-induced medium spiny neuron (MSN) dendritic atrophy and other abnormalities such as enlarged corticostriatal synapse and abnormal MSN excitability and spiking activity. Taken together, epidemiological studies, clinical observations, and animal research indicate that appropriately dosed physical activity and exercise may not only reduce the risk of developing PD in vulnerable populations but also benefit PD patients by potentially protecting the residual DA neurons or directly restoring the dysfunctional cortico-basal ganglia motor control circuit, and these benefits may be mediated by exercise-triggered production of endogenous neuroprotective molecules such as neurotrophic factors. Thus, exercise is a universally available, side effect-free medicine that should be prescribed to vulnerable populations as a preventive measure and to PD patients as a component of treatment. Future research needs to establish standardized exercise protocols that can reliably induce DA neuron protection, enabling the delineation of the underlying cellular and molecular mechanisms that in turn can maximize exercise-induced neuroprotection and neurorestoration in animal PD models and eventually in PD patients. PMID:29163139

Catalytic Conversion of Short-Chain Alcohols on Atomically Dispersed Au and Pd Supported on Nanoscale Metal Oxides

NASA Astrophysics Data System (ADS)

Wang, Chongyang

With the development of technologies for cellulosic biomass conversion to fuels and chemicals, bio-alcohols are among the main alternative feedstocks to fossil fuels. The research pursued in my thesis was the investigation of gold and palladium as catalysts for the application of short aliphatic alcohols to hydrogen generation and value-added chemicals production. Specifically, selective methanol steam reforming and non-oxidative ethanol dehydrogenation to hydrogen and acetaldehyde were investigated in this thesis work. A major aim of the thesis was to develop atomically efficient catalysts with tuned surface chemistry for the desired reactions, using suitable synthesis methods. Methanol steam reforming (SRM) for hydrogen production has recently been investigated on gold catalysts to overcome the drawbacks of copper catalysts (deactivation, pyrophoricity). Previous work at Tufts University has shown that both CeO2 and ZnO are suitable supports for gold. In this thesis, nanoscale composite oxides ZnZrOx were prepared by a carbon hard-template method, which resulted in homogeneous distribution of Zn species in the matrix of ZrO2. Tunable surface chemistry of ZnZrO x was demonstrated by varying the Zn/Zr ratio to suppress the strong Lewis acidity of ZrO2, which leads to undesired production of CO through methanol decomposition. With atomic dispersion of gold, Au/ZnZrO x catalyzes the SRM reaction exclusively via the methanol self-coupling pathway up to 375°C. The activity of Au/ZnZrOx catalysts was compared to Au/TiO2, which is another catalyst system demonstrating atomic dispersion of gold. Similarity in the apparent activation energy of SRM on all the supported gold catalysts studied in this thesis and in the literature further confirms the same single-site Au-Ox-MO centers as active sites for SRM with indirect effects of the supports exploited. With this fundamental understanding of gold-catalyzed C1 alcohol reforming, the Au/ZnZrOx catalyst was evaluated for the dehydrogenation of ethanol. Bare ZnZrOx activate ethanol conversion in the range of 280-300°C and produce undesired ethylene as product of ethanol dehydration, whereas, addition of small amount of gold (<1wt.%) was found to significantly change the product distribution in the low-temperature range (200°C-350°C). As gold passivates the strong Bronsted acid sites of ZrO2 and selectively facilitates the dehydrogenation of ethanol at low-temperature, a wide temperature range was found between the production of acetaldehyde (dehydrogenation products) and ethylene (dehydration product), which can be harnessed for the industrial application. Interestingly, the steam reforming of ethanol did not take place in the low-temperature region, thus the selectivity to acetaldehyde and hydrogen was 100% even in the presence of water. In addition to gold, palladium was also studied in this thesis work on the ZnZrOx composite oxides, and its activity and selectivity were compared to Au/ZnZrOx. Monometallic Pd catalyzes the decomposition of methanol and ethanol, resulting in different product distribution for C 1-C2 alcohol reactions. With ZnZrOx employed as the catalyst support in this thesis work, the finely dispersed ZnO species in ZrO2 were found to alloy with the supported palladium under reduction treatment. Alloying with Zn tunes the chemistry of Pd to catalyze the SRM reaction through the methanol coupling mechanism, shutting off the undesired methanol decomposition pathway. A preliminary study of the Pd/ZnZrO x system for ethanol dehydrogenation also demonstrated the modification of Pd when in the PdZn alloy form. Different from the monometallic Pd catalyst, which primarily catalyzes the C-C bond scission of ethanol, high selectivity to ethanol dehydrogenation products was found on PdZn, over the temperature range of 200-400°C. Formation of the PdZn alloy broadens the application of Pd and potentially other Group VIII metals for selective alcohol conversion reactions. In summary, this thesis work has investigated two noble metals Au and Pd from Group IB and Group VIII, respectively, for methanol and ethanol alcohol reforming reactions employing a novel ZnZrOx composite oxide as a platform catalyst support. Comprehensive study of Au catalyst has deepened our understanding of atomically dispersed Au anchored on various supports through oxygen bonds as the active sites for alcohol reforming reactions, and showed the support effect to be indirect, serving as the carrier and stabilizer of the gold species. For Pd, the Zn species of the composite oxide is necessary to modify the Pd catalyst and the PdZn alloy gives it the desired Au-like properties. Full characterization of the catalysts used here by ICP, XPS, XRD, FTIR and STEM imaging was conducted throughout the thesis to identify the stable species and correlate the catalyst performance with its composition and morphology. Surface acidity titration by isopropanol temperature-programmed desorption/mass spectrometry (IPA-TPD/MS) and pyridine-IR adsorption/desorption was conducted in parallel to temperature-programmed surface reaction (TPSR) studies and products from isothermal steady-state reactions were monitored online by mass spectrometry.

Fructose increases corticosterone production in association with NADPH metabolism alterations in rat epididymal white adipose tissue.

PubMed

Prince, Paula D; Santander, Yanina A; Gerez, Estefania M; Höcht, Christian; Polizio, Ariel H; Mayer, Marcos A; Taira, Carlos A; Fraga, Cesar G; Galleano, Monica; Carranza, Andrea

2017-08-01

Metabolic syndrome is an array of closely metabolic disorders that includes glucose intolerance/insulin resistance, central obesity, dyslipidemia, and hypertension. Fructose, a highly lipogenic sugar, has profound metabolic effects in adipose tissue, and has been associated with the etiopathology of many components of the metabolic syndrome. In adipocytes, the enzyme 11 β-HSD1 amplifies local glucocorticoid production, being a key player in the pathogenesis of central obesity and metabolic syndrome. 11 β-HSD1 reductase activity is dependent on NADPH, a cofactor generated by H6PD inside the endoplasmic reticulum. Our focus was to explore the effect of fructose overload on epididymal white adipose tissue (EWAT) machinery involved in glucocorticoid production and NADPH and oxidants metabolism. Male Sprague-Dawley rats fed with a fructose solution (10% (w/v) in tap water) during 9 weeks developed some characteristic features of metabolic syndrome, such as hypertriglyceridemia, and hypertension. In addition, high levels of plasma and EWAT corticosterone were detected. Activities and expressions of H6PD and 11 β-HSD1, NAPDH content, superoxide anion production, expression of NADPH oxidase 2 subunits, and indicators of oxidative metabolism were measured. Fructose overloaded rats showed an increased potential in oxidant production respect to control rats. In parallel, in EWAT from fructose overloaded rats we found higher expression/activity of H6PD and 11 β-HSD1, and NADPH/NADP + ratio. Our in vivo results support that fructose overload installs in EWAT conditions favoring glucocorticoid production through higher H6PD expression/activity supplying NADPH for enhanced 11 β-HSD1 expression/activity, becoming this tissue a potential extra-adrenal source of corticosterone under these experimental conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparative and Functional Genomics of Rhodococcus opacus PD630 for Biofuels Development

PubMed Central

Holder, Jason W.; Ulrich, Jil C.; DeBono, Anthony C.; Godfrey, Paul A.; Desjardins, Christopher A.; Zucker, Jeremy; Zeng, Qiandong; Leach, Alex L. B.; Ghiviriga, Ion; Dancel, Christine; Abeel, Thomas; Gevers, Dirk; Kodira, Chinnappa D.; Desany, Brian; Affourtit, Jason P.; Birren, Bruce W.; Sinskey, Anthony J.

2011-01-01

The Actinomycetales bacteria Rhodococcus opacus PD630 and Rhodococcus jostii RHA1 bioconvert a diverse range of organic substrates through lipid biosynthesis into large quantities of energy-rich triacylglycerols (TAGs). To describe the genetic basis of the Rhodococcus oleaginous metabolism, we sequenced and performed comparative analysis of the 9.27 Mb R. opacus PD630 genome. Metabolic-reconstruction assigned 2017 enzymatic reactions to the 8632 R. opacus PD630 genes we identified. Of these, 261 genes were implicated in the R. opacus PD630 TAGs cycle by metabolic reconstruction and gene family analysis. Rhodococcus synthesizes uncommon straight-chain odd-carbon fatty acids in high abundance and stores them as TAGs. We have identified these to be pentadecanoic, heptadecanoic, and cis-heptadecenoic acids. To identify bioconversion pathways, we screened R. opacus PD630, R. jostii RHA1, Ralstonia eutropha H16, and C. glutamicum 13032 for growth on 190 compounds. The results of the catabolic screen, phylogenetic analysis of the TAGs cycle enzymes, and metabolic product characterizations were integrated into a working model of prokaryotic oleaginy. PMID:21931557

Neuroinflammation in Parkinson's disease: role in neurodegeneration and tissue repair.

PubMed

Vivekanantham, Sayinthen; Shah, Savan; Dewji, Rizwan; Dewji, Abbas; Khatri, Chetan; Ologunde, Rele

2015-01-01

Neuroinflammation in Parkinson's disease [PD] is a process that occurs alongside the loss of dopaminergic neurons, and is associated with alterations to many cell types, most notably microglia. This review examines the key evidence contributing to our understanding of the role of inflammation-mediated degeneration of the dopaminergic (DA) nigrostriatal pathway in PD. It will consider the potential role inflammation plays in tissue repair within the brain, inflammation linked gene products that are associated with sporadic Parkinsonian phenotypes (alpha-synuclein, Parkin and Nurr 1), and developing anti-inflammatory drug treatments in PD. With growing evidence supporting the key role of neuroinflammation in PD pathogenesis, new molecular targets are being found that could potentially prevent or delay nigrostriatal DA neuron loss. Hence, this creates the opportunity for disease modifying treatment, to currently what is an incurable disease.

Excitation Functions of Helion-Induced Nuclear Reactions for the Production of the Medical Radioisotope 103Pd

NASA Astrophysics Data System (ADS)

Skakun, Ye.; Qaim, S. M.

2005-05-01

Excitation functions were measured by the stacked-foil technique for the reactions 100Ru(α,n)103Pd, 101Ru(α,2n)103Pd, 101Ru(3He,n)103Pd, and 102Ru(3He,2n)103Pd for incident energies up to 25 and 34 MeV for α-particles and 3He ions, respectively. The integral thick target yields of the product radionuclide 103Pd calculated from the excitation functions of the above-named four reactions amount to 960, 1050, 50, and 725 KBq/μAh, respectively, at the maximum energy of the incident particle. The data are compared with the results of statistical model calculations and other charged particle induced reaction investigations.

PD-1 suppresses protective immunity to Streptococcus pneumoniae through a B cell-intrinsic mechanism

PubMed Central

McKay, Jerome T.; Egan, Ryan P.; Yammani, Rama D.; Chen, Lieping; Shin, Tahiro; Yagita, Hideo; Haas, Karen M.

2015-01-01

Despite the emergence of the PD-1:PD-1 ligand (PD-L) regulatory axis as a promising target for treating multiple human diseases, remarkably little is known about how this pathway regulates responses to extracellular bacterial infections. We found that PD-1−/− mice, as well as wild type mice treated with a PD-1 blocking antibody, exhibited significantly increased survival against lethal Streptococcus pneumoniae infection following either priming with low-dose pneumococcal respiratory infection or S. pneumoniae-capsular polysaccharide immunization. Enhanced survival in mice with disrupted PD-1:PD-L interactions was explained by significantly increased proliferation, isotype switching, and IgG production by pneumococcal capsule-specific B cells. Both PD-1 ligands, B7-H1 and B7-DC, contributed to PD-1-mediated suppression of protective capsule-specific IgG. Importantly, PD-1 was induced on capsule-specific B cells and suppressed IgG production and protection against pneumococcal infection in a B cell-intrinsic manner. These results provide the first demonstration of a physiologic role for B cell-intrinsic PD-1 expression in vivo. In summary, our study reveals that B cell-expressed PD-1 plays a central role in regulating protection against S. pneumoniae, and thereby represents a promising target for bolstering immunity to encapsulated bacteria. PMID:25624454

Photocatalytic hydrogen evolution of palladium nanoparticles decorated black TiO2 calcined in argon atmosphere

NASA Astrophysics Data System (ADS)

Wu, Ming-Chung; Hsiao, Kai-Chi; Chang, Yin-Hsuan; Chan, Shun-Hsiang

2018-02-01

Black TiO2 nanoparticles (BTN) was prepared by sol-gel derived precursor calcined in an argon atmosphere. The synthesized BTN with trivalent titanium ion, structural defect, and oxygen vacancy shows a remarkably high absorbance in the visible light spectrum. BTN thus behaves a higher visible-active nanoreactor than white TiO2 nanoparticles (WTN) in the aqueous solution for organic pollutant degradation. Moreover, palladium decoration on the BTN surface (Pd-BTN) demonstrates a fascinating clean energy application. The obtained Pd-BTN fulfills a satisfied green material demand in the photocatalytic hydrogen production application. Pd-BTN calcined at 400 °C (Pd-BTN-400) shows the high photocatalytic hydrogen generation rate of 5200 μmol/g h under UV-A irradiation and 9300 μmol/g h under UV-B irradiation, respectively. The well-developed material, Pd-BTN-400, could be one of the best solutions in the concern of clean energy and water-purification with regard to the continuous environmental issue.

Scalable synthesis of palladium icosahedra in plug reactors for the production of oxygen reduction reaction catalysts

DOE PAGES

Wang, Helan; Niu, Guangda; Zhou, Ming; ...

2016-03-10

We have synthesized Pd icosahedra with uniform, controllable sizes in plug reactors separated by air. The oxygen contained in the air segments not only contributed to the generation of a reductant from diethylene glycol in situ, but also oxidized elemental Pd back to the ionic form by oxidative etching and thus slowed down the reduction kinetics. Compared to droplet reactors involving silicone oil or fluorocarbon, the use of air as a carrier phase could reduce the production cost by avoiding additional procedures for the separation of products from the oil. The average diameters of the Pd icosahedra could be readilymore » controlled in the range of 12–20 nm. The Pd icosahedra were further employed as seeds for the production of Pd@Pt 2–3L core-shell icosahedra, which could serve as a catalyst toward the oxygen reduction reaction with greatly enhanced activity. As a result, we believe that the plug reactors could be extended to other types of noble-metal nanocrystals for their scale-up production.« less

Conversion of Thin Stillage Compounds using Endemic Bacteria Augmented with Lactobacillus panis PM1B.

PubMed

Ratanapariyanuch, Kornsulee; Shim, Youn Young; Reaney, Martin J T

2016-10-04

A consortium of organisms endemic in wheat-based thin stillage (W-TS) obtained from a commercial ethanol production converts glycerol to 1,3-propanediol (1,3-PD) and lactic acid to acetic acid. We sought to improve conditions for 1,3-PD and acetic acid production to be used in future studies of industrial isolation of these compounds from two-stage fermentation. Occasionally stillage fermentation proceeded slowly but an inoculum of Lactobacillus panis PM1B augmented both fermentation rate and extent. Fermentation rate and product yield were enhanced by adjusting pH to 5 daily, adding glucose and glycerol (molar ratio 0.1:1), adding freeze-dried W-TS, and adding vitamins (B 2 , B 3 , and B 12 ). 1,3-PD and 3-HPA did not inhibit 1,3-PD production during fermentation. Moreover, agitation did not improve fermentation rate or extent. Corn sugar was a suitable substitute for glucose. Fermentation was performed at both 20 and 150 L, with 1,3-PD production of 2% (w/v, 20 g/L) being routinely achieved or exceeded.

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

Benipal, Neeva; Qi, Ji; Dalian Univ. of Technology, Dalian

Electro-oxidation of alcohol is the key reaction occurring at the anode of a direct alcohol fuel cell (DAFC), in which both reaction kinetics (rate) and selectivity (to deep oxidation products) need improvement to obtain higher power density and fuel utilization for a more efficient DAFC. We recently found that a PdAg bimetallic nanoparticle catalyst is more efficient than Pd for alcohol oxidation: Pd can facilitate deprotonation of alcohol in a base electrolyte, while Ag can promote intermediate aldehyde oxidation and cleavage of C-single bondC bond of C 3 species to C 2 species. Furthermore, a combination of the two activemore » sites (Pd and Ag) with two different functions, can simultaneously improve the reaction rates and deeper oxidation products of alcohols. In this continuing work, Pd, Ag mono, and bimetallic nanoparticles supported on carbon nanotubes (Ag/CNT, Pd/CNT, Pd 1Ag 1/CNT, and Pd 1Ag 3/CNT) were prepared using an aqueous-phase reduction method; they served as working catalysts for studying electrocatalytic oxidation of glycerol in an anion-exchange membrane-based direct glycerol fuel cell. Combined XRD, TEM, and HAADF-STEM analyses performed to fully characterize as-prepared catalysts suggested that they have small particle sizes: 2.0 nm for Pd/CNT, 2.3 nm for PdAg/CNT, 2.4 nm for PdAg 3/CNT, and 13.9 nm for Ag/CNT. XPS further shows that alloying with Ag results in more metal state Pd presented on the surface, and this may be related to their higher direct glycerol fuel cell (DGFC) performances. Single DGFC performance and product analysis results show that PdAg bimetallic nanoparticles can not only improve the glycerol reaction rate so that higher power output can be achieved, but also facilitate deep oxidation of glycerol so that a higher faradaic efficiency and fuel utilization can be achieved along with optimal reaction conditions (increased base-to-fuel ratio). Half-cell electrocatalytic activity measurement and single fuel cell product analysis of different glycerol oxidation intermediates, including C 3: glycerate, tartronate, mesoxalate, and lactate; C 2: glycolate and oxalate, over PdAg/CNT catalyst was further conducted and produced deeper insight into the synergistic effects and reaction pathways of bimetallic PdAg catalysts in glycerol electrocatalytic oxidation.« less

Stochastic modelling of direct costs of pancreas disease (PD) in Norwegian farmed Atlantic salmon (Salmo salar L.).

PubMed

Aunsmo, Arnfinn; Valle, Paul Steinar; Sandberg, Marianne; Midtlyng, Paul Johan; Bruheim, Torkjel

2010-02-01

An economic model for estimating the direct costs of disease in industrial aquaculture was developed to include the following areas: biological losses, extraordinary costs, costs of treatment, costs of prevention and insurance pay-out. Direct costs of a pancreas disease (PD) outbreak in Norwegian farmed Atlantic salmon were estimated in the model, using probability distributions for the biological losses and expenditures associated with the disease. The biological effects of PD on mortality, growth, feed conversion and carcass quality and their correlations, together with costs of prevention were established using elicited data from an expert panel, and combined with basal losses in a control model. Extraordinary costs and costs associated with treatment were collected through a questionnaire sent to staff managing disease outbreaks. Norwegian national statistics for 2007 were used for prices and production costs in the model. Direct costs associated with a PD-outbreak in a site stocked with 500,000 smolts (vs. a similar site without the disease) were estimated to NOK (Norwegian kroner) 14.4 million (5% and 95% percentile: 10.5 and 17.8) (NOK=euro0.12 or $0.17 for 2007). Production was reduced to 70% (5% and 95% percentile: 57% and 81%) saleable biomass, and at an increased production cost of NOK 6.0 per kg (5% and 95% percentile: 3.5 and 8.7). Copyright 2009 Elsevier B.V. All rights reserved.

Prevalence of glucose-6-phosphate dehydrogenase deficiency in jaundiced Egyptian neonates.

PubMed

M Abo El Fotoh, Wafaa Moustafa; Rizk, Mohammed Soliman

2016-12-01

The enzyme, Glucose-6-phosphate dehydrogenase (G6PD), deficiency leads to impaired production of reduced glutathione and predisposes the red cells to be damaged by oxidative metabolites, causing hemolysis. Deficient neonates may manifest clinically as hyperbilirubinemia or even kernicterus. This study was carried out to detect erythrocyte G6PD deficiency in neonatal hyperbilirubinemia. To determine the frequency and effect of G6PD deficiency, this study was conducted on 202 neonates with indirect hyperbilirubinemia. All term and preterm babies up to 13 day of age admitted with clinically evident jaundice were taken for the study. G6PD activity is measured by the UV-Kinetic Method using cellular enzyme determination reagents by spectrophotometry according to manufacturer's instructions. A total of 202 babies were enrolled in this study. Male babies outnumbered the female (71.3% versus 28.7%). Mean age of the study newborns was 3.75 ± 2.5 days. Eighteen neonates (8.9%) had G6PD deficiency, all are males. One case had combined G6PD deficiency and RH incompatibility. Mean serum total bilirubin was 17.2 ± 4.4 in G6PD deficient cases. There was significant positive correlation between the time of appearance of jaundice in days and G6PD levels in G6PD deficient cases. Neonatal hyperbilirubinemia is associated with various clinical comorbidities. G6PD deficiency is found to one important cause of neonatal jaundice developing on day 2 onwards.

Polar-phase indices of perioral muscle reciprocity during syllable production in Parkinson's disease.

PubMed

Chu, Shin Ying; Barlow, Steven M; Lee, Jaehoon; Wang, Jingyan

2017-12-01

This research characterised perioral muscle reciprocity and amplitude ratio in lower lip during bilabial syllable production [pa] at three rates to understand the neuromotor dynamics and scaling of motor speech patterns in individuals with Parkinson's disease (PD). Electromyographic (EMG) signals of the orbicularis oris superior [OOS], orbicularis oris inferior [OOI] and depressor labii inferioris [DLI] were recorded during syllable production and expressed as polar-phase notations. PD participants exhibited the general features of reciprocity between OOS, OOI and DLI muscles as reflected in the EMG during syllable production. The control group showed significantly higher integrated EMG amplitude ratio in the DLI:OOS muscle pairs than PD participants. No speech rate effects were found in EMG muscle reciprocity and amplitude magnitude across all muscle pairs. Similar patterns of muscle reciprocity in PD and controls suggest that corticomotoneuronal output to the facial nucleus and respective perioral muscles is relatively well-preserved in our cohort of mild idiopathic PD participants. Reduction of EMG amplitude ratio among PD participants is consistent with the putative reduction in the thalamocortical activation characteristic of this disease which limits motor cortex drive from generating appropriate commands which contributes to bradykinesia and hypokinesia of the orofacial mechanism.

(E)-α,β-unsaturated amides from tertiary amines, olefins and CO via Pd/Cu-catalyzed aerobic oxidative N-dealkylation.

PubMed

Shi, Renyi; Zhang, Hua; Lu, Lijun; Gan, Pei; Sha, Yuchen; Zhang, Heng; Liu, Qiang; Beller, Matthias; Lei, Aiwen

2015-02-21

A novel Pd/Cu-catalyzed chemoselective aerobic oxidative N-dealkylation/carbonylation reaction has been developed. Tertiary amines are utilized as a "reservoir" of "active" secondary amines in this transformation, which inhibits the formation of undesired by-products and the deactivation of the catalysts. This protocol allows for an efficient and straightforward construction of synthetically useful and bioactive (E)-α,β-unsaturated amide derivatives from easily available tertiary amines, olefins and CO.

Isolation of Cu Atoms in Pd Lattice: Forming Highly Selective Sites for Photocatalytic Conversion of CO2 to CH4.

PubMed

Long, Ran; Li, Yu; Liu, Yan; Chen, Shuangming; Zheng, Xusheng; Gao, Chao; He, Chaohua; Chen, Nanshan; Qi, Zeming; Song, Li; Jiang, Jun; Zhu, Junfa; Xiong, Yujie

2017-03-29

Photocatalytic conversion of CO 2 to CH 4 , a carbon-neutral fuel, represents an appealing approach to remedy the current energy and environmental crisis; however, it suffers from the large production of CO and H 2 by side reactions. The design of catalytic sites for CO 2 adsorption and activation holds the key to address this grand challenge. In this Article, we develop highly selective sites for photocatalytic conversion of CO 2 to CH 4 by isolating Cu atoms in Pd lattice. According to our synchrotron-radiation characterizations and theoretical simulations, the isolation of Cu atoms in Pd lattice can play dual roles in the enhancement of CO 2 -to-CH 4 conversion: (1) providing the paired Cu-Pd sites for the enhanced CO 2 adsorption and the suppressed H 2 evolution; and (2) elevating the d-band center of Cu sites for the improved CO 2 activation. As a result, the Pd 7 Cu 1 -TiO 2 photocatalyst achieves the high selectivity of 96% for CH 4 production with a rate of 19.6 μmol g cat -1 h -1 . This work provides fresh insights into the catalytic site design for selective photocatalytic CO 2 conversion, and highlights the importance of catalyst lattice engineering at atomic precision to catalytic performance.

Palladium-assisted electrodehalogenation of 1,1,2-trichloro-1,2,2-trifluoroethane on lead cathodes combined with hydrogen diffusion anodes

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

Cabot, P.L.; Centelles, M.; Segarra, L.

1997-11-01

In this work, the efficiency and product formation in the electroreduction of 1,1,2-trichloro-1,2,2-trifluoroethane (CFC 113) to obtain completely dechlorinated products has been studied using constant-current electrolysis at different current densities, gas chromatography, scanning electron microscopy, and energy dispersive x-ray. While chlorotrifluoroethene was the main product obtained from CFC 113 in MeOH-water solutions containing NH{sub 4}Cl, different and suitable conditions which lead to its complete dechlorination are described in this paper. In the presence of small amounts of Pd{sup 2+} in solution, a very thin film of Pd black was electrodeposited on the Pb cathode and the efficiency of the CFCmore » 113 electroreduction was about 98%. The efficiency was much smaller and the product composition very different in the absence of Pd{sup 2+} in solution, even in the presence of Pd black electrodeposited on the cathode. In the presence of Pd{sup 2+}, the main products in the gas were difluoroethene and trifluoroethene. Small amounts of 1,2-dichloro-1,1,2-trifluoroethane, chlorotrifluoroethene, difluoroethane, and fluoroethane were also present in the gas phase. The liquid composition was enriched in the less volatile compounds. A possible reaction pathway involving the removal of halides by successive reactions is discussed. The anode employed in these experiments was a thin Pd foil with electrodeposited Pd black, which permitted hydrogen diffusion and its further oxidation to H{sup +}. Because of this reaction, contamination of the working electrolyte by other oxidation products such as Cl{sub 2} or MeOH derivatives were avoided. This system allows new electrosynthetic processes along with CFC electrodegradation.« less

Dysbiosis of gut microbiota and microbial metabolites in Parkinson's Disease.

PubMed

Sun, Meng-Fei; Shen, Yan-Qin

2018-04-26

Gut microbial dysbiosis and alteration of microbial metabolites in Parkinson's disease (PD) have been increasingly reported. Dysbiosis in the composition and abundance of gut microbiota can affect both the enteric nervous system and the central nervous system (CNS), indicating the existence of a microbiota-gut-brain axis and thereby causing CNS diseases. Disturbance of the microbiota-gut-brain axis has been linked to specific microbial products that are related to gut inflammation and neuroinflammation. Future directions should therefore focus on the exploration of specific gut microbes or microbial metabolites that contribute to the development of PD. Microbiota-targeted interventions, such as antibiotics, probiotics and fecal microbiota transplantation, have been shown to favorably affect host health. In this review, recent findings regarding alterations and the role of gut microbiota and microbial metabolites in PD are summarized, and potential molecular mechanisms and microbiota-targeted interventions in PD are discussed. Copyright © 2018. Published by Elsevier B.V.

Green synthesis, characterization and catalytic activity of the Pd/TiO2 nanoparticles for the ligand-free Suzuki-Miyaura coupling reaction.

PubMed

Nasrollahzadeh, Mahmoud; Sajadi, S Mohammad

2016-03-01

A green synthesis process was developed for production of the Pd/TiO2 nanoparticles (NPs) without using toxic, hazardous and dangerous materials. Myrtus communis L. leaf extract serves as a mild, renewable and non-toxic reducing agent. The advantages of this biosynthesis method include use of cheap, clean, nontoxic and environmentally benign precursors and simple procedures without time-consuming polymerization and problems with treatment of a highly viscous polymeric resin. More importantly, the synthesized Pd/TiO2 NPs presented excellent catalytic activity for ligand-free Suzuki-Miyaura coupling which could be easily separated from the reaction mixture and reused many times with no loss of activity. Therefore, these properties indicate demonstrative benefits of the catalyst. The Pd/TiO2 NPs was characterized by FESEM, TEM, FT-IR, UV-vis spectroscopy and EDS. Copyright © 2015 Elsevier Inc. All rights reserved.

Subtypes of mild cognitive impairment in patients with Parkinson's disease: evidence from the LANDSCAPE study.

PubMed

Kalbe, Elke; Rehberg, Sarah Petra; Heber, Ines; Kronenbuerger, Martin; Schulz, Jörg B; Storch, Alexander; Linse, Katharina; Schneider, Christine; Gräber, Susanne; Liepelt-Scarfone, Inga; Berg, Daniela; Dams, Judith; Balzer-Geldsetzer, Monika; Hilker, Rüdiger; Oberschmidt, Carola; Witt, Karsten; Schmidt, Nele; Mollenhauer, Brit; Trenkwalder, Claudia; Spottke, Annika; Roeske, Sandra; Wittchen, Hans-Ulrich; Riedel, Oliver; Dodel, Richard

2016-10-01

Inconsistent results exist regarding the cognitive profile in patients with Parkinson's disease with mild cognitive impairment (PD-MCI). We aimed at providing data on this topic from a large cohort of patients with PD-MCI. Sociodemographic, clinical and neuropsychological baseline data from patients with PD-MCI recruited in the multicentre, prospective, observational DEMPARK/LANDSCAPE study were analysed. 269 patients with PD-MCI (age 67.8±7.4, Unified Parkinson's Disease Rating Scale (UPDRS-III) scores 23.2±11.6) were included. PD-MCI subtypes were 39.4% non-amnestic single domain, 30.5% amnestic multiple domain, 23.4% non-amnestic multiple domain and 6.7% amnestic single domain. Executive functions were most frequently impaired. The most sensitive tests to detect cognitive dysfunctions were the Modified Card Sorting Test, digit span backwards and word list learning direct recall. Multiple stepwise regression analyses showed that global cognition, gender and age, but not education or disease-related parameters predicted PD-MCI subtypes. This study with the so far largest number of prospectively recruited patients with PD-MCI indicates that non-amnestic PD-MCI is more frequent than amnestic PD-MCI; executive dysfunctions are the most typical cognitive symptom in PD-MCI; and age, gender and global cognition predict the PD-MCI subtype. Longitudinal data are needed to test the hypothesis that patients with PD-MCI with specific cognitive profiles have different risks to develop dementia. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Creative Thinking, Professional Artists, and Parkinson's Disease.

PubMed

Canesi, Margherita; Rusconi, Maria Luisa; Moroni, Federica; Ranghetti, Alessandra; Cereda, Emanuele; Pezzoli, Gianni

2016-01-01

An increase in artistic-like production in Parkinson's disease (PD) has been associated with compulsive and repetitive behaviours after the introduction of dopaminergic treatment (DT). Recent data suggest that it could be due to the emergence of artistic-like skills triggered by DT. In order to evaluate whether artistic production and creative thinking are influenced by DT or linked to artistic-like skills, we characterize creativity features in PD and healthy controls (HC) including professional artists. Three groups of PD out-patients were included consecutively: professional artists (PD-A), patients with (PD-C) and without artistic-like production (PD-NC). Twenty-four gender and age-matched HC were included: professional artists (HC-A) and non-artists (HC-NC). All patients were evaluated by means of a) a battery of neuropsychological tests and a semi-structured interview; b) the Abbreviated Torrance Test for Adults (ATTA) for creative thinking; c) the Minnesota Impulsive Disorders Interview (mMIDI) and a screening for impulse control disorders (ICDs) for compulsive behaviour. ATTA total score was significantly higher in HC-A and PD-A than in the other groups. Although PD-NC showed the lowest ATTA total score the difference vs HC-NC was not significant. ATTA scores were not significantly correlated with DT dosage and duration. mMIDI tests were positive only in PD. There were no differences in ICDs among PD groups. Our results do not support a relationship between DT and the emergence of artistic creativity. We believe that DT may increase the drive to create and that further studies in "on" and "off" medication are needed to clarify this issue.

Cost-Effective Method for Producing Self Supported Palladium Alloy Membranes for Use in Efficient Production of Coal Derived Hydrogen

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

K. Coulter

2008-03-31

Southwest Research Institute{reg_sign} (SwRI{reg_sign}) has utilized its expertise in large-area vacuum deposition methods to conduct research into the fabrication of dense, freestanding Pd-alloy membranes that are 3-5 microns thick and over 100 in{sup 2} in area. The membranes were deposited onto flexible and rigid supports that were subsequently removed and separated using novel techniques developed over the course of the project. Using these methods, the production of novel alloy compositions centered around the Pd-Cu system were developed with the objective of producing a thermally stable, nano-crystalline grain structure with the highest flux recorded as 242 SCFH/ft{sup 2} for a 2more » {micro}m thick Pd{sub 53}Cu{sub 47} at 400 C and 20 psig feed pressure which when extrapolated is over twice the 2010 Department of Energy pure H{sub 2} flux target. Several membranes were made with the same permeability, but with different thicknesses and these membranes were highly selective. Researchers at the Colorado School of Mines supported the effort with extensive testing of experimental membranes as well as design and modeling of novel alloy composite structures. IdaTech provided commercial bench testing and analysis of SwRI-manufactured membranes. The completed deliverables for the project include test data on the performance of experimental membranes fabricated by vacuum deposition and several Pd-alloy membranes that were supplied to IdaTech for testing.« less

Groups at potentially high risk from chlorine dioxide treated water.

PubMed

Moore, G S; Calabrese, E J; Ho, S C

1980-09-01

Chlorite, a by-product of chlorine dioxide disinfection of water, is a strong oxidant compound that produces markedly exaggerated effects in vitro on red cells of G6PD deficient humans when compared to normal human cells. Levels of methemoglobin are significantly greater and GSH levels significantly lower in the G6PD deficient cells than in normal cells after chlorite exposure. Persons with G6PD deficiency may be 3 to 4 times more likely to develop hemolytic anemia from chlorite exposure as persons with normal activity levels when GSH levels are used as a measure of susceptibility. The proposed use of chlorine dioxide as an alternate disinfectant for drinking water supplies should consider this potential high risk group.

Palladium-platinum core-shell electrocatalysts for oxygen reduction reaction prepared with the assistance of citric acid

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

Zhang, Lulu; Su, Dong; Zhu, Shangqian

Core–shell structure is a promising alternative to solid platinum (Pt) nanoparticles as electrocatalyst for oxygen reduction reaction (ORR) in proton exchange membrane fuel cells (PEMFCs). A simple method of preparing palladium (Pd)–platinum (Pt) core–shell catalysts (Pd@Pt/C) in a gram-batch was developed with the assistance of citric acid. The Pt shell deposition involves three different pathways: galvanic displacement reaction between Pd atoms and Pt cations, chemical reduction by citric acid, and reduction by negative charges on Pd surfaces. The uniform ultrathin (~0.4 nm) Pt shell was characterized by in situ X-ray diffraction (XRD) and high-angle annular dark-field scanning transmission electron microscopymore » (HAADF-STEM) images combined with electron energy loss spectroscopy (EELS). Compared with state-of-the-art Pt/C, the Pd@Pt/C core–shell catalyst showed 4 times higher Pt mass activity and much better durability upon potential cycling. As a result, both the mass activity and durability were comparable to that of Pd@Pt/C synthesized by a Cu-mediated-Pt-displacement method, which is more complicated and difficult for mass production.« less

Characterization of the Xylella fastidiosa PD1671 Gene Encoding Degenerate c-di-GMP GGDEF/EAL Domains, and Its Role in the Development of Pierce’s Disease

PubMed Central

Cursino, Luciana; Athinuwat, Dusit; Patel, Kelly R.; Galvani, Cheryl D.; Zaini, Paulo A.; Li, Yaxin; De La Fuente, Leonardo; Hoch, Harvey C.; Burr, Thomas J.; Mowery, Patricia

2015-01-01

Xylella fastidiosa is an important phytopathogenic bacterium that causes many serious plant diseases including Pierce’s disease of grapevines. X. fastidiosa is thought to induce disease by colonizing and clogging xylem vessels through the formation of cell aggregates and bacterial biofilms. Here we examine the role in X. fastidiosa virulence of an uncharacterized gene, PD1671, annotated as a two-component response regulator with potential GGDEF and EAL domains. GGDEF domains are found in c-di-GMP diguanylate cyclases while EAL domains are found in phosphodiesterases, and these domains are for c-di-GMP production and turnover, respectively. Functional analysis of the PD1671 gene revealed that it affected multiple X. fastidiosa virulence-related phenotypes. A Tn5 PD1671 mutant had a hypervirulent phenotype in grapevines presumably due to enhanced expression of gum genes leading to increased exopolysaccharide levels that resulted in elevated biofilm formation. Interestingly, the PD1671 mutant also had decreased motility in vitro but did not show a reduced distribution in grapevines following inoculation. Given these responses, the putative PD1671 protein may be a negative regulator of X. fastidiosa virulence. PMID:25811864

Characterization of the Xylella fastidiosa PD1671 gene encoding degenerate c-di-GMP GGDEF/EAL domains, and its role in the development of Pierce's disease.

PubMed

Cursino, Luciana; Athinuwat, Dusit; Patel, Kelly R; Galvani, Cheryl D; Zaini, Paulo A; Li, Yaxin; De La Fuente, Leonardo; Hoch, Harvey C; Burr, Thomas J; Mowery, Patricia

2015-01-01

Xylella fastidiosa is an important phytopathogenic bacterium that causes many serious plant diseases including Pierce's disease of grapevines. X. fastidiosa is thought to induce disease by colonizing and clogging xylem vessels through the formation of cell aggregates and bacterial biofilms. Here we examine the role in X. fastidiosa virulence of an uncharacterized gene, PD1671, annotated as a two-component response regulator with potential GGDEF and EAL domains. GGDEF domains are found in c-di-GMP diguanylate cyclases while EAL domains are found in phosphodiesterases, and these domains are for c-di-GMP production and turnover, respectively. Functional analysis of the PD1671 gene revealed that it affected multiple X. fastidiosa virulence-related phenotypes. A Tn5 PD1671 mutant had a hypervirulent phenotype in grapevines presumably due to enhanced expression of gum genes leading to increased exopolysaccharide levels that resulted in elevated biofilm formation. Interestingly, the PD1671 mutant also had decreased motility in vitro but did not show a reduced distribution in grapevines following inoculation. Given these responses, the putative PD1671 protein may be a negative regulator of X. fastidiosa virulence.

Genetic biomarkers for brain hemisphere differentiation in Parkinson's Disease

NASA Astrophysics Data System (ADS)

Hourani, Mou'ath; Mendes, Alexandre; Berretta, Regina; Moscato, Pablo

2007-11-01

This work presents a study on the genetic profile of the left and right hemispheres of the brain of a mouse model of Parkinson's disease (PD). The goal is to characterize, in a genetic basis, PD as a disease that affects these two brain regions in different ways. Using the same whole-genome microarray expression data introduced by Brown et al. (2002) [1], we could find significant differences in the expression of some key genes, well-known to be involved in the mechanisms of dopamine production control and PD. The problem of selecting such genes was modeled as the MIN (α,β)—FEATURE SET problem [2]; a similar approach to that employed previously to find biomarkers for different types of cancer using gene expression microarray data [3]. The Feature Selection method produced a series of genetic signatures for PD, with distinct expression profiles in the Parkinson's model and control mice experiments. In addition, a close examination of the genes composing those signatures shows that many of them belong to genetic pathways or have ontology annotations considered to be involved in the onset and development of PD. Such elements could provide new clues on which mechanisms are implicated in hemisphere differentiation in PD.

Palladium-platinum core-shell electrocatalysts for oxygen reduction reaction prepared with the assistance of citric acid

DOE PAGES

Zhang, Lulu; Su, Dong; Zhu, Shangqian; ...

2016-04-26

Core–shell structure is a promising alternative to solid platinum (Pt) nanoparticles as electrocatalyst for oxygen reduction reaction (ORR) in proton exchange membrane fuel cells (PEMFCs). A simple method of preparing palladium (Pd)–platinum (Pt) core–shell catalysts (Pd@Pt/C) in a gram-batch was developed with the assistance of citric acid. The Pt shell deposition involves three different pathways: galvanic displacement reaction between Pd atoms and Pt cations, chemical reduction by citric acid, and reduction by negative charges on Pd surfaces. The uniform ultrathin (~0.4 nm) Pt shell was characterized by in situ X-ray diffraction (XRD) and high-angle annular dark-field scanning transmission electron microscopymore » (HAADF-STEM) images combined with electron energy loss spectroscopy (EELS). Compared with state-of-the-art Pt/C, the Pd@Pt/C core–shell catalyst showed 4 times higher Pt mass activity and much better durability upon potential cycling. As a result, both the mass activity and durability were comparable to that of Pd@Pt/C synthesized by a Cu-mediated-Pt-displacement method, which is more complicated and difficult for mass production.« less

The Relationship between Speech Production and Speech Perception Deficits in Parkinson's Disease

ERIC Educational Resources Information Center

De Keyser, Kim; Santens, Patrick; Bockstael, Annelies; Botteldooren, Dick; Talsma, Durk; De Vos, Stefanie; Van Cauwenberghe, Mieke; Verheugen, Femke; Corthals, Paul; De Letter, Miet

2016-01-01

Purpose: This study investigated the possible relationship between hypokinetic speech production and speech intensity perception in patients with Parkinson's disease (PD). Method: Participants included 14 patients with idiopathic PD and 14 matched healthy controls (HCs) with normal hearing and cognition. First, speech production was objectified…

Impact of Professional Development on Preschool Teachers' Conversational Responsivity and Children's Linguistic Productivity and Complexity

ERIC Educational Resources Information Center

Piasta, Shayne B.; Justice, Laura M.; Cabell, Sonia Q.; Wiggins, Alice K.; Turnbull, Khara Pence; Curenton, Stephanie M.

2012-01-01

The present study investigated the effect of professional development (PD) on preschool teachers' conversational responsivity in the classroom, defined as teachers' use of strategies to promote children's participation in extended conversational exchanges (communication-facilitating strategies) and exposure to advanced linguistic models…

Blockade of bovine PD-1 increases T cell function and inhibits bovine leukemia virus expression in B cells in vitro

PubMed Central

2013-01-01

Programmed death-1 (PD-1) is a known immunoinhibitory receptor that contributes to immune evasion of various tumor cells and pathogens causing chronic infection, such as bovine leukemia virus (BLV) infection. First, in this study, to establish a method for the expression and functional analysis of bovine PD-1, hybridomas producing monoclonal antibodies (mAb) specific for bovine PD-1 were established. Treatment with these anti-PD-1 mAb enhanced interferon-gamma (IFN-γ) production of bovine peripheral blood mononuclear cells (PBMC). Next, to examine whether PD-1 blockade by anti-PD-1 mAb could upregulate the immune reaction during chronic infection, the expression and functional analysis of PD-1 in PBMC isolated from BLV-infected cattle with or without lymphoma were performed using anti-PD-1 mAb. The frequencies of both PD-1+ CD4+ T cells in blood and lymph node and PD-1+ CD8+ T cells in lymph node were higher in BLV-infected cattle with lymphoma than those without lymphoma or control uninfected cattle. PD-1 blockade enhanced IFN-γ production and proliferation and reduced BLV-gp51 expression and B-cell activation in PBMC from BLV-infected cattle in response to BLV-gp51 peptide mixture. These data show that anti-bovine PD-1 mAb could provide a new therapy to control BLV infection via upregulation of immune response. PMID:23876077

Highly Selective Upgrading of Biomass-Derived Alcohol Mixtures for Jet/Diesel-Fuel Components.

PubMed

Liu, Qiang; Xu, Guoqiang; Wang, Xicheng; Liu, Xiaoran; Mu, Xindong

2016-12-20

In light of the increasing concern about the energy and environmental problems caused by the combustion of petroleum-based fuels (e.g., jet and diesel fuels), the development of new procedures for their sustainable production from renewable biomass-derived platform compounds has attracted tremendous attention recently. Long-chain ketones/alcohols are promising fuel components owing to the fuel properties that closely resemble those of traditional fuels. The focus of this report is the production of long-chain ketones/alcohols by direct upgrading of biomass-derived short-chain alcohol mixtures (e.g., isopropanol-butanol-ethanol mixtures) in pure water. An efficient Pd catalyst system was developed for these highly selective transformations. Long-chain ketones/alcohols (C 8 -C 19 ), which can be used as precursors for renewable jet/diesel fuel, were obtained in good-to-high selectivity (>90 %) by using the developed Pd catalyst. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Catalytic and electrocatalytic oxidation of ethanol over palladium-based nanoalloy catalysts.

PubMed

Yin, Jun; Shan, Shiyao; Ng, Mei Shan; Yang, Lefu; Mott, Derrick; Fang, Weiqin; Kang, Ning; Luo, Jin; Zhong, Chuan-Jian

2013-07-23

The control of the nanoscale composition and structure of alloy catalysts plays an important role in heterogeneous catalysis. This paper describes novel findings of an investigation for Pd-based nanoalloy catalysts (PdCo and PdCu) for ethanol oxidation reaction (EOR) in gas phase and alkaline electrolyte. Although the PdCo catalyst exhibits a mass activity similar to Pd, the PdCu catalyst is shown to display a much higher mass activity than Pd for the electrocatalytic EOR in alkaline electrolyte. This finding is consistent with the finding on the surface enrichment of Pd on the alloyed PdCu surface, in contrast to the surface enrichment of Co in the alloyed PdCo surface. The viability of C-C bond cleavage was also probed for the PdCu catalysts in both gas-phase and electrolyte-phase EOR. In the gas-phase reaction, although the catalytic conversion rate for CO2 product is higher over Pd than PdCu, the nanoalloy PdCu catalyst appears to suppress the formation of acetic acid, which is a significant portion of the product in the case of pure Pd catalyst. In the alkaline electrolyte, CO2 was detected from the gas phase above the electrolyte upon acid treatment following the electrolysis, along with traces of aldehyde and acetic acid. An analysis of the electrochemical properties indicates that the oxophilicity of the base metal alloyed with Pd, in addition to the surface enrichment of metals, may have played an important role in the observed difference of the catalytic and electrocatalytic activities. In comparison with Pd alloyed with Co, the results for Pd alloyed with Cu showed a more significant positive shift of the reduction potential of the oxygenated Pd species on the surface. These findings have important implications for further fine-tuning of the Pd nanoalloys in terms of base metal composition toward highly active and selective catalysts for EOR.

Analysis of cystic fibrosis gener product (CFTR) function in patients with pancreas divisum and recurrent acute pancreatitis.

PubMed

Gelrud, Andres; Sheth, Sunil; Banerjee, Subhas; Weed, Deborah; Shea, Julie; Chuttani, Ram; Howell, Douglas A; Telford, Jennifer J; Carr-Locke, David L; Regan, Meredith M; Ellis, Lynda; Durie, Peter R; Freedman, Steven D

2004-08-01

The mechanism by which pancreas divisum may lead to recurrent episodes of acute pancreatitis in a subset of individuals is unknown. Abnormalities of the cystic fibrosis gene product (CFTR) have been implicated in the genesis of idiopathic chronic pancreatitis. The aim of this study was to determine if CFTR function is abnormal in patients with pancreas divisum and recurrent acute pancreatitis (PD/RAP). A total of 69 healthy control subjects, 12 patients with PD/RAP, 16 obligate heterozygotes with a single CFTR mutation, and 95 patients with cystic fibrosis were enrolled. CFTR function was analyzed by nasal transepithelial potential difference testing in vivo. The outcomes of the PD/RAP patients following endoscopic and surgical treatments were concomitantly analyzed. Direct measurement of CFTR function in nasal epithelium in response to isoproterenol demonstrated that the values for PD/RAP were intermediate between those observed for healthy controls and cystic fibrosis patients. The median value was 13 mV for PD/RAP subjects, which was statistically different from healthy controls (22 mV, p= 0.001) and cystic fibrosis pancreatic sufficient (-1 mV, p < 0.0001) and pancreatic insufficient (-3 mV, p < 0.0001) patients. These results suggest a link between CFTR dysfunction and recurrent acute pancreatitis in patients with pancreas divisum and may explain why a subset of patients with pancreas divisum develops recurrent acute pancreatitis. Copyright 2004 American College of Gastroenterology

Synthesis of Superparamagnetic Core-Shell Structure Supported Pd Nanocatalysts for Catalytic Nitrite Reduction with Enhanced Activity, No Detection of Undesirable Product of Ammonium, and Easy Magnetic Separation Capability.

PubMed

Sun, Wuzhu; Yang, Weiyi; Xu, Zhengchao; Li, Qi; Shang, Jian Ku

2016-01-27

Superparamagnetic nanocatalysts could minimize both the external and internal mass transport limitations and neutralize OH(-) produced in the reaction more effectively to enhance the catalytic nitrite reduction efficiency with the depressed product selectivity to undesirable ammonium, while possess an easy magnetic separation capability. However, commonly used qusi-monodispersed superparamagnetic Fe3O4 nanosphere is not suitable as catalyst support for nitrite reduction because it could reduce the catalytic reaction efficiency and the product selectivity to N2, and the iron leakage could bring secondary contamination to the treated water. In this study, protective shells of SiO2, polymethylacrylic acid, and carbon were introduced to synthesize Fe3O4@SiO2/Pd, Fe3O4@PMAA/Pd, and Fe3O4@C/Pd catalysts for catalytic nitrite reduction. It was found that SiO2 shell could provide the complete protection to Fe3O4 nanosphere core among these shells. Because of its good dispersion, dense structure, and complete protection to Fe3O4, the Fe3O4@SiO2/Pd catalyst demonstrated the highest catalytic nitrite reduction activity without the detection of NH4(+) produced. Due to this unique structure, the activity of Fe3O4@SiO2/Pd catalysts for nitrite reduction was found to be independent of the Pd nanoparticle size or shape, and their product selectivity was independent of the Pd nanoparticle size, shape, and content. Furthermore, their superparamagnetic nature and high saturation magnetization allowed their easy magnetic separation from treated water, and they also demonstrated a good stability during the subsequent recycling experiment.

Sentence Production in Parkinson Disease: Effects of Conceptual and Task Complexity

ERIC Educational Resources Information Center

Troche, Michelle S.; Altmann, Lori J. P.

2012-01-01

Experimental studies of sentence production in Parkinson disease (PD) are rare. This study examined the relationship between cognitive abilities and performance on two sentence production tasks, sentence repetition, and sentence generation, in which complexity was manipulated. Thirty-eight older adults aged 60 to 85, half with PD, completed the…

Electrochemical oxidation of methanol using dppm-bridged Ru/Pd, Ru/Pt and Ru/Au catalysts.

PubMed

Yang, Ying; McElwee-White, Lisa

2004-08-07

The electrochemical oxidation of methanol was carried out using a series of dppm-bridged Ru/Pd, Ru/Pt and Ru/Au heterobimetallic complexes as catalysts. The major oxidation products were formaldehyde dimethyl acetal (dimethoxymethane, DMM) and methyl formate (MF). The Ru/Pd and Ru/Pt bimetallic catalysts generally afforded lower product ratios of DMM/MF and higher current efficiencies than the Ru/Au catalysts. The Ru/Au bimetallics exhibited product ratios and current efficiencies similar to those obtained from the Ru mononuclear compound CpRu(PPh(3))(2)Cl. Increasing the methanol concentration afforded higher current efficiencies, while the addition of water to the samples shifted the product distribution toward the more highly oxidized product, MF.

Hydrodeoxygenation of phenol over zirconia supported Pd bimetallic catalysts. The effect of second metal on catalyst performance

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

Resende, Karen A.; Teles, Camila A.; Jacobs, Gary

Here, this work investigated the effect of the addition of a second metal (Cu, Ag, Zn, Sn) on the performance of Pd/ZrO 2 catalyst for HDO of phenol at 573 K in the gas phase. The incorporation of dopants resulted in the formation of Pd–X (Cu, Ag, Zn) alloys, which reduced the reaction rate for HDO and increased the selectivity to hydrogenation products (cyclohexanone and cyclohexanol). The lower activity of the bimetallic catalysts was due to the segregation of the second metal on the surface of the Pd particle. For PdSn/ZrO 2, alloying was also observed but tin oxide wasmore » still present on the surface after reduction at 773 K. For Pd and PdSn/ZrO 2, the oxophilic sites represented by Zr and Sn cations promotes the hydrogenation of the carbonyl group of the keto-tautomer intermediate formed, producing benzene as the main product. All catalysts significantly deactivated during the reaction but the deactivation degree depended on the type of the metal. Pd/ZrO 2 and PdZn/ZrO 2 and PdAg/ZrO 2 exhibited approximately the same deactivation degree. However, the loss of activity was less pronounced for PdSn/ZrO2 catalyst. Finally, Pd dispersion significantly decreased during the reaction, indicating that the sintering of Pd particles is one of the causes for catalyst deactivation.« less

Hydrodeoxygenation of phenol over zirconia supported Pd bimetallic catalysts. The effect of second metal on catalyst performance

DOE PAGES

Resende, Karen A.; Teles, Camila A.; Jacobs, Gary; ...

2018-03-21

Here, this work investigated the effect of the addition of a second metal (Cu, Ag, Zn, Sn) on the performance of Pd/ZrO 2 catalyst for HDO of phenol at 573 K in the gas phase. The incorporation of dopants resulted in the formation of Pd–X (Cu, Ag, Zn) alloys, which reduced the reaction rate for HDO and increased the selectivity to hydrogenation products (cyclohexanone and cyclohexanol). The lower activity of the bimetallic catalysts was due to the segregation of the second metal on the surface of the Pd particle. For PdSn/ZrO 2, alloying was also observed but tin oxide wasmore » still present on the surface after reduction at 773 K. For Pd and PdSn/ZrO 2, the oxophilic sites represented by Zr and Sn cations promotes the hydrogenation of the carbonyl group of the keto-tautomer intermediate formed, producing benzene as the main product. All catalysts significantly deactivated during the reaction but the deactivation degree depended on the type of the metal. Pd/ZrO 2 and PdZn/ZrO 2 and PdAg/ZrO 2 exhibited approximately the same deactivation degree. However, the loss of activity was less pronounced for PdSn/ZrO2 catalyst. Finally, Pd dispersion significantly decreased during the reaction, indicating that the sintering of Pd particles is one of the causes for catalyst deactivation.« less

Secondary organic aerosol production from pinanediol, a semi-volatile surrogate for first-generation oxidation products of monoterpenes

NASA Astrophysics Data System (ADS)

Ye, Penglin; Zhao, Yunliang; Chuang, Wayne K.; Robinson, Allen L.; Donahue, Neil M.

2018-05-01

We have investigated the production of secondary organic aerosol (SOA) from pinanediol (PD), a precursor chosen as a semi-volatile surrogate for first-generation oxidation products of monoterpenes. Observations at the CLOUD facility at CERN have shown that oxidation of organic compounds such as PD can be an important contributor to new-particle formation. Here we focus on SOA mass yields and chemical composition from PD photo-oxidation in the CMU smog chamber. To determine the SOA mass yields from this semi-volatile precursor, we had to address partitioning of both the PD and its oxidation products to the chamber walls. After correcting for these losses, we found OA loading dependent SOA mass yields from PD oxidation that ranged between 0.1 and 0.9 for SOA concentrations between 0.02 and 20 µg m-3, these mass yields are 2-3 times larger than typical of much more volatile monoterpenes. The average carbon oxidation state measured with an aerosol mass spectrometer was around -0.7. We modeled the chamber data using a dynamical two-dimensional volatility basis set and found that a significant fraction of the SOA comprises low-volatility organic compounds that could drive new-particle formation and growth, which is consistent with the CLOUD observations.

How should we teach faculty about research-based teaching?

NASA Astrophysics Data System (ADS)

Olmstead, Alice; Turpen, Chandra; Prather, Edward E.

2015-01-01

Faculty professional development (PD) workshops are the primary mechanism used to increase the adoption and adaptation of research-based instructional strategies (RBIS). PD workshops draw in large numbers of physics and astronomy instructors and can serve a critical role in changing instructional practices within our community. Our research focuses on two of the largest and longest-running PD workshops accessible to faculty: the New Physics and Astronomy Faculty Workshop and the Center for Astronomy Education Tier I Teaching Excellence Workshop. We seek to reveal opportunities to improve these workshops through increased awareness of instructors' experiences and prior knowledge, and increased awareness of how these workshops are designed and implemented.Other studies often assume that instructors have coherent theories of teaching and learning, and conclude that many have wrong ideas that need to be confronted or 'fixed'. Our approach is to first investigate the ideas that instructors have about teaching and learning, and identify what we call their 'potentially productive resources'. This approach is better suited to inform respectful PD efforts that build on instructors' intuitions, and we have analyzed interviews with several young astronomy/physics faculty members who were about to attend these PD workshops to demonstrate how this approach can be applied. The primary findings of our first study are: 1) instructors are trying out practices that show some alignment with common RBIS; 2) instructors' values show alignment with common discipline-based education research goals; and 3) instructors often experience dissatisfaction with specific aspects of their instruction. Taken together our findings are poised to inform changes to existing PD efforts.Our ongoing research focuses on the development of a real-time observation tool to document what happens during workshops and what learning opportunities these PD practices create for participants. We will show the preliminary results of this work.

The Power of One? Conditions Which Challenge Managerial Professional Development Practices

ERIC Educational Resources Information Center

Hardy, Ian

2014-01-01

This paper draws upon Bourdieu's concepts of habitus, capital and field to better understand and appreciate the conditions which encouraged the productive professional development (PD) practices of one very capable teacher working in a secondary school in the British Midlands. Rather than celebrating this teacher's practices and perspective as…

The antihistamine olopatadine regulates T cell activation in palladium allergy.

PubMed

Iguchi, Naohiko; Takeda, Yuri; Sato, Naoki; Ukichi, Kenichirou; Katakura, Akira; Ueda, Kyosuke; Narushima, Takayuki; Higuchi, Shigehito; Ogasawara, Kouetsu

2016-06-01

Because of its corrosion resistance palladium (Pd) has been widely used in many consumer products ranging from fashion accessories to dental materials. Recently, however, an increase in Pd allergy cases has been reported. Metal allergy is categorized as a Type IV allergy, which is characterized as a delayed-type hypersensitivity reaction in which T cells are known to play an important role; however, the precise mechanism of their action remains unclear. Here we defined the relationship between histamine and the Pd allergic reaction specifically with respect to T cell responses. To verify the effects of histamine on T cells, we examined whether there is a change in IFN-γ production following stimulation of histamine or the antihistamine, olopatadine hydrochloride (OLP), in vitro. In addition, we assessed whether OLP administration affected the degree of footpad swelling or IFN-γ production during the Pd allergy response in mice. We found that histamine stimulation increased IFN-γ production in T cells, specifically enhancing IFN-γ production in CD8(+) T cells compared with CD4(+) T cells. Interestingly, OLP suppressed the production of IFN-γ in CD8(+) T cells, and this compound inhibited footpad swelling and IFN-γ production in mice with Pd allergy. These results suggest that histamine promotes the Type IV allergic reaction and thus, the histamine 1 receptor (H1R) might be useful therapeutic target for treatment of metal allergy. Copyright © 2016 Elsevier B.V. All rights reserved.

Blockade of PD-1 Signaling Enhances Th2 Cell Responses and Aggravates Liver Immunopathology in Mice with Schistosomiasis japonica

PubMed Central

Zhou, Sha; Jin, Xin; Li, Yalin; Li, Wei; Chen, Xiaojun; Xu, Lei; Zhu, Jifeng; Xu, Zhipeng; Zhang, Yang; Liu, Feng; Su, Chuan

2016-01-01

Background More than 220 million people worldwide are chronically infected with schistosomes, causing severe disease or even death. The major pathological damage occurring in schistosomiasis is attributable to the granulomatous inflammatory response and liver fibrosis induced by schistosome eggs. The inflammatory response is tightly controlled and parallels immunosuppressive regulation, constantly maintaining immune homeostasis and limiting excessive immunopathologic damage in important host organs. It is well known that the activation of programmed death 1 (PD-1) signaling causes a significant suppression of T cell function. However, the roles of PD-1 signaling in modulating CD4+ T cell responses and immunopathology during schistosome infection, have yet to be defined. Methodology/Principal Findings Here, we show that PD-1 is upregulated in CD4+ T cells in Schistosoma japonicum (S. japonicum)-infected patients. We also show the upregulation of PD-1 expression in CD4+ T cells in the spleens, mesenteric lymph nodes, and livers of mice with S. japonicum infection. Finally, we found that the blockade of PD-1 signaling enhanced CD4+ T helper 2 (Th2) cell responses and led to more severe liver immunopathology in mice with S. japonicum infection, without a reduction of egg production or deposition in the host liver. Conclusions/Significance Overall, our study suggests that PD-1 signaling is specifically induced to control Th2-associated inflammatory responses during schistosome infection and is beneficial to the development of PD-1-based control of liver immunopathology. PMID:27792733

Plant Equipment Package Modernization Program. Volume 4-1. Model Lines. Shell, HE, M483/M107-155MM Case, Cartridge, M115B1, M148A1B1, M150B1-105MM Shell, HEAT-T, M456A1-105MM Fuze, PD, M739

DTIC Science & Technology

1976-04-01

Cartridge, M115B1, M148A1B1, M15#1B1-15MM J .. Shell, HEAT-T, M456A1-105MM Fuze, PD, M739 # prepared for Project Manager Munitions Production Base...ENGINEERS PLANT EQUIPMENT PACKAGE MODERNIZATION PROGRAM Volume 4-1 Report No. 75-86-R-4- MODEL LINE DEVELOPMENT FUZE,PD, M739 prepared for Project...In preparing the model line for the manufacture of piece parts for the M739 fuze, a number of facts became obvious and affect the detailed de- [ sign

Dietary cholesterol, fats and risk of Parkinson's disease in the Singapore Chinese Health Study.

PubMed

Tan, Louis C; Methawasin, Kulthida; Tan, Eng-King; Tan, June H; Au, Wing-Lok; Yuan, Jian-Min; Koh, Woon-Puay

2016-01-01

Prospective studies on lipids and risk of Parkinson's disease (PD) in Asian populations are sparse. This study prospectively examined the associations between dietary cholesterol and major fatty acids, and risk of PD among the Chinese in Singapore. This study used data from the Singapore Chinese Health Study, a population-based prospective cohort of 63 257 men and women aged 45-74 years in Singapore enrolled in 1993-1998. Dietary intakes of cholesterol and fatty acids were derived from a validated semiquantitative food frequency questionnaire and the Singapore Food Composition Table. Incident PD cases were identified either through follow-up interviews or record linkage analysis with hospital discharge and PD outpatient registries. After an average of 14.6 years, 218 men and 193 women in the cohort developed PD. Dietary cholesterol was associated with statistically significantly lower risk of PD in a dose-dependent manner among men after adjustment for established risk factors for PD and intakes of major fatty acids. Compared to the lowest quartile, HR (95% CI) for the highest quartile was 0.53 (95% CI 0.33 to 0.84) (P for trend=0.006). Among women, dietary monounsaturated fatty acid was inversely associated with PD risk (P for trend=0.033). Compared to the lowest quartile, HR for the highest quartile was 0.44 (95% CI 0.22 to 0.88). There was no statistically significant association between dietary saturated, n-3 and n-6 fatty acids and PD risk. Higher intakes of cholesterol and monounsaturated fatty acids may reduce risk of PD in men and women, respectively. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Effect of concurrent walking and interlocutor distance on conversational speech intensity and rate in Parkinson's disease.

PubMed

McCaig, Cassandra M; Adams, Scott G; Dykstra, Allyson D; Jog, Mandar

2016-01-01

Previous studies have demonstrated a negative effect of concurrent walking and talking on gait in Parkinson's disease (PD) but there is limited information about the effect of concurrent walking on speech production. The present study examined the effect of sitting, standing, and three concurrent walking tasks (slow, normal, fast) on conversational speech intensity and speech rate in fifteen individuals with hypophonia related to idiopathic Parkinson's disease (PD) and fourteen age-equivalent controls. Interlocuter (talker-to-talker) distance effects and walking speed were also examined. Concurrent walking was found to produce a significant increase in speech intensity, relative to standing and sitting, in both the control and PD groups. Faster walking produced significantly greater speech intensity than slower walking. Concurrent walking had no effect on speech rate. Concurrent walking and talking produced significant reductions in walking speed in both the control and PD groups. In general, the results of the present study indicate that concurrent walking tasks and the speed of concurrent walking can have a significant positive effect on conversational speech intensity. These positive, "energizing" effects need to be given consideration in future attempts to develop a comprehensive model of speech intensity regulation and they may have important implications for the development of new evaluation and treatment procedures for individuals with hypophonia related to PD. Crown Copyright © 2015. Published by Elsevier B.V. All rights reserved.

Clinical Scale Zinc Finger Nuclease-mediated Gene Editing of PD-1 in Tumor Infiltrating Lymphocytes for the Treatment of Metastatic Melanoma

PubMed Central

Beane, Joal D; Lee, Gary; Zheng, Zhili; Mendel, Matthew; Abate-Daga, Daniel; Bharathan, Mini; Black, Mary; Gandhi, Nimisha; Yu, Zhiya; Chandran, Smita; Giedlin, Martin; Ando, Dale; Miller, Jeff; Paschon, David; Guschin, Dmitry; Rebar, Edward J; Reik, Andreas; Holmes, Michael C; Gregory, Philip D; Restifo, Nicholas P; Rosenberg, Steven A; Morgan, Richard A; Feldman, Steven A

2015-01-01

Programmed cell death-1 (PD-1) is expressed on activated T cells and represents an attractive target for gene-editing of tumor targeted T cells prior to adoptive cell transfer (ACT). We used zinc finger nucleases (ZFNs) directed against the gene encoding human PD-1 (PDCD-1) to gene-edit melanoma tumor infiltrating lymphocytes (TIL). We show that our clinical scale TIL production process yielded efficient modification of the PD-1 gene locus, with an average modification frequency of 74.8% (n = 3, range 69.9–84.1%) of the alleles in a bulk TIL population, which resulted in a 76% reduction in PD-1 surface-expression. Forty to 48% of PD-1 gene-edited cells had biallelic PD-1 modification. Importantly, the PD-1 gene-edited TIL product showed improved in vitro effector function and a significantly increased polyfunctional cytokine profile (TNFα, GM-CSF, and IFNγ) compared to unmodified TIL in two of the three donors tested. In addition, all donor cells displayed an effector memory phenotype and expanded approximately 500–2,000-fold in vitro. Thus, further study to determine the efficiency and safety of adoptive cell transfer using PD-1 gene-edited TIL for the treatment of metastatic melanoma is warranted. PMID:25939491

Effect of Parkinson's disease on the production of structured and unstructured speaking tasks: Respiratory physiologic and linguistic considerations

PubMed Central

Huber, Jessica E.; Darling, Meghan

2012-01-01

Purpose The purpose of the present study was to examine the effects of cognitive-linguistic deficits and respiratory physiologic changes on respiratory support for speech in PD, using two speech tasks, reading and extemporaneous speech. Methods Five women with PD, 9 men with PD, and 14 age- and sex-matched control participants read a passage and spoke extemporaneously on a topic of their choice at comfortable loudness. Sound pressure level, syllables per breath group, speech rate, and lung volume parameters were measured. Number of formulation errors, disfluencies, and filled pauses were counted. Results Individuals with PD produced shorter utterances as compared to control participants. The relationships between utterance length and lung volume initiation and inspiratory duration were weaker in individuals with PD than for control participants, particularly for the extemporaneous speech task. These results suggest less consistent planning for utterance length by individuals with PD in extemporaneous speech. Individuals with PD produced more formulation errors in both tasks and significantly fewer filled pauses in extemporaneous speech. Conclusions Both respiratory physiologic and cognitive-linguistic issues affected speech production by individuals with PD. Overall, individuals with PD had difficulty planning or coordinating language formulation and respiratory support, in particular during extemporaneous speech. PMID:20844256

Photothermal Catalyst Engineering: Hydrogenation of Gaseous CO 2 with High Activity and Tailored Selectivity

DOE PAGES

Jia, Jia; Wang, Hong; Lu, Zhuole; ...

2017-07-25

This study has designed and implemented a library of hetero-nanostructured catalysts, denoted as Pd@Nb 2O 5, comprised of size-controlled Pd nanocrystals interfaced with Nb 2O 5 nanorods. This study also demonstrates that the catalytic activity and selectivity of CO 2 reduction to CO and CH 4 products can be systematically tailored by varying the size of the Pd nanocrystals supported on the Nb 2O 5 nanorods. Using large Pd nanocrystals, this study achieves CO and CH 4 production rates as high as 0.75 and 0.11 mol h –1 gPd –1, respectively. By contrast, using small Pd nanocrystals, a CO productionmore » rate surpassing 18.8 mol h –1 gPd –1 is observed with 99.5% CO selectivity. These performance metrics establish a new milestone in the champion league of catalytic nanomaterials that can enable solar-powered gas-phase heterogeneous CO 2 reduction. In conclusion, the remarkable control over the catalytic performance of Pd@Nb 2O 5 is demonstrated to stem from a combination of photothermal, electronic and size effects, which is rationally tunable through nanochemistry.« less

2D PdAg Alloy Nanodendrites for Enhanced Ethanol Electroxidation.

PubMed

Huang, Wenjing; Kang, Xiaolin; Xu, Cheng; Zhou, Junhua; Deng, Jun; Li, Yanguang; Cheng, Si

2018-03-01

The development of highly active and stable electrocatalysts for ethanol electroxidation is of decisive importance to the successful commercialization of direct ethanol fuel cells. Despite great efforts invested over the past decade, their progress has been notably slower than expected. In this work, the facile solution synthesis of 2D PdAg alloy nanodendrites as a high-performance electrocatalyst is reported for ethanol electroxidation. The reaction is carried out via the coreduction of Pd and Ag precursors in aqueous solution with the presence of octadecyltrimethylammonium chloride as the structural directing agent. Final products feature small thickness (5-7 nm) and random in-plane branching with enlarged surface areas and abundant undercoordinated sites. They exhibit enhanced electrocatalytic activity (large specific current ≈2600 mA mgPd-1) and excellent operation stability (as revealed from both the cycling and chronoamperometric tests) for ethanol electroxidation. Control experiments show that the improvement comes from the combined electronic and structural effects. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Formulaic Language in Parkinson's Disease and Alzheimer's Disease: Complementary Effects of Subcortical and Cortical Dysfunction

PubMed Central

Van Lancker Sidtis, Diana; Choi, JiHee; Alken, Amy

2015-01-01

Purpose The production of formulaic expressions (conversational speech formulas, pause fillers, idioms, and other fixed expressions) is excessive in the left hemisphere and deficient in the right hemisphere and in subcortical stroke. Speakers with Alzheimer's disease (AD), having functional basal ganglia, reveal abnormally high proportions of formulaic language. Persons with Parkinson's disease (PD), having dysfunctional basal ganglia, were predicted to show impoverished formulaic expressions in contrast to speakers with AD. This study compared participants with PD, participants with AD, and healthy control (HC) participants on protocols probing production and comprehension of formulaic expressions. Method Spontaneous speech samples were recorded from 16 individuals with PD, 12 individuals with AD, and 18 HC speakers. Structured tests were then administered as probes of comprehension. Results The PD group had lower proportions of formulaic expressions compared with the AD and HC groups. Comprehension testing yielded opposite contrasts: participants with PD showed significantly higher performance compared with participants with AD and did not differ from HC participants. Conclusions The finding that PD produced lower proportions of formulaic expressions compared with AD and HC supports the view that subcortical nuclei modulate the production of formulaic expressions. Contrasting results on formal testing of comprehension, whereby participants with AD performed significantly worse than participants with PD and HC participants, indicate differential effects on procedural and declarative knowledge associated with these neurological conditions. PMID:26183940

Product development public-private partnerships for public health: a systematic review using qualitative data.

PubMed

De Pinho Campos, Katia; Norman, Cameron D; Jadad, Alejandro R

2011-10-01

Almost a decade ago, public health initiated a number of innovative ventures to attract investments from multinational drug companies for the development of new drugs and vaccines to tackle neglected diseases (NDs). These ventures - known as product development public-private partnerships (PD PPPs) - represent the participation of the public and private actors toward the discovery and development of essential medicines to reduce the suffering of over one billion people worldwide living with NDs. This systematic review aimed to identify empirical-based descriptive articles to understand critical elements in the partnership process, and propose a framework to shed light on future guidelines to support better planning, design and management of existing and new forms of PPPs for public health. Ten articles met the inclusion criteria and were analyzed and synthesized using qualitative content analysis. The findings show that the development stage of PD PPPs requires a careful initiation and planning process including discussion on values and shared goals, agreement on mutual interests & equality of power relation, exchange of expertise & resources, stakeholder engagement, and assessment of the local health capacity. The management stage of PD PPPs entails transparency, extensive communication and participatory decision-making among partner organizations. This review illustrates the difficulties, challenges and effective responses during the partnering process. This model of collaboration may offer a way to advance population health at present, while creating streams of innovation that can yield future social and financial dividends in enhancing the public's health more widely. Copyright © 2011 Elsevier Ltd. All rights reserved.

Enhanced d-lactic acid production by recombinant Saccharomyces cerevisiae following optimization of the global metabolic pathway.

PubMed

Yamada, Ryosuke; Wakita, Kazuki; Mitsui, Ryosuke; Ogino, Hiroyasu

2017-09-01

Utilization of renewable feedstocks for the production of bio-based chemicals such as d-lactic acid by engineering metabolic pathways in the yeast Saccharomyces cerevisiae has recently become an attractive option. In this study, to realize efficient d-lactic acid production by S. cerevisiae, the expression of 12 glycolysis-related genes and the Leuconostoc mesenteroides d-LDH gene was optimized using a previously developed global metabolic engineering strategy, and repeated batch fermentation was carried out using the resultant strain YPH499/dPdA3-34/DLDH/1-18. Stable d-lactic acid production through 10 repeated batch fermentations was achieved using YPH499/dPdA3-34/DLDH/1-18. The average d-lactic acid production, productivity, and yield with 10 repeated batch fermentations were 60.3 g/L, 2.80 g/L/h, and 0.646, respectively. The present study is the first report of the application of a global metabolic engineering strategy for bio-based chemical production, and it shows the potential for efficient production of such chemicals by global metabolic engineering of the yeast S. cerevisiae. Biotechnol. Bioeng. 2017;114: 2075-2084. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Virtues in participatory design: cooperation, curiosity, creativity, empowerment and reflexivity.

PubMed

Steen, Marc

2013-09-01

In this essay several virtues are discussed that are needed in people who work in participatory design (PD). The term PD is used here to refer specifically to an approach in designing information systems with its roots in Scandinavia in the 1970s and 1980s. Through the lens of virtue ethics and based on key texts in PD, the virtues of cooperation, curiosity, creativity, empowerment and reflexivity are discussed. Cooperation helps people in PD projects to engage in cooperative curiosity and cooperative creativity. Curiosity helps them to empathize with others and their experiences, and to engage in joint learning. Creativity helps them to envision, try out and materialize ideas, and to jointly create new products and services. Empowerment helps them to share power and to enable other people to flourish. Moreover, reflexivity helps them to perceive and to modify their own thoughts, feelings and actions. In the spirit of virtue ethics-which focuses on specific people in concrete situations-several examples from one PD project are provided. Virtue ethics is likely to appeal to people in PD projects because it is practice-oriented, provides room for exploration and experimentation, and promotes professional and personal development. In closing, some ideas for practical application, for education and for further research are discussed.

Spallation reaction study for the long-lived fission product 107Pd

NASA Astrophysics Data System (ADS)

Wang, He; Otsu, Hideaki; Sakurai, Hiroyoshi; Ahn, DeukSoon; Aikawa, Masayuki; Ando, Takashi; Araki, Shouhei; Chen, Sidong; Nobuyuki, Chiga; Doornenbal, Pieter; Fukuda, Naoki; Isobe, Tadaaki; Kawakami, Shunsuke; Kawase, Shoichiro; Kin, Tadahiro; Kondo, Yosuke; Koyama, Shunpei; Kubono, Shigeru; Maeda, Yukie; Makinaga, Ayano; Matsushita, Masafumi; Matsuzaki, Teiichiro; Michimasa, Shin'ichiro; Momiyama, Satoru; Nagamine, Shunsuke; Nakamura, Takashi; Nakano, Keita; Niikura, Megumi; Ozaki, Tomoyuki; Saito, Atsumi; Saito, Takeshi; Shiga, Yoshiaki; Shikata, Mizuki; Shimizu, Yohei; Shimoura, Susumu; Sumikama, Toshiyuki; Söderström, Pär-Anders; Suzuki, Hiroshi; Takeda, Hiroyuki; Takeuchi, Satoshi; Taniuchi, Ryo; Togano, Yasuhiro; Tsubota, Junichi; Uesaka, Meiko; Watanabe, Yasushi; Watanabe, Yukinobu; Wimmer, Kathrin; Yamamoto, Tatsuya; Yoshida, Koichi

2017-02-01

Spallation reactions for the long-lived fission product 107Pd have been studied for the purpose of nuclear waste transmutation. The cross sections on the proton- and deuteron-induced spallation were obtained at 196 and 118 MeV/nucleon in inverse kinematics at the RIKEN Radioactive Isotope Beam Factory. Both the target and energy dependences of cross sections have been investigated systematically. It was found that the proton-induced cross sections at 196 MeV/nucleon are close to those for deuteron obtained at 118 MeV/nucleon for the light-mass products. The experimental data are compared with the SPACS semi-empirical parameterization and the PHITS calculations including both the intranuclear cascade and evaporation processes. Our data give a design goal of proton/deuteron flux for the transmutation of 107Pd using the spallation reaction. In addition, it is found that the spallation reaction at 118 MeV/nucleon may have an advantage over the 107Pd transmutation because of the low production of other long-lived radioactive isotopes.

Selective One-Pot Production of High-Grade Diesel-Range Alkanes from Furfural and 2-Methylfuran over Pd/NbOPO4.

PubMed

Xia, Qineng; Xia, Yinjiang; Xi, Jinxu; Liu, Xiaohui; Zhang, Yongguang; Guo, Yong; Wang, Yanqin

2017-02-22

A one-pot method for the selective production of high-grade diesel-range alkanes from biomass-derived furfural and 2-methylfuran (2-MF) was developed by combining the hydroxyalkylation/alkylation (HAA) condensation of furfural with 2-MF and the subsequent hydrodeoxygenation (HDO) over a multifunctional Pd/NbOPO 4 catalyst. The effects of various reaction conditions as well as a variety of solid-acid catalysts and metal-loaded NbOPO 4 catalysts were systematically investigated to optimize the reaction conditions for both reactions. Under the optimal reaction conditions up to 89.1 % total yield of diesel-range alkanes was obtained from furfural and 2-MF by this one-pot method. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Palladium-catalyzed C-H functionalization of acyldiazomethane and tandem cross-coupling reactions.

PubMed

Ye, Fei; Qu, Shuanglin; Zhou, Lei; Peng, Cheng; Wang, Chengpeng; Cheng, Jiajia; Hossain, Mohammad Lokman; Liu, Yizhou; Zhang, Yan; Wang, Zhi-Xiang; Wang, Jianbo

2015-04-08

Palladium-catalyzed C-H functionalization of acyldiazomethanes with aryl iodides has been developed. This reaction is featured by the retention of the diazo functionality in the transformation, thus constituting a novel method for the introduction of diazo functionality to organic molecules. Consistent with the experimental results, the density functional theory (DFT) calculation indicates that the formation of Pd-carbene species in the catalytic cycle through dinitrogen extrusion from the palladium ethyl diazoacetate (Pd-EDA) complex is less favorable. The reaction instead proceeds through Ag2CO3 assisted deprotonation and subsequently reductive elimination to afford the products with diazo functionality remained. This C-H functionalization transformation can be further combined with the recently evolved palladium-catalyzed cross-coupling reaction of diazo compounds with aryl iodides to develop a tandem coupling process for the synthesis of α,α-diaryl esters. DFT calculation supports the involvement of Pd-carbene as reactive intermediate in the catalytic cycle, which goes through facile carbene migratory insertion with a low energy barrier (3.8 kcal/mol).

Severe glucose-6-phosphate dehydrogenase deficiency leads to susceptibility to infection and absent NETosis.

PubMed

Siler, Ulrich; Romao, Susana; Tejera, Emilio; Pastukhov, Oleksandr; Kuzmenko, Elena; Valencia, Rocio G; Meda Spaccamela, Virginia; Belohradsky, Bernd H; Speer, Oliver; Schmugge, Markus; Kohne, Elisabeth; Hoenig, Manfred; Freihorst, Joachim; Schulz, Ansgar S; Reichenbach, Janine

2017-01-01

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymatic disorder of red blood cells in human subjects, causing hemolytic anemia linked to impaired nicotinamide adenine dinucleotide phosphate (NADPH) production and imbalanced redox homeostasis in erythrocytes. Because G6PD is expressed by a variety of hematologic and nonhematologic cells, a broader clinical phenotype could be postulated in G6PD-deficient patients. We describe 3 brothers with severe G6PD deficiency and susceptibility to bacterial infection. We sought to study the molecular pathophysiology leading to susceptibility to infection in 3 siblings with severe G6PD deficiency. Blood samples of 3 patients with severe G6PD deficiency were analyzed for G6PD enzyme activity, cellular oxidized nicotinamide adenine dinucleotide phosphate/NADPH levels, phagocytic reactive oxygen species production, neutrophil extracellular trap (NET) formation, and neutrophil elastase translocation. In these 3 brothers strongly reduced NADPH oxidase function was found in granulocytes, leading to impaired NET formation. Defective NET formation has thus far been only observed in patients with the NADPH oxidase deficiency chronic granulomatous disease, who require antibiotic and antimycotic prophylaxis to prevent life-threatening bacterial and fungal infections. Because severe G6PD deficiency can be a phenocopy of chronic granulomatous disease with regard to the cellular and clinical phenotype, careful evaluation of neutrophil function seems mandatory in these patients to decide on appropriate anti-infective preventive measures. Determining the level of G6PD enzyme activity should be followed by analysis of reactive oxygen species production and NET formation to decide on required antibiotic and antimycotic prophylaxis. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Effects of prenatal cocaine exposure on social development in mice.

PubMed

Kabir, Zeeba D; Kennedy, Bruce; Katzman, Aaron; Lahvis, Garet P; Kosofsky, Barry E

2014-01-01

Prenatal cocaine exposure (PCE) in humans and animals has been shown to impair social development. Molecules that mediate synaptic plasticity and learning in the medial prefrontal cortex (mPFC), specifically brain-derived neurotrophic factor (BDNF) and its downstream signaling molecule, early growth response protein 1 (egr1), have been shown to affect the regulation of social interactions (SI). In this study we determined the effects of PCE on SI and the corresponding ultrasonic vocalizations (USVs) in developing mice. Furthermore, we studied the PCE-induced changes in the constitutive expression of BDNF, egr1 and their transcriptional regulators in the mPFC as a possible molecular mechanism mediating the altered SI. In prenatal cocaine-exposed (PCOC) mice we identified increased SI and USV production at postnatal day (PD) 25, and increased SI but not USVs at PD35. By PD45 the expression of both social behaviors normalized in PCOC mice. At the molecular level, we found increased BDNF exon IV and egr1 mRNA in the mPFC of PCOC mice at PD30 that normalized by PD45. This was concurrent with increased EGR1 protein in the mPFC of PCOC mice at PD30, suggesting a role of egr1 in the enhanced SI observed in juvenile PCOC mice. Additionally, by measuring the association of acetylation of histone 3 at lysine residues 9 and 14 (acH3K9,14) and MeCP2 at the promoters of BDNF exons I and IV and egr1, our results provide evidence of promoter-specific alterations in the mPFC of PCOC juvenile mice, with increased association of acH3K9,14 only at the BDNF exon IV promoter. These results identify a potential PCE-induced molecular alteration as the underlying neurobiological mechanism mediating the altered social development in juvenile mice. © 2014 S. Karger AG, Basel.

Building Sustainable Professional Development Programs: Applying Strategies From Implementation Science to Translate Evidence Into Practice.

PubMed

Baldwin, Constance D; Chandran, Latha; Gusic, Maryellen E

2017-01-01

Multisite and national professional development (PD) programs for educators are challenging to establish. Use of implementation science (IS) frameworks designed to convert evidence-based intervention methods into effective health care practice may help PD developers translate proven educational methods and models into successful, well-run programs. Implementation of the national Educational Scholars Program (ESP) is used to illustrate the value of the IS model. Four adaptable elements of IS are described: (1) replication of an evidence-based model, (2) systematic stages of implementation, (3) management of implementation using three implementation drivers, and (4) demonstration of program success through measures of fidelity to proven models and sustainability. Implementation of the ESP was grounded on five established principles and methods for successful PD. The process was conducted in four IS stages over 10 years: Exploration, Installation, Initial Implementation, and Full Implementation. To ensure effective and efficient processes, attention to IS implementation drivers helped to manage organizational relationships, build competence in faculty and scholars, and address leadership challenges. We describe the ESP's fidelity to evidence-based structures and methods, and offer three examples of sustainability efforts that enabled achievement of targeted program outcomes, including academic productivity, strong networking, and career advancement of scholars. Application of IS frameworks to program implementation may help other PD programs to translate evidence-based methods into interventions with enhanced impact. A PD program can follow systematic developmental stages and be operationalized by practical implementation drivers, thereby creating successful and sustainable interventions that promote the academic vitality of health professions educators.

Neutral Solution Low in Glucose Degradation Products Is Associated with Less Peritoneal Fibrosis and Vascular Sclerosis in Patients Receiving Peritoneal Dialysis

PubMed Central

Kawanishi, Kunio; Honda, Kazuho; Tsukada, Misao; Oda, Hideaki; Nitta, Kosaku

2013-01-01

♦ Background: The effects of novel biocompatible peritoneal dialysis (PD) solutions on human peritoneal membrane pathology have yet to be determined. Quantitative evaluation of human peritoneal biopsy specimens may reveal the effects of the new solutions on peritoneal membrane pathology. ♦ Methods: Peritoneal specimens from 24 PD patients being treated with either acidic solution containing high-glucose degradation products [GDPs (n = 12)] or neutral solution with low GDPs (n = 12) were investigated at the end of PD. As controls, pre-PD peritoneal specimens, obtained from 13 patients at PD catheter insertion, were also investigated. The extent of peritoneal fibrosis, vascular sclerosis, and advanced glycation end-product (AGE) accumulation were evaluated by quantitative or semi-quantitative methods. The average densities of CD31-positive vessels and podoplanin-positive lymphatic vessels were also determined. ♦ Results: Peritoneal membrane fibrosis, vascular sclerosis, and AGE accumulation were significantly suppressed in the neutral group compared with the acidic group. The neutral group also showed lower peritoneal equilibration test scores and preserved ultrafiltration volume. The density of blood capillaries, but not of lymphatic capillaries, was significantly increased in the neutral group compared with the acidic and pre-PD groups. ♦ Conclusions: Neutral solutions with low GDPs are associated with less peritoneal membrane fibrosis and vascular sclerosis through suppression of AGE accumulation. However, contrary to expectation, blood capillary density was increased in the neutral group. The altered contents of the new PD solutions modified peritoneal membrane morphology and function in patients undergoing PD. PMID:23123670

Preparation of Pd-Loaded Hierarchical FAU Membranes and Testing in Acetophenone Hydrogenation.

PubMed

Molinari, Raffaele; Lavorato, Cristina; Mastropietro, Teresa F; Argurio, Pietro; Drioli, Enrico; Poerio, Teresa

2016-03-22

Pd-loaded hierarchical FAU (Pd-FAU) membranes, containing an intrinsic secondary non-zeolitic (meso)porosity, were prepared and tested in the catalytic transfer hydrogenation of acetophenone (AP) to produce phenylethanol (PE), an industrially relevant product. The best operating conditions were preliminarily identified by testing different solvents and organic hydrogen donors in a batch hydrogenation process where micron-sized FAU seeds were employed as catalyst support. Water as solvent and formic acid as hydrogen source resulted to be the best choice in terms of conversion for the catalytic hydrogenation of AP, providing the basis for the design of a green and sustainable process. The best experimental conditions were selected and applied to the Pd-loaded FAU membrane finding enhanced catalytic performance such as a five-fold higher productivity than with the unsupported Pd-FAU crystals (11.0 vs. 2.2 mgproduct gcat(-1)·h(-1)). The catalytic performance of the membrane on the alumina support was also tested in a tangential flow system obtaining a productivity higher than that of the batch system (22.0 vs. 11.0 mgproduct gcat(-1)·h(-1)).

GPER Agonist G1 Attenuates Neuroinflammation and Dopaminergic Neurodegeneration in Parkinson Disease.

PubMed

Guan, Jing; Yang, Beibei; Fan, Yi; Zhang, Ji

2017-01-01

Epidemiological studies have shown that women of reproductive age have much less possibility of developing Parkinson disease (PD) than men. The beneficial effect of estrogen also has been well-described in both culture and animal models of PD. G protein-coupled estrogen receptor (GPER) is a membrane-associated estrogen receptor, and displayed a neuroprotective role in a mouse model of PD. Since GPER is highly expressed in microglia, we speculate that GPER mediates the neuroprotective function of estradiol through suppressing the neuroinflammation of PD. We investigated the effects of GPER agonist G1 and GPER antagonist G15 on the neurodegeneration of dopaminergic neuron, the activation of microglia, and the production of IL-1β, TNF-α, and IL-6 in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced animal model of parkinsonism. Furthermore, we confirmed the effects of GPER activation on the production of IL-1β, TNF-α, and IL-6 in an in vitro MPP+ model in BV2 microglial cells. After 12-day treatment with G1, mice showed an increase in the number of tyrosine hydroxylase-immunoreactive cells, reduced activation of microglia, and the abatement of proinflammatory cytokines, and the anti-inflammatory effect of G1 was abolished by G15. Meanwhile, in vitro studies demonstrated that GPER activation also reduced the release of proinflammatory cytokines from BV2 microglial cells after MPP+ stimulation. Our data suggest that GPER mediates the anti-neuroinflammatory effect of estrogen in experimental PD progression. © 2017 S. Karger AG, Basel.

Pd0@Polyoxometalate Nanostructures as Green Electrocatalysts: Illustrative Example of Hydrogen Production

PubMed Central

Biboum, Rosa N.; Keita, Bineta; Franger, Sylvain; Njiki, Charles P. Nanseu; Zhang, Guangjin; Zhang, Jie; Liu, Tianbo; Mbomekalle, Israel-Martyr; Nadjo, Louis

2010-01-01

Green-chemistry type procedures were used to synthesize Pd0 nanostructures encapsulated by a vanadium-substituted Wells-Dawson-type polyoxometalate (Pd0@POM). The cyclic voltammogram run with the Pd0@POM-modified glassy carbon electrode shows well-defined waves, associated with Pd0 nanostructures and the VV/VIV redox couple. The Pd0@POM-modified electrode displayed remarkably reproducible cyclic voltammetry patterns. The hydrogen evolution reaction (HER) was selected as an illustrative example to test the electrocatalytic behavior of the electrode. The kinetic parameters of the HER show the high efficiency of the Pd0@POM-modified electrode. This is the first example of electrochemical characterization of a modified electrode based on a vanado-tungstic POM and Pd0 nanostructures.

Facile synthesis of bacitracin-templated palladium nanoparticles with superior electrocatalytic activity

NASA Astrophysics Data System (ADS)

Li, Yanji; Wang, Zi; Li, Xiaoling; Yin, Tian; Bian, Kexin; Gao, Faming; Gao, Dawei

2017-02-01

Palladium nanomaterials have attracted great attention on the development of electrocatalysts for fuel cells. Herein, we depicted a novel strategy in the synthesis of palladium nanoparticles with superior electrocatalytic activity. The new approach, based on the self-assembly of bacitracin biotemplate and palladium salt for the preparation of bacitracin-palladium nanoparticles (Bac-PdNPs), was simple, low-cost, and green. The complex, composed by a series of spherical Bac-PdNPs with a diameter of 70 nm, exhibited a chain-liked morphology in TEM and a face-centered cubic crystal structure in X-Ray diffraction and selected area electron diffraction. The palladium nanoparticles were mono-dispersed and stable in aqueous solution as shown in TEM and zeta potential. Most importantly, compared to the commercial palladium on carbon (Pd/C) catalyst (8.02 m2 g-1), the Bac-PdNPs showed a larger electrochemically active surface area (47.57 m2 g-1), which endowed the products an excellent electrocatalytic activity for ethanol oxidation in alkaline medium. The strategy in synthesis of Bac-PdNPs via biotemplate approach might light up new ideas in anode catalysts for direct ethanol fuel cells.

Nanobiocatalytic Degradation of Acid Orange 7

NASA Astrophysics Data System (ADS)

Hastings, Jason

The catalytic properties of various metal nanoparticles have led to their use in environmental remediation applications. However, these remediation strategies are limited by their ability to deliver catalytic nanoparticles and a suitable electron donor to large treatment zones. Clostridium pasteurianum BC1 cells, loaded with bio-Pd nanoparticles, were used to effectively catalyze the reductive degradation and removal of Acid Orange 7 (AO7), a model azo compound. Hydrogen produced fermentatively by the C. pasteurianum BC1 acted as the electron donor for the process. Pd-free bacterial cultures or control experiments conducted with heat-killed cells showed limited reduction of AO7. Experiments also showed that the in situ biological production of H2 by C. pasteurianum BC1 was essential for the degradation of AO7, which suggests a novel process where the in situ microbial production of hydrogen is directly coupled to the catalytic bio-Pd mediated reduction of AO7. The differences in initial degradation rate for experiments conducted using catalyst concentrations of 1ppm Pd and 5ppm Pd and an azo dye concentration of 100ppm AO7 was 0.39 /hr and 1.94 /hr respectively, demonstrating the importance of higher concentrations of active Pd(0). The degradation of AO7 was quick as demonstrated by complete reductive degradation of 50ppm AO7 in 2 hours in experiments conducted using a catalyst concentration of 5ppm Pd. Dye degradation products were analyzed via Gas Chromatograph-Mass Spectrometer (GCMS), High Performance Liquid Chromatography (HPLC), UltraViolet-Visible spectrophotometer (UV-Vis) and Matrix-Assisted Laser Desorption/Ionization (MALDI) spectrometry. The presence of 1-amino 2-naphthol, one of the hypothesized degradation products, was confirmed using mass spectrometry.

Production of verbs related to body movement in amyotrophic lateral sclerosis (ALS) and Parkinson's Disease (PD).

PubMed

Cousins, Katheryn A Q; Ash, Sharon; Grossman, Murray

2018-03-01

Theories of grounded cognition propose that action verb knowledge relies in part on motor processing regions, including premotor cortex. Accordingly, impaired action verb knowledge in patients with amyotrophic lateral sclerosis (ALS) and Parkinson's Disease (PD) is thought to be due to motor system degeneration. Upper motor neuron disease in ALS degrades the motor cortex and related pyramidal motor system, while disease in PD is centered in the basal ganglia and can spread to frontostriatal areas that are important to language functioning. These anatomical distinctions in disease may yield subtle differences in the action verb impairment between patient groups. Here we compare verbs where the body is the agent of the action to verbs where the body is the theme. To examine the role of motor functioning in body verb production, we split patient groups into patients with high motor impairment (HMI) and those with low motor impairment (LMI), using disease-specific measures of motor impairment. Regression analyses assessed how verb production in ALS and PD was related to motor system atrophy. We find a dissociation between agent- and theme-body verbs in ALS: ALS HMI were impaired for agent body verbs but not theme verbs, compared to ALS LMI. This dissociation was not present in PD patients, who instead show depressed production for all body verbs. Although patients with cognitive impairment were excluded from this study, cognitive performance significantly correlated with the production of theme verbs in ALS and cognitive/stative verbs in PD. Finally, regression analyses related the agent-theme dissociation in ALS to grey matter atrophy of premotor cortex. These findings support the view that motor dysfunction and disease in premotor cortex contributes to the agent body verb deficit in ALS, and begin to identify some distinct characteristics of impairment for verbs in ALS and PD. Copyright © 2017 Elsevier Ltd. All rights reserved.

Altered white matter microarchitecture in the cingulum bundle in women with primary dysmenorrhea: A tract-based analysis study.

PubMed

Liu, Jixin; Liu, Hongjuan; Mu, Junya; Xu, Qing; Chen, Tao; Dun, Wanghuan; Yang, Jing; Tian, Jie; Hu, Li; Zhang, Ming

2017-09-01

Primary dysmenorrhea (PD), as characterized by painful menstrual cramps without organic causes, is associated with central sensitization and brain function changes. Previous studies showed the integrated role of the default mode network (DMN) in the pain connectome and its key contribution on how an individual perceives and copes with pain disorders. Here, we aimed to investigate whether the cingulum bundle connecting hub regions of the DMN was disrupted in young women with PD. Diffusion tensor imaging was obtained in 41 PD patients and 41 matched healthy controls (HC) during their periovulatory phase. The production of prostaglandins (PGs) was obtained in PD patients during their pain-free and pain phases. As compared with HC, PD patients had similar scores of pain intensity, anxiety, and depression in their pain-free phase. However, altered white matter properties mainly located in the posterior section of the cingulum bundle were observed in PD. Besides PGs being related to menstrual pain, a close relationship was found between the white matter properties of the cingulum bundle during the pain-free phase and the severity of the menstrual pain in PD patients. Our study suggested that PD had trait changes of white matter integrities in the cingulum bundle that persisted beyond the time of menstruation. We inferred that altered anatomical connections may lead to less-flexible communication within the DMN, and/or between the DMN and other pain-related brain networks, which may result in the central susceptibility to develop chronic pain conditions in PD's later life. Hum Brain Mapp 38:4430-4443, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Interaction of polymorphisms in the genes encoding interleukin-6 and estrogen receptor beta on the susceptibility to Parkinson's disease.

PubMed

Håkansson, Anna; Westberg, Lars; Nilsson, Staffan; Buervenich, Silvia; Carmine, Andrea; Holmberg, Björn; Sydow, Olof; Olson, Lars; Johnels, Bo; Eriksson, Elias; Nissbrandt, Hans

2005-02-05

The multifunctional cytokine interleukin-6 (IL-6) is involved in inflammatory processes in the central nervous system and increased levels of IL-6 have been found in patients with Parkinson's disease (PD). It is known that estrogen inhibits the production of IL-6, via action on estrogen receptors, thereby pointing to an important influence of estrogen on IL-6. In a previous study, we reported an association between a G/A single nucleotide polymorphism (SNP) at position 1730 in the gene coding for estrogen receptor beta (ERbeta) and age of onset of PD. To investigate the influence of a G/C SNP at position 174 in the promoter of the IL-6 gene, and the possible interaction of this SNP and the ERbeta G-1730A SNP on the risk for PD, the G-174C SNP was genotyped, by pyrosequencing, in 258 patients with PD and 308 controls. A significantly elevated frequency of the GG genotype of the IL-6 SNP was found in the patient group and this was most obvious among patients with an early age of onset (

Unraveling the enhanced photocatalytic activity and phototoxicity of ZnO/metal hybrid nanostructures from generation of reactive oxygen species and charge carriers.

PubMed

He, Weiwei; Wu, Haohao; Wamer, Wayne G; Kim, Hyun-Kyung; Zheng, Jiwen; Jia, Huimin; Zheng, Zhi; Yin, Jun-Jie

2014-09-10

An effective way for promoting photocatalytic activity of a semiconductor is deposition of noble metal nanoparticles (NPs) onto it. In this paper, we deposited Ag and Pd onto ZnO NPs to form ZnO/Ag and ZnO/Pd hybrid nanostructures. It was found that both Ag and Pd nanocomponents can greatly enhance the photocatalytic activity and phototoxicity of ZnO toward human skin cells. Using electron spin resonance spectroscopy with spin trapping and spin labeling techniques, we observed that either deposition of Ag or Pd resulted in a significant increase in photogenerated electrons and holes and production of reactive oxygen species including hydroxyl radicals, superoxide, and singlet oxygen. We compared the enhancing effects of Ag and Pd and found that Pd is more effective than Ag in promoting the generation of hydroxyl radicals and holes and the photocatalytic activity of ZnO. Conversely, Ag is more effective than Pd in enhancing electron transfer and the generation of superoxide and singlet oxygen. The mechanism underlying the differences in the effects of Ag and Pd may be related to differences in Fermi levels for Ag and Pd and band bending accompanied by effects on Schottky barriers. The results of these studies provide information valuable for designing hybrid nanomaterials having photocatalytic and photobiological activities useful for applications such as water purification and formulation of antibacterial products.

Size control and catalytic activity of bio-supported palladium nanoparticles.

PubMed

Søbjerg, Lina Sveidal; Lindhardt, Anders T; Skrydstrup, Troels; Finster, Kai; Meyer, Rikke Louise

2011-07-01

The development of nanoparticles has greatly improved the catalytic properties of metals due to the higher surface to volume ratio of smaller particles. The production of nanoparticles is most commonly based on abiotic processes, but in the search for alternative protocols, bacterial cells have been identified as excellent scaffolds of nanoparticle nucleation, and bacteria have been successfully employed to recover and regenerate platinum group metals from industrial waste. We report on the formation of bio-supported palladium (Pd) nanoparticles on the surface of two bacterial species with distinctly different surfaces: the gram positive Staphylococcus sciuri and the gram negative Cupriavidus necator. We investigated how the type of bacterium and the amount of biomass affected the size and catalytic properties of the nanoparticles formed. By increasing the biomass:Pd ratio, we could produce bio-supported Pd nanoparticles smaller than 10nm in diameter, whereas lower biomass:Pd ratios resulted in particles ranging from few to hundreds of nm. The bio-supported Pd nanoparticle catalytic properties were investigated towards the Suzuki-Miyaura cross coupling reaction and hydrogenation reactions. Surprisingly, the smallest nanoparticles obtained at the highest biomass:Pd ratio showed no reactivity towards the test reactions. The lack of reactivity appears to be caused by thiol groups, which poison the catalyst by binding strongly to Pd. Different treatments intended to liberate particles from the biomass, such as burning or rinsing in acetone, did not re-establish their catalytic activity. Sulphur-free biomaterials should therefore be explored as more suitable scaffolds for Pd(0) nanoparticle formation. Copyright © 2011 Elsevier B.V. All rights reserved.

Occupational pesticide use and Parkinson's disease in the Parkinson Environment Gene (PEG) study.

PubMed

Narayan, Shilpa; Liew, Zeyan; Bronstein, Jeff M; Ritz, Beate

2017-10-01

To study the influence of occupational pesticide use on Parkinson's disease (PD) in a population with information on various occupational, residential, and household sources of pesticide exposure. In a population-based case control study in Central California, we used structured interviews to collect occupational history details including pesticide use in jobs, duration of use, product names, and personal protective equipment use from 360 PD cases and 827 controls. We linked reported products to California's pesticide product label database and identified pesticide active ingredients and occupational use by chemical class including fungicides, insecticides, and herbicides. Employing unconditional logistic regression, we estimated odds ratios and 95% confidence intervals for PD and occupational pesticide use. Ever occupational use of carbamates increased risk of PD by 455%, while organophosphorus (OP) and organochlorine (OC) pesticide use doubled risk. PD risk increased 110-211% with ever occupational use of fungicides, herbicides, and insecticides. Using any pesticide occupationally for >10years doubled the risk of PD compared with no occupational pesticide use. Surprisingly, we estimated higher risks among those reporting use of personal protective equipment (PPE). Our findings provide additional evidence that occupational pesticide exposures increase PD risk. This was the case even after controlling for other sources of pesticide exposure. Specifically, risk increased with occupational use of carbamates, OPs, and OCs, as well as of fungicides, herbicides, or insecticides. Interestingly, some types of PPE use may not provide adequate protection during pesticide applications. Copyright © 2017 Elsevier Ltd. All rights reserved.

Treatment of Parkinson's disease in rats by Nrf2 transfection using MRI-guided focused ultrasound delivery of nanomicrobubbles

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

Long, Ling; Cai, Xiaodong; Guo, Ruomi

Parkinson's disease (PD) is a very common neurological disorder. However, effective therapy is lacking. Although the blood-brain-barrier (BBB) protects the brain, it prevents the delivery of about 90% of drugs and nucleotides into the brain, thereby hindering the development of gene therapy for PD. Magnetic resonance imaging (MRI)-guided focused ultrasound delivery of microbubbles enhances the delivery of gene therapy vectors across the BBB and improves transfection efficiency. In the present study, we delivered nuclear factor E2-related factor 2 (Nrf2, NFE2L2) contained in nanomicrobubbles into the substantia nigra of PD rats by MRI-guided focused ultrasound, and we examined the effect ofmore » Nrf2 over-expression in this animal model of PD. The rat model of PD was established by injecting 6-OHDA in the right substantia nigra stereotactically. Plasmids (pDC315 or pDC315/Nrf2) were loaded onto nanomicrobubbles, and then injected through the tail vein with the assistance of MRI-guided focused ultrasound. MRI-guided focused ultrasound delivery of nanomicrobubbles increased gene transfection efficiency. Furthermore, Nrf2 gene transfection reduced reactive oxygen species levels, thereby protecting neurons in the target region. - Highlights: • MRI-guided focused ultrasound enhances gene transfection into the brain of rats. • Increased Nrf2 expression protects neurons in the rat model of PD. • Nrf2 protects neurons in PD by inhibiting ROS production.« less

Olfaction in Parkinson's disease and related disorders

PubMed Central

Doty, Richard L.

2012-01-01

Olfactory dysfunction is an early ‘pre-clinical’ sign of Parkinson's disease (PD). The present review is a comprehensive and up-to-date assessment of such dysfunction in PD and related disorders. The olfactory bulb is implicated in the dysfunction, since only those syndromes with olfactory bulb pathology exhibit significant smell loss. The role of dopamine in the production of olfactory system pathology is enigmatic, as overexpression of dopaminergic cells within the bulb's glomerular layer is a common feature of PD and most animal models of PD. Damage to cholinergic, serotonergic, and noradrenergic systems is likely involved, since such damage is most marked in those diseases with the most smell loss. When compromised, these systems, which regulate microglial activity, can influence the induction of localized brain inflammation, oxidative damage, and cytosolic disruption of cellular processes. In monogenetic forms of PD, olfactory dysfunction is rarely observed in asymptomatic gene carriers, but is present in many of those that exhibit the motor phenotype. This suggests that such gene-related influences on olfaction, when present, take time to develop and depend upon additional factors, such as those from aging, other genes, formation of α-synuclein- and tau-related pathology,or lowered thresholds to oxidative stress from toxic insults. The limited data available suggest that the physiological determinants of the early changes in PD-related olfactory function are likely multifactorial and may include the same determinants as those responsible for a number of other non-motor symptoms of PD, such as dysautonomia and sleep disturbances. PMID:22192366

Inflammation as a causative factor in the aetiology of Parkinson's disease

PubMed Central

Whitton, P S

2007-01-01

Parkinson's disease (PD) is a progressive neurodegenerative disorder affecting mainly the elderly, although a small proportion of PD patients develop the illness at a much younger age. In the former group, idiopathic PD patients, the causes of the illness have been the subject of longstanding debate with environmental toxins, mitochondrial dysfunction, abnormal protein handling and oxidative stress being suggested. One problem has been that the epidemiology of PD has offered few clues to provide evidence for a single major causative factor. Comparatively recently it has been found that in both patients and experimental models of PD in animals neuroinflammation appears to be a ubiquitous finding. These cases present with all of the classical features of inflammation including phagocyte activation, increased synthesis and release of proinflammatory cytokines and complement activation. Although this process is vital for normal function and protection in both the CNS, as in the periphery, it is postulated that in the aetiology of PD this process may spiral out of control with over activation of microglia, over production of cytokines and other proinflammatory mediators as well as the release of destructive molecules such as reactive oxygen species. Given that dopaminergic neurons in the substantia nigra are relatively vulnerable to ‘stress' and the region has a large population of microglia in comparison to other CNS structures, these events may easily trigger neurodegeneration. These factors are examined in this review along with a consideration of the possible use of anti-inflammatory drugs in PD. PMID:17339843

Palladium-catalyzed Reppe carbonylation.

PubMed

Kiss, G

2001-11-01

PdX2L2/L/HA (A = weakly coordinating anion, L = phosphine) complexes are active catalysts in the hydroesterification of alkenes, alkynes, and conjugated dienes. Shell, the only major corporate player in the field, recently developed two very active catalyst systems tailored to the hydroesterification of either alkenes or alkynes. The hydroesterification of propyne with their Pd(OAc)2/PN/HA (PN = (2-pyridyl)diphenylphosphine, HA = strong acid with weakly coordinating anion, like methanesulfonic acid) catalyst has been declared commercially ready. However, despite the significant progress in the activity of Pd-hydroesterification catalysts, further improvements are warranted. Thus, for example, activity maintenance still seems to be an issue. Homogeneous Pd catalysts are prone to a number of deactivation reactions. Activity and stability promoters are often corrosive and add to the complexity of the system, making it less attractive. Nonetheless, the versatility of the process and its tolerance toward the functional groups of substrates should appeal especially to the makers of specialty products. Although hydroesterification yields esters from alkenes, alkynes, and dienes in fewer steps than hydroformylation does, the latter has some advantages at the current state of the art. (1) Hydroformylation catalysts, particularly some recently published phosphine-modified Rh systems, can achieve very high regioselectivity for the linear product that hydroesterification catalysts cannot match yet. By analogy with hydroformylation, bulkier ligands ought to be tested in hydroesterification to increase normal-ester selectivity. (2) Hydroformylation is proven, commercial. Hydroesterification can only replace it if it can provide significant economic incentives. Similar or just marginally better performance could not justify the cost of development of a new technology. (3) Hydroesterification requires pure CO while hydroformylation uses syngas, a mixture of CO and H2. The latter is typically more available and less expensive (for industrial applications CO is most often separated from syngas). (4) The acid component of the hydroesterification catalyst makes the process corrosive. It would be desirable to develop new hydroesterification catalysts that do not require acid stabilizer/activity booster. Clearly, any new hydroesterification technology will directly compete with the hydroformylation route. This is especially true for olefin feeds, since both processes add one CO to the olefin, yielding oxygenates that can be converted into identical products. For some niche applications, like the production of MMA from propyne, hydroesterification seems to have an advantage as compared to hydroformylation due to the high activity and selectivity of the Pd(OAc)2/(2-pyridyl)diphenylphosphine catalyst. Since hydroesterification is an emerging technology, it is reasonable to assume that the potential for improvement is greater than in the mature hydroformylation. It is therefore possible that hydroesterification will become competitive in the future; thus, continued effort in the field is warranted.

Graft Product for Autologous Peripheral Blood Stem Cell Transplantation Enhances Thrombin Generation and Expresses Procoagulant Microparticles and Tissue Factor.

PubMed

Sidibe, Fatoumata; Spanoudaki, Anastasia; Vanneaux, Valerie; Mbemba, Elisabeth; Larghero, Jerome; Van Dreden, Patrick; Lotz, Jean-Pierre; Elalamy, Ismail; Larsen, Annette K; Gerotziafas, Grigoris T

2018-05-01

The beneficial effect of autologous peripheral blood stem cell transplantation (APBSCT) may be compromised by acute vascular complications related to hypercoagulability. We studied the impact of graft product on thrombin generation of normal plasma and the expression of tissue factor (TF) and procoagulant platelet-derived procoagulant microparticles (Pd-MPs) in samples of graft products. Graft products from 10 patients eligible for APBSCT were mixed with platelet-poor plasma (PPP) or platelet-rich plasma (PRP) from healthy volunteers and assessed for in vitro thrombin generation. In control experiments, thrombin generation was assessed in (1) PPP and PRP without any exogenous TF and/or procoagulant phospholipids, (2) PPP with the addition of TF (5 pM) and procoagulant phospholipids (4 μM), (3) in PRP with the addition of TF (5 pM). Graft products were assessed with Western blot assay for TF expression, with a specific clotting assay for TF activity and with flow cytometry assay for Pd-MPs. The graft product enhanced thrombin generation and its procoagulant activity was related to the presence of Pd-MPs and TF. The concentration of Pd-MPs in the graft product was characterized by a significant interindividual variability. The present study reveals the need for a thorough quality control of the graft products regarding their procoagulant potential.

Impact of Percutaneous Drainage on Outcome of Intra-abdominal Infection Associated With Pediatric Perforated Appendicitis.

PubMed

Bonadio, William; Langer, Miriam; Cueva, Julie; Haaland, Astrid

2017-10-01

Perforated appendicitis can result in potentially serious complications requiring prolonged medical care. The optimal approach to successfully managing this condition is controversial. Review of 80 consecutive cases of pediatric acute perforated appendicitis with intra-abdominal infection (IAI) medically managed with parenteral antibiotics and percutaneous drainage (PD) during a 7-year period. All patients received broad spectrum parenteral antibiotic therapy. One-third were hospitalized for >2 weeks. IAI was identified on admission in 60% compared with developing during hospitalization in 40% of cases. Before performing PD, the mean duration of antibiotic therapy in those who developed IAI during hospitalization was 6 days. IAI cultures yielded 127 bacterial isolates; polymicrobial infection occurred in 65% of cases. Only 7% of aspirates were sterile. The most common pathogens were Escherichia coli (82%), of which 5 isolates exhibited extended-spectrum β-lactamase production, and streptococci (40%). At the time of PD, 60% were febrile (mean duration of in-hospital fever, 7.5 days); 67% defervesced within 24 hours after the procedure. Posthospitalization abdominal complications (recurrent IAI or appendicitis) occurred in one-third of patients. Children with perforated appendicitis and IAI often have a complicated and prolonged clinical course. Medical management consisting solely of parenteral antibiotic therapy is frequently ineffective in resolving IAI. Rapid clinical improvement commonly follows PD.

A New Design Strategy for Observing Lithium Oxide Growth-Evolution Interactions Using Geometric Catalyst Positioning.

PubMed

Ryu, Won-Hee; Gittleson, Forrest S; Li, Jinyang; Tong, Xiao; Taylor, André D

2016-08-10

Understanding the catalyzed formation and evolution of lithium-oxide products in Li-O2 batteries is central to the development of next-generation energy storage technology. Catalytic sites, while effective in lowering reaction barriers, often become deactivated when placed on the surface of an oxygen electrode due to passivation by solid products. Here we investigate a mechanism for alleviating catalyst deactivation by dispersing Pd catalytic sites away from the oxygen electrode surface in a well-structured anodic aluminum oxide (AAO) porous membrane interlayer. We observe the cross-sectional product growth and evolution in Li-O2 cells by characterizing products that grow from the electrode surface. Morphological and structural details of the products in both catalyzed and uncatalyzed cells are investigated independently from the influence of the oxygen electrode. We find that the geometric decoration of catalysts far from the conductive electrode surface significantly improves the reaction reversibility by chemically facilitating the oxidation reaction through local coordination with PdO surfaces. The influence of the catalyst position on product composition is further verified by ex situ X-ray photoelectron spectroscopy and Raman spectroscopy in addition to morphological studies.

A new design strategy for observing lithium oxide growth-evolution interactions using geometric catalyst positioning

DOE PAGES

Ryu, Won -Hee; Gittleson, Forrest S.; Li, Jinyang; ...

2016-06-21

Understanding the catalyzed formation and evolution of lithium-oxide products in Li-O 2 batteries is central to the development of next-generation energy storage technology. Catalytic sites, while effective in lowering reaction barriers, often become deactivated when placed on the surface of an oxygen electrode due to passivation by solid products. Here we investigate a mechanism for alleviating catalyst deactivation by dispersing Pd catalytic sites away from the oxygen electrode surface in a well-structured anodic aluminum oxide (AAO) porous membrane interlayer. We observe the cross-sectional product growth and evolution in Li-O 2 cells by characterizing products that grow from the electrode surface.more » Morphological and structural details of the products in both catalyzed and uncatalyzed cells are investigated independently from the influence of the oxygen electrode. We find that the geometric decoration of catalysts far from the conductive electrode surface significantly improves the reaction reversibility by chemically facilitating the oxidation reaction through local coordination with PdO surfaces. Lastly, the influence of the catalyst position on product composition is further verified by ex situ Xray photoelectron spectroscopy and Raman spectroscopy in addition to morphological studies.« less

Production of an ordered (B2) CuPd nanoalloy by low-temperature annealing under hydrogen atmosphere.

PubMed

Yamauchi, Miho; Tsukuda, Tatsuya

2011-05-14

CuPd (1/1) nanoalloys composed of disordered body-centered-cubic crystals (crystal size = 1.6 nm) were prepared by synchronous reduction of Cu and Pd precursor ions with NaBH(4). In situ XRD measurement revealed that Cu and Pd atoms in the CuPd nanoalloys are arranged into an ordered B2 structure under exposure to H(2) (5 kPa) at 373 K. Ordering of Cu and Pd atoms over a longer distance (up to 3.6 nm) was achieved by annealing the nanoalloys for a longer time under a H(2) atmosphere.

Bicarbonate buffered peritoneal dialysis fluid upregulates angiopoietin-1 and promotes vessel maturation.

PubMed

Eich, Gwendolyn; Bartosova, Maria; Tischer, Christian; Wlodkowski, Tanja Tamara; Schaefer, Betti; Pichl, Sebastian; Kraewer, Nicole; Ranchin, Bruno; Vondrak, Karel; Liebau, Max Christoph; Hackert, Thilo; Schmitt, Claus Peter

2017-01-01

Ultrafiltration decline is a progressive issue for patients on chronic peritoneal dialysis (PD) and can be caused by peritoneal angiogenesis induced by PD fluids. A recent pediatric trial suggests better preservation of ultrafiltration with bicarbonate versus lactate buffered fluid; underlying molecular mechanisms are unknown. Angiogenic cytokine profile, tube formation capacity and Receptor Tyrosine Kinase translocation were assessed in primary human umbilical vein endothelial cells following incubation with bicarbonate (BPDF) and lactate buffered (LPDF), pH neutral PD fluid with low glucose degradation product content and lactate buffered, acidic PD fluid with high glucose degradation product content (CPDF). Peritoneal biopsies from age-, PD-vintage- and dialytic glucose exposure matched, peritonitis-free children on chronic PD underwent automated histomorphometry and immunohistochemistry. In endothelial cells angiopoietin-1 mRNA and protein abundance increased 200% upon incubation with BPDF, but decreased by 70% with LPDF as compared to medium control; angiopoietin-2 remained unchanged. Angiopoietin-1/Angiopoietin-2 protein ratio was 15 and 3-fold increased with BPDF compared to LPDF and medium. Time-lapse microscopy with automated network analysis demonstrated less endothelial cell tube formation with BPDF compared to LPDF and CPDF incubation. Receptor Tyrosine Kinase translocated to the cell membrane in BPDF but not in LPDF or CPDF incubated endothelial cells. In children dialyzed with BPDF peritoneal vessels were larger and angiopoietin-1 abundance in CD31 positive endothelium higher compared to children treated with LPDF. Bicarbonate buffered PD fluid promotes vessel maturation via upregulation of angiopoietin-1 in vitro and in children on dialysis. Our findings suggest a molecular mechanism for the observed superior preservation of ultrafiltration capacity with bicarbonate buffered PD fluid with low glucose degradation product content.

Vascular proliferation and enhanced expression of endothelial nitric oxide synthase in human peritoneum exposed to long-term peritoneal dialysis.

PubMed

Combet, S; Miyata, T; Moulin, P; Pouthier, D; Goffin, E; Devuyst, O

2000-04-01

Long-term peritoneal dialysis (PD) is associated with alterations in peritoneal permeability and loss of ultrafiltration. These changes originate from increased peritoneal surface area, but the morphologic and molecular mechanisms involved remain unknown. The hypothesis that modifications of activity and/or expression of nitric oxide synthase (NOS) isozymes might play a role in these modifications, via enhanced local production of nitric oxide, was tested in this study. NOS activities were measured by the L-citrulline assay in peritoneal biopsies from seven control subjects, eight uremic patients immediately before the onset of PD, and 13 uremic patients on short-term (<18 mo, n = 6) or long-term(>18 mo, n = 7) PD. Peritoneal NOS activity is increased fivefold in long-term PD patients compared with control subjects. In uremic patients, NOS activity is positively correlated with the duration of PD. Increased NOS activity is mediated solely by Ca(2+)-dependent NOS and, as shown by immunoblotting, an upregulation of endothelial NOS. The biologic relevance of increased NOS in long-term PD was demonstrated by enhanced nitrotyrosine immunoreactivity and a significant increase in vascular density and endothelial area in the peritoneum. Immunoblotting and immunostaining studies demonstrated an upregulation of vascular endothelial growth factor (VEGF) mostly along the endothelium lining peritoneal blood vessels in long-term PD patients. In the latter, VEGF colocalized with the advanced glycation end product pentosidine deposits. These data provide a morphologic (angiogenesis and increased endothelial area) and molecular (enhanced NOS activity and endothelial NOS upregulation) basis for explaining the permeability changes observed in long-term PD. They also support the implication of local advanced glycation end product deposits and liberation of VEGF in that process.

Targeting the programmed cell death 1: programmed cell death ligand 1 pathway reverses T cell exhaustion in patients with sepsis

PubMed Central

2014-01-01

Introduction A major pathophysiologic mechanism in sepsis is impaired host immunity which results in failure to eradicate invading pathogens and increased susceptibility to secondary infections. Although many immunosuppressive mechanisms exist, increased expression of the inhibitory receptor programmed cell death 1 (PD-1) and its ligand (PD-L1) are thought to play key roles. The newly recognized phenomenon of T cell exhaustion is mediated in part by PD-1 effects on T cells. This study tested the ability of anti-PD-1 and anti-PD-L1 antibodies to prevent apoptosis and improve lymphocyte function in septic patients. Methods Blood was obtained from 43 septic and 15 non-septic critically-ill patients. Effects of anti-PD-1, anti-PD-L1, or isotype-control antibody on lymphocyte apoptosis and interferon gamma (IFN-γ) and interleukin-2 (IL-2) production were quantitated by flow cytometry. Results Lymphocytes from septic patients produced decreased IFN-γ and IL-2 and had increased CD8 T cell expression of PD-1 and decreased PD-L1 expression compared to non-septic patients (P<0.05). Monocytes from septic patients had increased PD-L1 and decreased HLA-DR expression compared to non-septic patients (P<0.01). CD8 T cell expression of PD-1 increased over time in ICU as PD-L1, IFN-γ, and IL2 decreased. In addition, donors with the highest CD8 PD-1 expression together with the lowest CD8 PD-L1 expression also had lower levels of HLA-DR expression in monocytes, and an increased rate of secondary infections, suggestive of a more immune exhausted phenotype. Treatment of cells from septic patients with anti-PD-1 or anti-PD-L1 antibody decreased apoptosis and increased IFN-γ and IL-2 production in septic patients; (P<0.01). The percentage of CD4 T cells that were PD-1 positive correlated with the degree of cellular apoptosis (P<0.01). Conclusions In vitro blockade of the PD-1:PD-L1 pathway decreases apoptosis and improves immune cell function in septic patients. The current results together with multiple positive studies of anti-PD-1 and anti-PD-L1 in animal models of bacterial and fungal infections and the relative safety profile of anti-PD-1/anti-PD-L1 in human oncology trials to date strongly support the initiation of clinical trials testing these antibodies in sepsis, a disorder with a high mortality. PMID:24387680

Improved ethanol electrooxidation performance by shortening Pd-Ni active site distance in Pd-Ni-P nanocatalysts

NASA Astrophysics Data System (ADS)

Chen, Lin; Lu, Lilin; Zhu, Hengli; Chen, Yueguang; Huang, Yu; Li, Yadong; Wang, Leyu

2017-01-01

Incorporating oxophilic metals into noble metal-based catalysts represents an emerging strategy to improve the catalytic performance of electrocatalysts in fuel cells. However, effects of the distance between the noble metal and oxophilic metal active sites on the catalytic performance have rarely been investigated. Herein, we report on ultrasmall (~5 nm) Pd-Ni-P ternary nanoparticles for ethanol electrooxidation. The activity is improved up to 4.95 A per mgPd, which is 6.88 times higher than commercial Pd/C (0.72 A per mgPd), by shortening the distance between Pd and Ni active sites, achieved through shape transformation from Pd/Ni-P heterodimers into Pd-Ni-P nanoparticles and tuning the Ni/Pd atomic ratio to 1:1. Density functional theory calculations reveal that the improved activity and stability stems from the promoted production of free OH radicals (on Ni active sites) which facilitate the oxidative removal of carbonaceous poison and combination with CH3CO radicals on adjacent Pd active sites.

Nationwide peritoneal dialysis nurse training in Thailand: 3-year experience.

PubMed

Thaiyuenwong, Jutiporn; Mahatanan, Nanta; Jiravaranun, Somsong; Boonyakarn, Achara; Rodpai, Somrak; Eiam-Ong, Somchai; Tungsanga, Kriang; Dhanakijcharoen, Prateep; Kanjanabuch, Talerngsak

2011-09-01

Peritoneal dialysis (PD) center is not possible to operate if there is no availability of dedicated PD nurse. Generally, the nurse has to play many roles, including educator coordinator, and sometimes leader. As professionalism, the PD nurses need to have both theoretical and practical skills. With the tremendous leap of PD population after the launch of "PD First" policy in Thailand, the shortage of skillful PD nurse is concerned. Hence, the nationwide PD nurse training course was established with the collaborations of many organizations and institutes. Until now, 3 generations of 225 PD nurses are the productions of the course. This number represents 80 percent of PD nurses distributed throughout the whole nation. The survey operated in the year 2010 demonstrated that the output of the course was acceptable in terms of quality since most of the trained PD nurses had a confidence in taking care of PD patients. The quality of patient care is good as indicated by KPIs.

A quantitative approach to developing Parkinsonian monkeys (Macaca fascicularis) with intracerebroventricular 1-methyl-4-phenylpyridinium injections.

PubMed

Li, Hao; Lei, Xiaoguang; Huang, Baihui; Rizak, Joshua D; Yang, Lichuan; Yang, Shangchuan; Wu, Jing; Lü, Longbao; Wang, Jianhong; Yan, Ting; Li, Hongwei; Wang, Zhengbo; Hu, Yingzhou; Le, Weidong; Deng, Xingli; Li, Jiali; Xu, Lin; Zhang, Baorong; Hu, Xintian

2015-08-15

Non-human primate Parkinson's disease (PD) models are essential for PD research. The most extensively used PD monkey models are induced with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). However, the modeling processes of developing PD monkeys cannot be quantitatively controlled with MPTP. Therefore, a new approach to quantitatively develop chronic PD monkey models will help to advance the goals of "reduction, replacement and refinement" in animal experiments. A novel chronic PD monkey models was reported using the intracerebroventricular administration of 1-methyl-4-phenylpyridinium (MPP(+)) in Cynomolgus monkeys (Macaca fascicularis). This approach successfully produced stable and consistent PD monkeys with typical motor symptoms and pathological changes. More importantly, a sigmoidal relationship (Y=8.15801e(-0.245/x); R=0.73) was discovered between PD score (Y) and cumulative dose of MPP(+) (X). This relationship was then used to develop two additional PD monkeys under a specific time schedule (4 weeks), with planned PD scores (7) by controlling the dose and frequency of the MPP(+) administration as an independent validation of the formula. We developed Parkinsonian monkeys within controlled time frames by regulating the accumulated dose of MPP(+) intracerebroventricular administered, while limiting side effects often witnessed in models developed with the peripheral administration of MPTP, makes this model highly suitable for treatment development. This novel approach provides an edge in evaluating the mechanisms of PD pathology associated with environmental toxins and novel treatment approaches as the formula developed provides a "map" to control and predict the modeling processes. Copyright © 2015 Elsevier B.V. All rights reserved.

Impairments of Speech Fluency in Lewy Body Spectrum Disorder

ERIC Educational Resources Information Center

Ash, Sharon; McMillan, Corey; Gross, Rachel G.; Cook, Philip; Gunawardena, Delani; Morgan, Brianna; Boller, Ashley; Siderowf, Andrew; Grossman, Murray

2012-01-01

Few studies have examined connected speech in demented and non-demented patients with Parkinson's disease (PD). We assessed the speech production of 35 patients with Lewy body spectrum disorder (LBSD), including non-demented PD patients, patients with PD dementia (PDD), and patients with dementia with Lewy bodies (DLB), in a semi-structured…

Enhanced tumor control with combination mTOR and PD-L1 inhibition in syngeneic oral cavity cancers

PubMed Central

Moore, Ellen C.; Cash, Harrison A.; Caruso, Andria M.; Uppaluri, Ravindra; Hodge, James W.; Van Waes, Carter; Allen, Clint T.

2016-01-01

Significant subsets of patients with oral cancer fail to respond to single-agent programmed death (PD) blockade. Syngeneic models of oral cancer were used to determine if blocking oncogenic signaling improved in vivo responses to PD-L1 monoclonal antibody (mAb). Anti-PD-L1 enhanced durable primary tumor control and survival when combined with mTOR (rapamycin), but not in combination with MEK inhibition (PD901) in immunogenic MOC1 tumors. Conversely, PD-L1 mAb did not enhance tumor control in poorly immunogenic MOC2 tumors. Rapamycin enhanced expansion of peripheral antigen-specific CD8 T cells and IFNγ production following ex vivo antigen stimulation. More CD8 T cells infiltrated and were activated after PD-L1 mAb treatment in mice with immunogenic MOC1 tumors, which was stable or increased by the addition of rapamycin, but suppressed when PD901 was added. Rapamycin increased IFNγ production capacity in peripheral and tumor-infiltrating CD8 T cells. In vivo antibody depletion revealed a CD8 T cell, and not NK cell, -dependent mechanism of tumor growth inhibition after treatment with rapamycin and PD-L1 mAb, ruling out significant effects from NK cell–mediated antibody-dependent cellular cytotoxicity. Rapamycin also enhanced IFNγ or PD-L1 mAb treatment–associated induction of MHC class I expression on MOC1 tumor cells, an effect abrogated by depleting infiltrating CD8 T cells from the tumor microenvironment. This data conflicts with traditional views of rapamycin as a universal immunosuppressant, and when combined with evidence of enhanced antitumor activity with the combination of rapamycin and PD-L1 mAb, suggests that this treatment combination deserves careful evaluation in the clinical setting. PMID:27076449

Mobilizing the Forgotten Army: Improving Undergraduate Math and Science Education through Professional Development of Graduate Teaching Assistants

NASA Astrophysics Data System (ADS)

Gerton, Jordan

Evidence-based best practices for improving undergraduate STEM education abound. Unfortunately, these practices have not been widely adopted, in part because typical dissemination efforts are mediated in a top-down fashion and fail to obtain critical buy-in from key local stakeholders. Here, we present a novel framework to increase nationwide uptake of STEM-education best practices through grassroots propagation of Professional Development programs for Graduate Teaching Assistants (GTA-PD). Our model pays special attention to overcoming resistance to change by soliciting, from the very start, critical buy-in from departmental chairs, faculty, and GTAs who have direct control over and responsibility for instruction. A key component of our approach involves an annual National GTA Workshop where faculty-GTA leadership teams from many different Physics and Chemistry departments come together to develop best-practices-based GTA-PD improvement plans for their own departments while guided by a core group of nationally recognized expert practitioners in GTA-PD and STEM education. As a pre-condition for participation, each department chair must pledge to facilitate implementation of their leadership team's plan; additional and ongoing support is provided by the core group of experts, together with other teams from the workshop cohort. Our initial pilot efforts point to success via enthusiastic buy-in within each STEM department due to the potential for immediate positive impacts on both undergraduate instruction and the long term research productivity of GTAs. In the future, longitudinal data on the progress of the GTA-PD programs will be gathered and analyzed to provide guidance for improving the success of future GTA-PD programs. Financial support provided by the Research Corporation for Science Advancement and the American Chemical Society.

Mild deoxygenation of aromatic ketones and aldehydes over Pd/C using polymethylhydrosiloxane as the reducing agent.

PubMed

Volkov, Alexey; Gustafson, Karl P J; Tai, Cheuk-Wai; Verho, Oscar; Bäckvall, Jan-E; Adolfsson, Hans

2015-04-20

Herein, a practical and mild method for the deoxygenation of a wide range of benzylic aldehydes and ketones is described, which utilizes heterogeneous Pd/C as the catalyst together with the green hydride source, polymethylhydrosiloxane. The developed catalytic protocol is scalable and robust, as exemplified by the deoxygenation of ethyl vanillin, which was performed on a 30 mmol scale in an open-to-air setup using only 0.085 mol % Pd/C catalyst to furnish the corresponding deoxygenated product in 93 % yield within 3 hours at room temperature. Furthermore, the Pd/C catalyst was shown to be recyclable up to 6 times without any observable decrease in efficiency and it exhibited low metal leaching under the reaction conditions. © 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

A natural product from Cannabis sativa subsp. sativa inhibits homeodomain-interacting protein kinase 2 (HIPK2), attenuating MPP+-induced apoptosis in human neuroblastoma SH-SY5Y cells.

PubMed

Wang, Guan; Zhu, Lingjuan; Zhao, Yuqian; Gao, Suyu; Sun, Dejuan; Yuan, Jingquan; Huang, Yuxin; Zhang, Xue; Yao, Xinsheng

2017-06-01

Homeodomain-interacting protein kinase 2 (HIPK2) is a conserved serine/threonine kinase, which regulate transcription, cell differentiation, proliferation and apoptosis. Previous evidences indicated that HIPK2 could be involved in the pathogenesis of neurodegenerative diseases, suggesting as a novel target for Parkinson's disease (PD) therapeutic development. Herein, gene microarray analysis was performed to verify the key regulatory function of HIPK2 in PD. (Z)-methylp-hydroxycinnamate (ZMHC, 7) with other eighteen compounds were isolated from Cannabis sativa subsp. sativa, growing in Bama Yao Autonomous County, one of the five largest longevity regions of the world. Intriguingly, ZMHC was identified to bind HIPK2 with high affinity through molecular modeling and molecular dynamics (MD) simulations. Moreover, cell morphology, flow cytometry and western blot assay suggested that ZMHC inhibited HIPK2, which attenuated MPP + -induced apoptosis in SH-SY5Y cells. In conclusion, these findings discovered a natural product that inhibited HIPK2, and highlighted that ZMHC could be a potential precursor agent for future PD therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

KSC-04pd1397

NASA Image and Video Library

2004-06-30

KENNEDY SPACE CENTER, FLA. - Kimberly Beck, a college trainee in Controlled Biological Systems in the Spaceflight and Life Sciences Training Program, is helping with growth studies supporting payload development. Behind her is part of the WONDER (Water Offset Nutrient Delivery Experiment) flight payload that is investigating hydroponic plant crop production in microgravity.

KSC-04PD-1397

NASA Technical Reports Server (NTRS)

2004-01-01

KENNEDY SPACE CENTER, FLA. Kimberly Beck, a college trainee in Controlled Biological Systems in the Spaceflight and Life Sciences Training Program, is helping with growth studies supporting payload development. Behind her is part of the WONDER (Water Offset Nutrient Delivery Experiment) flight payload that is investigating hydroponic plant crop production in microgravity.

Available Resources | Division of Cancer Prevention

Cancer.gov

Preclinical pharmacology and efficacy studies Identification and evaluation of intermediate biomarkers Formulation optimization for enhanced bioavailability and clinical usefulness Analytical method development for investigational agents in bulk form and in biological fluids and tissues PK and PK-PD modeling to optimize dosing regimen Scale-up non-cGMP and cGMP production of

Contribution of programmed cell death receptor (PD)-1 to Kupffer cell dysfunction in murine polymicrobial sepsis.

PubMed

Wang, Fei; Huang, Xin; Chung, Chun-Shiang; Chen, Yaping; Hutchins, Noelle A; Ayala, Alfred

2016-08-01

Recent studies suggest that coinhibitory receptors appear to be important in contributing sepsis-induced immunosuppression. Our laboratory reported that mice deficient in programmed cell death receptor (PD)-1 have increased bacterial clearance and improved survival in experimental sepsis induced by cecal ligation and puncture (CLP). In response to infection, the liver clears the blood of bacteria and produces cytokines. Kupffer cells, the resident macrophages in the liver, are strategically situated to perform the above functions. However, it is not known if PD-1 expression on Kupffer cells is altered by septic stimuli, let alone if PD-1 ligation contributes to the altered microbial handling seen. Here we report that PD-1 is significantly upregulated on Kupffer cells during sepsis. PD-1-deficient septic mouse Kupffer cells displayed markedly enhanced phagocytosis and restoration of the expression of major histocompatibility complex II and CD86, but reduced CD80 expression compared with septic wild-type (WT) mouse Kupffer cells. In response to ex vivo LPS stimulation, the cytokine productive capacity of Kupffer cells derived from PD-1-/- CLP mice exhibited a marked, albeit partial, restoration of the release of IL-6, IL-12, IL-1β, monocyte chemoattractant protein-1, and IL-10 compared with septic WT mouse Kupffer cells. In addition, PD-1 gene deficiency decreased LPS-induced apoptosis of septic Kupffer cells, as indicated by decreased levels of cleaved caspase-3 and reduced terminal deoxynucleotidyl transferase dUTP nick end-labeling-positive cells. Exploring the signal pathways involved, we found that, after ex vivo LPS stimulation, septic PD-1-/- mouse Kupffer cells exhibited an increased Akt phosphorylation and a reduced p38 phosphorylation compared with septic WT mouse Kupffer cells. Together, these results indicate that PD-1 appears to play an important role in regulating the development of Kupffer cell dysfunction seen in sepsis. Copyright © 2016 the American Physiological Society.

Contribution of programmed cell death receptor (PD)-1 to Kupffer cell dysfunction in murine polymicrobial sepsis

PubMed Central

Wang, Fei; Huang, Xin; Chung, Chun-Shiang; Chen, Yaping; Hutchins, Noelle A.

2016-01-01

Recent studies suggest that coinhibitory receptors appear to be important in contributing sepsis-induced immunosuppression. Our laboratory reported that mice deficient in programmed cell death receptor (PD)-1 have increased bacterial clearance and improved survival in experimental sepsis induced by cecal ligation and puncture (CLP). In response to infection, the liver clears the blood of bacteria and produces cytokines. Kupffer cells, the resident macrophages in the liver, are strategically situated to perform the above functions. However, it is not known if PD-1 expression on Kupffer cells is altered by septic stimuli, let alone if PD-1 ligation contributes to the altered microbial handling seen. Here we report that PD-1 is significantly upregulated on Kupffer cells during sepsis. PD-1-deficient septic mouse Kupffer cells displayed markedly enhanced phagocytosis and restoration of the expression of major histocompatibility complex II and CD86, but reduced CD80 expression compared with septic wild-type (WT) mouse Kupffer cells. In response to ex vivo LPS stimulation, the cytokine productive capacity of Kupffer cells derived from PD-1−/− CLP mice exhibited a marked, albeit partial, restoration of the release of IL-6, IL-12, IL-1β, monocyte chemoattractant protein-1, and IL-10 compared with septic WT mouse Kupffer cells. In addition, PD-1 gene deficiency decreased LPS-induced apoptosis of septic Kupffer cells, as indicated by decreased levels of cleaved caspase-3 and reduced terminal deoxynucleotidyl transferase dUTP nick end-labeling-positive cells. Exploring the signal pathways involved, we found that, after ex vivo LPS stimulation, septic PD-1−/− mouse Kupffer cells exhibited an increased Akt phosphorylation and a reduced p38 phosphorylation compared with septic WT mouse Kupffer cells. Together, these results indicate that PD-1 appears to play an important role in regulating the development of Kupffer cell dysfunction seen in sepsis. PMID:27288425

Power partial-discard strategy to obtain improved performance for simulated moving bed chromatography.

PubMed

Chung, Ji-Woo; Kim, Kyung-Min; Yoon, Tae-Ung; Kim, Seung-Ik; Jung, Tae-Sung; Han, Sang-Sup; Bae, Youn-Sang

2017-12-22

A novel power partial-discard (PPD) strategy was developed as a variant of the partial-discard (PD) operation to further improve the separation performance of the simulated moving bed (SMB) process. The PPD operation varied the flow rates of discard streams by introducing a new variable, the discard amount (DA) as well as varying the reported variable, discard length (DL), while the conventional PD used fixed discard flow rates. The PPD operations showed significantly improved purities in spite of losses in recoveries. Remarkably, the PPD operation could provide more enhanced purity for a given recovery or more enhanced recovery for a given purity than the PD operation. The two variables, DA and DL, in the PPD operation played a key role in achieving the desired purity and recovery. The PPD operations will be useful for attaining high-purity products with reasonable recoveries. Copyright © 2017 Elsevier B.V. All rights reserved.

Development of sustainable Palladium-based catalysts for removal of persistent contaminants from drinking water

NASA Astrophysics Data System (ADS)

Shuai, Danmeng

Pd-based catalytic reduction has emerged as an advanced treatment technology for drinking water decontamination, and a suite of persistent contaminants including oxyanions, N-nitrosoamines, and halogenated compounds are amenable to catalytic reduction. The primary goal of this study is to develop novel Pd-based catalysts with enhanced performance (i.e., activity, selectivity, and sustainability) to remove contaminants from drinking water. The effects of water quality (i.e., co-contaminants in water matrix), catalyst support, and catalyst metal were explored, and they provide insights for preparing catalysts with faster kinetics, higher selectivity, and extended lifetime. Azo dyes are wide-spread contaminants, and they are potentially co-exisiting with target contaminants amenable for catalytic removal. The probe azo dye methyl orange (MO) enhanced catalytic reduction kinetics of a suite of oxyanions (i.e., nitrate, nitrite, bromate, chlorate, and perchlorate) and diatrizoate significantly but not N-nitrosodimethylamine (NDMA) with a variety of Pd-based catalysts. Nitrate was selected as a probe contaminant, and several different azo dyes (i.e., (methyl orange, methyl red, fast yellow AB, metanil yellow, acid orange 7, congo red, eriochrome black T, acid red 27, acid yellow 11, and acid yellow 17) were evaluated for their ability to enhance reduction. A hydrogen atom shuttling mechanism was proposed and a kinetic model was proposed based on Bronsted-Evans-Polanyi (BEP) theory, and they suggest sorbed azo dyes and reduced hydrazo dyes shuttle hydrogen atoms to oxyanions or diatrizoate to enhance their reduction kinetics. Next, vapor-grown carbon nanofiber (CNF) supports were used to explore the effects of Pd nanoparticle size and interior versus exterior loading on nitrite reduction activity and selectivity (i.e., dinitrogen over ammonia production). In order to evaluate the amount of interior versus exterior loading of Pd nanoparticles, a fast and accurate geometric model was developed based on two-dimensional transmission electron microscopy (2D TEM). Results from my method agree adequately with 3D scanning transmission electron microscopy (3D TEM), which is recognized as a convincing method to evaluate interior versus exterior loading. By using Pd CNF catalysts for nitrite reduction, results show that both activity and selectivity are not significantly impacted by Pd interior versus exterior loading. Turnover frequencies (TOFs) among all CNF catalysts are consistent, suggesting faster kinetics are achieved on catalysts with smaller Pd nanoparticles, and suggesting nitrite reduction is neither sensitive to Pd location on CNFs nor Pd structure. However selectivity to dinitrogen is more favorable on larger Pd nanoparticles. Therefore, an optimum Pd nanoparticle size on CNFs balances high reduction kinetics and selectivity to dinitrogen. CNF Pd catalysts perform better than conventional activated or alumina supported Pd catalysts in term of kinetics and selectivity for nitrite reduction, and they maintain consistent activity during multiple reduction cycles. Lastly, the structure-sensitivity of catalytic activity and selectivity for contaminant nitrite, NDMA, and diatrizoate removal were investigated on shape- and size-controlled Pd nanoparticles. Results show that TOFs for nitrite, NDMA, and diatrizoate are dependent on coordination numbers of surface Pd sites at low contaminant concentration, but TOFs for nitrite at high concentration are consistent. Selectivity to ammonia for nitrite reduction decreases with increasing surface Pd sites, i.e., decreasing Pd nanoparticle size irrespective of nitrite concentration, but NDMA reduction is neither shape- nor size-specific, and it exclusively proceeds to ammonia and dimethylamine. Diatrizoate reduction selectivity is also likely to be nonspecific to shape and size, and a series of deiodinated intermediates, 3,5-diacetamidobenzoic acid, and iodide are the produced. Hence, this study suggests that contaminant reduction kinetics and selectivity are Pd shape and size dependent, and the dependence varies by contaminant type and concentration. In summary, Pd-based catalysts can be tailored for enhanced activity, selectivity, and longevity, and catalytic treatment holds the promise for advanced drinking water treatment.

Hydrogenolysis of α-methylbenzyl alcohol to ethylbenzene over Pd/C catalyst

NASA Astrophysics Data System (ADS)

Feng, J.; Zhong, Y. H.; Dai, S. H.

2018-01-01

The hydrogenolysis of α-methylbenzyl alcohol (MBA) to ethylbenzene (EB) over Pd/C catalyst was studied. The XRD and TEM results show that Pd nanoparticles are well dispersed on the carbon support with good crystallinity. There is no 1-cyclohexylethanol or ethylcyclohexane in the products, indicating that Pd/C is excellent for inhibiting the hydrogenation of the aromatic ring. Alcohol solvents are beneficial to increase the catalytic activity because of their strong polarity and good solubility.

TRYCAT pathways link peripheral inflammation, nicotine, somatization and depression in the etiology and course of Parkinson's disease.

PubMed

Anderson, George; Maes, Michael

2014-02-01

Increased depression, somatization, gut inflammation and wider peripheral inflammation are all associated with the early stages of Parkinson's disease (PD). Classically such concurrent conditions have been viewed as "comorbidities", driven by high levels of stress in a still poorly understood and treated disorder. Here we review the data on how oxidative and nitrosative stress in association with immuno-inflammatory responses, drives alteration in tryptophan catabolites, including kynurenine, kynurenic acid and quinolinic acid that drive not only the 'comorbidities" of PD but also important processes in the etiology and course of PD per se. The induction of indoleamine 2,3-dioxygenase, leading to the driving of tryptophan into neuroregulatory tryptophan catabolite products and away from serotonin and melatonin production, has significant implications for understanding the role of nicotine, melatonin, and caffeine in regulating PD susceptibility. Tryptophan catabolite pathway activation will also regulate blood-brain barrier permeability, glia and mast cell reactivity as well as wider innate and adaptive immune cell responses, all relevant to the course of PD. As such, the "comorbidities" of PD such as depression, somatization and peripheral inflammatory disorders can all be conceptualized as being an intricate part of the biological underpinnings of both the etiology and course of PD. As a consequence, the data reviewed here has treatment implications; relevant to both the course of PD and in the management of L-DOPA induced dyskinesias.

PD2P: PanDA Dynamic Data Placement for ATLAS

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

Maeno, T.; De, K.; Panitkin, S.

2012-12-13

The PanDA (Production and Distributed Analysis) system plays a key role in the ATLAS distributed computing infrastructure. PanDA is the ATLAS workload management system for processing all Monte-Carlo (MC) simulation and data reprocessing jobs in addition to user and group analysis jobs. The PanDA Dynamic Data Placement (PD2P) system has been developed to cope with difficulties of data placement for ATLAS. We will describe the design of the new system, its performance during the past year of data taking, dramatic improvements it has brought about in the efficient use of storage and processing resources, and plans for the future.

Pd-Metalated Conjugated Nanoporous Polycarbazoles for Additive-Free Cyanation of Aryl Halides: Boosting Catalytic Efficiency through Spatial Modulation

DOE PAGES

Ding, Shunmin; Tian, Chengcheng; Zhu, Xiang; ...

2017-03-23

Transition-metal-catalyzed cyanation of aryl halides is a common route to benzonitriles, which are integral to many industrial procedures. However, traditional homogeneous catalysts for such processes are expensive and suffer poor recyclability, so a heterogeneous analogue is highly desired. A novel spatial modulation approach has been developed in this paper to fabricate a heterogeneous Pd-metalated nanoporous polymer, which catalyzes the cyanation of aryl halides without need for ligands. Finally, the catalyst displays high activity in the synthesis of benzonitriles, including high product yields, excellent stability and recycling, and broad functional-group tolerance.

Water homeostasis and diabetes insipidus in horses.

PubMed

Schott, Harold C

2011-04-01

Diabetes insipidus (DI) is a rare disorder of horses characterized by profound polyuria and polydipsia (PU/PD), which can be caused by loss of production of arginine vasopressin (AVP). This condition is termed neurogenic or central DI. DI may also develop with absence or loss of AVP receptors or activity on the basolateral membrane of collecting-duct epithelial cells. This condition is termed nephrogenic DI. Equine clinicians may differentiate true DI from more common causes of PU/PD by a systematic diagnostic approach. DI may not be a correctable disorder, and supportive care of affected horses requires an adequate water source. Copyright © 2011 Elsevier Inc. All rights reserved.

PD-1 regulates extrathymic regulatory T-cell differentiation

PubMed Central

Chen, Xiufen; Fosco, Dominick; Kline, Douglas E.; Meng, Liping; Nishi, Saki; Savage, Peter A.; Kline, Justin

2014-01-01

Regulatory T (Treg) cells and the programmed death-1/programmed death ligand-1 (PD-1/PD-L1) pathway are both critical for maintaining peripheral tolerance to self antigens. A significant subset of Treg cells constitutively expresses PD-1, which prompted an investigation into the role of PD-1/PD-L1 interactions in Treg-cell development, function and induction in vivo. The phenotype and abundance of Treg cells was not significantly altered in PD-1-deficient mice. The thymic development of polyclonal and monospecific Treg cells was not negatively impacted by PD-1 deficiency. The suppressive function of PD-1−/− Treg cells was similar to their PD-1+/+ counterparts both in vitro and in vivo. However, in three different in vivo experimental settings, PD-1−/− conventional CD4+ T cells demonstrated a strikingly diminished tendency toward differentiation into peripherally induced Treg (pTreg) cells. Our results demonstrate that PD-1 is dispensable for thymic (tTreg) Treg-cell development and suppressive function, but is critical for the extrathymic differentiation of pTreg cells in vivo. These data suggest that antibody blockade of the PD-1/PD-L1 pathway may augment T-cell responses by acting directly on conventional T cells, and also by suppressing the differentiation of pTreg cells. PMID:24975127

Synthesis and antimicrobial activity of palladium nanoparticles from Prunus × yedoensis leaf extract

USDA-ARS?s Scientific Manuscript database

The eco-friendly production of palladium nanoparticles (PdNPs) by Prunus × yedoensis tree leaf extract was studied for the first time. Initial confirmation of PdNP production was confirmed by a color change from light yellow to dark brown. The optimization parameters show that pH 7, 8% leaf extract,...

A convenient method for determination of malathion based on the resonance Rayleigh scattering enhancement

NASA Astrophysics Data System (ADS)

Wu, Huan; Zhao, Yanmei; Tan, Xuanping; Huang, Yunmei; Yuan, Haiyan; Yang, Jidong

2017-09-01

A convenient method for determination of malathion (Mala) based on resonance Rayleigh scattering (RRS) enhancement of L-Tryptophan (L-Try)-Pd(II)-Mala system was proposed in this paper. The interaction between L-Try, Pd(II) and malathion in the system was investigated by fluorescence, RRS and UV-Vis absorption spectroscopy. In the optimum conditions, the RRS intensity of L-Try-Pd(II)-Mala system had a remarkable enhancement because the hydrolysis products of malathion would interact with Pd(II) and L-Try each other formed new complexes, which enhanced intensity was directly proportional to the malathion concentration within a certain range. Based on the RRS enhancement of L-Try-Pd(II) system by Mala, a novel, convenient and specific method for Mala determination was developed. To our knowledge, the method is the first RRS method for determination of Mala was reported. The detection limit for Mala was 6.7 ng/mL and the quantitative determination range was 0.06-0.6 μg/mL. The influence of coexisting substances on RRS was also investigated, and the RRS method exhibited good anti-interference ability. The new analytical method has been applied to determine of malathion in real samples with satisfactory results.

Plasma breakdown in a capacitively-coupled radiofrequency argon discharge

NASA Astrophysics Data System (ADS)

Smith, H. B.; Charles, C.; Boswell, R. W.

1998-10-01

Low pressure, capacitively-coupled rf discharges are widely used in research and commercial ventures. Understanding of the non-equilibrium processes which occur in these discharges during breakdown is of interest, both for industrial applications and for a deeper understanding of fundamental plasma behaviour. The voltage required to breakdown the discharge V_brk has long been known to be a strong function of the product of the neutral gas pressure and the electrode seperation (pd). This paper investigates the dependence of V_brk on pd in rf systems using experimental, computational and analytic techniques. Experimental measurements of V_brk are made for pressures in the range 1 -- 500 mTorr and electrode separations of 2 -- 20 cm. A Paschen-style curve for breakdown in rf systems is developed which has the minimum breakdown voltage at a much smaller pd value, and breakdown voltages which are significantly lower overall, than for Paschen curves obtained from dc discharges. The differences between the two systems are explained using a simple analytic model. A Particle-in-Cell simulation is used to investigate a similar pd range and examine the effect of the secondary emission coefficient on the rf breakdown curve, particularly at low pd values. Analytic curves are fitted to both experimental and simulation results.

Hydrolytic cleavage of both CS2 carbon-sulfur bonds by multinuclear Pd(II) complexes at room temperature

NASA Astrophysics Data System (ADS)

Jiang, Xuan-Feng; Huang, Hui; Chai, Yun-Feng; Lohr, Tracy Lynn; Yu, Shu-Yan; Lai, Wenzhen; Pan, Yuan-Jiang; Delferro, Massimiliano; Marks, Tobin J.

2017-02-01

Developing homogeneous catalysts that convert CS2 and COS pollutants into environmentally benign products is important for both fundamental catalytic research and applied environmental science. Here we report a series of air-stable dimeric Pd complexes that mediate the facile hydrolytic cleavage of both CS2 carbon-sulfur bonds at 25 °C to produce CO2 and trimeric Pd complexes. Oxidation of the trimeric complexes with HNO3 regenerates the dimeric starting complexes with the release of SO2 and NO2. Isotopic labelling confirms that the carbon and oxygen atoms of CO2 originate from CS2 and H2O, respectively, and reaction intermediates were observed by gas-phase and electrospray ionization mass spectrometry, as well as by Fourier transform infrared spectroscopy. We also propose a plausible mechanistic scenario based on the experimentally observed intermediates. The mechanism involves intramolecular attack by a nucleophilic Pd-OH moiety on the carbon atom of coordinated µ-OCS2, which on deprotonation cleaves one C-S bond and simultaneously forms a C-O bond. Coupled C-S cleavage and CO2 release to yield [(bpy)3Pd3(µ3-S)2](NO3)2 (bpy, 2,2‧-bipyridine) provides the thermodynamic driving force for the reaction.

Early and advanced glycosylation end products. Kinetics of formation and clearance in peritoneal dialysis.

PubMed Central

Friedlander, M A; Wu, Y C; Elgawish, A; Monnier, V M

1996-01-01

The chronic contact of glucose-containing dialysate and proteins results in the deposition of advanced glycation end products (AGEs) on peritoneal tissues in patients treated by peritoneal dialysis (PD), yet plasma levels of the AGE pentosidine are significantly lower in PD than in hemodialysis (HD). We measured glycation of peritoneal proteins in patients on PD over the time course of intraperitoneal equilibration of fresh peritoneal dialysate. The glycated content of peritoneal proteins (furosine method) was initially identical to plasma but increased 200% within 4 h due to in situ glycation as also demonstrated in vitro. In contrast, peritoneal proteins contained a 2-4 x greater content of the AGE pentosidine at all equilibrium time points. Plasma protein furosine content was identical in patients on PD and on HD. Fractionation by gel filtration of serum from patients on PD and HD revealed that > 95% of the pentosidine was linked to proteins > 10,000 mol wt; < 1% to proteins < 10,000 mol wt; and < 1%, free. Neither HD nor PD affected protein-bound pentosidine. The HD treatment decreased free and < 10,000 mol wt bound pentosidine. However clearance of protein-associated pentosidine by the peritoneal membrane may explain lower steady state levels in patients treated by PD. PMID:8609229

Electrochemical Reduction of CO2 to Organic Acids by a Pd-MWNTs Gas-Diffusion Electrode in Aqueous Medium

PubMed Central

Lu, Guang; Bian, Zhaoyong; Liu, Xin

2013-01-01

Pd-multiwalled carbon nanotubes (Pd-MWNTs) catalysts for the conversion of CO2 to organic acids were prepared by the ethylene glycol reduction and fully characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), transmission electron microscope (TEM), X-ray photoelectron spectroscopy (XPS), and cyclic voltammetry (CV) technologies. The amorphous Pd particles with an average size of 5.7 nm were highly dispersed on the surface of carbon nanotubes. Functional groups of the MWNTs played a key role in the palladium deposition. The results indicated that Pd-MWNTs could transform CO2 into organic acid with high catalytic activity and CO2 could take part in the reduction reaction directly. Additionally, the electrochemical reduction of CO2 was investigated by a diaphragm electrolysis device, using a Pd-MWNTs gas-diffusion electrode as a cathode and a Ti/RuO2 net as an anode. The main products in present system were formic acid and acetic acid identified by ion chromatograph. The selectivity of the products could be achieved by reaction conditions changing. The optimum faraday efficiencies of formic and acetic acids formed on the Pd-MWNTs gas-diffusion electrode at 4 V electrode voltages under 1 atm CO2 were 34.5% and 52.3%, respectively. PMID:24453849

A driven active mass damper by using output of a neural oscillator (effects of position control system changes on vibration mitigation performance)

NASA Astrophysics Data System (ADS)

Hongu, J.; Iba, D.; Sasaki, T.; Nakamura, M.; Moriwaki, I.

2015-03-01

In this paper, a design method for a PD controller, which is a part of a new active mass damper system using a neural oscillator for high-rise buildings, is proposed. The new system mimicking the motion of bipedal mammals is a quite simple system, which has the neural oscillator synchronizing with the acceleration response of the structure. The travel distance and direction of the auxiliary mass of the active mass damper is decided by the output of the neural oscillator, and then, the auxiliary mass is transferred to the decided location by using the PD controller. Therefore, the performance of the PD controller must be evaluated by the vibration energy absorbing efficiency by the system. In order to bring the actual path driven by the PD controller in closer alignment with the ideal path, which is assumed to be a sinusoidal wave under resonance, firstly, the path of the auxiliary mass driven by the PD controller is analytically derived, and the inner product between the vector of ideal and analytical path is evaluated. And then, the PD gain is decided by the maximum value of the inner product. Finally, numerical simulations confirm the validity of the proposed design method of the PD controller.

Funding of Parkinson research from industry and US federal and foundation sources.

PubMed

Dorsey, E Ray; Thompson, Joel P; Frasier, Mark; Sherer, Todd; Fiske, Brian; Nicholson, Sean; Johnston, S Claiborne; Holloway, Robert G; Moses, Hamilton

2009-04-15

Funding for biomedical and neuroscience research has increased over the last decade but without a concomitant increase in new therapies. This study's objectives were to determine the level and principal sources of recent funding for Parkinson disease (PD) research and to determine the current state of PD drug development. We determined the level and principal sources of recent funding for PD research from the following sources: US federal agencies, large PD foundations based in the United States, and global industry. We assessed the status of PD drug development through the use of a proprietary drug pipeline database. Funding for PD research from the sources examined was approximately $1.1 billion in 2003 and $1.2 billion in 2005. Industry accounted for 77% of support from 2003 to 2005. The number of drugs in development for PD increased from 67 in 2003 to 97 in 2007. Of the companies with at least one compound in development for PD in 2007, most were small (62% had annual revenue of less than $100 million), and most (53%) were based outside the United States. These companies will likely require partnerships to drive successful development of new PD therapies.

Measures to Evaluate the Effects of DBS on Speech Production

PubMed Central

Weismer, Gary; Yunusova, Yana; Bunton, Kate

2011-01-01

The purpose of this paper is to review and evaluate measures of speech production that could be used to document effects of Deep Brain Stimulation (DBS) on speech performance, especially in persons with Parkinson disease (PD). A small set of evaluative criteria for these measures is presented first, followed by consideration of several speech physiology and speech acoustic measures that have been studied frequently and reported on in the literature on normal speech production, and speech production affected by neuromotor disorders (dysarthria). Each measure is reviewed and evaluated against the evaluative criteria. Embedded within this review and evaluation is a presentation of new data relating speech motions to speech intelligibility measures in speakers with PD, amyotrophic lateral sclerosis (ALS), and control speakers (CS). These data are used to support the conclusion that at the present time the slope of second formant transitions (F2 slope), an acoustic measure, is well suited to make inferences to speech motion and to predict speech intelligibility. The use of other measures should not be ruled out, however, and we encourage further development of evaluative criteria for speech measures designed to probe the effects of DBS or any treatment with potential effects on speech production and communication skills. PMID:24932066

Olfaction in Parkinson's disease and related disorders.

PubMed

Doty, Richard L

2012-06-01

Olfactory dysfunction is an early 'pre-clinical' sign of Parkinson's disease (PD). The present review is a comprehensive and up-to-date assessment of such dysfunction in PD and related disorders. The olfactory bulb is implicated in the dysfunction, since only those syndromes with olfactory bulb pathology exhibit significant smell loss. The role of dopamine in the production of olfactory system pathology is enigmatic, as overexpression of dopaminergic cells within the bulb's glomerular layer is a common feature of PD and most animal models of PD. Damage to cholinergic, serotonergic, and noradrenergic systems is likely involved, since such damage is most marked in those diseases with the most smell loss. When compromised, these systems, which regulate microglial activity, can influence the induction of localized brain inflammation, oxidative damage, and cytosolic disruption of cellular processes. In monogenetic forms of PD, olfactory dysfunction is rarely observed in asymptomatic gene carriers, but is present in many of those that exhibit the motor phenotype. This suggests that such gene-related influences on olfaction, when present, take time to develop and depend upon additional factors, such as those from aging, other genes, formation of α-synuclein- and tau-related pathology, or lowered thresholds to oxidative stress from toxic insults. The limited data available suggest that the physiological determinants of the early changes in PD-related olfactory function are likely multifactorial and may include the same determinants as those responsible for a number of other non-motor symptoms of PD, such as dysautonomia and sleep disturbances. Copyright © 2011 Elsevier Inc. All rights reserved.

Prediction of in vivo neutral detergent fiber digestibility and digestion rate of potentially digestible neutral detergent fiber: comparison of models.

PubMed

Huhtanen, P; Seppälä, A; Ahvenjärvi, S; Rinne, M

2008-10-01

Eleven 1-pool, seven 2-pool, and three 3-pool models were compared in fitting gas production data and predicting in vivo NDF digestibility and effective first-order digestion rate of potentially digestible NDF (pdNDF). Isolated NDF from 15 grass silages harvested at different stages of maturity was incubated in triplicate in rumen fluid-buffer solution for 72 h to estimate the digestion kinetics from cumulative gas production profiles. In vivo digestibility was estimated by the total fecal collection method in sheep fed at a maintenance level of feeding. The concentration of pdNDF was estimated by a 12-d in situ incubation. The parameter values from gas production profiles and pdNDF were used in a 2-compartment rumen model to predict pdNDF digestibility using 50 h of rumen residence time distributed in a ratio of 0.4:0.6 between the non-escapable and escapable pools. The effective first-order digestion rate was computed both from observed in vivo and model-predicted pdNDF digestibility assuming the passage kinetic model described above. There were marked differences between the models in fitting the gas production data. The fit improved with increasing number of pools, suggesting that silage pdNDF is not a homogenous substrate. Generally, the models predicted in vivo NDF digestibility and digestion rate accurately. However, a good fit of gas production data was not necessarily translated into improved predictions of the in vivo data. The models overestimating the asymptotic gas volumes tended to underestimate the in vivo digestibility. Investigating the time-related residuals during the later phases of fermentation is important when the data are used to estimate the first-order digestion rate of pdNDF. Relatively simple models such as the France model or even a single exponential model with discrete lag period satisfied the minimum criteria for a good model. Further, the comparison of feedstuffs on the basis of parameter values is more unequivocal than in the case of multiple-pool models.

The Evolution of Pd0/PdII-Catalyzed Aromatic Fluorination

PubMed Central

2016-01-01

Conspectus Aromatic fluorides are prevalent in both agrochemical and pharmaceutical agents. However, methods for their rapid and general preparation from widely available starting materials are limited. Traditional approaches such as the Balz–Schiemann and Halex reactions require harsh conditions that limit functional group tolerance and substrate scope. The use of transition metals to affect C–F bond formation has provided some useful alternatives, but a broadly applicable method remains elusive. In contrast to the widespread use of Pd0/PdII catalysis for aryl–Z bond formation (Z = C, N, O), the analogous C–F cross-coupling process was unknown until fairly recently. In large part, this is due to the challenging Ar–F reductive elimination from Pd(II) intermediates. We have discovered that certain biaryl monophosphine ligands are uniquely capable of promoting this transformation. In this Account, we describe the discovery and development of a Pd-catalyzed C–F cross-coupling process and the systematic developments that made this once hypothetical reaction possible. Key to these developments was the discovery of an unusual in situ ligand modification process in which a molecule of substrate is incorporated into the ligand scaffold and the identity of the modifying group is crucial to the outcome of the reaction. This prompted the synthesis of a variety of “premodified” ligands and the identification of one that led to an expanded substrate scope, including (hetero)aryl triflates and bromides. Contemporaneously, a new Pd(0) precatalyst was also discovered that avoids the need to reduce Pd(II) in situ, a process that was often inefficient and led to the formation of byproducts. The use of inexpensive but hygroscopic sources of fluoride necessitates a reaction setup inside of a N2-filled glovebox, limiting the practicality of the method. Thus, a preformed wax capsule was designed to isolate the catalyst and reagents from the atmosphere and permit benchtop storage and setup. This new technology thus removes the requirement to employ a glovebox for the aromatic fluorination process and other air-sensitive protocols. In every catalyst system that we have studied to date, we observed the formation of regioisomeric fluoride side products. Through deuterium labeling studies it was found that they likely arise from a deprotonation event resulting in the formation of HF and a Pd–benzyne intermediate. Through an investigation of the mechanism of this undesired pathway, a new ligand was designed that substantially reduces the formation of the aryl fluoride regioisomer and even allows room-temperature Ar–F reductive elimination from a Pd(II) intermediate. PMID:27656765

Method for the determination of Pd-catalyst residues in active pharmaceutical ingredients by means of high-energy polarized-beam energy dispersive X-ray fluorescence.

PubMed

Marguí, E; Van Meel, K; Van Grieken, R; Buendía, A; Fontàs, C; Hidalgo, M; Queralt, I

2009-02-15

In medicinal chemistry, Pd is perhaps the most-widely utilized precious metal, as catalyst in reactions which represent key transformations toward the synthesis of new active pharmaceutical ingredients (APIs). The disadvantage of this metal-catalyzed chemistry is that expensive and toxic metal residues are invariably left bound to the desired product. Thus, stringent regulatory guidelines exist for the amount of residual Pd that a drug candidate is allowed to contain. In this work, a rapid and simple method for the determination of Pd in API samples by high-energy polarized-beam energy dispersive X-ray fluorescence spectrometry has been developed and validated according to the specification limits of current legislation (10 mg kg(-1) Pd) and the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH guidelines). Sample and calibration standards preparation includes a first step of homogenization and then, in a second step, the pressing of the powdered material into pellets without any chemical treatment. The use of several synthetic calibration standards made of cellulose to simulate the API matrix appears to be an effective means to obtain reliable calibration curves with a good spread of data points over the working range. With the use of the best measuring conditions, the limit of detection (0.11 mg kg(-1) Pd) as well as the limit of quantitation (0.37 mg kg(-1) Pd) achieved meet rigorous requirements. The repeatability of the XRF measurement appeared to be less than 2%, while the precision of the whole method was around 7%. Trueness was evaluated by analyzing spiked API samples at the level of the specification limit and calculating the recovery factor, which was better than 95%. To study the applicability of the developed methodology for the intended purpose, three batches of the studied API were analyzed for their Pd content, and the attained results were comparable to those obtained by the daily routine method (acid digestion plus atomic spectroscopy) used in most pharmaceutical laboratories.

Gene–environment interactions: key to unraveling the mystery of Parkinson’s disease

PubMed Central

Gao, Hui-Ming; Hong, Jau-shyong

2011-01-01

Parkinson’s disease (PD) is the second most common neurodegenerative disease. The gradual, irreversible loss of dopamine neurons in the substantia nigra isthe signature lesion of PD. Clinical symptoms of PD become apparent when 50–60% of nigral dopamine neurons are lost. PD progresses insidiously for 5–7 years (preclinical period) and then continues to worsen even under the symptomatic treatment. To determine what triggers the disease onset and what drives the chronic, self-propelling neurodegenerative process becomes critical and urgent, since lack of such knowledge impedes the discovery of effective treatments to retard PD progression. At present, available therapeutics only temporarily relieve PD symptoms. While the identification of causative gene defects in familial PD uncovers important genetic influences in this disease, the majority of PD cases are sporadic and idiopathic. The current consensus suggests that PD develops from multiple risk factors including aging, genetic predisposition, and environmental exposure. Here, we briefly review research on the genetic and environmental causes of PD. We also summarize very recent genome-wide association studies on risk gene polymorphisms in the emergence of PD. We highlight the new converging evidence on gene-environment interplay in the development of PD with an emphasis on newly developed multiple-hit PD models involving both genetic lesions and environmental triggers. PMID:21439347

Application of aluminum-supported Pd, Rh, and Rh-Pd nanoparticles in supercritical carbon dioxide system for hydrodebromination of polybrominated diphenyl ethers.

PubMed

Wu, Ben-Zen; Sun, Yu-Jie; Chen, Yan-Hua; Yak, Hwa Kwang; Yu, Jya-Jyun; Liao, Weisheng; Chiu, KongHwa; Peng, Shie-Ming

2016-08-01

Al-powder-supported Pd, Rh, and Rh-Pd catalysts were synthesized through a spontaneous redox reaction in aqueous solutions. These catalysts hydrodebrominated 4- and 4,4'-bromodiphenyl ethers in supercritical carbon dioxide at 200 atm CO2 containing 10 atm H2 and 80 °C in 1 h. Diphenyl ether was the major product of Pd/Al. Rh/Al and Rh-Pd/Al further hydrogenated two benzene rings of diphenyl ether to form dicyclohexyl ether. The hydrogenolysis of CO bonds on diphenyl ether over Rh/Al and Rh-Pd/Al was observed to generate cyclohexanol and cyclohexane (<1%). With respect to hydrodebromination efficiency and catalyst stability, Rh-Pd/Al among three catalysts is suggested to be used for ex situ degradation of polybrominated diphenyl ethers in supercritical carbon dioxide. Copyright © 2016 Elsevier Ltd. All rights reserved.

Towards an integrated system for bio-energy: hydrogen production by Escherichia coli and use of palladium-coated waste cells for electricity generation in a fuel cell.

PubMed

Orozco, R L; Redwood, M D; Yong, P; Caldelari, I; Sargent, F; Macaskie, L E

2010-12-01

Escherichia coli strains MC4100 (parent) and a mutant strain derived from this (IC007) were evaluated for their ability to produce H(2) and organic acids (OAs) via fermentation. Following growth, each strain was coated with Pd(0) via bioreduction of Pd(II). Dried, sintered Pd-biomaterials ('Bio-Pd') were tested as anodes in a proton exchange membrane (PEM) fuel cell for their ability to generate electricity from H(2). Both strains produced hydrogen and OAs but 'palladised' cells of strain IC007 (Bio-Pd(IC007)) produced ~threefold more power as compared to Bio-Pd(MC4100) (56 and 18 mW respectively). The power output used, for comparison, commercial Pd(0) powder and Bio-Pd made from Desulfovibrio desulfuricans, was ~100 mW. The implications of these findings for an integrated energy generating process are discussed.

Expression of LAG-3 defines exhaustion of intratumoral PD-1+ T cells and correlates with poor outcome in follicular lymphoma

PubMed Central

Yang, Zhi-Zhang; Kim, Hyo Jin; Villasboas, Jose C.; Chen, Ya-Ping; Price-Troska, Tammy; Jalali, Shahrzad; Wilson, Mara; Novak, Anne J.; Ansell, Stephen M.

2017-01-01

Exhausted T-cells in follicular lymphoma (FL) typically express PD-1, but expression of PD-1 is not limited to exhausted cells. Although expected to be functionally suppressed, we found that the population of intratumoral PD-1+ T cells were predominantly responsible for production of cytokines and granules. This surprising finding prompted us to explore the involvement of LAG-3 to specifically identify functionally exhausted T cells. We found that LAG-3 was expressed on a subset of intratumoral T cells from FL and LAG-3+ T cells almost exclusively came from PD-1+ population. CyTOF analysis revealed that intratumoral LAG-3+ T cells were phenotypically heterogeneous as LAG-3 was expressed on a variety of T cell subsets. In contrast to PD-1+LAG-3- cells, intratumoral PD-1+LAG-3+ T cells exhibited reduced capacity to produce cytokines and granules. LAG-3 expression could be substantially upregulated on CD4+ or CD8+ T cells by IL-12, a cytokine that has been shown to induce T-cell exhaustion and be increased in the serum of lymphoma patients. Furthermore, we found that blockade of both PD-1 and LAG-3 signaling enhanced the function of intratumoral CD8+ T cells resulting in increased IFN-γ and IL-2 production. Clinically, LAG-3 expression on intratumoral T cells correlated with a poor outcome in FL patients. Taken together, we find that LAG-3 expression is necessary to identify the population of intratumoral PD-1+ T cells that are functionally exhausted and, in contrast, find that PD-1+LAG-3- T cells are simply activated cells that are immunologically functional. These findings may have important implications for immune checkpoint therapy in FL. PMID:28977875

Encapsulating peritoneal sclerosis in the era of a multi-disciplinary approach based on biocompatible solutions: the NEXT-PD study.

PubMed

Nakayama, Masaaki; Miyazaki, Masanobu; Honda, Kazuho; Kasai, Kenji; Tomo, Tadashi; Nakamoto, Hidetomo; Kawanishi, Hideki

2014-01-01

Encapsulating peritoneal sclerosis (EPS) is a serious complication of peritoneal dialysis (PD). Over the past decade in Japan, a multidisciplinary approach has been adopted to minimize the incidence and improve outcomes of EPS. This strategy includes planned PD discontinuation for high-risk patients and the introduction of biocompatible solutions. This study examined the current clinical status of EPS in representative PD centers in Japan. Patients (n = 1,338) from 55 PD centers in Japan who were using neutral-pH solutions from the initiation of therapy (mean age, 62 years; median PD duration, 32 months; concomitant use of icodextrin, 35.2%; PD and hemodialysis combination therapy, 12.2%) were assessed every 6 months to ascertain the reasons for PD discontinuation and the development of EPS development. Outcomes were also recorded. The study period was from November 2008 to March 2012. There were 727 patients who discontinued PD, including 163 deaths. Among all causes of PD withdrawal except for death, planned PD discontinuation to avoid EPS was utilized in 58 cases (7.1% in total). The strategy was increasingly utilized in proportion to the duration of PD: 0.5% for patients undergoing PD for < 3 years, 0.6% for patients undergoing PD for 5 years, 14.7% for patients undergoing PD for 8 years, and 35.5% for patients undergoing PD for > 8 years. Fourteen patients developed EPS (three cases after PD), which corresponded with an overall incidence of 1.0%. The incidence according to the duration of PD was 0.3% for PD < 3 years, 0.6% for PD = 5 years, 2.3% for PD = 8 years, and 1.2% for PD > 8 years. In terms of therapy, 11 patients were treated with prednisolone (PSL), and surgical enterolysis was utilized in two cases. Complete remission of abdominal symptoms was achieved in twelve patients (85.7%), and three died due to EPS (mortality rate of 21.4%). Use of the multidisciplinary approach described above reduces the risk of the development of EPS according to PD duration. In cases of de novo EPS cases in Japan, this strategy can also attenuate the clinical course of the condition. Copyright © 2014 International Society for Peritoneal Dialysis.

Higher Frequency of Circulating PD-1high CXCR5+CD4+ Tfh Cells in Patients with Chronic Schistosomiasis

PubMed Central

Zhang, Yumei; Jiang, Yanyan; Wang, Yanjuan; Liu, Hua; Shen, Yujuan; Yuan, Zhongying; Hu, Yuan; Xu, Yuxin; Cao, Jianping

2015-01-01

The current knowledge of immunological responses to schistosomiasis is insufficient for the development of vaccine and therapies. The role of T follicular helper (Tfh) cells in schistosome infections is not fully defined. The frequency of circulating Tfh cells and serum cytokine levels were analyzed in 11 patients with chronic schistosomiasis and 10 healthy controls (HC), who reside in an endemic area for Schistosomiasis japonicum. Significantly higher frequencies of circulating CXCR5+ CD4+ Tfh cells and higher expression levels of ICOS and PD-1 in CXCR5+ CD4+ Tfh cells were observed in patients with chronic schistosomiasis compared to HC. The levels of IL-21 in serum and the expression of IL-21 mRNA were higher in chronic schistosomiasis patients than in HC. Moreover, the frequency of circulating PD-1high CXCR5+ CD4+ Tfh cells positively correlated with the levels of IL-21 in serum from patients with chronic schistosomiasis. A positive correlation was also found between the frequency of PD-1high CXCR5+ CD4+ Tfh cells and the levels of soluble egg antigen (SEA)-specific antibodies in serum samples from the patient group. Our study is the first regarding Tfh cells in chronic human schistosomiasis and the finding indicate that PD-1high CXCR5+ CD4+Tfh cells might play an important role in the production of specific antibodies in schistosomiasis. This study contributes to the understanding of immune response to schistosomiasis and may provide helpful support in vaccine development. PMID:26221072

Higher Frequency of Circulating PD-1(high) CXCR5(+)CD4(+) Tfh Cells in Patients with Chronic Schistosomiasis.

PubMed

Zhang, Yumei; Jiang, Yanyan; Wang, Yanjuan; Liu, Hua; Shen, Yujuan; Yuan, Zhongying; Hu, Yuan; Xu, Yuxin; Cao, Jianping

2015-01-01

The current knowledge of immunological responses to schistosomiasis is insufficient for the development of vaccine and therapies. The role of T follicular helper (Tfh) cells in schistosome infections is not fully defined. The frequency of circulating Tfh cells and serum cytokine levels were analyzed in 11 patients with chronic schistosomiasis and 10 healthy controls (HC), who reside in an endemic area for Schistosomiasis japonicum. Significantly higher frequencies of circulating CXCR5(+) CD4(+) Tfh cells and higher expression levels of ICOS and PD-1 in CXCR5(+) CD4(+) Tfh cells were observed in patients with chronic schistosomiasis compared to HC. The levels of IL-21 in serum and the expression of IL-21 mRNA were higher in chronic schistosomiasis patients than in HC. Moreover, the frequency of circulating PD-1(high) CXCR5(+) CD4(+) Tfh cells positively correlated with the levels of IL-21 in serum from patients with chronic schistosomiasis. A positive correlation was also found between the frequency of PD-1(high) CXCR5(+) CD4(+) Tfh cells and the levels of soluble egg antigen (SEA)-specific antibodies in serum samples from the patient group. Our study is the first regarding Tfh cells in chronic human schistosomiasis and the finding indicate that PD-1(high) CXCR5(+) CD4(+)Tfh cells might play an important role in the production of specific antibodies in schistosomiasis. This study contributes to the understanding of immune response to schistosomiasis and may provide helpful support in vaccine development.

Differential roles of MAPK-Erk1/2 and MAPK-p38 in insulin or insulin-like growth factor-I (IGF-I) signaling pathways for progesterone production in human ovarian cells.

PubMed

Seto-Young, D; Avtanski, D; Varadinova, M; Park, A; Suwandhi, P; Leiser, A; Parikh, G; Poretsky, L

2011-06-01

Insulin and insulin like-growth factor-I (IGF-I) participate in the regulation of ovarian steroidogenesis. In insulin resistant states ovaries remain sensitive to insulin because insulin can activate alternative signaling pathways, such as phosphatidylinositol-3-kinase (PI-3 kinase) and mitogen-activated protein-kinase (MAPK) pathways, as well as insulin receptors and type 1 IGF receptors. We investigated the roles of MAPK-Erk1/2 and MAPK-p38 in insulin and IGF-I signaling pathways for progesterone production in human ovarian cells. Human ovarian cells were cultured in tissue culture medium in the presence of varying concentrations of insulin or IGF-I, with or without PD98059, a specific MAPK-Erk1/2 inhibitor, with or without SB203580, a specific MAPK-p38 inhibitor or with or without a specific PI-3-kinase inhibitor LY294002. Progesterone concentrations were measured using radioimmunoassay. PD98059 alone stimulated progesterone production in a dose-dependent manner by up to 65% (p<0.001). Similarly, LY294002 alone stimulated progesterone production by 13-18% (p<0.005). However, when used together, PD98059 and LY294002 inhibited progesterone production by 17-20% (p<0.001). SB203580 alone inhibited progesterone production by 20-30% (p<0.001). Insulin or IGF-I alone stimulated progesterone production by 40-60% (p<0.001). In insulin studies, PD98059 had no significant effect on progesterone synthesis while SB203580 abolished insulin-induced progesterone production. Either PD98059 or SB203580 abolished IGF-I-induced progesterone production. Both MAPK-Erk1/2 and MAPK-p38 participate in IGF-I-induced signaling pathways for progesterone production, while insulin-induced progesterone production requires MAPK-p38, but not MAPK-Erk1/2. These studies provide further evidence for divergence of insulin and IGF-I signaling pathways for human ovarian cell steroidogenesis. © Georg Thieme Verlag KG Stuttgart · New York.

Practice development: implementing a change of practice as a team.

PubMed

Covill, Carl; Hope, Angela

2012-08-01

Practice development (PD), as a framework for multiprofessional working, has immense potential, specifically within change management and the clinical governance agenda. It has been acknowledged as a vehicle for 'continuous improvement'. This article discusses PD through collaborative working using the example of a case study on change of practice in falls reduction within a localised community setting. The process is underpinned by a PD framework and facilitated by leaders of PD within a university setting. The article identifies that PD frameworks are conducive to developing leadership and management roles within a democratic process. The article discusses the potential for multiprofessional PD within the locality and further afield.

Methyl oleate deoxygenation for production of diesel fuel aliphatic hydrocarbons over Pd/SBA-15 catalysts

PubMed Central

2013-01-01

Background Catalytic deoxygenation is a prominent process for production of renewable fuels from vegetable oil. In this work, deoxygenation of technical grade methyl oleate to diesel fuel aliphatic hydrocarbons (C15 – C18) is evaluated with several parameters including temperature, hydrogen pressure and reaction time in a stirred batch reactor over Pd/SBA-15 catalysts. Results Two different SBA-15 morphologies i.e. spherelike and necklacelike structures have been synthesize as supports for Pd active metal. It is found that Pd dispersion on necklacelike SBA-15 is higher than that of spherelike SBA-15. Notably, higher Pd dispersion on necklacelike SBA-15 provides significant deoxygenation efficiency as compared to Pd/SBA-15-spherelike. Results show that H2 pressures greatly determine the total ester conversion and selectivity to C15 – C18 aliphatic hydrocarbons. Total ester conversions with 55< selectivity to n-heptadecane are achieved using Pd/SBA-15-necklacelike at 270°C and 60 bar H2 pressure within 6 h reaction time. Gas phase study reveals that formation of C17 is generated via indirect decarbonylation when the reaction time is prolonged. Conclusions Pd/SBA-15-necklacelike catalyst exhibits good catalytic performance with high selectivity to diesellike aliphatic hydrocarbons (C15 – C18). The physicochemical properties of the Pd supported on different SBA-15 morphologies influence the deoxygenation activity of the catalysts. Furthermore, the reaction pathways are governed by the H2 pressure as well as reaction duration. PMID:24011181

Liquid phase catalytic hydrodebromination of tetrabromobisphenol A on supported Pd catalysts

NASA Astrophysics Data System (ADS)

Wu, Ke; Zheng, Mengjia; Han, Yuxiang; Xu, Zhaoyi; Zheng, Shourong

2016-07-01

Tetrabromobisphenol A (TBBPA) is a widely used brominated flame retardant and reductive debromination is an effective method for the abatement of TBBPA pollution. In this study, Pd catalysts supported on TiO2, CeO2, Al2O3 and SiO2 were prepared by the impregnation (the resulting catalyst denoted as im-Pd/support), deposition-precipitation (the resulting catalyst denoted as dp-Pd/support), and photo-deposition (the resulting catalyst denoted as pd-Pd/support) methods. The catalysts were characterized by N2 adsorption-desorption isotherm, X-ray diffraction, transmission electron microscopy, measurement of zeta potential, CO chemisorption, and X-ray photoelectron spectroscopy. The results showed that at an identical Pd loading amount (2.0 wt.%) Pd particle size in dp-Pd/TiO2 was much smaller than those in im-Pd/TiO2 and pd-Pd/TiO2. Pd particle size of the dp-Pd/TiO2 catalyst increased with Pd loading amount. Additionally, Pd particles in the dp-Pd/TiO2 catalysts were positively charged due to the strong metal-support interaction, whereas the cationization effect was gradually attenuated with the increase of Pd loading amount. For the liquid phase catalytic hydrodebromination (HDB) of TBBPA, tri-bromobisphenol A (tri-BBPA), di-bromobisphenol A (di-BBPA), and mono-bromobisphenol A (mono-BBPA) were identified as the intermediate products, indicative of a stepwise debromination process. The catalytic HDB of TBBPA followed the Langmuir-Hinshelwood model, reflecting an adsorption enhanced catalysis mechanism. At an identical Pd loading amount, the Pd catalyst supported on TiO2 exhibited a much higher catalytic activity than those on other supports. Furthermore, dp-Pd/TiO2 was found to be more active than im-Pd/TiO2 and pd-Pd/TiO2.

Effect of Parkinson's Disease on the Production of Structured and Unstructured Speaking Tasks: Respiratory Physiologic and Linguistic Considerations

ERIC Educational Resources Information Center

Huber, Jessica E.; Darling, Meghan

2011-01-01

Purpose: To examine the effects of cognitive-linguistic deficits and respiratory physiologic changes on respiratory support for speech in individuals with Parkinson's disease (PD) using two speech tasks: reading and extemporaneous speech. Method: Five women with PD, 9 men with PD, and 14 age- and sex-matched control participants read a passage and…

Development of PD-1 and PD-L1 inhibitors as a form of cancer immunotherapy: a comprehensive review of registration trials and future considerations.

PubMed

Gong, Jun; Chehrazi-Raffle, Alexander; Reddi, Srikanth; Salgia, Ravi

2018-01-23

Early preclinical evidence provided the rationale for programmed cell death 1 (PD-1) and programmed death ligand 1 (PD-L1) blockade as a potential form of cancer immunotherapy given that activation of the PD-1/PD-L1 axis putatively served as a mechanism for tumor evasion of host tumor antigen-specific T-cell immunity. Early-phase studies investigating several humanized monoclonal IgG4 antibodies targeting PD-1 and PD-L1 in advanced solid tumors paved way for the development of the first PD-1 inhibitors, nivolumab and pembrolizumab, approved by the Food and Drug Administration (FDA) in 2014. The number of FDA-approved agents of this class is rapidly enlarging with indications for treatment spanning across a spectrum of malignancies. The purpose of this review is to highlight the clinical development of PD-1 and PD-L1 inhibitors in cancer therapy to date. In particular, we focus on detailing the registration trials that have led to FDA-approved indications of anti-PD-1 and anti-PD-L1 therapies in cancer. As the number of PD-1/PD-L1 inhibitors continues to grow, predictive biomarkers, mechanisms of resistance, hyperprogressors, treatment duration and treatment beyond progression, immune-related toxicities, and clinical trial design are key concepts in need of further consideration to optimize the anticancer potential of this class of immunotherapy.

Self-Delivering RNAi Targeting PD-1 Improves Tumor-Specific T Cell Functionality for Adoptive Cell Therapy of Malignant Melanoma.

PubMed

Ligtenberg, Maarten A; Pico de Coaña, Yago; Shmushkovich, Taisia; Yoshimoto, Yuya; Truxova, Iva; Yang, Yuan; Betancur-Boissel, Monica; Eliseev, Alexey V; Wolfson, Alexey D; Kiessling, Rolf

2018-06-06

Adoptive cell therapy (ACT) is becoming a prominent alternative therapeutic treatment for cancer patients relapsing on traditional therapies. In parallel, antibodies targeting immune checkpoint molecules, such as cytotoxic-T-lymphocyte-associated antigen 4 (CTLA-4) and cell death protein 1 pathway (PD-1), are rapidly being approved for multiple cancer types, including as first line therapy for PD-L1-expressing non-small-cell lung cancer. The combination of ACT and checkpoint blockade could substantially boost the efficacy of ACT. In this study, we generated a novel self-delivering small interfering RNA (siRNA) (sdRNA) that knocked down PD-1 expression on healthy donor T cells as well as patient-derived tumor-infiltrating lymphocytes (TIL). We have developed an alternative chemical modification of RNA backbone for improved stability and increased efficacy. Our results show that T cells treated with sdRNA specific for PD-1 had increased interferon γ (IFN-γ) secreting capacity and that this modality of gene expression interference could be utilized in our rapid expansion protocol for production of TIL for therapy. TIL expanded in the presence of PD-1-specific sdRNA performed with increased functionality against autologous tumor as compared to control TIL. This method of introducing RNAi into T cells to modify the expression of proteins could easily be adopted into any ACT protocol and will lead to the exploration of new combination therapies. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Specific Caleosin/Peroxygenase and Lipoxygenase Activities Are Tissue-Differentially Expressed in Date Palm (Phoenix dactylifera L.) Seedlings and Are Further Induced Following Exposure to the Toxin 2,3,7,8-tetrachlorodibenzo-p-dioxin.

PubMed

Hanano, Abdulsamie; Almousally, Ibrahem; Shaban, Mouhnad; Rahman, Farzana; Hassan, Mehedi; Murphy, Denis J

2016-01-01

Two caleosin/peroxygenase isoforms from date palm, Phoenix dactylifera L., PdCLO2 and PdCLO4, were characterized with respect to their tissue expression, subcellular localization, and oxylipin pathway substrate specificities in developing seedlings. Both PdCLO2 and PdCLO4 had peroxygenase activities that peaked at the mid-stage (radicle length of 2.5 cm) of seedling growth and were associated with the lipid droplet (LD) and microsomal fractions. Recombinant PdCLO2 and PdCLO4 proteins heterologously expressed in yeast cells were localized in both LD and microsomal fractions. Each of the purified recombinant proteins exhibited peroxygenase activity but they were catalytically distinct with respect to their specificity and product formation from fatty acid epoxide and hydroxide substrates. We recently showed that date palm CLO genes were upregulated following exposure to the potent toxin, 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD) (Hanano et al., 2016), and we show here that transcripts of 9- and 13-lipoxygenase (LOX) genes were also induced by TCDD exposure. At the enzyme level, 9-LOX and 13-LOX activities were present in a range of seedling tissues and responded differently to TCDD exposure, as did the 9- and 13-fatty acid hydroperoxide reductase activities. This demonstrates that at least two branches of the oxylipin pathway are involved in responses to the environmental organic toxin, TCDD in date palm.

A facile synthesis of mesoporous Pdsbnd ZnO nanocomposites as efficient chemical sensor

NASA Astrophysics Data System (ADS)

Ismail, Adel A.; Harraz, Farid A.; Faisal, M.; El-Toni, Ahmed Mohamed; Al-Hajry, A.; Al-Assiri, M. S.

2016-07-01

Mesoporous ZnO was synthesized through the sol-gel method in the presence of triblock co-polymer Pluronic (F-127) template as the structure directing agent. Palladium nanoparticles were photochemically reduced and deposited onto mesoporous ZnO to obtain 1 wt.% Pd/ZnO nanocomposite. Structural and morphological analysis revealed high homogeneity and monodispersity of Pd nanoclusters with small particle sizes ∼ 2-5 nm onto mesoporous ZnO. The electrochemical detection of ethanol in aqueous solutions was conducted at the newly developed Pd/ZnO modified glassy carbon electrode (GCE) by the current-potential (IV) and cyclic voltammetry (CV) techniques and compared with bare GCE or pure ZnO. The presence of Pd dopant greatly enhances the sensitivity of ZnO, and the obtained mesoporous Pd/ZnO sensor has an excellent performance for precision detection of ethanol in aqueous solution with low concentration. The sensitivity was found to be 33.08 μAcm-2 mM-1 at lower concentration zone (0.05-0.8 mM) and 2.13 μAcm-2 mM-1 at higher concentration zone (0.8-12 mM), with a limit of detection (LOD) 19.2 μM. The kinetics study of ethanol oxidation revealed a characteristic feature for a mixed surface and diffusion-controlled process. These excellent sensing characteristics make the mesoporous Pd/ZnO nanocomposite a good candidate for the production of high-performance electrochemical sensors at low ethanol concentration in aqueous solution.

Mathematical models of the simplest fuzzy PI/PD controllers with skewed input and output fuzzy sets.

PubMed

Mohan, B M; Sinha, Arpita

2008-07-01

This paper unveils mathematical models for fuzzy PI/PD controllers which employ two skewed fuzzy sets for each of the two-input variables and three skewed fuzzy sets for the output variable. The basic constituents of these models are Gamma-type and L-type membership functions for each input, trapezoidal/triangular membership functions for output, intersection/algebraic product triangular norm, maximum/drastic sum triangular conorm, Mamdani minimum/Larsen product/drastic product inference method, and center of sums defuzzification method. The existing simplest fuzzy PI/PD controller structures derived via symmetrical fuzzy sets become special cases of the mathematical models revealed in this paper. Finally, a numerical example along with its simulation results are included to demonstrate the effectiveness of the simplest fuzzy PI controllers.

Radiation therapy and PD-1/PD-L1 blockade: the clinical development of an evolving anticancer combination.

PubMed

Gong, Jun; Le, Thang Q; Massarelli, Erminia; Hendifar, Andrew E; Tuli, Richard

2018-06-04

Several inhibitors of programmed cell death-1 (PD-1) and programmed death ligand-1 (PD-L1) have been approved as a form of immunotherapy for multiple cancers. Ionizing radiation therapy (RT) has been shown to enhance the priming and effector phases of the antitumor T-cell response rendering it an attractive therapy to combine with PD-1/PD-L1 inhibitors. Preclinical data support the rational combination of the 2 modalities and has paved way for the clinical development of the combination across a spectrum of cancers. In this review, we highlight the preclinical and clinical development of combined RT and PD-1/PD-L1 blockade to date. In addition to a comprehensive evaluation of available safety and efficacy data, we discuss important points of consideration in clinical trial design for this promising combination.

Overexpression of a Domain of Unknown Function 266-containing protein results in high cellulose content, reduced recalcitrance, and enhanced plant growth in the bioenergy crop Populus.

PubMed

Yang, Yongil; Yoo, Chang Geun; Guo, Hao-Bo; Rottmann, William; Winkeler, Kimberly A; Collins, Cassandra M; Gunter, Lee E; Jawdy, Sara S; Yang, Xiaohan; Guo, Hong; Pu, Yunqiao; Ragauskas, Arthur J; Tuskan, Gerald A; Chen, Jin-Gui

2017-01-01

Domain of Unknown Function 266 (DUF266) is a plant-specific domain. DUF266-containing proteins (DUF266 proteins) have been categorized as 'not classified glycosyltransferases (GTnc)' due to amino acid similarity with GTs. However, little is known about the function of DUF266 proteins. Phylogenetic analysis revealed that DUF266 proteins are only present in the land plants including moss and lycophyte. We report the functional characterization of one member of DUF266 proteins in Populus, PdDUF266A. PdDUF266A was ubiquitously expressed with high abundance in the xylem. In Populus transgenic plants overexpressing PdDUF266A ( OXPdDUF266A ), the glucose and cellulose contents were significantly higher, while the lignin content was lower than that in the wild type. Degree of polymerization of cellulose in OXPdDUF266A transgenic plants was also higher, whereas cellulose crystallinity index remained unchanged. Gene expression analysis indicated that cellulose biosynthesis-related genes such as CESA and SUSY were upregulated in mature leaf and xylem of OXPdDUF266A transgenic plants. Moreover, PdDUF266A overexpression resulted in an increase of biomass production. Their glucose contents and biomass phenotypes were further validated via heterologous expression of PdDUF266A in Arabidopsis. Results from saccharification treatment demonstrated that the rate of sugar release was increased by approximately 38% in the OXPdDUF266A transgenic plants. These results suggest that the overexpression of PdDUF266A can increase cellulose content, reduce recalcitrance, and enhance biomass production, and that PdDUF266A is a promising target for genetic manipulation for biofuel production.

Pd-catalyzed allylic alkylation of dienyl carbonates with nitromethane with high C-5 regioselectivity.

PubMed

Yang, Xiao-Fei; Li, Xiao-Hui; Ding, Chang-Hua; Xu, Chao-Fan; Dai, Li-Xin; Hou, Xue-Long

2014-01-14

A highly regioselective palladium-catalyzed allylic alkylation of dienyl esters with nitromethane has been developed, providing selective access to the C-5 attacked products. The structures of the ligands as well as the steric effect of the substrates are important factors in determining the regiochemical outcome of the reaction.

Mortality from Parkinson's disease and other causes among a workforce manufacturing paraquat: a retrospective cohort study

PubMed Central

Campbell, Clive

2011-01-01

Objective To assess the risk of Parkinson's disease (PD) and update information on mortality from major causes of death among a UK workforce who manufactured paraquat (PQ) between 1961 and 1995. There have been no previous studies of the incidence of PD among PQ production workers, although much epidemiological literature exists concerning the relationship between pesticides and PD, and interest has focused on PQ and its users. Methods The cohort included all employees who had ever worked on any of the four plants at Widnes where PQ was manufactured between 1961 and 1995, and 926 male and 42 female workers were followed through 30 June 2009. Mortalities for males were compared with national and local rates, including rates for PD as a mentioned cause of death. Results Overall, 307 workers had died by 30 June 2009. One male death was due to PD, and no other death certificate mentioned PD. At least 3.3 death certificates of male employees would have been expected to have mentioned PD (standardised mortality ratio=31; 95% CI 1 to 171). Personal monitoring results were indicative that the exposure of a PQ production worker on a daily basis was at least comparable with that of a PQ sprayer or mixer/loader. Reduced mortalities compared with local rates were found for major causes of death. Conclusions The study provided no evidence of an increased risk of PD, or increased mortalities from other causes. PMID:22080539

Optimal level of Au nanoparticles on Pd nanostructures providing remarkable electro-catalysis in direct ethanol fuel cell

NASA Astrophysics Data System (ADS)

Dutta, Abhijit; Mondal, Achintya; Broekmann, Peter; Datta, Jayati

2017-09-01

The designing and fabrication of economically viable electro-catalysts for ethanol oxidation reaction (EOR) in direct ethanol fuel cell (DEFC) has been one of the challenging issues over the decades. The present work deals with controlled synthesis of Pd coupled Au nano structure, as the non Pt group of catalysts for DEFC. The catalytic proficiency of bimetallic NPs (2-10 nm) are found to be strongly dependent on the Pd:Au ratio. The over voltage of EOR is considerably reduced by ∼260 mV with 33% of Au content in PdAu composition compared to Pd alone, demonstrating the beneficial role of Au and/or its surface oxides providing oxygen species at much lower potentials compared to Pd. The catalysts are further subjected to electrochemical analysis through voltammetry along with the temperature study on activation parameters. The quantitative determination of EOR products during the electrolysis is carried out by ion chromatographic analysis; vis-a-vis the coulombic efficiency of the product yield were derived from each of the compositions. Furthermore, a strong correlation among catalytic performances and bimetallic composition is established by screening the catalysts in an in-house fabricated direct ethanol anion exchange membrane fuel cell, DE(AEM)FC. The performance testing demonstrates outstanding increase of peak power density (∼40 mWcm-2, 93%) for the best accomplishment Au (33%) covered Pd (67%) catalyst in comparison with the monometallic Pd.

An Overview on the Role of α -Synuclein in Experimental Models of Parkinson's Disease from Pathogenesis to Therapeutics.

PubMed

Javed, Hayate; Kamal, Mohammad Amjad; Ojha, Shreesh

2016-01-01

Parkinson's disease (PD) is a devastating and progressive movement disorder characterized by symptoms of muscles rigidity, tremor, postural instability and slow physical movements. Biochemically, PD is characterized by lack of dopamine production and its action due to loss of dopaminergic neurons and neuropathologically by the presence of intracytoplasmic inclusions known as Lewy bodies, which mainly consist of presynaptic neuronal protein, α-synuclein (α-syn). It is believed that alteration in α-syn homeostasis leads to increased accumulation and aggregation of α-syn in Lewy body. Based on the important role of α-syn from pathogenesis to therapeutics, the recent researches are mainly focused on deciphering the critical role of α-syn at advanced level. Being a major protein in Lewy body that has a key role in pathogenesis of PD, several model systems including immortalized cell lines (SH-SY5Y), primary neuronal cultures, yeast (saccharomyces cerevisiae), drosophila (fruit flies), nematodes (Caenorhabditis elegans) and rodents are being employed to understand the PD pathogenesis and treatment. In order to study the etiopathogensis and develop novel therapeutic target for α -syn aggregation, majority of investigators rely on toxin (rotenone, 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine, 6-hydroxydopamine, paraquat)-induced animal models of PD as a tool for basic research. Whereas, cell and tissue based models are mostly utilized to elucidate the mechanistic and molecular pathways underlying the α -syn induced toxicity and therapeutic approaches in PD. Gene modified mouse models based on α-syn expression are fascinating for modeling familial PD and toxin induced models provide a suitable approach for sporadic PD. The purpose of this review is to provide a summary and a critical review of the involvement of α-syn in various in vitro and in vivo models of PD based on use of neurotoxins as well as genetic modifications.

Active and Durable Hydrogen Evolution Reaction Catalyst Derived from Pd-Doped Metal-Organic Frameworks.

PubMed

Chen, Jitang; Xia, Guoliang; Jiang, Peng; Yang, Yang; Li, Ren; Shi, Ruohong; Su, Jianwei; Chen, Qianwang

2016-06-01

The water electrolysis is of critical importance for sustainable hydrogen production. In this work, a highly efficient and stable PdCo alloy catalyst (PdCo@CN) was synthesized by direct annealing of Pd-doped metal-organic frameworks (MOFs) under N2 atmosphere. In 0.5 M H2SO4 solution, PdCo@CN displays remarkable electrocatalytic performance with overpotential of 80 mV, a Tafel slope of 31 mV dec(-1), and excellent stability of 10 000 cycles. Our studies reveal that noble metal doped MOFs are ideal precursors for preparing highly active alloy electrocatalysts with low content of noble metal.

Cryopreservation of glucose-6-phosphate dehydrogenase activity inside red blood cells: developing a specimen repository in support of development and evaluation of glucose-6-phosphate dehydrogenase deficiency tests

PubMed Central

2013-01-01

Background Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common human enzyme deficiency. It is characterized by abnormally low levels of G6PD activity. Individuals with G6PD deficiency are at risk of undergoing acute haemolysis when exposed to 8‒aminoquinoline-based drugs, such as primaquine. For this reason it is imperative to identify individuals with G6PD deficiency prior to administering these anti-malarial drugs. There is a need for the development and evaluation of point-of-care G6PD deficiency screening tests suitable for areas of the developing world where malarial treatments are frequently administered. The development and evaluation of new G6PD tests will be greatly assisted with the availability of specimen repositories. Methods Cryopreservation of erythrocytes was evaluated as a means to preserve G6PD activity. Blood specimens from 31 patients including ten specimens with normal G6PD activity, three with intermediate activity, and 18 with deficient activity were cryopreserved for up to six months. Results Good correlation in G6PD activity between fresh and cryopreserved specimens (R2 = 0.95). The cryopreserved specimens show an overall small drop in mean G6PD activity of 0.23 U/g Hb (P=0.23). Cytochemical staining showed that intracellular G6PD activity distribution within the red blood cell populations is preserved during cryopreservation. Furthermore, the mosaic composition of red blood cells in heterozygous women is also preserved for six months or more. The fluorescent spot and the BinaxNOW qualitative tests for G6PD deficiency also showed high concordance in G6PD status determination between cryopreserved specimens and fresh specimens. Conclusions A methodology for establishing a specimen panel for evaluation of G6PD tests is described. The approach is similar to that used in several malaria research facilities for the cryopreservation of parasites in clinical specimens and axenic cultures. Specimens stored in this manner will aid both the development and evaluation of current and emerging G6PD tests. The availability of G6PD tests is a critical bottleneck to broader access to drugs that confer radical cure of Plasmodium vivax, a requirement for elimination of malaria. PMID:23961874

Cryopreservation of glucose-6-phosphate dehydrogenase activity inside red blood cells: developing a specimen repository in support of development and evaluation of glucose-6-phosphate dehydrogenase deficiency tests.

PubMed

Kahn, Maria; LaRue, Nicole; Bansil, Pooja; Kalnoky, Michael; McGray, Sarah; Domingo, Gonzalo J

2013-08-20

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common human enzyme deficiency. It is characterized by abnormally low levels of G6PD activity. Individuals with G6PD deficiency are at risk of undergoing acute haemolysis when exposed to 8‒aminoquinoline-based drugs, such as primaquine. For this reason it is imperative to identify individuals with G6PD deficiency prior to administering these anti-malarial drugs. There is a need for the development and evaluation of point-of-care G6PD deficiency screening tests suitable for areas of the developing world where malarial treatments are frequently administered. The development and evaluation of new G6PD tests will be greatly assisted with the availability of specimen repositories. Cryopreservation of erythrocytes was evaluated as a means to preserve G6PD activity. Blood specimens from 31 patients including ten specimens with normal G6PD activity, three with intermediate activity, and 18 with deficient activity were cryopreserved for up to six months. Good correlation in G6PD activity between fresh and cryopreserved specimens (R2 = 0.95). The cryopreserved specimens show an overall small drop in mean G6PD activity of 0.23 U/g Hb (P=0.23). Cytochemical staining showed that intracellular G6PD activity distribution within the red blood cell populations is preserved during cryopreservation. Furthermore, the mosaic composition of red blood cells in heterozygous women is also preserved for six months or more. The fluorescent spot and the BinaxNOW qualitative tests for G6PD deficiency also showed high concordance in G6PD status determination between cryopreserved specimens and fresh specimens. A methodology for establishing a specimen panel for evaluation of G6PD tests is described. The approach is similar to that used in several malaria research facilities for the cryopreservation of parasites in clinical specimens and axenic cultures. Specimens stored in this manner will aid both the development and evaluation of current and emerging G6PD tests. The availability of G6PD tests is a critical bottleneck to broader access to drugs that confer radical cure of Plasmodium vivax, a requirement for elimination of malaria.

Microstructural characterization of annealed U-12Zr-4Pd and U-12Zr-4Pd-5Ln: Investigating Pd as a metallic fuel additive

NASA Astrophysics Data System (ADS)

Benson, Michael T.; He, Lingfeng; King, James A.; Mariani, Robert D.

2018-04-01

Palladium is being investigated as a potential additive to metallic fuel to control fuel-cladding chemical interaction (FCCI). A primary cause of FCCI is the lanthanide fission products moving to the fuel periphery and interacting with the cladding. This interaction will lead to wastage of the cladding and, given enough time or burn-up, eventually to a cladding breach. The current study is a scanning electron microscopy (SEM) and transmission electron microscopy (TEM) characterization of annealed U-12Zr-4Pd and U-12Zr-4Pd-5Ln, where Ln = 53Nd-25Ce-16Pr-6La. The present study shows that Pd preferentially binds the lanthanides over other fuel constituents, which may prevent lanthanide migration and interaction with the cladding during irradiation. The SEM analysis indicates the 1:1 Pd-Ln compound is being formed, while the TEM analysis, due to higher resolution, found the 1:1 compound, as well as Pd-rich compounds Pd2Ln and Pd3Ln2.

Methane Oxidation on Pd-Ceria. A DFT Study of the Combustion Mechanism over Pd, PdO and Pd-ceria Sites

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

Mayernick, Adam D.; Janik, Michael J.

2010-12-24

Palladium/ceria exhibits unique catalytic activity for hydrocarbon oxidation; however, the chemical and structural properties of active sites on the palladium–ceria surface are difficult to characterize. Strong interactions between palladium and the ceria support stabilize oxidized Pd δ+ species, which may contribute to the significant activity of Pd/ceria for methane oxidation. We present a density functional theory (DFT + U) investigation into methane oxidation over Pd/ceria and quantify the activity of the Pd xCe 1-xO 2(1 1 1) mixed oxide surface in comparison with the PdO(1 0 0) and Pd(1 1 1) surfaces. The methane activation barrier is lowest over themore » Pd xCe 1-xO 2(1 1 1) surface, even lower than over the Pd(1 1 1) surface or low coordinated stepped or kinked Pd sites. Subsequent reaction steps in complete oxidation, including product desorption and vacancy refilling, are considered to substantiate that methane activation remains the rate-limiting step despite the low barrier over Pd xCe 1-xO 2(1 1 1). The low barrier over the Pd xCe 1-xO 2(1 1 1) surface demonstrates that mixed ceria-noble metal oxides offer the potential for improved hydrocarbon oxidation performance with respect to dispersed noble metal particles on ceria.« less

Identification of a subset of human natural killer cells expressing high levels of programmed death 1: A phenotypic and functional characterization.

PubMed

Pesce, Silvia; Greppi, Marco; Tabellini, Giovanna; Rampinelli, Fabio; Parolini, Silvia; Olive, Daniel; Moretta, Lorenzo; Moretta, Alessandro; Marcenaro, Emanuela

2017-01-01

Programmed death 1 (PD-1) is an immunologic checkpoint that limits immune responses by delivering potent inhibitory signals to T cells on interaction with specific ligands expressed on tumor/virus-infected cells, thus contributing to immune escape mechanisms. Therapeutic PD-1 blockade has been shown to mediate tumor eradication with impressive clinical results. Little is known about the expression/function of PD-1 on human natural killer (NK) cells. We sought to clarify whether human NK cells can express PD-1 and analyze their phenotypic/functional features. We performed multiparametric cytofluorimetric analysis of PD-1 + NK cells and their functional characterization using degranulation, cytokine production, and proliferation assays. We provide unequivocal evidence that PD-1 is highly expressed (PD-1 bright ) on an NK cell subset detectable in the peripheral blood of approximately one fourth of healthy subjects. These donors are always serologically positive for human cytomegalovirus. PD-1 is expressed by CD56 dim but not CD56 bright NK cells and is confined to fully mature NK cells characterized by the NKG2A - KIR + CD57 + phenotype. Proportions of PD-1 bright NK cells were higher in the ascites of a cohort of patients with ovarian carcinoma, suggesting their possible induction/expansion in tumor environments. Functional analysis revealed a reduced proliferative capability in response to cytokines, low degranulation, and impaired cytokine production on interaction with tumor targets. We have identified and characterized a novel subpopulation of human NK cells expressing high levels of PD-1. These cells have the phenotypic characteristics of fully mature NK cells and are increased in patients with ovarian carcinoma. They display low proliferative responses and impaired antitumor activity that can be partially restored by antibody-mediated disruption of PD-1/programmed death ligand interaction. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Local Immune Responsiveness of Mice Bearing Premalignant Oral Lesions to PD-1 Antibody Treatment.

PubMed

Levingston, Corinne A; Young, M Rita I

2017-06-02

A carcinogen-induced premalignant oral lesion model that progresses to oral cancer was used to examine the immunological impact of a 5-week treatment regimen to block programmed cell death protein 1 (PD-1). PD-1 antibody treatment resulted in concurrent, but transient, increases in interleukin (IL)-2, IFN-γ and IL-17, and delayed increases in IL-6 and IL-10 within the lesion-bearing tongue epithelium. In contrast, cytokine secretion by lymph node cells of PD-1 antibody-treated mice was lower than for mice treated with control antibodies, with the exception of interferon (IFN)-γ, whose secretion increased late in the treatment period. This delayed secretion of IFN-γ coincided with an increase in CD4⁺ lymph node cells expressing IFN-γ. Lymph node cells of PD-1 antibody-treated mice reacted to a challenge with lysates of lesions or cancer by early production of IFN-γ, but this rapidly subsided. There also was increased production IL-17 and tumor necrosis factor (TNF)-α in response to the challenge, but the response was greatest by cells of control lesion-bearing mice. Clinical assessment showed an early but transient, stabilization of disease in mice treated with PD-1 antibody. These results show an early beneficial, but time-limited, response to PD-1 antibody treatment, which then fails with continued lesion progression.

Applications of Palladium-Catalyzed C-N Cross-Coupling Reactions.

PubMed

Ruiz-Castillo, Paula; Buchwald, Stephen L

2016-10-12

Pd-catalyzed cross-coupling reactions that form C-N bonds have become useful methods to synthesize anilines and aniline derivatives, an important class of compounds throughout chemical research. A key factor in the widespread adoption of these methods has been the continued development of reliable and versatile catalysts that function under operationally simple, user-friendly conditions. This review provides an overview of Pd-catalyzed N-arylation reactions found in both basic and applied chemical research from 2008 to the present. Selected examples of C-N cross-coupling reactions between nine classes of nitrogen-based coupling partners and (pseudo)aryl halides are described for the synthesis of heterocycles, medicinally relevant compounds, natural products, organic materials, and catalysts.

Applications of Palladium-Catalyzed C–N Cross-Coupling Reactions

PubMed Central

2016-01-01

Pd-catalyzed cross-coupling reactions that form C–N bonds have become useful methods to synthesize anilines and aniline derivatives, an important class of compounds throughout chemical research. A key factor in the widespread adoption of these methods has been the continued development of reliable and versatile catalysts that function under operationally simple, user-friendly conditions. This review provides an overview of Pd-catalyzed N-arylation reactions found in both basic and applied chemical research from 2008 to the present. Selected examples of C–N cross-coupling reactions between nine classes of nitrogen-based coupling partners and (pseudo)aryl halides are described for the synthesis of heterocycles, medicinally relevant compounds, natural products, organic materials, and catalysts. PMID:27689804

The anticancer immune response of anti-PD-1/PD-L1 and the genetic determinants of response to anti-PD-1/PD-L1 antibodies in cancer patients

PubMed Central

Han, Weidong; Wang, Xian; Fang, Yong; Li, Da; Pan, Hongming; Zhang, Li

2015-01-01

The programmed death-1 (PD-1), a coinhibitory receptor expressed on activated T cells and B cells, is demonstrated to induce an immune-mediated response and play a critical role in tumor initiation and development. The cancer patients harboring PD-1 or PD ligand 1 (PD-L1) protein expression have often a poor prognosis and clinical outcome. Currently, targeting PD-1 pathway as a potential new anticancer strategy is attracting more and more attention in cancer treatment. Several monoclonal antibodies against PD-1 or PD-L1 have been reported to enhance anticancer immune responses and induce tumor cell death. Nonetheless, the precise molecular mechanisms by which PD-1 affects various cancers remain elusive. Moreover, this therapy is not effective for all the cancer patients and only a fraction of patients respond to the antibodies targeting PD-1 or PD-L1, indicating these antibodies may only works in a subset of certain cancers. Thus, understanding the novel function of PD-1 and genetic determinants of response to anti-PD-1 therapy will allow us to develop a more effective and individualized immunotherapeutic strategy for cancer. PMID:26305724

Professional Development for Adult Education Instructors. State Policy Update.

ERIC Educational Resources Information Center

Tolbert, Michelle

This State Policy Update provides background on professional development (PD) in adult education. Section 2 describes survey methods used to document how states funded and designed their PD systems. Section 3 reviews data collected by the survey of state PD systems, highlighting PD activities in Kentucky, New York, Oregon, and Tennessee. It…

Studying Teachers' Sensemaking to Investigate Teachers' Responses to Professional Development Focused on New Standards

ERIC Educational Resources Information Center

Allen, Carrie D.; Penuel, William R.

2015-01-01

Recent research on teacher professional development (PD) underscores the importance of the coherence of PD with standards, curriculum, and assessment. Teachers' judgments of the coherence of PD with larger system goals influence their decisions about what ideas and resources they appropriate from PD. Little research, however, has examined how…

Increasing the Aromatic Selectivity of Quinoline Hydrogenolysis Using Pd/MOx–Al2O3

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

Bachrach, Mark; Morlanes-Sanchez, Natalia; Canlas, Christian P.

2014-09-11

Catalysts consisting of Pd nanoparticles supported on highly dispersed TiOx–Al2O3, TaOx–Al2O3, and MoOx–Al2O3 are studied for catalytic quinoline hydrogenation and selective C–N bond cleavage at 275 °C and 20 bar H2. The Pd/MOx–Al2O3 materials exhibit significantly greater aromatic product selectivity and thus 10–15 % less required H2 for a given level of denitrogenation relative to an unmodified Pd/Al2O3 catalyst.

Continuous flow room temperature reductive aqueous homo-coupling of aryl halides using supported Pd catalysts

PubMed Central

Feiz, Afsaneh; Bazgir, Ayoob; Balu, Alina M.; Luque, Rafael

2016-01-01

A convenient and environmentally friendly protocol for the preparation of biaryls at room temperature under continuous flow conditions is reported. A simple reductive homo-coupling Ullmann-type reaction was performed in an H-Cube mini using commercially available supported Pd catalysts under mild reaction conditions, with quantitative conversion to target products. Commercial Pd catalysts were found to be highly stable under the investigated reaction conditions, with a minimum Pd leaching into solution after several reaction runs (ca. 20 h on stream). PMID:27600989

Synthesis of vanadium-doped palladium nanoparticles for hydrogen storage materials

NASA Astrophysics Data System (ADS)

Yamamoto, Yuki; Miyachi, Mariko; Yamanoi, Yoshinori; Minoda, Ai; Maekawa, Shunsuke; Oshima, Shinji; Kobori, Yoshihiro; Nishihara, Hiroshi

2011-12-01

Palladium-vanadium (Pd/V) alloy nanoparticles stabilized with n-pentyl isocyanide were prepared as new hydrogen storage materials by a facile polyol-based synthetic route with tetraethylene glycol and NaOH at 250 °C. The size distribution of the nanoparticles thus obtained featured two peaks at 4.0 ± 1.1 and 1.4 ± 0.3 nm in diameter, which were the mixture of Pd/V alloy and Pd nanoparticles. The ratio between the number of Pd/V and that of Pd nanoparticles was 51:49, and the Pd:V ratio of the overall product was 9:1 in wt%, indicating that the 4.0 nm Pd/V nanoparticles were composed of 81% Pd and 19% V. The inclusion of vanadium caused the increase in the d-spacing and thus expansion of lattice constant. A rapid increase in hydrogen content at low H2 pressures was observed for the Pd/V nanoparticles, and a 0.47 wt% H2 adsorption capacity was achieved under a H2 pressure of 10 MPa at 303 K. Hydrogen storage performances of Pd/V alloy nanoparticles was superior compared with Pd nanoparticles.

Sustainability Logistics Basing - Science and Technology Objective - Demonstration; 50, 300, 1000- Person Base Camp, Analysis of FY12 Operationally Relevant Technical Baseline

DTIC Science & Technology

2017-04-10

Natick Soldier Research , Development and Engineering Center’s Sustainability/Logistics- Basing -Science and Technology Objective – Demonstration to...CERDEC)  Tank Automotive Research , Development, and Engineering Center (TARDEC)  Product Director Contingency Basing Infrastructure (PdD – CBI...assessed using the QoL (O) tool, developed for the SLB-STO-D program by the Consumer Research Team (NSRDEC), based upon the assumptions documented within

Batch recall of French plasma-derived products due to variant Creutzfeldt-Jakob disease risk: the psychological impact on haemophilic patients, changes in their therapeutic demands and behaviour and ethical considerations.

PubMed

Aouba, A; Harroche, A; Frenzel, L; Torchet, M-F; Rothschild, C; François, I; Mamzer-Bruneel, M-F

2015-01-01

The choice of plasma-derived products (PdP) vs. recombinant products (RP) for treating haemophilia is influenced by the infectious and perceived safety of the products. Batch recall of PdP due to the risk of variant Creutzfeldt-Jakob disease (vCJD) may have unfavourable psychological impacts on haemophilia patients and influence their product preferences. This study aimed to assess the psychological impact of batch recalls of PdP in six haemophilia patients and their therapeutic demands, and to discuss the ethical problems in physicians' management of this event. A survey was conducted using a new interview form and an existing anxiety and depression questionnaire. Batch recalls produce recurrent negative emotional outcomes in haemophiliacs and their families. The quality, understanding and efficiency of the batch recall announcements were unsatisfactory in some respects. Only one patient still had some of the vials in question, and only three patients understood the real reason for the batch recall. Four patients asked to change their PdP for RP; a fifth patient was considering doing so. Here, topics for discussion include the delivery of an unclear message to patients about a very uncertain risk of a frightening disease, the reasons to maintain PdP when RP are largely available, except in specific cases, and the related discomfort for caregivers. The ethical questions revealed by batch recalls and the high psychological impact of vCJD risk on patients can no longer be ignored, and require surveys assessing the rationales and choices of the healthcare authorities, manufacturers, prescribers and users. © 2014 John Wiley & Sons Ltd.

Highly efficient catalytic systems based on Pd-coated microbeads

NASA Astrophysics Data System (ADS)

Lim, Jin Hyun; Cho, Ahyoung; Lee, Seung Hwan; Park, Bumkyo; Kang, Dong Woo; Koo, Chong Min; Yu, Taekyung; Park, Bum Jun

2018-01-01

The efficiency of two prototype catalysis systems using palladium (Pd)-coated microparticles was investigated with regard to the recovery and recyclability of the catalytic particles. One such system was the interface-adsorption method, in which polymer particles coated with Pd nanoparticles strongly and irreversibly attach to the oil-water interface. Due to the irreversible adsorption of the catalytic particles to the interface, particle loss was completely prevented while mixing the aqueous solution and while collecting the products. The other system was based on the magnetic field-associated particle recovery method. The use of polymeric microparticles containing Pd nanoparticles and magnetite nanoparticles accelerated the sedimentation of the particles in the aqueous phase by applying a strong magnetic field, consequently suppressing drainage of the particles from the reactor along the product stream. Upon multiple runs of the catalytic reactions, it was found that conversion does not change significantly, demonstrating the excellent recyclability and performance efficiency in the catalytic processes.

Dechlorination of DDT, DDD and DDE in soil (slurry) phase using magnesium/palladium system.

PubMed

Gautam, Sumit Kumar; Suresh, Sumathi

2006-12-01

Mg0/Pd4+ was able to dechlorinate >99% of extractable DDT (initial concentration of 10 mg DDT kg(-1) of soil) and >90% of extractable DDT (initial concentration of 50 mg DDT kg(-1) of soil) in soil slurry. Mg0/Pd4+ was also found to be effective in dechlorinating of 50 mg kg(-1) DDD and DDE, in soil aged for varying time periods. GC-MS analyses revealed the formation of 1,1-diphenylethane as an end product from DDT, DDE and DDD. To the best of our knowledge this is the first report describing the application Mg0/Pd4+ system for remediation of DDT, DDD and DDE contaminated soil. We conclude that reductive dechlorination reaction catalyzed by Mg0/Pd4+ may be a promising system to remediate soil contaminated with DDT and its dechlorinated products such as DDD and DDE.

Dechlorination of disinfection by-product monochloroacetic acid in drinking water by nanoscale palladized iron bimetallic particle.

PubMed

Chen, Chao; Wang, Xiangyu; Chang, Ying; Liu, Huiling

2008-01-01

Nanoscale palladized iron (Pd/Fe) bimetallic particles were prepared by reductive deposition method. The particles were characterized by X-ray diffraction (XRD), X-ray fluorescence (XRF), scanning electron microscope (SEM), transmission electron microscope (TEM), and Brunauer-Emmett-Teller-nitrogen (BET-N2) method. Data obtained from those methods indicated that nanoscale Pd/Fe bimetallic particles contained alpha-Fe0. Detected Pd to Fe ratio by weight (Pd/Fe ratio) was close to theoretical value. Spherical granules with diameter of 47 +/- 11.5 nm connected with one another to form chains and the chains composed nanoscale Pd/Fe bimetallic particles. Specific surface area of particles was 51 m2/g. The factors, such as species of reductants, Pd/Fe ratio, dose of nanoscale Pd/Fe bimetallic particles added into solutions, solution initial pH, and a variety of solvents were studied. Dechlorination effect of monochloroacetic acid by different reductants followed the trend: nanoscale Pd/Fe bimetallic particles of 0.182% Pd/Fe > nanoscale Fe > reductive Fe. When the Pd/Fe ratio was lower than 0.083%, increasing Pd/Fe ratio would increase dechlorination efficiency (DE) of MCAA. When the Pd/Fe ratio was higher than 0.083%, increasing Pd/Fe ratio caused a decrease in DE. Adding more nanoscale Pd/Fe bimetallic particles to solution would enhance DE. The DE of MCAA decreased as initial pH of solution increased.

Finger force changes in the absence of visual feedback in patients with Parkinson’s disease

PubMed Central

Jo, Hang Jin; Ambike, Satyajit; Lewis, Mechelle M.; Huang, Xuemei; Latash, Mark L.

2015-01-01

Objectives We investigated the unintentional drift in total force and in sharing of the force between fingers in two-finger accurate force production tasks performed without visual feedback by patients with Parkinson’s disease (PD) and healthy controls. In particular, we were testing a hypothesis that adaptation to the documented loss of action stability could lead to faster force drop in PD. Methods PD patients and healthy controls performed accurate constant force production tasks without visual feedback by different finger pairs, starting with different force levels and different sharing patterns of force between the two fingers. Results Both groups showed an exponential force drop with time and a drift of the sharing pattern towards 50:50. The PD group showed a significantly faster force drop without a change in speed of the sharing drift. These results were consistent across initial force levels, sharing patterns, and finger pairs. A pilot test of four subjects, two PD and two controls, showed no consistent effects of memory on the force drop. Conclusions We interpret the force drop as a consequence of back-coupling between the actual and referent finger coordinates that draws the referent coordinate towards the actual one. The faster force drop in the PD group is interpreted as adaptive to the loss of action stability in PD. The lack of group differences in the sharing drift suggests two potentially independent physiological mechanisms contributing to the force and sharing drifts. Significance The hypothesis on adaptive changes in PD with the purpose to ensure stability of steady states may have important implications for treatment of PD. The speed of force drop may turn into a useful tool to quantify such adaptive changes. PMID:26072437

Status of renal replacement therapy and peritoneal dialysis in Mexico.

PubMed

Cueto-Manzano, Alfonso M; Rojas-Campos, Enrique

2007-01-01

Mexico is struggling to gain a place among developed countries; however, there are many socioeconomic and health problems still waiting for resolution. While Mexico has the twelfth largest economy in the world, a large portion of its population is impoverished. Treatment for end-stage renal disease (377 patients per million population) is determined by the individual's access to resources such as private medical care (approximately 3%) and public sources (Social Security System: approximately 40%; Health Secretariat: approximately 57%). With only 6% of the gross national product spent on healthcare and most treatment providers being public health institutions that are often under economic restrictions, it is not surprising that many Mexican patients do not receive renal replacement therapy. Mexico is still the country with the largest utilization of peritoneal dialysis (PD) in the world, with 18% on automated PD, 56% on continuous ambulatory PD (CAPD), and 26% on hemodialysis. Results of PD (patient morbi-mortality, peritonitis rate, and technique survival) in Mexico are comparable to other countries. However, malnutrition and diabetes mellitus are highly prevalent in Mexican patients on CAPD programs, and these conditions are among the most important risk factors for a poor outcome in our setting.

Knowledge sharing and organizational learning in the context of hospital infection prevention.

PubMed

Rangachari, Pavani

2010-01-01

Recently, hospitals that have been successful in preventing infections have labeled their improvement approaches as either the Toyota Production System (TPS) approach or the Positive Deviance (PD) approach. PD has been distinguished from TPS as being a bottom-up approach to improvement, as against top-down. Facilities that have employed both approaches have suggested that PD may be more effective than TPS for infection prevention. This article integrates organizational learning, institutional, and knowledge network theories to develop a theoretical framework for understanding the structure and evolution of effective knowledge-sharing networks in health care organizations, that is, networks most conducive to learning and improvement. Contrary to arguments put forth by hospital success stories, the framework suggests that networks rich in brokerage and hierarchy (ie, top-down, "TPS-like" structures) may be more effective for learning and improvement in health care organizations, compared with a networks rich in density (ie, bottom-up, "PD-like" structures). The theoretical framework and ensuing analysis help identify several gaps in the literature related to organization learning and improvement in the infection prevention context. This, in turn, helps put forth recommendations for health management research and practice.

Enhanced Hydrogen Transport over Palladium Ultrathin Films through Surface Nanostructure Engineering.

PubMed

Abate, Salvatore; Giorgianni, Gianfranco; Gentiluomo, Serena; Centi, Gabriele; Perathoner, Siglinda

2015-11-01

Palladium ultrathin films (around 2 μm) with different surface nanostructures are characterized by TEM, SEM, AFM, and temperature programmed reduction (TPR), and evaluated in terms of H2 permeability and H2-N2 separation. A change in the characteristics of Pd seeds by controlled oxidation-reduction treatments produces films with the same thickness, but different surface and bulk nanostructure. In particular, the films have finer and more homogeneous Pd grains, which results in lower surface roughness. Although all samples show high permeo-selectivity to H2 , the samples with finer grains exhibit enhanced permeance and lower activation energy for H2 transport. The analysis of the data suggests that grain boundaries between the Pd grains at the surface favor H2 transfer from surface to subsurface. Thus, the surface nanostructure plays a relevant role in enhancing the transport of H2 over the Pd ultrathin film, which is an important aspect to develop improved membranes that function at low temperatures and toward new integrated process architectures in H2 and syngas production with enhanced sustainability. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Electrochemical characterization of Pt-Ru-Pd catalysts for methanol oxidation reaction in direct methanol fuel cells.

PubMed

Choi, M; Han, C; Kim, I T; An, J C; Lee, J J; Lee, H K; Shim, J

2011-01-01

PtRuPd nanoparticles on carbon black were prepared and characterized as electrocatalysts for methanol oxidation reaction in direct methanol fuel cells. Nano-sized Pd (2-4 nm) particles were deposited on Pt/C and PtRu/C (commercial products) by a simple chemical reduction process. The structural and physical information of the PtRuPd/C were confirmed by TEM and XRD, and their electrocatalytic activities were measured by cyclic voltammetry and linear sweep voltammetry. The catalysts containing Pd showed higher electrocatalytic activity for methanol oxidation reaction than the other catalysts. This might be attributed to an increase in the electrochemical surface area of Pt, which is caused by the addition of Pd; this results in increased catalyst utilization.

Plasmodesmata: channels for intercellular signaling during plant growth and development.

PubMed

Sevilem, Iris; Yadav, Shri Ram; Helariutta, Ykä

2015-01-01

Plants have evolved strategies for short- and long-distance communication to coordinate plant development and to adapt to changing environmental conditions. Plasmodesmata (PD) are intercellular nanochannels that provide an effective pathway for both selective and nonselective movement of various molecules that function in diverse biological processes. Numerous non-cell-autonomous proteins (NCAP) and small RNAs have been identified that have crucial roles in cell fate determination and organ patterning during development. Both the density and aperture size of PD are developmentally regulated, allowing formation of spatial symplastic domains for establishment of tissue-specific developmental programs. The PD size exclusion limit (SEL) is controlled by reversible deposition of callose, as well as by some PD-associated proteins. Although a large number of PD-associated proteins have been identified, many of their functions remain unknown. Despite the fact that PD are primarily membranous structures, surprisingly very little is known about their lipid composition. Thus, future studies in PD biology will provide deeper insights into the high-resolution structure and tightly regulated functions of PD and the evolution of PD-mediated cell-to-cell communication in plants.

Fission product palladium-silicon carbide interaction in htgr fuel particles

NASA Astrophysics Data System (ADS)

Minato, Kazuo; Ogawa, Toru; Kashimura, Satoru; Fukuda, Kousaku; Shimizu, Michio; Tayama, Yoshinobu; Takahashi, Ishio

1990-07-01

Interaction of fission product palladium (Pd) with the silicon carbide (SiC) layer was observed in irradiated Triso-coated uranium dioxide particles for high temperature gas-cooled reactors (HTGR) with an optical microscope and electron probe microanalyzers. The SiC layers were attacked locally or the reaction product formed nodules at the attack site. Although the main element concerned with the reaction was palladium, rhodium and ruthenium were also detected at the corroded areas in some particles. Palladium was detected on both the hot and cold sides of the particles, but the corroded areas and the palladium accumulations were distributed particularly on the cold side of the particles. The observed Pd-SiC reaction depths were analyzed on the assumption that the release of palladium from the fuel kernel controls the whole Pd-SiC reaction.

Clinical trials for authorized biosimilars in the European Union: a systematic review

PubMed Central

Mielke, Johanna; Koenig, Franz; Jones, Byron

2016-01-01

Aim In 2006, Omnitrope (by Sandoz) was the first approved biosimilar in Europe. To date, 21 biosimilars for seven different biologics are on the market. The present study compared the clinical trials undertaken to obtain market authorization. Methods We summarized the findings of a comprehensive review of all clinical trials up to market authorization of approved biosimilars, using the European public assessment reports (EPARs) published by the European Medicines Agency (EMA). The features compared were, among others, the number of patients enrolled, the number of trials, the types of trial design, choice of endpoints and equivalence margins for pharmacokinetic (PK)/pharmacodynamic (PD) and phase III trials. Results The variability between the clinical development strategies is high. Some differences are explainable by the characteristics of the product; if, for example, the PD marker can be assumed to predict the clinical outcome, no efficacy trials might be necessary. However, even for products with the same reference product, the sample size, endpoints and statistical models are not always the same. Conclusions There seems to be flexibility for sponsors regarding the decision as to how best to prove biosimilarity. PMID:27580073

A facile self-assembly approach to prepare palladium/carbon nanotubes catalyst for the electro-oxidation of ethanol

NASA Astrophysics Data System (ADS)

Wen, Cuilian; Zhang, Xinyuan; Wei, Ying; Zhang, Teng; Chen, Changxin

2018-02-01

A facile self-assembly approach is reported to prepare palladium/carbon nanotubes (Pd/CNTs) catalyst for the electro-oxidation of ethanol. In this method, the Pd-oleate/CNTs was decomposed into the Pd/CNTs at an optimal temperature of 195 °C in air, in which no inert gas is needed for the thermal decomposition process due to the low temperature used and the decomposed products are also environmental friendly. The prepared Pd/CNTs catalyst has a high metallic Pd0 content and the Pd particles in the catalyst are disperse, uniform-sized with an average size of ˜2.1 nm, and evenly distributed on the CNTs. By employing our strategy, the problems including the exfoliation of the metal particles from the CNTs and the aggregation of the metal particles can be solved. Comparing with the commercial Pd/C one, the prepared Pd/CNTs catalyst exhibits a much higher electrochemical activity and stability for the electro-oxidation of ethanol in the direct ethanol fuel cells.

Measurements of the thermal neutron cross-section and resonance integral for the 108Pd(n,γ)109Pd reaction

NASA Astrophysics Data System (ADS)

Hien, Nguyen Thi; Kim, Guinyun; Kim, Kwangsoo; Do, Nguyen Van; Khue, Pham Duc; Thanh, Kim Tien; Shin, Sung-Gyun; Cho, Moo-Hyun

2018-06-01

The thermal neutron capture cross-section (σ0) and resonance integral (I0) of the 108Pd(n,γ)109Pd reaction have been measured relative to that of the monitor reaction 197Au(n,γ)198Au. The measurements were carried out using the neutron activation with the cadmium ratio method. Both the samples and monitors were irradiated with and without cadmium cover of 0.5 mm thickness. The induced activities of the reaction products were measured with a well calibrated HPGe γ-ray detector. In order to improve the accuracy of the results, the necessary corrections for the counting losses were made. The thermal neutron capture cross-section and resonance integral of the 108Pd(n,γ)109Pd reaction were determined to be σ0,Pd = 8.68 ± 0.41 barn and I0,Pd = 245.6 ± 24.8 barn, respectively. The obtained results are compared with literature values and discussed.

PD-1/PD-L1, but not PD-1/PD-L2, interactions regulate the severity of experimental autoimmune encephalomyelitis.

PubMed

Carter, Laura L; Leach, Michael W; Azoitei, Mihai L; Cui, Junqing; Pelker, Jeffrey W; Jussif, Jason; Benoit, Steve; Ireland, Gretchen; Luxenberg, Deborah; Askew, G Roger; Milarski, Kim L; Groves, Christopher; Brown, Tom; Carito, Brenda A; Percival, Karen; Carreno, Beatriz M; Collins, Mary; Marusic, Suzana

2007-01-01

Interactions between PD-1 and its two differentially expressed ligands, PD-L1 and PD-L2, attenuate T cell activation and effector function. To determine the role of these molecules in autoimmune disease of the CNS, PD-1-/-, PD-L1-/- and PD-L2-/- mice were generated and immunized to induce experimental autoimmune encephalomyelitis (EAE). PD-1-/- and PD-L1-/- mice developed more severe EAE than wild type and PD-L2-/- mice. Consistent with this, PD-1-/- and PD-L1-/- cells produced elevated levels of the pro-inflammatory cytokines IFN-gamma, TNF, IL-6 and IL-17. These results demonstrate that interactions between PD-1/PD-L1, but not PD-1/PDL-2, are crucial in attenuating T cell responses in EAE.

Polydatin promotes Nrf2-ARE anti-oxidative pathway through activating Sirt1 to resist AGEs-induced upregulation of fibronetin and transforming growth factor-β1 in rat glomerular messangial cells.

PubMed

Huang, Kaipeng; Chen, Cheng; Hao, Jie; Huang, Junying; Wang, Shaogui; Liu, Peiqing; Huang, Heqing

2015-01-05

Sirt1 and nuclear factor-E2 related factor 2 (Nrf2)-anti-oxidant response element (ARE) anti-oxidative pathway play important regulatory roles in the pathological progression of diabetic nephropathy (DN) induced by advanced glycation-end products (AGEs). Polydatin (PD), a glucoside of resveratrol, has been shown to possess strong anti-oxidative bioactivity. Our previous study demonstrated that PD markedly resists the progression of diabetic renal fibrosis and thus, inhibits the development of DN. Whereas, whether PD could resist DN through regulating Sirt1 and consequently promoting Nrf2-ARE pathway needs further investigation. Here, we found that concomitant with decreasing RAGE (the specific receptor for AGEs) expression, PD significantly reversed the downregulation of Sirt1 in terms of protein expression and deacetylase activity and attenuated FN and TGF-β1 expression in GMCs exposed to AGEs. Under AGEs-treatment condition, PD could decrease Keap1 expression and promote the nuclear content, ARE-binding ability, and transcriptional activity of Nrf2. In addition, PD increased the protein levels of heme oxygenase 1 (HO-1) and superoxide dismutase 1 (SOD1), two target genes of Nrf2. The activation of Nrf2-ARE pathway by PD eventually led to the quenching of ROS overproduction sharply boosted by AGEs. Depletion of Sirt1 blocked Nrf2-ARE pathway activation and reversed FN and TGF-β1 downregulation induced by PD in GMCs challenged with AGEs. Along with reducing HO-1 and SOD1 expression, silencing of Nrf2 increased FN and TGF-β1 levels. PD treatment elevated Sirt1 and Nrf2 levels in the kidney tissues of diabetic rats, then improved the anti-oxidative capacity and renal dysfunction of diabetic models, and finally reversed the upregulation of FN and TGF-β1. Taken together, the resistance of PD on upregulated FN and TGF-β1 induced by AGEs via oxidative stress in GMCs is closely associated with its activation of Sirt1-Nrf2-ARE pathway. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

RpfF-dependent regulon of Xylella fastidiosa.

PubMed

Wang, Nian; Li, Jian-Liang; Lindow, Steven E

2012-11-01

ABSTRACT Xylella fastidiosa regulates traits important to both virulence of grape as well as colonization of sharpshooter vectors via its production of a fatty acid signal molecule known as DSF whose production is dependent on rpfF. Although X. fastidiosa rpfF mutants exhibit increased virulence to plants, they are unable to be spread from plant to plant by insect vectors. To gain more insight into the traits that contribute to these processes, a whole-genome Agilent DNA microarray for this species was developed and used to determine the RpfF-dependent regulon by transcriptional profiling. In total, 446 protein coding genes whose expression was significantly different between the wild type and an rpfF mutant (false discovery rate < 0.05) were identified when cells were grown in PW liquid medium. Among them, 165 genes were downregulated in the rpfF mutant compared with the wild-type strain whereas 281 genes were over-expressed. RpfF function was required for regulation of 11 regulatory and σ factors, including rpfE, yybA, PD1177, glnB, rpfG, PD0954, PD0199, PD2050, colR, rpoH, and rpoD. In general, RpfF is required for regulation of genes involved in attachment and biofilm formation, enhancing expression of hemagglutinin genes hxfA and hxfB, and suppressing most type IV pili and gum genes. A large number of other RpfF-dependent genes that might contribute to virulence or insect colonization were also identified such as those encoding hemolysin and colicin V, as well as genes with unknown functions.

Construction of a Genetic System for Streptomyces albulus PD-1 and Improving Poly(ε-L-lysine) Production Through Expression of Vitreoscilla Hemoglobin.

PubMed

Xu, Zhaoxian; Cao, Changhong; Sun, Zhuzhen; Li, Sha; Xu, Zheng; Feng, Xiaohai; Xu, Hong

2015-11-01

Poly(ε-L-lysine) (ε-PL) is a novel bioactive polymer secreted by filamentous bacteria. Owing to lack of a genetic system for most ε-PL-producing strains, very little research on enhancing ε-PL biosynthesis by genetic manipulation has been reported. In this study, an effective genetic system was established via intergeneric conjugal transfer for Streptomyces albulus PD-1, a famous ε-PL-producing strain. Using the established genetic system, the Vitreoscilla hemoglobin (VHb) gene was integrated into the chromosome of S. albulus PD-1 to alleviate oxygen limitation and to enhance the biosynthesis of ε-PL in submerged fermentation. Ultimately, the production of ε-PL increased from 22.7 g/l to 34.2 g/l after fed-batch culture in a 5 L bioreactor. Determination of the oxygen uptake rate, transcriptional level of ε-PL synthetase gene, and ATP level unveiled that the expression of VHb in S. albulus PD-1 enhanced ε-PL biosynthesis by improving respiration and ATP supply. To the best of our knowledge, this is the first report on enhancing ε-PL production by chromosomal integration of the VHb gene in an ε-PL-producing strain, and it will open a new avenue for ε-PL production.

A novel sputtered Pd mesh architecture as an advanced electrocatalyst for highly efficient hydrogen production

NASA Astrophysics Data System (ADS)

de Lucas-Consuegra, Antonio; de la Osa, Ana R.; Calcerrada, Ana B.; Linares, José J.; Horwat, David

2016-07-01

This study reports the preparation, characterization and testing of a sputtered Pd mesh-like anode as an advanced electrocatalyst for H2 production from alkaline ethanol solutions in an Alkaline Membrane Electrolyzer (AEM). Pd anodic catalyst is prepared by magnetron sputtering technique onto a microfiber carbon paper support. Scanning Electron Microscopy images reveal that the used preparation technique enables to cover the surface of the carbon microfibers exposed to the Pd target, leading to a continuous network that also maintains part of the original carbon paper macroporosity. Such novel anodic architecture (organic binder free) presents an excellent electro-chemical performance, with a maximum current density of 700 mA cm-2 at 1.3 V, and, concomitantly, a large H2 production rate with low energy requirement compared to water electrolysis. Potassium hydroxide emerges as the best electrolyte, whereas temperature exerts the expected promotional effect up to 90 °C. On the other hand, a 1 mol L-1 ethanol solution is enough to guarantee an efficient fuel supply without any mass transfer limitation. The proposed system also demonstrates to remain stable over 150 h of operation along five consecutives cycles, producing highly pure H2 (99.999%) at the cathode and potassium acetate as the main anodic product.

Ultrasound findings predict progression to inflammatory arthritis in anti-CCP antibody-positive patients without clinical synovitis.

PubMed

Nam, Jackie L; Hensor, Elizabeth M A; Hunt, Laura; Conaghan, Philip G; Wakefield, Richard J; Emery, Paul

2016-12-01

To determine whether ultrasound can identify anti-cyclic citrullinated peptide (anti-CCP) antibody-positive patients without clinical synovitis (CS) who progress to inflammatory arthritis (IA). In a prospective study, anti-CCP-positive patients without CS underwent ultrasound imaging of 32 joints (wrists, metacarpophalangeal joints, proximal interphalangeal joints and metatarsophalangeal joints (MTPs)) and were monitored for the development of IA. Associations between baseline ultrasound findings (grey scale (GS), power Doppler (PD) and erosions) and (1) progression to IA and (2) development of CS within an individual joint were measured. Consecutive anti-CCP-positive patients (n=136; mean age 51 years, 100 women) were followed up for median of 18.3 months (range 0.1-79.6). At baseline 96% had GS, 30% had PD and 21% had one or more erosions. IA developed in 57 patients (42%) after median of 8.6 months (range 0.1-52.4). Ultrasound abnormalities (GS ≥2, PD ≥1 or erosion ≥1) were found in 86% at baseline compared with 67% of non-progressors (χ 2 =6.3, p=0.012). Progression to IA was significantly higher in those with ultrasound findings in any joint (excluding MTPs for GS) (GS ≥2: 55% vs 24%, HR (95% CI) 2.3 (1.0 to 4.9), p=0.038; PD ≥2: 75% vs 32%, 3.7 (2.0 to 6.9), p<0.001 and erosion ≥1: 71% vs 34%, 2.9 (1.7 to 5.1), p<0.001). Furthermore, progression occurred earlier with PD ≥2 (median 7.1 vs 52.4 months) and erosion ≥1 (15.4 vs 46.5). At the individual joint level, the trend for progression to CS was more significant for GS and PD (GS ≥2: 26% vs 3%, 9.4 (5.1 to 17.5), p<0.001; PD ≥2: 55% vs 4%, 31.3 (15.6 to 62.9), p<0.001). Ultrasound features of joint inflammation may be detected in anti-CCP-positive patients without CS. Ultrasound findings predict progression (and rate of progression) to IA, with the risk of progression highest in those with PD signal. NCT02012764; Results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Solvent-free Hydrodeoxygenation of Bio-oil Model Compounds Cyclopentanone and Acetophenone over Flame-made Bimetallic Pt-Pd/ZrO2 Catalysts

PubMed Central

Jiang, Yijiao; Büchel, Robert; Huang, Jun; Krumeich, Frank; Pratsinis, Sotiris E.; Baiker, Alfons

2013-01-01

Bimetallic Pt-Pd/ZrO2 catalysts with different Pt/Pd atomic ratio and homogeneous dispersion of the metal nanoparticles were prepared in a single step by flame-spray pyrolysis. The catalysts show high activity and tuneable product selectivity for the solvent-free hydrodeoxygenation of the bio-oil model compounds cyclopentanone and acetophenone. PMID:22674738

Carbon-supported bimetallic Pd–Fe catalysts for vapor-phase hydrodeoxygenation of guaiacol

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

Sun, Junming; Karim, Ayman M.; Zhang, He

2013-10-01

Abstract Carbon supported metal catalysts (Cu/C, Fe/C, Pd/C, Pt/C, PdFe/C and Ru/C) have been prepared, characterized and tested for vapor-phase hydrodeoxygenation (HDO) of guaiacol (GUA) at atmospheric pressure. Phenol was the major intermediate on all catalysts. Over the noble metal catalysts saturation of the aromatic ring was the major pathway observed at low temperature (250 °C), forming predominantly cyclohexanone and cyclohexanol. Substantial ring opening reaction was observed on Pt/C and Ru/C at higher reaction temperatures (e.g., 350 °C). Base metal catalysts, especially Fe/C, were found to exhibit high HDO activity without ring-saturation or ring-opening with the main products being benzene,more » phenol along with small amounts of cresol, toluene and trimethylbenzene (TMB). A substantial enhancement in HDO activity was observed on the PdFe/C catalysts. Compared with Fe/C, the yield to oxygen-free aromatic products (i.e., benzene/toluene/TMB) on PdFe/C increased by a factor of four at 350 °C, and by approximately a factor of two (83.2% versus 43.3%) at 450 °C. The enhanced activity of PdFe/C is attributed to the formation of PdFe alloy as evidenced by STEM, EDS and TPR.« less

Triple tracks in CR-39 as the result of Pd-D Co-deposition: evidence of energetic neutrons.

PubMed

Mosier-Boss, Pamela A; Szpak, Stanislaw; Gordon, Frank E; Forsley, Lawrence P G

2009-01-01

Since the announcement by Fleischmann and Pons that the excess enthalpy generated in the negatively polarized Pd-D-D(2)O system was attributable to nuclear reactions occurring inside the Pd lattice, there have been reports of other manifestations of nuclear activities in this system. In particular, there have been reports of tritium and helium-4 production; emission of energetic particles, gamma or X-rays, and neutrons; as well as the transmutation of elements. In this communication, the results of Pd-D co-deposition experiments conducted with the cathode in close contact with CR-39, a solid-state nuclear etch detector, are reported. Among the solitary tracks due to individual energetic particles, triple tracks are observed. Microscopic examination of the bottom of the triple track pit shows that the three lobes of the track are splitting apart from a center point. The presence of three alpha-particle tracks outgoing from a single point is diagnostic of the (12)C(n,n')3alpha carbon breakup reaction and suggests that DT reactions that produce > or = 9.6 MeV neutrons are occurring inside the Pd lattice. To our knowledge, this is the first report of the production of energetic (> or = 9.6 MeV) neutrons in the Pd-D system.

A Conserved Role for p48 Homologs in Protecting Dopaminergic Neurons from Oxidative Stress

PubMed Central

Bou Dib, Peter; Gnägi, Bettina; Daly, Fiona; Sabado, Virginie; Tas, Damla; Glauser, Dominique A.; Meister, Peter; Nagoshi, Emi

2014-01-01

Parkinson's disease (PD) is the most common neurodegenerative movement disorder characterized by the progressive loss of dopaminergic (DA) neurons. Both environmental and genetic factors are thought to contribute to the pathogenesis of PD. Although several genes linked to rare familial PD have been identified, endogenous risk factors for sporadic PD, which account for the majority of PD cases, remain largely unknown. Genome-wide association studies have identified many single nucleotide polymorphisms associated with sporadic PD in neurodevelopmental genes including the transcription factor p48/ptf1a. Here we investigate whether p48 plays a role in the survival of DA neurons in Drosophila melanogaster and Caenorhabditis elegans. We show that a Drosophila p48 homolog, 48-related-2 (Fer2), is expressed in and required for the development and survival of DA neurons in the protocerebral anterior medial (PAM) cluster. Loss of Fer2 expression in adulthood causes progressive PAM neuron degeneration in aging flies along with mitochondrial dysfunction and elevated reactive oxygen species (ROS) production, leading to the progressive locomotor deficits. The oxidative stress challenge upregulates Fer2 expression and exacerbates the PAM neuron degeneration in Fer2 loss-of-function mutants. hlh-13, the worm homolog of p48, is also expressed in DA neurons. Unlike the fly counterpart, hlh-13 loss-of-function does not impair development or survival of DA neurons under normal growth conditions. Yet, similar to Fer2, hlh-13 expression is upregulated upon an acute oxidative challenge and is required for the survival of DA neurons under oxidative stress in adult worms. Taken together, our results indicate that p48 homologs share a role in protecting DA neurons from oxidative stress and degeneration, and suggest that loss-of-function of p48 homologs in flies and worms provides novel tools to study gene-environmental interactions affecting DA neuron survival. PMID:25340742

Clinical-genetic model predicts incident impulse control disorders in Parkinson's disease.

PubMed

Kraemmer, Julia; Smith, Kara; Weintraub, Daniel; Guillemot, Vincent; Nalls, Mike A; Cormier-Dequaire, Florence; Moszer, Ivan; Brice, Alexis; Singleton, Andrew B; Corvol, Jean-Christophe

2016-10-01

Impulse control disorders (ICD) are commonly associated with dopamine replacement therapy (DRT) in patients with Parkinson's disease (PD). Our aims were to estimate ICD heritability and to predict ICD by a candidate genetic multivariable panel in patients with PD. Data from de novo patients with PD, drug-naïve and free of ICD behaviour at baseline, were obtained from the Parkinson's Progression Markers Initiative cohort. Incident ICD behaviour was defined as positive score on the Questionnaire for Impulsive-Compulsive Disorders in PD. ICD heritability was estimated by restricted maximum likelihood analysis on whole exome sequencing data. 13 candidate variants were selected from the DRD2, DRD3, DAT1, COMT, DDC, GRIN2B, ADRA2C, SERT, TPH2, HTR2A, OPRK1 and OPRM1 genes. ICD prediction was evaluated by the area under the curve (AUC) of receiver operating characteristic (ROC) curves. Among 276 patients with PD included in the analysis, 86% started DRT, 40% were on dopamine agonists (DA), 19% reported incident ICD behaviour during follow-up. We found heritability of this symptom to be 57%. Adding genotypes from the 13 candidate variants significantly increased ICD predictability (AUC=76%, 95% CI (70% to 83%)) compared to prediction based on clinical variables only (AUC=65%, 95% CI (58% to 73%), p=0.002). The clinical-genetic prediction model reached highest accuracy in patients initiating DA therapy (AUC=87%, 95% CI (80% to 93%)). OPRK1, HTR2A and DDC genotypes were the strongest genetic predictive factors. Our results show that adding a candidate genetic panel increases ICD predictability, suggesting potential for developing clinical-genetic models to identify patients with PD at increased risk of ICD development and guide DRT management. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

From bio-mineralisation to fuel cells: biomanufacture of Pt and Pd nanocrystals for fuel cell electrode catalyst.

PubMed

Yong, P; Paterson-Beedle, M; Mikheenko, I P; Macaskie, L E

2007-04-01

Biosynthesis of nano-scale platinum and palladium was achieved via enzymatically-mediated deposition of metal ions from solution. The bio-accumulated Pt(0) and Pd(0) crystals were dried, applied onto carbon paper and tested as anodes in a polymer electrolyte membrane (PEM) fuel cell for power production. Up to 100% and 81% of the maximum power generation was achieved by the bio-Pt and bio-Pd catalysts, respectively, compared to commercial fuel cell grade Pt catalyst. Hence, biomineralisation could pave the way for economical production of fuel cell catalysts since previous studies have shown that precious metals can be biorecovered from wastes into catalytically active bionanomaterials.

How Parkinsonian Toxins Dysregulate the Autophagy Machinery

PubMed Central

Dagda, Ruben K.; Das Banerjee, Tania; Janda, Elzbieta

2013-01-01

Since their discovery, Parkinsonian toxins (6-hydroxydopamine, MPP+, paraquat, and rotenone) have been widely employed as in vivo and in vitro chemical models of Parkinson’s disease (PD). Alterations in mitochondrial homeostasis, protein quality control pathways, and more recently, autophagy/mitophagy have been implicated in neurotoxin models of PD. Here, we highlight the molecular mechanisms by which different PD toxins dysregulate autophagy/mitophagy and how alterations of these pathways play beneficial or detrimental roles in dopamine neurons. The convergent and divergent effects of PD toxins on mitochondrial function and autophagy/mitophagy are also discussed in this review. Furthermore, we propose new diagnostic tools and discuss how pharmacological modulators of autophagy/mitophagy can be developed as disease-modifying treatments for PD. Finally, we discuss the critical need to identify endogenous and synthetic forms of PD toxins and develop efficient health preventive programs to mitigate the risk of developing PD. PMID:24217228

Subchronic infusion of the product of inflammation prostaglandin J2 models sporadic Parkinson's disease in mice.

PubMed

Pierre, Sha-Ron; Lemmens, Marijke A M; Figueiredo-Pereira, Maria E

2009-07-25

Chronic neuroinflammation is implicated in Parkinson's disease (PD). Inflammation involves the activation of microglia and astrocytes that release high levels of prostaglandins. There is a profound gap in our understanding of how cyclooxygenases and their prostaglandin products redirect cellular events to promote PD neurodegeneration. The major prostaglandin in the mammalian brain is prostaglandin D2, which readily undergoes spontaneous dehydration to generate the bioactive cyclopentenone prostaglandins of the J2 series. These J2 prostaglandins are highly reactive and neurotoxic products of inflammation shown in cellular models to impair the ubiquitin/proteasome pathway and cause the accumulation of ubiquitinated proteins. PD is a disorder that exhibits accumulation of ubiquitinated proteins in neuronal inclusions (Lewy bodies). The role of J2 prostaglandins in promoting PD neurodegeneration has not been investigated under in vivo conditions. We addressed the neurodegenerative and behavioral effects of the administration of prostaglandin J2 (PGJ2) simultaneously into the substantia nigra/striatum of adult male FVB mice by subchronic microinjections. One group received unilateral injections of DMSO (vehicle, n = 6) and three groups received PGJ2 [3.4 microg or 6.7 microg (n = 6 per group) or 16.7 microg (n = 5)] per injection. Immunohistochemical and behavioral analyses were applied to assess the effects of the subchronic PGJ2 microinfusions. Immunohistochemical analysis demonstrated a PGJ2 dose-dependent significant and selective loss of dopaminergic neurons in the substantia nigra while the GABAergic neurons were spared. PGJ2 also triggered formation of aggregates immunoreactive for ubiquitin and alpha-synuclein in the spared dopaminergic neurons. Moreover, PGJ2 infusion caused a massive microglia and astrocyte activation that could initiate a deleterious cascade leading to self-sustained progressive neurodegeneration. The PGJ2-treated mice also exhibited locomotor and posture impairment. Our studies establish the first model of inflammation in which administration of an endogenous highly reactive product of inflammation, PGJ2, recapitulates key aspects of PD. Our novel PGJ2-induced PD model strongly supports the view that localized and chronic production of highly reactive and neurotoxic prostaglandins, such as PGJ2, in the CNS could be an integral component of inflammation triggered by insults evoked by physical, chemical or microbial stimuli and thus establishes a link between neuroinflammation and PD neurodegeneration.

Structural analysis of linear and conformational epitopes of allergens

PubMed Central

Ivanciuc, Ovidiu; Schein, Catherine H.; Garcia, Tzintzuni; Oezguen, Numan; Negi, Surendra S.; Braun, Werner

2009-01-01

In many countries regulatory agencies have adopted safety guidelines, based on bioinformatics rules from the WHO/FAO and EFSA recommendations, to prevent potentially allergenic novel foods or agricultural products from reaching consumers. We created the Structural Database of Allergenic Proteins (SDAP, http://fermi.utmb.edu/SDAP/) to combine data that had previously been available only as flat files on Web pages or in the literature. SDAP was designed to be user friendly, to be of maximum use to regulatory agencies, clinicians, as well as to scientists interested in assessing the potential allergenic risk of a protein. We developed methods, unique to SDAP, to compare the physicochemical properties of discrete areas of allergenic proteins to known IgE epitopes. We developed a new similarity measure, the property distance (PD) value that can be used to detect related segments in allergens with clinical observed crossreactivity. We have now expanded this work to obtain experimental validation of the PD index as a quantitative predictor of IgE cross-reactivity, by designing peptide variants with predetermined PD scores relative to known IgE epitopes. In complementary work we show how sequence motifs characteristic of allergenic proteins in protein families can be used as fingerprints for allergenicity. PMID:19121639

Influences of synthesis methods and modifier addition on the properties of Ni-based catalysts supported on reticulated ceramic foams

NASA Astrophysics Data System (ADS)

Nikolić, Vesna; Kamberović, Željko; Anđić, Zoran; Korać, Marija; Sokić, Miroslav; Maksimović, Vesna

2014-08-01

A method of synthesizing Ni-based catalysts supported on α-Al2O3-based foams was developed. The foams were impregnated with aqueous solutions of metal chlorides under an air atmosphere using an aerosol route. Separate procedures involved calcination to form oxides and drying to obtain chlorides on the foam surface. The synthesized samples were subsequently reduced with hydrogen. With respect to the Ni/Al2O3 catalysts, the chloride reduction route enabled the formation of a Ni coating without agglomerates or cracks. Further research included catalyst modification by the addition of Pd, Cu, and Fe. The influences of the additives on the degree of reduction and on the low-temperature reduction effectiveness (533 and 633 K) were examined and compared for the catalysts obtained from oxides and chlorides. Greater degrees of reduction were achieved with chlorides, whereas Pd was the most effective modifier among those investigated. The reduction process was nearly complete at 533 K in the sample that contained 0.1wt% Pd. A lower reduction temperature was utilized, and the calcination step was avoided, which may enhance the economical and technological aspects of the developed catalyst production method.

Development of personality and the remission and onset of personality pathology.

PubMed

Wright, Aidan G C; Pincus, Aaron L; Lenzenweger, Mark F

2011-12-01

The current study used the Longitudinal Study of Personality Disorders data set (Lenzenweger, 1999) to examine the development of personality traits in the context of the remission and onset of personality disorder (PD) symptoms. Despite high levels of stability, past research on the development of basic personality traits has also found a mean trend toward increased maturity and that individuals vary in their trajectories of trait development. Research on PD change has shown a similar pattern. We employed individual growth curve modeling to examine the relationship between personality trait development and PD symptom course. We found that both are indeed related and that remission in PD symptoms is associated with patterns of trait development associated with more rapid maturity. In contrast, deviating from the mean of trait development either through no change (i.e., stagnation) or change in the opposite direction (i.e., regression) was associated with developing PD symptoms over the course of the study.

Platinum and palladium incorporation into phosphate/viologen-phosphonates of zirconium and hafnium: synthesis and characterization

NASA Astrophysics Data System (ADS)

Dokoutchaev, Alexandre; Krishnan, Venkatesan V.; Thompson, Mark E.; Balasubramanian, Mahalingam

1998-10-01

We have continued previous efforts to synthesize and characterize a microporous metal phosphate/viologen-phosphonate compound, [(ZrF) 2(PO 4)(O 3PCH 2CH 2-4,4'-bipyridinium-CH 2CH 2PO 3)] ṡF·2H 2O, ZrPO PV. A derivative of this material has been shown to be an efficient catalyst for the production of hydrogen peroxide from hydrogen and oxygen. This paper has two objectives—one is to optimize the synthetic routes leading to the preparation of MPO PV (M=zirconium or hafnium) and the second is to characterize MPO PV and the derivatives formed by Pt or Pd incorporation by transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray powder diffraction (XRD), inductively coupled plasma-mass spectrometry (ICP-MS) and X-ray absorption fine structure analysis (XAFS). Powder XRD data have shown much higher crystallinity in MPO PV samples prepared by hydrothermal methods than those prepared by reflux methods. In the hydrothermal synthesis, the amount of mineralizer (HF) present controlled the crystallite size (as determined from TEM micrographs). The larger the quantity of HF in the bomb, the larger the size of the crystals but the lower the yield of the MPO PV material. Crystal sizes of about 2.5 μm in length and 0.15 μm in diameter have been made with very large quantities of HF as mineralizer (10 times the required stoichiometric amount). Ion exchange of the material by PdCl 42- has resulted in the incorporation of the PdCl 42- ions in place of X - in the material. This has been confirmed by XAFS studies that demonstrate the oxidation state of Pd is 2+ and show four Cl atoms bound to Pd. Upon reduction it has been confirmed (by XAFS) that the palladium exists as metal with oxidation state of zero. Ion exchange by PdCl 42- and PtCl 42- and subsequent reduction of the material suspension by hydrogen result in the formation of separate Pt and Pd colloids in the close vicinity of the crystallites. TEM micrographs show clearly that the Pt metal obtained after reduction forms much smaller particles in comparison to Pd. These exchanged and reduced materials have also been investigated as catalysts for production of hydrogen peroxide in mixed acetone/water medium. The production of hydrogen peroxide is enhanced by increasing amounts of Pd in the catalyst. Hydrogen peroxide yields are the highest for catalysts containing only Pd as opposed to a mixture of Pt and Pd.

Higher-resolution selective metallization on alumina substrate by laser direct writing and electroless plating

NASA Astrophysics Data System (ADS)

Lv, Ming; Liu, Jianguo; Wang, Suhuan; Ai, Jun; Zeng, Xiaoyan

2016-03-01

How to fabricate conductive patterns on ceramic boards with higher resolution is a challenge in the past years. The fabrication of copper patterns on alumina substrate by laser direct writing and electroless copper plating is a low cost and high efficiency method. Nevertheless, the lower resolution limits its further industrial applications in many fields. In this report, the mechanisms of laser direct writing and electroless copper plating were studied. The results indicated that as the decomposed products of precursor PdCl2 have different chemical states respectively in laser-irradiated zone (LIZ) and laser-affected zone (LAZ). This phenomenon was utilized and a special chemical cleaning method with aqua regia solution was taken to selectively remove the metallic Pd in LAZ, while kept the PdO in LIZ as the only active seeds. As a result, the resolution of subsequent copper patterns was improved significantly. This technique has a great significance to develop the microelectronics devices.

The thermal environment effect on the comfort of electronic factory worker

NASA Astrophysics Data System (ADS)

Nurul Huda, Listiani

2018-03-01

In this paper, thermal comfort issues of the operators working on one of the electronics companies in the evaporator area are observed. The objective of this study is to reduce Percentage of Dissatisfied (PD) of operators in an effort to improve the work productivity. PD is predicted using CBE Thermal Comfort Tool by measuring the thermal variables around the evaporator area and by calculating the Heat Stress Index (HSI). The operator productivity is analyzed by Wet Bulb Globe Thermometer (WBGT) Work-Rest Chart. The PD of operators before and after improvement is compared. The results showed that the average temperature around the operators area at evaporator station is high with average WBGT of 33,6°C. HSI value is 51.95 indicating that the effect of 8-h exposure is severe strain with work impact is health threat for unit operators and acclimatization is necessary. The PD value is 96% indicating that almost all operators feel uncomfortable at work. These indicate that the thermal environment should be improved. The proposed improvement is by installing water cooled and sprayed into the evaporator area. This installation is able to reduce HSI and PD by more 70% and more 60%, respectively. These findings indicate that improving the thermal environment will be able to improve working comfort which will further affect the level of work productivity.

Effect of palladium doping on the stability and fragmentation patterns of cationic gold clusters

NASA Astrophysics Data System (ADS)

Ferrari, P.; Hussein, H. A.; Heard, C. J.; Vanbuel, J.; Johnston, R. L.; Lievens, P.; Janssens, E.

2018-05-01

We analyze in detail how the interplay between electronic structure and cluster geometry determines the stability and the fragmentation channels of single Pd-doped cationic Au clusters, PdA uN-1+ (N =2 -20 ). For this purpose, a combination of photofragmentation experiments and density functional theory calculations was employed. A remarkable agreement between the experiment and the calculations is obtained. Pd doping is found to modify the structure of the Au clusters, in particular altering the two-dimensional to three-dimensional transition size, with direct consequences on the stability of the clusters. Analysis of the electronic density of states of the clusters shows that depending on cluster size, Pd delocalizes one 4 d electron, giving an enhanced stability to PdA u6 + , or remains with all 4 d10 electrons localized, closing an electronic shell in PdA u9 + . Furthermore, it is observed that for most clusters, Au evaporation is the lowest-energy decay channel, although for some sizes Pd evaporation competes. In particular, PdA u7 + and PdA u9 + decay by Pd evaporation due to the high stability of the A u7 + and A u9 + fragmentation products.

Collaboratively Exploring the Use of a Video Case-Based Book as a Professional Development Tool

ERIC Educational Resources Information Center

Smithenry, Dennis W.; Prouty, Jessica; Capobianco, Brenda M.

2013-01-01

Although the literature contains many examples of extensive professional development (PD) programs, most science teachers experience only a few hours of PD each year. To address this reality, alternative PD delivery tools need to be examined. Since the mid-1990s, video cases have emerged as a flexible form of PD where in-service teachers can…

A hierarchical flower-like hollow alumina supported bimetallic AuPd nanoparticle catalyst for enhanced solvent-free ethylbenzene oxidation.

PubMed

Dong, Huijuan; Xie, Renfeng; Yang, Lan; Li, Feng

2018-06-12

Currently, oxidation of alkylaromatics is considered as one of the most crucial chemical technologies to produce high added-value alcohols, ketones and carboxylic acids, due to its significant importance both in fine synthetic chemistry and in the academic field. In this work, a novel hierarchical marigold-like hollow alumina supported bimetallic AuPd nanoparticle catalyst was successfully fabricated and employed for highly efficient solvent-free ethylbenzene oxidation to produce acetophenone with the coexistence of both molecular oxygen and tert-butyl hydroperoxide as the oxidant and the initiator. The as-fabricated bimetallic AuPd nanocatalyst conferred a superior catalytic performance to the corresponding monometallic counterparts and commercial Al2O3 or solid Al2O3 microsphere supported AuPd ones, along with a high acetophenone selectivity of 88.2% at a conversion of 50.9% under mild reaction conditions (120 °C and oxygen pressure of 1.0 MPa), as well as an unprecedentedly high turnover frequency value of 46 768 h-1. Such exceptional efficiency of the catalyst was related to both the significant synergy between the Au-Pd atoms and strong metal-support interactions, and the unique hierarchical micro/nanostructure of the support being beneficial to the close contact of reactants with surface adsorption and reaction sites and easy product diffusion. Moreover, the present bimetallic AuPd catalyst was recyclable and stable. The developed approach is expected to offer exciting opportunities for designing other supported monometallic or bimetallic catalysts with various active components applied in heterogeneous catalysis.

Specific Caleosin/Peroxygenase and Lipoxygenase Activities Are Tissue-Differentially Expressed in Date Palm (Phoenix dactylifera L.) Seedlings and Are Further Induced Following Exposure to the Toxin 2,3,7,8-tetrachlorodibenzo-p-dioxin

PubMed Central

Hanano, Abdulsamie; Almousally, Ibrahem; Shaban, Mouhnad; Rahman, Farzana; Hassan, Mehedi; Murphy, Denis J.

2017-01-01

Two caleosin/peroxygenase isoforms from date palm, Phoenix dactylifera L., PdCLO2 and PdCLO4, were characterized with respect to their tissue expression, subcellular localization, and oxylipin pathway substrate specificities in developing seedlings. Both PdCLO2 and PdCLO4 had peroxygenase activities that peaked at the mid-stage (radicle length of 2.5 cm) of seedling growth and were associated with the lipid droplet (LD) and microsomal fractions. Recombinant PdCLO2 and PdCLO4 proteins heterologously expressed in yeast cells were localized in both LD and microsomal fractions. Each of the purified recombinant proteins exhibited peroxygenase activity but they were catalytically distinct with respect to their specificity and product formation from fatty acid epoxide and hydroxide substrates. We recently showed that date palm CLO genes were upregulated following exposure to the potent toxin, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (Hanano et al., 2016), and we show here that transcripts of 9- and 13-lipoxygenase (LOX) genes were also induced by TCDD exposure. At the enzyme level, 9-LOX and 13-LOX activities were present in a range of seedling tissues and responded differently to TCDD exposure, as did the 9- and 13-fatty acid hydroperoxide reductase activities. This demonstrates that at least two branches of the oxylipin pathway are involved in responses to the environmental organic toxin, TCDD in date palm. PMID:28111588

Neuromelanin detection by magnetic resonance imaging (MRI) and its promise as a biomarker for Parkinson's disease.

PubMed

Sulzer, David; Cassidy, Clifford; Horga, Guillermo; Kang, Un Jung; Fahn, Stanley; Casella, Luigi; Pezzoli, Gianni; Langley, Jason; Hu, Xiaoping P; Zucca, Fabio A; Isaias, Ioannis U; Zecca, Luigi

2018-01-01

The diagnosis of Parkinson's disease (PD) occurs after pathogenesis is advanced and many substantia nigra (SN) dopamine neurons have already died. Now that therapies to block this neuronal loss are under development, it is imperative that the disease be diagnosed at earlier stages and that the response to therapies is monitored. Recent studies suggest this can be accomplished by magnetic resonance imaging (MRI) detection of neuromelanin (NM), the characteristic pigment of SN dopaminergic, and locus coeruleus (LC) noradrenergic neurons. NM is an autophagic product synthesized via oxidation of catecholamines and subsequent reactions, and in the SN and LC it increases linearly during normal aging. In PD, however, the pigment is lost when SN and LC neurons die. As shown nearly 25 years ago by Zecca and colleagues, NM's avid binding of iron provides a paramagnetic source to enable electron and nuclear magnetic resonance detection, and thus a means for safe and noninvasive measure in living human brain. Recent technical improvements now provide a means for MRI to differentiate between PD patients and age-matched healthy controls, and should be able to identify changes in SN NM with age in individuals. We discuss how MRI detects NM and how this approach might be improved. We suggest that MRI of NM can be used to confirm PD diagnosis and monitor disease progression. We recommend that for subjects at risk for PD, and perhaps generally for older people, that MRI sequences performed at regular intervals can provide a pre-clinical means to detect presymptomatic PD.

Plasma biomarkers of decreased vesicular storage distinguish Parkinson disease with orthostatic hypotension from the parkinsonian form of multiple system atrophy.

PubMed

Goldstein, David S; Kopin, Irwin J; Sharabi, Yehonatan; Holmes, Courtney

2015-02-01

Parkinson disease with orthostatic hypotension (PD + OH) and the parkinsonian form of multiple system atrophy (MSA-P) can be difficult to distinguish clinically. Recent studies indicate that PD entails a vesicular storage defect in catecholaminergic neurons. Although cardiac sympathetic neuroimaging by (18)F-dopamine positron emission tomography can identify decreased vesicular storage, this testing is not generally available. We assessed whether plasma biomarkers of a vesicular storage defect can separate PD + OH from MSA-P. We conceptualized that after F-dopamine injection, augmented production of F-dihydroxyphenylacetic acid (F-DOPAC) indicates decreased vesicular storage, and we therefore predicted that arterial plasma F-DOPAC would be elevated in PD + OH but not in MSA-P. We measured arterial plasma F-DOPAC after (18)F-dopamine administration (infused i.v. over 3 min) in patients with PD + OH (N = 12) or MSA-P (N = 21) and in healthy control subjects (N = 26). Peak F-DOPAC:dihydroxyphenylglycol (DHPG) was also calculated to adjust for effects of denervation on F-DOPAC production. Plasma F-DOPAC accumulated rapidly after initiation of (18)F-dopamine infusion. Peak F-DOPAC (5-10 min) in PD + OH averaged three times that in MSA-P (P < 0.0001). Among MSA-P patients, none had peak F-DOPAC > 300 nCi-kg/cc-mCi, in contrast with 7 of 12 PD + OH patients (χ(2) = 16.6, P < 0.0001). DHPG was lower in PD + OH (3.83 ± 0.36 nmol/L) than in MSA-P (5.20 ± 0.29 nmol/L, P = 0.007). All MSA-P patients had peak F-DOPAC:DHPG < 60, in contrast with 9 of 12 PD + OH patients (χ(2) = 17.5, P < 0.0001). Adjustment of peak F-DOPAC for DHPG increased test sensitivity from 58 to 81% at similar high specificity. After F-dopamine injection, plasma F-DOPAC and F-DOPAC:DHPG distinguish PD + OH from MSA-P.

Reactive glia promote development of CD103+ CD69+ CD8+ T-cells through programmed cell death-ligand 1 (PD-L1).

PubMed

Prasad, Sujata; Hu, Shuxian; Sheng, Wen S; Chauhan, Priyanka; Lokensgard, James R

2018-06-01

Previous work from our laboratory has demonstrated in vivo persistence of CD103 + CD69 + brain resident memory CD8 + T-cells (bT RM ) following viral infection, and that the PD-1: PD-L1 pathway promotes development of these T RM cells within the brain. Although glial cells express low basal levels of PD-L1, its expression is upregulated upon IFN-γ-treatment, and they have been shown to modulate antiviral T-cell effector responses through the PD-1: PD-L1 pathway. We performed flow cytometric analysis of cells from co-cultures of mixed glia and CD8 + T-cells obtained from wild type mice to investigate the role of glial cells in the development of bT RM . In this study, we show that interactions between reactive glia and anti-CD3 Ab-stimulated CD8 + T-cells promote development of CD103 + CD69 + CD8 + T-cells through engagement of the PD-1: PD-L1 pathway. These studies used co-cultures of primary murine glial cells obtained from WT animals along with CD8 + T-cells obtained from either WT or PD-1 KO mice. We found that αCD3 Ab-stimulated CD8 + T-cells from WT animals increased expression of CD103 and CD69 when co-cultured with primary murine glial cells. In contrast, significantly reduced expression of CD103 and CD69 was observed using CD8 + T-cells from PD-1 KO mice. We also observed that reactive glia promoted high levels of CD127, a marker of memory precursor effector cells (MPEC), on CD69 + CD8 + T-cells, which promotes development of T RM cells. Interestingly, results obtained using T-cells from PD-1 KO animals showed significantly reduced expression of CD127 on CD69 + CD8 + cells. Additionally, blocking of glial PD-L1 resulted in decreased expression of CD103, along with reduced CD127 on CD69 + CD8 + T-cells. Taken together, these results demonstrate a role for activated glia in promoting development of bT RM through the PD-1: PD-L1 pathway. © 2018 The Authors. Immunity, Inflammation and Disease Published by John Wiley & Sons Ltd.

Risk factors of periodontal disease in maintenance hemodialysis patients

PubMed Central

Hou, Yue; Wang, Xin; Zhang, Cong-Xiao; Wei, Yu-Dan; Jiang, Li-Li; Zhu, Xiao-Yu; Du, Yu-Jun

2017-01-01

Abstract To explore the characteristics and relevant risk factors of periodontal disease (PD) among hemodialysis patients. Uremic patients on maintenance hemodialysis from November 2015 to March 2016 were retrospectively reviewed. Patients were divided into a PD group and a non-PD group. Demographic and laboratory data were collected and analyzed. In all, 136 uremic patients (79 males and 57 females, aged 50.8 ± 15.3 years) on maintenance hemodialysis were included in this study. The incidence of PD increased with age. Hemodialysis patients most likely developed PD if they were male, smokers, or diabetic (P = .009, <.001, and <.001, respectively). Patients brushing their teeth twice daily had significantly less chance of developing PD as compared with those only brushing once daily (P < .001). Hemodialysis patients in the PD group had significantly higher levels of total cholesterol, high-sensitivity C-reactive protein, fasting blood glucose, and peripheral white blood cell counts, compared with the non-PD group (all P < .001). Logistic regression analysis revealed that diabetes, total cholesterol, high-sensitivity C-reactive protein, and peripheral white blood cell count were independent risk factors for developing PD, whereas teeth brushing twice daily and serum calcium were favorable factors for maintenance hemodialysis patients against PD. Identification of risk factors provides a theoretical basis for prevention and improvement of PD among maintenance hemodialysis patients. PMID:28858105

Increasing the Aromatic Selectivity of Quinoline Hydrogenolysis Using Pd/MO x–Al 2O 3

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

Bachrach, Mark; Morlanes-Sanchez, Natalia; Canlas, Christian P.

2014-09-11

Catalysts consisting of Pd nanoparticles supported on highly dispersed TiO x–Al 2O 3, TaO x–Al 2O 3, and MoO x–Al 2O 3 are studied for catalytic quinoline hydrogenation and selective C–N bond cleavage at 275 °C and 20 bar H 2. Lastly, the Pd/MO x–Al 2O 3 materials exhibit significantly greater aromatic product selectivity and thus 10–15 % less required H 2 for a given level of denitrogenation relative to an unmodified Pd/Al 2O 3 catalyst.

MOF-253-Pd(OAc) 2 : a recyclable MOF for transition-metal catalysis in water

DOE PAGES

Van Zeeland, Ryan; Li, Xinle; Huang, Wenyu; ...

2016-06-06

We report palladium(II)-functionalized MOF-253 (MOF-253-Pd(OAc) 2) as a recyclable catalyst to form all-carbon quaternary centers via conjugate additions of arylboronic acids to β,β-disubstituted enones in aqueous media. We demonstrate MOF-253-Pd(OAc) 2 can be reused 8 times to form ketone products in yields above 75% while maintaining its crystallinity. Additions of a range of stereoelectronically diverse arylboronic acids to a variety of β,β-disubstituted enones catalyzed by MOF-253-Pd(OAc) 2 occur in modest-to-high yields (34–95%).

Rare variants analysis of cutaneous malignant melanoma genes in Parkinson's disease.

PubMed

Lubbe, S J; Escott-Price, V; Brice, A; Gasser, T; Pittman, A M; Bras, J; Hardy, J; Heutink, P; Wood, N M; Singleton, A B; Grosset, D G; Carroll, C B; Law, M H; Demenais, F; Iles, M M; Bishop, D T; Newton-Bishop, J; Williams, N M; Morris, H R

2016-12-01

A shared genetic susceptibility between cutaneous malignant melanoma (CMM) and Parkinson's disease (PD) has been suggested. We investigated this by assessing the contribution of rare variants in genes involved in CMM to PD risk. We studied rare variation across 29 CMM risk genes using high-quality genotype data in 6875 PD cases and 6065 controls and sought to replicate findings using whole-exome sequencing data from a second independent cohort totaling 1255 PD cases and 473 controls. No statistically significant enrichment of rare variants across all genes, per gene, or for any individual variant was detected in either cohort. There were nonsignificant trends toward different carrier frequencies between PD cases and controls, under different inheritance models, in the following CMM risk genes: BAP1, DCC, ERBB4, KIT, MAPK2, MITF, PTEN, and TP53. The very rare TYR p.V275F variant, which is a pathogenic allele for recessive albinism, was more common in PD cases than controls in 3 independent cohorts. Tyrosinase, encoded by TYR, is the rate-limiting enzyme for the production of neuromelanin, and has a role in the production of dopamine. These results suggest a possible role for another gene in the dopamine-biosynthetic pathway in susceptibility to neurodegenerative Parkinsonism, but further studies in larger PD cohorts are needed to accurately determine the role of these genes/variants in disease pathogenesis. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

PD-1 expression on dendritic cells suppresses CD8+ T cell function and antitumor immunity.

PubMed

Lim, Tong Seng; Chew, Valerie; Sieow, Je Lin; Goh, Siting; Yeong, Joe Poh-Sheng; Soon, Ai Ling; Ricciardi-Castagnoli, Paola

2016-03-01

Programmed death one (PD-1) is a well-established co-inhibitory regulator that suppresses proliferation and cytokine production of T cells. Despite remarkable progress in delineating the functional roles of PD-1 on T lymphocytes, little is known about the regulatory role of PD-1 expressed on myeloid cells such as dendritic cells (DCs). Here, we show that CD8 + T cells can be more potently activated to secrete IL-2 and IFNγ by PD-1-deficient DCs compared to wild-type DCs. Adoptive transfer of PD-1-deficient DCs demonstrated their superior capabilities in inducing antigen-specific CD8 + T cell proliferation in vivo . In addition, we provide first evidence demonstrating the existence of peripheral blood DCs and CD11c + tumor-infiltrating myeloid cells that co-express PD-1 in patients with hepatocellular carcinoma (HCC). The existence of PD-1-expressing HCC-infiltrating DCs (HIDCs) was further supported in a mouse model of HCC. Intratumoral transfer of PD-1-deficient DCs rendered recipient mice resistant to the growth of HCC by promoting tumor-infiltrating CD8 + effector T cells to secrete perforin and granzyme B. This novel finding provides a deeper understanding of the role of PD-1 in immune regulation and has significant implications for cancer immunotherapies targeting PD-1.

PD-1 expression on dendritic cells suppresses CD8+ T cell function and antitumor immunity

PubMed Central

Lim, Tong Seng; Chew, Valerie; Sieow, Je Lin; Goh, Siting; Yeong, Joe Poh-Sheng; Soon, Ai Ling; Ricciardi-Castagnoli, Paola

2016-01-01

ABSTRACT Programmed death one (PD-1) is a well-established co-inhibitory regulator that suppresses proliferation and cytokine production of T cells. Despite remarkable progress in delineating the functional roles of PD-1 on T lymphocytes, little is known about the regulatory role of PD-1 expressed on myeloid cells such as dendritic cells (DCs). Here, we show that CD8+ T cells can be more potently activated to secrete IL-2 and IFNγ by PD-1-deficient DCs compared to wild-type DCs. Adoptive transfer of PD-1-deficient DCs demonstrated their superior capabilities in inducing antigen-specific CD8+ T cell proliferation in vivo. In addition, we provide first evidence demonstrating the existence of peripheral blood DCs and CD11c+ tumor-infiltrating myeloid cells that co-express PD-1 in patients with hepatocellular carcinoma (HCC). The existence of PD-1-expressing HCC-infiltrating DCs (HIDCs) was further supported in a mouse model of HCC. Intratumoral transfer of PD-1-deficient DCs rendered recipient mice resistant to the growth of HCC by promoting tumor-infiltrating CD8+ effector T cells to secrete perforin and granzyme B. This novel finding provides a deeper understanding of the role of PD-1 in immune regulation and has significant implications for cancer immunotherapies targeting PD-1. PMID:27141339

Interfacial processes in the Pd/a-Ge:H system

NASA Astrophysics Data System (ADS)

Edelman, F.; Cytermann, C.; Brener, R.; Eizenberg, M.; Weil, R.; Beyer, W.

1993-06-01

The kinetics of phase transformation has been studied in a two-layer structure of Pd/a-Ge:H after vacuum annealing at temperatures from 180 to 500°C. The a-Ge:H was deposited at 250°C on both c-Si and cleaved NaCl substrates in an RF glow discharge from a GeH 4/H 2 mixture. It was found that, similarly to the Pd/c-Ge and the Pd/a-Ge (e-gun deposited) systems, in the case of 0.15-0.2 μm Pd/0.6-1.0 μm a-Ge:H interfacial germanides formed first through the production of Pd 2Ge (plus a small amount of PdGe), and then PdGe was produced. The growth of both compounds was found to be diffusion-controlled. The nonreacted a-Ge:H layer beneath the germanide overlayer crystallized at 400-500°C. A reverse sequence of germanides formation was revealed in the case of 50 nm Pd/30 nm a-Ge:H, studied by in situ heat treatment in the TEM utilizing non-supported samples. The first germanide detected was PdGe and then, as a result of PdGe and Ge reaction or the PdGe decomposition, Pd 2Ge formed. The temperature dependence of the incubation time before the first ˜ 10 nm PdGe grains formed, followed an Arrhenius curve with an activation energy of 1.45 eV.

Biomarkers in Prodromal Parkinson Disease: a Qualitative Review.

PubMed

Cooper, Christine A; Chahine, Lama M

2016-11-01

Over the past several years, the concept of prodromal Parkinson disease (PD) has been increasingly recognized. This term refers to individuals who do not fulfill motor diagnostic criteria for PD, but who have clinical, genetic, or biomarker characteristics suggesting risk of developing PD in the future. Clinical diagnosis of prodromal PD has low specificity, prompting the need for objective biomarkers with higher specificity. In this qualitative review, we discuss objectively defined putative biomarkers for PD and prodromal PD. We searched Pubmed and Embase for articles pertaining to objective biomarkers for PD and their application in prodromal cohorts. Articles were selected based on relevance and methodology. Objective biomarkers of demonstrated utility in prodromal PD include ligand-based imaging and transcranial sonography. Development of serum, cerebrospinal fluid, and tissue-based biomarkers is underway, but their application in prodromal PD has yet to meaningfully occur. Combining objective biomarkers with clinical or genetic prodromal features increases the sensitivity and specificity for identifying prodromal PD. Several objective biomarkers for prodromal PD show promise but require further study, including their application to and validation in prodromal cohorts followed longitudinally. Accurate identification of prodromal PD will likely require a multimodal approach. (JINS, 2016, 22, 956-967).

Parkinson's disease with mild cognitive impairment: severe cortical thinning antedates dementia.

PubMed

Gasca-Salas, Carmen; García-Lorenzo, Daniel; Garcia-Garcia, David; Clavero, Pedro; Obeso, José A; Lehericy, Stephane; Rodríguez-Oroz, María C

2017-07-14

Mild cognitive impairment (MCI) in Parkinson's disease (PD) is a risk factor for dementia and thus, it is of interest to elucidate if specific patterns of atrophy in PD-MCI patients are associated with a higher risk of developing dementia. We aim to define pattern(s) of regional atrophy in PD-MCI patients who developed dementia during 31 months of follow-up using cortical thickness analysis Twenty-three PD-MCI patients and 18 controls underwent brain MRI and completed a neuropsychological examination at baseline, PD-MCI patients were followed after a 31 month follow-up in order to assess their progression to dementia. At follow up, 8 PD-MCI patients had converted to dementia (PD-MCI converters) whereas 15 remained as PD-MCI (PD-MCI non-converters). All patients were at least 60 years old and suffered PD ≥ 10 years. There were no baseline differences between the two groups of patients in clinical and neuropsychological variables. The cortex of PD-MCI converters was thinner than that of PD-MCI non-converters, bilaterally in the frontal, insula and the left middle temporal areas, also displaying a more widespread pattern of cortical thinning relative to the controls. This study shows that aged and long-term PD patients with MCI who convert to dementia in the short-mid term suffer a thinning of the cortex in several areas (frontal cortex, and middle temporal lobe and insula), even when their cognitive impairment was similar to that of PD-MCI non-converters. Thus, MRI analysis of cortical thickness may represent a useful measure to identify PD-MCI patients at a higher risk of developing dementia.

Linking canopy reflectance to crop structure and photosynthesis to capture and interpret spatiotemporal dimensions of per-field photosynthetic productivity

NASA Astrophysics Data System (ADS)

Xue, Wei; Jeong, Seungtaek; Ko, Jonghan; Tenhunen, John

2017-03-01

Nitrogen and water availability alter canopy structure and physiology, and thus crop growth, yielding large impacts on ecosystem-regulating/production provisions. However, to date, explicitly quantifying such impacts remains challenging partially due to lack of adequate methodology to capture spatial dimensions of ecosystem changes associated with nitrogen and water effects. A data fitting, where close-range remote-sensing measurements of vegetation indices derived from a handheld instrument and an unmanned aerial vehicle (UAV) system are linked to in situ leaf and canopy photosynthetic traits, was applied to capture and interpret inter- and intra-field variations in gross primary productivity (GPP) in lowland rice grown under flooded conditions (paddy rice, PD) subject to three nitrogen application rates and under rainfed conditions (RF) in an East Asian monsoon region of South Korea. Spatial variations (SVs) in both GPP and light use efficiency (LUEcabs) early in the growing season were enlarged by nitrogen addition. The nutritional effects narrowed over time. A shift in planting culture from flooded to rainfed conditions strengthened SVs in GPP and LUEcabs. Intervention of prolonged drought late in the growing season dramatically intensified SVs that were supposed to seasonally decrease. Nevertheless, nitrogen addition effects on SV of LUEcabs at the early growth stage made PD fields exert greater SVs than RF fields. SVs of GPP across PD and RF rice fields were likely related to leaf area index (LAI) development less than to LUEcabs, while numerical analysis suggested that considering strength in LUEcabs and its spatial variation for the same crop type tends to be vital for better evaluation in landscape/regional patterns of ecosystem photosynthetic productivity at critical phenology stages.

Development of an inter-atomic potential for the Pd-H binary system.

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

Zimmerman, Jonathan A.; Hoyt, Jeffrey John; Leonard, Francois Leonard

2007-09-01

Ongoing research at Sandia National Laboratories has been in the area of developing models and simulation methods that can be used to uncover and illuminate the material defects created during He bubble growth in aging bulk metal tritides. Previous efforts have used molecular dynamics calculations to examine the physical mechanisms by which growing He bubbles in a Pd metal lattice create material defects. However, these efforts focused only on the growth of He bubbles in pure Pd and not on bubble growth in the material of interest, palladium tritide (PdT), or its non-radioactive isotope palladium hydride (PdH). The reason formore » this is that existing inter-atomic potentials do not adequately describe the thermodynamics of the Pd-H system, which includes a miscibility gap that leads to phase separation of the dilute (alpha) and concentrated (beta) alloys of H in Pd at room temperature. This document will report the results of research to either find or develop inter-atomic potentials for the Pd-H and Pd-T systems, including our efforts to use experimental data and density functional theory calculations to create an inter-atomic potential for this unique metal alloy system.« less

Bimetallic redox synergy in oxidative palladium catalysis.

PubMed

Powers, David C; Ritter, Tobias

2012-06-19

Polynuclear transition metal complexes, which are embedded in the active sites of many metalloenzymes, are responsible for effecting a diverse array of oxidation reactions in nature. The range of chemical transformations remains unparalleled in the laboratory. With few noteworthy exceptions, chemists have primarily focused on mononuclear transition metal complexes in developing homogeneous catalysis. Our group is interested in the development of carbon-heteroatom bond-forming reactions, with a particular focus on identifying reactions that can be applied to the synthesis of complex molecules. In this context, we have hypothesized that bimetallic redox chemistry, in which two metals participate synergistically, may lower the activation barriers to redox transformations relevant to catalysis. In this Account, we discuss redox chemistry of binuclear Pd complexes and examine the role of binuclear intermediates in Pd-catalyzed oxidation reactions. Stoichiometric organometallic studies of the oxidation of binuclear Pd(II) complexes to binuclear Pd(III) complexes and subsequent C-X reductive elimination from the resulting binuclear Pd(III) complexes have confirmed the viability of C-X bond-forming reactions mediated by binuclear Pd(III) complexes. Metal-metal bond formation, which proceeds concurrently with oxidation of binuclear Pd(II) complexes, can lower the activation barrier for oxidation. We also discuss experimental and theoretical work that suggests that C-X reductive elimination is also facilitated by redox cooperation of both metals during reductive elimination. The effect of ligand modification on the structure and reactivity of binuclear Pd(III) complexes will be presented in light of the impact that ligand structure can exert on the structure and reactivity of binuclear Pd(III) complexes. Historically, oxidation reactions similar to those discussed here have been proposed to proceed via mononuclear Pd(IV) intermediates, and the hypothesis of mononuclear Pd(II/IV) catalysis has guided the successful development of many reactions. Herein we discuss differences between monometallic Pd(IV) and bimetallic Pd(III) redox catalysis. We address whether appreciation of the relevance of bimetallic Pd(III) redox catalysis is of academic interest exclusively, serving to provide a more nuanced description of catalysis, or if the new insight regarding bimetallic Pd(III) chemistry can be a platform to enable future reaction development. To this end, we describe an example in which the hypothesis of bimetallic redox chemistry guided reaction development, leading to the discovery of reactivity distinct from monometallic catalysts.

PD-1/PD-L1 Inhibitors for Immuno-oncology: From Antibodies to Small Molecules.

PubMed

Geng, Qiaohong; Jiao, Peifu; Jin, Peng; Su, Gaoxing; Dong, Jinlong; Yan, Bing

2018-02-12

The recent regulatory approvals of immune checkpoint protein inhibitors, such as ipilimumab, pembrolizumab, nivolumab, atezolizumab, durvalumab, and avelumab ushered a new era in cancer therapy. These inhibitors do not attack tumor cells directly but instead mobilize the immune system to re-recognize and eradicate tumors, which endows them with unique advantages including durable clinical responses and substantial clinical benefits. PD-1/PD-L1 inhibitors, a pillar of immune checkpoint protein inhibitors, have demonstrated unprecedented clinical efficacy in more than 20 cancer types. Besides monoclonal antibodies, diverse PD- 1/PD-L1 inhibiting candidates, such as peptides, small molecules have formed a powerful collection of weapons to fight cancer. The goal of this review is to summarize and discuss the current PD-1/PD-L1 inhibitors including candidates under clinical development, their molecular interactions with PD-1 or PD-L1, the disclosed structureactivity relationships of peptides and small molecules as inhibitors. Current PD-1/PD-L1 inhibitors under clinical development are exclusively dominated by antibodies. The molecular interactions of therapeutic antibodies with PD-1 or PD-L1 have been gradually elucidated for the design of novel inhibitors. Various peptides and traditional small molecules have been investigated in preclinical model to discover novel PD-1/PD-L1 inhibitors. Peptides and small molecules may play an important role in immuno-oncology because they may bind to multiple immune checkpoint proteins via rational design, opening opportunity for a new generation of novel PD-1/PD-L1 inhibitors. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Development of Chemical and Metabolite Sensors for Rhodococcus opacus PD630.

PubMed

DeLorenzo, Drew M; Henson, William R; Moon, Tae Seok

2017-10-20

Rhodococcus opacus PD630 is a nonmodel, Gram-positive bacterium that possesses desirable traits for biomass conversion, including consumption capabilities for lignocellulose-based sugars and toxic lignin-derived aromatic compounds, significant triacylglycerol accumulation, relatively rapid growth rate, and genetic tractability. However, few genetic elements have been directly characterized in R. opacus, limiting its application for lignocellulose bioconversion. Here, we report the characterization and development of genetic tools for tunable gene expression in R. opacus, including: (1) six fluorescent reporters for quantifying promoter output, (2) three chemically inducible promoters for variable gene expression, and (3) two classes of metabolite sensors derived from native R. opacus promoters that detect nitrogen levels or aromatic compounds. Using these tools, we also provide insights into native aromatic consumption pathways in R. opacus. Overall, this work expands the ability to control and characterize gene expression in R. opacus for future lignocellulose-based fuel and chemical production.

Measurement of activation cross-section of long-lived products in deuteron induced nuclear reactions on palladium in the 30-50MeV energy range.

PubMed

Ditrói, F; Tárkányi, F; Takács, S; Hermanne, A; Ignatyuk, A V

2017-10-01

Excitation functions were measured in the 31-49.2MeV energy range for the nat Pd(d,xn) 111,110m,106m,105,104g,103 Ag, nat Pd(d,x) 111m,109,101,100 Pd, nat Pd(d,x), 105,102m,102g,101m,101g,100,99m,99g Rh and nat Pd(d,x) 103,97 Ru nuclear reactions by using the stacked foil irradiation technique. The experimental results are compared with our previous results and with the theoretical predictions calculated with the ALICE-D, EMPIRE-D and TALYS (TENDL libraries) codes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Glucose 6-phosphate dehydrogenase and the kidney.

PubMed

Spencer, Netanya Y; Stanton, Robert C

2017-01-01

Glucose 6-phosphate dehydrogenase (G6PD) is the rate-limiting enzyme of the pentose phosphate pathway. G6PD is the main source of the essential cellular reductant, NADPH. The purpose of this review is to describe the biochemistry of G6PD and NADPH, cellular factors that regulate G6PD, normal physiologic roles of G6PD, and the pathogenic role altered G6PD/NADPH plays in kidney disease. NADPH is required for many essential cellular processes such as the antioxidant system, nitric oxide synthase, cytochrome p450 enzymes, and NADPH oxidase. Decreased G6PD activity and, as a result, decreased NADPH level have been associated with diabetic kidney disease, altered nitric oxide production, aldosterone-mediated endothelial dysfunction, and dialysis-associated anemia. Increased G6PD activity is associated with all cancers including kidney cancer. Inherited G6PD deficiency is the most common mutation in the world that is thought to be a relatively mild disorder primarily associated with anemia. Yet, intriguing studies have shown an increased prevalence of diabetes mellitus in G6PD-deficient people. It is not known if G6PD-deficient people are at more risk for other diseases. Much more research needs to be done to determine the role of altered G6PD activity (inherited or acquired) in the pathogenesis of kidney disease.

Methane oxidation on Pd–Ceria: A DFT study of the mechanism over PdxCe1-xO2, Pd, and PdO

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

Mayernick, Adam D.; Janik, Michael J.

2011-02-14

Palladium/ceria exhibits unique catalytic activity for hydrocarbon oxidation; however, the chemical and structural properties of active sites on the palladium–ceria surface are difficult to characterize. Strong interactions between palladium and the ceria support stabilize oxidized Pdδ+ species, which may contribute to the significant activity of Pd/ceria for methane oxidation. We present a density functional theory (DFT + U) investigation into methane oxidation over Pd/ceria and quantify the activity of the Pd xCe 1-xO 2(1 1 1) mixed oxide surface in comparison with the PdO(1 0 0) and Pd(1 1 1) surfaces. The methane activation barrier is lowest over the Pdmore » xCe 1-xO 2(1 1 1) surface, even lower than over the Pd(1 1 1) surface or low coordinated stepped or kinked Pd sites. Subsequent reaction steps in complete oxidation, including product desorption and vacancy refilling, are considered to substantiate that methane activation remains the rate-limiting step despite the low barrier over Pd xCe 1-xO 2(1 1 1). The low barrier over the Pd xCe 1-xO 2(1 1 1) surface demonstrates that mixed ceria-noble metal oxides offer the potential for improved hydrocarbon oxidation performance with respect to dispersed noble metal particles on ceria.« less

X-Ray Photoelectron Spectroscopy Study of the Heating Effects on Pd/6H-SiC Schottky Structure

NASA Technical Reports Server (NTRS)

Chen, Liang-Yu; Hunter, Gary W.; Neudeck, Philip G.; Knight, Dak

1998-01-01

X-ray photoelectron spectroscopy is used to study the effects of heat treatment on the Pd/6H-SiC Schottky diode structure. After heating the structure at 425 C for 140 h, a very thin surface layer of PdO mixed with SiO(x) formed on the palladium surface of the Schottky structure. Heat treatment promoted interfacial diffusion and reaction which significantly broadened the interfacial region. In the interfacial region, the palladium concentration decreases with depth, and the interfacial products are Pd(x)Si (x = 1,2,3,4). In the high Pd concentration regions, Pd4Si is the major silicide component while gr and Pd2Si are major components in the low Pd concentration region. At the center of the interface, where the total palladium concentration equals that of silicon, the concentrations of palladium associated with various palladium silicides (Pd(x)Si, x= 1,2,3,4) are approximately equal. The surface passivation layer composed of PdO and SiO, may significantly affect the electronic and catalytic properties of the surface of the Schottky diode which plays a major role in gas detection. The electronic properties of the Schottky structure may be dominated by a (Pd+Pd(x)Si)/SiC interface. In order to stabilize the properties of the Schottky structure the surface and interface diffusion and reactions must be controlled.

Frequency of puncture holes in peritoneal dialysis catheters related to the beta cap adapter.

PubMed

Ohashi, Yasushi; Kansal, Sheru; Schreiber, Martin

2012-01-01

Between November 2009 and September 2011, 12 patients (6 women, 6 men) undergoing continuous peritoneal dialysis (PD) or automated PD developed puncture-like holes in the PD catheter near the interface of the adapter with the superior aspect of the Silastic PD catheter The adapter is used to connect the PD catheter to the PD transfer set. Over the course of 23 months, the 12 patients presented to the PD unit with 19 separate instances of catheter holes, for an event rate of 0.23 holes per patient-year Data including socio-demographic information, PD modality, need for antibiotic treatment, event recurrence, infectious complications, and time from catheter placement were collected from patients whose catheters did and did not develop holes. We observed no differences between patients whose catheters developed holes and those whose catheters did not. The location of the individual holes suggested a relationship between the adapter and the catheter holes. The holes, which led to increased patient morbidity and costs, may be related to structural changes made in 2006 to the adapter.

Intonation contrast in Cantonese speakers with hypokinetic dysarthria associated with Parkinson's disease.

PubMed

Ma, Joan K-Y; Whitehill, Tara L; So, Susanne Y-S

2010-08-01

Speech produced by individuals with hypokinetic dysarthria associated with Parkinson's disease (PD) is characterized by a number of features including impaired speech prosody. The purpose of this study was to investigate intonation contrasts produced by this group of speakers. Speech materials with a question-statement contrast were collected from 14 Cantonese speakers with PD. Twenty listeners then classified the productions as either questions or statements. Acoustic analyses of F0, duration, and intensity were conducted to determine which acoustic cues distinguished the production of questions from statements, and which cues appeared to be exploited by listeners in identifying intonational contrasts. The results show that listeners identified statements with a high degree of accuracy, but the accuracy of question identification ranged from 0.56% to 96% across the 14 speakers. The speakers with PD used similar acoustic cues as nondysarthric Cantonese speakers to mark the question-statement contrast, although the contrasts were not observed in all speakers. Listeners mainly used F0 cues at the final syllable for intonation identification. These data contribute to the researchers' understanding of intonation marking in speakers with PD, with specific application to the production and perception of intonation in a lexical tone language.

Pb-free surface-finishing on electronic components' terminals for Pb-free soldering assembly

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

Tanaka, Hitoshi; Tanimoto, Morimasa; Matsuda, Akira

1999-11-01

Pb-free solderable surface finishing is essential to implement Pb-free solder assembly in order to meet with the growing demand of environmental consciousness to eliminate Pb from electronic products. Two types of widely applicable Pb-free surface finishing technologies are developed. One is the multilayer-system including Pd with Ni undercoat. Heat-resistance of Pd enables whole-surface-plating on to leadframe before IC-assembling process. The other is the double-layer-system with low-melting-point-materials, for example, thicker Sn underlayer and thinner Sn-Bi alloy overlayer, dilutes Sn-Bi alloy's defects of harmful reactivity along with substrate metal and mechanical brittleness with keeping its advantages of solder-wettability and no whisker.

Some advances in the silver physical development of latent prints on paper

NASA Astrophysics Data System (ADS)

Cantu, Antonio A.; Leben, Deborah A.; Wilson, Kelley

2003-09-01

Silver physical development, a now-abandoned technique used for developing photographic film or paper, is one of the most powerful methods for visualizing latent prints on paper. The method develops the water-insoluble components in the print residue. These components include the "fats and oils" or lipids found on the skin of fingers. The resulting developed print, referred to as a silver physically developed (Ag-PD) print, is made up of (gray to black) silver particles adhered to the fingerprint residue. Such prints are usually intensified (made darker) with a hypochlorite treatment. This process converts silver to silver oxide making the Ag-PD print become a Ag2O-PD prints. Often such (Ag-PD or Ag2O-PD) prints are found on areas with heavy or patterned printing making them difficult to see. This work resolves this problem by chemically lightening the print and darkening (suppressing) the interfering background.

European Training and Research in Peritoneal Dialysis: scientific objectives, training, implementation and impact of the programme.

PubMed

Foster, Tom L; Ferrantelli, Evelina; van Wier-van der Schaaf, Tanja; Beelen, Robert H J

2014-03-01

Peritoneal dialysis (PD) offers many advantages over hospital-based haemodialysis, including better quality of life. Despite this, there is a general under-utilisation of PD in Europe, which, to some extent, can be attributed to a lack of knowledge and education amongst renal clinicians and nurses. The specific aim of the European Training and Research in Peritoneal Dialysis (EuTRiPD) programme is to address this lack of knowledge, to develop a minimum of five biomarkers that allow the prediction of outcome in PD and three therapeutic treatments to improve outcome in PD. EuTRiPD is a EU-wide consortium with clinical, academic and commercial partners set up to address this knowledge gap. By training through research and close collaboration between academic and commercial entities we hope to improve the outcome and uptake of PD. It is the goal of EuTRiPD to improve the currently hampered diagnostic therapeutic developments in renal replacement therapy (RRT) and structure existing high-quality PD-related research across Europe. It is hoped that EuTRiPD can and will have a significant impact on socio-economic and scientific aspects of PD. It is the aim for EuTRiPD to boost the uptake of PD throughout Europe by making PD the obvious choice for patients. © 2013 European Dialysis and Transplant Nurses Association/European Renal Care Association.

Expanding the clinical and genetic spectrum of G6PD deficiency: The occurrence of BCGitis and novel missense mutation.

PubMed

Khan, Taj Ali; Mazhar, Humaira; Nawaz, Mehboob; Kalsoom, Kalsoom; Ishfaq, Muhammad; Asif, Huma; Rahman, Hazir; Qasim, Muhammad; Naz, Farkhanda; Hussain, Mubashir; Khattak, Baharullah; Ullah, Waheed; Cabral-Marques, Otavio; Butt, Jawad; Iqbal, Asif

2017-01-01

Glucose-6-phosphate dehydrogenase (G6PD) is a key enzyme in the pentose phosphate pathway that ensures sufficient production of coenzyme nicotinamide adenine dinucleotide phosphate (NADPH) by catalyzing the reduction of NADP+ to NADPH. Noteworthy, the latter mediates the production of reactive oxygen species (ROS) by phagocytic cells such as neutrophils and monocytes. Therefore, patients with severe forms of G6PD deficiency may present impaired NADPH oxidase activity and become susceptible to recurrent infections. This fact, highlights the importance to characterize the immunopathologic mechanisms underlying the susceptibility to infections in patients with G6PD deficiency. Here we report the first two cases of G6PD deficiency with Bacille Calmette-Guérin (BCG) adverse effect, besides jaundice, hemolytic anemia and recurrent infections caused by Staphylococcus aureus. The qualitative G6PD screening was performed and followed by oxidative burst analysis using flow cytometry. Genetic and in silico analyses were carried out by Sanger sequencing and mutation pathogenicity predicted using bioinformatics tools, respectively. Activated neutrophils and monocytes from patients displayed impaired oxidative burst. The genetic analysis revealed the novel missense mutation c.1157T>A/p.L386Q in G6PD. In addition, in silico analysis indicated that this mutation is pathogenic, thereby hampering the oxidative burst of neutrophils and monocytes from patients. Our data expand the clinical and genetic spectrum of G6PD deficiency, and suggest that impaired oxidative burst in this severe primary immune deficiency is an underlying immunopathologic mechanism that predisposes to mycobacterial infections. Copyright © 2016 Elsevier Ltd. All rights reserved.

PD-1 ligand expression by human colonic myofibroblasts/fibroblasts regulates CD4+ T-cell activity.

PubMed

Pinchuk, Irina V; Saada, Jamal I; Beswick, Ellen J; Boya, Gushyalatha; Qiu, Sumin M; Mifflin, Randy C; Raju, Gottumukkala S; Reyes, Victor E; Powell, Don W

2008-10-01

A prominent role for inhibitory molecules PD-L1 and PD-L2 in peripheral tolerance has been proposed. However, the phenotype and function of PD-L-expressing cells in human gut remains unclear. Recent studies suggest that colonic myofibroblasts (CMFs) and fibroblasts are important in the switch from acute inflammation to adaptive immunity. In the normal human colon, CMFs represent a distinct population of major histocompatibility complex class II(+) cells involved in the regulation of mucosal CD4(+) T-cell responses. PD-L1 and PD-L2 expression on human CMFs was determined using Western blot, fluorescence-activated cell sorter analysis and confocal microscopy. Lymphoproliferation assays and cytokine enzyme-linked immunosorbent assays were used to evaluate the role of B7 costimulators expressed by CMFs with regard to the regulation of preactivated T-helper cell responses. We demonstrate here the expression of PD-L1/2 molecules by normal human CMF and fibroblasts in situ and in culture. Both molecules support suppressive functions of CMFs in the regulation of activated CD4(+) T-helper cell proliferative responses; blocking this interaction reverses the suppressive effect of CMFs on T-cell proliferation and leads to increased production of the major T-cell growth factor, interleukin (IL)-2. PD-L1/2-mediated CMF suppressive functions are mainly due to the inhibition of IL-2 production, because supplementation of the coculture media with exogenous IL-2 led to partial recovery of activated T-cell proliferation. Our data suggest that stromal myofibroblasts and fibroblasts may limit T-helper cell proliferative activity in the gut and, thus, might play a prominent role in mucosal intestinal tolerance.

Active sites and mechanisms for H2O2 decomposition over Pd catalysts

PubMed Central

Plauck, Anthony; Stangland, Eric E.; Dumesic, James A.; Mavrikakis, Manos

2016-01-01

A combination of periodic, self-consistent density functional theory (DFT-GGA-PW91) calculations, reaction kinetics experiments on a SiO2-supported Pd catalyst, and mean-field microkinetic modeling are used to probe key aspects of H2O2 decomposition on Pd in the absence of cofeeding H2. We conclude that both Pd(111) and OH-partially covered Pd(100) surfaces represent the nature of the active site for H2O2 decomposition on the supported Pd catalyst reasonably well. Furthermore, all reaction flux in the closed catalytic cycle is predicted to flow through an O–O bond scission step in either H2O2 or OOH, followed by rapid H-transfer steps to produce the H2O and O2 products. The barrier for O–O bond scission is sensitive to Pd surface structure and is concluded to be the central parameter governing H2O2 decomposition activity. PMID:27006504

Improving gold catalysis of nitroarene reduction with surface Pd

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

Pretzer, Lori A.; Heck, Kimberly N.; Kim, Sean S.

2016-04-01

Nitroarene reduction reactions are commercialized catalytic processes that play a key role in the synthesisof many products including medicines, rubbers, dyes, and herbicides. Whereas bimetallic compositionshave been studied, a better understanding of the bimetallic structure effects may lead to improved indus-trial catalysts. In this work, the influence of surface palladium atoms supported on 3-nm Au nanoparticles(Pd-on-Au NPs) on catalytic activity for 4-nitrophenol reduction is explored. Batch reactor studies indi-cate Pd-on-Au NPs exhibit maximum catalytic activity at a Pd surface coverage of 150 sc%, with aninitial turnover frequency of ~3.7 mol-nitrophenol/mol-metalsurface/s, which was ~5.5× and ~13× moreactive than pure Au NPsmore » and Pd NPs, respectively. Pd NPs, Au NPs, and Pd-on-Au NPs below 175 sc%show compensation behavior. Three-dimensional Pd surface ensembles (with ~4–5 atoms) previouslyidentified through X-ray adsorption spectroscopy provide the active sites responsible for the catalyticmaximum. These results demonstrate the ability to adjust systematically a structural feature (i.e., Pdsurface coverage) to yield a more active material.« less

Upregulation of PD-L1 by EML4-ALK fusion protein mediates the immune escape in ALK positive NSCLC: Implication for optional anti-PD-1/PD-L1 immune therapy for ALK-TKIs sensitive and resistant NSCLC patients.

PubMed

Hong, Shaodong; Chen, Nan; Fang, Wenfeng; Zhan, Jianhua; Liu, Qing; Kang, Shiyang; He, Xiaobo; Liu, Lin; Zhou, Ting; Huang, Jiaxing; Chen, Ying; Qin, Tao; Zhang, Yaxiong; Ma, Yuxiang; Yang, Yunpeng; Zhao, Yuanyuan; Huang, Yan; Zhang, Li

2016-03-01

Driver mutations were reported to upregulate programmed death-ligand 1 (PD-L1) expression. However, how PD-L1 expression and immune function was affected by ALK-TKIs and anti-PD-1/PD-L1 treatment in ALK positive non-small-cell lung cancer (NSCLC) remains poorly understood. In the present study, western-blot, real-time PCR, flow cytometry and immunofluorescence were employed to explore how PD-L1 was regulated by ALK fusion protein. ALK-TKIs and relevant inhibitors were used to identify the downstream signaling pathways involved in PD-L1 regulation. Cell apoptosis, viability and Elisa test were used to study the immune suppression by ALK activation and immune reactivation by ALK-TKIs and/or PD-1 blocking in tumor cells and DC-CIK cells co-culture system. We found that PD-L1 expression was associated with EGFR mutations and ALK fusion genes in NSCLC cell lines. Over-expression of ALK fusion protein increased PD-L1 expression. PD-L1 mediated by ALK fusion protein increased the apoptosis of T cells in tumor cells and DC-CIK cells co-culture system. Inhibiting ALK by sensitive TKIs could enhance the production of IFNγ. Anti-PD-1 antibody was effective in both crizotinib sensitive and resistant NSCLC cells. Synergistic tumor killing effects were not observed with ALK-TKIs and anti-PD-1 antibody combination in co-culture system. ALK-TKIs not only directly inhibited tumor viability but also indirectly enhanced the antitumor immunity via the downregulation of PD-L1. Anti-PD-1/PD-L1 antibodies could be an optional therapy for crizotinib sensitive, especially crizotinib resistant NSCLC patients with ALK fusion gene. Combination of ALK-TKIs and anti-PD-1/PD-L1 antibodies treatment for ALK positive NSCLC warrants more data before moving into clinical practice.

Upregulation of PD-L1 by EML4-ALK fusion protein mediates the immune escape in ALK positive NSCLC: Implication for optional anti-PD-1/PD-L1 immune therapy for ALK-TKIs sensitive and resistant NSCLC patients

PubMed Central

Hong, Shaodong; Chen, Nan; Fang, Wenfeng; Zhan, Jianhua; Liu, Qing; Kang, Shiyang; He, Xiaobo; Liu, Lin; Zhou, Ting; Huang, Jiaxing; Chen, Ying; Qin, Tao; Zhang, Yaxiong; Ma, Yuxiang; Yang, Yunpeng; Zhao, Yuanyuan; Huang, Yan; Zhang, Li

2016-01-01

ABSTRACT Driver mutations were reported to upregulate programmed death-ligand 1 (PD-L1) expression. However, how PD-L1 expression and immune function was affected by ALK-TKIs and anti-PD-1/PD-L1 treatment in ALK positive non-small-cell lung cancer (NSCLC) remains poorly understood. In the present study, western-blot, real-time PCR, flow cytometry and immunofluorescence were employed to explore how PD-L1 was regulated by ALK fusion protein. ALK-TKIs and relevant inhibitors were used to identify the downstream signaling pathways involved in PD-L1 regulation. Cell apoptosis, viability and Elisa test were used to study the immune suppression by ALK activation and immune reactivation by ALK-TKIs and/or PD-1 blocking in tumor cells and DC-CIK cells co-culture system. We found that PD-L1 expression was associated with EGFR mutations and ALK fusion genes in NSCLC cell lines. Over-expression of ALK fusion protein increased PD-L1 expression. PD-L1 mediated by ALK fusion protein increased the apoptosis of T cells in tumor cells and DC-CIK cells co-culture system. Inhibiting ALK by sensitive TKIs could enhance the production of IFNγ. Anti-PD-1 antibody was effective in both crizotinib sensitive and resistant NSCLC cells. Synergistic tumor killing effects were not observed with ALK-TKIs and anti-PD-1 antibody combination in co-culture system. ALK-TKIs not only directly inhibited tumor viability but also indirectly enhanced the antitumor immunity via the downregulation of PD-L1. Anti-PD-1/PD-L1 antibodies could be an optional therapy for crizotinib sensitive, especially crizotinib resistant NSCLC patients with ALK fusion gene. Combination of ALK-TKIs and anti-PD-1/PD-L1 antibodies treatment for ALK positive NSCLC warrants more data before moving into clinical practice. PMID:27141355

Distribution of fission products palladium, silver, cerium and cesium in the un-corroded areas of the locally corroded SiC layer of a neutron irradiated TRISO fuel particle

DOE PAGES

Wen, Haiming; van Rooyen, Isabella J.

2017-04-14

Here, detailed electron microscopy studies were performed to investigate the distribution and composition of fission products in the SiC layer of a tristructural isotropic coated particle exhibiting localized corrosion. Previous studies on this particle indicated that pure carbon areas in the SiC layer, resulting from localized corrosion of SiC by Pd, provide pathways for Ag, Cd and Cs migration. This study reveals the presence of Ag- and/or Cd-containing precipitates in un-corroded SiC areas. Ag/Cd may exist by themselves or coexist with Pd. Ag/Cd mainly transport along SiC grain boundaries. An Ag-Pd-Cd precipitate was identified at a stacking fault inside amore » SiC grain, suggesting that intragranular transport of Ag/Cd is possible. Ce is present with Pd or Pd-U in some precipitates >50 nm. U and Ce frequently coexist with each other, whereas Ag/Cd usually does not coexist with U or Ce. No Cs was detected in any precipitates in the areas examined.« less

MIF induces osteoclast differentiation and contributes to progression of periodontal disease in mice.

PubMed

Madeira, Mila Fernandes Moreira; Queiroz-Junior, Celso Martins; Costa, Graciela Mitre; Santos, Patrícia Campi; Silveira, Elcia Maria; Garlet, Gustavo Pompermaier; Cisalpino, Patrícia Silva; Teixeira, Mauro Martins; Silva, Tarcília Aparecida; Souza, Daniele da Glória

2012-02-01

Periodontal disease (PD) is a chronic inflammatory and alveolar bone destructive disease triggered by microorganisms from the oral biofilm. Oral inoculation of mice with the periodontopathogen Aggregatibacter actinomycetemcomitans (Aa) induces marked alveolar bone loss and local production of inflammatory mediators, including Macrophage Migration Inhibitory Factor (MIF). The role of MIF for alveolar bone resorption during PD is not known. In the present study, experimental PD was induced in BALB/c wild-type mice (WT) and MIF knockout mice (MIF⁻/⁻) through oral inoculation of Aa. Despite enhanced number of bacteria, MIF⁻/⁻ mice had reduced infiltration of TRAP-positive cells and reduced alveolar bone loss. This was associated with decreased neutrophil accumulation and increased levels of IL-10 in periodontal tissues. TNF-α production was similar in both groups. In vitro, LPS from Aa enhanced osteoclastic activity in a MIF-dependent manner. In conclusion, MIF has role in controlling bacterial growth in the context of PD but contributes more significantly to the progression of bone loss during PD by directly affecting differentiation and activity of osteoclasts. Copyright © 2011 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Product Distribution Theory for Control of Multi-Agent Systems

NASA Technical Reports Server (NTRS)

Lee, Chia Fan; Wolpert, David H.

2004-01-01

Product Distribution (PD) theory is a new framework for controlling Multi-Agent Systems (MAS's). First we review one motivation of PD theory, as the information-theoretic extension of conventional full-rationality game theory to the case of bounded rational agents. In this extension the equilibrium of the game is the optimizer of a Lagrangian of the (probability distribution of) the joint stare of the agents. Accordingly we can consider a team game in which the shared utility is a performance measure of the behavior of the MAS. For such a scenario the game is at equilibrium - the Lagrangian is optimized - when the joint distribution of the agents optimizes the system's expected performance. One common way to find that equilibrium is to have each agent run a reinforcement learning algorithm. Here we investigate the alternative of exploiting PD theory to run gradient descent on the Lagrangian. We present computer experiments validating some of the predictions of PD theory for how best to do that gradient descent. We also demonstrate how PD theory can improve performance even when we are not allowed to rerun the MAS from different initial conditions, a requirement implicit in some previous work.

Callose biosynthesis regulates symplastic trafficking during root development.

PubMed

Vatén, Anne; Dettmer, Jan; Wu, Shuang; Stierhof, York-Dieter; Miyashima, Shunsuke; Yadav, Shri Ram; Roberts, Christina J; Campilho, Ana; Bulone, Vincent; Lichtenberger, Raffael; Lehesranta, Satu; Mähönen, Ari Pekka; Kim, Jae-Yean; Jokitalo, Eija; Sauer, Norbert; Scheres, Ben; Nakajima, Keiji; Carlsbecker, Annelie; Gallagher, Kimberly L; Helariutta, Ykä

2011-12-13

Plant cells are connected through plasmodesmata (PD), membrane-lined channels that allow symplastic movement of molecules between cells. However, little is known about the role of PD-mediated signaling during plant morphogenesis. Here, we describe an Arabidopsis gene, CALS3/GSL12. Gain-of-function mutations in CALS3 result in increased accumulation of callose (β-1,3-glucan) at the PD, a decrease in PD aperture, defects in root development, and reduced intercellular trafficking. Enhancement of CALS3 expression during phloem development suppressed loss-of-function mutations in the phloem abundant callose synthase, CALS7 indicating that CALS3 is a bona fide callose synthase. CALS3 alleles allowed us to spatially and temporally control the PD aperture between plant tissues. Using this tool, we are able to show that movement of the transcription factor SHORT-ROOT and microRNA165 between the stele and the endodermis is PD dependent. Taken together, we conclude that regulated callose biosynthesis at PD is essential for cell signaling. Copyright © 2011 Elsevier Inc. All rights reserved.

Professional Development to Promote Teacher Adaptability

ERIC Educational Resources Information Center

Parsons, Allison Ward; Ankrum, Julie Winneur; Morewood, Aimee

2016-01-01

Effective professional development (PD) follows adaptive teaching principles; it increases teacher understanding and instructional purpose, which ultimately supports and extends adaptive teaching. Through this article, we compare and contrast training models with educative models of PD (Duffy, 2004). We discuss characteristics of effective PD that…

Development of Personality and the Remission and Onset of Personality Pathology

PubMed Central

Wright, Aidan G. C.; Pincus, Aaron L.; Lenzenweger, Mark F.

2011-01-01

The current study uses the Longitudinal Study of Personality Disorders dataset (Lenzenweger, 1999) to examine the development of personality traits in the context of the remission and onset of personality disorder (PD) symptoms. Despite high levels of stability, past research that has examined the development of basic personality traits has also found a mean trend towards increased maturity, and that individuals vary in their trajectories of trait development. Research on PD change has shown a similar pattern. We employ individual growth curve modeling to examine the relationship between personality trait development and PD symptom course. We found that the two are indeed related, and that remission in PD symptoms is associated with patterns of trait development associated with more rapid maturity. In contrast, deviating from the mean of trait development either through no change (i.e., stagnation) or change in the opposite direction (i.e., regression) was associated with developing PD symptoms over the course of the study. PMID:21967009

Parkinson disease and musculoskeletal pain: an 8-year population-based cohort study.

PubMed

Lien, Wei-Hung; Lien, Wei-Chih; Kuan, Ta-Shen; Wu, Shang-Te; Chen, Yi-Ting; Chiu, Ching-Ju

2017-07-01

The aim of this study was to evaluate the incidence and clinical features of musculoskeletal pain (MSP) in patients with Parkinson disease (PD) compared with a control group without the disease. The retrospective cohort study used a subset of the Taiwan National Health Insurance Research Database (NHIRD) comprising information on 1 million beneficiaries randomly sampled from the entire population of Taiwan. A total of 490 patients aged 50 and above with newly diagnosed Parkinson disease were identified during a period from 2000 to 2005. Among them, 199 developed MSP after PD. The control group consisted of 1960 participants without PD over the study period randomly selected by matching PD cases according to the date of PD incidence, age, and sex. The study groups were then followed to the end of 2007. Musculoskeletal pain was the end point. The incidence rate ratios of MSP were higher in the PD group than in the control group, representing an adjusted hazard ratio of 1.31 (95% confidence interval 1.09 to 1.58). PD was associated with a significantly elevated risk of MSP in all sex and age stratifications, with the highest hazard ratio noted for middle-aged male patients with PD, followed by older male patients with PD. This study showed that the PD may significantly increase the risk of developing MSP. The risk of developing MSP seems to be greatest for middle-aged male patients with PD. Clinicians should be more alert for MSP in patients with PD, and early intervention should be considered.

Bio‐palladium: from metal recovery to catalytic applications

PubMed Central

De Corte, Simon; Hennebel, Tom; De Gusseme, Bart; Verstraete, Willy; Boon, Nico

2012-01-01

Summary While precious metals are available to a very limited extent, there is an increasing demand to use them as catalyst. This is also true for palladium (Pd) catalysts and their sustainable recycling and production are required. Since Pd catalysts exist nowadays mostly under the form of nanoparticles, these particles need to be produced in an environment‐friendly way. Biological synthesis of Pd nanoparticles (‘bio‐Pd’) is an innovative method for both metal recovery and nanocatalyst synthesis. This review will discuss the different bio‐Pd precipitating microorganisms, the applications of the catalyst (both for environmental purposes and in organic chemistry) and the state of the art of the reactors based on the bio‐Pd concept. In addition, some main challenges are discussed, which need to be overcome in order to create a sustainable nanocatalyst. Finally, some outlooks for bio‐Pd in environmental technology are presented. PMID:21554561

Spectators Control Selectivity in Surface Chemistry: Acrolein Partial Hydrogenation Over Pd

PubMed Central

2015-01-01

We present a mechanistic study on selective hydrogenation of acrolein over model Pd surfaces—both single crystal Pd(111) and Pd nanoparticles supported on a model oxide support. We show for the first time that selective hydrogenation of the C=O bond in acrolein to form an unsaturated alcohol is possible over Pd(111) with nearly 100% selectivity. However, this process requires a very distinct modification of the Pd(111) surface with an overlayer of oxopropyl spectator species that are formed from acrolein during the initial stages of reaction and turn the metal surface selective toward propenol formation. By applying pulsed multimolecular beam experiments and in situ infrared reflection–absorption spectroscopy, we identified the chemical nature of the spectator and the reactive surface intermediate (propenoxy species) and experimentally followed the simultaneous evolution of the reactive intermediate on the surface and formation of the product in the gas phase. PMID:26481220

European Training and Research in Peritoneal Dialysis--A Network to Deliver Scientific Peritoneal Dialysis Training to a New Generation of Researchers.

PubMed

Machowska, Anna; van Wier, Tanja; Aufricht, Christoph; Beelen, Rob; Rutherford, Peter

2015-01-01

Peritoneal dialysis (PD) utilization varies across countries, and of the factors that explain the variation, the scientific and clinical knowledge of health care professionals is potentially important. In this paper, we describe a European collaboration--between 8 academic PD research programs, a small-to-medium-sized enterprise, and a large PD product manufacturer--that received significant research funding from the EU commission to establish a training network. European Training and Research in Peritoneal Dialysis (EuTRiPD) is providing training to 12 PhD students who have moved within the European Union and are completing research training. The underlying structure and processes within EuTRiPD (http://www.eutripd. eu) are described, and the benefits of the collaborative approach are discussed. This model could be useful to other research groups and will assist in maintaining and growing scientific expertise in PD research.

Atezolizumab for the treatment of non-small cell lung cancer.

PubMed

Santini, Fernando C; Rudin, Charles M

2017-09-01

The immune system can restrain or promote cancer development and growth. Antibodies targeting immune checkpoints have revolutionized cancer treatment. Among the best responses have been in non-small cell lung cancer (NSCLC) which is largely caused by chronic exposure to carcinogens; associated with high neoantigen creation and sensitization to immune recognition. Atezolizumab was the first approved antibody that targets the PD-1 ligand (PD-L1). Areas covered: This drug profile article covers the basics of the cancer-immunity cycle and reviews some aspects of innate and adaptive immunology. We discuss the discovery of PD-L1 and PD-L2 while highlight the potential differences in targeting PD-L1 versus PD-1. In addition, we briefly summarized the available pre-clinical and clinical data of atezolizumab use in NSCLC. A special section covers the challenges of PD-L1 immunohistochemistry assay. Expert commentary: PD-1:PD-L1 blockade has taken the lead in the immunotherapeutics field and represents the backbone of developing combination immunotherapies. Atezolizumab represents a step forward in the treatment of advanced NSCLC, nonetheless PD1:PD-L1 blockade in early-stage lung cancer is still a matter of debate.

Exploring risk factors for stuttering development in Parkinson disease after deep brain stimulation.

PubMed

Picillo, Marina; Vincos, Gustavo B; Sammartino, Francesco; Lozano, Andres M; Fasano, Alfonso

2017-05-01

Stuttering is a speech disorder with disruption of verbal fluency, occasionally present in Parkinson's disease (PD). PD co-incident stuttering may either worsen or improve after Deep Brain Stimulation (DBS). Sixteen out of 453 PD patients (3.5%) exhibited stuttering after DBS (PD-S) and were compared with a group of patients without stuttering (PD-NS) using non-parametric statistics. After DBS, stuttering worsened in 3 out of 4 patients with co-incidental stuttering. Most PD-S underwent subthalamic (STN) DBS, but 4 were implanted in the globus pallidus (GPi). Nine out of 16 PD-S (56.3%) reported a positive familial history for stuttering compared to none of the PD-NS. PD-S were mainly male (81.3%) with slight worse motor features compared to PD-NS. Herein, we describe a group of PD patients developing stuttering after DBS and report the presence of a positive familial history for stuttering as the most relevant risk factor, suggesting a possible underlying genetic cause. The fact that stuttering occurred after either STN or GPi DBS is an argument against the impact of medication reduction on stuttering. Copyright © 2017 Elsevier Ltd. All rights reserved.

Preclinical pharmacokinetic/pharmacodynamic modeling and simulation in the pharmaceutical industry: an IQ consortium survey examining the current landscape.

PubMed

Schuck, Edgar; Bohnert, Tonika; Chakravarty, Arijit; Damian-Iordache, Valeriu; Gibson, Christopher; Hsu, Cheng-Pang; Heimbach, Tycho; Krishnatry, Anu Shilpa; Liederer, Bianca M; Lin, Jing; Maurer, Tristan; Mettetal, Jerome T; Mudra, Daniel R; Nijsen, Marjoleen Jma; Raybon, Joseph; Schroeder, Patricia; Schuck, Virna; Suryawanshi, Satyendra; Su, Yaming; Trapa, Patrick; Tsai, Alice; Vakilynejad, Majid; Wang, Shining; Wong, Harvey

2015-03-01

The application of modeling and simulation techniques is increasingly common in preclinical stages of the drug discovery and development process. A survey focusing on preclinical pharmacokinetic/pharmacodynamics (PK/PD) analysis was conducted across pharmaceutical companies that are members of the International Consortium for Quality and Innovation in Pharmaceutical Development. Based on survey responses, ~68% of companies use preclinical PK/PD analysis in all therapeutic areas indicating its broad application. An important goal of preclinical PK/PD analysis in all pharmaceutical companies is for the selection/optimization of doses and/or dose regimens, including prediction of human efficacious doses. Oncology was the therapeutic area with the most PK/PD analysis support and where it showed the most impact. Consistent use of more complex systems pharmacology models and hybrid physiologically based pharmacokinetic models with PK/PD components was less common compared to traditional PK/PD models. Preclinical PK/PD analysis is increasingly being included in regulatory submissions with ~73% of companies including these data to some degree. Most companies (~86%) have seen impact of preclinical PK/PD analyses in drug development. Finally, ~59% of pharmaceutical companies have plans to expand their PK/PD modeling groups over the next 2 years indicating continued growth. The growth of preclinical PK/PD modeling groups in pharmaceutical industry is necessary to establish required resources and skills to further expand use of preclinical PK/PD modeling in a meaningful and impactful manner.

Exchange coupling interaction in L10-FePd/α-Fe nanocomposite magnets with large maximum energy products.

PubMed

Sakuma, Noritsugu; Ohshima, Tsubasa; Shoji, Tetsuya; Suzuki, Yoshihito; Sato, Ryota; Wachi, Ayako; Kato, Akira; Kawai, Yoichiro; Manabe, Akira; Teranishi, Toshiharu

2011-04-26

Nanocomposite magnets (NCMs) consisting of hard and soft magnetic phases are expected to be instrumental in overcoming the current theoretical limit of magnet performance. In this study, structural analyses were performed on L1(0)-FePd/α-Fe NCMs with various hard/soft volume fractions, which were formed by annealing Pd/γ-Fe(2)O(3) heterostructured nanoparticles and pure Pd nanoparticles. The sample with a hard/soft volume ratio of 82/18 formed by annealing at 773 K had the largest maximum energy product (BH(max) = 10.3 MGOe). In such a sample, the interface between the hard and soft phases was coherent and the phase sizes were optimized, both of which effectively induced exchange coupling. This exchange coupling was directly observed by visualizing the magnetic interaction between the hard and soft phases using a first-order reversal curve diagram, which is a valuable tool to improve the magnetic properties of NCMs.

C-C Coupling on Single-Atom-Based Heterogeneous Catalyst.

PubMed

Zhang, Xiaoyan; Sun, Zaicheng; Wang, Bin; Tang, Yu; Nguyen, Luan; Li, Yuting; Tao, Franklin Feng

2018-01-24

Compared to homogeneous catalysis, heterogeneous catalysis allows for ready separation of products from the catalyst and thus reuse of the catalyst. C-C coupling is typically performed on a molecular catalyst which is mixed with reactants in liquid phase during catalysis. This homogeneous mixing at a molecular level in the same phase makes separation of the molecular catalyst extremely challenging and costly. Here we demonstrated that a TiO 2 -based nanoparticle catalyst anchoring singly dispersed Pd atoms (Pd 1 /TiO 2 ) is selective and highly active for more than 10 Sonogashira C-C coupling reactions (R≡CH + R'X → R≡R'; X = Br, I; R' = aryl or vinyl). The coupling between iodobenzene and phenylacetylene on Pd 1 /TiO 2 exhibits a turnover rate of 51.0 diphenylacetylene molecules per anchored Pd atom per minute at 60 °C, with a low apparent activation barrier of 28.9 kJ/mol and no cost of catalyst separation. DFT calculations suggest that the single Pd atom bonded to surface lattice oxygen atoms of TiO 2 acts as a site to dissociatively chemisorb iodobenzene to generate an intermediate phenyl, which then couples with phenylacetylenyl bound to a surface oxygen atom. This coupling of phenyl adsorbed on Pd 1 and phenylacetylenyl bound to O ad of TiO 2 forms the product molecule, diphenylacetylene.

Diastereoselective sp2-sp3 coupling of sugar enol ethers with unactivated cycloalkenes: new entries to C-branched sugars.

PubMed

Hussain, Nazar; Tatina, Madhu Babu; Rasool, Faheem; Mukherjee, Debaraj

2016-10-25

Sugar enol ethers undergo efficient coupling at C-2 with unactivated cycloalkenes under a low Pd loading affording allylic substitution products. High diastereoselectivity was observed at the allylic centre with sterically hindered substrates. Generation of a π-allyl complex by the Pd(ii) catalyst via cleavage of the allylic C-H bond of the cycloalkene may be responsible for the formation of sp 2 -sp 3 coupling products.

The influence of nano-architectured CeOx supports in RhPd/CeO₂ for the catalytic ethanol steam reforming reaction

DOE PAGES

Divins, N. J.; Senanayake, S. D.; Casanovas, A.; ...

2015-01-19

The ethanol steam reforming (ESR) reaction has been tested over RhPd supported on polycrystalline ceria in comparison to structured supports composed of nanoshaped CeO₂ cubes and CeO₂ rods tailored towards the production of hydrogen. At 650-700 K the hydrogen yield follows the trend RhPd/CeO₂-cubes > RhPd/CeO₂ -rods > RhPd/CeO₂- polycrystalline, whereas at temperatures higher than 800 K the catalytic performance of all samples is similar and close to the thermodynamic equilibrium. The improved performance of RhPd/CeO₂-cubes and RhPd/CeO₂ -rods for ESR at low temperature is mainly ascribed to higher water-gas shift activity and a strong interaction between the bimetallic -more » oxide support interaction. STEM analysis shows the existence of RhPd alloyed nanoparticles in all samples, with no apparent relationship between ESR performance and RhPd particle size. X-ray diffraction under operating conditions shows metal reorganization on {100} and {110} ceria crystallographic planes during catalyst activation and ESR, but not on {111} ceria crystallographic planes. The RhPd reconstructing and tuned activation over ceria nanocubes and nanorods is considered the main reason for better catalytic activity with respect to conventional catalysts based on polycrystalline ceria« less

Biorefining of precious metals from wastes: an answer to manufacturing of cheap nanocatalysts for fuel cells and power generation via an integrated biorefinery?

PubMed

Yong, Ping; Mikheenko, Iryna P; Deplanche, Kevin; Redwood, Mark D; Macaskie, Lynne E

2010-12-01

Bio-manufacturing of nano-scale palladium was achieved via enzymatically-mediated deposition of Pd from solution using Desulfovibrio desulfuricans, Escherichia coli and Cupriavidus metallidurans. Dried 'Bio-Pd' materials were sintered, applied onto carbon papers and tested as anodes in a proton exchange membrane (PEM) fuel cell for power production. At a Pd(0) loading of 25% by mass the fuel cell power using Bio-Pd( D. desulfuricans ) (positive control) and Bio-Pd( E. coli ) (negative control) was ~140 and ~30 mW respectively. Bio-Pd( C. metallidurans ) was intermediate between these with a power output of ~60 mW. An engineered strain of E. coli (IC007) was previously reported to give a Bio-Pd that was >3-fold more active than Bio-Pd of the parent E. coli MC4100 (i.e. a power output of >110 mW). Using this strain, a mixed metallic catalyst was manufactured from an industrial processing waste. This 'Bio-precious metal' ('Bio-PM') gave ~68% of the power output as commercial Pd(0) and ~50% of that of Bio-Pd( D. desulfuricans ) when used as fuel cell anodic material. The results are discussed in relation to integrated bioprocessing for clean energy.

Aerobic Exercise Improves Mood, Cognition, and Language Function in Parkinson's Disease: Results of a Controlled Study.

PubMed

Altmann, Lori J P; Stegemöller, Elizabeth; Hazamy, Audrey A; Wilson, Jonathan P; Bowers, Dawn; Okun, Michael S; Hass, Chris J

2016-10-01

Parkinson's disease (PD) results in a range of non-motor deficits that can affect mood, cognition, and language, and many of these issues are unresponsive to pharmacological intervention. Aerobic exercise can improve mood and cognition in healthy older adults, although only a few studies have examined exercise effects on these domains in PD. The current study assesses the effects of aerobic exercise on aspects of cognition, mood, and language production in people with PD. This study compares the effects of aerobic exercise to stretch-balance training and a no-contact control group in participants with idiopathic PD. The aerobic and stretch-balance groups trained three times a week for 16 weeks, while controls continued normal activities. Outcome measures included disease severity, mood, cognition (speed of processing, memory, and executive function), and language production (picture descriptions). Cognition and language were assessed in single and dual task conditions. Depressive symptoms increased only in the control group (p<.02). Executive function improved in the aerobic exercise group only in the single task (p=.007) and declined in controls in the dual task. Completeness of picture descriptions improved significantly more in the aerobic group than in the stretch-balance group (p<.02). Aerobic exercise is a viable intervention for PD that can be protective against increased depressive symptoms, and can improve several non-motor domains, including executive dysfunction and related aspects of language production. (JINS, 2016, 22, 878-889).

Old-Fashioned Bus Trips: New Age Professional Development

ERIC Educational Resources Information Center

Feldhues, Katherine; Epley, Hannah K.

2018-01-01

Two 4-H Camp-related bus tours offered new nontraditional professional development (PD) experiences that better align Extension's PD opportunities with the organization's experiential education pedagogy. Creating quality PD opportunities for employees is important because such experiences can affect overall work performance, community connections,…

Programmed cell death 1 (PD-1) regulates the effector function of CD8 T cells via PD-L1 expressed on target keratinocytes.

PubMed

Okiyama, Naoko; Katz, Stephen I

2014-09-01

Programmed cell death 1 (PD-1) is an inhibitory molecule expressed by activated T cells. Its ligands (PD-L1 and -L2; PD-Ls) are expressed not only by a variety of leukocytes but also by stromal cells. To assess the role of PD-1 in CD8 T cell-mediated diseases, we used PD-1-knockout (KO) OVA-specific T cell-receptor transgenic (Tg) CD8 T cells (OT-I cells) in a murine model of mucocutaneous graft-versus-host disease (GVHD). We found that mice expressing OVA on epidermal keratinocytes (K14-mOVA mice) developed markedly enhanced GVHD-like disease after transfer of PD-1-KO OT-I cells as compared to those mice transferred with wild-type OT-I cells. In addition, K14-mOVA × OT-I double Tg (DTg) mice do not develop GVHD-like disease after adoptive transfer of OT-I cells, while transfer of PD-1-KO OT-I cells caused GVHD-like disease in a Fas/Fas-L independent manner. These results suggest that PD-1/PD-Ls-interactions have stronger inhibitory effects on pathogenic CD8 T cells than does Fas/Fas-L-interactions. Keratinocytes from K14-mOVA mice with GVHD-like skin lesions express PD-L1, while those from mice without the disease do not. These findings reflect the fact that primary keratinocytes express PD-L1 when stimulated by interferon-γ in vitro. When co-cultured with K14-mOVA keratinocytes for 2 days, PD-1-KO OT-I cells exhibited enhanced proliferation and activation compared to wild-type OT-I cells. In addition, knockdown of 50% PD-L1 expression on the keratinocytes with transfection of PD-L1-siRNA enhanced OT-I cell proliferation. In aggregate, our data strongly suggest that PD-L1, expressed on activated target keratinocytes presenting autoantigens, regulates autoaggressive CD8 T cells, and inhibits the development of mucocutaneous autoimmune diseases. Published by Elsevier Ltd.

Synergetic effect of palladium-ruthenium nanostructures for ethanol electrooxidation in alkaline media

NASA Astrophysics Data System (ADS)

Monyoncho, Evans A.; Ntais, Spyridon; Soares, Felipo; Woo, Tom K.; Baranova, Elena A.

2015-08-01

Palladium-ruthenium nanoparticles supported on carbon PdxRu1-x/C (x = 1, 0.99, 0.95, 0.90, 0.80, 0.50) were prepared using a polyol method for ethanol electrooxidation in alkaline media. The resulting bimetallic catalysts were found to be primarily a mix of Pd metal, Ru oxides and Pd oxides. Their electrocatalytic activity towards ethanol oxidation reaction (EOR) in 1M KOH was studied using cyclic voltammetry and chronoamperometry techniques. Addition of 1-10 at.% Ru to Pd not only lowers the onset oxidation potential for EOR but also produces higher current densities at lower potentials compared to Pd by itself. Thus, Pd90Ru10/C and Pd99Ru1/C provide the current densities of up to six times those of Pd/C at -0.96 V and -0.67 V vs MSE, respectively. The current density at different potentials was found to be dependent on the surface composition of PdxRu1-x/C nanostructures. Pd90Ru10/C catalyst with more surface oxides was found to be active at lower potential compared to Pd99Ru1/C with less surface oxides, which is active at higher potentials. The steady-state current densities of the two best catalysts, Pd90Ru10/C and Pd99Ru1/C, showed minimal surface deactivation from EOR intermediates/products during chronoamperometry.

Role of the immune modulator programmed cell death-1 during development and apoptosis of mouse retinal ganglion cells

PubMed Central

Chen, Ling; Sham, Caroline W.; Chan, Ann M.; Francisco, Loise M.; Wu, Yin; Mareninov, Sergey; Sharpe, Arlene H.; Freeman, Gordon J.; Yang, Xian-Jie; Braun, Jonathan; Gordon, Lynn K.

2011-01-01

PURPOSE Mammalian programmed cell death-1 (PD-1) is a membrane-associated receptor regulating the balance between T cell activation, tolerance and immunopathology, however its role in neurons has not yet been defined. We investigate the hypothesis that PD-1 signaling actively promotes retinal ganglion cell (RGC) death within the developing mouse retina. METHODS Mature retinal cell types expressing PD-1 were identified by immunofluorescence staining of vertical retina sections; developmental expression was localized by immunostaining and quantified by Western analysis. PD-1 involvement in developmental RGC survival was assessed in vitro using retina explants and in vivo using PD-1 knockout mice. PD-1 ligand gene expression was detected by RT-PCR. RESULTS PD-1 is expressed in most adult RGCs, and undergoes dynamic upregulation during the early postnatal window of retinal cell maturation and physiological programmed cell death (PCD). In vitro blockade of PD-1 signaling during this time selectively increases survival of RGCs. Furthermore, PD-1 deficient mice show a selective increase in RGC number in the neonatal retina at the peak of developmental RGC death. Lastly, throughout postnatal retina maturation, we find gene expression of both immune PD-1 ligand genes, PD-L1 and PD-L2. CONCLUSIONS These findings collectively support a novel role for a PD-1-mediated signaling pathway in developmental PCD during postnatal RGC maturation. PMID:19420345

Insights into the Role of Humic Acid on Pd-catalytic Electro-Fenton Transformation of Toluene in Groundwater

PubMed Central

Liao, Peng; Al-Ani, Yasir; Malik Ismael, Zainab; Wu, Xiaohui

2015-01-01

A recently developed Pd-based electro-Fenton (E-Fenton) process enables efficient in situ remediation of organic contaminants in groundwater. In the process, H2O2, Fe(II), and acidic conditions (~pH 3) are produced in situ to facilitate the decontamination, but the role of ubiquitous natural organic matters (NOM) remain unclear. This study investigated the effect of Aldrich humic acid (HA) on the transformation of toluene by the Pd-based E-Fenton process. At pH 3 with 50 mA current, the presence of HA promoted the efficiency of toluene transformation, with pseudo-first-order rate constants increase from 0.01 to 0.016 as the HA concentration increases from 0 to 20 mg/L. The HA-enhanced toluene transformation was attributed to the accelerated thermal reduction of Fe(III) to Fe(II), which led to production of more hydroxyl radicals. The correlation of the rate constants of toluene transformation and HA decomposition validated hydroxyl radical (·OH) as the predominant reactive species for HA decomposition. The finding of this study highlighted that application of the novel Pd-based E-Fenton process in groundwater remediation may not be concerned by the fouling from humic substances. PMID:25783864

Insights into the role of humic acid on Pd-catalytic electro-Fenton transformation of toluene in groundwater.

PubMed

Liao, Peng; Al-Ani, Yasir; Malik Ismael, Zainab; Wu, Xiaohui

2015-03-18

A recently developed Pd-based electro-Fenton (E-Fenton) process enables efficient in situ remediation of organic contaminants in groundwater. In the process, H₂O₂, Fe(II), and acidic conditions (~pH 3) are produced in situ to facilitate the decontamination, but the role of ubiquitous natural organic matters (NOM) remain unclear. This study investigated the effect of Aldrich humic acid (HA) on the transformation of toluene by the Pd-based E-Fenton process. At pH 3 with 50 mA current, the presence of HA promoted the efficiency of toluene transformation, with pseudo-first-order rate constants increase from 0.01 to 0.016 as the HA concentration increases from 0 to 20 mg/L. The HA-enhanced toluene transformation was attributed to the accelerated thermal reduction of Fe(III) to Fe(II), which led to production of more hydroxyl radicals. The correlation of the rate constants of toluene transformation and HA decomposition validated hydroxyl radical (·OH) as the predominant reactive species for HA decomposition. The finding of this study highlighted that application of the novel Pd-based E-Fenton process in groundwater remediation may not be concerned by the fouling from humic substances.

Biocompatibility of peritoneal dialysis fluids: long-term exposure of nonuremic rats.

PubMed

Musi, Barbara; Braide, Magnus; Carlsson, Ola; Wieslander, Anders; Albrektsson, Ann; Ketteler, Markus; Westenfeld, Ralf; Floege, Jürgen; Rippe, Bengt

2004-01-01

Long-term peritoneal dialysis (PD) leads to structural and functional changes in the peritoneum. The aim of the present study was to investigate the long-term effects of PD fluid components, glucose and glucose degradation products (GDP), and lactate-buffered solution on morphology and transport characteristics in a nonuremic rat model. Rats were subjected to two daily intraperitoneal injections (20 mL/day) during 12 weeks of one of the following: commercial PD fluid (Gambrosol, 4%; Gambro AB, Lund, Sweden), commercial PD fluid with low GDP levels (Gambrosol trio, 4%; Gambro AB), sterile-filtered PD fluid (4%) without GDP, or a glucose-free lactate-buffered PD fluid. Punctured and untreated controls were used. Following exposure, the rats underwent a single 4-hour PD dwell (30 mL, 4% glucose) to determine peritoneal function. Additionally, submesothelial tissue thickness, percentage of high mesothelial cells (perpendicular diameter > 2 microm), vascular density, vascular endothelial growth factor (VEGF), and transforming growth factor (TGF) beta1 mRNA expression were determined. Submesothelial collagen concentration was estimated by van Gieson staining. Submesothelial tissue thickness and vascular density, mediated by VEGF and TGFbeta production, in the diaphragmatic peritoneum increased significantly in rats exposed to any PD fluid. Gambrosol induced a marked increased fibrosis of the hepatic peritoneum. A significant increase in high mesothelial cells was observed in the Gambrosol group only. Net ultrafiltration was reduced in the Gambrosol and in the glucose-free groups compared to untreated controls. Small solute transport was unchanged, but all groups exposed to fluids showed significantly increased lymph flow. Our results show that long-term exposure to different components of PD fluids leads to mesothelial cell damage, submesothelial fibrosis, and neoangiogenesis. Mesothelial cell damage could be connected to the presence of GDP; the other changes were similar for all fluids. Peritoneal transport characteristics did not change in any consistent way and the neoangiogenesis observed was not paralleled by increased solute transport.

Probing neurodegeneration and aging: A PET approach

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

VanBrocklin, H.F.

1995-12-31

Positron Emission Tomography (PET) imaging has received wide application to the study of the aging brain and its diseases, most notably Parkinson`s Disease (PD) and Alzheimer`s Disease (AD). Basic neurological processes such as blood flow and glucose metabolism have been most often measured. Radioligands developed for specific neurochemical systems have amplified the flow and metabolism studies by more precisely defining the changes associated with degenerative processes. Our present research focuses on two additional applications of radiopharmaceutical development and PET imaging - (1) investigating the fundamental mechanisms of neurodegeneration and aging, and (2) assessing novel therapeutic intervention for PD with PETmore » imaging. We have synthesized fluorine-18 labeled analogs of rotenone, a natural product that possesses high affinity to Complex I of the mitochondrial electron transport chain, and evaluated their potential to study changes in neuronal mitochondrial density and function. A large body evidence points to mitochondrial dysfunction as a key factor in aging and neurodegeneration. We are also currently evaluating the use of genetically transfected cells to treat PD. Primates are being imaged with [{sup 18}F]flouro-m-L-tyrosine before and after MPTP Parkinsonian type lesioning and following implantation of genetically altered cells capable of secreting tyrosine hydroxylase into the lesioned area. The ability to develop and apply PET probes has significantly enhanced the understanding of normal, aging, and degenerative processes of the brain.« less

Armed oncolytic adenovirus expressing PD-L1 mini-body enhances anti-tumor effects of chimeric antigen receptor T-cells in solid tumors

PubMed Central

Tanoue, Kiyonori; Shaw, Amanda Rosewell; Watanabe, Norihiro; Porter, Caroline; Rana, Bhakti; Gottschalk, Stephen; Brenner, Malcolm; Suzuki, Masataka

2017-01-01

Chimeric antigen receptor-modified T cells (CAR T-cells) produce pro-inflammatory cytokines that increase expression of T cell checkpoint signals such as PD-L1, which may inhibit their functionality against solid tumors. In this study, we evaluated in human tumor xenograft models the pro-inflammatory properties of an oncolytic adenovirus (Onc.Ad) with a helper-dependent Ad (HDAd) that expresses a PD-L1 blocking mini-antibody (mini-body) (HDPDL1), as a strategy to enhance CAR T-cell killing. Co-administration of these agents (CAd-VECPDL1) exhibited oncolytic effects with production of PD-L1 mini-body locally at the tumor site. On their own, HDPDL1 exhibited no anti-tumor effect and CAd-VECPDL1 alone reduced tumors only to volumes comparable to Onc.Ad treatment. However, combining CAd-VECPDL1 with HER2.CAR T-cells enhanced anti-tumor activity compared to treatment with either HER2.CAR T-cells alone, or HER2.CAR T-cells plus Onc.Ad. The benefits of locally produced PD-L1 mini-body by CAd-VECPDL1 could not be replicated by infusion of anti-PD-L1 IgG plus HER2.CAR T-cells and co-administration of Onc.Ad in a HER2+ prostate cancer xenograft model. Overall, our data document the superiority of local production of PD-L1 mini-body by CAd-VECPDL1 combined with administration of tumor-directed CAR T-cells to control the growth of solid tumors. PMID:28235763

Decision-making impairments in Parkinson's disease as a by-product of defective cost-benefit analysis and feedback processing.

PubMed

Ryterska, Agata; Jahanshahi, Marjan; Osman, Magda

2014-01-01

Studies examining decision-making in people with Parkinson's disease (PD) show impaired performance on a variety of tasks. However, there are also demonstrations that patients with PD can make optimal decisions just like healthy age-matched controls. We propose that the reason for these mixed findings is that PD does not produce a generalized impairment of decision-making, but rather affects sub-components of this process. In this review we evaluate this hypothesis by considering the empirical evidence examining decision-making in PD. We suggest that of the various stages of the decision-making process, the most affected in PD are (1) the cost-benefit analysis stage and (2) the outcome evaluation stage. We consider the implications of this proposal for research in this area.

Evaluation of the Catalytic Activity and Cytotoxicity of Palladium Nanocubes. The Role of Oxygen

PubMed Central

Dahal, Eshan; Curtiss, Jessica; Subedi, Deepak; Chen, Gen; Houston, Jessica P.; Smirnov, Sergei

2015-01-01

Recently it has been reported that palladium nanocubes (PdNC) are capable of generating singlet oxygen without photo-excitation simply via chemisorption of molecular oxygen on its surface. Such a trait would make PdNC a highly versatile catalyst suitable in organic synthesis and a Reactive Oxygen Species (ROS) inducing cancer treatment reagent. Here we thoroughly investigated the catalytic activity of PdNC with respect to their ability to produce singlet oxygen and to oxidize 3,5,3′,5′-tetramethyl-benzidine (TMB), as well as, analyzed the cytotoxic properties of PdNC on HeLa cells. Our findings showed no evidence of singlet oxygen production by PdNC. The nanocubes’ activity is not necessarily linked to activation of oxygen. The oxidation of substrate on PdNC can be a first step followed by PdNC regeneration with oxygen or other oxidant. The catalytic activity of PdNC towards oxidation of TMB is very high and shows direct two-electrons oxidation when the surface of PdNC is clean and the ratio of TMB/PdNC is not very high. Sequential one electron oxidation is observed when the pristine quality of PdNC surface is compromised by serum or uncontrolled impurities and/or the ratio of TMB/PdNC is high. Clean PdNC in serum-free media efficiently induce apoptosis of HeLa cells. It is the primary route of cell death and is associated with hyperpolarization of mitochondria, contrary to a common mitochondrial depolarization initiated by ROS. Again, the effects are very sensitive to how well the pristine surface of PdNC is preserved, suggesting that PdNC can be used as an apoptosis inducing agent but only with appropriate drug delivery system. PMID:25886644

Development of electrochemical sensor for the determination of palladium ions (Pd2+) using flexible screen printed un-modified carbon electrode.

PubMed

Velmurugan, Murugan; Thirumalraj, Balamurugan; Chen, Shen-Ming; Al-Hemaid, Fahad M A; Ajmal Ali, M; Elshikh, Mohamed S

2017-01-01

To date, the development of different modified electrodes have received much attention in electrochemistry. The modified electrodes have some drawbacks such as high cost, difficult to handle and not eco friendly. Hence, we report an electrochemical sensor for the determination of palladium ions (Pd 2+ ) using an un-modified screen printed carbon electrode has been developed for the first time, which are characterized and studied via scanning electron microscope and cyclic voltammetry. Prior to determination of Pd 2+ ions, the operational conditions of un-modified SPCE was optimized using cyclic voltammetry and showed excellent electro-analytical behavior towards the determination of Pd 2+ ions. Electrochemical determination of Pd 2+ ions reveal that the un-modified electrode showed lower detection limit of 1.32μM with a linear ranging from 3 to 133.35μM towards the Pd 2+ ions concentration via differential pulse voltammetry. The developed sensor also applied to the successfully determination of trace level Pd 2+ ions in spiked water samples. In addition, the advantage of this type of electrode is simple, disposable and cost effective in electrochemical sensors. Copyright © 2016 Elsevier Inc. All rights reserved.

Facile Aqueous Phase Synthesis of Pd3Cu-B/C Nanocatalyst for Glucose Electrooxidation

NASA Astrophysics Data System (ADS)

Chai, Dan; Lu, Haibin; Wang, Yaqian; Hua, Xiuwen; Ren, Na; Zhang, Xiongwen

2018-01-01

A novel Pd3Cu-B/C nanocatalyst was facilely synthesized through an aqueous phase process. And it was developed for use in the glucose electrooxidation reaction in fuel cells. Cyclic voltammetry shown that the electrochemical surface area of Pd3Cu-B/C is 2.25 times that of Pd/C. Glucose electrooxidation curves revealed that peak current on the Pd3Cu-B/C is actually 1.73 times of the Pd/C. This high performance of Pd3Cu-B/C could be ascribed to the synergistic effect between Pd, Cu and B.

Professional development for primary science teaching in Thailand: Knowledge, orientations, and practices of professional developers and professional development participants

NASA Astrophysics Data System (ADS)

Musikul, Kusalin

The purpose of this study was to examine an entire PD project as a case to understand the dynamic nature of science PD in a holistic manner. I used a pedagogical content knowledge model by Magnusson, Krajcik, and Borko (1999) as my theoretical framework in examining the professional developers' and teacher participants' knowledge, orientation, and practice for professional development and elementary science teaching. The case study is my research tradition; I used grounded theory for data analysis. The primary data sources were interview, card sort activity, and observation field notes collected during the PD and subsequently in teacher participants' classrooms. Secondary data sources were documents and artifacts that I collected from the professional developers and teachers. An analysis of the data led me to interpret the following findings: (a) the professional developers displayed multiple orientations. These orientations included activity-driven, didactic, discovery, and pedagogy-driven orientations. The orientations that were found among the professional developers deviated from the reformed Thai Science Education Standards; (b) the professional developers had limited PCK for PD, which were knowledge of teachers' learning, knowledge of PD strategies, knowledge of PD curriculum, and knowledge of assessment.; (c) the professional developers' knowledge and orientations influenced their decisions in selecting PD activities and teaching approaches; (d) their orientations and PCK as well as the time factor influenced the design and implementation of the professional development; (e) the elementary teachers displayed didactic, activity-driven, and academic rigor orientations. The orientations that the teachers displayed deviated from the reformed Thai Science Education Standards; and (f) the elementary teachers exhibited limited PCK. It is evident that the limitation of one type of knowledge resulted in an ineffective use of other components of PCK. This study demonstrates the nature of PD in the context of Thailand in a holistic view to understand knowledge, orientation, and implementation of professional developers and professional development participants. Furthermore, the findings have implications for professional development and professional developers in Thailand and include worldwide with respect to promoting sustain and intensive professional development and developing professional developers.

N-heterocycle carbene (NHC)-ligated cyclopalladated N,N-dimethylbenzylamine: a highly active, practical and versatile catalyst for the Heck-Mizoroki reaction.

PubMed

Peh, Guang-Rong; Kantchev, Eric Assen B; Zhang, Chi; Ying, Jackie Y

2009-05-21

The wide dissemination of catalytic protocols in academic and industrial laboratories is facilitated by the development of catalysts that are not only highly active but also user-friendly, stable to moisture, air and long term storage and easy to prepare on a large scale. Herein we describe a protocol for the Heck-Mizoroki reaction mediated by cyclopalladated N,N-dimethylbenzylamine (dmba) ligated with a N-heterocyclic carbene, 1,3-bis(mesityl)imidazol-2-ylidene (IMes), that fulfils these criteria. The precatalyst can be synthesized on approximately 100 g scale by a tri-component, sequential, one-pot reaction of N,N-dimethylbenzylamine, PdCl2 and IMes.HCl in refluxing acetonitrile in air in the presence of K2CO3. This single component catalyst is stable to air, moisture and long term storage and can be conveniently dispensed as a stock solution in NMP. It mediates the Heck-Mizoroki reaction of a range of aryl- and heteroaryl bromides in reagent grade NMP at the 0.1-2 mol% range without the need for rigorous anhydrous techniques or a glovebox, and is active even in air. The catalyst is capable of achieving very high levels of catalytic activity (TON of up to 5.22 x 10(5)) for the coupling of a deactivated arylbromide, p-bromoanisole, with tBu acrylate as a benchmark substrate pair. A wide range of aryl bromides, iodides and, for the first time with a NHC-Pd catalyst, a triflate was coupled with diverse acrylate derivatives (nitrile, tert-butyl ester and amides) and styrene derivatives. The use of excess (>2 equiv.) of the aryl bromide and tert-butyl acrylate leads to mixture of tert-butyl beta,beta-diarylacrylate and tert-butyl cinnamate derivatives depending on the substitution pattern of the aryl bromide. Electron rich m- and p-substituted arylbromides give the diarylated products exclusively, whereas electron-poor aryl bromides give predominantly mono-arylated products. For o-substituted aryl bromides, no doubly arylated products could be obtained under any conditions. Overall, the active catalyst (IMes-Pd) shows higher activity with electron-rich aryl halides, a marked difference compared with the more commonly used phosphane-Pd or non-ligated Pd catalysts.

Evaluating the Impact of Teacher Professional Development: An Evidence-Based Framework

ERIC Educational Resources Information Center

King, Fiona

2014-01-01

Does teacher professional development make a difference? How do we know? While researchers and policy-makers acknowledge that teacher professional development (PD) needs to be assessed and evaluated, there is often little clarity as to how this can be achieved. Evaluation of teacher PD by schools has been described as the weak link in the PD chain…

Development and Fit-for-Purpose Validation of a Soluble Human Programmed Death-1 Protein Assay.

PubMed

Ni, Yan G; Yuan, Xiling; Newitt, John A; Peterson, Jon E; Gleason, Carol R; Haulenbeek, Jonathan; Santockyte, Rasa; Lafont, Virginie; Marsilio, Frank; Neely, Robert J; DeSilva, Binodh; Piccoli, Steven P

2015-07-01

Programmed death-1 (PD-1) protein is a co-inhibitory receptor which negatively regulates immune cell activation and permits tumors to evade normal immune defense. Anti-PD-1 antibodies have been shown to restore immune cell activation and effector function-an exciting breakthrough in cancer immunotherapy. Recent reports have documented a soluble form of PD-1 (sPD-1) in the circulation of normal and disease state individuals. A clinical assay to quantify sPD-1 would contribute to the understanding of sPD-1-function and facilitate the development of anti-PD-1 drugs. Here, we report the development and validation of a sPD-1 protein assay. The assay validation followed the framework for full validation of a biotherapeutic pharmacokinetic assay. A purified recombinant human PD-1 protein was characterized extensively and was identified as the assay reference material which mimics the endogenous analyte in structure and function. The lower limit of quantitation (LLOQ) was determined to be 100 pg/mL, with a dynamic range spanning three logs to 10,000 pg/mL. The intra- and inter-assay imprecision were ≤15%, and the assay bias (percent deviation) was ≤10%. Potential matrix effects were investigated in sera from both normal healthy volunteers and selected cancer patients. Bulk-prepared frozen standards and pre-coated Streptavidin plates were used in the assay to ensure consistency in assay performance over time. This assay appears to specifically measure total sPD-1 protein since the human anti-PD-1 antibody, nivolumab, and the endogenous ligands of PD-1 protein, PDL-1 and PDL-2, do not interfere with the assay.

What can the treatment of Parkinson's disease learn from dementia care; applying a bio-psycho-social approach to Parkinson's disease.

PubMed

Gibson, Grant

2017-12-01

Within contemporary medical practice, Parkinson's disease (PD) is treated using a biomedical, neurological approach, which although bringing numerous benefits can struggle to engage with how people with PD experience the disease. A bio-psycho-social approach has not yet been established in PD; however, bio-psycho-social approaches adopted within dementia care practice could bring significant benefit to PD care. This paper summarises existing bio-psycho-social models of dementia care and explores how these models could also usefully be applied to care for PD. Specifically, this paper adapts the bio-psycho-social model for dementia developed by Spector and Orrell (), to suggest a bio-psycho-social model, which could be used to inform routine care in PD. Drawing on the biopsychosocial model of Dementia put forward by Spector and Orrell (), this paper explores the application of a bio-psycho-social model of PD. This model conceptualises PD as a trajectory, in which several interrelated fixed and tractable factors influence both PD's symptomology and the various biological and psychosocial challenges individuals will face as their disease progresses. Using an individual case study, this paper then illustrates how such a model can assist clinicians in identifying suitable interventions for people living with PD. This model concludes by discussing how a bio-psycho-social model could be used as a tool in PD's routine care. The model also encourages the development of a theoretical and practical framework for the future development of the role of the PD specialist nurse within routine practice. A biopsychosocial approach to Parkinson's Disease provides an opportunity to move towards a holistic model of care practice which addresses a wider range of factors affecting people living with PD. The paper puts forward a framework through which PD care practice can move towards a biopsychosocial perspective. PD specialist nurses are particularly well placed to adopt such a model within routine clinical practice, and should therefore be encouraged within PD services. © 2017 John Wiley & Sons Ltd.

Asian G6PD-Mahidol Reticulocytes Sustain Normal Plasmodium Vivax Development

PubMed Central

Bancone, Germana; Malleret, Benoit; Suwanarusk, Rossarin; Chowwiwat, Nongnud; Chu, Cindy S; McGready, Rose; Rénia, Laurent; Nosten, François

2017-01-01

Abstract Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymatic disorder in humans and appears to be protective against falciparum severe malaria. Controversially, it is also thought that Plasmodium vivax has driven the recent selection of G6PD alleles. We use an experimental approach to determine whether G6PD-MahidolG487A variant, a widespread cause of severe G6PD deficiency in Southeast Asia, provides a barrier against vivax malaria. Our results show that the immature reticulocytes (CD71+) targeted by P. vivax invasion are enzymatically normal, even in hemizygous G6PD-Mahidol G487A mutants; thus, allowing the normal growth, development, and high parasite density in severely deficient samples. PMID:28591790

Supporting University Content Specialists in Providing Effective Professional Development: The Educative Role of Evaluation

ERIC Educational Resources Information Center

Arbaugh, Fran; Marra, Rose; Lannin, John K.; Cheng, Ya-Wen; Merle-Johnson, Dominike; Smith, Rena'

2016-01-01

Evaluation of professional development (PD) has traditionally been composed of summative and formative feedback, and has focused on assessing the extent to which the PD impacts participating teachers' knowledge, beliefs, and practices. This study establishes an additional purpose for PD evaluation--as "educative opportunities" for…

Research Reports into Professional Development.

ERIC Educational Resources Information Center

Australian National Training Authority, Brisbane.

Five reports present findings of research into professional development (PD) issues in vocational education and training (VET) in Australia. "Lessons Learnt: An Analysis of Findings of Recent Evaluation Reports on PD in VET" (Kate Perkins) provides an overview of issues, insights, and ideas emerging from past PD experience that may be…

Differences across Academic Subjects in Teachers' Attitudes about Professional Development

ERIC Educational Resources Information Center

Torff, Bruce; Byrnes, Katherine

2011-01-01

A survey study examined how attitudes about professional development (PD) vary among teachers of different subjects. Elementary teachers were more supportive of PD than health and physical education, social studies, and science teachers; special education teachers were more supportive of PD than social studies and science teachers; and five…

Rectal Microbicide Development

PubMed Central

Dezzutti, Charlene

2014-01-01

The last few years have seen important progress in demonstrating the efficacy of oral pre-exposure prophylaxis, vaginal microbicides, and treatment as prevention as effective strategies for reducing the risk of acquiring or transmitting HIV infection. There has also been significant progress in the development of rectal microbicides. Preclinical non-human primate studies have demonstrated that antiretroviral microbicides can provide significant protection from rectal challenge with SIV or SHIV. Recent Phase 1 rectal microbicide studies have characterized the safety, acceptability, compartmental pharmacokinetics (PK), and pharmaco-dynamics (PD) of both UC781 and tenofovir gels. The tenofovir gel formulation used in vaginal studies was not well tolerated in the rectum and newer rectal-specific formulations have been developed and evaluated in Phase 1 studies. The PK/PD data generated in these Phase 1 studies may reduce the risk of advancing ineffective candidate rectal microbicides into late stage development. Tenofovir gel is currently poised to move into Phase 2 evaluation and it is possible that a Phase 2B/3 effectiveness study with this product could be initiated in the next 2–3 years. PMID:23612991

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

Dagle, Robert A.; Lizarazo Adarme, Jair A.; Lebarbier, Vanessa MC

A composite Pd/ZnO/Al2O3-HZSM-5 (Si/Al=40) catalytic system was evaluated for the synthesis of gasoline-range hydrocarbons directly from synthesis gas. Bifunctional catalyst comprising PdZn metal and acid sites present the required catalytically active sites necessary for the methanol synthesis, methanol dehydration, and methanol-to-gasoline reactions. This system provides a unique catalytic pathway for the production of liquid hydrocarbons directly from syngas. However, selectivity control is difficult and poses many challenges. The composite catalytic system was evaluated under various process conditions. Investigated were the effects of temperature (310-375oC), pressure (300-1000 psig), time-on-stream (50 hrs), and gas-hour space velocity (740-2970 hr-1), using a H2/CO molarmore » syngas ratio of 2.0. By operating at the lower end of the temperature range investigated, liquid hydrocarbon formation was favored, as was decreased amounts of undesirable light hydrocarbons. However, lower operating temperatures also facilitated undesirable CO2 formation via the water-gas shift reaction. Higher operating pressures slightly favored liquid synthesis. Operating at relatively low pressures (e.g. 300 psig) was made possible, whereas for methanol synthesis alone higher pressure are usually required to achieve similar conversion levels (e.g. 1000 psig). Thermodynamic constraints on methanol synthesis are eased by pushing the equilibrium through hydrocarbon formation. Catalytic performance was also evaluated by altering Pd and Zn composition of the Pd/ZnO/Al2O3 catalyst. Of the catalysts and conditions tested, selectivity toward liquid hydrocarbon was highest when using a 5% Pd metal loading and Pd/Zn molar ratio of 0.25 and mixed with HZMS-5, operating at 310oC and 300 psig, CO conversion was 43 % and selectivity (carbon weight basis) to hydrocarbons was 49 wt. %. Of the hydrocarbon fraction, 44wt. % was in the C5-C12 liquid product range and consisted primarily of aromatic polymethylbenzenes. However, as syngas conversion increases with increasing temperature, selectivity to liquid product diminished. This is attributed, in large part, to increased saturation of the olefinic intermediates over PdZn metal sites. Under all the conditions and catalysts evaluated in this study, generating liquid product in high yield was challenging (<10 wt. % C5+ yield).« less

Capitalizing on Teacher Expertise: Motivations for Contemplating Transfer from Professional Development to the Classroom

NASA Astrophysics Data System (ADS)

van Duzor, Andrea Gay

2011-08-01

Of primary concern in professional development (PD) are the ways in which teachers transfer knowledge from PD to the classroom. This qualitative case study of a chemistry PD course for elementary teachers investigates the first step in the transfer process by examining why and how K-8 teachers consider transfer to the classroom. Motivations for considering transfer were the same whether teachers only proposed how they could use PD content or teachers actively utilized PD experiments and concepts in their own classrooms. Teacher learning of chemistry concepts, activities, and pedagogical strategies were motivating factors for considering transfer. Teachers appropriated and adapted PD materials based on the specific learning needs of their own students, the constraints of their teaching contexts, and their desired outcomes, including making science learning relevant for students. Understanding teachers' motivations and means of adaptations in considering PD can inform PD provider programs how to be more effective and responsive to teacher needs. Furthermore, teachers' active consideration of appropriations and adaptations highlights how teachers leverage their expertise in shaping their PD experiences.

The Interaction of Lexical Characteristics and Speech Production in Parkinson's Disease

ERIC Educational Resources Information Center

Chiu, Yi-Fang; Forrest, Karen

2017-01-01

Purpose: This study sought to investigate the interaction of speech movement execution with higher order lexical parameters. The authors examined how lexical characteristics affect speech output in individuals with Parkinson's disease (PD) and healthy control (HC) speakers. Method: Twenty speakers with PD and 12 healthy speakers read sentences…

77 FR 65999 - Assessments, Large Bank Pricing

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-31

... period for PD estimation, as opposed to a longer history, to capture the consumer behavior that generated... default behavior of consumers during a period of economic stress, the default rate is to be calculated as... consumer behavior that affect the riskiness of different product types. To ensure that the PD methodology...

Maximum surgical blood order schedule for pancreatoduodenectomy: a long way from uniform applicability!

PubMed

Barreto, Savio G; Singh, Amanjeet; Perwaiz, Azhar; Singh, Tanveer; Singh, Manish Kumar; Chaudhary, Adarsh

2017-04-01

Unnecessary preoperative ordering of blood and blood products results in wastage of a valuable life-saving resource and poses a significant financial burden on healthcare systems. To determine patient-specific factors associated with intra-operative transfusions, and if intra-operative blood transfusions impact postoperative morbidity. Analysis of consecutive patients undergoing pancreatoduodenectomy (PD) for pancreatic tumors. A total of 384 patients underwent a classical PD with an estimated median blood loss of 200 cc and percentage transfused being 9.6%. Pre-existing hypertension, synchronous vascular resection, end-to-side pancreaticojejunostomy and nodal disease burden significantly associated with the need for intra-operative transfusions. Intra-operative blood transfusion not associated with postoperative morbidity. Optimization of MSBOS protocols for PD is required for more judicious use of blood products.

Immortalized Parkinson's disease lymphocytes have enhanced mitochondrial respiratory activity

PubMed Central

Annesley, Sarah J.; Lay, Sui T.; De Piazza, Shawn W.; Sanislav, Oana; Hammersley, Eleanor; Allan, Claire Y.; Francione, Lisa M.; Bui, Minh Q.; Chen, Zhi-Ping; Ngoei, Kevin R. W.; Tassone, Flora; Kemp, Bruce E.; Storey, Elsdon; Evans, Andrew; Loesch, Danuta Z.

2016-01-01

ABSTRACT In combination with studies of post-mortem Parkinson's disease (PD) brains, pharmacological and genetic models of PD have suggested that two fundamental interacting cellular processes are impaired – proteostasis and mitochondrial respiration. We have re-examined the role of mitochondrial dysfunction in lymphoblasts isolated from individuals with idiopathic PD and an age-matched control group. As previously reported for various PD cell types, the production of reactive oxygen species (ROS) by PD lymphoblasts was significantly elevated. However, this was not due to an impairment of mitochondrial respiration, as is often assumed. Instead, basal mitochondrial respiration and ATP synthesis are dramatically elevated in PD lymphoblasts. The mitochondrial mass, genome copy number and membrane potential were unaltered, but the expression of indicative respiratory complex proteins was also elevated. This explains the increased oxygen consumption rates by each of the respiratory complexes in experimentally uncoupled mitochondria of iPD cells. However, it was not attributable to increased activity of the stress- and energy-sensing protein kinase AMPK, a regulator of mitochondrial biogenesis and activity. The respiratory differences between iPD and control cells were sufficiently dramatic as to provide a potentially sensitive and reliable biomarker of the disease state, unaffected by disease duration (time since diagnosis) or clinical severity. Lymphoblasts from control and PD individuals thus occupy two distinct, quasi-stable steady states; a ‘normal’ and a ‘hyperactive’ state characterized by two different metabolic rates. The apparent stability of the ‘hyperactive’ state in patient-derived lymphoblasts in the face of patient ageing, ongoing disease and mounting disease severity suggests an early, permanent switch to an alternative metabolic steady state. With its associated, elevated ROS production, the ‘hyperactive’ state might not cause pathology to cells that are rapidly turned over, but brain cells might accumulate long-term damage leading ultimately to neurodegeneration and the loss of mitochondrial function observed post-mortem. Whether the ‘hyperactive’ state in lymphoblasts is a biomarker specifically of PD or more generally of neurodegenerative disease remains to be determined. PMID:27638668

A humanized antibody for imaging immune checkpoint ligand PD-L1 expression in tumors

PubMed Central

Gabrielson, Matthew; Lisok, Ala; Wharram, Bryan; Sysa-Shah, Polina; Azad, Babak Behnam; Pomper, Martin G.; Nimmagadda, Sridhar

2016-01-01

Antibodies targeting the PD-1/PD-L1 immune checkpoint lead to tumor regression and improved survival in several cancers. PD-L1 expression in tumors may be predictive of response to checkpoint blockade therapy. Because tissue samples might not always be available to guide therapy, we developed and evaluated a humanized antibody for non-invasive imaging of PD-L1 expression in tumors. Radiolabeled [111In]PD-L1-mAb and near-infrared dye conjugated NIR-PD-L1-mAb imaging agents were developed using the mouse and human cross-reactive PD-L1 antibody MPDL3280A. We tested specificity of [111In]PD-L1-mAb and NIR-PD-L1-mAb in cell lines and in tumors with varying levels of PD-L1 expression. We performed SPECT/CT imaging, biodistribution and blocking studies in NSG mice bearing tumors with constitutive PD-L1 expression (CHO-PDL1) and in controls (CHO). Results were confirmed in triple negative breast cancer (TNBC) (MDAMB231 and SUM149) and non-small cell lung cancer (NSCLC) (H2444 and H1155) xenografts with varying levels of PD-L1 expression. There was specific binding of [111In]PD-L1-mAb and NIR-PD-L1-mAb to tumor cells in vitro, correlating with PD-L1 expression levels. In mice bearing subcutaneous and orthotopic tumors, there was specific and persistent high accumulation of signal intensity in PD-L1 positive tumors (CHO-PDL1, MDAMB231, H2444) but not in controls. These results demonstrate that [111In]PD-L1-mAb and NIR-PD-L1-mAb can detect graded levels of PD-L1 expression in human tumor xenografts in vivo. As a humanized antibody, these findings suggest clinical translation of radiolabeled versions of MPDL3280A for imaging. Specificity of NIR-PD-L1-mAb indicates the potential for optical imaging of PD-L1 expression in tumors in relevant pre-clinical as well as clinical settings. PMID:26848870

Improved resection and prolonged overall survival with PD-1-IRDye800CW fluorescence probe-guided surgery and PD-1 adjuvant immunotherapy in 4T1 mouse model

PubMed Central

Li, Yuan; Jin, Zhengyu; Xue, Huadan; Wan, Yihong; Tian, Jie

2017-01-01

An intraoperative technique to accurately identify microscopic tumor residuals could decrease the risk of positive surgical margins. Several lines of evidence support the expression and immunotherapeutic effect of PD-1 in breast cancer. Here, we sought to develop a fluorescence-labeled PD-1 probe for in vivo breast tumor imaging and image-guided surgery. The efficacy of PD-1 monoclonal antibody (PD-1 mAb) as adjuvant immunotherapy after surgery was also assessed. PD-1-IRDye800CW was developed and examined for its application in tumor imaging and image-guided tumor resection in an immunocompetent 4T1 mouse tumor model. Fluorescence molecular imaging was performed to monitor probe biodistribution and intraoperative imaging. Bioluminescence imaging was performed to monitor tumor growth and evaluate postsurgical tumor residuals, recurrences, and metastases. The PD-1-IRDye800CW exhibited a specific signal at the tumor region compared with the IgG control. Furthermore, PD-1-IRDye800CW-guided surgery combined with PD-1 adjuvant immunotherapy inhibited tumor regrowth and microtumor metastases and thus improved survival rate. Our study demonstrates the feasibility of using PD-1-IRDye800CW for breast tumor imaging and image-guided tumor resection. Moreover, PD-1 mAb adjuvant immunotherapy reduces cancer recurrences and metastases emanating from tumor residuals. PMID:29200846

Functional brain imaging of cognitive dysfunction in Parkinson's disease.

PubMed

Hirano, Shigeki; Shinotoh, Hitoshi; Eidelberg, David

2012-10-01

Multiple factors are involved in the development of cognitive impairment in Parkinson's disease (PD) and related disorders. Notably, several underlying factors, such as monoaminergic dysfunction, Lewy body pathology, Alzheimer disease-like pathology and cerebrovascular disease are implied in the PD pathophysiology of cognitive impairment. The mesocortical dopaminergic system is associated with executive functions which are frequently affected in PD and are influenced by local levodopa concentration, dopamine metabolism and baseline performance status. The ventral striatum and frontal cortex are associated with impulse control disorders reported in PD patients treated with dopamine replacement therapy. Cholinergic impairment in PD plays a cardinal role in the development of dementia. Acetylcholinesterase positron emission tomography demonstrates that posterior brain areas are related to cognitive decline in PD patients. Amyloid radiotracer illustrates that patients with PD with severe cognitive impairment were prone to accompanied cortical amyloid deposition. Metabolism/perfusion change associated with cognitive impairment in PD, so-called PD related cognitive pattern, is characterised by reduced frontoparietal activity and is an effective way to differentiate and monitor cognitive function of individual PD patients. Cognitive impairment in PD cannot be explained by a single mechanism and is entangled by multiple factors. Imaging studies can unravel each pathological domain, further shed light on the interrelation between different pathomechanisms, not only in PD but also in other dementia related disorders, and thereby integrate its interpretation to apply to therapeutics in individual patients.

The production of radionuclides for nuclear medicine from a compact, low-energy accelerator system.

PubMed

Webster, William D; Parks, Geoffrey T; Titov, Dmitry; Beasley, Paul

2014-05-01

The field of nuclear medicine is reliant on radionuclides for medical imaging procedures and radioimmunotherapy (RIT). The recent shut-downs of key radionuclide producers have highlighted the fragility of the current radionuclide supply network, however. To ensure that nuclear medicine can continue to grow, adding new diagnostic and therapy options to healthcare, novel and reliable production methods are required. Siemens are developing a low-energy, high-current - up to 10 MeV and 1 mA respectively - accelerator. The capability of this low-cost, compact system for radionuclide production, for use in nuclear medicine procedures, has been considered. The production of three medically important radionuclides - (89)Zr, (64)Cu, and (103)Pd - has been considered, via the (89)Y(p,n), (64)Ni(p,n) and (103)Rh(p,n) reactions, respectively. Theoretical cross-sections were generated using TALYS and compared to experimental data available from EXFOR. Stopping power values generated by SRIM have been used, with the TALYS-generated excitation functions, to calculate potential yields and isotopic purity in different irradiation regimes. The TALYS excitation functions were found to have a good agreement with the experimental data available from the EXFOR database. It was found that both (89)Zr and (64)Cu could be produced with high isotopic purity (over 99%), with activity yields suitable for medical diagnostics and therapy, at a proton energy of 10MeV. At 10MeV, the irradiation of (103)Rh produced appreciable quantities of (102)Pd, reducing the isotopic purity. A reduction in beam energy to 9.5MeV increased the radioisotopic purity to 99% with only a small reduction in activity yield. This work demonstrates that the low-energy, compact accelerator system under development by Siemens would be capable of providing sufficient quantities of (89)Zr, (64)Cu, and (103)Pd for use in medical diagnostics and therapy. It is suggested that the system could be used to produce many other isotopes currently useful to nuclear medicine. Copyright © 2014 Elsevier Inc. All rights reserved.

Stability-Indicating TLC-Densitometric and HPLC Methods for the Simultaneous Determination of Piracetam and Vincamine in the Presence of Their Degradation Products.

PubMed

Ahmed, Amal B; Abdelrahman, Maha M; Abdelwahab, Nada S; Salama, Fathy M

2016-11-01

Newly established TLC-densitometric and RP-HPLC methods were developed and validated for the simultaneous determination of Piracetam (PIR) and Vincamine (VINC) in their pharmaceutical formulation and in the presence of PIR and VINC degradation products, PD and VD, respectively. The proposed TLC-densitometric method is based on the separation and quantitation of the studied components using a developing system that consists of chloroform-methanol-glacial acetic acid-triethylamine (8 + 2 + 0.1 + 0.1, v/v/v/v) on TLC silica gel 60 F254 plates, followed by densitometric scanning at 230 nm. On the other hand, the developed RP-HPLC method is based on the separation of the studied components using an isocratic elution of 0.05 M KH2PO4 (containing 0.1% triethylamine adjusted to pH 3 with orthophosphoric acid)-methanol (95 + 5, v/v) on a C8 column at a flow rate of 1 mL/min with diode-array detection at 230 nm. The developed methods were validated according to International Conference on Harmonization guidelines and demonstrated good accuracy and precision. Moreover, the developed TLC-densitometric and RP-HPLC methods are suitable as stability-indicating assay methods for the simultaneous determination of PD and VD either in bulk powder or pharmaceutical formulation. The results were statistically compared with those obtained by the reported RP-HPLC method using t- and F-tests.

Cerebral glucose metabolism and cognition in newly diagnosed Parkinson's disease: ICICLE-PD study.

PubMed

Firbank, M J; Yarnall, A J; Lawson, R A; Duncan, G W; Khoo, T K; Petrides, G S; O'Brien, J T; Barker, R A; Maxwell, R J; Brooks, D J; Burn, D J

2017-04-01

To assess reductions of cerebral glucose metabolism in Parkinson's disease (PD) with 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET), and their associations with cognitive decline. FDG-PET was performed on a cohort of 79 patients with newly diagnosed PD (mean disease duration 8 months) and 20 unrelated controls. PD participants were scanned while on their usual dopaminergic medication. Cognitive testing was performed at baseline, and after 18 months using the Cognitive Drug Research (CDR) and Cambridge Neuropsychological Test Automated Battery (CANTAB) computerised batteries, the Mini-Mental State Examination (MMSE), and the Montreal Cognitive Assessment (MoCA). We used statistical parametric mapping (SPM V.12) software to compare groups and investigate voxelwise correlations between FDG metabolism and cognitive score at baseline. Linear regression was used to evaluate how levels of cortical FDG metabolism were predictive of subsequent cognitive decline rated with the MMSE and MoCA. PD participants showed reduced glucose metabolism in the occipital and inferior parietal lobes relative to controls. Low performance on memory-based tasks was associated with reduced FDG metabolism in posterior parietal and temporal regions, while attentional performance was associated with more frontal deficits. Baseline parietal to cerebellum FDG metabolism ratios predicted MMSE (β=0.38, p=0.001) and MoCA (β=0.3, p=0.002) at 18 months controlling for baseline score. Reductions in cortical FDG metabolism were present in newly diagnosed PD, and correlated with performance on neuropsychological tests. A reduced baseline parietal metabolism is associated with risk of cognitive decline and may represent a potential biomarker for this state and the development of PD dementia. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

PD-1/PD-L1 blockade together with vaccine therapy facilitates effector T cell infiltration into pancreatic tumors

PubMed Central

Soares, Kevin C.; Rucki, Agnieszka A.; Wu, Annie A.; Olino, Kelly; Xiao, Qian; Chai, Yi; Wamwea, Anthony; Bigelow, Elaine; Lutz, Eric; Liu, Linda; Yao, Sheng; Anders, Robert A.; Laheru, Daniel; Wolfgang, Christopher L.; Edil, Barish H.; Schulick, Richard D.; Jaffee, Elizabeth M.; Zheng, Lei

2014-01-01

Pancreatic ductal adenocarcinoma (PDA) has a poor prognosis due to late detection and resistance to conventional therapies. Published studies show that the PDA tumor microenvironment (TME) is predominantly infiltrated with immune suppressive cells and signals that if altered, would allow effective immunotherapy. However, single-agent checkpoint inhibitors including agents that alter immune suppressive signals in other human cancers such as cytotoxic T lymphocyte antigen-4 (CTLA-4), programmed death 1 (PD-1) and its ligand PD-L1, have failed to demonstrate objective responses when given as single agents to PDA patients. We recently reported that inhibition of the CTLA-4 pathway when given together with a T cell inducing vaccine gives objective responses in metastatic PDA patients. In this study, we evaluated blockade of the PD-1/PD-L1 pathway. We found that PD-L1 is weakly expressed at a low frequency in untreated human and murine PDAs but treatment with a GM-CSF secreting PDA vaccine (GVAX) significantly upregulates PD-L1 membranous expression after treatment of tumor bearing mice. In addition, combination therapy with vaccine and PD-1 antibody blockade improved murine survival compared to PD-1 antibody monotherapy or GVAX therapy alone. Furthermore, PD-1 blockade increased effector CD8+ T lymphocytes and tumor-specific interferon-γ production of CD8+ T cells in the TME. Immunosuppressive pathways, including regulatory T cells (Tregs) and CTLA-4 expression on T cells were overcome by the addition of vaccine and low dose cyclophosphamide to PD-1 blockade. Collectively, our study supports combining PD-1 or PD-L1 antibody therapy with a T cell inducing agent for PDA treatment. PMID:25415283

Combined PD-1 blockade and GITR triggering induce a potent antitumor immunity in murine cancer models and synergizes with chemotherapeutic drugs

PubMed Central

2014-01-01

Background The coinhibitory receptor Programmed Death-1 (PD-1) inhibits effector functions of activated T cells and prevents autoimmunity, however, cancer hijack this pathway to escape from immune attack. The costimulatory receptor glucocorticoid-induced TNFR related protein (GITR) is up-regulated on activated T cells and increases their proliferation, activation and cytokine production. We hypothesize that concomitant PD-1 blockade and GITR triggering would synergistically improve the effector functions of tumor-infiltrating T cells and increase the antitumor immunity. In present study, we evaluated the antitumor effects and mechanisms of combined PD-1 blockade and GITR triggering in a clinically highly relevant murine ID8 ovarian cancer model. Methods Mice with 7 days-established peritoneal ID8 ovarian cancer were treated intraperitoneally (i.p.) with either control, anti-PD-1, anti-GITR or anti-PD-1/GITR monoclonal antibody (mAb) and their survival was evaluated; the phenotype and function of tumor-associated immune cells in peritoneal cavity of treated mice was analyzed by flow cytometry, and systemic antigen-specific immune response was evaluated by ELISA and cytotoxicity assay. Results Combined anti-PD-1/GITR mAb treatment remarkably inhibited peritoneal ID8 tumor growth with 20% of mice tumor free 90 days after tumor challenge while treatment with either anti-PD-1 or anti-GITR mAb alone exhibited little antitumor effect. The durable antitumor effect was associated with a memory immune response and conferred by CD4+ cells and CD8+ T cells. The treatment of anti-PD-1/GITR mAb increased the frequencies of interferon-γ-producing effector T cells and decreased immunosuppressive regulatory T cells and myeloid-derived suppressor cells, shifting an immunosuppressive tumor milieu to an immunostimulatory state in peritoneal cavity. In addition, combined treatment of anti-PD-1/GITR mAb mounted an antigen-specific immune response as evidenced by antigen-specific IFN-γ production and cytolytic activity of spleen cells from treated mice. More importantly, combined treatment of anti-PD-1/GITR mAb and chemotherapeutic drugs (cisplatin or paclitaxel) further increased the antitumor efficacy with 80% of mice obtaining tumor-free long-term survival in murine ID8 ovarian cancer and 4 T1 breast cancer models. Conclusions Combined anti-PD-1/GITR mAb treatment induces a potent antitumor immunity, which can be further promoted by chemotherapeutic drugs. A combined strategy of anti-PD-1/GITR mAb plus cisplatin or paclitaxel should be considered translation into clinic. PMID:24502656

Porous Nanocrystalline Silicon Supported Bimetallic Pd-Au Catalysts: Preparation, Characterization, and Direct Hydrogen Peroxide Synthesis

PubMed Central

Potemkin, Dmitriy I.; Maslov, Dmitry K.; Loponov, Konstantin; Snytnikov, Pavel V.; Shubin, Yuri V.; Plyusnin, Pavel E.; Svintsitskiy, Dmitry A.; Sobyanin, Vladimir A.; Lapkin, Alexei A.

2018-01-01

Bimetallic Pd-Au catalysts were prepared on the porous nanocrystalline silicon (PSi) for the first time. The catalysts were tested in the reaction of direct hydrogen peroxide synthesis and characterized by standard structural and chemical techniques. It was shown that the Pd-Au/PSi catalyst prepared from conventional H2[PdCl4] and H[AuCl4] precursors contains monometallic Pd and a range of different Pd-Au alloy nanoparticles over the oxidized PSi surface. The PdAu2/PSi catalyst prepared from the [Pd(NH3)4][AuCl4]2 double complex salt (DCS) single-source precursor predominantly contains bimetallic Pd-Au alloy nanoparticles. For both catalysts the surface of bimetallic nanoparticles is Pd-enriched and contains palladium in Pd0 and Pd2+ states. Among the catalysts studied, the PdAu2/PSi catalyst was the most active and selective in the direct H2O2 synthesis with H2O2 productivity of 0.5 mol gPd-1 h-1 at selectivity of 50% and H2O2 concentration of 0.023 M in 0.03 M H2SO4-methanol solution after 5 h on stream at −10°C and atmospheric pressure. This performance is due to high activity in the H2O2 synthesis reaction and low activities in the undesirable H2O2 decomposition and hydrogenation reactions. Good performance of the PdAu2/PSi catalyst was associated with the major part of Pd in the catalyst being in the form of the bimetallic Pd-Au nanoparticles. Porous silicon was concluded to be a promising catalytic support for direct hydrogen peroxide synthesis due to its inertness with respect to undesirable side reactions, high thermal stability, and conductivity, possibility of safe operation at high temperatures and pressures and a well-established manufacturing process. PMID:29637068

Relationship between mathematics teacher subject matter knowledge, pedagogical content knowledge and professional development needs

NASA Astrophysics Data System (ADS)

Tajudin, Nor'ain Mohd; Chinnappan, Mohan; Saad, Noor Shah

2017-05-01

Two key variables emerged from the literature review is that Specific Matter Knowledge [SMK] and Pedagogical Content Knowledge [PCK] can influence the mathematics teachers' Professional Development [PD] needs. However, the key variables of SMK and PCK that were being investigated were not defined clearly. Empirical evidence that support relationship between SMK and PD and PCK and PD were not verified. In addition, how does PCK mediate SMK and PD is not clear and somewhat lacking. Therefore, the purpose of this paper was to examine the relationship between primary mathematics teacher's SMK, PCK and PD needs. Results of path analysis with SmartPLS indicated that the direct effect of SMK on PD was mediated via PCK. This data provide support for the claim that PD programs for future teachers of primary mathematics should be driven by a more nuanced understanding of the link between SMK and PCK.

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.

Tumor cell-intrinsic PD-L1 promotes tumor-initiating cell generation and functions in melanoma and ovarian cancer

PubMed Central

Gupta, Harshita B; Clark, Curtis A; Yuan, Bin; Sareddy, Gangadhara; Pandeswara, Srilakshmi; Padron, Alvaro S; Hurez, Vincent; Conejo-Garcia, José; Vadlamudi, Ratna; Li, Rong; Curiel, Tyler J

2016-01-01

As tumor PD-L1 provides signals to anti-tumor PD-1+ T cells that blunt their functions, αPD-1 and αPD-L1 antibodies have been developed as anti-cancer immunotherapies based on interrupting this signaling axis. However, tumor cell-intrinsic PD-L1 signals also regulate immune-independent tumor cell proliferation and mTOR signals, among other important effects. Tumor-initiating cells (TICs) generate carcinomas, resist treatments and promote relapse. We show here that in murine B16 melanoma and ID8agg ovarian carcinoma cells, TICs express more PD-L1 versus non-TICs. Silencing PD-L1 in B16 and ID8agg cells by shRNA (‘PD-L1lo’) reduced TIC numbers, the canonical TIC genes nanog and pou5f1 (oct4), and functions as assessed by tumorosphere development, immune-dependent and immune-independent tumorigenesis, and serial transplantability in vivo. Strikingly, tumor PD-L1 sensitized TIC to interferon-γ and rapamycin in vitro. Cell-intrinsic PD-L1 similarly drove functional TIC generation, canonical TIC gene expression and sensitivity to interferon-γ and rapamycin in human ES2 ovarian cancer cells. Thus, tumor-intrinsic PD-L1 signals promote TIC generation and virulence, possibly by promoting canonical TIC gene expression, suggesting that PD-L1 has novel signaling effects on cancer pathogenesis and treatment responses. PMID:28798885

Facile preparation of dendritic Ag-Pd bimetallic nanostructures on the surface of Cu foil for application as a SERS-substrate

NASA Astrophysics Data System (ADS)

Yi, Zao; Tan, Xiulan; Niu, Gao; Xu, Xibin; Li, Xibo; Ye, Xin; Luo, Jiangshan; Luo, Binchi; Wu, Weidong; Tang, Yongjian; Yi, Yougen

2012-05-01

Dendritic Ag-Pd bimetallic nanostructures have been synthesized on the surface of Cu foil via a multi-stage galvanic replacement reaction (MGRR) of Ag dendrites in a Na2PdCl4 solution. After five stages of replacement reaction, one obtained structures with protruding Ag-Pd flakes; these will mature into many porous structures with a few Ag atoms that are left over dendrites. The dendritic Ag-Pd bimetallic nanostructures were characterized by transmission electron microscopy (TEM), high-resolution transmission electron microscopy (HRTEM), field emission scanning electron microscopy (FESEM), energy-dispersive X-ray (EDX), selected area electron diffraction (SAED) and X-ray photoelectron spectroscopy (XPS). The morphology of the products strongly depended on the stage of galvanic replacement reaction and reaction temperature. The morphology and composition-dependent surface-enhanced Raman scattering (SERS) of the as-synthesized Ag-Pd bimetallic nanostructures were investigated. The effectiveness of these dendritic Ag-Pd bimetallic nanostructures on the surface of Cu foil as substrates toward SERS detection was evaluated by using rhodamine 6G (R6G) as a probe molecule. The results indicate that as-synthesized dendritic Ag-Pd bimetallic nanostructures are good candidates for SERS spectroscopy.

Heat-sterilized PD fluid blocks leukocyte adhesion and increases flow velocity in rat peritoneal venules.

PubMed

Jonasson, P; Bagge, U; Wieslander, A; Braide, M

1996-01-01

Data from cell culture experiments indicate that heat sterilization of peritoneal dialysis (PD) fluids produces cytotoxic glucose degradation products. The present vital microscopic study investigated the effects of different sterilization methods on the biocompatibility of PD fluids. Thus, heat-sterilized (commercially obtained and experimentally produced) and filter-sterilized PD fluids (pH = 5.30-5.40; 1.5% glucose) were compared with Tyrode buffer, with respect to the effects on microvascular blood flow velocity and leukocyte adhesion in the rat mesentery. Exteriorization of the mesentery produced a mild inflammation, known from the literature and characterized by the adhesive rolling of leukocytes along venular walls. Superfusion of the mesentery with filter-sterilized PD fluid had no significant effects on leukocyte rolling or flow velocity in venules 25-40 microns in diameter compared with buffer superfusion. Heat-sterilized PD fluid decreased the concentration of rolling leukocytes and increased flow velocity significantly, as compared with buffer and filter-sterilized PD fluid. The results indicate that heat sterilization of PD fluids produces substances that interact with microvascular tone and leukocyte-endothelial adhesion, which hypothetically could impair the acute, granulocyte-mediated defense against bacterial infections.

Strangeness Production at COSY

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

Hinterberger, Frank; Machner, Hartmut; Siudak, Regina

2011-10-24

The paper gives an overview of strangeness-production experiments at the Cooler Synchrotron COSY. Results on kaon-pair and {phi} meson production in pp, pd and dd collisions, hyperon-production experiments and {Lambda}p final-state interaction studies are presented.

Dopaminergic Dysregulation, Artistic Expressiveness, and Parkinson's Disease

PubMed Central

López-Pousa, S.; Lombardía-Fernández, C.; Olmo, J. Garre; Monserrat-Vila, S.; Vilalta-Franch, J.; Calvó-Perxas, L.

2012-01-01

Background The most frequent behavioral manifestations in Parkinson's disease (PD) are attributed to the dopaminergic dysregulation syndrome (DDS), which is considered to be secondary to the iatrogenic effects of the drugs that replace dopamine. Over the past few years some cases of patients improving their creative abilities after starting treatment with dopaminergic pharmaceuticals have been reported. These effects have not been clearly associated to DDS, but a relationship has been pointed out. Methods Case study of a patient with PD. The evolution of her paintings along medication changes and disease advance has been analyzed. Results The patient showed a compulsive increase of pictorial production after the diagnosis of PD was made. She made her best paintings when treated with cabergolide, and while painting, she reported a feeling of well-being, with loss of awareness of the disease and reduction of physical limitations. Conclusions Dopaminergic antagonists (DA) trigger a dopaminergic dysfunction that alters artistic creativity in patients having a predisposition for it. The development of these skills might be due to the dopaminergic overstimulation due to the therapy with DA, which causes a neurophysiological alteration that globally determines DDS. PMID:23185168

Therapeutic potential of natural products in Parkinson's disease.

PubMed

Mythri, Rajeswara B; Harish, Gangadharappa; Bharath, M M

2012-09-01

The central objective in treating patients with Parkinson's disease (PD) is two-fold (i) to increase the striatal dopamine content and (ii) to prevent further degeneration of the surviving dopaminergic neurons in the substantia nigra region of the ventral midbrain. Most of the current PD drugs contribute to the former and provide symptomatic relief. Although compounds such as Levodopa (L-DOPA) improve the striatal dopamine content, their long-term usage is associated with progressive decrease in drug response, motor fluctuations, dyskinesias and drug-induced toxicity. In addition, these drugs fail to prevent the progression of the degenerative process. This has shifted the focus onto alternative therapeutic approaches involving natural products that could provide independent therapy or offer neuroprotective support to the existing drugs. The current review describes the neuroprotective and therapeutic utility of such natural products including herbal extracts, phytochemicals and bioactive ingredients from other natural sources either in isolation or in combination, with potential application in PD, highlighting the relevant patents.

Influence of SiC grain boundary character on fission product transport in irradiated TRISO fuel

NASA Astrophysics Data System (ADS)

Lillo, T. M.; van Rooyen, I. J.

2016-05-01

In this study, the fission product precipitates at silicon carbide grain boundaries from an irradiated TRISO particle were identified and correlated with the associated grain boundary characteristics. Precession electron diffraction in the transmission electron microscope provided the crystallographic information needed to identify grain boundary misorientation and boundary type (i.e., low angle, random high angle or coincident site lattice (CSL)-related). The silicon carbide layer was found to be composed mainly of twin boundaries and small fractions of random high angle and low angle grain boundaries. Most fission products were found at random, high-angle grain boundaries, with small fractions at low-angle and CSL-related grain boundaries. Palladium (Pd) was found at all types of grain boundaries while Pd-uranium and Pd-silver precipitates were only associated with CSL-related and random, high-angle grain boundaries. Precipitates containing only Ag were found only at random, high-angle grain boundaries, but not at low angle or CSL-related grain boundaries.

Exploring environment-dependent effects of Pd nanostructures on reactive oxygen species (ROS) using electron spin resonance (ESR) technique: implications for biomedical applications.

PubMed

Wen, Tao; He, Weiwei; Chong, Yu; Liu, Yi; Yin, Jun-Jie; Wu, Xiaochun

2015-10-14

Recently, because of the great advances in tailoring their shape and structure, palladium nanoparticles (Pd NPs) have been receiving increasing attention in biomedical fields apart from their traditional application as industrial catalysts. When considering the potential uses of Pd NPs in biomedicine, their catalytic properties need to be evaluated under physiologically relevant conditions. In this article, we demonstrate that Pd nanostructures (NSs, both commercial Pd NPs and in-house-prepared Au@Pd nanorods) can induce O2 or ˙OH production depending on pH values in the presence of H2O2. We observed that O2 is produced under neutral and alkaline conditions but ˙OH under acidic conditions. We also found that Pd NSs can scavenge superoxide and singlet oxygen, which may provide protection in biological systems. On the other hand, their oxidase-like activity may accelerate the oxidation of ascorbic acid and thus may produce negative biological effects. The presented study will provide useful guidance for designing noble metal nanostructures with desired catalytic and biological properties in biomedical applications.

Improved ethanol electrooxidation performance by shortening Pd–Ni active site distance in Pd–Ni–P nanocatalysts

PubMed Central

Chen, Lin; Lu, Lilin; Zhu, Hengli; Chen, Yueguang; Huang, Yu; Li, Yadong; Wang, Leyu

2017-01-01

Incorporating oxophilic metals into noble metal-based catalysts represents an emerging strategy to improve the catalytic performance of electrocatalysts in fuel cells. However, effects of the distance between the noble metal and oxophilic metal active sites on the catalytic performance have rarely been investigated. Herein, we report on ultrasmall (∼5 nm) Pd–Ni–P ternary nanoparticles for ethanol electrooxidation. The activity is improved up to 4.95 A per mgPd, which is 6.88 times higher than commercial Pd/C (0.72 A per mgPd), by shortening the distance between Pd and Ni active sites, achieved through shape transformation from Pd/Ni–P heterodimers into Pd–Ni–P nanoparticles and tuning the Ni/Pd atomic ratio to 1:1. Density functional theory calculations reveal that the improved activity and stability stems from the promoted production of free OH radicals (on Ni active sites) which facilitate the oxidative removal of carbonaceous poison and combination with CH3CO radicals on adjacent Pd active sites. PMID:28071650

Teachers' Perceptions of Edcamp Professional Development: A Q Method Study

ERIC Educational Resources Information Center

Brown, Toby

2015-01-01

This study described the subjective opinions of teachers about their experiences at Edcamp, an unconference-style form of teacher professional development (PD). Traditional PD has been maligned for being overly expensive and ineffectual in affecting changes in teacher practice. In order to defend teachers' decisions to partake in Edcamp-style PD,…

New Instruments for Studying the Impacts of Science Teacher Professional Development

ERIC Educational Resources Information Center

Trygstad, Peggy J.; Banilower, Eric R.; Smith, P. Sean; Nelson, Courtney L.

2014-01-01

The logic model that implicitly drives most professional development (PD) efforts asserts that PD leads to changes in teacher knowledge and beliefs, which leads to improved classroom practice, and ultimately, better student outcomes. However, efforts to study the impacts of PD programs are often hampered by the scarcity of high-quality…

High-Quality Music Teacher Professional Development: A Review of the Literature

ERIC Educational Resources Information Center

Bautista, Alfredo; Yau, Xenia; Wong, Joanne

2017-01-01

Most published journal articles describing professional development (PD) initiatives for K-12 music teachers have not explicitly alluded to the "features of high-quality PD", a solid theoretical framework arisen in content areas with more tradition in PD research (e.g. mathematics and science education). The goal of this review was to…

Improving Vocabulary and Pre-Literacy Skills of At-Risk Preschoolers through Teacher Professional Development

ERIC Educational Resources Information Center

Wasik, Barbara A.; Hindman, Annemarie H.

2011-01-01

In a randomized control study, Head Start teachers were assigned to either an intervention group that received intensive, ongoing professional development (PD) or to a comparison group that received the "business as usual" PD provided by Head Start. The PD intervention provided teachers with conceptual knowledge and instructional…

N-Boc amines to oxazolidinones via Pd(II)/bis-sulfoxide/Brønsted acid co-catalyzed allylic C-H oxidation.

PubMed

Osberger, Thomas J; White, M Christina

2014-08-06

A Pd(II)/bis-sulfoxide/Brønsted acid catalyzed allylic C-H oxidation reaction for the synthesis of oxazolidinones from simple N-Boc amines is reported. A range of oxazolidinones are furnished in good yields (avg 63%) and excellent diastereoselectivities (avg 15:1) to furnish products regioisomeric from those previously obtained using allylic C-H amination reactions. Mechanistic studies suggest the role of the phosphoric acid is to furnish a Pd(II)bis-sulfoxide phosphate catalyst that promotes allylic C-H cleavage and π-allylPd functionalization with a weak, aprotic oxygen nucleophile and to assist in catalyst regeneration.

N-Boc Amines to Oxazolidinones via Pd(II)/Bis-sulfoxide/Brønsted Acid Co-Catalyzed Allylic C–H Oxidation

PubMed Central

2015-01-01

A Pd(II)/bis-sulfoxide/Brønsted acid catalyzed allylic C–H oxidation reaction for the synthesis of oxazolidinones from simple N-Boc amines is reported. A range of oxazolidinones are furnished in good yields (avg 63%) and excellent diastereoselectivities (avg 15:1) to furnish products regioisomeric from those previously obtained using allylic C–H amination reactions. Mechanistic studies suggest the role of the phosphoric acid is to furnish a Pd(II)bis-sulfoxide phosphate catalyst that promotes allylic C–H cleavage and π-allylPd functionalization with a weak, aprotic oxygen nucleophile and to assist in catalyst regeneration. PMID:24999765

Pd Nanoparticles and MOFs Synergistically Hybridized Halloysite Nanotubes for Hydrogen Storage.

PubMed

Jin, Jiao; Ouyang, Jing; Yang, Huaming

2017-12-01

Natural halloysite nanotubes (HNTs) were hybridized with metal-organic frameworks (MOFs) to prepare novel composites. MOFs were transformed into carbon by carbonization calcination, and palladium (Pd) nanoparticles were introduced to build an emerging ternary compound system for hydrogen adsorption. The hydrogen adsorption capacities of HNT-MOF composites were 0.23 and 0.24 wt%, while those of carbonized products were 0.24 and 0.27 wt% at 25 °C and 2.65 MPa, respectively. Al-based samples showed higher hydrogen adsorption capacities than Zn-based samples on account of different selectivity between metal and hydrogen and approximate porous characteristics. More pore structures are generated by the carbonization reaction from metal-organic frameworks into carbon; high specific surface area, uniform pore size, and large pore volume benefited the hydrogen adsorption ability of composites. Moreover, it was also possible to promote hydrogen adsorption capacity by incorporating Pd. The hydrogen adsorption capacity of ternary compound, Pd-C-H3-MOFs(Al), reached 0.32 wt% at 25 °C and 2.65 MPa. Dissociation was assumed to take place on the Pd particles, then atomic and molecule hydrogen spilled over to the structure of carboxylated HNTs, MOFs, and the carbon products for enhancing the hydrogen adsorption capacity.

Synthesis of disaccharides using β-glucosidases from Aspergillus niger, A. awamori and Prunus dulcis.

PubMed

da Silva, Ayla Sant'Ana; Molina, Javier Freddy; Teixeira, Ricardo Sposina Sobral; Valdivieso Gelves, Luis G; Bon, Elba P S; Ferreira-Leitão, Viridiana S

2017-11-01

Glucose conversion into disaccharides was performed with β-glucosidases from Prunus dulcis (β-Pd), Aspergillus niger (β-An) and A. awamori (β-Aa), in reactions containing initial glucose of 700 and 900 g l -1 . The reactions' time courses were followed regarding glucose and product concentrations. In all cases, there was a predominant formation of gentiobiose over cellobiose and also of oligosaccharides with a higher molecular mass. For reactions containing 700 g glucose l -1 , the final substrate conversions were 33, 38, and 23.5% for β-An, β-Aa, and β-Pd, respectively. The use of β-An yielded 103 g gentiobiose l -1 (15.5% yield), which is the highest reported for a fungal β-glucosidase. The increase in glucose concentration to 900 g l -1 resulted in a significant increase in disaccharide synthesis by β-Pd, reaching 128 g gentiobiose l -1 (15% yield), while for β-An and β-Aa, there was a shift toward the synthesis of higher oligosaccharides. β-Pd and the fungal β-An and β-Aa β-glucosidases present quite dissimilar kinetics and selective properties regarding the synthesis of disaccharides; while β-Pd showed the highest productivity for gentiobiose synthesis, β-An presented the highest specificity.

Pd Nanoparticles and MOFs Synergistically Hybridized Halloysite Nanotubes for Hydrogen Storage

NASA Astrophysics Data System (ADS)

Jin, Jiao; Ouyang, Jing; Yang, Huaming

2017-03-01

Natural halloysite nanotubes (HNTs) were hybridized with metal-organic frameworks (MOFs) to prepare novel composites. MOFs were transformed into carbon by carbonization calcination, and palladium (Pd) nanoparticles were introduced to build an emerging ternary compound system for hydrogen adsorption. The hydrogen adsorption capacities of HNT-MOF composites were 0.23 and 0.24 wt%, while those of carbonized products were 0.24 and 0.27 wt% at 25 °C and 2.65 MPa, respectively. Al-based samples showed higher hydrogen adsorption capacities than Zn-based samples on account of different selectivity between metal and hydrogen and approximate porous characteristics. More pore structures are generated by the carbonization reaction from metal-organic frameworks into carbon; high specific surface area, uniform pore size, and large pore volume benefited the hydrogen adsorption ability of composites. Moreover, it was also possible to promote hydrogen adsorption capacity by incorporating Pd. The hydrogen adsorption capacity of ternary compound, Pd-C-H3-MOFs(Al), reached 0.32 wt% at 25 °C and 2.65 MPa. Dissociation was assumed to take place on the Pd particles, then atomic and molecule hydrogen spilled over to the structure of carboxylated HNTs, MOFs, and the carbon products for enhancing the hydrogen adsorption capacity.

Clinical Features of Nivolumab-Induced Thyroiditis: A Case Series Study.

PubMed

Yamauchi, Ichiro; Sakane, Yoriko; Fukuda, Yorihide; Fujii, Toshihito; Taura, Daisuke; Hirata, Masakazu; Hirota, Keisho; Ueda, Yohei; Kanai, Yugo; Yamashita, Yui; Kondo, Eri; Sone, Masakatsu; Yasoda, Akihiro; Inagaki, Nobuya

2017-07-01

The programmed cell death-1 (PD-1) pathway is a novel therapeutic target in immune checkpoint therapy for cancer. It consists of the PD-1 receptor and its two ligands, programmed death-ligand 1 (PD-L1) and programmed death-ligand 2 (PD-L2). Nivolumab is an anti-PD-1 monoclonal antibody approved for malignant melanoma, advanced non-small cell lung cancer, and advanced renal cell carcinoma in Japan. Thyrotoxicosis and hypothyroidism have both been reported in international Phase 3 studies and national post-marketing surveillance of nivolumab in Japan. This study analyzed five consecutive cases with thyroid dysfunction associated with nivolumab therapy. Second, it examined the mRNA and protein expressions of PD-L1 and PD-L2 by reverse transcription polymerase chain reaction and Western blotting. All patients were diagnosed with painless thyroiditis. Thyrotoxicosis developed within four weeks from the first administration of nivolumab and normalized within four weeks of onset in three of the five patients. Hypothyroidism after transient thyrotoxicosis developed in two patients, and preexisting hypothyroidism persisted in one patient. The other two patients were treated with glucocorticoids and discontinued nivolumab therapy for comorbid adverse events. One did not develop hypothyroidism, and the other developed mild, transient hypothyroidism. In addition, it was verified that normal thyroid tissue expresses PD-L1 and PD-L2 mRNA and those proteins. In the present cases, nivolumab-induced thyrotoxicosis seemed to be associated with painless thyroiditis, while no patient with Graves' disease was observed. A transient and rapid course with subsequent hypothyroidism was observed in nivolumab-induced thyroiditis. In addition, it was verified that PD-L1 and PD-L2 are expressed in normal thyroid tissue. This suggests that nivolumab therapy reduces immune tolerance, even in normal thyroid tissue, and leads to the development of thyroiditis. Treating thyrotoxicosis with only supportive care and considering levothyroxine replacement therapy once subsequent hypothyroidism occurs is proposed. Further investigations are required to confirm whether glucocorticoid therapy and discontinuation of nivolumab therapy prevent subsequent hypothyroidism.

Measurement of excitation functions of helion-induced reactions on enriched Ru targets for production of medically important 103Pd and 101mRh and some other radionuclides.

PubMed

Skakun, Ye; Qaim, S M

2008-05-01

Excitation functions were determined by the stacked-foil and induced radioactivity measurement technique for the reactions (100)Ru(alpha,n)(103)Pd, (101)Ru(alpha,2n)(103)Pd, (101)Ru((3)He,n)(103)Pd, and (102)Ru((3)He,2n)(103)Pd, producing the therapeutic radionuclide (103)Pd, and for the reactions (101)Ru((3)He,x)(101 m)Rh(Cum) and (102)Ru((3)He,x)(101 m)Rh(Cum), producing the medically interesting radionuclide (101 m)Rh. Data were also measured for the reactions (101)Ru((3)He,pn+d)(102 m,g)Rh, (102)Ru((3)He,p2n+dn+t)(102 m,g)Rh, (101)Ru((3)He,x)(101 g)Rh(Cum), (102)Ru((3)He,x)(101 g)Rh(Cum), (101)Ru((3)He,3n)(101)Pd, (102)Ru((3)He,4n)(101)Pd, (101)Ru((3)He,4n)(100)Pd, and (101)Ru((3)He,p3n+d2n+tn)(100)Rh, producing other palladium and rhodium isotopes/isomers. The energy ranges covered were up to 25 MeV for alpha-particles and up to 34 MeV for (3)He ions. The radioactivity of the radionuclide (103)Pd induced in thin metallic foils of the enriched ruthenium isotopes was measured by high-resolution X-ray spectrometry and the radioactivities of other radionuclides by gamma-ray spectrometry. The integral thick target yields of the radionuclide (103)Pd calculated from the excitation functions of the first four of the above-named reactions amount to 960, 1050, 50, and 725 kBq/microAh, respectively, at the maximum investigated energies of the incident particles. The integral thick target yields of the radionuclide (101 m)Rh amount to 16.1 and 2.9 MBq/microAh for (101)Ru and (102)Ru targets, respectively, at 34 MeV energy of incident (3)He ions. The integral yields of the other observed radionuclides were also deduced from the excitation functions of the above-mentioned respective nuclear reactions. The excitation functions and integral yields of some rare reaction products were also determined. The experimental excitation functions of some reactions are compared with the predictions of nuclear model calculations. In general, good agreement was obtained.

Selectivity Control in the Tandem Aromatization of Bio‐Based Furanics Catalyzed by Solid Acids and Palladium

PubMed Central

Genuino, Homer C.; Thiyagarajan, Shanmugam; van der Waal, Jan C.; van Haveren, Jacco; Weckhuysen, Bert M.

2016-01-01

Abstract Bio‐based furanics can be aromatized efficiently by sequential Diels–Alder (DA) addition and hydrogenation steps followed by tandem catalytic aromatization. With a combination of zeolite H‐Y and Pd/C, the hydrogenated DA adduct of 2‐methylfuran and maleic anhydride can thus be aromatized in the liquid phase and, to a certain extent, decarboxylated to give high yields of the aromatic products 3‐methylphthalic anhydride and o‐ and m‐toluic acid. Here, it is shown that a variation in the acidity and textural properties of the solid acid as well as bifunctionality offers a handle on selectivity toward aromatic products. The zeolite component was found to dominate selectivity. Indeed, a linear correlation is found between 3‐methylphthalic anhydride yield and the product of (strong acid/total acidity) and mesopore volume of H‐Y, highlighting the need for balanced catalyst acidity and porosity. The efficient coupling of the dehydration and dehydrogenation steps by varying the zeolite‐to‐Pd/C ratio allowed the competitive decarboxylation reaction to be effectively suppressed, which led to an improved 3‐methylphthalic anhydride/total aromatics selectivity ratio of 80 % (89 % total aromatics yield). The incorporation of Pd nanoparticles in close proximity to the acid sites in bifunctional Pd/H‐Y catalysts also afforded a flexible means to control aromatic products selectivity, as further demonstrated in the aromatization of hydrogenated DA adducts from other diene/dienophile combinations. PMID:27557889

High-cell-density batch fermentation of Rhodococcus opacus PD630 using a high glucose concentration for triacylglycerol production.

PubMed

Kurosawa, Kazuhiko; Boccazzi, Paolo; de Almeida, Naomi M; Sinskey, Anthony J

2010-06-01

Biodiesel, monoalkyl esters of long-chain fatty acids with short-chain alcohols derived from triacylglycerols (TAGs), can be produced from renewable biomass sources. Recently, there has been interest in producing microbial oils from oleaginous microorganisms. Rhodococcus opacus PD630 is known to accumulate large amounts of TAGs. Following on these earlier works we demonstrate that R. opacus PD630 has the uncommon capacity to grow in defined media supplemented with glucose at a concentration of 300 g l(-1) during batch-culture fermentations. We found that we could significantly increase concentrations of both glucose and (NH4)2SO4 in the production medium resulting in a dramatic increase in fatty acid production when pH was controlled. We describe the experimental design protocol used to achieve the culture conditions necessary to obtain both high-cell-density and TAG accumulation; specifically, we describe the importance of the C/N ratio of the medium composition. Our bioprocess results demonstrate that R. opacus PD630 grown in batch-culture with an optimal production medium containing 240 g l(-1) glucose and 13.45 g l(-1) (NH4)2SO4 (C/N of 17.8) yields 77.6 g l(-1) of cell dry weight composed of approximately 38% TAGs indicating that this strain holds great potential as a future source of industrial biodiesel on starchy cellulosic feedstocks that are glucose polymers. 2010 Elsevier B.V. All rights reserved.

Time-Dependent Density Functional Theory Analysis of Triphenylamine-Functionalized Graphene Doped with Transition Metals for Photocatalytic Hydrogen Production.

PubMed

Mota, Elder A V; Neto, Abel F G; Marques, Francisco C; Mota, Gunar V S; Martins, Marcelo G; Costa, Fabio L P; Borges, Rosivaldo S; Neto, Antonio M J C

2018-07-01

The electronic structures and optical properties of triphenylamine-functionalized graphene (G-TPA) doped with transition metals, using water as a solvent, were theoretically investigated to verify the efficiency of photocatalytic hydrogen production with the use of transition metals. This study was performed by Density Functional Theory and Time-dependent Density Functional Theory through Gaussian 09W software, adopting the B3LYP functional for all structures. The 6-31g(d) basis set was used for H, C and N atoms, and the LANL2DZ basis set for transition metals using the Effective Core Potentials method. Two approaches were adopted: (1) using single metallic dopants (Ni, Pd, Fe, Os and Pt) and (2) using combinations of Ni with the other dopants (NiPd, NiPt, NiFe and NiOs). The DOS spectra reveal an increase of accessible states in the valence shell, in addition to a gap decrease for all dopants. This doping also increases the absorption in the visible region of solar radiation where sunlight is most intense (400 nm to 700 nm), with additional absorption peaks. The results lead us to propose the G-TPA structures doped with Ni, Pd, Pt, NiPt or NiPd to be novel catalysts for the conversion of solar energy for photocatalytic hydrogen production, since they improve the absorption of solar energy in the range of interest for solar radiation; and act as reaction centers, reducing the required overpotential for hydrogen production from water.

Increased Oxidative Stress Markers in Cerebrospinal Fluid from Healthy Subjects with Parkinson's Disease-Associated LRRK2 Gene Mutations.

PubMed

Loeffler, David A; Klaver, Andrea C; Coffey, Mary P; Aasly, Jan O; LeWitt, Peter A

2017-01-01

Mutations in the leucine-rich repeat kinase 2 ( LRRK2 ) gene are the most frequent cause of inherited Parkinson's disease (PD). The most common PD-associated LRRK2 mutation, G2019S, induces increased production of reactive oxygen species in vitro . We therefore hypothesized that individuals with PD-associated LRRK2 mutations might have increased concentrations of oxidative stress markers and/or decreased total antioxidant capacity (TAC) in their cerebrospinal fluid (CSF). We measured two oxidative stress markers, namely 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-isoprostane (8-ISO), and TAC in CSF from LRRK2 mutation-bearing PD patients ( LRRK2 PD = 19), sporadic PD patients (sPD = 31), and healthy control subjects with or without these mutations ( LRRK2 CTL = 30, CTL = 27). 8-OHdG and 8-ISO levels were increased in LRRK2 CTL subjects, while TAC was similar between groups. 8-ISO was negatively correlated, and TAC was positively correlated, with Montreal Cognitive Assessment scores in LRRK2 PD, LRRK2 CTL, and CTL subjects. Correlations in both groups of PD patients between the two oxidative stress markers and Unified Parkinson Disease Rating Scale Total scores were weak, while TAC was negatively correlated with these scores. These findings suggest that oxidative stress may be increased in the CNS in healthy individuals with PD-associated LRRK2 mutations. Further, TAC may decrease in the CNS with the progression of PD, and when cognitive impairment is present regardless of the presence or absence of PD.

Increased Oxidative Stress Markers in Cerebrospinal Fluid from Healthy Subjects with Parkinson’s Disease-Associated LRRK2 Gene Mutations

PubMed Central

Loeffler, David A.; Klaver, Andrea C.; Coffey, Mary P.; Aasly, Jan O.; LeWitt, Peter A.

2017-01-01

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most frequent cause of inherited Parkinson’s disease (PD). The most common PD-associated LRRK2 mutation, G2019S, induces increased production of reactive oxygen species in vitro. We therefore hypothesized that individuals with PD-associated LRRK2 mutations might have increased concentrations of oxidative stress markers and/or decreased total antioxidant capacity (TAC) in their cerebrospinal fluid (CSF). We measured two oxidative stress markers, namely 8-hydroxy-2′-deoxyguanosine (8-OHdG) and 8-isoprostane (8-ISO), and TAC in CSF from LRRK2 mutation-bearing PD patients (LRRK2 PD = 19), sporadic PD patients (sPD = 31), and healthy control subjects with or without these mutations (LRRK2 CTL = 30, CTL = 27). 8-OHdG and 8-ISO levels were increased in LRRK2 CTL subjects, while TAC was similar between groups. 8-ISO was negatively correlated, and TAC was positively correlated, with Montreal Cognitive Assessment scores in LRRK2 PD, LRRK2 CTL, and CTL subjects. Correlations in both groups of PD patients between the two oxidative stress markers and Unified Parkinson Disease Rating Scale Total scores were weak, while TAC was negatively correlated with these scores. These findings suggest that oxidative stress may be increased in the CNS in healthy individuals with PD-associated LRRK2 mutations. Further, TAC may decrease in the CNS with the progression of PD, and when cognitive impairment is present regardless of the presence or absence of PD. PMID:28420983

Preoperative clinical and diagnostic characteristics of patients who require delayed IPP after primary Peyronies repair.

PubMed

Alphs, Hannah H; Navai, Neema; Köhler, Tobias S; McVary, Kevin T

2010-03-01

Penile vascular abnormalities occur in a high proportion of patients with Peyronie's disease (PD). Penile duplex ultrasonography (PDU) and dynamic infusion cavernosometry and cavernosography (DICC) are tools that can be used to help tailor individualized treatment for patients undergoing surgical intervention for their PD. However, precisely which parameters can be used to predict those patients with PD at risk for developing erectile dysfunction (ED) after intervention without inflatable penile prosthesis (IPP) has not been previously elucidated. To evaluate preoperative vascular parameters that predispose PD patients for developing ED after intervention without IPP. Twenty-six patients receiving surgical intervention for their PD at a single center were retrospectively identified. Of these, 11 (42.3%) opted for primary repair without placement of an IPP. Three (27.2%) of these 11 patients went on to develop ED postoperatively. We compared various demographic, PDU, and DICC parameters between patients who did and did not fail primary repair of their PD. Mean age and follow-up of patients who went on to develop ED after repair of PD without IPP were not significantly different (P < 0.05). Resistive index (RI) and end diastolic volume were significantly different between these two groups (P < 0.05), while peak systolic volume, flow to maintain, and pressure decay were not significantly different. An RI cutoff of <0.80 was found to identify all patients who would later develop ED and fail primary repair without IPP. Penile vascular assessment can aid in counseling patients about their risk of developing delayed ED after primary repair of PD. In our cohort of patients, PDU provided preoperative risk stratification for postoperative erectile dysfunction in men undergoing Peyronie's repair without IPP. We propose the prospective study of an RI cutoff to identify patients at risk of failing primary PD repair without IPP.

Porous nanocrystalline silicon supported bimetallic Pd-Au catalysts: preparation, characterization and direct hydrogen peroxide synthesis

NASA Astrophysics Data System (ADS)

Potemkin, Dmitriy I.; Maslov, Dmitry K.; Loponov, Konstantin; Snytnikov, Pavel V.; Shubin, Yuri V.; Plyusnin, Pavel E.; Svintsitskiy, Dmitry A.; Sobyanin, Vladimir A.; Lapkin, Alexei A.

2018-03-01

Bimetallic Pd-Au catalysts were prepared on the porous nanocrystalline silicon (PSi) for the first time. The catalysts were tested in the reaction of direct hydrogen peroxide synthesis and characterised by standard structural and chemical techniques. It was shown that the Pd-Au/PSi catalyst prepared from conventional H2[PdCl4] and H[AuCl4] precursors contains monometallic Pd and a range of different Pd-Au alloy nanoparticles over the oxidized PSi surface. The PdAu2/PSi catalyst prepared from the [Pd(NH3)4][AuCl4]2 double complex salt single-source precursor predominantly contains bimetallic Pd-Au alloy nanoparticles. For both catalysts the surface of bimetallic nanoparticles is Pd-enriched and contains palladium in Pd0 and Pd2+ states. Among the catalysts studied, the PdAu2/PSi catalyst was the most active and selective in the direct H2O2 synthesis with H2O2 productivity of 0.5 at selectivity of 50 % and H2O2 concentration of 0.023 M in 0.03 M H2SO4-methanol solution after 5 h on stream at -10 °C and atmospheric pressure. This performance is due to high activity in the H2O2 synthesis reaction and low activities in the undesirable H2O2 decomposition and hydrogenation reactions. Good performance of the PdAu2/PSi catalyst was associated with the major part of Pd in the catalyst being in the form of the bimetallic Pd-Au nanoparticles. Porous silicon was concluded to be a promising catalytic support for direct hydrogen peroxide synthesis due to its inertness with respect to undesirable side reactions, high thermal stability and conductivity, possibility of safe operation at high temperatures and pressures and a well-established manufacturing process.

Revisiting the Paraquat-Induced Sporadic Parkinson's Disease-Like Model.

PubMed

Bastías-Candia, Sussy; Zolezzi, Juan M; Inestrosa, Nibaldo C

2018-06-03

Parkinson's disease (PD) is a major neurodegenerative disorder that affects 1-2% of the total global population. Despite its high prevalence and publication of several studies focused on understanding its pathology, an effective treatment that stops and/or reverses the damage to dopaminergic neurons is unavailable. Similar to other neurodegenerative disorders, PD etiology may be linked to several factors, including genetic susceptibility and environmental elements. Regarding environmental factors, several neurotoxic pollutants, including 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), have been identified. Moreover, some pesticides/herbicides, such as rotenone, paraquat (PQ), maneb (MB), and mancozeb (MZ), cause neurotoxicity and induce a PD-like pathology. Based on these findings, several in vitro and in vivo PD-like models have been developed to understand the pathophysiology of PD and evaluate different therapeutic strategies to fight dopaminergic neurodegeneration. 6-OHDA and MPTP are common models used in PD research, and pesticide-based approaches have become secondary models of study. However, some herbicides, such as PQ, are commonly used by farming laborers in developing countries. Thus, the present review summarizes the relevant scientific background regarding the use and effects of chronic exposure to PQ in the context of PD. Similarly, we discuss the relevance of PD-like models developed using this agrochemical compound.

Higher Dialysate Matrix Metalloproteinase-2 Levels Are Associated with Peritoneal Membrane Dysfunction

PubMed Central

Cho, Yeoungjee; Johnson, David W.; Vesey, David A.; Hawley, Carmel M.; Pascoe, Elaine M.; Clarke, Margaret; Topley, Nicholas

2016-01-01

♦ Background: Peritoneal dialysis (PD) patients develop progressive and cumulative peritoneal injury with longer time spent on PD. The present study aimed to a) describe the trend of peritoneal injury biomarkers, matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-1 (TIMP-1), in incident PD patients, b) to explore the capacity of dialysate MMP-2 to predict peritoneal solute transport rate (PSTR) and peritonitis, and c) to evaluate the influence of neutral pH, low glucose degradation product (GDP) PD solution on these outcomes. ♦ Methods: The study included 178 participants from the balANZ trial who had at least 1 stored dialysate sample. Changes in PSTR and peritonitis were primary outcome measures, and the utility of MMP-2 in predicting these outcomes was analyzed using multilevel linear regression and multilevel Poisson regression, respectively. ♦ Results: Significant linear increases in dialysate MMP-2 and TIMP-1 concentrations were observed (p < 0.001), but neither was affected by the type of PD solutions received (MMP-2: p = 0.07; TIMP-1: p = 0.63). An increase in PSTR from baseline was associated with higher levels of MMP-2 (p = 0.02), and the use of standard solutions over longer PD duration (p = 0.001). The risk of peritonitis was independently predicted by higher dialysate MMP-2 levels (incidence rate ratio [IRR] per ng/mL 1.01, 95% confidence interval [CI] 1.005 – 1.02, p = 0.002) and use of standard solutions (Biocompatible solution: IRR 0.45, 95% CI 0.24 – 0.85, p = 0.01). ♦ Conclusion: Dialysate MMP-2 and TIMP-1 concentrations increased with longer PD duration. Higher MMP-2 levels were associated with faster PSTR and future peritonitis risk. Administration of biocompatible solutions exerted no significant effect on dialysate levels of MMP-2 or TIMP-1, but did counteract the increase in PSTR and the risk of peritonitis associated with the use of standard PD solutions. This is the first longitudinal study to examine the clinical utility of MMP-2 as a predictor of patient-level outcomes. PMID:25292407

The Brave New World of Personality Disorder-Trait Specified: Effects of Additional Definitions on Coverage, Prevalence, and Comorbidity

PubMed Central

Clark, Lee Anna; Vanderbleek, Emily N.; Shapiro, Jaime L.; Nuzum, Hallie; Allen, Xia; Daly, Elizabeth; Kingsbury, Thomas J.; Oiler, Morgan; Ro, Eunyoe

2015-01-01

The alternative dimensional model for personality disorder (PD) in DSM-5, Section III (DSM-5-III) includes two main criteria: (A) personality-functioning impairment, and (B) personality-trait pathology; provides specific functioning-and-trait criteria for six PD-type diagnoses; and introduces PD-trait specified (PD-TS), which requires meeting the general PD criteria and not meeting criteria for any specific PD type. We termed this Simple PD-TS and developed two additional definitions: Mixed PD-TS, meeting criteria for one or two PD types and having five or more additional pathological traits; and Complex PD-TS, meeting criteria for three or more PD types. In a mixed sample of 165 outpatients and 215 community adults screened to be at high-risk for PD, we investigated the effect of these additional definitions on prevalence, coverage, comorbidity, and within-diagnosis heterogeneity, and conclude that eliminating the PD-type diagnoses and thus having PD-TS as the only PD diagnosis would be both more parsimonious and more useful clinically. PMID:26097740

Comparative proteomic profiling of the choline transporter-like1 (CHER1) mutant provides insights into plasmodesmata composition of fully developed Arabidopsis thaliana leaves.

PubMed

Kraner, Max E; Müller, Carmen; Sonnewald, Uwe

2017-11-01

In plants, intercellular communication and exchange are highly dependent on cell wall bridging structures between adhering cells, so-called plasmodesmata (PD). In our previous genetic screen for PD-deficient Arabidopsis mutants, we described choline transporter-like 1 (CHER1) being important for PD genesis and maturation. Leaves of cher1 mutant plants have up to 10 times less PD, which do not develop to complex structures. Here we utilize the T-DNA insertion mutant cher1-4 and report a deep comparative proteomic workflow for the identification of cell-wall-embedded PD-associated proteins. Analyzing triplicates of cell-wall-enriched fractions in depth by fractionation and quantitative high-resolution mass spectrometry, we compared > 5000 proteins obtained from fully developed leaves. Comparative data analysis and subsequent filtering generated a list of 61 proteins being significantly more abundant in Col-0. This list was enriched for previously described PD-associated proteins. To validate PD association of so far uncharacterized proteins, subcellular localization analyses were carried out by confocal laser-scanning microscopy. This study confirmed the association of PD for three out of four selected candidates, indicating that the comparative approach indeed allowed identification of so far undescribed PD-associated proteins. Performing comparative cell wall proteomics of Nicotiana benthamiana tissue, we observed an increase in abundance of these three selected candidates during sink to source transition. Taken together, our comparative proteomic approach revealed a valuable data set of potential PD-associated proteins, which can be used as a resource to unravel the molecular composition of complex PD and to investigate their function in cell-to-cell communication. © 2017 The Authors. The Plant Journal published by John Wiley & Sons Ltd and Society for Experimental Biology.

Panic disorder as a risk factor for post-partum depression: Results from the Perinatal Depression-Research & Screening Unit (PND-ReScU) study.

PubMed

Rambelli, C; Montagnani, M S; Oppo, A; Banti, S; Borri, C; Cortopassi, C; Ramacciotti, D; Camilleri, V; Mula, M; Cassano, G B; Mauri, M

2010-04-01

Although the role of anxiety disorders on the development of Post-partum Depression (PPD) have already been studied in literature, that of individual anxiety disorders has not received specific attention. The aim of this study is to investigate the role of Panic Disorder (PD) and family history for PD as risk factors for PPD. Six hundred women were recruited in a prospective, observational study at the 3rd month of pregnancy and followed up until the 6th month after delivery. At baseline, risk factors for PPD, Axis-I disorders and family history for psychiatric disorders were assessed. We investigated minor and major depression (mMD) occurred at 1st, 3rd and 6th months post-partum. Logistic regression models were used to estimate the association between PD, family history for PD and PPD. Forty women had mMD in the post-partum. PD during pregnancy (RR=4.25; 95%CI:1.48-12.19), a history of PD (RR 2.47; 95%CI:1.11-5.49) and family history for PD (RR=2.1; 95%CI:1.06-4.4) predicted PPD after adjusting for lifetime depression and risk factors for PPD. The response rate is moderately low, but it is similar to other studies. The drop out rate is slightly high, however the 600 women who completed the 6th month follow-up did not differ from the presence of PD at baseline. PD is an independent risk factor for PPD, underscoring need to assess PD symptoms during pregnancy. Furthermore, PD represents an important risk factor for the development of PPD and should be routinely screened in order to develop specific preventive interventions. Copyright 2009 Elsevier B.V. All rights reserved.

Rapid, general synthesis of PdPt bimetallic alloy nanosponges and their enhanced catalytic performance for ethanol/methanol electrooxidation in an alkaline medium.

PubMed

Zhu, Chengzhou; Guo, Shaojun; Dong, Shaojun

2013-01-14

We have demonstrated a rapid and general strategy to synthesize novel three-dimensional PdPt bimetallic alloy nanosponges in the absence of a capping agent. Significantly, the as-prepared PdPt bimetallic alloy nanosponges exhibited greatly enhanced activity and stability towards ethanol/methanol electrooxidation in an alkaline medium, which demonstrates the potential of applying these PdPt bimetallic alloy nanosponges as effective electrocatalysts for direct alcohol fuel cells. In addition, this simple method has also been applied for the synthesis of AuPt, AuPd bimetallic, and AuPtPd trimetallic alloy nanosponges. The as-synthesized three-dimensional bimetallic/trimetallic alloy nanosponges, because of their convenient preparation, well-defined sponge-like network, large-scale production, and high electrocatalytic performance for ethanol/methanol electrooxidation, may find promising potential applications in various fields, such as formic acid oxidation or oxygen reduction reactions, electrochemical sensors, and hydrogen-gas sensors. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Dreaming and cognition in patients with frontotemporal dysfunction.

PubMed

Paiva, Teresa; Bugalho, Paulo; Bentes, Carla

2011-12-01

Individuals with Parkinson's disease (PD) and temporal lobe epilepsy (TLE) have hallucinations and mild cognitive dysfunction. The objective of this work was to study dreams in PD and TLE patients using a common functional model of dream production involving the limbic and paralimbic structures. Dreams were characterised in early-stage PD (19 males) and TLE patients (52) with dream diaries classified by the Hall van de Castle system and were compared with matched controls. In PD, there were significant differences between patients' dreams and those of controls: animals, physical aggression, and a befriender were more common in patients, and aggressor and bodily misfortunes were less common. The dreams of patients with frontal dysfunction showed more aggressive features. TLE patients had lower recall than PD patients and a higher proportion of dreams involving family and familiar settings, lower proportions involving success, and a higher incidence of frontal dysfunction. The dreams of PD and TLE patients share important features. Copyright © 2011. Published by Elsevier Inc.

Anthrobiogeochemical platinum, palladium and rhodium cycles of earth: Emerging environmental contamination

NASA Astrophysics Data System (ADS)

Mitra, Arijeet; Sen, Indra Sekhar

2017-11-01

Anthrobiogeochemical cycles have been a subject of scientific research for many decades as they are important for identifying possible sources, sinks, and pathways of an element in the environment. In this study, we quantified global cycles for the platinum group elements (PGE; platinum (Pt), palladium (Pd) and rhodium (Rh)). We quantified the stocks of Pt, Pd, and Rh in Earth's various reservoirs, such as the core, mantle, consolidated crust, biomass, seawater, unconsolidated sediments, and atmosphere, as well as coal and petroleum deposits. We further quantified their fluxes, both natural and anthropogenic, between each reservoir, by identifying the flows across the hydrosphere, geosphere, biosphere, atmosphere and anthroposphere, including from mining activities, fossil fuel and biomass burning, construction activities, soil erosion, human contributions to net primary productivity, riverine transport, aeolian dust movement, primary production, volcanic eruption, sea-salt spray, crustal subduction, crust formation at mid ocean ridges, PGE recovery from recycling processes, and cosmic dust inputs at the Earth's surface. Stocks of PGEs were quantified by multiplying the mass of the reservoir by the average Pt, Pd and Rh concentration in the reservoir, whereas Pt, Pd and Rh fluxes were calculated by multiplying the rate of mass movement across the reservoirs with the Pt, Pd and Rh concentrations of the material. Uncertainties were explicitly incorporated in stock and flow estimations through Monte Carlo simulations. Our calculations reveal that the total surficial anthropogenic Pt, Pd, and Rh mobilizations were greater than their corresponding natural surficial mobilizations. We show that crustal subduction and crustal formation is the most important natural flow and contributes 21-42% of total PGE mobilization. When Earth's surficial processes are considered, soil erosion is the dominant flow for Rh and Pt mobilization, comprising 33% and 13%, respectively, of the total mobilization on Earth's surface, whereas NPP dominates the natural Pd mobilization. On the other hand, mining activities, fossil fuel burning and automobile emissions are the most important anthropogenic flows. Therefore, our qualitative and quantitative assessment indicates that mining activities contribute almost 60-80% of the total anthropogenic flow on Earth, and crustal subduction and production dominates the total global PGE cycle.

HYDROGENATION OF 4-OXOISOPHORONE OVER PD/AL2/O2 CATALYST UNDER SUPERCRITICAL CO2 MEDIUM

EPA Science Inventory

Hydrogenation of 4-oxoisophorone has been studied over 1% Pd/Al2O3 impregnated catalyst in supercritical CO2 medium at different reaction conditions. The effect of temperature, pressure and reaction medium on the conversion and product selectivity is discussed. Phase behavior stu...

SELECTIVE OXIDATION OF ALCOHOLS BY MOLECULAR OXYGEN OVER A PD/MGO CATALYST IN THE ABSENCE OF ANY ADDITIVES

EPA Science Inventory

Selective oxidation of alcohols to the corresponding carbonyl products using molecular oxygen is achieved over a simple and easily recyclable 1% Pd/MgO impregnated heterogeneous catalyst in the presence of trifluorotoluene. A variety of activated and non-activated alcohols are ef...

Thermal Measurement during Electrolysis of Pd-Ni Thin-film -Cathodes in Li2SO4/H2O Solution

NASA Astrophysics Data System (ADS)

Castano, C. H.; Lipson, A. G.; S-O, Kim; Miley, G. H.

2002-03-01

Using LENR - open type calorimeters, measurements of excess heat production were carried out during electrolysis in Li_2SO_4/H_2O solution with a Pt-anode and Pd-Ni thin film cathodes (2000-8000 Åthick) sputtered on the different dielectric substrates. In order to accurately evaluate actual performance during electrolysis runs in the open-type calorimeter used, considering effects of heat convection, bubbling and possible H_2+O2 recombination, smooth Pt sheets were used as cathodes. Pt provides a reference since it does not produce excess heat in the light water electrolyte. To increase the accuracy of measurements the water dissociation potential was determined for each cathode taking into account its individual over-voltage value. It is found that this design for the Pd-Ni cathodes resulted in the excess heat production of ~ 20-25 % of input power, equivalent to ~300 mW. In cases of the Pd/Ni- film fracture (or detachment from substrate) no excess heat was detected, providing an added reference point. These experiments plus use of optimized films will be presented.

The pedunculopontine nucleus is related to visual hallucinations in Parkinson's disease: preliminary results of a voxel-based morphometry study.

PubMed

Janzen, J; van 't Ent, D; Lemstra, A W; Berendse, H W; Barkhof, F; Foncke, E M J

2012-01-01

Visual hallucinations (VH) are common in Parkinson's disease (PD) and lead to a poor quality of life. For a long time, dopaminergic therapy was considered to be the most important risk factor for the development of VH in PD. Recently, the cholinergic system, including the pedunculopontine nucleus (PPN), has been implicated in the pathophysiology of VH. The aim of the present study was to investigate grey matter density of the PPN region and one of its projection areas, the thalamus. Thirteen non-demented PD patients with VH were compared to 16 non-demented PD patients without VH, 13 demented PD patients (PDD) with VH and 11 patients with dementia with Lewy bodies (DLB). Isotropic 3-D T1-weighted MRI images (3T) were analysed using voxel-based morphometry (VBM) with the PPN region and thalamus as ROIs. PD and PDD patients with VH showed grey matter reductions of the PPN region and the thalamus compared to PD patients without VH. VH in PD(D) patients are associated with atrophy of the PPN region and its thalamic target area, suggesting that a cholinergic deficit may be involved in the development of VH in PD(D).

Anti–PD-1/PD-L1 therapy of human cancer: past, present, and future

PubMed Central

Chen, Lieping; Han, Xue

2015-01-01

Major progress has been made toward our understanding of the programmed death-1/programmed death ligand-1 (PD-1/PD-L1) pathway (referred to as the PD pathway). mAbs are already being used to block the PD pathway to treat human cancers (anti-PD therapy), especially advanced solid tumors. This therapy is based on principles that were discovered through basic research more than a decade ago, but the great potential of this pathway to treat a broad spectrum of advanced human cancers is just now becoming apparent. In this Review, we will briefly review the history and development of anti-PD therapy, from the original benchwork to the most up-to-date clinical results. We will then focus the discussion on three basic principles that define this unique therapeutic approach and highlight how anti-PD therapy is distinct from other immunotherapeutic approaches, namely tumor site immune modulation, targeting tumor-induced immune defects, and repairing ongoing (rather than generating de novo) tumor immunity. We believe that these fundamental principles set the standard for future immunotherapies and will guide our efforts to develop more efficacious and less toxic immune therapeutics to treat human cancers. PMID:26325035

Engineering Defect-Free Nanoporous Pd from Optimized Pd-Ni Precursor Alloy by Understanding Palladium-Hydrogen Interactions During Dealloying

NASA Astrophysics Data System (ADS)

Schoop, Julius; Balk, T. John

2014-04-01

Thin films of nanoporous palladium (np-Pd) were produced from binary palladium-nickel (Pd-Ni) precursor alloys. A suitable precursor alloy and a method of dealloying to yield optimum nanoporosity (average pore/ligament size of 7 nm) were developed by studying the effects of various processing parameters on final microstructure. To obtain crack-free np-Pd, a 100 nm thin film of 20 at. pct Pd (80 at. pct Ni) can be dealloyed for ~5 hours in a 1 M solution of sulfuric acid, with oleic acid and oleylamine added as surfactants. Both shorter and longer dealloying times, as well as heating, inhibit the formation of crack-free np-Pd. Stress measurements at different stages of dealloying revealed that the necessary dealloying time is determined by the diffusion-controlled corrosion reaction occurring within the thin film during dealloying. Strong interaction between hydrogen and np-Pd was reflected in the stress evolution during dealloying. A mechanism is proposed for the formation of a Ni-rich dense top layer that results from H-induced swelling during initial dealloying and permits the development of defect-free np-Pd beneath, by limiting the speed of dealloying.

Mechanisms of PD-L1/PD-1-mediated CD8 T-cell dysfunction in the context of aging-related immune defects in the Eµ-TCL1 CLL mouse model.

PubMed

McClanahan, Fabienne; Riches, John C; Miller, Shaun; Day, William P; Kotsiou, Eleni; Neuberg, Donna; Croce, Carlo M; Capasso, Melania; Gribben, John G

2015-07-09

T-cell defects, immune suppression, and poor antitumor immune responses are hallmarks of chronic lymphocytic leukemia (CLL), and PD-1/PD-L1 inhibitory signaling has emerged as a major immunosuppressive mechanism. However, the effect of different microenvironments and the confounding influence of aging are poorly understood. The current study uses the Eμ-TCL1 mouse model, which replicates human T-cell defects, as a preclinical platform to longitudinally examine patterns of T-cell dysfunction alongside developing CLL and in different microenvironments, with a focus on PD-1/PD-L1 interactions. The development of CLL was significantly associated with changes in T-cell phenotype across all organs and function. Although partly mirrored in aging wild-type mice, CLL-specific T-cell changes were identified. Murine CLL cells highly expressed PD-L1 and PD-L2 in all organs, with high PD-L1 expression in the spleen. CD3(+)CD8(+) T cells from leukemic and aging healthy mice highly expressed PD-1, identifying aging as a confounder, but adoptive transfer experiments demonstrated CLL-specific PD-1 induction. Direct comparisons of PD-1 expression and function between aging CLL mice and controls identified PD-1(+) T cells in CLL as a heterogeneous population with variable effector function. This is highly relevant for therapeutic targeting of CD8(+) T cells, showing the potential of reprogramming and selective subset expansion to restore antitumor immunity. © 2015 by The American Society of Hematology.

Mechanisms of PD-L1/PD-1–mediated CD8 T-cell dysfunction in the context of aging-related immune defects in the Eµ-TCL1 CLL mouse model

PubMed Central

McClanahan, Fabienne; Riches, John C.; Miller, Shaun; Day, William P.; Kotsiou, Eleni; Neuberg, Donna; Croce, Carlo M.; Capasso, Melania

2015-01-01

T-cell defects, immune suppression, and poor antitumor immune responses are hallmarks of chronic lymphocytic leukemia (CLL), and PD-1/PD-L1 inhibitory signaling has emerged as a major immunosuppressive mechanism. However, the effect of different microenvironments and the confounding influence of aging are poorly understood. The current study uses the Eμ-TCL1 mouse model, which replicates human T-cell defects, as a preclinical platform to longitudinally examine patterns of T-cell dysfunction alongside developing CLL and in different microenvironments, with a focus on PD-1/PD-L1 interactions. The development of CLL was significantly associated with changes in T-cell phenotype across all organs and function. Although partly mirrored in aging wild-type mice, CLL-specific T-cell changes were identified. Murine CLL cells highly expressed PD-L1 and PD-L2 in all organs, with high PD-L1 expression in the spleen. CD3+CD8+ T cells from leukemic and aging healthy mice highly expressed PD-1, identifying aging as a confounder, but adoptive transfer experiments demonstrated CLL-specific PD-1 induction. Direct comparisons of PD-1 expression and function between aging CLL mice and controls identified PD-1+ T cells in CLL as a heterogeneous population with variable effector function. This is highly relevant for therapeutic targeting of CD8+ T cells, showing the potential of reprogramming and selective subset expansion to restore antitumor immunity. PMID:25979947

Glucocerebrosidase Mutations in Parkinson Disease.

PubMed

O'Regan, Grace; deSouza, Ruth-Mary; Balestrino, Roberta; Schapira, Anthony H

2017-01-01

Following the discovery of a higher than expected incidence of Parkinson Disease (PD) in Gaucher disease, a lysosomal storage disorder, mutations in the glucocerebrocidase (GBA) gene, which encodes a lysosomal enzyme involved in sphingolipid degradation were explored in the context of idiopathic PD. GBA mutations are now known to be the single largest risk factor for development of idiopathic PD. Clinically, on imaging and pharmacologically, GBA PD is almost identical to idiopathic PD, other than certain features that can be identified in the specialist research setting but not in routine clinical practice. In patients with a known GBA mutation, it is possible to monitor for prodromal signs of PD. The clinical similarity with idiopathic PD and the chance to identify PD at a pre-clinical stage provides a unique opportunity to research therapeutic options for early PD, before major irreversible neurodegeneration occurs. However, to date, the molecular mechanisms which lead to this increased PD risk in GBA mutation carriers are not fully elucidated. Experimental models to define the molecular mechanisms and test therapeutic options include cell culture, transgenic mice and other in vivo models amenable to genetic manipulation, such as drosophilia. Some key pathological pathways of interest in the context of GBA mutations include alpha synuclein aggregation, lysosomal-autophagy axis changes and endoplasmic reticulum stress. Therapeutic agents that exploit these pathways are being developed and include the small molecule chaperone Ambroxol. This review aims to summarise the main features of GBA-PD and provide insights into the pathological relevance of GBA mutations on molecular pathways and the therapeutic implications for PD resulting from investigation of the role of GBA in PD.

Lexical effects on speech production and intelligibility in Parkinson's disease

NASA Astrophysics Data System (ADS)

Chiu, Yi-Fang

Individuals with Parkinson's disease (PD) often have speech deficits that lead to reduced speech intelligibility. Previous research provides a rich database regarding the articulatory deficits associated with PD including restricted vowel space (Skodda, Visser, & Schlegel, 2011) and flatter formant transitions (Tjaden & Wilding, 2004; Walsh & Smith, 2012). However, few studies consider the effect of higher level structural variables of word usage frequency and the number of similar sounding words (i.e. neighborhood density) on lower level articulation or on listeners' perception of dysarthric speech. The purpose of the study is to examine the interaction of lexical properties and speech articulation as measured acoustically in speakers with PD and healthy controls (HC) and the effect of lexical properties on the perception of their speech. Individuals diagnosed with PD and age-matched healthy controls read sentences with words that varied in word frequency and neighborhood density. Acoustic analysis was performed to compare second formant transitions in diphthongs, an indicator of the dynamics of tongue movement during speech production, across different lexical characteristics. Young listeners transcribed the spoken sentences and the transcription accuracy was compared across lexical conditions. The acoustic results indicate that both PD and HC speakers adjusted their articulation based on lexical properties but the PD group had significant reductions in second formant transitions compared to HC. Both groups of speakers increased second formant transitions for words with low frequency and low density, but the lexical effect is diphthong dependent. The change in second formant slope was limited in the PD group when the required formant movement for the diphthong is small. The data from listeners' perception of the speech by PD and HC show that listeners identified high frequency words with greater accuracy suggesting the use of lexical knowledge during the recognition process. The relationship between acoustic results and perceptual accuracy is limited in this study suggesting that listeners incorporate acoustic and non-acoustic information to maximize speech intelligibility.

Sustaining Student Gains from Online On-Demand Professional Development

ERIC Educational Resources Information Center

Shaha, Steven H.; Glassett, Kelly; Copas, Aimee

2015-01-01

A multi-State, quasi-experimental study was conducted as a longitudinal, two-year follow-up of participation in an online, on-demand professional development (PD) program. The purpose was to ascertain whether student gains were sustained in a second year of PD participation. Data verified gains in Year 1 versus Pre-PD baseline, with continued…

Focusing on Mathematical Knowledge: The Impact of Content-Intensive Teacher Professional Development. NCEE 2016-4010

ERIC Educational Resources Information Center

Garet, Michael S.; Heppen, Jessica B.; Walters, Kirk; Parkinson, Julia; Smith, Toni M.; Song, Mengli; Garrett, Rachel; Yang, Rui; Borman, Geoffrey D.

2016-01-01

This report examines the impact of content-intensive Professional Development (PD) on teachers' math content knowledge, their instructional practice, and their students' achievement. The study's PD had three components, totaling 93 hours. The core of the PD was "Intel Math," an intensive 80-hour workshop delivered in summer 2013 that…

Teacher Perceptions of Professional Development in the Context of National Educational Reform: The Case of Qatar

ERIC Educational Resources Information Center

Nasser, Ramzi; Romanowski, Michael

2011-01-01

In light of nationally mandated educational changes in Qatar, this study investigates in-service teachers' perceptions of professional development (PD). The aims are to identify challenges facing teachers' PD. The respondents were 40 in-service teachers from two schools in Doha, Qatar, who had received PD connected with national educational…

The Impact of Teacher Observations with Coordinated Professional Development on Student Performance: A 27-State Program Evaluation

ERIC Educational Resources Information Center

Shaha, Steven H.; Glassett, Kelly F.; Copas, Aimee

2015-01-01

The impact of teacher observations in alignment with professional development (PD) on teacher efficacy was quantified for 292 schools in 110 districts within 27 U.S. States. Teacher observations conducted by school leaders or designated internal coaches were coordinated with PD offerings aligned with intended teacher improvements. The PD involved…

Parameters for the Design of Group Randomized Studies for Teacher Professional Development

ERIC Educational Resources Information Center

Kelcey, Ben; Phelps, Geoffrey; Jones, Nathan

2013-01-01

Teacher professional development (PD) is seen as critical to improving the quality of US schools (National Commission on Teaching and America's Future, 1997). PD is increasingly viewed as one of the primary levers for improving teaching quality and ultimately student achievement (Correnti, 2007). One factor that is driving interest in PD is…

Reframing Professional Development for South African Schools: An Appreciative Inquiry Approach

ERIC Educational Resources Information Center

Steyn, G. M.

2012-01-01

Often research on the professional development (PD) of staff is framed within a problem-based context that focuses on the PD-related problems experienced by staff. This study pursued a different approach by using the appreciative inquiry (AI) theoretical perspective to study the positive experiences of staff in respect of PD and their desire to…

Using participatory design to develop (public) health decision support systems through GIS.

PubMed

Dredger, S Michelle; Kothari, Anita; Morrison, Jason; Sawada, Michael; Crighton, Eric J; Graham, Ian D

2007-11-27

Organizations that collect substantial data for decision-making purposes are often characterized as being 'data rich' but 'information poor'. Maps and mapping tools can be very useful for research transfer in converting locally collected data into information. Challenges involved in incorporating GIS applications into the decision-making process within the non-profit (public) health sector include a lack of financial resources for software acquisition and training for non-specialists to use such tools. This on-going project has two primary phases. This paper critically reflects on Phase 1: the participatory design (PD) process of developing a collaborative web-based GIS tool. A case study design is being used whereby the case is defined as the data analyst and manager dyad (a two person team) in selected Ontario Early Year Centres (OEYCs). Multiple cases are used to support the reliability of findings. With nine producer/user pair participants, the goal in Phase 1 was to identify barriers to map production, and through the participatory design process, develop a web-based GIS tool suited for data analysts and their managers. This study has been guided by the Ottawa Model of Research Use (OMRU) conceptual framework. Due to wide variations in OEYC structures, only some data analysts used mapping software and there was no consistency or standardization in the software being used. Consequently, very little sharing of maps and data occurred among data analysts. Using PD, this project developed a web-based mapping tool (EYEMAP) that was easy to use, protected proprietary data, and permit limited and controlled sharing between participants. By providing data analysts with training on its use, the project also ensured that data analysts would not break cartographic conventions (e.g. using a chloropleth map for count data). Interoperability was built into the web-based solution; that is, EYEMAP can read many different standard mapping file formats (e.g. ESRI, MapInfo, CSV). Based on the evaluation of Phase 1, the PD process has served both as a facilitator and a barrier. In terms of successes, the PD process identified two key components that are important to users: increased data/map sharing functionality and interoperability. Some of the challenges affected developers and users; both individually and as a collective. From a development perspective, this project experienced difficulties in obtaining personnel skilled in web application development and GIS. For users, some data sharing barriers are beyond what a technological tool can address (e.g. third party data). Lastly, the PD process occurs in real time; both a strength and a limitation. Programmatic changes at the provincial level and staff turnover at the organizational level made it difficult to maintain buy-in as participants changed over time. The impacts of these successes and challenges will be evaluated more concretely at the end of Phase 2. PD approaches, by their very nature, encourage buy-in to the development process, better addresses user-needs, and creates a sense of user-investment and ownership.

Ultrasound-accelerated synthesis of biphenyl compounds using novel Pd(0) nanoparticles immobilized on bio-composite.

PubMed

Baran, Talat

2018-07-01

This study describes (i) an eco-friendly approach for design of Pd(0) nanoparticles on a natural composite, which is composed of carboxymethyl cellulose/agar polysaccharides (CMC/AG), without using any toxic reducing agents and (ii) development of ultrasound assisted simple protocol for synthesis of biphenyl compounds. Chemical characterization studies of Pd(0) nanoparticles (Pd NPs@CMC/AG) revealed that size of the particles were in the range of 37-55 nm. Catalytic performance of Pd NPs@CMC/AG was evaluated in synthesis of various biphenyl compounds by using the ultrasound-assisted method that was developed in this study. Pd NPs@CMC/AG exhibited excellent catalytic performance by producing high reaction yields. In addition, Pd NPs@CMC/AG was successfully used up to six reaction cycles without losing its catalytic activity, indicating high reproducibility of Pd NPs@CMC/AG. Additionally, compared to conventional the methods, new ultrasound-assisted synthesis technique that was followed in this study exhibited some advantages such as shorter reaction time, greener reaction conditions, higher yields and easier work-up. Copyright © 2018 Elsevier B.V. All rights reserved.

Investigating plasmodesmata genetics with virus-induced gene silencing and an agrobacterium-mediated GFP movement assay.

PubMed

Brunkard, Jacob O; Burch-Smith, Tessa M; Runkel, Anne M; Zambryski, Patricia

2015-01-01

Plasmodesmata (PD) are channels that connect the cytoplasm of adjacent plant cells, permitting intercellular transport and communication. PD function and formation are essential to plant growth and development, but we still know very little about the genetic pathways regulating PD transport. Here, we present a method for assaying changes in the rate of PD transport following genetic manipulation. Gene expression in leaves is modified by virus-induced gene silencing. Seven to ten days after infection with Tobacco rattle virus carrying a silencing trigger, the gene(s) of interest is silenced in newly arising leaves. In these new leaves, individual cells are then transformed with Agrobacterium to express GFP, and the rate of GFP diffusion via PD is measured. By measuring GFP diffusion both within the epidermis and between the epidermis and mesophyll, the assay can be used to study the effects of silencing a gene(s) on PD transport in general, or transport through secondary PD specifically. Plant biologists working in several fields will find this assay useful, since PD transport impacts plant physiology, development, and defense.

Computerized Adaptive Assessment of Personality Disorder: Introducing the CAT-PD Project

PubMed Central

Simms, Leonard J.; Goldberg, Lewis R.; Roberts, John E.; Watson, David; Welte, John; Rotterman, Jane H.

2011-01-01

Assessment of personality disorders (PD) has been hindered by reliance on the problematic categorical model embodied in the most recent Diagnostic and Statistical Model of Mental Disorders (DSM), lack of consensus among alternative dimensional models, and inefficient measurement methods. This article describes the rationale for and early results from an NIMH-funded, multi-year study designed to develop an integrative and comprehensive model and efficient measure of PD trait dimensions. To accomplish these goals, we are in the midst of a five-phase project to develop and validate the model and measure. The results of Phase 1 of the project—which was focused on developing the PD traits to be assessed and the initial item pool—resulted in a candidate list of 59 PD traits and an initial item pool of 2,589 items. Data collection and structural analyses in community and patient samples will inform the ultimate structure of the measure, and computerized adaptive testing (CAT) will permit efficient measurement of the resultant traits. The resultant Computerized Adaptive Test of Personality Disorder (CAT-PD) will be well positioned as a measure of the proposed DSM-5 PD traits. Implications for both applied and basic personality research are discussed. PMID:22804677

Excessive daytime sleepiness and subsequent development of Parkinson disease.

PubMed

Abbott, R D; Ross, G W; White, L R; Tanner, C M; Masaki, K H; Nelson, J S; Curb, J D; Petrovitch, H

2005-11-08

To determine if excessive daytime sleepiness (EDS) can predate future Parkinson disease (PD). EDS was assessed in 3,078 men aged 71 to 93 years in the Honolulu-Asia Aging Study from 1991 to 1993. All were free of prevalent PD and dementia. Follow-up for incident PD was based on three repeat neurologic assessments from 1994 to 2001. During the course of follow-up, 43 men developed PD (19.9/10,000 person-years). After age adjustment, there was more than a threefold excess in the risk of PD in men with EDS vs men without EDS (55.3 vs 17.0/10,000 person-years; odds ratio [OR] = 3.3; 95% CI = 1.4 to 7.0; p = 0.004). Additional adjustment for insomnia, cognitive function, depressed mood, midlife cigarette smoking and coffee drinking, and other factors failed to alter the association between EDS and PD (OR = 2.8; 95% CI = 1.1 to 6.4; p = 0.014). Other sleep related features such as insomnia, daytime napping, early morning grogginess, and frequent nocturnal awakening showed little relation with the risk of PD. Excessive daytime sleepiness may be associated with an increased risk of developing Parkinson disease.

Asian G6PD-Mahidol Reticulocytes Sustain Normal Plasmodium Vivax Development.

PubMed

Bancone, Germana; Malleret, Benoit; Suwanarusk, Rossarin; Chowwiwat, Nongnud; Chu, Cindy S; McGready, Rose; Rénia, Laurent; Nosten, François; Russell, Bruce

2017-07-15

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymatic disorder in humans and appears to be protective against falciparum severe malaria. Controversially, it is also thought that Plasmodium vivax has driven the recent selection of G6PD alleles. We use an experimental approach to determine whether G6PD-MahidolG487A variant, a widespread cause of severe G6PD deficiency in Southeast Asia, provides a barrier against vivax malaria. Our results show that the immature reticulocytes (CD71+) targeted by P. vivax invasion are enzymatically normal, even in hemizygous G6PD-Mahidol G487A mutants; thus, allowing the normal growth, development, and high parasite density in severely deficient samples. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Frontline Science: Defects in immune function in patients with sepsis are associated with PD-1 or PD-L1 expression and can be restored by antibodies targeting PD-1 or PD-L1

PubMed Central

Patera, Andriani C.; Drewry, Anne M.; Chang, Katherine; Beiter, Evan R.; Osborne, Dale; Hotchkiss, Richard S.

2016-01-01

Sepsis is a heterogeneous syndrome comprising a highly diverse and dynamic mixture of hyperinflammatory and compensatory anti-inflammatory immune responses. This immune phenotypic diversity highlights the importance of proper patient selection for treatment with the immunomodulatory drugs that are entering clinical trials. To better understand the serial changes in immunity of critically ill patients and to evaluate the potential efficacy of blocking key inhibitory pathways in sepsis, we undertook a broad phenotypic and functional analysis of innate and acquired immunity in the same aliquot of blood from septic, critically ill nonseptic, and healthy donors. We also tested the ability of blocking the checkpoint inhibitors programmed death receptor-1 (PD-1) and its ligand (PD-L1) to restore the function of innate and acquired immune cells. Neutrophil and monocyte function (phagocytosis, CD163, cytokine expression) were progressively diminished as sepsis persisted. An increasing frequency in PD-L1+-suppressor phenotype neutrophils [low-density neutrophils (LDNs)] was also noted. PD-L1+ LDNs and defective neutrophil function correlated with disease severity, consistent with the potential importance of suppressive neutrophil populations in sepsis. Reduced neutrophil and monocyte function correlated both with their own PD-L1 expression and with PD-1 expression on CD8+ T cells and NK cells. Conversely, reduced CD8+ T cell and NK cell functions (IFN-γ production, granzyme B, and CD107a expression) correlated with elevated PD-L1+ LDNs. Importantly, addition of antibodies against PD-1 or PD-L1 restored function in neutrophil, monocyte, T cells, and NK cells, underlining the impact of the PD-1:PD-L1 axis in sepsis-immune suppression and the ability to treat multiple deficits with a single immunomodulatory agent. PMID:27671246

In vivo blockade of the PD-1 pathway using soluble rPD-1-Fc enhances CD4+ and CD8+ T cell responses but has limited clinical benefit

PubMed Central

Amancha, Praveen K.; Hong, Jung Joo; Rogers, Kenneth; Ansari, Aftab A.; Villinger, Francois

2013-01-01

The PD-1/PD-Ligand pathway has been shown to limit cell mediated effector functions during chronic viral infections impeding clearance of pathogens. As a strategy to reverse this exhaustion and increase T cell poly-functionality, PD-1 ligands were blocked in vivo using a recombinant macaque PD1-Fc fusion protein (rPD-1-Fc) in SIVmac239 infected rhesus macaques during the early chronic phase of infection, either alone or in combination with ART. In vitro blockade showed improvement of antigen specific CD4+ and CD8+ T cells from monkeys chronically infected with SIV. Of note, a prolonged 5-day blockade in culture was beneficial for both gag specific CD4+ and CD8+ T cells based on proliferation and dual cytokine production. While the in vivo administration of a recombinant rhesus PD-1 Fc fusion protein (rPD-1-Fc) induced enhanced SIV specific CD4 and CD8 T cell proliferation both in the blood and gut, it failed to alter plasma viremia. However, rPD-1-Fc administration in the context of ART interruption induced a significant delay of viral load rebound. In addition, rPD-1-Fc administration in MamuA*001+ monkeys led to both an increase in the frequencies and Ki67 expression of GagCM9+ CD8+ T cells in the blood and rectal mucosa and poly-functionality of GagCM9+ CD8+ T cells in blood. In conclusion, however, our data suggest that PD-1/PD-Ligand blockade using soluble rPD-1-Fc instead of anti-PD1 Mab, while effective in rescuing the effector function of SIV-specific CD4+ and CD8+ T cells during the early chronic phase of infection, has limited clinical benefit. PMID:24227774

The dynamics of surface-catalyzed reactions studied by infrared chemiluminescence of the CO and CO{sub 2} products

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

Watanabe, K.; Uetsuka, H.; Ohnuma, H.

The infrared chemiluminescence technique has been applied to the selective formation of syngas (CO + H{sub 2}) from the oxidation of small alkanes on Pt, the decomposition and oxidation of CH{sub 3}OH and HCOOH on Pt and Ni, and CO oxidation on Pd(111) and Pd(110). The different internal (vibrational and rotational) energy states of the CO and CO{sub 2} products have been observed, which reflect the difference in the dynamics of these reactions.

Experimental Evidence for LENR in a Polarized Pd/D Lattice

NASA Astrophysics Data System (ADS)

Szpak, S.

2005-03-01

Experimental evidence in support of claims that excess enthalpy production in a polarized Pd/D lattice is of a nuclear origin is questioned on various grounds, eg marginal intensity and difficulty in reproducing. Here, evidence is presented that is 100% reproducible and of sufficient intensity to be well outside of experimental errors. In addition to the thermal behavior, the nuclear manifestations include: X-ray emission; tritium production; and, when an operating cell is placed in an external electric field, fusion to create heavier metals such as Ca, Al, Mg, and Zn.

Development of Chemical and Metabolite Sensors for Rhodococcus opacus PD630

DOE PAGES

DeLorenzo, Drew M.; Henson, William R.; Moon, Tae Seok

2017-07-26

Rhodococcus opacus PD630 is a non-model, gram positive bacterium that possesses desirable traits for biomass conversion, including consumption capabilities for lignocellulose-based sugars and toxic lignin-derived aromatic compounds, significant triacylglycerol accumulation, relatively rapid growth rate, and genetic tractability. However, few genetic elements have been directly characterized in R. opacus, limiting its application for lignocellulose bioconversion. Here, we report the characterization and development of genetic tools for tunable gene expression in R. opacus, including: 1) six fluorescent reporters for quantifying promoter output, 2) three chemically inducible promoters for variable gene expression, and 3) two classes of metabolite sensors derived from native R.more » opacus promoters that detect nitrogen levels or aromatic compounds. Using these tools, we also provide insights into native aromatic consumption pathways in R. opacus. Overall, this work expands the ability to control and characterize gene expression in R. opacus for future lignocellulose-based fuel and chemical production.« less

Combination therapy strategies for improving PD-1 blockade efficacy: a new era in cancer immunotherapy.

PubMed

Chowdhury, P S; Chamoto, K; Honjo, T

2018-02-01

Programmed death 1 (PD-1) is an immune checkpoint molecule that negatively regulates T-cell immune function through the interaction with its ligand PD-L1. Blockage of this interaction unleashes the immune system to fight cancer. Immunotherapy using PD-1 blockade has led to a paradigm shift in the field of cancer drug discovery, owing to its durable effect against a wide variety of cancers with limited adverse effects. A brief history and development of PD-1 blockade, from the initial discovery of PD-1 to the recent clinical output of this therapy, have been summarized here. Despite its tremendous clinical success rate over other cancer treatments, PD-1 blockade has its own pitfall; a significant fraction of patients remains unresponsive to this therapy. The key to improve the PD-1 blockade therapy is the development of combination therapies. As this approach has garnered worldwide interest, here, we have summarized the recent trends in the development of PD-1 blockade-based combination therapies and the ongoing clinical trials. These include combinations with checkpoint inhibitors, radiation therapy, chemotherapy and several other existing cancer treatments. Importantly, FDA has approved PD-1 blockade agent to be used in combination with either CTLA-4 blockade or chemotherapy. Responsiveness to the PD-1 blockade therapy is affected by tumour and immune system-related factors. The role of the immune system, especially T cells, in determining the responsiveness has been poorly studied compared with those factors related to the tumour side. Energy metabolism has emerged as one of the important regulatory mechanisms for the function and differentiation of T cells. We have documented here the recent results regarding the augmentation of PD-1 blockade efficacy by augmenting mitochondrial energy metabolism of T cell. © 2017 The Association for the Publication of the Journal of Internal Medicine.

Conversion of corn stover alkaline pre-treatment waste streams into biodiesel via Rhodococci

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

Le, Rosemary K.; Wells Jr., Tyrone; Das, Parthapratim

We present the bioconversion of second-generation cellulosic ethanol waste streams into biodiesel via oleaginous bacteria is a novel optimization strategy for biorefineries with substantial potential for rapid development. In this study, one- and two-stage alkali/alkali-peroxide pretreatment waste streams of corn stover were separately implemented as feedstocks in 96 h batch reactor fermentations with wild-type Rhodococcus opacus PD 630, R. opacus DSM 1069, and R. jostii DSM 44719 T . Here we show using 31P-NMR, HPAECPAD, and SEC analyses, that the more rigorous and chemically-efficient two-stage chemical pretreatment effluent provided higher concentrations of solubilized glucose and lower molecular weight (70 300more » g mol1 ) lignin degradation products thereby enabling improved cellular density, viability, and oleaginicity in each respective strain. The most significant yields were by R. opacus PD 630, which converted 6.2% of organic content with a maximal total lipid production of 1.3 g L1 and accumulated 42.1% in oils based on cell dry weight after 48 h.« less

Synthesis of N₄ donor macrocyclic Schiff base ligands and their Ru (II), Pd (II), Pt (II) metal complexes for biological studies and catalytic oxidation of didanosine in pharmaceuticals.

PubMed

Ravi Krishna, E; Muralidhar Reddy, P; Sarangapani, M; Hanmanthu, G; Geeta, B; Shoba Rani, K; Ravinder, V

2012-11-01

A series of tetraaza (N(4) donor) macrocyclic ligands (L(1)-L(4)) were derived from the condensation of o-phthalaldehyde (OPA) with some substituted aromatic amines/azide, and subsequently used to synthesize the metal complexes of Ru(II), Pd(II) and Pt(II). The structures of macrocyclic ligands and their metal complexes were characterized by elemental analyses, IR, (1)H &(13)C NMR, mass and electronic spectroscopy, thermal, magnetic and conductance measurements. Both the ligands and their complexes were screened for their antibacterial activities against Gram positive and Gram negative bacteria by MIC method. Besides, these macrocyclic complexes were investigated as catalysts in the oxidation of pharmaceutical drug didanosine. The oxidized products were further treated with sulphanilic acid to develop the colored products to determine by spectrophotometrically. The current oxidation method is an environmentally friendly, simple to set-up, requires short reaction time, produces high yields and does not require co-oxidant. Copyright © 2012 Elsevier B.V. All rights reserved.

Conversion of corn stover alkaline pre-treatment waste streams into biodiesel via Rhodococci

DOE PAGES

Le, Rosemary K.; Wells Jr., Tyrone; Das, Parthapratim; ...

2017-01-13

We present the bioconversion of second-generation cellulosic ethanol waste streams into biodiesel via oleaginous bacteria is a novel optimization strategy for biorefineries with substantial potential for rapid development. In this study, one- and two-stage alkali/alkali-peroxide pretreatment waste streams of corn stover were separately implemented as feedstocks in 96 h batch reactor fermentations with wild-type Rhodococcus opacus PD 630, R. opacus DSM 1069, and R. jostii DSM 44719 T . Here we show using 31P-NMR, HPAECPAD, and SEC analyses, that the more rigorous and chemically-efficient two-stage chemical pretreatment effluent provided higher concentrations of solubilized glucose and lower molecular weight (70 300more » g mol1 ) lignin degradation products thereby enabling improved cellular density, viability, and oleaginicity in each respective strain. The most significant yields were by R. opacus PD 630, which converted 6.2% of organic content with a maximal total lipid production of 1.3 g L1 and accumulated 42.1% in oils based on cell dry weight after 48 h.« less

Electrolytic Migration of Ag-Pd Alloy Wires with Various Pd Contents

NASA Astrophysics Data System (ADS)

Lin, Yan-Cheng; Chen, Chun-Hao; He, Yu-Zhen; Chen, Sheng-Chi; Chuang, Tung-Han

2018-07-01

During Ag ion migration in an aqueous water drop covering a pair of parallel Ag-Pd wires under current stressing, hydrogen bubbles form first from the cathode, followed by the appearance of pure Ag dendrites on the cathodic wire. In this study, Ag dendrites with a diameter of 0.2-0.4 μm grew toward the anodic wire. The growth rate ( v) of these dendrites decreased with the Pd content ( c) with a linear relationship of: v = 10.02 - 0.43 c . Accompanying the growth of pure Ag dendrites was the formation of a continuous layer of crystallographic Ag2O particles on the surface of the anodic wire. The deposition of such insulating Ag2O products did not prevent the contact of Ag dendrites with the anodic Ag-Pd wire or the short circuit of the wire couple.

PD-1 Inhibition Minimally Affects Cisplatin-Induced Toxicities in a Murine Model.

PubMed

Spielbauer, Katie; Cunningham, Lisa; Schmitt, Nicole

2018-03-01

Immune checkpoint inhibition used in combination with standard cisplatin-based chemotherapy regimens is currently under evaluation in clinical trials for head and neck squamous cell carcinoma (HNSCC). The impact of anti-PD-1 therapy on cisplatin-induced ototoxicity and nephrotoxicity has not been established. Here we use a murine model of cisplatin-induced hearing loss to investigate the impact of anti-PD-1 immunotherapy on auditory brainstem responses (ABRs), distortion product otoacoustic emissions (DPOAEs), serum creatinine, and hair cell and renal histology. We demonstrate only mild worsening of DPOAEs at 14.4 and 16 kHz as well as a mild increase in serum creatinine. Renal and hair cell histology as well as ABR measures were unchanged by PD-1 inhibition. Thus, our data suggest that the use of PD-1 inhibition in conjunction with cisplatin results in toxicities that are similar to those of cisplatin alone.

Electrolytic Migration of Ag-Pd Alloy Wires with Various Pd Contents

NASA Astrophysics Data System (ADS)

Lin, Yan-Cheng; Chen, Chun-Hao; He, Yu-Zhen; Chen, Sheng-Chi; Chuang, Tung-Han

2018-03-01

During Ag ion migration in an aqueous water drop covering a pair of parallel Ag-Pd wires under current stressing, hydrogen bubbles form first from the cathode, followed by the appearance of pure Ag dendrites on the cathodic wire. In this study, Ag dendrites with a diameter of 0.2-0.4 μm grew toward the anodic wire. The growth rate (v) of these dendrites decreased with the Pd content (c) with a linear relationship of: v = 10.02 - 0.43 c . Accompanying the growth of pure Ag dendrites was the formation of a continuous layer of crystallographic Ag2O particles on the surface of the anodic wire. The deposition of such insulating Ag2O products did not prevent the contact of Ag dendrites with the anodic Ag-Pd wire or the short circuit of the wire couple.

High-affinity PD-1 molecules deliver improved interaction with PD-L1 and PD-L2.

PubMed

Li, Yanyan; Liang, Zhaoduan; Tian, Ye; Cai, Wenxuan; Weng, Zhiming; Chen, Lin; Zhang, Huanling; Bao, Yifeng; Zheng, Hongjun; Zeng, Sihai; Bei, Chunhua; Li, Yi

2018-06-11

The inhibitory checkpoint molecule programmed death (PD)-1 plays a vital role in maintaining immune homeostasis upon binding to its ligands, PD-L1 and PD-L2. Several recent studies have demonstrated that soluble PD-1 (sPD-1) can block the interaction between membrane PD-1 and PD-L1 to enhance the anti-tumor capability of T cells. However, the affinity of natural sPD-1 binding to PD-L1 is too low to permit therapeutic applications. Here a PD-1 variant with ~3,000-fold and ~70-fold affinity increase to bind PD-L1 and PD-L2, respectively, was generated through directed molecular evolution and phage display technology. Structural analysis showed that mutations at amino acid positions 124 and 132 of PD-1 played major roles in enhancing the affinity of PD-1 binding to its ligands. The high-affinity PD-1 mutant could compete with the binding of antibodies specific to PD-L1 or PD-L2 on cancer cells or dendritic cells (DCs), and it could enhance the proliferation and IFN-γ release of activated lymphocytes. These features potentially qualify the high-affinity PD-1 variant as a unique candidate for the development of a new class of PD-1 immune checkpoint blockade therapeutics. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Zinc Induces Dendritic Cell Tolerogenic Phenotype and Skews Regulatory T cell – Th17 Balance

PubMed Central

George, Mariam Mathew; Vignesh, Kavitha Subramanian; Landero Figueroa, Julio A.; Caruso, Joseph A.; Deepe, George S.

2016-01-01

Zn is an essential metal for development and maintenance of both the innate and adaptive compartments of the immune system. Zn homeostasis impacts maturation of dendritic cells (DCs) that are important in shaping T cell responses. The mechanism by which Zn regulates the tolerogenic phenotype of DCs remains largely unknown. In this study, we investigated the effect of Zn on DC phenotype and the generation of forkhead box P3 (FoxP3+) regulatory T cells (Tregs) using a model of Histoplasma capsulatum fungal infection. Exposure of bone marrow derived DCs to Zn in vitro induced a tolerogenic phenotype by diminishing surface major histocompatibility complex (MHC)II and promoting the tolerogenic markers, programmed death-ligand (PD-L)1, PD-L2 and the tryptophan degrading enzyme, indoleamine 2,3 dioxygenase (IDO). Zn triggered tryptophan degradation by IDO and kynurenine production by DCs and strongly suppressed the proinflammatory response to stimulation by toll like receptor (TLR) ligands. In vivo, Zn supplementation and subsequent H. capsulatum infection supressed MHCII on DCs, enhanced PD-L1 and PD-L2 expression on MHCIIlo DCs and skewed the Treg - Th17 balance in favour of FoxP3+ Tregs while decreasing Th17 cells. Thus, Zn shapes the tolerogenic potential of DCs in vitro and in vivo and promotes Tregs during fungal infection. PMID:27465530

Heterogeneous Pd catalysts as emulsifiers in Pickering emulsions for integrated multistep synthesis in flow chemistry.

PubMed

Hiebler, Katharina; Lichtenegger, Georg J; Maier, Manuel C; Park, Eun Sung; Gonzales-Groom, Renie; Binks, Bernard P; Gruber-Woelfler, Heidrun

2018-01-01

Within the "compartmentalised smart factory" approach of the ONE-FLOW project the implementation of different catalysts in "compartments" provided by Pickering emulsions and their application in continuous flow is targeted. We present here the development of heterogeneous Pd catalysts that are ready to be used in combination with biocatalysts for catalytic cascade synthesis of active pharmaceutical ingredients (APIs). In particular, we focus on the application of the catalytic systems for Suzuki-Miyaura cross-coupling reactions, which is the key step in the synthesis of the targeted APIs valsartan and sacubitril. An immobilised enzyme will accomplish the final product formation via hydrolysis. In order to create a large interfacial area for the catalytic reactions and to keep the reagents separated until required, the catalyst particles are used to stabilise Pickering emulsions of oil and water. A set of Ce-Sn-Pd oxides with the molecular formula Ce 0.99- x Sn x Pd 0.01 O 2-δ ( x = 0-0.99) has been prepared utilising a simple single-step solution combustion method. The high applicability of the catalysts for different functional groups and their minimal leaching behaviour is demonstrated with various Suzuki-Miyaura cross-coupling reactions in batch as well as in continuous flow employing the so-called "plug & play reactor". Finally, we demonstrate the use of these particles as the sole emulsifier of oil-water emulsions for a range of oils.

Fast-scan cyclic voltammetry reveals that L-Dopa produces regionally selective, bimodal influences on striatal dopamine kinetics in vivo

PubMed Central

Harun, R; Munoz, M; Grassi, C; Hare, K; Brough, E; Torres, GE; Grace, AA; Wagner, AK

2016-01-01

Parkinson’s disease (PD) is a debilitating condition that is caused by a relatively specific degeneration of dopaminergic (DAergic) neurons of the substantia nigra pars compacta. Levodopa (L-Dopa) was introduced as a viable treatment option for PD over 40 years ago and still remains the most common and effective therapy for PD. Though the effects of L-Dopa to augment striatal DA production are well known, little is actually known about how L-Dopa alters the kinetics of DA neurotransmission that contribute to its beneficial and adverse effects. In this study, we examined the effects of L-Dopa administration (100mg/kg carbidopa/250mg/kg L-Dopa) on regional electrically stimulated DA response kinetics using fast-scan cyclic voltammetry (FSCV) in anesthetized rats. We demonstrate that L-Dopa enhances DA release in both the dorsal striatum (D-STR) and nucleus accumbens (NAc), but surprisingly causes a delayed inhibition of release in the D-STR, a finding that may be related to high-dose L-Dopa effects. In both regions, L-Dopa progressively attenuated reuptake kinetics through a decrease in Vmax and an increase in Km. This finding is consistent with recent clinical studies suggesting that L-Dopa chronically down-regulates the DA transporter (DAT), which may relate to the common development of L-Dopa induced dyskinesias (LID) in PD subjects. PMID:26611352

Equatorial potassium currents in lenses.

PubMed

Wind, B E; Walsh, S; Patterson, J W

1988-02-01

Earlier work with the vibrating probe demonstrated the existence of outward potassium currents at the equator and inward sodium currents at the optical poles of the lens. By adding microelectrodes to the system, it is possible to relate steady currents (J) to the potential difference (PD) measured with a microelectrode. By injecting an outward current (I), it is possible to determine resistances and also the PD at which the steady outward potassium current becomes zero (PDJ = 0). At this PD the concentration gradient for potassium efflux and the electrical gradient for potassium influx are balanced so that there is no net flow of potassium across the membranes associated with the production of J. The PDJ = 0 for 18 rat lenses was 86 mV and that for 12 frogs lenses was -95 mV. This agrees with the potassium equilibrium potential and provides strong evidence to support the view that the outward equatorial current, J, is a potassium current. With the injection of outward current, I, the PD becomes more negative, the outward equatorial current, J, decreases, and the inward current at the optical poles increases. This suggests that there are separate electrical loops for K+ and Na+ that are partially linked by the Na, K-pump. Using Ohm's law, it is possible to calculate the input resistance (R = delta PD/I), the resistance related to the production of J (RJ = delta PD/delta J), and the effect of the combined resistances (delta J/I). The driving force for J can be estimated (PDJ = 0-PD). The relationships among currents, voltages and resistance can be used to determine the characteristics of the membranes that are associated with the outward potassium current observed at the equator. The effects of graded deformation of the lens were determined. The effects were reversible. The sites of inward and outward currents were not altered. Following deformation, the equatorial current, J, increased, and the PD became less negative. The PDJ = 0 remains the same so the ratio of K+ concentrations across the membrane responsible for J is unchanged. Therefore, the decrease in PD is ascribed to an increase in Na+ permeance with a resultant increase in driving force accounting for the increase in J.

The phenomenology of the first panic attack in clinical and community-based samples.

PubMed

Pané-Farré, Christiane A; Stender, Jan P; Fenske, Kristin; Deckert, Jürgen; Reif, Andreas; John, Ulrich; Schmidt, Carsten Oliver; Schulz, Andrea; Lang, Thomas; Alpers, Georg W; Kircher, Tilo; Vossbeck-Elsebusch, Anna N; Grabe, Hans J; Hamm, Alfons O

2014-08-01

The purpose of the study was to contrast first panic attacks (PAs) of patients with panic disorder (PD) with vs. without agoraphobia and to explore differences between first PAs leading to the development of PD and those that remain isolated. Data were drawn from a community survey (N=2259 including 88 isolated PAs and 75 PD cases). An additional sample of 234 PD patients was recruited in a clinical setting. A standardized interview assessed the symptoms of the first PA, context of its occurrence and subsequent coping attempts. Persons who developed PD reported more severe first PAs, more medical service utilization and exposure-limiting coping attempts than those with isolated PAs. The context of the first PA did not differ between PD and isolated PAs. PD with agoraphobia was specifically associated with greater symptom severity and occurrence of first attacks in public. Future research should validate these findings using a longitudinal approach. Copyright © 2014 Elsevier Ltd. All rights reserved.

Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for rasburicase therapy in the context of G6PD deficiency genotype.

PubMed

Relling, M V; McDonagh, E M; Chang, T; Caudle, K E; McLeod, H L; Haidar, C E; Klein, T; Luzzatto, L

2014-08-01

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is associated with development of acute hemolytic anemia (AHA) induced by a number of drugs. We provide guidance as to which G6PD genotypes are associated with G6PD deficiency in males and females. Rasburicase is contraindicated in G6PD-deficient patients due to the risk of AHA and possibly methemoglobinemia. Unless preemptive genotyping has established a positive diagnosis of G6PD deficiency, quantitative enzyme assay remains the mainstay of screening prior to rasburicase use. The purpose of this article is to help interpret the results of clinical G6PD genotype tests so that they can guide the use of rasburicase. Detailed guidelines on other aspects of the use of rasburicase, including analyses of cost-effectiveness, are beyond the scope of this document. Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines are published and updated periodically on https://www.pharmgkb.org/page/cpic to reflect new developments in the field.

PD-1 signalling in CD4+ T cells restrains their clonal expansion to an immunogenic stimulus, but is not critically required for peptide-induced tolerance

PubMed Central

Konkel, Joanne E; Frommer, Friederike; Leech, Melanie D; Yagita, Hideo; Waisman, Ari; Anderton, Stephen M

2010-01-01

The ultimate outcome of T-cell recognition of peptide–major histocompatibility complex (MHC) complexes is determined by the molecular context in which antigen presentation is provided. The paradigm is that, after exposure to peptides presented by steady-state dendritic cells (DCs), inhibitory signals dominate, leading to the deletion and/or functional inactivation of antigen-reactive T cells. This has been utilized in a variety of models providing peptide antigen in soluble form in the absence of adjuvant. A co-inhibitory molecule of considerable current interest is PD-1. Here we show that there is the opportunity for the PD-1/PD-L1 interaction to function in inhibiting the T-cell response during tolerance induction. Using traceable CD4+ T-cell receptor (TCR) transgenic cells, together with a blocking antibody to disrupt PD-1 signalling, we explored the roles of PD-1 in the induction of tolerance versus a productive immune response. Intact PD-1 signalling played a role in limiting the extent of CD4+ T-cell accumulation in response to an immunogenic stimulus. However, PD-1 signalling was not required for either the induction, or the maintenance, of peptide-induced tolerance; a conclusion underlined by successful tolerance induction in TCR transgenic cells genetically deficient for PD-1. These observations contrast with the reported requirement for PD-1 signals in CD8+ T-cell tolerance. PMID:20113370

Anti-PD-1 inhibits Foxp3+ Treg cell conversion and unleashes intratumoural effector T cells thereby enhancing the efficacy of a cancer vaccine in a mouse model.

PubMed

Dyck, Lydia; Wilk, Mieszko M; Raverdeau, Mathilde; Misiak, Alicja; Boon, Louis; Mills, Kingston H G

2016-12-01

The co-inhibitory molecule PD-1 suppresses T cell responses and has been targeted in the treatment of cancer. Here, we examined the role of PD-1 in regulating the balance between regulatory and effector T cells and whether blocking PD-1 could enhance tumour vaccine-induced protective immunity. A significantly higher proportion of tumour-resident T cells expressed PD-1 and Foxp3 compared with T cells in the tumour circulation or draining lymph nodes, and this correlated with a lower frequency of IFN-γ- and TNF-secreting CD8 T cells. Blocking PD-1 with a specific antibody reduced Foxp3 + regulatory T (Treg) cell induction and enhanced proliferation, cytokine production, and tumour killing by CD8 T cells. Treatment of CT26 tumour-bearing mice with anti-PD-1 in combination with a vaccine, comprising heat-shocked irradiated tumour cells and a TLR 7/8 agonist, significantly reduced tumour growth and enhanced survival. Furthermore, surviving mice resisted tumour re-challenge. The rejection of tumours in mice treated with the anti-PD-1 vaccine combination was associated with a reduction in tumour-infiltrating Treg cells and enhancement of IFN-γ-secreting CD8 T cells. Our findings demonstrate that high PD-1 expression correlates with increased tumour-infiltrating Treg cells and reduced effector T cells and that when combined with a potent antigen-adjuvant combination, blocking PD-1 effectively enhances anti-tumour immunity.

Participatory Design in Gerontechnology: A Systematic Literature Review.

PubMed

Merkel, Sebastian; Kucharski, Alexander

2018-05-19

Participatory design (PD) is widely used within gerontechnology but there is no common understanding about which methods are used for what purposes. This review aims to examine what different forms of PD exist in the field of gerontechnology and how these can be categorized. We conducted a systematic literature review covering several databases. The search strategy was based on 3 elements: (1) participatory methods and approaches with (2) older persons aiming at developing (3) technology for older people. Our final review included 26 studies representing a variety of technologies designed/developed and methods/instruments applied. According to the technologies, the publications reviewed can be categorized in 3 groups: Studies that (1) use already existing technology with the aim to find new ways of use; (2) aim at creating new devices; (3) test and/or modify prototypes. The implementation of PD depends on the questions: Why a participatory approach is applied, who is involved as future user(s), when those future users are involved, and how they are incorporated into the innovation process. There are multiple ways, methods, and instruments to integrate users into the innovation process. Which methods should be applied, depends on the context. However, most studies do not evaluate if participatory approaches will lead to a better acceptance and/or use of the co-developed products. Therefore, participatory design should follow a comprehensive strategy, starting with the users' needs and ending with an evaluation if the applied methods have led to better results.

INFLUENCE OF DIETARY SUBSTANCES ON INTESTINAL DRUG METABOLISM AND TRANSPORT

PubMed Central

Won, Christina S.; Oberlies, Nicholas H.; Paine, Mary F.

2011-01-01

Successful delivery of promising new chemical entities via the oral route is rife with challenges, some of which cannot be explained or foreseen during drug development. Further complicating an already multifaceted problem is the obvious, yet often overlooked, effect of dietary substances on drug disposition and response. Some dietary substances, particularly fruit juices, have been shown to inhibit biochemical processes in the intestine, leading to altered pharmacokinetic (PK), and potentially pharmacodynamic (PD), outcomes. Inhibition of intestinal CYP3A-mediated metabolism is the major mechanism by which fruit juices, including grapefruit juice, enhances systemic exposure to new and already marketed drugs. Inhibition of intestinal non-CYP3A enzymes and apically-located transport proteins represent recently identified mechanisms that can alter PK and PD. Several fruit juices have been shown to inhibit these processes in vitro, but some interactions have not translated to the clinic. The lack of in vitro-in vivo concordance is due largely to a lack of rigorous methods to elucidate causative ingredients prior to clinical testing. Identification of specific components and underlying mechanisms is challenging, as dietary substances frequently contain multiple, often unknown, bioactive ingredients that vary in composition and bioactivity. A translational research approach, combining expertise from clinical pharmacologists and natural products chemists, is needed to develop robust models describing PK/PD relationships between a given dietary substance and drug of interest. Validation of these models through well-designed clinical trials would facilitate development of common practice guidelines for managing drug-dietary substance interactions appropriately. PMID:21189136

Composition-Dependent Morphology of Bi- and Trimetallic Phosphides: Construction of Amorphous Pd-Cu-Ni-P Nanoparticles as a Selective and Versatile Catalyst.

PubMed

Zhao, Ming; Ji, Yuan; Wang, Mengyue; Zhong, Ning; Kang, Zinan; Asao, Naoki; Jiang, Wen-Jie; Chen, Qiang

2017-10-11

Amorphous materials have been widely researched in heterogeneous catalysis and for next-generation batteries. However, the well-defined production of high-quality (e.g., monodisperse and high surface area) amorphous alloy nanomaterials has rarely been reported. In this work, we investigated the correlations among the composition, morphology, and catalysis of various Pd-M-P nanoparticles (NPs) (M = Cu or Ni), which indicated that less Cu (≤20 atom %) was necessary for the formation of an amorphous morphology. The amorphous Pd-Cu-Ni-P NPs were fabricated with a controllable size and characterized carefully, which show excellent selective catalysis in the semihydrogenation of alkynes, hydrogenation of quinoline, and oxidation of primary alcohols. The uniqueness of the catalytic performance was confirmed by control experiments with monometallic Pd, amorphous Pd-Ni-P NPs, crystalline Pd-Cu-P NPs, and a crystalline counterpart of Pd-Cu-Ni-P catalyst. The catalytic selectivity likely arose from improved Pd-M (M = Cu or Ni) synergistic effects in the amorphous phase and the electron deficiency of Pd. The model reactions proceeded under H 2 or O 2 gas without any additives, bases, or metal oxide supports, and the catalyst could be reused several times. This report is expected to shed light on the design of amorphous alloy nanomaterials as green and inexpensive catalysts for atom-economic and selective reactions.

Deletion of PdMit1, a homolog of yeast Csg1, affects growth and Ca(2+) sensitivity of the fungus Penicillium digitatum, but does not alter virulence.

PubMed

Zhu, Congyi; Wang, Weili; Wang, Mingshuang; Ruan, Ruoxin; Sun, Xuepeng; He, Meixian; Mao, Cungui; Li, Hongye

2015-04-01

GDP-mannose:inositol-phosphorylceramide (MIPC) and its derivatives are important for Ca(2+) sensitization of Saccharomyces cerevisiae and for the virulence of Candida albicans, but its role in the virulence of plant fungal pathogens remains unclear. In this study, we report the identification and functional characterization of PdMit1, the gene encoding MIPC synthase in Penicillium digitatum, one of the most important pathogens of postharvest citrus fruits. To understand the function of PdMit1, a PdMit1 deletion mutant was generated. Compared to its wild-type control, the PdMit1 deletion mutant exhibited slow radial growth, decreased conidia production and delayed conidial germination, suggesting that PdMit1 is important for the growth of mycelium, sporulation and conidial germination. The PdMit1 deletion mutant also showed hypersensitivity to Ca(2+). Treatment with 250 mmol/l Ca(2+) induced vacuole fusion in the wild-type strain, but not in the PdMit1 deletion mutant. Treatment with 250mmol/lCaCl2 upregulated three Ca(2+)-ATPase genes in the wild-type strain, and this was significantly inhibited in the PdMit1 deletion mutant. These results suggest that PdMit1 may have a role in regulating vacuole fusion and expression of Ca(2+)-ATPase genes by controlling biosynthesis of MIPC, and thereby imparts P. digitatum Ca(2+) tolerance. However, we found that PdMit1 is dispensable for virulence of P. digitatum. Copyright © 2015 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Cutaneous adverse events (AEs) of anti-programmed cell death (PD)-1 therapy in patients with metastatic melanoma: A single-institution cohort.

PubMed

Hwang, Shelley Ji Eun; Carlos, Giuliana; Wakade, Deepal; Byth, Karen; Kong, Benjamin Y; Chou, Shaun; Carlino, Matteo S; Kefford, Richard; Fernandez-Penas, Pablo

2016-03-01

Anti-programmed cell death (PD)-1 therapy is emerging as the backbone of new standard of care immunotherapy for metastatic melanoma. Immune-related cutaneous events are observed in these patients. We sought to describe cutaneous adverse events observed in patients with metastatic melanoma on anti-PD-1 therapy. We reviewed the clinical and histologic information of all patients treated with single-agent anti-PD-1 therapy for metastatic melanoma at Westmead Hospital, Sydney, Australia, from May 2012 to February 2015. Of the 82 patients included in the study, 34 had dermatology assessments. Forty (49%) developed a form of anti-PD-1-associated cutaneous adverse events. In all, 17% developed lichenoid reactions and eczema, and 15% developed vitiligo. An estimated 25% of patients were expected to develop their first lichenoid reactions within 8.3 months, and eczema and vitiligo within 10.3 months of therapy. These adverse events tend to appear together in patients on anti-PD-1 therapy. The study was from a single center and clinical information was reviewed retrospectively in patients not referred to dermatology. Anti-PD-1 therapy is associated with the development of immune-related cutaneous events. Lichenoid reactions, eczema, and vitiligo are the 3 most prevalent lesions observed in our population. There is a tendency for lichenoid reactions and eczema to occur with vitiligo. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Alterations in bioenergetic function induced by Parkinson's disease mimetic compounds: Lack of correlation with superoxide generation

PubMed Central

Dranka, Brian P.; Zielonka, Jacek; Kanthasamy, Anumantha G.; Kalyanaraman, Balaraman

2012-01-01

In vitro and in vivo models of Parkinson's disease (PD) suggest that increased oxidant production leads to mitochondrial dysfunction in dopaminergic neurons and subsequent cell death. However, it remains unclear if cell death in these models is caused by inhibition of mitochondrial function or oxidant production. The objective of the present study was to determine the relationship between mitochondrial dysfunction and oxidant production in response to multiple PD neurotoxicant mimetics. MPP+ caused a dose-dependent decrease in the basal oxygen consumption rate (OCR) in dopaminergic N27 cells, indicating a loss of mitochondrial function. In parallel, we found that MPP+ only modestly increased oxidation of hydroethidine as a diagnostic marker of superoxide production in these cells. Similar results were found using rotenone as a mitochondrial inhibitor, or 6-hydroxydopamine as a mechanistically distinct PD neurotoxicant, but not with exposure to paraquat. Additionally, the Extracellular Acidification Rate, used as a marker of glycolysis, was stimulated to compensate for OCR inhibition after exposure to MPP+, rotenone, or 6-hydroxydopamine, but not paraquat. Together these data indicate that MPP+, rotenone and 6-hydroxydopamine dramatically shift bioenergetic function away from the mitochondria and towards glycolysis in N27 cells. PMID:22708893

Computer simulations for bioequivalence trials: Selection of analyte in BCS class II and IV drugs with first-pass metabolism, two metabolic pathways and intestinal efflux transporter.

PubMed

Mangas-Sanjuan, Victor; Navarro-Fontestad, Carmen; García-Arieta, Alfredo; Trocóniz, Iñaki F; Bermejo, Marival

2018-05-30

A semi-physiological two compartment pharmacokinetic model with two active metabolites (primary (PM) and secondary metabolites (SM)) with saturable and non-saturable pre-systemic efflux transporter, intestinal and hepatic metabolism has been developed. The aim of this work is to explore in several scenarios which analyte (parent drug or any of the metabolites) is the most sensitive to changes in drug product performance (i.e. differences in in vivo dissolution) and to make recommendations based on the simulations outcome. A total of 128 scenarios (2 Biopharmaceutics Classification System (BCS) drug types, 2 levels of K M Pgp , in 4 metabolic scenarios at 2 dose levels in 4 quality levels of the drug product) were simulated for BCS class II and IV drugs. Monte Carlo simulations of all bioequivalence studies were performed in NONMEM 7.3. Results showed the parent drug (PD) was the most sensitive analyte for bioequivalence trials in all the studied scenarios. PM and SM revealed less or the same sensitivity to detect differences in pharmaceutical quality as the PD. Another relevant result is that mean point estimate of C max and AUC methodology from Monte Carlo simulations allows to select more accurately the most sensitive analyte compared to the criterion on the percentage of failed or successful BE studies, even for metabolites which frequently show greater variability than PD. Copyright © 2018 Elsevier B.V. All rights reserved.

The challenges of heat sterilization of peritoneal dialysis solutions: is there an alternative?

PubMed

Hanrahan, Conor T; Himmele, Rainer; Diaz-Buxo, Jose A

2012-01-01

Peritoneal dialysis (PD) solutions are currently sterilized in an autoclave using high-temperature saturated steam. Although thermal methods are an effective means of sterilization, the heating of PD solutions results in the formation of toxic glucose degradation products (GDPs). Here, we review basic concepts in the sterilization of PD solutions and discuss possible alternatives to steam sterilization, including filtration, ohmic heat, ionizing radiation, and pulsed ultraviolet light. Although the latter methods have several advantages, many also have prohibitive limitations or have not been adequately studied for use on PD solutions. Thus, in the absence of suitable alternatives, conventional heat sterilization, in combination with low-GDP manufacturing practices, remains the best option at the present time.

Prenatal exposure to lambda-cyhalothrin alters brain dopaminergic signaling in developing rats.

PubMed

Dhuriya, Yogesh K; Srivastava, Pranay; Shukla, Rajendra K; Gupta, Richa; Singh, Dhirendra; Parmar, Devendra; Pant, Aditya B; Khanna, Vinay K

2017-07-01

The present study is focused to decipher the molecular mechanisms associated with dopaminergic alterations in corpus striatum of developing rats exposed prenatally to lambda-cyhalothrin (LCT), a new generation type II synthetic pyrethroid. There was no significant change in the mRNA and protein expression of DA-D1 receptors at any of the doses of LCT (0.5, 1 and 3mg/kg body weight) in corpus striatum of developing rats exposed prenatally to LCT on PD22 and PD45. Prenatal exposure to LCT (1 and 3mg/kg body weight) resulted to decrease the levels of mRNA and protein of DA-D2 receptors in corpus stratum of developing rats on PD22 as compared to controls. Decrease in the binding of 3H-Spiperone in corpus striatum, known to label DA-D2 receptors was also distinct in developing rats on PD22. These rats also exhibited decrease in the expression of proteins - TH, DAT and VMAT2 involved in pre-dopaminergic signaling. Further, decrease in the expression of DARPP-32 and pCREB associated with increased expression of PP1α was evident in developing rats on PD22 as compared to controls. Interestingly, a trend of recovery in the expression of these proteins was observed in developing rats exposed to LCT at moderate dose (1.0mg/kg body weight) while alteration in the expression of these proteins continued to persist in those exposed at high dose (3.0mg/kg body weight) on PD45 as compared to respective controls. No significant change in the expression of any of these proteins was observed in corpus striatum of developing rats prenatally exposed to LCT at low dose (0.5mg/kg body weight) on PD22 and PD45 as compared to respective controls. The results provide interesting evidence that alterations in dopaminergic signaling on LCT exposure are due to selective changes in DA-D2 receptors in corpus striatum of developing rats. Further, these changes could be attributed to impairment in spontaneous motor activity on LCT exposure in developing rats. Copyright © 2017 Elsevier B.V. All rights reserved.

Impulse control disorders in Parkinson's disease: the role of personality and cognitive status.

PubMed

Poletti, Michele; Bonuccelli, Ubaldo

2012-11-01

This study reviews empirical findings on two debated issues related to the phenomenon of impulse control disorders (ICD) in patients with Parkinson's disease (PD) treated with dopamine agonists: the role of "premorbid" or "baseline" personality traits and the role of cognitive status. A review of both these issues may help clinicians to understand why only some PD patients, when treated with dopamine agonists, develop an ICD: besides the treatment, which other neuropsychiatric characteristics represent a risk factor to develop an ICD? A literature review was performed on studies of ICD in PD patients, in electronic databases ISI Web of Knowledge, Medline and PsychInfo, conducted in January 2011. In the general population, impulsivity, depression and difficulties with executive functions, especially of inhibitory control, are factors associated with ICD development. As regards cognitive functions, PD patients present executive difficulties, and patients with ICD present more difficulties in comparison to patients without ICD. As regards personality characteristics, PD patients present a trait of negative affect, which could predispose them to affective disorders and could represent an affective risk factor for the development of ICD; as regards impulsivity, preliminary findings support the hypothesis that premorbid "baseline" levels may moderate the decrease of impulsivity because of the progressive dopaminergic deficit in PD patients and therefore also moderate the development of ICD. Longitudinal psychometric and cognitive studies, following PD patients since the clinical diagnosis and during dopaminergic treatment, are needed to confirm the role of personality traits and cognitive status on ICD development in this clinical population.

XAS analysis of iron and palladium bonded to a polysaccharide produced anaerobically by a strain of Klebsiella oxytoca.

PubMed

Arčon, Iztok; Paganelli, Stefano; Piccolo, Oreste; Gallo, Michele; Vogel-Mikuš, Katarina; Baldi, Franco

2015-09-01

Klebsiella oxytoca BAS-10 ferments citrate to acetic acid and CO2, and secretes a specific exopolysaccharide (EPS), which is able to bind different metallic species. These biomaterials may be used for different biotechnological purposes, including applications as innovative green biogenerated catalysts. In production of biogenerated Pd species, the Fe(III) as ferric citrate is added to anaerobic culture of K. oxytoca BAS-10, in the presence of palladium species, to increase the EPS secretion and improve Pd-EPS yield. In this process, bi-metallic (FePd-EPS) biomaterials were produced for the first time. The morphology of bi-metallic EPS, and the chemical state of the two metals in the FePd-EPS, are investigated by transmission electron microscopy, Fourier transform infra-red spectroscopy, micro-X-ray fluorescence, and X-ray absorption spectroscopy methods (XANES and EXAFS), and compared with mono-metallic Pd-EPS and Fe-EPS complexes. Iron in FePd-EPS is in the mineralized form of iron oxides/hydroxides, predominantly in the form of Fe(3+), with a small amount of Fe(2+) in the structure, most probably a mixture of different nano-crystalline iron oxides and hydroxides, as in mono-metallic Fe-EPS. Palladium is found as Pd(0) in the form of metallic nanoparticles with face-centred cubic structure in both bi-metallic (FePd-EPS) and mono-metallic (Pd-EPS) species. In bi-metallic species, Pd and Fe nanoparticles agglomerate in larger clusters, but they remain spatially separated. The catalytic ability of bi-metallic species (FePd-EPS) in a hydrodechlorination reaction is improved in comparison with mono-metallic Pd-EPS.

Supporting Change in Teacher Practice: Examining Shifts of Teachers' Professional Development Preferences and Needs for Technology Integration

ERIC Educational Resources Information Center

Liao, Yin-Chan; Ottenbreit-Leftwich, Anne; Karlin, Michael; Glazewski, Krista; Brush, Thomas

2017-01-01

Studies have shown that when K-12 school districts implement a new technology initiative, it is not always accompanied by effective teacher professional development (PD). Many teachers have indicated that effective technology PD experiences should incorporate their individual PD needs. The authors surveyed technology-using K-12 teachers at two…

Teaching Argumentative Writing to Teachers and Students: Effects of Professional Development

ERIC Educational Resources Information Center

Howell, Emily; Hunt-Barron, Sarah; Kaminski, Rebecca; Sanders, Rachel

2018-01-01

This multiple-case study design with embedded units of analysis examined a two-year professional development (PD) program in which two rural districts received at least 90 hours of PD. This PD was provided through an Investing in Innovation (i3) grant that the United States Department of Education awarded to the National Writing Project. Two of…

A Design-Based Research Approach to Improving Professional Development and Teacher Knowledge: The Case of the Smithsonian Learning Lab

ERIC Educational Resources Information Center

Zinger, Doron; Naranjo, Ashley; Amador, Isabel; Gilbertson, Nicole; Warschauer, Mark

2017-01-01

Incorporating technology in classrooms to promote student learning is an ongoing instructional challenge. Teacher professional development (PD) is a central component of teacher education to support student use of technology and can improve student learning, but PD has had mixed results. In this study, researchers investigated a PD program…

Hands-On Professional Development: Middle School Teachers' Experiences with a Curriculum Intervention Research Project

ERIC Educational Resources Information Center

Green, Jennifer D.; Gonzalez, Eileen M.; López-Velásquez, Angela M.; Howard, Elizabeth R.

2013-01-01

The importance of professional development (PD) is clearly understood; however, little is known about how the most effective PD influences teachers' learning and how teachers perceive PD that goes beyond the typical two-hour session on an aspect of instruction. In this article, the authors present the response of a group of middle school teachers…

You Seize What Pops Up: A Qualitative Investigation of the Core Features of School-Based Agricultural Education Professional Development

ERIC Educational Resources Information Center

Easterly, R.G., III.; Myers, Brian E.

2017-01-01

Desimone's core features of professional development (PD) guides the PD for teachers. The purpose of this study was to examine the PD practice of School-Based Agricultural Education (SBAE) teachers in the enthusiastic and growing career stage. Semi-structured telephone interviews were conducted with five teachers from five different states. The…

A review of acute and chronic peritoneal dialysis in developing countries

PubMed Central

Abraham, Georgi; Varughese, Santosh; Mathew, Milly; Vijayan, Madhusudan

2015-01-01

Various modalities of renal replacement therapy (RRT) are available for the management of acute kidney injury (AKI) and end-stage renal disease (ESRD). While developed countries mainly use hemodialysis as a form of RRT, peritoneal dialysis (PD) has been increasingly utilized in developing countries. Chronic PD offers various benefits including lower cost, home-based therapy, single access, less requirement of highly trained personnel and major infrastructure, higher number of patients under a single nephrologist with probably improved quality of life and freedom of activities. PD has been found to be lifesaving in the management of AKI in patients in developing countries where facilities for other forms of RRT are not readily available. The International Society of Peritoneal Dialysis has published guidelines regarding the use of PD in AKI, which has helped in ensuring uniformity. PD has also been successfully used in certain special situations of AKI due to snake bite, malaria, febrile illness, following cardiac surgery and in poisoning. Hemodialysis is the most common form of RRT used in ESRD worldwide, but some countries have begun to adopt a ‘PD first’ policy to reduce healthcare costs of RRT and ensure that it reaches the underserved population. PMID:26034593

The neurobiology of impulse control disorders in Parkinson's disease: from neurotransmitters to neural networks.

PubMed

Vriend, Chris

2018-01-30

Impulse control disorders (ICD) are common neuropsychiatric disorders that can arise in Parkinson's disease (PD) patients after commencing dopamine replacement therapy. Approximately 15% of all patients develop these disorders and many more exhibit subclinical symptoms of impulsivity. ICD is thought to develop due to an interaction between the use of dopaminergic medication and an as yet unknown neurobiological vulnerability that either pre-existed before PD onset (possibly genetic) or is associated with neural alterations due to the PD pathology. This review discusses genes, neurotransmitters and neural networks that have been implicated in the pathophysiology of ICD in PD. Although dopamine and the related reward system have been the main focus of research, recently, studies have started to look beyond those systems to find new clues to the neurobiological underpinnings of ICD and come up with possible new targets for treatment. Studies on the whole-brain connectome to investigate the global alterations due to ICD development are currently lacking. In addition, there is a dire need for longitudinal studies that are able to disentangle the contributions of individual (genetic) traits and secondary effects of the PD pathology and chronic dopamine replacement therapy to the development of ICD in PD.

Seeing is believing: anti-PD-1/PD-L1 monoclonal antibodies in action for checkpoint blockade tumor immunotherapy

PubMed Central

Tan, Shuguang; Zhang, Catherine W-H; Gao, George F

2016-01-01

Structural immunology, focusing on structures of host immune related molecules, enables the immunologists to see what the molecules look like, and more importantly, how they work together. Antibody-based PD-1/PD-L1 blockade therapy has achieved brilliant successes in clinical applications. The recent breakthrough of the complex structures of checkpoint blockade antibodies with their counterparts, pembrolizumab with PD-1 and avelumab with PD-L1, have made it clear how these monoclonal antibodies compete the binding of PD-1/PD-L1 and function to blockade the receptor-ligand interaction. Herein, we summarize the structural findings of these two reports and look into the future for how this information would facilitate the development of more efficient PD-1/PD-L1 targeting antibodies, small molecule drugs, and other protein or non-protein inhibitors. PMID:29263905

Peritoneal Dialysis in Asia.

PubMed

Kwong, Vickie Wai-Ki; Li, Philip Kam-Tao

2015-12-01

There is a growing demand of dialysis in Asia for end-stage renal failure patients. Diabetes mellitus is the leading cause of end-stage renal failure in many countries in Asia. The growth of peritoneal dialysis (PD) in Asia is significant and seeing a good trend. With the enhanced practices of PD, the quality of care in PD in Asia is also improved. Overall, PD and hemodialysis (HD) are comparable in clinical outcome. There is a global trend in the reduction of peritonitis rates and Asian countries also witness such improvement. The socio-economic benefits of PD for end-stage renal failure patients in both urban and rural areas in the developed and developing regions of Asia are an important consideration. This can help to reduce the financial burden of renal failure in addressing the growing demand of patients on dialysis. Initiatives should be considered to further drive down the cost of PD in Asia. Growing demand for dialysis by an increasing number of end-stage renal failure patients requires the use of a cost-effective quality dialysis modality. PD is found to be comparable to HD in outcome and quality. In most countries in Asia, PD should be more cost-effective than HD. A 'PD-first' or a 'PD as first considered therapy' policy can be an overall strategy in many countries in Asia in managing renal failure patients, taking the examples of Hong Kong and Thailand. (1) PD is cheaper than HD and provides a better quality of life worldwide, but its prevalence is significantly lower than that of HD in all countries, with the exception of Hong Kong. Allowing reimbursement of PD but not HD has permitted to increase the use of PD over HD in many Asian countries like Hong Kong, Vietnam, Taiwan, Thailand, as well as in New Zealand and Australia over the last years. In the Western world, however, HD is still promoted, and the proportion of patients treated with PD decreases. Japan remains an exception in Asia where PD penetration is very low. Lack of adequate education of practitioners and information of patients might as well be reasons for the low penetration of PD in both the East and West. (2) Patient survival of PD varies between and within countries but is globally similar to HD. (3) Peritonitis remains the main cause of morbidity in PD patients. South Asian countries face specific issues such as high tuberculosis and mycobacterial infections, which are rare in developed Asian and Western countries. The infection rate is affected by climatic and socio-economic factors and is higher in hot, humid and rural areas. (4) Nevertheless, the promotion of a PD-first policy might be beneficial particularly for remote populations in emerging countries where the end-stage renal disease rate is increasing dramatically.

Protectin D1 reduces concanavalin A-induced liver injury by inhibiting NF-κB-mediated CX3CL1/CX3CR1 axis and NLR family, pyrin domain containing 3 inflammasome activation.

PubMed

Ren, Jun; Meng, Shanshan; Yan, Bingdi; Yu, Jinyan; Liu, Jing

2016-04-01

Protectin D1 (PD1) is a bioactive product generated from docosahexaenoic acid, which may exert anti-inflammatory effects in various inflammatory diseases. However, the underlying molecular mechanism of its anti‑inflammatory activity on concanavalin A (Con A)-induced hepatitis remains unknown. The aim of the present study was to investigate the protective effects of PD1 against Con A‑induced liver injury and the underlying mechanisms via intravenous injection of PD1 prior to Con A administration. C57BL/6 mice were randomly divided into four experimental groups as follows: Control group, Con A group (30 mg/kg), 20 µg/kg PD1 + Con A (30 mg/kg) group and 10 µg/kg PD1 + Con A (30 mg/kg) group. PD1 pretreatment was demonstrated to significantly inhibit elevated plasma aminotransferase levels, high mobility group box 1 and liver necrosis, which were observed in Con A‑induced hepatitis. Furthermore, compared with the Con A group, PD1 pretreatment prevented the production of pro‑inflammatory cytokines, including tumor necrosis factor‑α, interferon‑γ and interleukin‑2, ‑1β and ‑6. In addition, pretreatment with PD1 markedly downregulated cluster of differentiation (CD)4+, CD8+ and natural killer T (NKT) cell infiltration in the liver. PD1 pretreatment was observed to suppress the messenger RNA and protein expression levels of NLR family, pyrin domain containing 3 and Toll‑like receptor (TLR) 4 in liver tissue samples. Further data indicated that PD1 pretreatment inhibited the activation of the nuclear factor κ‑light‑chain‑enhancer of activated B cells (NF‑κB) signaling pathway and chemokine (C‑X3‑C motif) ligand 1 (CX3CL1)/chemokine (C-X3-C motif) receptor 1 (CX3CR1) axis by preventing phosphorylation of nuclear factor of κ light polypeptide gene enhancer in B-cells inhibitor, α and NF‑κB in Con A‑induced liver injury. Therefore, these results suggest that PD1 administration protects mice against Con A‑induced liver injury via inhibition of various inflammatory cytokines and, in part, by suppressing CD4+, CD8+ and NKT cell infiltration in the liver and the NF‑κB‑activated CX3CL1/CX3CR1 signaling pathway. The beneficial effect of PD1 may be associated with the inhibition of TLR4 expression and the downregulation of NF‑κB activation. In conclusion, PD1 appears to be a potential natural bioproduct, and provide a promising strategy, for the prevention of hepatic injury in patients with chronic or acute liver disease.

Spectroscopic and first-principles calculation studies of the chemical forms of palladium ion in nitric acid solution for development of disposal of high-level radioactive nuclear wastes

NASA Astrophysics Data System (ADS)

Watanabe, Shinta; Sato, Toshikazu; Yoshida, Tomoko; Nakaya, Masato; Yoshino, Masahito; Nagasaki, Takanori; Inaba, Yusuke; Takeshita, Kenji; Onoe, Jun

2018-04-01

We have investigated the chemical forms of palladium (Pd) ion in nitric acid solution, using XAFS/UV-vis spectroscopic and first-principles methods in order to develop the disposal of high-level radioactive nuclear liquid wastes (HLLW: radioactive metal ions in 2 M nitric acid solution). The results of theoretical calculations and XAFS/UV-vis spectroscopy indicate that Pd is a divalent ion and forms a square-planar complex structure coordinated with four nitrate ions, [Pd(NO3)4]2-, in nitric acid solution. This complex structure is also thermodynamically predicted to be most stable among complexes [Pd(H2O)x(NO3)4-x]x-2 (x = 0-4). Since the overall feature of UV-vis spectra of the Pd complex was independent of nitric acid concentration in the range 1-6 M, the structure of the Pd complex remains unchanged in this range. Furthermore, we examined the influence of γ-ray radiation on the [Pd(NO3)4]2- complex, using UV-vis spectroscopy, and found that UV-vis spectra seemed not to be changed even after 1.0 MGy irradiation. This implies that the Pd complex structure will be still stable in actual HLLW. These findings obtained above are useful information to develop the vitrification processes for disposal of HLLW.

Electrical and NO2 sensing characteristics of Pd/ZnO nanoparticles based Schottky diode at room temperature

NASA Astrophysics Data System (ADS)

Chandra, Lalit; Sahu, Praveen Kumar; Dwivedi, R.; Mishra, V. N.

2017-12-01

The present work deals with Pd/ZnO nanoparticles based Schottky diode for detection of NO2 at room temperature (298 K). To fabricate Pd/ZnO Schottky diode, zinc oxide (ZnO) nanoparticles (NPs) based film was developed on glass substrate using sol-gel spin coating process. Subsequently; Pd was deposited on ZnO using thermal evaporation technique. The structural properties of developed ZnO film were studied using energy dispersive x-ray spectroscopy (EDS), x-ray diffraction (XRD) and field emission scanning electron microscopy (FE-SEM). The particles size of the developed film was in range of ~25 to ~110 nm. The response of fabricated Pd/ZnO Schottky diode was studied upon exposure to NO2 in terms of change in I-V characteristics. The magnitude of barrier height and ideality factor has been evaluated with concentration of NO2 ranging from 10 to 50 ppm. The developed sensor has good sensitivity of ~45.2%, with fast response and recovery time; 67 s and 250 s respectively for 50 ppm concentration of NO2 with excellent repeatability. The obtained results have been explained in terms of surface and subsurface adsorption of NO2 on Pd, subsequently dissociation of NO2 and its diffusion, which creates dipole moment at the Pd/ZnO interface.

Design of Pd/PANI/Pd sandwich-structured nanotube array catalysts with special shape effects and synergistic effects for ethanol electrooxidation.

PubMed

Wang, An-Liang; Xu, Han; Feng, Jin-Xian; Ding, Liang-Xin; Tong, Ye-Xiang; Li, Gao-Ren

2013-07-24

Low cost, high activity, and long-term durability are the main requirements for commercializing fuel cell electrocatalysts. Despite tremendous efforts, developing non-Pt anode electrocatalysts with high activity and long-term durability at low cost remains a significant technical challenge. Here we report a new type of hybrid Pd/PANI/Pd sandwich-structured nanotube array (SNTA) to exploit shape effects and synergistic effects of Pd-PANI composites for the oxidation of small organic molecules for direct alcohol fuel cells. These synthesized Pd/PANI/Pd SNTAs exhibit significantly improved electrocatalytic activity and durability compared with Pd NTAs and commercial Pd/C catalysts. The unique SNTAs provide fast transport and short diffusion paths for electroactive species and high utilization rate of catalysts. Besides the merits of nanotube arrays, the improved electrocatalytic activity and durability are especially attributed to the special Pd/PANI/Pd sandwich-like nanostructures, which results in electron delocalization between Pd d orbitals and PANI π-conjugated ligands and in electron transfer from Pd to PANI.

Supporting palladium metal on gold nanoparticles improves its catalysis for nitrite reduction

NASA Astrophysics Data System (ADS)

Qian, Huifeng; Zhao, Zhun; Velazquez, Juan C.; Pretzer, Lori A.; Heck, Kimberly N.; Wong, Michael S.

2013-12-01

Nitrate (NO3-) and nitrite (NO2-) anions are often found in groundwater and surface water as contaminants globally, especially in agricultural areas due to nitrate-rich fertilizer use. One popular approach to studying the removal of nitrite/nitrate from water has been their degradation to dinitrogen via Pd-based reduction catalysis. However, little progress has been made towards understanding how the catalyst structure can improve activity. Focusing on the catalytic reduction of nitrite in this study, we report that Au NPs supporting Pd metal ("Pd-on-Au NPs") show catalytic activity that varies with volcano-shape dependence on Pd surface coverage. At room temperature, in CO2-buffered water, and under H2 headspace, the NPs were maximally active at a Pd surface coverage of 80%, with a first-order rate constant (kcat = 576 L gPd-1 min-1) that was 15x and 7.5x higher than monometallic Pd NPs (~4 nm; 40 L gPd-1 min-1) and Pd/Al2O3 (1 wt% Pd; 76 L gPd-1 min-1), respectively. Accounting only for surface Pd atoms, these NPs (576 L gsurface-Pd-1 min-1) were 3.6x and 1.6x higher than monometallic Pd NPs (160 L gsurface-Pd-1 min-1) and Pd/Al2O3 (361 L gsurface-Pd-1 min-1). These NPs retained ~98% of catalytic activity at a chloride concentration of 1 mM, whereas Pd/Al2O3 lost ~50%. The Pd-on-Au nanostructure is a promising approach to improve the catalytic reduction process for nitrite and, with further development, also for nitrate anions.Nitrate (NO3-) and nitrite (NO2-) anions are often found in groundwater and surface water as contaminants globally, especially in agricultural areas due to nitrate-rich fertilizer use. One popular approach to studying the removal of nitrite/nitrate from water has been their degradation to dinitrogen via Pd-based reduction catalysis. However, little progress has been made towards understanding how the catalyst structure can improve activity. Focusing on the catalytic reduction of nitrite in this study, we report that Au NPs supporting Pd metal ("Pd-on-Au NPs") show catalytic activity that varies with volcano-shape dependence on Pd surface coverage. At room temperature, in CO2-buffered water, and under H2 headspace, the NPs were maximally active at a Pd surface coverage of 80%, with a first-order rate constant (kcat = 576 L gPd-1 min-1) that was 15x and 7.5x higher than monometallic Pd NPs (~4 nm; 40 L gPd-1 min-1) and Pd/Al2O3 (1 wt% Pd; 76 L gPd-1 min-1), respectively. Accounting only for surface Pd atoms, these NPs (576 L gsurface-Pd-1 min-1) were 3.6x and 1.6x higher than monometallic Pd NPs (160 L gsurface-Pd-1 min-1) and Pd/Al2O3 (361 L gsurface-Pd-1 min-1). These NPs retained ~98% of catalytic activity at a chloride concentration of 1 mM, whereas Pd/Al2O3 lost ~50%. The Pd-on-Au nanostructure is a promising approach to improve the catalytic reduction process for nitrite and, with further development, also for nitrate anions. Electronic supplementary information (ESI) available. See DOI: 10.1039/c3nr04540d

Teacher Perceptions of Their Curricular and Pedagogical Shifts: Outcomes of a Project-Based Model of Teacher Professional Development in the Next Generation Science Standards

PubMed Central

Shernoff, David J.; Sinha, Suparna; Bressler, Denise M.; Schultz, Dawna

2017-01-01

In this study, we conducted a model of teacher professional development (PD) on the alignment of middle and high school curricula and instruction to the Next Generation Science Standards (NGSSs), and evaluated the impact of the PD on teacher participants’ development. The PD model included a 4-day summer academy emphasizing project-based learning (PBL) in the designing of NGSS-aligned curricula and instruction, as well as monthly follow-up Professional Learning Community meetings throughout the year providing numerous opportunities for teachers to develop and implement lesson plans, share results of lesson writing and implementation (successes and challenges), provide mutual feedback, and refine curricula and assessments. Following the summer academy, six female teachers were interviewed about their current conceptualizations of NGSS, the extent of curricular shifts made that are required by NGSS, their self-perceptions regarding their level of accomplishment in curriculum writing, and the benefits of the PD in reaching their goals related to NGSS. Interviews were supplemented with an analysis of lesson plans written while participating in the PD program. The interviewed teachers suggested that they had made important conceptual and pedagogical shifts required by NGSS as they participated in the PD, and also noted a variety of challenges as they made this shift. While all teachers were relative novices at NGSS curriculum writing before the PD, most of the teachers interviewed felt that they had achieved the status of an “accomplished novice” following the summer academy. An analysis of their written lessons suggested a great range in the extent to which teachers effectively applied their understanding of NGSS to write lessons aligned to NGSS. Interviewed teachers believed that the PD model was helpful to their development as science teachers, and all reported that there were no aspects of the PD that were not helpful. Even though most teachers obtained a basic understanding and conceptualization of NGSS and PBL, their application of this understanding in their curriculum writing varied. The present study may help to inform future efforts to support teachers to align curricula and instruction to NGSS through teacher PD. PMID:28670294

Teacher Perceptions of Their Curricular and Pedagogical Shifts: Outcomes of a Project-Based Model of Teacher Professional Development in the Next Generation Science Standards.

PubMed

Shernoff, David J; Sinha, Suparna; Bressler, Denise M; Schultz, Dawna

2017-01-01

In this study, we conducted a model of teacher professional development (PD) on the alignment of middle and high school curricula and instruction to the Next Generation Science Standards (NGSSs), and evaluated the impact of the PD on teacher participants' development. The PD model included a 4-day summer academy emphasizing project-based learning (PBL) in the designing of NGSS-aligned curricula and instruction, as well as monthly follow-up Professional Learning Community meetings throughout the year providing numerous opportunities for teachers to develop and implement lesson plans, share results of lesson writing and implementation (successes and challenges), provide mutual feedback, and refine curricula and assessments. Following the summer academy, six female teachers were interviewed about their current conceptualizations of NGSS, the extent of curricular shifts made that are required by NGSS, their self-perceptions regarding their level of accomplishment in curriculum writing, and the benefits of the PD in reaching their goals related to NGSS. Interviews were supplemented with an analysis of lesson plans written while participating in the PD program. The interviewed teachers suggested that they had made important conceptual and pedagogical shifts required by NGSS as they participated in the PD, and also noted a variety of challenges as they made this shift. While all teachers were relative novices at NGSS curriculum writing before the PD, most of the teachers interviewed felt that they had achieved the status of an "accomplished novice" following the summer academy. An analysis of their written lessons suggested a great range in the extent to which teachers effectively applied their understanding of NGSS to write lessons aligned to NGSS. Interviewed teachers believed that the PD model was helpful to their development as science teachers, and all reported that there were no aspects of the PD that were not helpful. Even though most teachers obtained a basic understanding and conceptualization of NGSS and PBL, their application of this understanding in their curriculum writing varied. The present study may help to inform future efforts to support teachers to align curricula and instruction to NGSS through teacher PD.

Association Between Gastroesophageal Reflux Disease After Pneumatic Balloon Dilatation and Clinical Course in Patients With Achalasia

PubMed Central

Min, Yang Won; Lee, Jin Hee; Min, Byung-Hoon; Lee, Jun Haeng; Kim, Jae J; Rhee, Poong-Lyul

2014-01-01

Background/Aims The occurrence of gastroesophageal reflux disease (GERD) is known to be associated with lower post-treatment lower esophageal sphincter pressure in patients with achalasia. This study aimed to elucidate whether GERD after pneumatic balloon dilatation (PD) has a prognostic role and to investigate how the clinical course of GERD is. Methods A total of 79 consecutive patients who were first diagnosed with primary achalasia and underwent PD as an initial treatment were included in this retrospective study. Single PD was performed using a 3.0 cm balloon. The patients were divided into two groups: 1) who developed GERD after PD (GERD group) and 2) who did not develop GERD after PD (non-GERD group). GERD was defined as pathological acid exposure, reflux esophagitis or typical reflux symptoms. Results Twenty one patients (26.6%) developed GERD after PD during follow-up. There were no significant differences between the two groups in demographic or clinical factors including pre- and post-treatment manometric results. All patients in GERD group were well responsive to maintenance proton pump inhibitor therapy including on demand therapy or did not require maintenance. During a median follow-up of 17.8 months (interquartile range, 7.1–42.7 months), achalasia recurred in 15 patients (19.0%). However, the incidence of recurrence did not differ according to the occurrence of GERD after PD. Conclusions GERD often occurs after even a single PD for achalasia. However, GERD after PD is well responsive to PPI therapy. Our data suggest that GERD after PD during follow-up does not appear to have a prognostic role. PMID:24840373

Expression of PD-L1 and other immunotherapeutic targets in thymic epithelial tumors

PubMed Central

Steele, Keith E.; Ni, Ai; Moreira, Andre L.; Rekhtman, Natasha; Robbins, Paul B.; Karakunnel, Joyson; Rimner, Andreas; Huang, James; Riely, Gregory J.; Hellmann, Matthew D.

2017-01-01

Introduction The thymus is a critical organ for the development of the adaptive immune system and thymic epithelial tumors (TETs; thymomas and thymic carcinomas) are often associated with auto-immune paraneoplastic conditions. However, the immunobiology of TETs is not well described. An evaluation of the tumor microenvironment, with particular focus on expression of immunotherapeutic targets, may facilitate and prioritize development of immunotherapy strategies for patients with TETs. Methods Tumor tissues from 23 patients with WHO Type B2/B3 thymoma (n = 12) and thymic carcinoma (n = 11) were identified and clinical outcomes were annotated. The expression of membranous PD-L1 on tumor cells, CD3+ and CD8+ tumor infiltrating lymphocytes (TILs), co-stimulatory (CD137, GITR, ICOS), and co-inhibitory immune checkpoint molecules (PD-1, CTLA-4, TIM-3) were assessed semi-quantitatively using immunohistochemistry. Results PD-L1 positivity (≥ 25% of tumor membrane expression) was frequent in TETs (15/23, 65%), more common in thymomas compared to thymic carcinomas (p<0.01), and was associated with longer overall survival (p = 0.02). TIM-3 and GITR were expressed in all TETs, including 18/23 and 12/23 with at least moderate/high expression, respectively. Moderate/high CD137 expression correlated with CD8+ (p = 0.01) and moderate/high GITR expression co-associated with PD-1 (p = 0.043). Conclusions TETs are characterized by frequent PD-L1 expression and PD-L1 is associated with improved survival, suggesting PD-L1 signaling may be biologically important in TETs. Robust expression of markers of immune activation and immunotherapeutic target molecules in TETs emphasizes the potential for development of anti-PD-1/PD-L1 therapies. PMID:28771603

Noyce SWARMS Scholars and Two Professional Development Models (LASSI and RAMPED): Summer 2015, 2016, and 2017

NASA Astrophysics Data System (ADS)

Burrows, Andrea C.; Myers, Adam D.; Borowczak, Mike

2018-06-01

This poster showcases an astronomy professional development (PD) for 41 K-12 teachers. The project was entitled Launching Astronomy Standards and STEM Integration (LASSI). A project description (activities in the 18 months - Summer 2015 and 2016) for the astronomy, authentic science, and pre-service teacher opportunities is included. The PD team utilized real-world problems, participant-generated questions, science instruments, technology, evidence, communication, dissemination, and collaboration in the LASSI PD model. Computer science was a feature of the PD and the K-12 teacher participants showcased various methods of its use. Embracing an engineering process with an authentic astronomy PD allowed participants to make connections to current topics and create shareable projects. The PD team highlights teacher work from LASSI entitled - A Model for Determining Size of Objects in an Artificial Solar System. The Sustaining Wyoming's Advancing Reach in Mathematics and Science (SWARMS) Scholars (NSF Noyce funded) interacted with and used the materials from the LASSI PD. The poster highlights PD use from the LASSI participants and SWARMS Scholars as well as explains lessons learned to date as a follow-up PD Robotics, Applied Mathematics, Physics, and Engineering Design (RAMPED) was implemented in Summer 2017 and carried methods from LASSI. The LASSI and RAMPED PD teams included faculty from the College of Education, College of Engineering and Applied Science, College of Arts and Sciences, graduate students, and the teachers themselves. The PD teams created a website with these and other PD materials - UWpd.org - for others to view and change to meet their needs.

PD-L1 expression in pancreatic ductal adenocarcinoma is a poor prognostic factor in patients with high CD8+ tumor-infiltrating lymphocytes: highly sensitive detection using phosphor-integrated dot staining.

PubMed

Yamaki, So; Yanagimoto, Hiroaki; Tsuta, Koji; Ryota, Hironori; Kon, Masanori

2017-08-01

Pancreatic ductal adenocarcinoma (PDAC) has an extremely poor prognosis. For the development of more effective immunotherapies, it is first necessary to elucidate the immunological escape mechanisms. In this study, we applied our recently developed highly sensitive immunostaining method employing fluorescent phosphor-integrated dot (PID) nanoparticles to evaluate the prevalence of programmed death ligand 1 (PD-L1) in patients with PDAC. This study included 42 patients with PDAC who underwent pancreatectomy. We evaluated PD-L1 expression in these patients using PID staining and correlated PD-L1 expression level with each patient's clinico-pathological features. PD-L1 expression was detected in 61.9% (26/42) of the patients with PDAC by PID staining. There was a significant difference in overall survival between PD-L1-positive and PD-L1-negative patients [hazard ratio (HR) 2.07, 95% confidence interval (CI) 1.00-4.54; P = 0.049]. Among CD8 + -tumor-infiltrating lymphocyte-positive cases, the overall survival of PD-L1-positive patients was significantly poorer than that of PD-L1-negative patients (HR 3.84, 95% CI 1.59-10.35; P = 0.003). Univariate and multivariate analyses indicated that PD-L1 expression was an independent predictive poor prognostic factor in patients with PDAC. PD-L1 expression appears to be an important prognostic factor in patients with PDAC who underwent surgical resection.

Rapid PD-L1 detection in tumors with PET using a highly specific peptide

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

Chatterjee, Samit; Lesniak, Wojciech G.; Miller, Michelle S.

Molecular imaging can report on the status of the tumor immune microenvironment and guide immunotherapeutic strategies to enhance the efficacy of immune modulation therapies. Imaging agents that can rapidly report on targets of immunomodulatory therapies are few. The programmed death ligand 1 (PD-L1) is an immune checkpoint protein over-expressed in several cancers and contributes to tumor immune suppression. Tumor PD-L1 expression is indicative of tumor response to PD-1 and PD-L1 targeted therapies. Herein, we report a highly specific peptide-based positron emission tomography (PET) imaging agent for PD-L1. We assessed the binding modes of the peptide WL12 to PD-L1 by dockingmore » studies, developed a copper-64 labeled WL12 ([{sup 64}Cu]WL12), and performed its evaluation in vitro, and in vivo by PET imaging, biodistribution and blocking studies. Our results show that [{sup 64}Cu]WL12 can be used to detect tumor PD-L1 expression specifically and soon after injection of the radiotracer, to fit within the standard clinical workflow of imaging within 60 min of administration. - Highlights: • A highly specific PD-L1 binding peptide, WL12, was developed as a PET imaging agent. • [{sup 64}Cu]WL12 demonstrates specific binding to PD-L1 in vitro and in vivo. • [{sup 64}Cu]WL12-PET allows PD-L1 detection in cancers within 60 min of administration. • WL12 binding interactions with PD-L1 overlaps with that of PD-1.« less

Parkinson's disease psychosis: symptoms, management, and economic burden.

PubMed

Hermanowicz, Neal; Edwards, Kari

2015-08-01

Parkinson’s disease psychosis (PDP) is a costly,debilitating condition that generally develops several years after diagnosis of Parkinson’s disease (PD).PD is the second-most common neurodegenerative disease, and it imposes a significant burden on the healthcare system. Non-motor symptoms commonly manifest in PD, contributing to the severity of a patient’s disability. The neuropsychiatric symptoms that are common in PD can be a significant source of distress to patients and caregivers. Recent studies have shown that more than 50% of patients with PD will develop psychosis at some time over the course of the disease. The responsibility for caring for a person with PDP frequently falls on family members. Caregiver distress is frequently predicted when patients with PD have symptoms of psychosis.Hallucinations and delusions are independent predictors of nursing home placement for patients with PDP. The authors sought to examine total healthcare expenditures among patients with PDP compared with patients with PD without psychosis.All costs were higher for patients with PDP than for those with PD without psychosis and all-Medicare cohorts, with the highest cost differentials found in long-term care costs ($31,178 for PDP vs $14,461 forPD without psychosis), skilled nursing facility costs($6601 for PDP vs $2067 for PD without psychosis),and inpatient costs ($10,125 for PDP vs $6024 for PD without psychosis). Patients with PDP spent an average of 179 days in long-term care, compared with 83 days for patients with PD without psychosis. As expected, long-term care utilization and expenditures were significantly higher for patients with PDP than for patients with PD without psychosis. Reducing long-term care utilization by patients with PDP may significantly lower the overall economic burden associated with PDP.

Evidence for Anti-Pseudogymnoascus destructans (Pd) Activity of Propolis.

PubMed

Ghosh, Soumya; McArthur, Robyn; Guo, Zhi Chao; McKerchar, Rory; Donkor, Kingsley; Xu, Jianping; Cheeptham, Naowarat

2017-12-21

White-nose syndrome (WNS) in bats, caused by Pseudogymnoascus destructans ( Pd ), is a cutaneous infection that has devastated North American bat populations since 2007. At present, there is no effective method for controlling this disease. Here, we evaluated the effect of propolis against Pd in vitro. Using Sabouraud dextrose agar (SDA) medium, approximately 1.7 × 10⁷ conidia spores of the Pd strain M3906-2/mL were spread on each plate and grown to form a consistent lawn. A Kirby-Bauer disk diffusion assay was employed using different concentrations of propolis (1%, 2%, 3%, 4%, 5%, 10%, 15%, 20%, 25%), in plates incubated at 8 °C and 15 °C. At 8 °C and 15 °C, as the concentration of propolis increased, there was an increasing zone of inhibition (ZOI), reaching the highest degree at 10% and 25% concentrations, respectively. A germule suppression assay showed a similar effect on Pd conidia germination. A MALDI-TOF-MS analysis of propolis revealed multiple constituents with a potential anti- Pd activity, including cinnamic acid, p-coumaric acid, and dihydrochalcones, which could be further tested for their individual effects. Our study suggests that propolis or its individual constituents might be suitable products against Pd .

MOF-derived Cu-Pd/nanoporous carbon composite as an efficient catalyst for hydrogen evolution reaction: A comparison between hydrothermal and electrochemical synthesis

NASA Astrophysics Data System (ADS)

Mandegarzad, Sakineh; Raoof, Jahan Bakhsh; Hosseini, Sayed Reza; Ojani, Reza

2018-04-01

In this study, a novel catalyst based on Cu-Pd bimetallic nanoparticles supported on nanoporous carbon composite (NPCC) is successfully fabricated through three-step process and used as an electrocatalyst towards hydrogen evolution reaction (HER). At the first step, MOF-199 is synthesized via two distinct strategies; (1) hydrothermal (HT) and (2) electrochemical (EC). Next, the synthesized MOF-199 is used as a template in order to prepare Cu/NPCC by direct carbonization under N2 atmosphere followed by galvanic replacement reaction of Cu metals by PdII ions. All the prepared materials are characterized by X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy (EDS), scanning electron microscopy (SEM), and nitrogen adsorption/desorption measurements. The effect of synthesis method of MOF-199 on the electrocatalytic activity of the final product towards HER is investigated. The electrochemical measurements indicate that Cu-Pd/NPCC derived from the MOF prepared by EC method (Cu-Pd/NPCC/EC) exhibits an enhanced catalytic activity towards HER in H2SO4 solution than the Cu-Pd/NPCC/HT. This improvement may be attributed to using of supporting electrolyte in the preparation of Cu-Pd/NPCC/EC.

Formic acid-assisted synthesis of palladium nanocrystals and their electrocatalytic properties.

PubMed

Wang, Qinchao; Wang, Yiqian; Guo, Peizhi; Li, Qun; Ding, Ruixue; Wang, Baoyan; Li, Hongliang; Liu, Jingquan; Zhao, X S

2014-01-14

Palladium (Pd) nanocrystals have been synthesized by using formic acid as the reducing agent at room temperature. When the concentration of formic acid was increased continuously, the size of Pd nanocrystals first decreased to a minimum and then increased slightly again. The products have been investigated by a series of techniques, including X-ray diffraction, high-resolution transmission electron microscopy (HRTEM), UV-vis absorption, and electrochemical measurements. The formation of Pd nanocrystals is proposed to be closely related to the dynamical imbalance of the growth and dissolution rate of Pd nanocrystals associated with the adsorption of formate ions onto the surface of the intermediates. It is found that small Pd nanocrystals showed blue-shifted adsorption peaks compared with large ones. Pd nanocrystals with the smallest size display the highest electrocatalytic activity for the electrooxidation of formic acid and ethanol on the basis of cyclic voltammetry and chronoamperometric data. It is suggested that both the electrochemical active surface area and the small size effect are the key roles in determining the electrocatalytic performances of Pd nanocrystals. A "dissolution-deposition-aggregation" process is proposed to explain the variation of the electrocatalytic activity during the electrocatalysis according to the HRTEM characterization.

Factors influencing the development of early- or late-onset Parkinson's disease in a cohort of South African patients.

PubMed

van der Merwe, Celia; Haylett, William; Harvey, Justin; Lombard, Debbie; Bardien, Soraya; Carr, Jonathan

2012-10-01

Neurodegenerative disorders such as Parkinson's disease (PD) contribute significantly to global disease burden. PD can be categorised into early-onset PD (EOPD) with an age at onset (AAO) of ≤50 years and late-onset PD (LOPD) with an AAO of 50 years. To identify factors influencing EOPD and LOPD development in a group of patients in South Africa (SA). A total of 397 unrelated PD patients were recruited from the Movement Disorders Clinic at Tygerberg Hospital and via the Parkinson's Association of SA. Patient demographic and environmental data were recorded and associations with PD onset (EOPD v. LOPD) were analysed with a Pearson's Chi-squared test. The English- and Afrikaans-speaking (Afrikaner) white patients were analysed separately. Logistic regression analysis showed that ethnicity (p<0.001) and family history (p=0.004) were independently associated with AAO of PD. Average AAO was younger in black, coloured and Afrikaner patients than English-speaking white patients. A positive family history of PD, seen in 31.1% of LOPD patients, was associated with a younger AAO in the study population. These associations may be attributed to specific genetic and/or environmental risk factors that increase PD susceptibility and influence the clinical course of the disorder. More studies on PD in the unique SA populations are required to provide novel insights into mechanisms underlying this debilitating condition.

The development of the rotigotine transdermal patch: a historical perspective.

PubMed

Waters, Cheryl

2013-08-01

The rotigotine transdermal system is a dopamine receptor agonist delivered over a 24-hour period. It is approved for the treatment of idiopathic Parkinson's disease (PD). This article reviews the development of the rotigotine transdermal system, including rotigotine's receptor profile, steady-state pharmacokinetics, and metabolism. Preclinical studies of rotigotine in animal models of PD and proof-of-concept studies in patients with PD are reviewed. These preclinical and clinical studies established this system as an effective method for providing continuous rotigotine delivery across the skin providing the basis for continued clinical development of rotigotine for the treatment of early and advanced PD. Copyright © 2013 Elsevier Inc. All rights reserved.

Developing a Web-Based Mechanism for Assessing Teacher Science Content Knowledge

NASA Astrophysics Data System (ADS)

Byers, Al; Koba, Susan; Sherman, Greg; Scheppke, Joan; Bolus, Roger

2011-04-01

The National Science Teachers Association (NSTA) recently launched a comprehensive electronic professional development (e-PD) online portal, the NSTA Learning Center. This support site for educators currently includes over 6,000 e-PD resources and opportunities available on-demand, as well as various tools designed to help educators maximize the effectiveness of using NSTA resources. One tool, the PD Indexer, helps teachers identify their own areas of content strengths and weaknesses by selecting content-specific assessments. Individual NSTA resources are recommended based on assessment outcomes. This paper presents a detailed description of the procedures employed by NSTA to develop valid and reliable PD Indexer content-specific multiple-choice assessment items.

Intercellular transfer of pathogenic α-synuclein by extracellular vesicles is induced by the lipid peroxidation product 4-hydroxynonenal.

PubMed

Zhang, Shi; Eitan, Erez; Wu, Tsung-Yu; Mattson, Mark P

2018-01-01

Parkinson's disease (PD) is characterized by accumulations of toxic α-synuclein aggregates in vulnerable neuronal populations in the brainstem, midbrain, and cerebral cortex. Recent findings suggest that α-synuclein pathology can be propagated transneuronally, but the underlying molecular mechanisms are unknown. Advances in the genetics of rare early-onset familial PD indicate that increased production and/or reduced autophagic clearance of α-synuclein can cause PD. The cause of the most common late-onset PD is unclear, but may involve metabolic compromise and oxidative stress upstream of α-synuclein accumulation. As evidence, the lipid peroxidation product 4-hydroxynonenal (HNE) is elevated in the brain during normal aging and moreso in brain regions afflicted with α-synuclein pathology. Here, we report that HNE increases aggregation of endogenous α-synuclein in primary neurons and triggers the secretion of extracellular vesicles (EVs) containing cytotoxic oligomeric α-synuclein species. EVs released from HNE-treated neurons are internalized by healthy neurons which as a consequence degenerate. Levels of endogenously generated HNE are elevated in cultured cells overexpressing human α-synuclein, and EVs released from those cells are toxic to neurons. The EV-associated α-synuclein is located both inside the vesicles and on their surface, where it plays a role in EV internalization by neurons. On internalization, EVs harboring pathogenic α-synuclein are transported both anterogradely and retrogradely within axons. Focal injection of EVs containing α-synuclein into the striatum of wild-type mice results in spread of synuclein pathology to anatomically connected brain regions. Our findings suggest a scenario for late-onset PD in which lipid peroxidation promotes intracellular accumulation and then extrusion of EVs containing toxic α-synuclein species; the EVs are then internalized by adjacent neurons, so propagating the neurodegenerative process. Published by Elsevier Inc.

Glucose-6-phosphate dehydrogenase deficiency and antimalarial drug development.

PubMed

Beutler, Ernest; Duparc, Stephan

2007-10-01

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is relatively common in populations exposed to malaria. This deficiency appears to provide some protection from this infection, but it can also cause hemolysis after administration of some antimalarial drugs, especially primaquine. The risk of drug-induced G6PD deficiency-related hemolysis depends on a number of factors including the G6PD variant, the drug and drug dosage schedule, patient status, and disease factors. Although a great deal is known about the molecular biology of G6PD, determining the potential for drug-induced hemolysis in the clinical setting is still challenging. This report discusses the potential strategies for assessing drug-induced G6PD deficiency-related hemolytic risk preclinically and in early clinical trials. Additionally, the issues important for conducting larger clinical trials in populations in which G6PD deficiency is prevalent are examined, with a particular focus on antimalarial drug development.

Programmed death 1-mediated T cell exhaustion during visceral leishmaniasis impairs phagocyte function.

PubMed

Esch, Kevin J; Juelsgaard, Rachel; Martinez, Pedro A; Jones, Douglas E; Petersen, Christine A

2013-12-01

Control of Leishmania infantum infection is dependent upon Th1 CD4(+) T cells to promote macrophage intracellular clearance of parasites. Deficient CD4(+) T cell effector responses during clinical visceral leishmaniasis (VL) are associated with elevated production of IL-10. In the primary domestic reservoir of VL, dogs, we define occurrence of both CD4(+) and CD8(+) T cell exhaustion as a significant stepwise loss of Ag-specific proliferation and IFN-γ production, corresponding to increasing VL symptoms. Exhaustion was associated with a 4-fold increase in the population of T cells with surface expression of programmed death 1 (PD-1) between control and symptomatic populations. Importantly, exhausted populations of CD8(+) T cells and to a lesser extent CD4(+) T cells were present prior to onset of clinical VL. VL-exhausted T cells did not undergo significant apoptosis ex vivo after Ag stimulation. Ab block of PD-1 ligand, B7.H1, promoted return of CD4(+) and CD8(+) T cell function and dramatically increased reactive oxygen species production in cocultured monocyte-derived phagocytes. As a result, these phagocytes had decreased parasite load. To our knowledge, we demonstrate for the first time that pan-T cell, PD-1-mediated, exhaustion during VL influenced macrophage-reactive oxygen intermediate production. Blockade of the PD-1 pathway improved the ability of phagocytes isolated from dogs presenting with clinical VL to clear intracellular parasites. T cell exhaustion during symptomatic canine leishmaniasis has implications for the response to vaccination and therapeutic strategies for control of Leishmania infantum in this important reservoir species.

Serotonergic mechanisms responsible for levodopa-induced dyskinesias in Parkinson’s disease patients

PubMed Central

Politis, Marios; Wu, Kit; Loane, Clare; Brooks, David J.; Kiferle, Lorenzo; Turkheimer, Federico E.; Bain, Peter; Molloy, Sophie; Piccini, Paola

2014-01-01

Levodopa-induced dyskinesias (LIDs) are the most common and disabling adverse motor effect of therapy in Parkinson’s disease (PD) patients. In this study, we investigated serotonergic mechanisms in LIDs development in PD patients using 11C-DASB PET to evaluate serotonin terminal function and 11C-raclopride PET to evaluate dopamine release. PD patients with LIDs showed relative preservation of serotonergic terminals throughout their disease. Identical levodopa doses induced markedly higher striatal synaptic dopamine concentrations in PD patients with LIDs compared with PD patients with stable responses to levodopa. Oral administration of the serotonin receptor type 1A agonist buspirone prior to levodopa reduced levodopa-evoked striatal synaptic dopamine increases and attenuated LIDs. PD patients with LIDs that exhibited greater decreases in synaptic dopamine after buspirone pretreatment had higher levels of serotonergic terminal functional integrity. Buspirone-associated modulation of dopamine levels was greater in PD patients with mild LIDs compared with those with more severe LIDs. These findings indicate that striatal serotonergic terminals contribute to LIDs pathophysiology via aberrant processing of exogenous levodopa and release of dopamine as false neurotransmitter in the denervated striatum of PD patients with LIDs. Our results also support the development of selective serotonin receptor type 1A agonists for use as antidyskinetic agents in PD. PMID:24531549

Small-sized PdCu nanocapsules on 3D graphene for high-performance ethanol oxidation

NASA Astrophysics Data System (ADS)

HuThese Authors Contributed Equally To This Work., Chuangang; Zhai, Xiangquan; Zhao, Yang; Bian, Ke; Zhang, Jing; Qu, Liangti; Zhang, Huimin; Luo, Hongxia

2014-02-01

A one-pot solvothermal process has been developed for direct preparation of PdCu nanocapsules (with a size of ca. 10 nm) on three-dimensional (3D) graphene. Due to the 3D pore-rich network of graphene and the unique hollow structure of PdCu nanocapsules with a wall thickness of ca. 3 nm, the newly-prepared PdCu/3D graphene hybrids activated electrochemically have great electrocatalytic activity towards ethanol oxidation in alkaline media, much better than single-phase Pd and commercial E-TEK 20% Pt/C catalysts promising for application in direct ethanol fuel cells.A one-pot solvothermal process has been developed for direct preparation of PdCu nanocapsules (with a size of ca. 10 nm) on three-dimensional (3D) graphene. Due to the 3D pore-rich network of graphene and the unique hollow structure of PdCu nanocapsules with a wall thickness of ca. 3 nm, the newly-prepared PdCu/3D graphene hybrids activated electrochemically have great electrocatalytic activity towards ethanol oxidation in alkaline media, much better than single-phase Pd and commercial E-TEK 20% Pt/C catalysts promising for application in direct ethanol fuel cells. Electronic supplementary information (ESI) available. See DOI: 10.1039/c3nr05722d