Developing neurons use a putative pioneer's peripheral arbor to establish their terminal fields.

PubMed

Gan, W B; Macagno, E R

1995-05-01

Pioneer neurons are known to guide later developing neurons during the initial phases of axonal outgrowth. To determine whether they are also important in the formation of terminal fields by the follower cells, we studied the role of a putative leech pioneer neuron, the pressure-sensitive (PD) neuron, in the establishment of other neurons' peripheral arbors. The PD neuron has a major axon that exits from its segmental ganglion to grow along the dorsal-posterior (DP) nerve to the dorsal body wall, where it arborizes extensively mainly in its own segment. It also has two minor axons that project to the two adjacent segments but branch to a lesser degree. We found that the peripheral projections of several later developing neurons, including the AP motor neuron and the TD sensory neuron, followed, with great precision, the major axon and peripheral arbor of the consegmental PD neuron, up to its fourth-order branches. When a PD neuron was ablated before it had grown to the body wall, the AP and TD axons grew normally toward and reached the target area, but then formed terminal arbors that were greatly reduced in size and abnormal in morphology. Further, if the ablation of a PD neuron was accompanied by the induction, in the same segment, of greater outgrowth of the minor axon of a PD neuron from the adjacent segment, the arbors of the same AP neurons grew along these novel PD neuron branches. These results demonstrate that the peripheral arbor of a PD neuron is a both necessary and sufficient template for the formation of normal terminal fields by certain later growing follower neurons.

Parkinson disease with and without Dementia: A prevalence study and future projections.

PubMed

Savica, Rodolfo; Grossardt, Brandon R; Rocca, Walter A; Bower, James H

2018-04-01

Limited population-based information is available on the co-occurrence of dementia and PD. However, projecting the prevalence of PD with and without dementia during the next 50 years is crucial for planning public-health and patient-care initiatives. The objective of this study was to project the prevalence of PD with and without dementia in the United States by 2060. We used the Rochester Epidemiology Project medical records-linkage system to identify all persons with PD with or without dementia residing in Olmsted County, Minnesota, on January 1, 2006. A movement disorders specialist reviewed the complete medical records of each person to confirm the presence of PD. We calculated the age- and sex-specific prevalence of PD with and without dementia and projected U.S. prevalence through 2060. We identified 296 persons with PD with and without dementia on the prevalence date (187 men, 109 women); the overall prevalence increased with age from 0.01% (30-39 years) to 2.83% (≥90 years). The prevalence of PD without dementia increased with age from 0.01% (30-39 years) to 1.25% (≥90 years). The prevalence of PD with dementia increased with age from 0.10% (60-69 years) to 1.59% (≥90 years). The prevalence was higher in men than in women for all subtypes and all age groups. We project by 2060 an approximate doubling of the number of persons with PD without dementia and a tripling of the number of persons with PD with dementia in the United States. The prevalence of PD with and without dementia increases with age and is higher in men than women. We project that the number of persons with PD in the United States will increase substantially by 2060. © 2018 International Parkinson and Movement Disorder Society. © 2018 International Parkinson and Movement Disorder Society.

Mathematics Teachers' Take-Aways from Morning Math Problems in a Long-Term Professional Development Project

ERIC Educational Resources Information Center

Sevis, Serife; Cross, Dionne; Hudson, Rick

2017-01-01

Considering the role of mathematics-focused professional development programs in improving teachers' content knowledge and quality of teaching, we provided teachers opportunities for dealing with mathematics problems and positioning themselves as students in a large-scale long-term professional development (PD) project. In this proposal, we aimed…

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).

School-Based Learning for Individual Diversity in Education: The SLIDE Project

ERIC Educational Resources Information Center

Harrington, Ingrid

2013-01-01

Whole-School Professional Development (PD) days held regularly in schools are designed to promote and up-skill school staff on relevant areas of educational policy and practice. An aim of PD days is to empower participants with new knowledges and skills, and to confirm that current practices and interpretations of education policy and procedure…

School-Based Learning for Individual Diversity in Education: The SLIDE Project

ERIC Educational Resources Information Center

Harrington, Ingrid

2013-01-01

Whole-School Professional Development (PD) days held regularly in schools are designed to promote and up-skill teaching and administrative staff on relevant areas of educational policy and practice. An aim of PD days is to empower participants with new knowledges and skills, and to confirm that current practices and interpretations of education…

Big Outcrops and Big Ideas in Earth Science K-8 Professional Development

NASA Astrophysics Data System (ADS)

Baldwin, K. A.; Cooper, C. M.; Cavagnetto, A.; Morrison, J.; Adesope, O.

2014-12-01

Washington State has recently adopted the Next Generation Science Standards (NGSS) and state leaders are now working toward supporting teachers' implementation of the new standards and the pedagogical practices that support them. This poster encompasses one of one such professional development (PD) effort. The Enhancing Understanding of Concepts and Processes of Science (EUCAPS) project serves 31 K-8 in-service teachers in two southeast Washington school districts. In year two of this three year PD project, in-service teachers explored the Earth sciences and pedagogical approaches such as the Science Writing Heuristic, concept mapping, and activities which emphasized the epistemic nature of science. The goals of the EUCAPS PD project are to increase in-service teachers' big ideas in science and to provide support to in-service teachers as they transition to the NGSS. Teachers used concepts maps to document their knowledge of Earth science processes before and after visiting a local field site in Lewiston, Idaho. In the context of immersive inquiries, teachers collected field-based evidence to support their claims about the geological history of the field site. Teachers presented their claims and evidence to their peers in the form a story about the local geologic history. This poster will present an overview of the PD as well as provide examples of teacher's work and alignment with the NGSS.

Impact Evaluation of National Writing Project Professional Development Program

ERIC Educational Resources Information Center

Gallagher, H. Alix; Woodworth, Katrina; McCaffrey, Teresa; Park, Christina J.; Wang, Haiwen

2014-01-01

Improving teacher effectiveness is a key strategy to ensure student readiness for college and careers and to address achievement gaps and persistent low performance. In response to the new Common Core State Standards for English Language Arts (CCSS-ELA) the National Writing Project (NWP) created a professional development (PD) program to support…

What Makes Professional Development Coherent? Uncovering Teacher Perspectives on a Science Literacy Project

ERIC Educational Resources Information Center

Kohnen, Angela M.; Whitacre, Michelle P.

2017-01-01

In this study, the authors sought to uncover the characteristics of professional development (PD) that were identified by teacher-participants as being important to their implementation of project ideas. Using phenomenological interviewing, the authors talked with nine teacher-participants about changes to their teaching practices after they…

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

Evaluation of a Web-Based Professional Development Program (Project ACE) for Teachers of Children with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Rakap, Salih; Jones, Hazel A.; Emery, Alice Kaye

2015-01-01

This article describes the development, implementation, and second-year evaluation of Project Autism Competencies for Endorsement (ACE), a web-based professional development (PD) program that is designed to train teachers currently working in the field to meet the unique and diverse needs of children with autism spectrum disorders (ASDs). A…

A Data-Driven Preschool PD Model for Literacy and Oral Language Instruction

ERIC Educational Resources Information Center

Abbott, Mary; Atwater, Jane; Lee, Younwoo; Edwards, Liesl

2011-01-01

The purpose of this article is to describe the professional development (PD) model for preschool literacy and language instruction that took place in a 3-year, 2-tiered Early Reading First project in 9 Head Start and community-based school classrooms. In our tiered model, the Tier 1 level was classroom instruction and Tier 2 was intervention…

Chemistry Teachers' Emerging Expertise in Inquiry Teaching: The Effect of a Professional Development Model on Beliefs and Practice

NASA Astrophysics Data System (ADS)

Rushton, Gregory T.; Lotter, Christine; Singer, Jonathan

2011-02-01

This study investigates the beliefs and practices of seven high school chemistry teachers as a result of their participation in a year-long inquiry professional development (PD) project. An analysis of oral interviews, written reflections, and in-class observations were used to determine the extent to which the PD affected the teachers' beliefs and practice. The data indicated that the teachers developed more complete conceptions of classroom inquiry, valued a "phenomena first" approach to scientific investigations, and viewed inquiry approaches as helpful for facilitating improved student thinking. Analysis of classroom observations with the Reformed Teaching Observation Protocol indicated that features of the PD were observed in the teachers' practice during the academic year follow-up. Implications for effective science teacher professional development models are discussed.

An Ethnographically Informed Participatory Design of Primary Healthcare Information Technology in a Developing Country Setting.

PubMed

Shidende, Nima Herman; Igira, Faraja Teddy; Mörtberg, Christina Margaret

2017-01-01

Ethnography, with its emphasis on understanding activities where they occur, and its use of qualitative data gathering techniques rich in description, has a long tradition in Participatory Design (PD). Yet there are limited methodological insights in its application in developing countries. This paper proposes an ethnographically informed PD approach, which can be applied when designing Primary Healthcare Information Technology (PHIT). We use findings from a larger multidisciplinary project, Health Information Systems Project (HISP) to elaborate how ethnography can be used to facilitate participation of health practitioners in developing countries settings as well as indicating the importance of ethnographic approach to participatory Health Information Technology (HIT) designers. Furthermore, the paper discusses the pros and cons of using an ethnographic approach in designing HIT.

Development and validation of a new screening questionnaire for dysphagia in early stages of Parkinson's disease.

PubMed

Simons, Janine A; Fietzek, Urban M; Waldmann, Annika; Warnecke, Tobias; Schuster, Tibor; Ceballos-Baumann, Andrés O

2014-09-01

Dysphagia in patients with Parkinson's disease (PD) significantly reduces quality of life and predicted lifetime. Current screening procedures are insufficiently evaluated. We aimed to develop and validate a patient-reported outcome questionnaire for early diagnosis of dysphagia in patients with PD. The two-phased project comprised the questionnaire, diagnostic scales construction (N = 105), and a validation study (N = 82). Data for the project were gathered from PD patients at a German Movement Disorder Center. For validation purposes, a clinical evaluation focusing on swallowing tests, tests of sensory reflexes, and fiberoptic endoscopic evaluation of swallowing (FEES) was performed that yielded a criteria sum score against which the results of the questionnaire were compared. Specificity and sensitivity were evaluated for the detection of noticeable dysphagia and for the risk of aspiration. The Munich Dysphagia Test - Parkinson's disease (MDT-PD) consists of 26 items that show high internal consistency (α = 0.91). For the validation study, 82 patients, aged 70.9 ± 8.7 (mean ± SD), with a median Hoehn & Yahr stage of 3, were assessed. 73% of patients had dysphagia with noticeable oropharyngeal symptoms (44%) or with penetration/aspiration (29%). The criteria sum score correlated positively with the screening result (r = 0.70, p < 0.001). The MDT-PD sum score classified not noticeable dysphagia vs. risk of aspiration (noticeable dysphagia) with a sensitivity of 90% (82%) and a specificity of 86% (71%), and yielded similar results in cross-validation, respectively. MDT-PD is a valid screening tool for early diagnosis of swallowing problems and aspiration risk, as well as initial graduation of dysphagia severity in PD patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

Old and new challenges in Parkinson's disease therapeutics.

PubMed

Pires, Ana O; Teixeira, F G; Mendes-Pinheiro, B; Serra, Sofia C; Sousa, Nuno; Salgado, António J

2017-09-01

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the degeneration of dopaminergic neurons and/or loss od neuronal projections, in several dopaminergic networks. Current treatments for idiopathic PD rely mainly on the use of pharmacologic agents to improve motor symptomatology of PD patients. Nevertheless, so far PD remains an incurable disease. Therefore, it is of utmost importance to establish new therapeutic strategies for PD treatment. Over the last 20 years, several molecular, gene and cell/stem-cell therapeutic approaches have been developed with the aim of counteracting or retarding PD progression. The scope of this review is to provide an overview of PD related therapies and major breakthroughs achieved within this field. In order to do so, this review will start by focusing on PD characterization and current treatment options covering thereafter molecular, gene and cell/stem cell-based therapies that are currently being studied in animal models of PD or have recently been tested in clinical trials. Among stem cell-based therapies, those using MSCs as possible disease modifying agents for PD therapy and, specifically, the MSCs secretome contribution to meet the clinical challenge of counteracting or retarding PD progression, will be more deeply explored. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

PD5: a general purpose library for primer design software.

PubMed

Riley, Michael C; Aubrey, Wayne; Young, Michael; Clare, Amanda

2013-01-01

Complex PCR applications for large genome-scale projects require fast, reliable and often highly sophisticated primer design software applications. Presently, such applications use pipelining methods to utilise many third party applications and this involves file parsing, interfacing and data conversion, which is slow and prone to error. A fully integrated suite of software tools for primer design would considerably improve the development time, the processing speed, and the reliability of bespoke primer design software applications. The PD5 software library is an open-source collection of classes and utilities, providing a complete collection of software building blocks for primer design and analysis. It is written in object-oriented C(++) with an emphasis on classes suitable for efficient and rapid development of bespoke primer design programs. The modular design of the software library simplifies the development of specific applications and also integration with existing third party software where necessary. We demonstrate several applications created using this software library that have already proved to be effective, but we view the project as a dynamic environment for building primer design software and it is open for future development by the bioinformatics community. Therefore, the PD5 software library is published under the terms of the GNU General Public License, which guarantee access to source-code and allow redistribution and modification. The PD5 software library is downloadable from Google Code and the accompanying Wiki includes instructions and examples: http://code.google.com/p/primer-design.

New concepts for HgI2 scintillator gamma ray spectroscopy

NASA Technical Reports Server (NTRS)

Iwanczyk, Jan S.

1994-01-01

The primary goals of this project are development of the technology for HgI2 photodetectors (PD's), development of a HgI2/scintillator gamma detector, development of electronics, and development of a prototype gamma spectrometer. Work on the HgI2 PD's involved HgI2 purification and crystal growth, detector surface and electrical contact studies, PD structure optimization, encapsulation and packaging, and testing. Work on the HgI2/scintillator gamma detector involved a study of the optical - mechanical coupling for the optimization of CsI(Tl)/HgI2 gamma ray detectors and determination of the relationship between resolution versus scintillator type and size. The development of the electronics focused on low noise amplification circuits using different preamp input FET's and the use of a coincidence technique to maximize the signal, minimize the noise contribution in the gamma spectra, and improve the overall system resolution.

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.

Lessons Learned from Participatory Design in Dementia Care: Placing Care Partners at the Centre.

PubMed

Hendriks, Niels; Slegers, Karin; Wilkinson, Andrea

2017-01-01

In this paper we analyze the participatory design (PD) process of a health information technology (HIT) project. This project, AToM was situated in dementia care and involved partners from academia, industry and care. The analysis specifically focuses on the role of the care partners in the PD process. We will show that the conditions to enable 'good participatory design' were not fully met and we present a set of actions to prevent this in future HIT projects. Central to our recommended approach is placing the care partners at the centre of the PD project.

Interest and limitations of projective techniques in the assessment of personality disorders.

PubMed

Petot, J M

2000-06-01

Assessing personality disorders (PD) remains a difficult task because of persistent problems linked to concurrent validity of existing instruments, which are all structured interviews or self-report inventories. It has been advocated that indirect methods, projective techniques in particular, can strengthen PD assessment methods. The thematic apperception test (TAT) may be a significant adjuvant method of PD assessment.

Increasing Efficiency of Recruitment in Early Parkinson's Disease Trials: A Case Study Examination of the STEADY-PD III Trial.

PubMed

Berk, Sarah; Greco, Brittany L; Biglan, Kevin; Kopil, Catherine M; Holloway, Robert G; Meunier, Claire; Simuni, Tanya

2017-01-01

Challenges in clinical trial recruitment threaten the successful development of improved therapies. This is particularly true in Parkinson's disease (PD) studies of disease modification where the population of interest is difficult to find and study design is more complex. This paper seeks to understand how STEADY PD III, a National Institute of Neurological Disorders and Stroke (NINDS) funded phase 3 trial evaluating the efficacy of isradipine as a disease modifying agent for PD, was able to recruit their full target population 6 months ahead of schedule. STEADY PD III aimed to enroll 336 individuals with early stage idiopathic PD within 18 months using 57 sites across the United States and Canada. The study included a 10% NIH minority recruitment goal. Eligible participants agreed to be followed for up to 36 months, complete 12 in-person visits and 4 telephone visits. A Recruitment Committee of key stakeholders was critical in the development of a comprehensive recruitment strategy involving: multi-modal outreach, protocol modifications and comprehensive site selection and activation. Efforts to increase site-specific minority recruitment strategies were encouraged through additional funding. A total of 336 individuals, including 34 minorities, were enrolled within 12 months - 6 months ahead of the projected timeline. Quantitative analysis of recruitment activity questionnaires found that of the sites that completed them (n = 54), (20.4%) met goals, (24.1%) exceeded goals, and (55.6%) fell below projected goals. Referral sources completed at time of screening indicate top four study referral sources as: site personnel (53.8%); neurologists (24%); Fox Trial Finder (10.2%); and communications from The Michael J. Fox Foundation (3.9%). STEADY PD III serves as an important example of methods that can be used to increase clinical trial recruitment. This research highlights a continued need to improve site infrastructure and dedicate more resources to increased participation of minorities in clinical research.

Increasing Efficiency of Recruitment in Early Parkinson’s Disease Trials: A Case Study Examination of the STEADY-PD III Trial

PubMed Central

Berk, Sarah; Greco, Brittany L.; Biglan, Kevin; Kopil, Catherine M.; Holloway, Robert G.; Meunier, Claire; Simuni, Tanya

2017-01-01

Background: Challenges in clinical trial recruitment threaten the successful development of improved therapies. This is particularly true in Parkinson’s disease (PD) studies of disease modification where the population of interest is difficult to find and study design is more complex. Objective: This paper seeks to understand how STEADY PD III, a National Institute of Neurological Disorders and Stroke (NINDS) funded phase 3 trial evaluating the efficacy of isradipine as a disease modifying agent for PD, was able to recruit their full target population 6 months ahead of schedule. Methods: STEADY PD III aimed to enroll 336 individuals with early stage idiopathic PD within 18 months using 57 sites across the United States and Canada. The study included a 10% NIH minority recruitment goal. Eligible participants agreed to be followed for up to 36 months, complete 12 in-person visits and 4 telephone visits. A Recruitment Committee of key stakeholders was critical in the development of a comprehensive recruitment strategy involving: multi-modal outreach, protocol modifications and comprehensive site selection and activation. Efforts to increase site-specific minority recruitment strategies were encouraged through additional funding. Results: A total of 336 individuals, including 34 minorities, were enrolled within 12 months – 6 months ahead of the projected timeline. Quantitative analysis of recruitment activity questionnaires found that of the sites that completed them (n = 54), (20.4%) met goals, (24.1%) exceeded goals, and (55.6%) fell below projected goals. Referral sources completed at time of screening indicate top four study referral sources as: site personnel (53.8%); neurologists (24%); Fox Trial Finder (10.2%); and communications from The Michael J. Fox Foundation (3.9%). Conclusions: STEADY PD III serves as an important example of methods that can be used to increase clinical trial recruitment. This research highlights a continued need to improve site infrastructure and dedicate more resources to increased participation of minorities in clinical research. PMID:29103052

Chemogenetic stimulation of striatal projection neurons modulates responses to Parkinson’s disease therapy

PubMed Central

Alcacer, Cristina; Andreoli, Laura; Sebastianutto, Irene; Jakobsson, Johan; Fieblinger, Tim; Cenci, Maria Angela

2017-01-01

Parkinson’s disease (PD) patients experience loss of normal motor function (hypokinesia), but can develop uncontrollable movements known as dyskinesia upon treatment with L-DOPA. Poverty or excess of movement in PD has been attributed to overactivity of striatal projection neurons forming either the indirect (iSPNs) or the direct (dSPNs) pathway, respectively. Here, we investigated the two pathways’ contribution to different motor features using SPN type–specific chemogenetic stimulation in rodent models of PD (PD mice) and L-DOPA–induced dyskinesia (LID mice). Using the activatory Gq-coupled human M3 muscarinic receptor (hM3Dq), we found that chemogenetic stimulation of dSPNs mimicked, while stimulation of iSPNs abolished the therapeutic action of L-DOPA in PD mice. In LID mice, hM3Dq stimulation of dSPNs exacerbated dyskinetic responses to L-DOPA, while stimulation of iSPNs inhibited these responses. In the absence of L-DOPA, only chemogenetic stimulation of dSPNs mediated through the Gs-coupled modified rat muscarinic M3 receptor (rM3Ds) induced appreciable dyskinesia in PD mice. Combining D2 receptor agonist treatment with rM3Ds-dSPN stimulation reproduced all symptoms of LID. These results demonstrate that dSPNs and iSPNs oppositely modulate both therapeutic and dyskinetic responses to dopamine replacement therapy in PD. We also show that chemogenetic stimulation of different signaling pathways in dSPNs leads to markedly different motor outcomes. Our findings have important implications for the design of effective antiparkinsonian and antidyskinetic drug therapies. PMID:28112685

Using participatory design to develop (public) health decision support systems through GIS

PubMed Central

Dredger, S Michelle; Kothari, Anita; Morrison, Jason; Sawada, Michael; Crighton, Eric J; Graham, Ian D

2007-01-01

Background 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. Methods 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. Results 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). Discussion 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. Conclusion 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. PMID:18042298

MODEL DEVELOPMENT AND APPLICATION FOR ASSESSING HUMAN EXPOSURE AND DOSE TO TOXIC CHEMICALS AND POLLUTANTS

EPA Science Inventory

This project aims to strengthen the general scientific foundation of EPA's exposure and risk assessment processes by developing state-of-the-art exposure to dose computational models. This research will produce physiologically-based pharmacokinetic (PBPK) and pharmacodynamic (PD)...

Introduction to NEPA and mitigation for TxDOT PDP : workshop material.

DOT National Transportation Integrated Search

2014-10-01

The purpose of this workshop is to provide transportation planners, engineers, : environmental practitioners, and local officials with an introduction to National : Environemntal policy Act (EPA), mitigation, and the project development : process (PD...

Progressive levels of physical dependence to tobacco coincide with changes in the anterior cingulum bundle microstructure.

PubMed

Huang, Wei; DiFranza, Joseph R; Kennedy, David N; Zhang, Nanyin; Ziedonis, Douglas; Ursprung, Sanouri; King, Jean A

2013-01-01

The tobacco withdrawal syndrome indicates the development of neurophysiologic dependence. Clinical evidence indicates that neurophysiologic dependence develops through a set sequence of symptom presentation that can be assessed with a new 3-item survey measure of wanting, craving, and needing tobacco, the Level of Physical Dependence (PD). This study sought to determine if advancing neurophysiologic dependence as measured by the Level of PD correlates with characteristics of white matter structure measured by Fractional Anisotropy (FA). Diffusion-MRI based FA and diffusion tensor imaging probabilistic tractography were used to evaluate 11 smokers and 10 nonsmokers. FA was also examined in relation to two additional measures of dependence severity, the Hooked on Nicotine Checklist (HONC), and the Fagerström Test for Nicotine Dependence (FTND). Among smokers, FA in the left anterior cingulate bundle (ACb) correlated negatively with the Level of PD (r = -0.68, p = 0.02) and HONC scores (r = -0.65, p = 0.03), but the correlation for the FTND did not reach statistical significance (r = -49, p = 0.12). With advancing Levels of PD, the density of streamlines between the ACb and precuneus increased (r = -0.67, p<0.05) and those between the ACb and white matter projecting to the superior-frontal cortex (r = -0.86, p = 0.0006) decreased significantly. The correlations between neural structure and both the clinical Level of PD survey measure and the HONC suggest that the Level of PD and the HONC may reflect the microstructural integrity of white matter, as influenced by tobacco abuse. Given that the Level of PD is measuring a sequence of symptoms of neurophysiologic dependence that develops over time, the correlation between the Level of PD and neural structure suggests that these features might represent neuroplastic changes that develop over time to support the development of neurophysiologic dependence.

Evidence-based design and development of a VR-based treadmill system for gait research and rehabilitation of patients with Parkinson's disease.

PubMed

Pérez-Sanpablo, Alberto Isaac; González-Mendoza, Arturo; Quiñones-Uriostegui, Ivett; Rodríguez-Reyes, Gerardo; Núñez-Carrera, Lidia; Hernández-Arenas, Claudia; Boll-Woehrlen, Marie Catherine; Alessi Montero, Aldo

2014-07-01

Virtual reality (VR) in neurorehabilitation allows to reduce patient's risk and allows him to learn on a faster way. Up to now VR has been used in patients with Parkinson disease (PD) as a research tool and none of the developed systems are used in clinical practice. The goal of this project is to develop a VR-based system for gait therapy, and gait research of patients with PD designed based on published evidence. The developed system uses a digital camera to measure spatiotemporal gait parameters. The software was developed in C#, using Open-Source libraries that facilitates VR programming. The system has potential uses in clinical and research settings.

Dulce Wireless Tijuana: A Randomized Control Trial Evaluating the Impact of Project Dulce and Short-Term Mobile Technology on Glycemic Control in a Family Medicine Clinic in Northern Mexico.

PubMed

Anzaldo-Campos, María Cecilia; Contreras, Sonia; Vargas-Ojeda, Adriana; Menchaca-Díaz, Rufino; Fortmann, Addie; Philis-Tsimikas, Athena

2016-04-01

The global epidemic of diabetes calls for innovative interventions. This study evaluated the effectiveness of the Project Dulce model, with and without wireless technology, on glycemic control and other clinical and self-reported outcomes in patients with poorly controlled type 2 diabetes in Mexico. Adults with type 2 diabetes and a glycated hemoglobin A1c (HbA1c) level of ≥8% were recruited from Family Medical Unit #27 of the Instituto Mexicano del Seguro Social (IMSS) in Tijuana, México, and randomly assigned to one of three groups: Project Dulce-only (PD); Project Dulce technology-enhanced with mobile tools (PD-TE); or IMSS standard of care/control group (CG). Clinical and self-reported outcomes were assessed at baseline, Month 4, and Month 10. Time-by-group interactions and within-group changes were analyzed. HbA1c reductions from baseline to Month 10 were significantly greater in PD-TE (-3.0% [-33 mmol/mol]) and PD (-2.6% [-28.7 mmol/mol]) compared with CG (-1.3% [-14.2 mmol/mol]) (P = 0.009 and 0.001, respectively). PD-TE and PD also exhibited significant improvement in diabetes knowledge when compared with CG (P < 0.05 for both). No statistically significant differences were detected between PD and PD-TE on these indicators (P = 0.54 and 0.86, respectively). Several within-group improvements were observed on other clinical and self-report indicators but did not vary significantly across groups. Project Dulce with and without wireless technology substantially improved glycemic control and diabetes knowledge in high-risk patients with type 2 diabetes in a Mexican family medical unit, suggesting that integrating peer-led education, nurse coordination, and 3G wireless technology is an effective approach for improving diabetes outcomes in high-risk populations.

Aggravated stuttering following subthalamic deep brain stimulation in Parkinson's disease - two cases

PubMed Central

2011-01-01

Stuttering is a speech disorder with disruption of verbal fluency which is occasionally present in patients with Parkinson's disease (PD). Long-term medical management of PD is frequently complicated by fluctuating motor functions and dyskinesias. High-frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment of motor fluctuations and is the most common surgical procedure in PD. Here we report the re-occurrence and aggravation of stuttering following STN-DBS in two male patients treated for advanced PD. In both patients the speech fluency improved considerably when the neurostimulator was turned off, indicating that stuttering aggravation was related to neurostimulation of the STN itself, its afferent or efferent projections and/or to structures localized in the immediate proximity. This report supports previous studies demonstrating that lesions of the basal ganglia-thalamocortical motor circuit, including the STN, is involved in the development of stuttering. In advanced PD STN-DBS is generally an effective and safe treatment. However, patients with PD and stuttering should be informed about the risk of aggravated symptoms following surgical therapy. PMID:21477305

UK Renal Registry 15th annual report: Chapter 8 UK multisite peritoneal dialysis access catheter audit for first PD catheters 2011.

PubMed

Briggs, Victoria; Pitcher, David; Braddon, Fiona; Fogarty, Damian; Wilkie, Martin

2013-01-01

The central paradigm of effective peritoneal dialysis (PD) is an appropriate standard of PD catheter function. The aim of the project was to develop an effective national PD access audit which would identify an 'appropriate standard' of PD catheter function. The UK Renal Registry collected centre specific information on various PD access outcome measures including catheter functionality and post-insertion complications. The first PD access audit covering England, Northern Ireland and Wales was conducted during April to June 2012 looking at incident dialysis patients in 2011. Forty three data collection spreadsheets were returned from a total of 65 centres describing 917 PD catheter placements. The median age of PD patients was 61 years and 61.5% were male. The proportion of patients initiated on PD in comparison to HD was lower in socially deprived areas. There was a relationship between the timing of nephrology referral and the likelihood of surgical assessment regarding PD catheter placement. Patients with diabetes did not have higher rates of PD catheter failure or of early peritonitis. A comparative PD catheter audit has the potential to provide valuable information on an important patient related outcome measure and lead to an improvement in patient experience. There was wide variation between centres of PD catheter use for late presenting patients. Overall patients were more likely to get a PD catheter if they had been known to the service for more than 1 year. The percutaneous insertion technique was associated with a higher early (less than 2 week) peritonitis rate and more catheter flow problems. Copyright © 2013 S. Karger AG, Basel.

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

Centro TORTUGA's Integrated Research and Professional Development Training for Early Stage Hispanic Students in Puerto Rico

NASA Astrophysics Data System (ADS)

Moser, F. C.; Allen, M. R.; Barberena-Arias, M.; Clark, J.; Harris, L.; Maldonado, P. M.; Olivo-Delgado, C.; Pierson, J. J.

2017-12-01

Over the last five years our multidisciplinary team explored different undergraduate research and professional development (PD) strategies to improve early stage Hispanic student retention in marine science with the objective of interesting them in pursuing degrees that may ultimately lead to geoscience careers. This research led to the 2016 launch of our current project, Centro TORTUGA (Tropical Oceanography Research Training for Undergraduate Academics). Our overarching goal is to increase the number of underrepresented students from minority serving institutions in geoscience-relevant disciplines and careers. Critical to success is building a program rich in both research and PD. Based on qualitative and quantitative evaluations we found students benefited from PD efforts to increase skills in areas such as: 1) speaking and writing English; 2) science communication; 3) teamwork; 4) project management; and 5) completing internship/graduate school applications. To build student self-confidence, networking, and science skills Centro Tortuga involves students' families, bridges cultural gaps across research and non-research institutions inside and outside of Puerto Rico, and provides a gathering place (Centro TORTUGA) for students. With our partners, Universidad del Turabo (UT), Universidad Metropolitana (UMET), and University of Maryland Center for Environmental Sciences, we are now testing a 12-month integrated research and PD curriculum. Initial results suggest areas for improved student training include: 1) science communication (reports and graphs); 2) science ethics; and 3) poster and oral presentations. Students also identified specific preparation they would like included in the Centro TORTUGA curriculum.

Designing a Self-Management App for Young People With Type 1 Diabetes: Methodological Challenges, Experiences, and Recommendations

PubMed Central

Reventlov Husted, Gitte; Teilmann, Grete; Hommel, Eva; Olsen, Birthe Susanne; Kensing, Finn

2017-01-01

Background Young people with type 1 diabetes often struggle to self-manage their disease. Mobile health (mHealth) apps show promise in supporting self-management of chronic conditions such as type 1 diabetes. Many health care providers become involved in app development. Unfortunately, limited information is available to guide their selection of appropriate methods, techniques, and tools for a participatory design (PD) project in health care. Objective The aim of our study was to develop an mHealth app to support young people in self-managing type 1 diabetes. This paper presents our methodological recommendations based on experiences and reflections from a 2-year research study. Methods A mixed methods design was used to identify user needs before designing the app and testing it in a randomized controlled trial. App design was based on qualitative, explorative, interventional, and experimental activities within an overall iterative PD approach. Several techniques and tools were used, including workshops, a mail panel, think-aloud tests, and a feasibility study. Results The final mHealth solution was “Young with Diabetes” (YWD). The iterative PD approach supported researchers and designers in understanding the needs of end users (ie, young people, parents, and health care providers) and their assessment of YWD, as well as how to improve app usability and feasibility. It is critical to include all end user groups during all phases of a PD project and to establish a multidisciplinary team to provide the wide range of expertise required to build a usable and useful mHealth app. Conclusions Future research is needed to develop and evaluate more efficient PD techniques. Health care providers need guidance on what tools and techniques to choose for which subgroups of users and guidance on how to introduce an app to colleagues to successfully implement an mHealth app in health care organizations. These steps are important for anyone who wants to design an mHealth app for any illness. PMID:29061552

Imaging, biodistribution, and dosimetry of radionuclide-labeled PD-L1 antibody in an immunocompetent mouse model of breast cancer

PubMed Central

Josefsson, Anders; Nedrow, Jessie R.; Park, Sunju; Banerjee, Sangeeta Ray; Rittenbach, Andrew; Jammes, Fabien; Tsui, Benjamin; Sgouros, George

2015-01-01

The programmed cell death ligand 1 (PD-L1) participates in an immune checkpoint system involved in preventing autoimmunity. PD-L1 is expressed on tumor cells, tumor-associated macrophages, and other cells in the tumor microenvironment. Anti-PD-L1 antibodies are active against a variety of cancers, and combined anti-PD-L1 therapy with external beam radiotherapy has been shown to increase therapeutic efficacy. PD-L1 expression status is an important indicator of prognosis and therapy responsiveness, but methods to precisely capture the dynamics of PD-L1 expression in the tumor microenvironment are still limited. In this study, we developed a murine anti-PD-L1 antibody conjugated to the radioactive isotope Indium-111 (111In) for imaging and biodistribution studies in an immune-intact mouse model of breast cancer. The distribution of 111In-DTPA-anti-PD-L1 in tumors as well as the spleen, liver, thymus, heart, and lungs peaked 72 hours after injection. Co-injection of labeled and 100-fold unlabeled antibody significantly reduced spleen uptake at 24 hours, indicating that an excess of unlabeled antibody effectively blocked PD-L1 sites in the spleen, thus shifting the concentration of 111In-DTPA-anti-PD-L1 into the blood stream and potentially increasing tumor uptake. Clearance of 111In-DTPA-anti-PD-L1 from all organs occurred at 144 hours. Moreover, dosimetry calculations revealed that radionuclide-labeled anti-PD-L1 antibody yielded tolerable projected marrow doses, further supporting its use for radiopharmaceutical therapy. Taken together, these studies demonstrate the feasibility of using anti-PD-L1 antibody for radionuclide imaging and radioimmunotherapy, and highlight a new opportunity to optimize and monitor the efficacy of immune checkpoint inhibition therapy. PMID:26554829

Assessing Teacher and Student Effects of the Research Goes to School Project

ERIC Educational Resources Information Center

Kararo, Alex T.

2017-01-01

There have been calls by the Federal government and policymakers for improvements in science, technology, engineering and mathematics (STEM) education through the development of excellent teachers with the content knowledge and skills to teach and motivate students. A shared goal among teacher professional development (PD) programs is to improve…

Enabling breakthroughs in Parkinson’s disease with wearable technologies and big data analytics

PubMed Central

Cohen, Shahar; Martig, Adria K.

2016-01-01

Parkinson’s disease (PD) is a progressive, degenerative disorder of the central nervous system that is diagnosed and measured clinically by the Unified Parkinson’s Disease Rating Scale (UPDRS). Tools for continuous and objective monitoring of PD motor symptoms are needed to complement clinical assessments of symptom severity to further inform PD therapeutic development across several arenas, from developing more robust clinical trial outcome measures to establishing biomarkers of disease progression. The Michael J. Fox Foundation for Parkinson’s Disease Research and Intel Corporation have joined forces to develop a mobile application and an Internet of Things (IoT) platform to support large-scale studies of objective, continuously sampled sensory data from people with PD. This platform provides both population and per-patient analyses, measuring gait, activity level, nighttime activity, tremor, as well as other structured assessments and tasks. All data collected will be available to researchers on an open-source platform. Development of the IoT platform raised a number of engineering considerations, including wearable sensor choice, data management and curation, and algorithm validation. This project has successfully demonstrated proof of concept that IoT platforms, wearable technologies and the data they generate offer exciting possibilities for more robust, reliable, and low-cost research methodologies and patient care strategies. PMID:28293596

Enabling breakthroughs in Parkinson's disease with wearable technologies and big data analytics.

PubMed

Cohen, Shahar; Bataille, Lauren R; Martig, Adria K

2016-01-01

Parkinson's disease (PD) is a progressive, degenerative disorder of the central nervous system that is diagnosed and measured clinically by the Unified Parkinson's Disease Rating Scale (UPDRS). Tools for continuous and objective monitoring of PD motor symptoms are needed to complement clinical assessments of symptom severity to further inform PD therapeutic development across several arenas, from developing more robust clinical trial outcome measures to establishing biomarkers of disease progression. The Michael J. Fox Foundation for Parkinson's Disease Research and Intel Corporation have joined forces to develop a mobile application and an Internet of Things (IoT) platform to support large-scale studies of objective, continuously sampled sensory data from people with PD. This platform provides both population and per-patient analyses, measuring gait, activity level, nighttime activity, tremor, as well as other structured assessments and tasks. All data collected will be available to researchers on an open-source platform. Development of the IoT platform raised a number of engineering considerations, including wearable sensor choice, data management and curation, and algorithm validation. This project has successfully demonstrated proof of concept that IoT platforms, wearable technologies and the data they generate offer exciting possibilities for more robust, reliable, and low-cost research methodologies and patient care strategies.

Section 107 Detailed Project Report. Fort Gaines Channel (Government Cut) at Dauphin Island, Alabama

DTIC Science & Technology

1990-03-01

Engineer District, Mobile AREA &WORK UNIT NUMBERS Plan Dev. Sec., Planning Div., (CESAM-PD-FP)- P. 0. Box 2-288, Mobi,L.3.a6628-OO.....,__ 11I...C’ONTAOLLING OFFICE NAME AND ADDRESS M 2 REPORT DATE US. Army Engineer District, Mobile March 1990 Pian Development Sec., Plan. Div., (CESAM-PD-FP) 13 NUMBER...OF PAGES P- 0. Box 2288, Mobile , AL 36628-0001 162 t4. MONITORING AGENCY NAME & ADORESS(11 different from Controlling Office) 15. SECURITY CLASS. (ol

Dulce Wireless Tijuana: A Randomized Control Trial Evaluating the Impact of Project Dulce and Short-Term Mobile Technology on Glycemic Control in a Family Medicine Clinic in Northern Mexico

PubMed Central

Contreras, Sonia; Vargas-Ojeda, Adriana; Menchaca-Díaz, Rufino; Fortmann, Addie; Philis-Tsimikas, Athena

2016-01-01

Abstract Background: The global epidemic of diabetes calls for innovative interventions. This study evaluated the effectiveness of the Project Dulce model, with and without wireless technology, on glycemic control and other clinical and self-reported outcomes in patients with poorly controlled type 2 diabetes in Mexico. Subjects and Methods: Adults with type 2 diabetes and a glycated hemoglobin A1c (HbA1c) level of ≥8% were recruited from Family Medical Unit #27 of the Instituto Mexicano del Seguro Social (IMSS) in Tijuana, México, and randomly assigned to one of three groups: Project Dulce–only (PD); Project Dulce technology-enhanced with mobile tools (PD-TE); or IMSS standard of care/control group (CG). Clinical and self-reported outcomes were assessed at baseline, Month 4, and Month 10. Time-by-group interactions and within-group changes were analyzed. Results: HbA1c reductions from baseline to Month 10 were significantly greater in PD-TE (−3.0% [−33 mmol/mol]) and PD (−2.6% [−28.7 mmol/mol]) compared with CG (−1.3% [−14.2 mmol/mol]) (P = 0.009 and 0.001, respectively). PD-TE and PD also exhibited significant improvement in diabetes knowledge when compared with CG (P < 0.05 for both). No statistically significant differences were detected between PD and PD-TE on these indicators (P = 0.54 and 0.86, respectively). Several within-group improvements were observed on other clinical and self-report indicators but did not vary significantly across groups. Conclusions: Project Dulce with and without wireless technology substantially improved glycemic control and diabetes knowledge in high-risk patients with type 2 diabetes in a Mexican family medical unit, suggesting that integrating peer-led education, nurse coordination, and 3G wireless technology is an effective approach for improving diabetes outcomes in high-risk populations. PMID:26914371

Noradrenergic Dysfunction in Alzheimer's and Parkinson's Diseases-An Overview of Imaging Studies.

PubMed

Peterson, Andrew C; Li, Chiang-Shan R

2018-01-01

Noradrenergic dysfunction contributes to cognitive impairment in Alzheimer's Disease (AD) and Parkinson's Disease (PD). Conventional therapeutic strategies seek to enhance cholinergic and dopaminergic neurotransmission in AD and PD, respectively, and few studies have examined noradrenergic dysfunction as a target for medication development. We review the literature of noradrenergic dysfunction in AD and PD with a focus on human imaging studies that implicate the locus coeruleus (LC) circuit. The LC sends noradrenergic projections diffusely throughout the cerebral cortex and plays a critical role in attention, learning, working memory, and cognitive control. The LC undergoes considerable degeneration in both AD and PD. Advances in magnetic resonance imaging have facilitated greater understanding of how structural and functional alteration of the LC may contribute to cognitive decline in AD and PD. We discuss the potential roles of the noradrenergic system in the pathogenesis of AD and PD with an emphasis on postmortem anatomical studies, structural MRI studies, and functional MRI studies, where we highlight changes in LC connectivity with the default mode network (DMN). LC degeneration may accompany deficient capacity in suppressing DMN activity and increasing saliency and task control network activities to meet behavioral challenges. We finish by proposing potential and new directions of research to address noradrenergic dysfunction in AD and PD.

Unimpaired postprandial pancreatic polypeptide secretion in Parkinson's disease and REM sleep behavior disorder.

PubMed

Unger, Marcus M; Ekman, Rolf; Björklund, Anna-Karin; Karlsson, Gösta; Andersson, Chatarina; Mankel, Katharina; Bohne, Katharina; Tebbe, Johannes J; Stiasny-Kolster, Karin; Möller, Jens C; Mayer, Geert; Kann, Peter H; Oertel, Wolfgang H

2013-04-01

Pancreatic polypeptide is released immediately after food ingestion. The release is operated by vagal-abdominal projections and has therefore been suggested as a test for vagal nerve integrity. Pathoanatomical and clinical studies indicate vagal dysfunction in early Parkinson's disease (PD). We assessed the postprandial secretion of pancreatic polypeptide and motilin in healthy controls (n = 18) and patients with idiopathic rapid-eye-movement sleep behavior disorder (iRBD, n = 10), a potential premotor stage of PD, as well as in drug-naive (n = 19) and treated (n = 19) PD patients. The postprandial pancreatic polypeptide secretion showed a physiological pattern in all groups and even an enhanced response in drug-naive PD and iRBD. Motilin concentrations correlated with pancreatic polypeptide concentrations. Postprandial pancreatic polypeptide secretion is not a suitable test for vagal nerve integrity in PD. The unimpaired pancreatic polypeptide response in iRBD and PD might be explained by partially intact vagal-abdominal projections or compensatory mechanisms substituting a defective neuronal brain-gut axis. Copyright © 2012 Movement Disorders Society.

Motivations of Educators for Participating in an Authentic Astronomy Research Experience Professional Development Program

ERIC Educational Resources Information Center

Rebull, L. M.; Roberts, T.; Laurence, W.; Fitzgerald, M. T.; French, D. A.; Gorjian, V.; Squires, G. K.

2018-01-01

[This paper is part of the Focused Collection on Astronomy Education Research.] The NASA/IPAC Teacher Archive Research Program (NITARP) partners small groups of educators with a research astronomer for a year-long authentic research project. This program aligns well with the characteristics of high-quality professional development (PD) programs…

Enhancing Literacy Practices in Science Classrooms through a Professional Development Program for Canadian Minority-Language Teachers

ERIC Educational Resources Information Center

Rivard, Léonard P.; Gueye, Ndeye R.

2016-01-01

'Literacy in the Science Classroom Project" was a three-year professional development (PD) program supporting minority-language secondary teachers' use of effective language-based instructional strategies for teaching science. Our primary objective was to determine how teacher beliefs and practices changed over time and how these were enacted…

Multi-Year Professional Development Grounded in Educative Curriculum Focused on Integrating Technology with Reformed Science Teaching Principles

ERIC Educational Resources Information Center

Longhurst, Max L.; Coster, Daniel C.; Wolf, Paul G.; Duffy, Aaron M.; Lee, Hyunju; Campbell, Todd

2016-01-01

Visions of science teaching and learning in the newest U.S. standards documents are dramatically different than those found in most classrooms. This research addresses these differences through closely examining one professional development (PD) project that connects teacher learning and teacher practice with student learning/achievement. This…

Teacher Transformation: An Exploration of Science Teachers' Changing Professional Identities, Knowledge, and Classroom Practices

NASA Astrophysics Data System (ADS)

Whitacre, Michelle Phillips

This qualitative, multiple case study examines five teachers' experiences with a National Science Foundation-funded professional development (PD) program focused on science literacy. Using a three dimensional conceptual framework combining transformative learning theory, communities of practice, and sociocultural conceptions of identity it explores: the ways the "Science Literacy through Science Journalism" (SciJourn) project built professional community and influenced teacher learning; the influence of the project on participating science teachers' professional identities, knowledge, and classroom practices; and the ways teachers were or were not transformed by participation in the project. To this end, data from surveys and phenomenological interviews were analyzed through qualitative textual analysis and narrative analysis. Four of the teachers experienced a change in their stories to live by, aka, an identity shift. Three predominant themes emerged across these cases. These included a changed conceptualization of science literacy, the importance of student engagement and authenticity, and the value of SciJourn's professional development and community. The changed conceptualization of science literacy was particularly salient as it challenged these teachers' assumptions, led them to rethink how they teach science literacy, and also influenced them to re-evaluate their teaching priorities beyond the PD. Consequently, this study concludes that PD efforts should focus as much, or more, on influencing teachers' ideas regarding what and how they teach and less on teaching strategies. A close comparison between two teachers' diverging experiences with the program showed that student engagement played a significant role in teachers' perceptions of the value of project, suggesting that whether or not teachers sustain a new practice is closely tied to their students' feedback. Additionally, this analysis showed that a teacher's individualized needs and sense of efficacy in implementing a specific reform effort are of consequence. Thus, in order to be influential, PD must somehow speak to a teacher's individualized needs, whether or not these needs are specifically stated at the program's onset. Aside from wanting to implement a project, a teacher also needs to believe that he or she is capable of successfully doing so. In considering transformative learning theory as a conceptual framework, the research presented here gives evidence that certain phases of transformation may be more significant than others, and phase two (self-examination with feelings of fear, anger, guilt, or shame) should be expanded to include a wider range of emotions.

In pursuit of rigour and accountability in participatory design☆

PubMed Central

Frauenberger, Christopher; Good, Judith; Fitzpatrick, Geraldine; Iversen, Ole Sejer

2015-01-01

The field of Participatory Design (PD) has greatly diversified and we see a broad spectrum of approaches and methodologies emerging. However, to foster its role in designing future interactive technologies, a discussion about accountability and rigour across this spectrum is needed. Rejecting the traditional, positivistic framework, we take inspiration from related fields such as Design Research and Action Research to develop interpretations of these concepts that are rooted in PD׳s own belief system. We argue that unlike in other fields, accountability and rigour are nuanced concepts that are delivered through debate, critique and reflection. A key prerequisite for having such debates is the availability of a language that allows designers, researchers and practitioners to construct solid arguments about the appropriateness of their stances, choices and judgements. To this end, we propose a “tool-to-think-with” that provides such a language by guiding designers, researchers and practitioners through a process of systematic reflection and critical analysis. The tool proposes four lenses to critically reflect on the nature of a PD effort: epistemology, values, stakeholders and outcomes. In a subsequent step, the coherence between the revealed features is analysed and shows whether they pull the project in the same direction or work against each other. Regardless of the flavour of PD, we argue that this coherence of features indicates the level of internal rigour of PD work and that the process of reflection and analysis provides the language to argue for it. We envision our tool to be useful at all stages of PD work: in the planning phase, as part of a reflective practice during the work, and as a means to construct knowledge and advance the field after the fact. We ground our theoretical discussions in a specific PD experience, the ECHOES project, to motivate the tool and to illustrate its workings. PMID:26109833

A mobile cloud-based Parkinson's disease assessment system for home-based monitoring.

PubMed

Pan, Di; Dhall, Rohit; Lieberman, Abraham; Petitti, Diana B

2015-03-26

Parkinson's disease (PD) is the most prevalent movement disorder of the central nervous system, and affects more than 6.3 million people in the world. The characteristic motor features include tremor, bradykinesia, rigidity, and impaired postural stability. Current therapy based on augmentation or replacement of dopamine is designed to improve patients' motor performance but often leads to levodopa-induced adverse effects, such as dyskinesia and motor fluctuation. Clinicians must regularly monitor patients in order to identify these effects and other declines in motor function as soon as possible. Current clinical assessment for Parkinson's is subjective and mostly conducted by brief observations made during patient visits. Changes in patients' motor function between visits are hard to track and clinicians are not able to make the most informed decisions about the course of therapy without frequent visits. Frequent clinic visits increase the physical and economic burden on patients and their families. In this project, we sought to design, develop, and evaluate a prototype mobile cloud-based mHealth app, "PD Dr", which collects quantitative and objective information about PD and would enable home-based assessment and monitoring of major PD symptoms. We designed and developed a mobile app on the Android platform to collect PD-related motion data using the smartphone 3D accelerometer and to send the data to a cloud service for storage, data processing, and PD symptoms severity estimation. To evaluate this system, data from the system were collected from 40 patients with PD and compared with experts' rating on standardized rating scales. The evaluation showed that PD Dr could effectively capture important motion features that differentiate PD severity and identify critical symptoms. For hand resting tremor detection, the sensitivity was .77 and accuracy was .82. For gait difficulty detection, the sensitivity was .89 and accuracy was .81. In PD severity estimation, the captured motion features also demonstrated strong correlation with PD severity stage, hand resting tremor severity, and gait difficulty. The system is simple to use, user friendly, and economically affordable. The key contribution of this study was building a mobile PD assessment and monitoring system to extend current PD assessment based in the clinic setting to the home-based environment. The results of this study proved feasibility and a promising future for utilizing mobile technology in PD management.

A Mobile Cloud-Based Parkinson’s Disease Assessment System for Home-Based Monitoring

PubMed Central

Petitti, Diana B

2015-01-01

Background Parkinson’s disease (PD) is the most prevalent movement disorder of the central nervous system, and affects more than 6.3 million people in the world. The characteristic motor features include tremor, bradykinesia, rigidity, and impaired postural stability. Current therapy based on augmentation or replacement of dopamine is designed to improve patients’ motor performance but often leads to levodopa-induced adverse effects, such as dyskinesia and motor fluctuation. Clinicians must regularly monitor patients in order to identify these effects and other declines in motor function as soon as possible. Current clinical assessment for Parkinson’s is subjective and mostly conducted by brief observations made during patient visits. Changes in patients’ motor function between visits are hard to track and clinicians are not able to make the most informed decisions about the course of therapy without frequent visits. Frequent clinic visits increase the physical and economic burden on patients and their families. Objective In this project, we sought to design, develop, and evaluate a prototype mobile cloud-based mHealth app, “PD Dr”, which collects quantitative and objective information about PD and would enable home-based assessment and monitoring of major PD symptoms. Methods We designed and developed a mobile app on the Android platform to collect PD-related motion data using the smartphone 3D accelerometer and to send the data to a cloud service for storage, data processing, and PD symptoms severity estimation. To evaluate this system, data from the system were collected from 40 patients with PD and compared with experts’ rating on standardized rating scales. Results The evaluation showed that PD Dr could effectively capture important motion features that differentiate PD severity and identify critical symptoms. For hand resting tremor detection, the sensitivity was .77 and accuracy was .82. For gait difficulty detection, the sensitivity was .89 and accuracy was .81. In PD severity estimation, the captured motion features also demonstrated strong correlation with PD severity stage, hand resting tremor severity, and gait difficulty. The system is simple to use, user friendly, and economically affordable. Conclusions The key contribution of this study was building a mobile PD assessment and monitoring system to extend current PD assessment based in the clinic setting to the home-based environment. The results of this study proved feasibility and a promising future for utilizing mobile technology in PD management. PMID:25830687

DEVELOPMENT OF A NEONATAL RAT PHYSIOLOGICALLY BASED PHARMACOKINETIC/PHARMACODYNAMIC (PBPK/PD) MODEL FOR CHLORPYRIFOS. (R828608)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

Operations planning and analysis handbook for NASA/MSFC phase B development projects

NASA Technical Reports Server (NTRS)

Batson, Robert C.

1986-01-01

Current operations planning and analysis practices on NASA/MSFC Phase B projects were investigated with the objectives of (1) formalizing these practices into a handbook and (2) suggesting improvements. The study focused on how Science and Engineering (S&E) Operational Personnel support Program Development (PD) Task Teams. The intimate relationship between systems engineering and operations analysis was examined. Methods identified for use by operations analysts during Phase B include functional analysis, interface analysis methods to calculate/allocate such criteria as reliability, Maintainability, and operations and support cost.

KSC-02pd0629

NASA Image and Video Library

2002-04-30

KENNEDY SPACE CENTER, FLA. -- At the 2002 Space Congress, Cape Canaveral, Fla., Frank Ceppolina, project manager, Hubble Space Telescope Development Project, gives a presentation on "Hubble Discoveries." The Space Congress is held annually to highlight military and space initiatives, new technologies, and Florida's role in programs and research. This year's theme is Beginning a New Era - Initiatives in Space. NASA presented several paper sessions, including Advancements in Technology. Space Congress is sponsored by the Canaveral Council of Technical Societies

One Science Teacher's Professional Development Experience: A Case Study Exploring Changes in Students' Perceptions of Their Fluency with Innovative Technologies

ERIC Educational Resources Information Center

Ebenezer, Jazlin; Columbus, Russell; Kaya, Osman Nafiz; Zhang, Lin; Ebenezer, Devairakkam Luke

2012-01-01

The purpose of this case-study is to narrate a secondary science teacher's experience of his professional development (PD) education and training in innovative technologies (IT) in the context of engaging students in environmental research projects. The sources from which the narrative is derived include (1) the science teacher's reflective…

Designing a Self-Management App for Young People With Type 1 Diabetes: Methodological Challenges, Experiences, and Recommendations.

PubMed

Castensøe-Seidenfaden, Pernille; Reventlov Husted, Gitte; Teilmann, Grete; Hommel, Eva; Olsen, Birthe Susanne; Kensing, Finn

2017-10-23

Young people with type 1 diabetes often struggle to self-manage their disease. Mobile health (mHealth) apps show promise in supporting self-management of chronic conditions such as type 1 diabetes. Many health care providers become involved in app development. Unfortunately, limited information is available to guide their selection of appropriate methods, techniques, and tools for a participatory design (PD) project in health care. The aim of our study was to develop an mHealth app to support young people in self-managing type 1 diabetes. This paper presents our methodological recommendations based on experiences and reflections from a 2-year research study. A mixed methods design was used to identify user needs before designing the app and testing it in a randomized controlled trial. App design was based on qualitative, explorative, interventional, and experimental activities within an overall iterative PD approach. Several techniques and tools were used, including workshops, a mail panel, think-aloud tests, and a feasibility study. The final mHealth solution was "Young with Diabetes" (YWD). The iterative PD approach supported researchers and designers in understanding the needs of end users (ie, young people, parents, and health care providers) and their assessment of YWD, as well as how to improve app usability and feasibility. It is critical to include all end user groups during all phases of a PD project and to establish a multidisciplinary team to provide the wide range of expertise required to build a usable and useful mHealth app. Future research is needed to develop and evaluate more efficient PD techniques. Health care providers need guidance on what tools and techniques to choose for which subgroups of users and guidance on how to introduce an app to colleagues to successfully implement an mHealth app in health care organizations. These steps are important for anyone who wants to design an mHealth app for any illness. ©Pernille Castensøe-Seidenfaden, Gitte Reventlov Husted, Grete Teilmann, Eva Hommel, Birthe Susanne Olsen, Finn Kensing. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 23.10.2017.

Legitimating Multilingual Teacher Identities in the Mainstream Classroom

ERIC Educational Resources Information Center

Higgins, Christina; Ponte, Eva

2017-01-01

This article explores the identities of a group of elementary teachers who participated in a professional development (PD) project on multilingual language learners. We study how the participating teachers drew on different aspects of their identities to respond to encouragement to increase their attention to students' diverse multilingual…

Individual and Contextual Factors Influencing Special Education Teacher Learning in Literacy Learning Cohorts

ERIC Educational Resources Information Center

Brownell, Mary T.; Lauterbach, Alexandra A.; Dingle, Mary P.; Boardman, Alison G.; Urbach, Jennifer E.; Leko, Melinda M.; Benedict, Amber E.; Park, Yujeong

2014-01-01

In this study, researchers operated from cognitive and situated perspectives to understand how individual qualities and contextual factors influenced elementary special education teachers' learning in a multifaceted professional development (PD) project, Literacy Learning Cohort, focused on word study and fluency instruction. Grounded theory…

KSC-02pd0626

NASA Image and Video Library

2002-04-30

KENNEDY SPACE CENTER, FLA. -- At the 2002 Space Congress, Cape Canaveral, Fla., attendees listen to a presentation on "Hubble Discoveries" by Frank Ceppolina, project manager, Hubble Space Telescope Development Project. The Space Congress is held annually to highlight military and space initiatives, new technologies, and Florida's role in programs and research. This year's theme is Beginning a New Era - Initiatives in Space. NASA presented several paper sessions, including Advancements in Technology. Space Congress is sponsored by the Canaveral Council of Technical Societies

High School Football and Risk of Neurodegeneration: A Community-Based Study

PubMed Central

Savica, Rodolfo; Parisi, Joseph E.; Wold, Lester E.; Josephs, Keith A.; Ahlskog, J. Eric

2012-01-01

Objective To assess whether high school football played between 1946 and 1956, when headgear was less protective than today, was associated with development of neurodegenerative diseases later in life. Methods All male students who played football from 1946 to 1956 in the high schools of Rochester, Minnesota, plus a non–football-playing referent group of male students in the band, glee club, or choir were identified. Using the records-linkage system of the Rochester Epidemiology Project, we reviewed (from October 31, 2010, to March 30, 2011) all available medical records to assess later development of dementia, Parkinson disease (PD), or amyotrophic lateral sclerosis (ALS). We also compared the frequency of dementia, PD, or ALS with incidence data from the general population of Olmsted County, Minnesota. Results We found no increased risk of dementia, PD, or ALS among the 438 football players compared with the 140 non–football-playing male classmates. Parkinson disease and ALS were slightly less frequent in the football group, whereas dementia was slightly more frequent, but not significantly so. When we compared these results with the expected incidence rates in the general population, only PD was significantly increased; however, this was true for both groups, with a larger risk ratio in the non–football group. Conclusion Our findings suggest that high school students who played American football from 1946 to 1956 did not have an increased risk of later developing dementia, PD, or ALS compared with non–football-playing high school males, despite poorer equipment and less regard for concussions compared with today and no rules prohibiting head-first tackling (spearing). PMID:22469346

Alternate electrode materials for the SP100 reactor

NASA Astrophysics Data System (ADS)

Randich, E.

1992-05-01

This work was performed in response to a request by the Astro-Space Division of the General Electric Co. to develop alternate electrodes materials for the electrodes of the PD2 modules to be used in the SP100 thermoelectric power conversion system. Initially, the project consisted of four tasks: (1) development of a ZrB2 (C) CVD coating on SiMo substrates; (2) development of a ZrB2 (C) CVD coating on SiGe substrates; (3) development of CVI W for porous graphite electrodes; and (4) technology transfer of pertinent developed processes. The project evolved initially into developing only ZrB2 coatings on SiGe and graphite substrates, and later into developing ZrB2 coatings only on graphite substrates. Several sizes of graphite and pyrolytic carbon-coated graphite substrates were coated with ZrB2 during the project. For budgetary reasons, the project was terminated after half the allotted time had passed. Apart from the production of coated specimens for evaluation, the major accomplishment of the project was the development of the CVD processing to produce the desired coatings.

Mental Health Technologies: Designing With Consumers.

PubMed

Orlowski, Simone; Matthews, Ben; Bidargaddi, Niranjan; Jones, Gabrielle; Lawn, Sharon; Venning, Anthony; Collin, Philippa

2016-01-28

Despite growing interest in the promise of e-mental and well-being interventions, little supporting literature exists to guide their design and the evaluation of their effectiveness. Both participatory design (PD) and design thinking (DT) have emerged as approaches that hold significant potential for supporting design in this space. Each approach is difficult to definitively circumscribe, and as such has been enacted as a process, a mind-set, specific practices/techniques, or a combination thereof. At its core, however, PD is a design research tradition that emphasizes egalitarian partnerships with end users. In contrast, DT is in the process of becoming a management concept tied to innovation with strong roots in business and education. From a health researcher viewpoint, while PD can be reduced to a number of replicable stages that involve particular methods, techniques, and outputs, projects often take vastly different forms and effective PD projects and practice have traditionally required technology-specific (eg, computer science) and domain-specific (eg, an application domain, such as patient support services) knowledge. In contrast, DT offers a practical off-the-shelf toolkit of approaches that at face value have more potential to have a quick impact and be successfully applied by novice practitioners (and those looking to include a more human-centered focus in their work). Via 2 case studies we explore the continuum of similarities and differences between PD and DT in order to provide an initial recommendation for what health researchers might reasonably expect from each in terms of process and outcome in the design of e-mental health interventions. We suggest that the sensibilities that DT shares with PD (ie, deep engagement and collaboration with end users and an inclusive and multidisciplinary practice) are precisely the aspects of DT that must be emphasized in any application to mental health provision and that any technology development process must prioritize empathy and understanding over innovation for the successful uptake of technology in this space.

Mental Health Technologies: Designing With Consumers

PubMed Central

Matthews, Ben; Bidargaddi, Niranjan; Jones, Gabrielle; Lawn, Sharon; Venning, Anthony; Collin, Philippa

2016-01-01

Despite growing interest in the promise of e-mental and well-being interventions, little supporting literature exists to guide their design and the evaluation of their effectiveness. Both participatory design (PD) and design thinking (DT) have emerged as approaches that hold significant potential for supporting design in this space. Each approach is difficult to definitively circumscribe, and as such has been enacted as a process, a mind-set, specific practices/techniques, or a combination thereof. At its core, however, PD is a design research tradition that emphasizes egalitarian partnerships with end users. In contrast, DT is in the process of becoming a management concept tied to innovation with strong roots in business and education. From a health researcher viewpoint, while PD can be reduced to a number of replicable stages that involve particular methods, techniques, and outputs, projects often take vastly different forms and effective PD projects and practice have traditionally required technology-specific (eg, computer science) and domain-specific (eg, an application domain, such as patient support services) knowledge. In contrast, DT offers a practical off-the-shelf toolkit of approaches that at face value have more potential to have a quick impact and be successfully applied by novice practitioners (and those looking to include a more human-centered focus in their work). Via 2 case studies we explore the continuum of similarities and differences between PD and DT in order to provide an initial recommendation for what health researchers might reasonably expect from each in terms of process and outcome in the design of e-mental health interventions. We suggest that the sensibilities that DT shares with PD (ie, deep engagement and collaboration with end users and an inclusive and multidisciplinary practice) are precisely the aspects of DT that must be emphasized in any application to mental health provision and that any technology development process must prioritize empathy and understanding over innovation for the successful uptake of technology in this space. PMID:27026210

Healthcare Data Analytics for Parkinson's Disease Patients: A Study of Hospital Cost and Utilization in the United States.

PubMed

Mukherjee, Sunanda; Wu, Huanmei; Jones, Josette

2016-01-01

Parkinson's Disease (PD), a prevalent problem, especially for the aged populations, is a progressive but non-fatal nervous system disorder. PD patients have special motor as well as non-motor symptoms over time. There are several limitations in the study of PD such as unavailability of data, proper diagnosis and treatment methods. These limitations significantly reduce the quality of PD patient life quality, either directly or indirectly. PD also imposes great financial burdens to PD patients and their family. This project aims to analyze the most common reasons for PD patient hospitalization, review complications that occur during inpatient stays, and measure the costs associated with PD patient characteristics. Using the HCUP NIS data, comprehensive data analysis has been performed. The results are customized visualized using Tableau and other software systems. The preliminary findings sheds light into how to improve the life quality of PD patients.

Science Teaching Orientations and Technology-Enhanced Tools for Student Learning

ERIC Educational Resources Information Center

Campbell, Todd; Longhurst, Max; Duffy, Aaron M.; Wolf, Paul G.; Shelton, Brett E.

2013-01-01

This qualitative study examines teacher orientations and technology-enhanced tools for student learning within a science literacy framework. Data for this study came from a group of 10 eighth grade science teachers. Each of these teachers was a participant in a professional development (PD) project focused on reformed and technology-enhanced…

"Flipping" educational technology professional development for K-12 educators

NASA Astrophysics Data System (ADS)

Spencer, Daniel

As the demand for more effective professional development increases in K-12 schools, trainers must adjust their training methods to meet the needs of their teacher learners. Just as lecture-heavy, teacher-centered instruction only meet the learning needs of a small minority of students, "sit and get" professional development rarely results in the teachers gaining the skills and confidence necessary to use technology effectively in their instruction. To resolve the frustrations of teachers related to ineffective professional development, a "Flipped PD" training model was developed based on the learning needs of adult learners, the integration of technological, pedagogical, and content knowledge (TPACK), learning activities, and the Flipped Classroom concept. Under this model, training shifts from a passive, trainer-centered format, to an active, learner-centered format where teachers learn to use technology in their classrooms by first focusing on pedagogical issues, then choosing the options that work best for addressing those issues in their unique situation, and completing "learn-by-doing" projects. Those who participate in "Flipped PD" style trainings tend to have more confidence upon completion that they can use the tools they were trained on in their teaching, as well as believe that the PD was engaging and a good use of their time.

First-order reversal curve investigated magnetization switching in Pd/Co/Pd wedge film

NASA Astrophysics Data System (ADS)

Li, Yan; He, Wei; Sun, Rui; Gong, Zi-Zhao; Li, Na; Gul, Qeemat; Zhang, Xiang-Qun; Cheng, Zhao-Hua

2018-04-01

Not Available Project supported by the National Basic Research Program of China (Grant Nos. 2015CB921403 and 2016YFA0300701) and the National Natural Science Foundation of China (Grant Nos. 51427801, 11374350, and 51671212).

Dissecting the steps of CO2 reduction: 2. The interaction of CO and CO2 with Pd/γ-Al2O3: an in situ FTIR study

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

Szanyi, Janos; Kwak, Ja Hun

2014-08-07

Alumina supported Pd catalysts with metal loadings of 0.5, 2.5 and 10 wt% were investigated by in situ FTIR spectroscopy in order to understand the nature of adsorbed species formed during their exposure to CO2 and CO. Exposing the annealed samples to CO2 at 295 K resulted in the formation of alumina support-bound surface species only: linear adsorbed CO2, bidentate carbonates and bicarbonates. Room temperature exposure of all three samples to CO produced IR features characteristic of both ionic and metallic Pd, as well as bands we observed upon CO2 adsorption (alumina support-bound species). Low temperature (100 K) adsorption ofmore » CO on the three samples provided information about the state of Pd after oxidation and reduction. Oxidized samples contained exclusively ionic Pd, while mostly metallic Pd was present in the reduced samples. Subsequent annealing of the CO-saturated samples revealed the facile (low temperature) reduction of PdOx species by adsorbed CO. This process was evidenced by the variations in IR bands characteristic of ionic and metallic Pd-bound CO, as well as by the appearance of IR bands associated with CO2 adsorption as a function of annealing temperature. Samples containing oxidized Pd species (oxidized, annealed or reduced) always produced CO2 upon their exposure to CO, while CO2-related surface entities were observed on samples having only fully reduced (metallic) Pd. Acknowledgements: The catalyst preparation was supported by a Laboratory Directed Research and Development (LDRD) project. This work was supported by the US Department of Energy Basic Energy Sciences, Division of Chemical Sciences, Geosciences & Biosciences. Pacific Northwest National Laboratory is operated by Battelle for the US Department of Energy. JHK also acknowledges the support of this work by the 2013 Research Fund of UNIST (Ulsan National Institute of Science and Technology, Ulsan, Korea).« less

Professional Development of Faculty: How Do We Know It Is Effective?

NASA Astrophysics Data System (ADS)

Derting, T. L.; Ebert-May, D.; Hodder, J.

2011-12-01

Professional development (PD) of faculty has been an integral component of curriculum reform efforts in STEM. Traditionally, PD occurs through workshops that last from hours to several days. Regardless of the particular model of PD used during a workshop, its effectiveness is usually assessed through self-report surveys of faculty satisfaction, perceived learning, and reports of applications in faculty classrooms. My presentation focuses on ways of assessing the effectiveness of models of PD, with an emphasis on the need for objective measures of change in faculty teaching. The data that I present raise two significant questions about faculty PD. Are traditional approaches to faculty PD effective in changing classroom teaching practices and improving student learning? What evidence is needed to determine the effectiveness of different models of PD? Self-report data have been useful in identifying variables that can influence the extent to which faculty implement new teaching strategies. These variables include faculty beliefs about student learning, self-efficacy, level of dissatisfaction with student learning, departmental rewards for teaching and learning, time limitations, and peer interactions. Self-report data do not, however, provide a complete or necessarily accurate assessment of the impacts of PD on classroom practices and student learning. Objective assessment of teaching and learning is also necessary, yet seldom conducted. Two approaches to such assessment will be presented, one based on student performance and the other based on observations of faculty teaching. In multiple sections of a student-centered, inquiry-based course, learning gains were higher for students taught by faculty who were trained in student-centered teaching compared with faculty with no such training. In two national projects that focused on faculty PD, self-report data indicated that faculty increased their use of student-centered teaching following PD. Objective assessment measures, however, showed that most faculty actually used teacher-centered methods with only minor use of student-centered teaching practices. Moreover, variables that have been associated with change in teaching practices, or the lack thereof, contributed little to explaining observed classroom teaching practice after PD. For example, faculty with less teaching experience engaged in more student-centered teaching compared with faculty with more years of teaching experience. Also, departmental and peer support for faculty use of non-lecture approaches to teaching had no significant relationship with the classroom practices used by faculty. These and other data suggest that assumptions about the effectiveness of traditional models of PDs need to be validated using objective, as well as subjective measures. The data also indicate a need for new models of PD for STEM faculty.

Naringin treatment induces neuroprotective effects in a mouse model of Parkinson's disease in vivo, but not enough to restore the lesioned dopaminergic system.

PubMed

Kim, Heung Deok; Jeong, Kyoung Hoon; Jung, Un Ju; Kim, Sang Ryong

2016-02-01

We recently reported that treatment with naringin, a major flavonoid found in grapefruit and citrus fruits, attenuated neurodegeneration in a rat model of Parkinson's disease (PD) in vivo. In order to investigate whether its effects are universally applied to a different model of PD and whether its treatment induces restorative effects on the lesioned nigrostriatal dopaminergic (DA) projection, we observed the effects of pre-treatment or post-treatment with naringin in a mouse model of PD. For neuroprotective effects, 6-hydroxydopamine (6-OHDA) was unilaterally injected into the striatum of mouse brains for a neurotoxin model of PD in the presence or absence of naringin by daily intraperitoneal injection. Our results showed that naringin protected the nigrostriatal DA projection from 6-OHDA-induced neurotoxicity. Moreover, similar to the effects in rat brains, this treatment induced the activation of mammalian target of rapamycin complex 1 (mTORC1), which is well known as an important survival factor for DA neurons, and inhibited microglial activation in the substantia nigra (SN) of mouse brains treated with 6-OHDA. However, there was no significant change of DA phenotypes in the SN and striatum post-treated with naringin compared with 6-OHDA-lesioned mice, despite the treatment being continued for 12 weeks. These results suggest that post-treatment with naringin alone may not be enough to restore the nigrostriatal DA projection in a mouse model of PD. However, our results apparently suggest that naringin is a beneficial natural product to prevent DA degeneration, which is involved in PD. Copyright © 2015 Elsevier Inc. All rights reserved.

Development and application of noninvasive technology for study of combustion in a combustion chamber of gas turbine engine

NASA Astrophysics Data System (ADS)

Inozemtsev, A. A.; Sazhenkov, A. N.; Tsatiashvili, V. V.; Abramchuk, T. V.; Shipigusev, V. A.; Andreeva, T. P.; Gumerov, A. R.; Ilyin, A. N.; Gubaidullin, I. T.

2015-05-01

The paper formulates the issue of development of experimental base with noninvasive optical-electronic tools for control of combustion in a combustion chamber of gas turbine engine. The design and specifications of a pilot sample of optronic system are explained; this noninvasive system was created in the framework of project of development of main critical technologies for designing of aviation gas turbine engine PD-14. The testbench run data are presented.

A Fundamental Approach to Developing Aluminium based Bulk Amorphous Alloys based on Stable Liquid Metal Structures and Electronic Equilibrium - 154041

DTIC Science & Technology

2017-03-28

AFRL-AFOSR-JP-TR-2017-0027 A Fundamental Approach to Developing Aluminium-based Bulk Amorphous Alloys based on Stable Liquid -Metal Structures and...to 16 Dec 2016 4.  TITLE AND SUBTITLE A Fundamental Approach to Developing Aluminium-based Bulk Amorphous Alloys based on Stable Liquid -Metal...including Al, Cu, Ni, Zr, Mg, Pd, Ga , Ca. Many new Al-based amorphous alloys were found within the numerous alloy systems studied in this project, and

Pawcatuck and Woonasquatucket River Basins and Narragansett Bay Local Drainage Area. Main Report.

DTIC Science & Technology

1981-10-01

building and housing codes are recommended. Flood warning systems, urban renewal, tax incentives, and public open space acquisition will also help...RIVER GROUP WATERSHEDLD LOCAL DRAINAGE PD, WOONASQUATUCKET - MOSI4ASSUCK - PROVIDENCE RIVERS SUB-BASIN PD2 BLACKSTONE RIVER SUB-BASIN orPD 3 TENMiLE...of the Taunton River Basin in Massachusetts, 1979 PNB Water Supply Study, January 1979 Big River Reservoir Project, July 1981 Blackstone River

Schools' Capacity to Absorb a "Healthy School" Approach into Their Operations: Insights from a Realist Evaluation

ERIC Educational Resources Information Center

Deschesnes, Marthe; Drouin, Nathalie; Tessier, Caroline; Couturier, Yves

2014-01-01

Purpose: The purpose of this paper is to understand how a Canadian intervention based on a professional development (PD) model did or did not influence schools' capacities to absorb a Healthy School (HS) approach into their operations. This study is the second part of a research project: previously published results regarding this research…

Genotypic and phenotypic characterization of G6PD deficiency in Bengali adults with severe and uncomplicated malaria.

PubMed

Plewes, Katherine; Soontarawirat, Ingfar; Ghose, Aniruddha; Bancone, Germana; Kingston, Hugh W F; Herdman, M Trent; Leopold, Stije J; Ishioka, Haruhiko; Faiz, Md Abul; Anstey, Nicholas M; Day, Nicholas P J; Hossain, Md Amir; Imwong, Mallika; Dondorp, Arjen M; Woodrow, Charles J

2017-03-29

Control of malaria increasingly involves administration of 8-aminoquinolines, with accompanying risk of haemolysis in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Few data on the prevalence and genotypic basis of G6PD deficiency are available from Bangladesh, where malaria remains a major problem in the South (Chittagong Division). The aim of this study was to determine the prevalence of G6PD deficiency, and associated G6PD genotypes, in adults with falciparum malaria in southern Bangladesh. G6PD status was assessed via a combination of fluorescent spot testing (FST) and genotyping in 141 Bengali patients admitted with falciparum malaria to two centres in Chittagong Division from 2012 to 2014. In addition, an analysis of genomic data from 1000 Genomes Project was carried out among five healthy Indian subcontinent populations. One male patient with uncomplicated malaria was found to have G6PD deficiency on FST and a genotype associated with deficiency (hemizygous Orissa variant). In addition, there were two female patients heterozygous for deficiency variants (Orissa and Kerala-Kalyan). These three patients had a relatively long duration of symptoms prior to admission compared to G6PD normal cases, possibly suggesting an interaction with parasite multiplication rate. In addition, one of 27 healthy local controls was deficient on FST and hemizygous for the Mahidol variant of G6PD deficiency. Examination of 1000 Genomes Project sequencing data across the Indian subcontinent showed that 19/723 chromosomes (2.63%) carried a variant associated with deficiency. In the Bengali from Bangladesh 1000 Genomes population, three of 130 chromosomes (2.31%) carried deficient alleles; this included single chromosomes carrying the Kerala-Kalyan and Orissa variants. In line with other recent work, G6PD deficiency is uncommon in Bengalis in Bangladesh. Further studies of particular ethnic groups are needed to evaluate the potential risk of wide deployment of primaquine in malaria control efforts in Bangladesh.

Neuropathological Staging of Brain Pathology in Sporadic Parkinson's disease: Separating the Wheat from the Chaff.

PubMed

Braak, Heiko; Del Tredici, Kelly

2017-01-01

A relatively small number of especially susceptible nerve cell types within multiple neurotransmitter systems of the human central, peripheral, and enteric nervous systems (CNS, PNS, ENS) become involved in the degenerative process underlying sporadic Parkinson's disease (sPD). The six-stage model we proposed for brain pathology related to sPD (Neurobiol Aging 2003) was a retrospective study of incidental and clinically diagnosed cases performed on unconventionally thick tissue sections (100 μm) from a large number of brain regions.The staging model emphasized what we perceived to be a sequential development of increasing degrees of Lewy pathology in anatomically interconnected regions together with the loss of aminergic projection neurons in, but not limited to, the locus coeruleus and substantia nigra. The same weight was assigned to axonal and somatodendritic Lewy pathology, and the olfactory bulb was included for the first time in a sPD staging system. After years of research, it now appears that the earliest lesions could develop at nonnigral (dopamine agonist nonresponsive) sites, where the surrounding environment is potentially hostile: the olfactory bulb and, possibly, the ENS. The current lack of knowledge regarding the development of Lewy pathology within the peripheral autonomic nervous system, however, means that alternative extra-CNS sites of origin cannot be disregarded as possible candidates. The PD staging system not only caused controversy but contributed a framework for (1) assessing pathology in the spinal cord, ENS, and PNS in relationship to that evolving in the brain, (2) defining prodromal disease and cohorts of at-risk individuals, (3) developing potential prognostic biomarkers for very early disease, (4) testing novel hypotheses and experimental models of α-synuclein propagation and disease progression, and (5) finding causally-oriented therapies that intervene before the substantia nigra becomes involved. The identification of new disease mechanisms at the molecular and cellular levels indicates that physical contacts (transsynaptic) and transneuronal transmission between vulnerable nerve cells are somehow crucial to the pathogenesis of sPD.

Synaptic plasticity and levodopa-induced dyskinesia: electrophysiological and structural abnormalities.

PubMed

Picconi, Barbara; De Leonibus, Elvira; Calabresi, Paolo

2018-02-28

Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive degeneration of dopaminergic neurons located in the midbrain. The gold-standard therapy for PD is the restoration of dopamine (DA) levels through the chronic administration of the DA precursor levodopa (L-DOPA). Although levodopa therapy is the main therapeutic approach for PD, its use is limited by the development of very disabling dyskinetic movements, mainly due to the fluctuation of DA cerebral content. Experimental animal models of PD identified in DA D1/ERK-signaling pathway aberrant activation, occurring in striatal projection neurons, coupled with structural spines abnormalities, the molecular and neuronal basis of L-DOPA-induced dyskinesia (LIDs) occurrence. Different electrophysiological approaches allowed the identification of  the alteration of homeostatic structural and synaptic changes, the neuronal bases of LIDs either in vivo in parkinsonian patients or in vitro in experimental animals. Here, we report the most recent studies showing electrophysiological and morphological evidence of aberrant synaptic plasticity in parkinsonian patients during LIDs in different basal ganglia nuclei and also in cortical transmission, accounting for the complexity of the synaptic changes during dyskinesias. All together, these studies suggest that LIDs are associated with a loss of homeostatic synaptic mechanisms.

KSC-03PD-2384

NASA Technical Reports Server (NTRS)

2003-01-01

KENNEDY SPACE CENTER, FLA. Research team members aboard one of the watercraft being utilized to conduct underwater acoustic research in the Launch Complex 39 turn basin retrieve some of the project's equipment from the water. Several government agencies, including NASA, NOAA, the Navy, the Coast Guard, and the Florida Fish and Wildlife Commission are involved in the testing. The research involves demonstrations of passive and active sensor technologies, with applications in fields ranging from marine biological research to homeland security. The work is also serving as a pilot project to assess the cooperation between the agencies involved. Equipment under development includes a passive acoustic monitor developed by NASAs Jet Propulsion Laboratory, and mobile robotic sensors from the Navys Mobile Diving and Salvage Unit.

KSC-03PD-2381

NASA Technical Reports Server (NTRS)

2003-01-01

KENNEDY SPACE CENTER, FLA. Research team members aboard one of the watercraft being utilized to conduct underwater acoustic research in the Launch Complex 39 turn basin release some of the project's equipment into the water. Several government agencies, including NASA, NOAA, the Navy, the Coast Guard, and the Florida Fish and Wildlife Commission are involved in the testing. The research involves demonstrations of passive and active sensor technologies, with applications in fields ranging from marine biological research to homeland security. The work is also serving as a pilot project to assess the cooperation between the agencies involved. Equipment under development includes a passive acoustic monitor developed by NASAs Jet Propulsion Laboratory, and mobile robotic sensors from the Navys Mobile Diving and Salvage Unit.

One Step Biomass Gas Reforming-Shift Separation Membrane Reactor

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

Roberts, Michael J.; Souleimanova, Razima

2012-12-28

GTI developed a plan where efforts were concentrated in 4 major areas: membrane material development, membrane module development, membrane process development, and membrane gasifier scale-up. GTI assembled a team of researchers to work in each area. Task 1.1 Ceramic Membrane Synthesis and Testing was conducted by Arizona State University (ASU), Task 1.2 Metallic Membrane Synthesis and Testing was conducted by the U.S. National Energy Technology Laboratory (NETL), Task 1.3 was conducted by SCHOTT, and GTI was to test all membranes that showed potential. The initial focus of the project was concentrated on membrane material development. Metallic and glass-based membranes weremore » identified as hydrogen selective membranes under the conditions of the biomass gasification, temperatures above 700C and pressures up to 30 atmospheres. Membranes were synthesized by arc-rolling for metallic type membranes and incorporating Pd into a glass matrix for glass membranes. Testing for hydrogen permeability properties were completed and the effects of hydrogen sulfide and carbon monoxide were investigated for perspective membranes. The initial candidate membrane of Pd80Cu20 chosen in 2008 was selected for preliminary reactor design and cost estimates. Although the H2A analysis results indicated a $1.96 cost per gge H2 based on a 5A (micron) thick PdCu membrane, there was not long-term operation at the required flux to satisfy the go/no go decision. Since the future PSA case yielded a $2.00/gge H2, DOE decided that there was insufficient savings compared with the already proven PSA technology to further pursue the membrane reactor design. All ceramic membranes synthesized by ASU during the project showed low hydrogen flux as compared with metallic membranes. The best ceramic membrane showed hydrogen permeation flux of 0.03 SCFH/ft2 at the required process conditions while the metallic membrane, Pd80Cu20 showed a flux of 47.2 SCFH/ft2 (3 orders of magnitude difference). Results from NETL showed Pd80Cu20 with the highest flux, therefore it was chosen as the initial and eventually, final candidate membrane. The criteria for choice were high hydrogen flux, long-term stability, and H2S tolerance. Results from SCHOTT using glass membranes showed a maximum of 0.25 SCFH/ft2, that is an order of magnitude better than the ceramic membrane but still two orders of magnitude lower than the metallic membrane. A membrane module was designed to be tested with an actual biomass gasifier. Some parts of the module were ordered but the work was stopped when a no go decision was made by the DOE.« less

Magnetic properties and magnetocaloric effects in HoPd intermetallic

NASA Astrophysics Data System (ADS)

Zhao-Jun, Mo; Jun, Shen; Xin-Qiang, Gao; Yao, Liu; Jian-Feng, Wu; Bao-Gen, Shen; Ji-Rong, Sun

2015-03-01

A large reversible magnetocaloric effect accompanied by a second order magnetic phase transition from PM to FM is observed in the HoPd compound. Under the magnetic field change of and the refrigerant capacity RC for the compound are evaluated to be 20 J/(kg · K) and 342 J/kg, respectively. In particular, large (11.3 J/(kg · K)) and RC (142 J/kg) are achieved under a low magnetic field change of 0-2 T with no thermal hysteresis and magnetic hysteresis loss. The large reversible magnetocaloric effect (both the large -ΔSM and the high RC) indicates that HoPd is a promising material for magnetic refrigeration at low temperature. Project supported by the National Natural Science Foundation of China (Grant Nos. 51322605, 11104337, 51271192, and 11274357) and the Knowledge Innovation Project of the Chinese Academy of Sciences.

Structural genomic variations and Parkinson's disease.

PubMed

Bandrés-Ciga, Sara; Ruz, Clara; Barrero, Francisco J; Escamilla-Sevilla, Francisco; Pelegrina, Javier; Vives, Francisco; Duran, Raquel

2017-10-01

Parkinson's disease (PD) is the second most common neurodegenerative disease, whose prevalence is projected to be between 8.7 and 9.3 million by 2030. Until about 20 years ago, PD was considered to be the textbook example of a "non-genetic" disorder. Nowadays, PD is generally considered a multifactorial disorder that arises from the combination and complex interaction of genes and environmental factors. To date, a total of 7 genes including SNCA, LRRK2, PARK2, DJ-1, PINK 1, VPS35 and ATP13A2 have been seen to cause unequivocally Mendelian PD. Also, variants with incomplete penetrance in the genes LRRK2 and GBA are considered to be strong risk factors for PD worldwide. Although genetic studies have provided valuable insights into the pathogenic mechanisms underlying PD, the role of structural variation in PD has been understudied in comparison with other genomic variations. Structural genomic variations might substantially account for such genetic substrates yet to be discovered. The present review aims to provide an overview of the structural genomic variants implicated in the pathogenesis of PD.

The Impact of a Multi-Year, Multi-School District K-6 Professional Development Programme Designed to Integrate Science Inquiry and Language Arts on Students' High-Stakes Test Scores

NASA Astrophysics Data System (ADS)

Shymansky, James A.; Wang, Tzu-Ling; Annetta, Leonard A.; Yore, Larry D.; Everett, Susan A.

2013-04-01

This paper is a report of a quasi-experimental study on the impact of a systemic 5-year, K-6 professional development (PD) project on the 'high stakes' achievement test scores of different student groups in rural mid-west school districts in the USA. The PD programme utilized regional summer workshops, district-based leadership teams and distance delivery technologies to help teachers learn science concepts and inquiry teaching strategies associated with a selection of popular science inquiry kits and how to adapt inquiry science lessons in the kits to teach and reinforce skills in the language arts-i.e. to teach more than science when doing inquiry science. Analyses of the school district-level pre-post high-stakes achievement scores of 33 school districts participating in the adaptation of inquiry PD and a comparative group of 23 school districts revealed that both the Grade 3 and Grade 6 student-cohorts in the school districts utilizing adapted science inquiry lessons significantly outscored their student-cohort counterparts in the comparative school districts. The positive school district-level high-stakes test results, which serve as the basis for state and local decision making, suggest that an inquiry adaptation strategy and a combination of regional live workshop and distance delivery technologies with ongoing local leadership and support can serve as a viable PD option for K-6 science.

Stage- and tissue-expression of genes involved in the biosynthesis and signalling of ethylene in reproductive organs of damson plum (Prunus domestica L. subsp. insititia).

PubMed

Fernández-Otero, C I; de la Torre, F; Iglesias, R; Rodríguez-Gacio, M C; Matilla, A J

2007-01-01

In this work, four cDNA clones (Pd-ACS1,AJ890088; Pd-ETR1 and Pd-ERS1, AJ890092, AJ890091; and Pd-CTR1, AJ890089) encoding an ACC-synthase, two putative ethylene (ET) receptors, and a putative MAPKKK, respectively, were isolated and phylogenetically characterized in Prunus domestica L. subsp. insititia. Their expression was studied by real-time PCR during flower (closed, open and senescent) and fruit (early green, late green, maturation and ripening) development of damson plum, which is climateric. While two peaks of ET production were quantified at early green and ripening stages in whole fruits, the seed was not able to produce it during maturation and ripening stages. All studied genes were differentially expressed during flower and fruit development. In general, the level of transcripts of Pd-ACS1 was higher in fruits than in flowers. However, it was noteworthy that: (1) Pd-ACS1 expression was hardly detected in closed flowers and at low levels during early green stage; and fruit development provoked a notable differential expression in seeds, and pericarp; (2) the results of Pd-ACS1 expression during fruit development suggest a preponderant role of this gene from late green stage onward. The stamen was the only floral organ in which expression of both Pd-ETR1 and Pd-ERS1 receptor genes was not significantly altered during development; however, their expression decreased concomitantly with development of pistil (only floral organ to register a net ET production when fertilized) and during first days of ovary development (the highest ET production during all fruit development). Contrary to Pd-ERS1, the level of Pd-ETR1 mRNA was temporally quite similar in the seed. With regard Pd-ETR1, even its expression was very scarce during maturation of mesocarp, was stimulated during ripening. In the epicarp, Pd-ERS1 and Pd-ETR1 were low expressed during pit hardening increasing onward and decreasing during ripening. Pd-CTR1 expression was in the seed>mesocarp>epicarp. Spatial and temporal levels of Pd-ACS1, Pd-ETR1, Pd-ERS1 and Pd-CTR1 mRNAs described in this work demonstrate that the expression of these genes is not always constitutive and that control of its transcription may play an important role in regulating the development of reproductive organs of damson plum.

Lentivirus-mediated delivery of sonic hedgehog into the striatum stimulates neuroregeneration in a rat model of Parkinson disease.

PubMed

Zhang, Yi; Dong, Weiren; Guo, Suiqun; Zhao, Shu; He, Suifen; Zhang, Lihua; Tang, Yinjuan; Wang, Haihong

2014-12-01

Parkinson disease (PD) is a progressive neurodegenerative disorder in which the nigrostriatal pathway, consisting of dopaminergic neuronal projections from the substantia nigra to the striatum, degenerates. Viral transduction is currently the most promising in vivo strategy for delivery of therapeutic proteins into the brain for treatment of PD. Sonic hedgehog (Shh) is necessary for cell proliferation, differentiation and neuroprotection in the central nervous system. In this study, we investigated the effects of overexpressed N-terminal product of SHH (SHH-N) in a PD model rat. A lentiviral vector containing SHH-N was stereotactically injected into the striatum 24 h after a striatal 6-OHDA lesion. We found that overexpressed SHH-N attenuated behavioral deficits and reduced the loss of dopamine neurons in the substantia nigra and the loss of dopamine fibers in the striatum. In addition, fluoro-ruby-labeled nigrostriatal projections were also repaired. Together, our results demonstrate the feasibility and efficacy of using the strategy of lentivirus-mediated Shh-N delivery to delay nigrostriatal pathway degeneration. This strategy holds the potential for therapeutic application in the treatment of PD.

Designing and Validating Ternary Pd Alloys for Optimum Sulfur/Carbon Resistance in Hydrogen Separation and Carbon Capture Membrane Systems Using High-Throughput Combinatorial Methods

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

Lewis, Amanda; Zhao, Hongbin; Hopkins, Scott

2014-12-01

This report summarizes the work completed under the U.S. Department of Energy Project Award No.: DE-FE0001181 titled “Designing and Validating Ternary Pd Alloys for Optimum Sulfur/Carbon Resistance in Hydrogen Separation and Carbon Capture Membrane Systems Using High-Throughput Combinatorial Methods.” The project started in October 1, 2009 and was finished September 30, 2014. Pall Corporation worked with Cornell University to sputter and test palladium-based ternary alloys onto silicon wafers to examine many alloys at once. With the specialized equipment at Georgia Institute of Technology that analyzed the wafers for adsorbed carbon and sulfur species six compositions were identified to have resistancemore » to carbon and sulfur species. These compositions were deposited on Pall AccuSep® supports by Colorado School of Mines and then tested in simulated synthetic coal gas at the Pall Corporation. Two of the six alloys were chosen for further investigations based on their performance. Alloy reproducibility and long-term testing of PdAuAg and PdZrAu provided insight to the ability to manufacture these compositions for testing. PdAuAg is the most promising alloy found in this work based on the fabrication reproducibility and resistance to carbon and sulfur. Although PdZrAu had great initial resistance to carbon and sulfur species, the alloy composition has a very narrow range that hindered testing reproducibility.« less

XANES study of hydrogen incorporation in a Pd-capped Nb thin film

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

Ruckman, M.W.; Reisfeld, G.; Jisrawi, N.M.

X-ray absorption near-edge structure (XANES) measurements were used to probe the H-charging-induced electronic structure changes of a 2400 {Angstrom} Nb film capped with Pd. These results are discussed in terms of {ital ab initio} linear augmented plane-wave (LAPW) band-structure calculations for this material. The Pd-L{sub 3}-edge XANES clearly manifested the spectral (Pd-d state related) changes expected for Pd-hydride formation, a white line feature degradation, and the appearance of a Pd-H antibonding feature at 6 eV above the threshold. The Nb-L{sub 2,3} edge changes with H charging show a distinct enhancement of the white line strength; a feature 6 eV abovemore » the edges, associated with Nb-H antibonding states in analogy with the Pd results; the suppression of a threshold-onset feature of Nb metal; and a shift of the centrum of the white line feature towards the threshold. Comparison of the Nb sphere projection of the d{sub 3/2} component of the LAPW density of states (DOS) to the Nb-L{sub 2}-edge spectra yields good basic agreement with the observed spectral changes. In particular, the substantial theoretical reduction in the DOS at, and just above, the Fermi energy (E{sub f}) is directly related to the near threshold Nb-L{sub 2,3} spectral changes. The more modest white line enhancement in the theoretical DOS is noted and discussed. Nb-K-edge XANES are also discussed in terms of the Nb-site p-state projected LAPW DOS. This last comparison indicates a p-state reduction near E{sub f} upon H charging of the Nb. {copyright} {ital 1998} {ital The American Physical Society}« less

A Review of the Pedunculopontine Nucleus in Parkinson's Disease.

PubMed

French, Isobel T; Muthusamy, Kalai A

2018-01-01

The pedunculopontine nucleus (PPN) is situated in the upper pons in the dorsolateral portion of the ponto-mesencephalic tegmentum. Its main mass is positioned at the trochlear nucleus level, and is part of the mesenphalic locomotor region (MLR) in the upper brainstem. The human PPN is divided into two subnuclei, the pars compacta (PPNc) and pars dissipatus (PPNd), and constitutes both cholinergic and non-cholinergic neurons with afferent and efferent projections to the cerebral cortex, thalamus, basal ganglia (BG), cerebellum, and spinal cord. The BG controls locomotion and posture via GABAergic output of the substantia nigra pars reticulate (SNr). In PD patients, GABAergic BG output levels are abnormally increased, and gait disturbances are produced via abnormal increases in SNr-induced inhibition of the MLR. Since the PPN is vastly connected with the BG and the brainstem, dysfunction within these systems lead to advanced symptomatic progression in Parkinson's disease (PD), including sleep and cognitive issues. To date, the best treatment is to perform deep brain stimulation (DBS) on PD patients as outcomes have shown positive effects in ameliorating the debilitating symptoms of this disease by treating pathological circuitries within the parkinsonian brain. It is therefore important to address the challenges and develop this procedure to improve the quality of life of PD patients.

A Review of the Pedunculopontine Nucleus in Parkinson's Disease

PubMed Central

French, Isobel T.; Muthusamy, Kalai A.

2018-01-01

The pedunculopontine nucleus (PPN) is situated in the upper pons in the dorsolateral portion of the ponto-mesencephalic tegmentum. Its main mass is positioned at the trochlear nucleus level, and is part of the mesenphalic locomotor region (MLR) in the upper brainstem. The human PPN is divided into two subnuclei, the pars compacta (PPNc) and pars dissipatus (PPNd), and constitutes both cholinergic and non-cholinergic neurons with afferent and efferent projections to the cerebral cortex, thalamus, basal ganglia (BG), cerebellum, and spinal cord. The BG controls locomotion and posture via GABAergic output of the substantia nigra pars reticulate (SNr). In PD patients, GABAergic BG output levels are abnormally increased, and gait disturbances are produced via abnormal increases in SNr-induced inhibition of the MLR. Since the PPN is vastly connected with the BG and the brainstem, dysfunction within these systems lead to advanced symptomatic progression in Parkinson's disease (PD), including sleep and cognitive issues. To date, the best treatment is to perform deep brain stimulation (DBS) on PD patients as outcomes have shown positive effects in ameliorating the debilitating symptoms of this disease by treating pathological circuitries within the parkinsonian brain. It is therefore important to address the challenges and develop this procedure to improve the quality of life of PD patients. PMID:29755338

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.

KSC-03PD-2383

NASA Technical Reports Server (NTRS)

2003-01-01

KENNEDY SPACE CENTER, FLA. Research team members aboard one of the watercraft being utilized to conduct underwater acoustic research in the Launch Complex 39 turn basin monitor some of the project's equipment just released into the water. Several government agencies, including NASA, NOAA, the Navy, the Coast Guard, and the Florida Fish and Wildlife Commission are involved in the testing. The research involves demonstrations of passive and active sensor technologies, with applications in fields ranging from marine biological research to homeland security. The work is also serving as a pilot project to assess the cooperation between the agencies involved. Equipment under development includes a passive acoustic monitor developed by NASAs Jet Propulsion Laboratory, and mobile robotic sensors from the Navys Mobile Diving and Salvage Unit.

KSC-03PD-2380

NASA Technical Reports Server (NTRS)

2003-01-01

KENNEDY SPACE CENTER, FLA. Research team members aboard one of the watercraft being utilized to conduct underwater acoustic research in the Launch Complex 39 turn basin prepare to release some of the project's equipment into the water. Several government agencies, including NASA, NOAA, the Navy, the Coast Guard, and the Florida Fish and Wildlife Commission are involved in the testing. The research involves demonstrations of passive and active sensor technologies, with applications in fields ranging from marine biological research to homeland security. The work is also serving as a pilot project to assess the cooperation between the agencies involved. Equipment under development includes a passive acoustic monitor developed by NASAs Jet Propulsion Laboratory, and mobile robotic sensors from the Navys Mobile Diving and Salvage Unit.

KSC-03PD-2385

NASA Technical Reports Server (NTRS)

2003-01-01

KENNEDY SPACE CENTER, FLA. A research team member aboard one of the watercraft being utilized to conduct underwater acoustic research in the Launch Complex 39 turn basin lifts some of the project's equipment from the water. Several government agencies, including NASA, NOAA, the Navy, the Coast Guard, and the Florida Fish and Wildlife Commission are involved in the testing. The research involves demonstrations of passive and active sensor technologies, with applications in fields ranging from marine biological research to homeland security. The work is also serving as a pilot project to assess the cooperation between the agencies involved. Equipment under development includes a passive acoustic monitor developed by NASAs Jet Propulsion Laboratory, and mobile robotic sensors from the Navys Mobile Diving and Salvage Unit.

KSC-03PD-2382

NASA Technical Reports Server (NTRS)

2003-01-01

KENNEDY SPACE CENTER, FLA. A research team member aboard one of the watercraft being utilized to conduct underwater acoustic research in the Launch Complex 39 turn basin releases some of the project's equipment into the water. Several government agencies, including NASA, NOAA, the Navy, the Coast Guard, and the Florida Fish and Wildlife Commission are involved in the testing. The research involves demonstrations of passive and active sensor technologies, with applications in fields ranging from marine biological research to homeland security. The work is also serving as a pilot project to assess the cooperation between the agencies involved. Equipment under development includes a passive acoustic monitor developed by NASAs Jet Propulsion Laboratory, and mobile robotic sensors from the Navys Mobile Diving and Salvage Unit.

KSC-03PD-2378

NASA Technical Reports Server (NTRS)

2003-01-01

KENNEDY SPACE CENTER, FLA. A research team member aboard one of the watercraft being utilized to conduct underwater acoustic research in the Launch Complex 39 turn basin prepares some of the project's equipment for placement in the water. Several government agencies, including NASA, NOAA, the Navy, the Coast Guard, and the Florida Fish and Wildlife Commission are involved in the testing. The research involves demonstrations of passive and active sensor technologies, with applications in fields ranging from marine biological research to homeland security. The work is also serving as a pilot project to assess the cooperation between the agencies involved. Equipment under development includes a passive acoustic monitor developed by NASAs Jet Propulsion Laboratory, and mobile robotic sensors from the Navys Mobile Diving and Salvage Unit.

KSC-03PD-2386

NASA Technical Reports Server (NTRS)

2003-01-01

KENNEDY SPACE CENTER, FLA. Research team members aboard one of the watercraft being utilized to conduct underwater acoustic research in the Launch Complex 39 turn basin secure some of the project's equipment back into the vessel. Several government agencies, including NASA, NOAA, the Navy, the Coast Guard, and the Florida Fish and Wildlife Commission are involved in the testing. The research involves demonstrations of passive and active sensor technologies, with applications in fields ranging from marine biological research to homeland security. The work is also serving as a pilot project to assess the cooperation between the agencies involved. Equipment under development includes a passive acoustic monitor developed by NASAs Jet Propulsion Laboratory, and mobile robotic sensors from the Navys Mobile Diving and Salvage Unit.

The Neurobiological Basis of Cognitive Impairment in Parkinson'S Disease

PubMed Central

Halliday, Glenda M.; Leverenz, James B.; Schneider, Jay S.; Adler, Charles H.

2014-01-01

The recent formalization of clinical criteria for PD with dementia (PD-D) codifies many studies on this topic, including those assessing biological correlates. These studies show that the emergence of PD-D occurs on the background of severe dopamine deficits with the main pathological drivers of cognitive decline being a synergistic effect between α -synuclein and Alzheimer's disease pathology. The presence of these pathologies correlates with a marked loss of limbic and cortically projecting dopamine, noradrenaline, serotonin and acetylcholine neurons, although the exact timing of these relationships remains to be determined. Genetic factors, such as triplications in the α-synuclein gene, lead to a clear increased risk of PD-D, while others, such as parkin mutations, are associated with a reduced risk of PD-D. The very recent formalization of clinical criteria for PD with mild cognitive impairment (PD-MCI) allows only speculation on its biological and genetic bases. Critical assessment of animal models shows that chronic low dose MPTP treatment in primates recapitulates PD-MCI over time, enhancing the current biological concept of PD-MCI as having enhanced dopamine deficiency in frontostriatal pathways as well as involvement of other neurotransmitter systems. Data from other animal models support multiple transmitter involvement in cognitive impairment in PD. While dopamine dysfunction has been highlighted because of its obvious role in PD, the role of the other neurotransmitter systems, neurodegenerative pathologies and genetic factors in PD-MCI remain to be fully elucidated. PMID:24757112

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

Insights into gait disorders: walking variability using phase plot analysis, Parkinson's disease.

PubMed

Esser, Patrick; Dawes, Helen; Collett, Johnny; Howells, Ken

2013-09-01

Gait variability may have greater utility than spatio-temporal parameters and can, be an indication for risk of falling in people with Parkinson's disease (PD). Current methods rely on prolonged data collection in order to obtain large datasets which may be demanding to obtain. We set out to explore a phase plot variability analysis to differentiate typically developed adults (TDAs) from PD obtained from two 10 m walks. Fourteen people with PD and good mobility (Rivermead Mobility Index≥8) and ten aged matched TDA were recruited and walked over 10-m at self-selected walking speed. An inertial measurement unit was placed over the projected centre of mass (CoM) sampling at 100 Hz. Vertical CoM excursion was derived to determine modelled spatiotemporal data after which the phase plot analysis was applied producing a cloud of datapoints. SDA described the spread and SDB the width of the cloud with β the angular vector of the data points. The ratio (∀) was defined as SDA: SDB. Cadence (p=.342) and stride length (p=.615) did not show a significance between TDA and PD. A difference was found for walking speed (p=.041). Furthermore a significant difference was found for β (p=.010), SDA (p=.004) other than SDB (p=.385) or ratio ∀ (p=.830). Two sequential 10-m walks showed no difference in PD for cadence (p=.193), stride length (p=.683), walking speed (p=.684) and β (p=.194), SDA (p=.051), SDB (p=.145) or ∀ (p=.226). The proposed phase plot analysis, performed on CoM motion could be used to reliably differentiate PD from TDA over a 10-m walk. Copyright © 2013 Elsevier B.V. All rights reserved.

Superconductivity and ferromagnetism in Pd doped Y9Co7

NASA Astrophysics Data System (ADS)

Klimczuk, Tomasz; Strychalska, Judyta; Thompson, Joe; Cava, Robert

The ferromagnetic superconductor Y9Co7 was chemically doped with Pd in an attempt to form Y9Co7-xPdx for 0

Development and characterization of monoclonal antibodies against canine PD-1 and PD-L1.

PubMed

Nemoto, Yuki; Shosu, Kazuha; Okuda, Masaru; Noguchi, Shunsuke; Mizuno, Takuya

2018-04-01

Recent research has focused on immunotherapy, particularly with regard to cancer treatment. Programmed death-1 and programmed death ligand 1 (PD-1/PD-L1) pathway blockade is a central topic of the promising immunotherapy field. In veterinary medicine, observations of the PD-1/PD-L1 pathway, including the relationship between immune cells and diseases, have increased. In this study, monoclonal antibodies specific to canine PD-1 and PD-L1 were developed, and the antibodies against PD-1 and PD-L1 bind to PD-1 and PD-L1 overexpressing cells, respectively. Additionally, each antibody interfered with the interaction between PD-1 and PD-L1. The expression of PD-1 and PD-L1 was detected on activated T cells from canine peripheral blood mononuclear cells (PBMC), and, remarkably, was the first recorded instance of PD-L1 expression on canine immature dendritic cells. Production of IFN-γ by activated T cells increased significantly when incubated with anti-PD-1 antibody alone and with both anti-PD-1 and anti-PD-L1 antibodies, revealing the functional effects of the antibodies. The antibodies will be useful for research on immune systems and may be the first passive immunotherapy approach in canine cancer patients. Copyright © 2018 Elsevier B.V. All rights reserved.

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.

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

Synthesis and electrochemical study of palladium-based nanomaterials for green energy applications

NASA Astrophysics Data System (ADS)

Ostrom, Cassandra K.

Rising global energy consumption leads to increased environmental impacts. The continued use of current energy resources, e.g. fossil fuels, will exaggerate the cumulative nature of CO2 byproduct emissions in the atmosphere. The development and implementation of a hydrogen economy, as a solution to offset degradative environmental impacts, will likely enable opportunities for maintaining or improving standards of living while significantly lowering carbon emissions. Palladium has proven to be a strong contender as an enabling material that encompasses many aspects of a prospective hydrogen economy, lending promise to applications such as hydrogen purification, storage and fuel cell catalysis. In my M.Sc. study, Pd-based nanomaterials have been synthesized and examined for their applications in hydrogen storage and fuel cell catalysis. The surface properties of synthesized Pd-based nanomaterials were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersive X-ray spectrometry (EDS), X-ray diffraction (XRD), X-ray Photoelectron spectroscopy (XPS), and N2 gas adsorption/desorption. Electrochemical analysis of the fabricated materials was performed using cyclic voltammetry (CV), linear sweep voltammetry (LSV), chronoamperometry (CA), and electrochemical impedance spectroscopy (EIS). Inductively coupled plasma atomic emission spectroscopy (ICP-AES) was employed to characterize the composition of the formed samples. Hydrogen electrosorption onto activated carbon materials modified with different trimetallic dissociation catalysts (Pd-Ag-Cd) was investigated in an acidic medium. A uniform distribution of the Pd-Ag-Cd catalysts was achieved using a facile room temperature sodium borohydride reduction method. By varying the composition of the alloys, synergistic effects between the metal and carbon support resulted in drastic increases in hydrogen sorption capabilities in contrast to bi-metallic PdAg and PdCd catalysts. Utilizing electrochemical methods, the optimal composition of the Pd-Ag-Cd alloys was determined to be Pd80Ag10Cd10, with the highest hydrogen sorption capacity at a hydrogen desorption charge of 18.49 C/cm2˙mg. Further enhancement of the electroactivity of synthesized titanium dioxide nanotubes (TiO2 NTs) was achieved using UV light and electrochemical pretreatment methods. The effects of these pretreatment methods on TiO2 NTs were systematically investigated and compared. Using Pd as a dispersed catalyst, Pd/TiO2 NT electrodes were examined in acidic medium, with both UV and electrochemical pretreatment methods revealing significant enhancements in the electroactivity of the TiO2 NT substrate. The UV pretreated samples were found to dominate, when compared to those that underwent electrochemical pretreatment, in terms of overall efficacy for hydrogen sorption and the electrooxidation of formic acid. Improvements in nanotube conductivity resulted in an effective reduction of noble metal coating loads. Nanostructured PdPb electrocatalysts were loaded directly onto TiO2 NT substrates and tested for their activity towards formic acid oxidation. Comparative studies revealed the enhanced electrochemical oxidation of formic acid on Pd95Pb5/TiO2 NTs in comparison to Pd/TiO2 NTs, resulting in the successful reduction of Pd noble metal load. The work performed in this M. Sc. thesis project reveals that modifications to both Pd catalysts and their associated supports can drastically alter their geometric and electronic properties. This has a major influence on the development of more cost effective materials with enhanced activity for use towards the commercialization of fuel cells.

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.

KSC-02pd0627

NASA Image and Video Library

2002-04-30

KENNEDY SPACE CENTER, FLA. -- At the 2002 Space Congress, Cape Canaveral, Fla., a presentation on "Hubble Discoveries" by Dr. Mark Clampin (with microphone), Advanced Camera for Surveys team, included an image of an eye (seen on the screen) comprising hundreds of photos of all the people who worked on Hubble. On the right is Frank Ceppolina, project manager, Hubble Space Telescope Development Project. The Space Congress is held annually to highlight military and space initiatives, new technologies, and Florida's role in programs and research. This year's theme is Beginning a New Era - Initiatives in Space. NASA presented several paper sessions, including Advancements in Technology. Space Congress is sponsored by the Canaveral Council of Technical Societies

Cell transplantation in the damaged adult brain.

PubMed

Jaber, M; Benoit-Marand, M; Prestoz, L; Gaillard, A

2013-11-01

Parkinson's disease (PD) is the most common movement disorder in Europe, affecting more than two million people between 50 and 70 years of age. The current therapeutic approaches are of symptomatic nature and fail to halt the progressive neurodegenerative course of the disease. The development of innovative and complementary approaches to promote cellular repair may pave the way for disease-modifying therapies which may lead to less suffering for the patients and their families and finally to more cost-effective therapies. To date, cell replacement trials in PD aiming at replacing lost dopamine neurons were mainly focused on placing the transplanted cells within the target site, the striatum, and not within the lesioned site, the substantia nigra (SN). This was based on the misconception that the adult brain constitutes a non-permissive barrier not allowing the outgrowth of long distance axons originating from transplanted embryonic neurons. A growing body of evidence is challenging this concept and proposing instead to place the graft within its ontogenic site. This has been performed in several lesional animal models for various traumatic or neurodegenerative pathologies of the brain. For instance, transplanted neurons within the lesioned motor cortex were shown to be able to send distant and appropriate projections to target areas including the spinal cord. Similarly, in an animal model of PD, mesencephalic embryonic cells transplanted within the lesioned SN send massive projections to the striatum and, to a lesser extent, the frontal cortex and the nucleus accumbens. This has lead to the proposal that homotopic transplantation may be an alternative in cell-based therapies as transplanted neurons can integrate within the host brain, send projections to target areas, restore the damaged circuitry, increase neurotransmitter levels and ameliorate behavior. We will discuss also the potential of replacing embryonic neuronal cells by stem cell derived neurons as the use of embryonic cells is not without an ethical and logistical burden; in this line many have thrived to derive neurons from embryonic stem cells (ESC) in order to use them for cell transplantation. These studies are already yielding important information for future approaches in the field of cell therapies in PD but also in other neurodegenerative disorders where cell transplantation therapy may be considered. While the field of cell replacement therapies has been recently called into question with contrasting results in transplanted PD patients, these new sets of findings are raising new hopes and opening new avenues in this rejuvenated field. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

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.

Associations between disaster exposures, peritraumatic distress, and posttraumatic stress responses in Fukushima nuclear plant workers following the 2011 nuclear accident: the Fukushima NEWS Project study.

PubMed

Shigemura, Jun; Tanigawa, Takeshi; Nishi, Daisuke; Matsuoka, Yutaka; Nomura, Soichiro; Yoshino, Aihide

2014-01-01

The 2011 Fukushima Daiichi Nuclear Power Plant accident was the worst nuclear disaster since Chernobyl. The nearby Daini plant also experienced substantial damage but remained intact. Workers for the both plants experienced multiple stressors as disaster victims and workers, as well as the criticism from the public due to their company's post-disaster management. Little is known about the psychological pathway mechanism from nuclear disaster exposures, distress during and immediately after the event (peritraumatic distress; PD), to posttraumatic stress responses (PTSR). A self-report questionnaire was administered to 1,411 plant employees (Daiichi, n = 831; Daini, n = 580) 2-3 months post-disaster (total response rate: 80.2%). The socio-demographic characteristics and disaster-related experiences were assessed as independent variables. PD and PTSR were measured by the Japanese versions of Peritraumatic Distress Inventory and the Impact of Event Scale-Revised, respectively. The analysis was conducted separately for the two groups. Bivariate regression analyses were performed to assess the relationships between independent variables, PD, and PTSR. Significant variables were subsequently entered in the multiple regression analyses to explore the pathway mechanism for development of PTSR. For both groups, PTSR highly associated with PD (Daiichi: adjusted β, 0.66; p<0.001; vs. Daini: adjusted β, 0.67; p<0.001). PTSR also associated with discrimination/slurs experience (Daiichi: 0.11; p<0.001; vs. Daini, 0.09; p = 0.005) and presence of preexisting illness(es) (Daiichi: 0.07; p = 0.005; vs. Daini: 0.15; p<.0001). Other disaster-related variables were likely to be associated with PD than PTSR. Among the Fukushima nuclear plant workers, disaster exposures associated with PD. PTSR was highly affected by PD along with discrimination/slurs experience.

Associations between Disaster Exposures, Peritraumatic Distress, and Posttraumatic Stress Responses in Fukushima Nuclear Plant Workers following the 2011 Nuclear Accident: The Fukushima NEWS Project Study

PubMed Central

Shigemura, Jun; Tanigawa, Takeshi; Nishi, Daisuke; Matsuoka, Yutaka; Nomura, Soichiro; Yoshino, Aihide

2014-01-01

Background The 2011 Fukushima Daiichi Nuclear Power Plant accident was the worst nuclear disaster since Chernobyl. The nearby Daini plant also experienced substantial damage but remained intact. Workers for the both plants experienced multiple stressors as disaster victims and workers, as well as the criticism from the public due to their company's post-disaster management. Little is known about the psychological pathway mechanism from nuclear disaster exposures, distress during and immediately after the event (peritraumatic distress; PD), to posttraumatic stress responses (PTSR). Methods A self-report questionnaire was administered to 1,411 plant employees (Daiichi, n = 831; Daini, n = 580) 2–3 months post-disaster (total response rate: 80.2%). The socio-demographic characteristics and disaster-related experiences were assessed as independent variables. PD and PTSR were measured by the Japanese versions of Peritraumatic Distress Inventory and the Impact of Event Scale-Revised, respectively. The analysis was conducted separately for the two groups. Bivariate regression analyses were performed to assess the relationships between independent variables, PD, and PTSR. Significant variables were subsequently entered in the multiple regression analyses to explore the pathway mechanism for development of PTSR. Results For both groups, PTSR highly associated with PD (Daiichi: adjusted β, 0.66; p<0.001; vs. Daini: adjusted β, 0.67; p<0.001). PTSR also associated with discrimination/slurs experience (Daiichi: 0.11; p<0.001; vs. Daini, 0.09; p = 0.005) and presence of preexisting illness(es) (Daiichi: 0.07; p = 0.005; vs. Daini: 0.15; p<.0001). Other disaster-related variables were likely to be associated with PD than PTSR. Conclusion Among the Fukushima nuclear plant workers, disaster exposures associated with PD. PTSR was highly affected by PD along with discrimination/slurs experience. PMID:24586278

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.

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.

Developing a Deep Brain Stimulation Neuromodulation Network for Parkinson Disease, Essential Tremor, and Dystonia: Report of a Quality Improvement Project

PubMed Central

O’Suilleabhain, Padraig E.; Sanghera, Manjit; Patel, Neepa; Khemani, Pravin; Lacritz, Laura H.; Chitnis, Shilpa; Whitworth, Louis A.; Dewey, Richard B.

2016-01-01

Objective To develop a process to improve patient outcomes from deep brain stimulation (DBS) surgery for Parkinson disease (PD), essential tremor (ET), and dystonia. Methods We employed standard quality improvement methodology using the Plan-Do-Study-Act process to improve patient selection, surgical DBS lead implantation, postoperative programming, and ongoing assessment of patient outcomes. Results The result of this quality improvement process was the development of a neuromodulation network. The key aspect of this program is rigorous patient assessment of both motor and non-motor outcomes tracked longitudinally using a REDCap database. We describe how this information is used to identify problems and to initiate Plan-Do-Study-Act cycles to address them. Preliminary outcomes data is presented for the cohort of PD and ET patients who have received surgery since the creation of the neuromodulation network. Conclusions Careful outcomes tracking is essential to ensure quality in a complex therapeutic endeavor like DBS surgery for movement disorders. The REDCap database system is well suited to store outcomes data for the purpose of ongoing quality assurance monitoring. PMID:27711133

Developing a Deep Brain Stimulation Neuromodulation Network for Parkinson Disease, Essential Tremor, and Dystonia: Report of a Quality Improvement Project.

PubMed

Dewey, Richard B; O'Suilleabhain, Padraig E; Sanghera, Manjit; Patel, Neepa; Khemani, Pravin; Lacritz, Laura H; Chitnis, Shilpa; Whitworth, Louis A; Dewey, Richard B

2016-01-01

To develop a process to improve patient outcomes from deep brain stimulation (DBS) surgery for Parkinson disease (PD), essential tremor (ET), and dystonia. We employed standard quality improvement methodology using the Plan-Do-Study-Act process to improve patient selection, surgical DBS lead implantation, postoperative programming, and ongoing assessment of patient outcomes. The result of this quality improvement process was the development of a neuromodulation network. The key aspect of this program is rigorous patient assessment of both motor and non-motor outcomes tracked longitudinally using a REDCap database. We describe how this information is used to identify problems and to initiate Plan-Do-Study-Act cycles to address them. Preliminary outcomes data is presented for the cohort of PD and ET patients who have received surgery since the creation of the neuromodulation network. Careful outcomes tracking is essential to ensure quality in a complex therapeutic endeavor like DBS surgery for movement disorders. The REDCap database system is well suited to store outcomes data for the purpose of ongoing quality assurance monitoring.

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.

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.

Emerging therapies for Parkinson's disease: from bench to bedside.

PubMed

Tarazi, F I; Sahli, Z T; Wolny, M; Mousa, S A

2014-11-01

The prevalence of Parkinson's disease (PD) increases with age and is projected to increase in parallel to the rising average age of the population. The disease can have significant health-related, social, and financial implications not only for the patient and the caregiver, but for the health care system as well. While the neuropathology of this neurodegenerative disorder is fairly well understood, its etiology remains a mystery, making it difficult to target therapy. The currently available drugs for treatment provide only symptomatic relief and do not control or prevent disease progression, and as a result patient compliance and satisfaction are low. Several emerging pharmacotherapies for PD are in different stages of clinical development. These therapies include adenosine A2A receptor antagonists, glutamate receptor antagonists, monoamine oxidase inhibitors, anti-apoptotic agents, and antioxidants such as coenzyme Q10, N-acetyl cysteine, and edaravone. Other emerging non-pharmacotherapies include viral vector gene therapy, microRNAs, transglutaminases, RTP801, stem cells and glial derived neurotrophic factor (GDNF). In addition, surgical procedures including deep brain stimulation, pallidotomy, thalamotomy and gamma knife surgery have emerged as alternative interventions for advanced PD patients who have completely utilized standard treatments and still suffer from persistent motor fluctuations. While several of these therapies hold much promise in delaying the onset of the disease and slowing its progression, more pharmacotherapies and surgical interventions need to be investigated in different stages of PD. It is hoped that these emerging therapies and surgical procedures will strengthen our clinical armamentarium for improved treatment of PD. Copyright © 2014 Elsevier Inc. All rights reserved.

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.

Report of the Snowmass M6 Working Group on high intensity proton sources

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

Weiren Chou and J. Wei

The U.S. high-energy physics program needs an intense proton source, a 1-4 MW Proton Driver (PD), by the end of this decade. This machine will serve as a stand-alone facility that will provide neutrino superbeams and other high intensity secondary beams such as kaons, muons, neutrons, and anti-protons (cf. E1 and E5 group reports) and also serve as the first stage of a neutrino factory (cf. M1 group report). It can also be a high brightness source for a VLHC. Based on present accelerator technology and project construction experience, it is both feasible and cost-effective to construct a 1-4 MWmore » Proton Driver. Two recent PD design studies have been made, one at FNAL and the other at the BNL. Both designed PD's for 1 MW proton beams at a cost of about U.S. $200M (excluding contingency and overhead) and both designs were upgradeable to 4 MW. An international collaboration between FNAL, BNL and KEK on high intensity proton facilities is addressing a number of key design issues. The superconducting (sc) RF cavities, cryogenics, and RF controls developed for the SNS can be directly adopted to save R&D efforts, cost, and schedule. PD studies are also actively being pursued at Europe and Japan.« less

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.

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…

Naringin protects the nigrostriatal dopaminergic projection through induction of GDNF in a neurotoxin model of Parkinson's disease.

PubMed

Leem, Eunju; Nam, Jin Han; Jeon, Min-Tae; Shin, Won-Ho; Won, So-Yoon; Park, Sang-Joon; Choi, Myung-Sook; Jin, Byung Kwan; Jung, Un Ju; Kim, Sang Ryong

2014-07-01

This study investigated the effect of naringin, a major flavonoid in grapefruit and citrus fruits, on the degeneration of the nigrostriatal dopaminergic (DA) projection in a neurotoxin model of Parkinson's disease (PD) in vivo and the potential underlying mechanisms focusing on the induction of glia-derived neurotrophic factor (GDNF), well known as an important neurotrophic factor involved in the survival of adult DA neurons. 1-Methyl-4-phenylpyridinium (MPP(+)) was unilaterally injected into the medial forebrain bundle of rat brains for a neurotoxin model of PD in the presence or absence of naringin by daily intraperitoneal injection. To ascertain whether naringin-induced GDNF contributes to neuroprotection, we further investigated the effects of intranigral injection of neutralizing antibodies against GDNF in the MPP(+) rat model of PD. Our observations demonstrate that naringin could increase the level of GDNF in DA neurons, contributing to neuroprotection in the MPP(+) rat model of PD, with activation of mammalian target of rapamycin complex 1. Moreover, naringin could attenuate the level of tumor necrosis factor-α in microglia increased by MPP(+)-induced neurotoxicity in the substantia nigra. These results indicate that naringin could impart to DA neurons the important ability to produce GDNF as a therapeutic agent against PD with anti-inflammatory effects, suggesting that naringin is a beneficial natural product for the prevention of DA degeneration in the adult brain. Copyright © 2014 Elsevier Inc. All rights reserved.

KSC-03pd1448

NASA Image and Video Library

2003-05-06

KENNEDY SPACE CENTER, FLA. - Pictured is one of the microcapsules removed from the Commercial ITA Biomedical Experiments payload recovered during the search for Columbia debris. The drug delivery system and spaceflight hardware was developed jointly by JSC, the Institute for Research Inc. and Instrumentation Technology Associates Inc. to conduct microencapsulation experiments under microgravity conditions. This microcapsule contains an antibiotic for treating deep resistant pulmonary infections. Dr. Dennis Morrison, senior biotech project scientist, is principle investigator on microencapsulation and urokinase crystal growth.

KSC-03pd1447

NASA Image and Video Library

2003-05-06

KENNEDY SPACE CENTER, FLA. - Pictured is one of the microcapsules removed from the Commercial ITA Biomedical Experiments payload recovered during the search for Columbia debris. The drug delivery system and spaceflight hardware was developed jointly by JSC, the Institute for Research Inc. and Instrumentation Technology Associates Inc. to conduct microencapsulation experiments under microgravity conditions. This microcapsule contains an antibiotic for treating deep resistant pulmonary infections. Dr. Dennis Morrison, senior biotech project scientist, is principle investigator on microencapsulation and urokinase crystal growth.

KSC-03pd1449

NASA Image and Video Library

2003-05-06

KENNEDY SPACE CENTER, FLA. - Pictured is one of the microcapsules removed from the Commercial ITA Biomedical Experiments payload recovered during the search for Columbia debris. The drug delivery system and spaceflight hardware was developed jointly by JSC, the Institute for Research Inc. and Instrumentation Technology Associates Inc. to conduct microencapsulation experiments under microgravity conditions. This microcapsule contains an antibiotic for treating deep resistant pulmonary infections. Dr. Dennis Morrison, senior biotech project scientist, is principle investigator on microencapsulation and urokinase crystal growth.

KSC-03PD-1449

NASA Technical Reports Server (NTRS)

2003-01-01

KENNEDY SPACE CENTER, FLA. - Pictured is one of the microcapsules removed from the Commercial ITA Biomedical Experiments payload recovered during the search for Columbia debris. The drug delivery system and spaceflight hardware was developed jointly by JSC, the Institute for Research Inc. and Instrumentation Technology Associates Inc. to conduct microencapsulation experiments under microgravity conditions. This microcapsule contains an antibiotic for treating deep resistant pulmonary infections. Dr. Dennis Morrison, senior biotech project scientist, is principle investigator on microencapsulation and urokinase crystal growth.

KSC-03PD-1447

NASA Technical Reports Server (NTRS)

2003-01-01

KENNEDY SPACE CENTER, FLA. - Pictured is one of the microcapsules removed from the Commercial ITA Biomedical Experiments payload recovered during the search for Columbia debris. The drug delivery system and spaceflight hardware was developed jointly by JSC, the Institute for Research Inc. and Instrumentation Technology Associates Inc. to conduct microencapsulation experiments under microgravity conditions. This microcapsule contains an antibiotic for treating deep resistant pulmonary infections. Dr. Dennis Morrison, senior biotech project scientist, is principle investigator on microencapsulation and urokinase crystal growth.

KSC-03PD-1448

NASA Technical Reports Server (NTRS)

2003-01-01

KENNEDY SPACE CENTER, FLA. - Pictured is one of the microcapsules removed from the Commercial ITA Biomedical Experiments payload recovered during the search for Columbia debris. The drug delivery system and spaceflight hardware was developed jointly by JSC, the Institute for Research Inc. and Instrumentation Technology Associates Inc. to conduct microencapsulation experiments under microgravity conditions. This microcapsule contains an antibiotic for treating deep resistant pulmonary infections. Dr. Dennis Morrison, senior biotech project scientist, is principle investigator on microencapsulation and urokinase crystal growth.

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.

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.

Comorbid Parkinson's disease, falls and fractures in the 2010 National Emergency Department Sample

PubMed Central

Beydoun, Hind A.; Beydoun, May A.; Mishra, Nishant K.; Rostant, Ola S.; Zonderman, Alan B.; Eid, Shaker M.

2017-01-01

Introduction Parkinson's disease (PD) is a progressive, neurodegenerative disorder of multifactorial etiology affecting ~1% of older adults. Research focused on linking PD to falls and bone fractures has been limited in Emergency Department (ED) settings, where most injuries are identified. We assessed whether injured U.S. ED admissions with PD diagnoses were more likely to exhibit comorbid fall- or non-fall related bone fractures and whether a PD diagnosis with a concomitant fall or bone fracture is linked to worse prognosis. Methods We performed secondary analyses of 2010 Healthcare Utilization Project National ED Sample from 4,253,987 admissions to U.S. EDs linked to injured elderly patients. ED discharges with ICD-9-CM code (332.0) were identified as PD and those with ICD-9-CM code (800.0–829.0) were used to define bone fracture location. Linear and logistic regression models were constructed to estimate slopes (B) and odds ratios (OR) with 95% confidence intervals (CI). Results PD admissions had 28% increased adjusted prevalence of bone fracture. Non-fall injuries showed stronger relationship between PD and bone fracture (ORadj = 1.33, 95% CI: 1.22–1.45) than fall injuries (ORadj = 1.06, 95% CI: 1.01–1.10). PD had the strongest impact on hospitalization length when bone fracture and fall co-occurred, and total charges were directly associated with PD only for fall injuries. Finally, PD status was not related to in-hospital death in this population. Conclusions Among injured U.S. ED elderly patient visits, those with PD had higher bone fracture prevalence and more resource utilization especially among fall-related injuries. No association of PD with in-hospital death was noted. PMID:27887896

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

Kerisit, Sebastien N.; Gao, Fei; Xie, YuLong

This Final Report presents work carried out at Pacific Northwest National Laboratory (PNNL) under the project entitled “Validated Models for Radiation Response and Signal Generation in Scintillators” (Project number: PL10-Scin-theor-PD2Jf) and led by Drs. Fei Gao and Sebastien N. Kerisit. This project was divided into four tasks: 1) Electronic response functions (ab initio data model) 2) Electron-hole yield, variance, and spatial distribution 3) Ab initio calculations of information carrier properties 4) Transport of electron-hole pairs and scintillation efficiency Detailed information on the results obtained in each of the four tasks is provided in this Final Report. Furthermore, published peer-reviewed articlesmore » based on the work carried under this project are included in Appendix. This work was supported by the National Nuclear Security Administration, Office of Nuclear Nonproliferation Research and Development (DNN R&D/NA-22), of the U.S. Department of Energy (DOE).« less

Development of a closed-loop system for tremor suppression in patients with Parkinson's disease.

PubMed

Xu, F L; Hao, M Z; Xu, S Q; Hu, Z X; Xiao, Q; Lan, N

2016-08-01

More than 70% of patients suffering Parkinson's disease (PD) exhibit resting tremor in their extremities, hampering their ability to perform daily activities. Based on our earlier studies on corticospinal transmission of tremor signals [10,11], we hypothesize that cutaneous afferents evoked by surface stimulation can produce an inhibitory effect on propriospinal neurons (PN), which in turn will suppress tremor signals passing through the PN. This paper presents the development of a closed-loop system for tremor suppression by transcutaneous electrical nerve stimulation (TENS) of sensory fibers beneath the skin. The closed-loop system senses EMGs of forearm muscles, and detects rhythmic bursting in the EMG signal. When a tremor is detected by the system, a command signal triggers a stimulator to output a train of bi-phasic, current regulated pulses to a pair of surface electrodes. The stimulation electrode is placed on the dorsal hand skin near the metacarpophalangeal joint of index finger, which is innervated by the superficial radial nerve that projects an inhibitory afferent to PNs of forearm muscles. We tested the closed-loop system in 3 normal subjects to verify the algorithm and in 2 tremor dominated PD subjects for feasibility of tremor detecting and suppression. Preliminary results indicate that the closed-loop system can detect tremor in all subjects, and tremor in PD patients was suppressed significantly by electrical stimulation of cutaneous afferents.

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

Thermodynamical study of boron doped CeX{sub 3} (X=Pd, Rh)

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

Sharma, Ramesh; Dwivedi, Shalini; Sharma, Yamini, E-mail: sharma.yamini62@gmail.com

2016-05-06

The structural, electronic, thermal, and optical properties of cubic non magnetic CeX{sub 3}(X=Pd, Rh) compounds which crystallize in the Au{sub 3}Cu structure have been studied using the projected augmented wave (PAW) method within the density functional theory (DFT) with generalized gradient approximation (GGA) for exchange correlation potential. In this paper we have calculated the band structure which are interpreted using the density of states. The optical properties such as extinction coefficients clearly illustrate the changes in CeX{sub 3} due to intercalation of boron. Lattice instability is observed in CePd{sub 3}B from the calculated dynamical properties.

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.

California’s Parkinson’s Disease Registry Pilot Project - Coordination Center and Northern California Ascertainment

DTIC Science & Technology

2011-03-01

project effort is being directed to investigate possible associations between PD and toxicant exposure using state databases, to define disease ... prevalence and care patterns among registrants, and to assess the value of the registry to stakeholders.

California’s Parkinson’s Disease Registry Pilot Project - Coordination Center and Northern California Ascertainment

DTIC Science & Technology

2012-03-01

project effort is being directed to investigate possible associations between PD and toxicant exposure using state databases, to define disease ... prevalence and care patterns among registrants, and to assess the value of the registry to stakeholders.

The research status of immune checkpoint blockade by anti-CTLA4 and anti-PD1/PD-l1 antibodies in tumor immunotherapy in China: A bibliometrics study.

PubMed

Zhao, Xiaoqin; He, Liangmei; Mao, Kaiyun; Chen, Daming; Jiang, Hongbo; Liu, Zhiping

2018-04-01

Using bibliometrics, we analyzed the research status of immune checkpoint blockade (ICB, a popular tumor immunotherapy method represented by antibodies targeted CTLA-4 and PD-1/PD-L1) in tumor immunotherapy in China during the past 2 decades. Articles in Science Citation Index Expanded (SCI-EXPANDED), patents in Thomson Innovation, and drugs in Cortellis Competitive Intelligence in the field of ICB for tumor immunotherapy from 1996 to 2015 were the subjects of bibliometric analysis. Using database-attached software and Excel, quantitative analyses were performed including examination of the number of documents, citation frequency, h-index, key projects, quantity of publications, public patents, and status of new drug research. The number of publications from 1996 to 2015 in the field of ICB for tumor immunotherapy that came out of China was 380, which was 14.3% of the total publications worldwide and was second only to that of the USA. In the past decade, China has rapidly increased the number of publications and patents in this field. However, indicators of publication influence, such as citation frequency and h-index, were far behind other advanced countries. In addition, the total number of patents in China was much lower than that of the USA. China has introduced 5 drugs for ICB that are being developed for the healthcare market. Tumor immunotherapy research such as ICB in China has developed rapidly with increasing influence in the last 2 decades. However, there is still a relatively large gap compared with the USA. It is expected that China will have greater influence on tumor immunotherapy research in the near future.

The research status of immune checkpoint blockade by anti-CTLA4 and anti-PD1/PD-l1 antibodies in tumor immunotherapy in China

PubMed Central

Zhao, Xiaoqin; He, Liangmei; Mao, Kaiyun; Chen, Daming; Jiang, Hongbo; Liu, Zhiping

2018-01-01

Abstract Purpose: Using bibliometrics, we analyzed the research status of immune checkpoint blockade (ICB, a popular tumor immunotherapy method represented by antibodies targeted CTLA-4 and PD-1/PD-L1) in tumor immunotherapy in China during the past 2 decades. Methods: Articles in Science Citation Index Expanded (SCI-EXPANDED), patents in Thomson Innovation, and drugs in Cortellis Competitive Intelligence in the field of ICB for tumor immunotherapy from 1996 to 2015 were the subjects of bibliometric analysis. Using database-attached software and Excel, quantitative analyses were performed including examination of the number of documents, citation frequency, h-index, key projects, quantity of publications, public patents, and status of new drug research. Results: The number of publications from 1996 to 2015 in the field of ICB for tumor immunotherapy that came out of China was 380, which was 14.3% of the total publications worldwide and was second only to that of the USA. In the past decade, China has rapidly increased the number of publications and patents in this field. However, indicators of publication influence, such as citation frequency and h-index, were far behind other advanced countries. In addition, the total number of patents in China was much lower than that of the USA. China has introduced 5 drugs for ICB that are being developed for the healthcare market. Conclusion: Tumor immunotherapy research such as ICB in China has developed rapidly with increasing influence in the last 2 decades. However, there is still a relatively large gap compared with the USA. It is expected that China will have greater influence on tumor immunotherapy research in the near future. PMID:29642147

Chemical Reactivity Testing for the National Spent Nuclear Fuel Program. Quality Assurance Project Plan

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

Newsom, H.C.

This quality assurance project plan (QAPjP) summarizes requirements used by Lockheed Martin Energy Systems, Incorporated (LMES) Development Division at Y-12 for conducting chemical reactivity testing of Department of Energy (DOE) owned spent nuclear fuel, sponsored by the National Spent Nuclear Fuel Program (NSNFP). The requirements are based on the NSNFP Statement of Work PRO-007 (Statement of Work for Laboratory Determination of Uranium Hydride Oxidation Reaction Kinetics.) This QAPjP will utilize the quality assurance program at Y-12, QA-101PD, revision 1, and existing implementing procedures for the most part in meeting the NSNFP Statement of Work PRO-007 requirements, exceptions will be noted.

Transfer of Analytical Skills From Subject to Subject - Reality or Fiction?

NASA Astrophysics Data System (ADS)

de Oliveira, G.; Murray, D. P.; Veeger, A.; Caulkin, J.; Brand, S.; Fogleman, J.; Dooley, H.

2013-12-01

The Rhode Island Technology Enhanced Science (RITES) Project is a partnership aimed at improving science education in Rhode Island. Most of the school districts in the state and five institutions of higher education participate in it. RITES was funded by the NSF Math and Science Partnership program, to a large extent because a statewide partnership would elucidate strategies that could be implemented in a diversity of environments throughout the country. The project has become an authentic and equal partnership that benefits both K-12 and higher education institutions; it has succeeded in improving science education by several measures, including gains in teacher content knowledge and in student performance on standardized exams. One of the centerpieces of the project is a professional development (PD) program, which has engaged more than 65% of the middle and secondary levels science teachers in the state. In this presentation we discuss outcomes of the PD, which shed light on questions of general interest to science educators. It is widely held that inquiry skills should be transferrable from one scientific domain to another regardless of content, and this premise was central to the original design philosophy of RITES PD. Nevertheless, although many educators embrace this view, it is a hypothesis that has been mostly untested. That is because there are few environments where an appropriate tool is in place to measure inquiry skills. RITES was uniquely positioned to measure the impact of its PD on student inquiry skills, and whether those skills would translate to topics not covered in classroom activities. New England has a multi-state consortium with a common assessment program, which measures inquiry skills in addition to content knowledge. Inquiry tasks on the New England Common Assessment Program (NECAP) may use any science topic. RITES offers technology-based classroom investigations for all areas of science, but it is nigh impossible to match inquiry opportunities during the academic year with the content of the NECAP inquiry tasks, as the latter continually change. An analysis of the NECAP inquiry assessment shows that students of RITES teachers do significantly better than others on inquiry. Moreover, no correlation has been found between the topics of the PDs and the NECAP inquiry tasks. These results will be discussed in this presentation along with insights from pre/post assessments of content knowledge specific to RITES investigations.

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…

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

KSC-03PD-2364

NASA Technical Reports Server (NTRS)

2003-01-01

KENNEDY SPACE CENTER, FLA. Researchers conduct underwater acoustic research in the Launch Complex 39 turn basin. Several government agencies, including NASA, NOAA, the Navy, the Coast Guard, and the Florida Fish and Wildlife Commission are involved in the testing. The research involves demonstrations of passive and active sensor technologies, with applications in fields ranging from marine biological research to homeland security. The work is also serving as a pilot project to assess the cooperation between the agencies involved. Equipment under development includes a passive acoustic monitor developed by NASAs Jet Propulsion Laboratory, and mobile robotic sensors from the Navys Mobile Diving and Salvage Unit.

Respiratory manifestations of panic disorder: causes, consequences and therapeutic implications.

PubMed

Sardinha, Aline; Freire, Rafael Christophe da Rocha; Zin, Walter Araújo; Nardi, Antonio Egidio

2009-07-01

Multiple respiratory abnormalities can be found in anxiety disorders, especially in panic disorder (PD). Individuals with PD experience unexpected panic attacks, characterized by anxiety and fear, resulting in a number of autonomic and respiratory symptoms. Respiratory stimulation is a common event during panic attacks. The respiratory abnormality most often reported in PD patients is increased CO2 sensitivity, which has given rise to the hypothesis of fundamental abnormalities in the physiological mechanisms that control breathing in PD. There is evidence that PD patients with dominant respiratory symptoms are more sensitive to respiratory tests than are those who do not manifest such symptoms, and that the former group constitutes a distinct subtype. Patients with PD tend to hyperventilate and to panic in response to respiratory stimulants such as CO2, triggering the activation of a hypersensitive fear network. Although respiratory physiology seems to remain normal in these subjects, recent evidence supports the idea that they present subclinical abnormalities in respiration and in other functions related to body homeostasis. The fear network, composed of the hippocampus, the medial prefrontal cortex, the amygdala and its brain stem projections, might be oversensitive in PD patients. This theory might explain why medication and cognitive-behavioral therapy are both clearly effective. Our aim was to review the relationship between respiration and PD, addressing the respiratory subtype of PD and the hyperventilation syndrome, with a focus on respiratory challenge tests, as well as on the current mechanistic concepts and the pharmacological implications of this relationship.

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.

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).

Programmed cell death 1 inhibits inflammatory helper T-cell development through controlling the innate immune response

PubMed Central

Rui, Yuxiang; Honjo, Tasuku; Chikuma, Shunsuke

2013-01-01

Programmed cell death 1 (PD-1) is an inhibitory coreceptor on immune cells and is essential for self-tolerance because mice genetically lacking PD-1 (PD-1−/−) develop spontaneous autoimmune diseases. PD-1−/− mice are also susceptible to severe experimental autoimmune encephalomyelitis (EAE), characterized by a massive production of effector/memory T cells against myelin autoantigen, the mechanism of which is not fully understood. We found that an increased primary response of PD-1−/− mice to heat-killed mycobacteria (HKMTB), an adjuvant for EAE, contributed to the enhanced production of T-helper 17 (Th17) cells. Splenocytes from HKMTB-immunized, lymphocyte-deficient PD-1−/− recombination activating gene (RAG)2−/− mice were found to drive antigen-specific Th17 cell differentiation more efficiently than splenocytes from HKMTB-immunized PD-1+/+ RAG2−/− mice. This result suggested PD-1’s involvement in the regulation of innate immune responses. Mice reconstituted with PD-1−/− RAG2−/− bone marrow and PD-1+/+ CD4+ T cells developed more severe EAE compared with the ones reconstituted with PD-1+/+ RAG2−/− bone marrow and PD-1+/+ CD4+ T cells. We found that upon recognition of HKMTB, CD11b+ macrophages from PD-1−/− mice produced very high levels of IL-6, which helped promote naive CD4+ T-cell differentiation into IL-17–producing cells. We propose a model in which PD-1 negatively regulates antimycobacterial responses by suppressing innate immune cells, which in turn prevents autoreactive T-cell priming and differentiation to inflammatory effector T cells. PMID:24043779

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.

A Novel Passive Millimeter Imager for Broad-Area Search - Final Report on Project PL09-NPMI-PD07 (PNNL-55180)

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

Tedeschi, Jonathan R.; Bernacki, Bruce E.; Kelly, James F.

2011-12-31

This report describes research and development efforts toward a novel passive millimeter-wave (mm-wave) electromagnetic imaging device for broad-area search. It addresses the technical challenge of detecting anomalies that occupy a small fraction of a pixel. The purpose of the imager is to pinpoint suspicious locations for cuing subsequent higher-resolution imaging. The technical basis for the approach is to exploit thermal and polarization anomalies that distinguish man-made features from natural features.

KSC-03pd1204

NASA Image and Video Library

2003-04-23

KENNEDY SPACE CENTER, FLA. - JoAnn Morgan, director, External Relations and Business Development, speaks to the students of MESA, the New Mexico Mathematics, Engineering and Science Achievement Program. The students are visiting KSC, touring facilities and meeting with mentors. MESA students, high school seniors who hold grade-point averages of at least 3.2 and who tutor other students in math and science, have made the spring trip for the past 14 years. The MESA program has close ties to the NASA Training Project at the University of New Mexico.

KSC-03pd1203

NASA Image and Video Library

2003-04-23

KENNEDY SPACE CENTER, FLA. - JoAnn Morgan, director, External Relations and Business Development, speaks to the students of MESA, the New Mexico Mathematics, Engineering and Science Achievement Program. The students are visiting KSC, touring facilities and meeting with mentors. MESA students, high school seniors who hold grade-point averages of at least 3.2 and who tutor other students in math and science, have made the spring trip for the past 14 years. The MESA program has close ties to the NASA Training Project at the University of New Mexico.

KSC-03pd1205

NASA Image and Video Library

2003-04-23

KENNEDY SPACE CENTER, FLA. - JoAnn Morgan, director, External Relations and Business Development, speaks to the students of MESA, the New Mexico Mathematics, Engineering and Science Achievement Program. The students are visiting KSC, touring facilities and meeting with mentors. MESA students, high school seniors who hold grade-point averages of at least 3.2 and who tutor other students in math and science, have made the spring trip for the past 14 years. The MESA program has close ties to the NASA Training Project at the University of New Mexico.

KSC-04pd1309

NASA Image and Video Library

2004-06-17

KENNEDY SPACE CENTER, FLA. - In the KSC Space Life Sciences Lab’s Resource Recovery lab, bioengineer Tony Rector checks the ARMS reactor vessel. ARMS, or Aerobic Rotational Membrane System, is a wastewater processing project being tested for use on the International Space Station to collect, clean and reuse wastewater. It could be adapted for use on the Moon and Mars. The Lab is exploring various aspects of a bioregenerative life support system. Such research and technology development will be crucial to long-term habitation of space by humans.

KSC-04pd1310

NASA Image and Video Library

2004-06-17

KENNEDY SPACE CENTER, FLA. - In the KSC Space Life Sciences Lab’s Resource Recovery lab, bioengineer Tony Rector checks the clear plexiglass ARMS reactor vessel. ARMS, or Aerobic Rotational Membrane System, is a wastewater processing project being tested for use on the International Space Station to collect, clean and reuse wastewater. It could be adapted for use on the Moon and Mars. The Lab is exploring various aspects of a bioregenerative life support system. Such research and technology development will be crucial to long-term habitation of space by humans.

KSC-03PD-1203

NASA Technical Reports Server (NTRS)

2003-01-01

KENNEDY SPACE CENTER, FLA. - JoAnn Morgan, director, External Relations and Business Development, speaks to the students of MESA, the New Mexico Mathematics, Engineering and Science Achievement Program. The students are visiting KSC, touring facilities and meeting with mentors. MESA students, high school seniors who hold grade-point averages of at least 3.2 and who tutor other students in math and science, have made the spring trip for the past 14 years. The MESA program has close ties to the NASA Training Project at the University of New Mexico.

KSC-03PD-1205

NASA Technical Reports Server (NTRS)

2003-01-01

KENNEDY SPACE CENTER, FLA. - JoAnn Morgan, director, External Relations and Business Development, speaks to the students of MESA, the New Mexico Mathematics, Engineering and Science Achievement Program. The students are visiting KSC, touring facilities and meeting with mentors. MESA students, high school seniors who hold grade-point averages of at least 3.2 and who tutor other students in math and science, have made the spring trip for the past 14 years. The MESA program has close ties to the NASA Training Project at the University of New Mexico.

KSC-03PD-1201

NASA Technical Reports Server (NTRS)

2003-01-01

KENNEDY SPACE CENTER, FLA. -- Gregg Buckingham, University Affairs officer, External Relations and Business Development Directorate, addresses students of MESA, the New Mexico Mathematics, Engineering and Science Achievement Program. The students are visiting KSC, touring facilities and meeting with mentors. MESA students, high school seniors who hold grade-point averages of at least 3.2 and who tutor other students in math and science, have made the spring trip for the past 14 years. The MESA program has close ties to the NASA Training Project at the University of New Mexico.

KSC-03PD-1202

NASA Technical Reports Server (NTRS)

2003-01-01

KENNEDY SPACE CENTER, FLA. - Gregg Buckingham, University Affairs officer, External Relations and Business Development Directorate, addresses students of MESA, the New Mexico Mathematics, Engineering and Science Achievement Program. The students are visiting KSC, touring facilities and meeting with mentors. MESA students, high school seniors who hold grade-point averages of at least 3.2 and who tutor other students in math and science, have made the spring trip for the past 14 years. The MESA program has close ties to the NASA Training Project at the University of New Mexico.

KSC-03PD-1204

NASA Technical Reports Server (NTRS)

2003-01-01

KENNEDY SPACE CENTER, FLA. - JoAnn Morgan, director, External Relations and Business Development, speaks to the students of MESA, the New Mexico Mathematics, Engineering and Science Achievement Program. The students are visiting KSC, touring facilities and meeting with mentors. MESA students, high school seniors who hold grade-point averages of at least 3.2 and who tutor other students in math and science, have made the spring trip for the past 14 years. The MESA program has close ties to the NASA Training Project at the University of New Mexico.

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.

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.

'Posture for Learning': meeting the postural care needs of children with physical disabilities in mainstream primary schools in England--a research into practice exploratory study.

PubMed

Hutton, Eve; Coxon, Kirstie

2011-01-01

 To explore teachers and teaching assistants' (TAs) views of how to manage the postural care needs of children with physical disabilities (PD) in mainstream primary schools, with the aim of developing strategies to support teachers and assistants in this role.  Qualitative data were gathered from a purposive sample of four primary schools in one county in the U.K. Individual and focus group interviews with 36 teachers and TAs were carried out and used to generate an explanatory framework around their experiences of managing the postural care needs of children with PD.  Teachers and TAs in schools were found to have limited understanding of postural management. Very few had personal experience of the benefits of postural care--instead, most appeared to think in terms of 'doing' rather than 'knowing' about postural care. When implementing therapy programmes, teaching staff followed therapists' instructions carefully, but did not understand the purpose of their actions. Participants described the emotional impact of caring for a child with PD and expressed anxieties about causing discomfort when using equipment such as specialist seating and standing frames. Equipment was viewed as bulky, uncomfortable and restrictive and not suited to the school environment. When asked which kinds of support would be valuable, participants identified practical solutions such as additional space or resources. Based on these findings, therapists, specialist teachers and parents developed an 'A-Z of postural care'. This information resource aimed to address the gaps in knowledge and understanding highlighted by teachers and TAs in the interviews and to acknowledge their anxieties when teaching and caring for children with PD. Stakeholder involvement in all aspects of the project from setting the research question to the development of the A-Z resource has assisted in the dissemination of the resource and its integration into the mainstream school system within the county.

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.

Positive deviance--the West Bengal experience.

PubMed

Mustaphi, P; Dobe, M

2005-01-01

There are 11.1 million children in the age group 0-6 years in West Bengal. Of these, every second child under 3 years of age is underweight, more than four out of ten are stunted, and one out of eight are wasted. The Integrated Child Development Services (ICDS) programme in West Bengal has 355 operational projects covering 53,064 operational anganwadi centers reaching out to more than four million beneficiaries--approximately half of whom are children in the age group 0-3 years. The Department of Women and Child Development (DWCD) is trying to identify and replicate innovative, community-based, sustainable approaches. One such innovative initiative has been the "Keno Parbo Na" project based on the Positive Deviance (PD) approach which aims to reduce and prevent malnutrition among children under 3 years of age by focusing on local solutions and resources, local behaviors and practices. Behavior change is emphasized through participatory learning and community mobilization. The pilot phase of the project has been completed in two districts [Four blocks (2 in each District) and 32 villages/AWCs (8 in each block)] of West Bengal (Murshidabad and South 24 Parganas). The analysis of the project activities so far reveals that the issue of malnutrition and its prevention is now visible in the villages covered. Acceptance of desirable behavioral practices is observed within the community. A steady reduction in the moderate and severe level of malnutrition was noted across four districts. A general preponderance of girl children was noted at the entry stage indicating higher levels of severe and moderate malnutrition among girl children to begin with but also suggesting PD as an important strategy in reducing the gender gap in malnutrition. The boys gain in terms of nutritional status faster than the girls so in the intermediate phase malnourished girls are more in number. However, by the sixth / ninth round, as the malnutrition levels decline substantially, the gender gap tends to close.

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.

Implementation and evaluation of Parkinson disease management in an outpatient clinical pharmacist-run neurology telephone clinic.

PubMed

Stefan, Teodora Cristina; Elharar, Nicole; Garcia, Guadalupe

2018-05-01

Parkinson disease (PD) is a progressive, debilitating neurodegenerative disease that often requires complex pharmacologic treatment regimens. Prior to this clinic, there was no involvement of a clinical pharmacy specialist (CPS) in the outpatient neurology clinic at the West Palm Beach Veterans Affairs Medical Center. This was a prospective, quality-improvement project to develop a clinical pharmacist-run neurology telephone clinic and evaluate pharmacologic and nonpharmacologic interventions in an effort to improve the quality of care for patients with PD. Additionally, the CPS conducted medication education groups to 24 patients with PD and their caregivers, if applicable, at this medical center with the purpose of promoting patient knowledge and medication awareness. Medication management was performed via telephone rather than face to face. Only patients with a concomitant mental health diagnosis for which they were receiving at least one psychotropic medication were included for individual visits due to the established scope of practice of the CPS being limited to mental health and primary care medications. Data collection included patient and clinic demographics as well as pharmacologic and nonpharmacologic interventions made for patients enrolled from January 6, 2017, through March 31, 2017. A total of 49 pharmacologic and nonpharmacologic interventions were made for 10 patients. We successfully implemented and evaluated a clinical pharmacist-run neurology telephone clinic for patients with PD. Expansion of this clinic to patients with various neurological disorders may improve access to care using an innovative method of medication management expertise by a CPS.

Heterogeneous Pd catalysts as emulsifiers in Pickering emulsions for integrated multistep synthesis in flow chemistry

PubMed Central

Hiebler, Katharina; Lichtenegger, Georg J; Maier, Manuel C; Park, Eun Sung; Gonzales-Groom, Renie

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 Ce0.99− xSnxPd0.01O2−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. PMID:29623127

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…

Enhancing literacy practices in science classrooms through a professional development program for Canadian minority-language teachers

NASA Astrophysics Data System (ADS)

Rivard, Léonard P.; Gueye, Ndeye R.

2016-05-01

Literacy in the Science Classroom Project was a three-year professional development (PD) program supporting minority-language secondary teachers' use of effective language-based instructional strategies for teaching science. Our primary objective was to determine how teacher beliefs and practices changed over time and how these were enacted in different classrooms. We also wanted to identify the challenges and enablers to implementing these literacy strategies and practices at the classroom, school, and district levels. Data collection involved both qualitative and quantitative methodologies: student questionnaires; interviews with teachers, principals, and mentor; and focus groups with students. The findings suggest that the program had an impact on beliefs and practices commensurate with the workshop participation of individual teachers. These language-enhanced teacher practices also had a positive impact on the use of talking, reading and writing by students in the science classroom. Finally, continuing PD support may be needed in certain jurisdictions for strengthening minority-language programs given the high teacher mobility in content-area classrooms evident in this study.

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.

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.

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.

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

Coaching in Early Mathematics.

PubMed

Germeroth, Carrie; Sarama, Julie

2017-01-01

Falling scores in math have prompted a renewed interest in math instruction at early ages. By their own admission, early childhood educators are generally underprepared and not always comfortable teaching math. Professional development (PD) in early mathematics is widely considered a main way to increase teachers' skills and efficacy (e.g., Guskey, 2000; Hyson & Woods, 2014; Munby, Russell, & Martin, 2001; Piasta, Logan, Pelatti, Capps, & Petrill, 2015; Richardson & Placier, 2001; Sarama, Clements, Wolfe, & Spitler, 2016; Sarama & DiBiase, 2004; Zaslow, 2014). However, it has been documented that stand-alone PD is not as effective in changing practice (e.g., Biancarosa & Bryk, 2011; Garet et al., 2008; Guskey, 2000; Hyson & Woods, 2014; Institute of Medicine and National Research Council, 2015; Joyce & Showers, 2002; Zaslow, 2014). Site-embedded ongoing support in the form of coaching or mentoring has been shown to be critical for successful implementation (Neuman & Cunningham, 2009; Powell, Diamond, Burchinal, & Koehler, 2010). In this chapter, we describe coaching models and abstract characteristics of effective coaching from the research. With this background, we provide an in-depth view of the coaching aspect of two large empirical studies in early mathematics. We introduce the theoretical framework from which the coaching models for these projects were developed and describe the research on which they were based. We then summarize how the planned models were instantiated and challenges to their implementation within each project. In the final section, we summarize what we have learned and described implications and challenges for the field. © 2017 Elsevier Inc. All rights reserved.

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.

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.

Pt-decorated PdCo@Pd/C core-shell nanoparticles with enhanced stability and electrocatalytic activity for the oxygen reduction reaction.

PubMed

Wang, Deli; Xin, Huolin L; Yu, Yingchao; Wang, Hongsen; Rus, Eric; Muller, David A; Abruña, Hector D

2010-12-22

A simple method for the preparation of PdCo@Pd core-shell nanoparticles supported on carbon based on an adsorbate-induced surface segregation effect has been developed. The stability of these PdCo@Pd nanoparticles and their electrocatalytic activity for the oxygen reduction reaction (ORR) were enhanced by decoration with a small amount of Pt deposited via a spontaneous displacement reaction. The facile method described herein is suitable for large-scale, lower-cost production and significantly lowers the Pt loading and thus the cost. The as-prepared PdCo@Pd and Pd-decorated PdCo@Pd nanocatalysts have a higher methanol tolerance than Pt/C in the ORR and are promising cathode catalysts for fuel cell applications.

Pt-Decorated PdCo@Pd/C Core-Shell Nanoparticles with Enhanced Stability and Electrocatalytic Activity for the Oxygen Reduction Reaction

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

Wang, Deli; Xin, Huolin L.; Yu, Yingchao

2010-11-24

A simple method for the preparation of PdCo@Pd core-shell nanoparticles supported on carbon based on an adsorbate-induced surface segregation effect has been developed. The stability of these PdCo@Pd nanoparticles and their electrocatalytic activity for the oxygen reduction reaction (ORR) were enhanced by decoration with a small amount of Pt deposited via a spontaneous displacement reaction. The facile method described herein is suitable for large-scale, lower-cost production and significantly lowers the Pt loading and thus the cost. The as-prepared PdCo@Pd and Pd-decorated PdCo@Pd nanocatalysts have a higher methanol tolerance than Pt/C in the ORR and are promising cathode catalysts for fuelmore » cell applications.« less

COPPADIS-2015 (COhort of Patients with PArkinson's DIsease in Spain, 2015), a global--clinical evaluations, serum biomarkers, genetic studies and neuroimaging--prospective, multicenter, non-interventional, long-term study on Parkinson's disease progression.

PubMed

Santos-García, Diego; Mir, Pablo; Cubo, Esther; Vela, Lydia; Rodríguez-Oroz, Mari Cruz; Martí, Maria José; Arbelo, José Matías; Infante, Jon; Kulisevsky, Jaime; Martínez-Martín, Pablo

2016-02-25

Parkinson's disease (PD) is a progressive neurodegenerative disorder causing motor and non-motor symptoms that can affect independence, social adjustment and the quality of life (QoL) of both patients and caregivers. Studies designed to find diagnostic and/or progression biomarkers of PD are needed. We describe here the study protocol of COPPADIS-2015 (COhort of Patients with PArkinson's DIsease in Spain, 2015), an integral PD project based on four aspects/concepts: 1) PD as a global disease (motor and non-motor symptoms); 2) QoL and caregiver issues; 3) Biomarkers; 4) Disease progression. Observational, descriptive, non-interventional, 5-year follow-up, national (Spain), multicenter (45 centers from 15 autonomous communities), evaluation study. Specific goals: (1) detailed study (clinical evaluations, serum biomarkers, genetic studies and neuroimaging) of a population of PD patients from different areas of Spain, (2) comparison with a control group and (3) follow-up for 5 years. COPPADIS-2015 has been specifically designed to assess 17 proposed objectives. approximately 800 non-dementia PD patients, 600 principal caregivers and 400 control subjects. Study evaluations: (1) baseline includes motor assessment (e.g., Unified Parkinson's Disease Rating Scale part III), non-motor symptoms (e.g., Non-Motor Symptoms Scale), cognition (e.g., Parkinson's Disease Cognitive Rating Scale), mood and neuropsychiatric symptoms (e.g., Neuropsychiatric Inventory), disability, QoL (e.g., 39-item Parkinson's disease Quality of Life Questionnaire Summary-Index) and caregiver status (e.g., Zarit Caregiver Burden Inventory); (2) follow-up includes annual (patients) or biannual (caregivers and controls) evaluations. Serum biomarkers (S-100b protein, TNF-α, IL-1, IL-2, IL-6, vitamin B12, methylmalonic acid, homocysteine, uric acid, C-reactive protein, ferritin, iron) and brain MRI (volumetry, tractography and MTAi [Medial Temporal Atrophy Index]), at baseline and at the end of follow-up, and genetic studies (DNA and RNA) at baseline will be performed in a subgroup of subjects (300 PD patients and 100 control subjects). Study periods: (1) recruitment period, from November, 2015 to February, 2017 (basal assessment); (2) follow-up period, 5 years; (3) closing date of clinical follow-up, May, 2022. Public/Private. COPPADIS-2015 is a challenging initiative. This project will provide important information on the natural history of PD and the value of various biomarkers.

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…

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.

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.

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.

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

Performance of a high-sensitivity dedicated cardiac SPECT scanner for striatal uptake quantification in the brain based on analysis of projection data

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

Park, Mi-Ae; Moore, Stephen C.; McQuaid, Sarah J.

Purpose: The authors have previously reported the advantages of high-sensitivity single-photon emission computed tomography (SPECT) systems for imaging structures located deep inside the brain. DaTscan (Isoflupane I-123) is a dopamine transporter (DaT) imaging agent that has shown potential for early detection of Parkinson disease (PD), as well as for monitoring progression of the disease. Realizing the full potential of DaTscan requires efficient estimation of striatal uptake from SPECT images. They have evaluated two SPECT systems, a conventional dual-head gamma camera with low-energy high-resolution collimators (conventional) and a dedicated high-sensitivity multidetector cardiac imaging system (dedicated) for imaging tasks related to PD.more » Methods: Cramer-Rao bounds (CRB) on precision of estimates of striatal and background activity concentrations were calculated from high-count, separate acquisitions of the compartments (right striata, left striata, background) of a striatal phantom. CRB on striatal and background activity concentration were calculated from essentially noise-free projection datasets, synthesized by scaling and summing the compartment projection datasets, for a range of total detected counts. They also calculated variances of estimates of specific-to-nonspecific binding ratios (BR) and asymmetry indices from these values using propagation of error analysis, as well as the precision of measuring changes in BR on the order of the average annual decline in early PD. Results: Under typical clinical conditions, the conventional camera detected 2 M counts while the dedicated camera detected 12 M counts. Assuming a normal BR of 5, the standard deviation of BR estimates was 0.042 and 0.021 for the conventional and dedicated system, respectively. For an 8% decrease to BR = 4.6, the signal-to-noise ratio were 6.8 (conventional) and 13.3 (dedicated); for a 5% decrease, they were 4.2 (conventional) and 8.3 (dedicated). Conclusions: This implies that PD can be detected earlier with the dedicated system than with the conventional system; therefore, earlier identification of PD progression should be possible with the high-sensitivity dedicated SPECT camera.« less

KSC-03PD-2379

NASA Technical Reports Server (NTRS)

2003-01-01

KENNEDY SPACE CENTER, FLA. Researchers are positioned on one of the watercraft being utilized to conduct underwater acoustic research in the Launch Complex 39 turn basin. Several government agencies, including NASA, NOAA, the Navy, the Coast Guard, and the Florida Fish and Wildlife Commission are involved in the testing. The research involves demonstrations of passive and active sensor technologies, with applications in fields ranging from marine biological research to homeland security. The work is also serving as a pilot project to assess the cooperation between the agencies involved. Equipment under development includes a passive acoustic monitor developed by NASAs Jet Propulsion Laboratory, and mobile robotic sensors from the Navys Mobile Diving and Salvage Unit.

KSC-03PD-2365

NASA Technical Reports Server (NTRS)

2003-01-01

KENNEDY SPACE CENTER, FLA. Researchers utilize several types of watercraft to conduct underwater acoustic research in the Launch Complex 39 turn basin. Several government agencies, including NASA, NOAA, the Navy, the Coast Guard, and the Florida Fish and Wildlife Commission are involved in the testing. The research involves demonstrations of passive and active sensor technologies, with applications in fields ranging from marine biological research to homeland security. The work is also serving as a pilot project to assess the cooperation between the agencies involved. Equipment under development includes a passive acoustic monitor developed by NASAs Jet Propulsion Laboratory, and mobile robotic sensors from the Navys Mobile Diving and Salvage Unit.

KSC-03PD-2376

NASA Technical Reports Server (NTRS)

2003-01-01

KENNEDY SPACE CENTER, FLA. Researchers are positioned on one of the watercraft being utilized to conduct underwater acoustic research in the Launch Complex 39 turn basin. Several government agencies, including NASA, NOAA, the Navy, the Coast Guard, and the Florida Fish and Wildlife Commission are involved in the testing. The research involves demonstrations of passive and active sensor technologies, with applications in fields ranging from marine biological research to homeland security. The work is also serving as a pilot project to assess the cooperation between the agencies involved. Equipment under development includes a passive acoustic monitor developed by NASAs Jet Propulsion Laboratory, and mobile robotic sensors from the Navys Mobile Diving and Salvage Unit.

KSC-03PD-2366

NASA Technical Reports Server (NTRS)

2003-01-01

KENNEDY SPACE CENTER, FLA. Researchers utilize several types of watercraft to conduct underwater acoustic research in the Launch Complex 39 turn basin near Launch Pad 39A. Several government agencies, including NASA, NOAA, the Navy, the Coast Guard, and the Florida Fish and Wildlife Commission are involved in the testing. The research involves demonstrations of passive and active sensor technologies, with applications in fields ranging from marine biological research to homeland security. The work is also serving as a pilot project to assess the cooperation between the agencies involved. Equipment under development includes a passive acoustic monitor developed by NASAs Jet Propulsion Laboratory, and mobile robotic sensors from the Navys Mobile Diving and Salvage Unit.

The Effect of the Nunn-McCurdy Amendment on Unit-Cost-Growth of Defense Acquisition Projects

DTIC Science & Technology

2010-07-01

Congressional testimony: “I consider Virginia Class cost-reduction efforts a model for all our ships, submarines, and aircraft” (Roughhead, 2009...PATRIOT/MEADS CAP- MISSLE 2004 DE STRYKER 2004 PdE WIN-T INCREMENT 1 2007 PdE WIN-T INCREMENT 2 2007 DE Subtot~l Navy: ADS (ANJWOR-3) 2005 DE AGM...JAVELIN JLENS LONGBOW APACHE LUH PATRIOT PAC-3 PATRIOT/MEADS CAP - FIRE UNIT PATRIOT/MEADS CAP - MISSLE STRYKER WIN-T INCREMENT 1 WIN-T

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…

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.

KSC-03pd1446

NASA Image and Video Library

2003-05-06

KENNEDY SPACE CENTER, FLA. - The apparatus shown was designed to hold microcapsules for research on mission STS-107. It is one over several included in the Commercial ITA Biomedical Experiments payload. The box was recently recovered during the search for Columbia debris. The drug delivery system and spaceflight hardware was developed jointly by JSC, the Institute for Research Inc. and Instrumentation Technology Associates Inc. to conduct microencapsulation experiments under microgravity conditions. This microcapsule contains an antibiotic for treating deep resistant pulmonary infections. Dr. Dennis Morrison, senior biotech project scientist, is principle investigator on microencapsulation and urokinase crystal growth.

KSC-07pd3322

NASA Image and Video Library

2007-11-14

KENNEDY SPACE CENTER, FLA. -- In the Orbiter Processing Facility, technicians install the second Materials International Space Station Experiments, or MISSE, in space shuttle Endeavour's payload bay. The MISSE is part of the payload onboard Endeavour for mission STS-123. The MISSE project is a NASA/Langley Research Center-managed cooperative endeavor to fly materials and other types of space exposure experiments on the International Space Station. The objective is to develop early, low-cost, non-intrusive opportunities to conduct critical space exposure tests of space materials and components planned for use on future spacecraft. Photo credit: NASA/Kim Shiflett

KSC-03PD-1446

NASA Technical Reports Server (NTRS)

2003-01-01

KENNEDY SPACE CENTER, FLA. - The apparatus shown was designed to hold microcapsules for research on mission STS-107. It is one over several included in the Commercial ITA Biomedical Experiments payload. The box was recently recovered during the search for Columbia debris. The drug delivery system and spaceflight hardware was developed jointly by JSC, the Institute for Research Inc. and Instrumentation Technology Associates Inc. to conduct microencapsulation experiments under microgravity conditions. This microcapsule contains an antibiotic for treating deep resistant pulmonary infections. Dr. Dennis Morrison, senior biotech project scientist, is principle investigator on microencapsulation and urokinase crystal growth.

KSC-04pd1139

NASA Image and Video Library

2004-05-13

KENNEDY SPACE CENTER, FLA. -- Adm. Craig E. Steidle (center), NASA’s associate administrator, Office of Exploration Systems, tours the Orbiter Processing Facility on a visit to KSC. At right (hands up) is Conrad Nagel, chief of the Shuttle Project Office. They are standing under the orbiter Discovery. The Office of Exploration Systems was established to set priorities and direct the identification, development and validation of exploration systems and related technologies to support the future space vision for America. Steidle’s visit included a tour of KSC to review the facilities and capabilities to be used to support the vision.

Neuroprotective and Therapeutic Strategies against Parkinson’s Disease: Recent Perspectives

PubMed Central

Sarkar, Sumit; Raymick, James; Imam, Syed

2016-01-01

Parkinsonism is a progressive motor disease that affects 1.5 million Americans and is the second most common neurodegenerative disease after Alzheimer’s. Typical neuropathological features of Parkinson’s disease (PD) include degeneration of dopaminergic neurons located in the pars compacta of the substantia nigra that project to the striatum (nigro-striatal pathway) and depositions of cytoplasmic fibrillary inclusions (Lewy bodies) which contain ubiquitin and α-synuclein. The cardinal motor signs of PD are tremors, rigidity, slow movement (bradykinesia), poor balance, and difficulty in walking (Parkinsonian gait). In addition to motor symptoms, non-motor symptoms that include autonomic and psychiatric as well as cognitive impairments are pressing issues that need to be addressed. Several different mechanisms play an important role in generation of Lewy bodies; endoplasmic reticulum (ER) stress induced unfolded proteins, neuroinflammation and eventual loss of dopaminergic neurons in the substantia nigra of mid brain in PD. Moreover, these diverse processes that result in PD make modeling of the disease and evaluation of therapeutics against this devastating disease difficult. Here, we will discuss diverse mechanisms that are involved in PD, neuroprotective and therapeutic strategies currently in clinical trial or in preclinical stages, and impart views about strategies that are promising to mitigate PD pathology. PMID:27338353

Gastric motor dysfunctions in Parkinson's disease: Current pre-clinical evidence.

PubMed

Pellegrini, Carolina; Antonioli, Luca; Colucci, Rocchina; Ballabeni, Vigilio; Barocelli, Elisabetta; Bernardini, Nunzia; Blandizzi, Corrado; Fornai, Matteo

2015-12-01

Parkinson's disease (PD) is associated with several non-motor symptoms, such as behavioral changes, urinary dysfunction, sleep disorders, fatigue and, above all, gastrointestinal (GI) dysfunction, including gastric dysmotility, constipation and anorectal dysfunction. Delayed gastric emptying, progressing to gastroparesis, is reported in up to 100% of patients with PD, and it occurs at all stages of the disease with severe consequences to the patient's quality of life. The presence of α-synuclein (α-syn) aggregates in myenteric neurons throughout the digestive tract, as well as morpho-functional alterations of the enteric nervous system (ENS), have been documented in PD. In particular, gastric dysmotility in PD has been associated with an impairment of the brain-gut axis, involving the efferent fibers of the vagal pathway projecting directly to the gastric myenteric plexus. The present review intends to provide an integrated overview of available knowledge on the possible role played by the ENS, considered as a semi-autonomous nervous network, in the pathophysiology of gastric dysmotility in PD. Particular attention has been paid review how translational evidence in humans and studies in pre-clinical models are allowing a better understanding of the functional, neurochemical and molecular alterations likely underlying gastric motor abnormalities occurring in PD. Copyright © 2015 Elsevier Ltd. All rights reserved.

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.

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.

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.

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.

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…

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.

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.

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

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.

An approximation algorithm for the Noah's Ark problem with random feature loss.

PubMed

Hickey, Glenn; Blanchette, Mathieu; Carmi, Paz; Maheshwari, Anil; Zeh, Norbert

2011-01-01

The phylogenetic diversity (PD) of a set of species is a measure of their evolutionary distinctness based on a phylogenetic tree. PD is increasingly being adopted as an index of biodiversity in ecological conservation projects. The Noah's Ark Problem (NAP) is an NP-Hard optimization problem that abstracts a fundamental conservation challenge in asking to maximize the expected PD of a set of taxa given a fixed budget, where each taxon is associated with a cost of conservation and a probability of extinction. Only simplified instances of the problem, where one or more parameters are fixed as constants, have as of yet been addressed in the literature. Furthermore, it has been argued that PD is not an appropriate metric for models that allow information to be lost along paths in the tree. We therefore generalize the NAP to incorporate a proposed model of feature loss according to an exponential distribution and term this problem NAP with Loss (NAPL). In this paper, we present a pseudopolynomial time approximation scheme for NAPL.

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.

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.

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.

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.

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…

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…

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.

Afferent projections to the different medial amygdala subdivisions: a retrograde tracing study in the mouse.

PubMed

Cádiz-Moretti, Bernardita; Otero-García, Marcos; Martínez-García, Fernando; Lanuza, Enrique

2016-03-01

The medial amygdaloid nucleus (Me) is a key node in the socio-sexual brain, composed of anterior (MeA), posteroventral (MePV) and posterodorsal (MePD) subdivisions. These subdivisions have been suggested to play a different role in reproductive and defensive behaviours. In the present work we analyse the afferents of the three Me subdivisions using restricted injections of fluorogold in female outbred CD1 mice. The results reveal that the MeA, MePV and MePD share a common pattern of afferents, with some differences in the density of retrograde labelling in several nuclei. Common afferents to Me subdivisions include: the accessory olfactory bulbs, piriform cortex and endopiriform nucleus, chemosensory amygdala (receiving direct inputs from the olfactory bulbs), posterior part of the medial bed nucleus of the stria terminalis (BSTM), CA1 in the ventral hippocampus and posterior intralaminar thalamus. Minor projections originate from the basolateral amygdala and amygdalo-hippocampal area, septum, ventral striatum, several allocortical and periallocortical areas, claustrum, several hypothalamic structures, raphe and parabrachial complex. MeA and MePV share minor inputs from the frontal cortex (medial orbital, prelimbic, infralimbic and dorsal peduncular cortices), but differ in the lack of main olfactory projections to the MePV. By contrast, the MePD receives preferential projections from the rostral accessory olfactory bulb, the posteromedial BSTM and the ventral premammillary nucleus. In summary, the common pattern of afferents to the Me subdivisions and their interconnections suggest that they play cooperative instead of differential roles in the various behaviours (e.g., sociosexual, defensive) in which the Me has been shown to be involved.

Effect of Ag and Pd promotion on CH4 selectivity in Fe(100) Fischer-Tröpsch catalysis.

PubMed

Psarras, Peter C; Wilcox, Jennifer; Ball, David W

2017-02-15

The current CO 2 utilization market is dominated by enhanced oil recovery and urea manufacturing; yet, the scale of demand falls well short of that deemed necessary to make a significant impact on climate change. CO 2 conversion to fuels, however, is a utilization technology that can theoretically match the scale of projected CO 2 capture. Fischer-Tröpsch (FT) processing is a long-established technology for converting non-petroleum based precursors into transportation fuels and other valuable chemicals. Here, we report the effects of Pd and Ag doping on CH 4 selectivity over Fe(100), a common FT catalyst, as these metals have shown potential in the direct conversion of co-fed CO 2 . Adsorption energies for pathway specific C1 and C2 species were weakened in the presence of Ag and Pd by ca. 0.55 eV and 0.35 eV, respectively. Further, while both Ag- and Pd-promoted surfaces show decreased CH 4 production, Ag introduces a prohibitively high coupling barrier; thus, only Pd offered a decrease in CH 4 selectivity (-36%) relative to unmodified Fe(100).

Electrical Power Systems for NASA's Space Transportation Program

NASA Technical Reports Server (NTRS)

Lollar, Louis F.; Maus, Louis C.

1998-01-01

Marshall Space Flight Center (MSFC) is the National Aeronautics and Space Administration's (NASA) lead center for space transportation systems development. These systems include earth to orbit launch vehicles, as well as vehicles for orbital transfer and deep space missions. The tasks for these systems include research, technology maturation, design, development, and integration of space transportation and propulsion systems. One of the key elements in any transportation system is the electrical power system (EPS). Every transportation system has to have some form of electrical power and the EPS for each of these systems tends to be as varied and unique as the missions they are supporting. The Preliminary Design Office (PD) at MSFC is tasked to perform feasibility analyses and preliminary design studies for new projects, particularly in the space transportation systems area. All major subsystems, including electrical power, are included in each of these studies. Three example systems being evaluated in PD at this time are the Liquid Fly Back Booster (LFBB) system, the Human Mission to Mars (HMM) study, and a tether based flight experiment called the Propulsive Small Expendable Deployer System (ProSEDS). These three systems are in various stages of definition in the study phase.

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.

Differential efferent projections of the anterior, posteroventral, and posterodorsal subdivisions of the medial amygdala in mice

PubMed Central

Pardo-Bellver, Cecília; Cádiz-Moretti, Bernardita; Novejarque, Amparo; Martínez-García, Fernando; Lanuza, Enrique

2012-01-01

The medial amygdaloid nucleus (Me) is a key structure in the control of sociosexual behavior in mice. It receives direct projections from the main and accessory olfactory bulbs (AOB), as well as an important hormonal input. To better understand its behavioral role, in this work we investigate the structures receiving information from the Me, by analysing the efferent projections from its anterior (MeA), posterodorsal (MePD) and posteroventral (MePV) subdivisions, using anterograde neuronal tracing with biotinylated and tetrametylrhodamine-conjugated dextranamines. The Me is strongly interconnected with the rest of the chemosensory amygdala, but shows only moderate projections to the central nucleus and light projections to the associative nuclei of the basolateral amygdaloid complex. In addition, the MeA originates a strong feedback projection to the deep mitral cell layer of the AOB, whereas the MePV projects to its granule cell layer. The Me (especially the MeA) has also moderate projections to different olfactory structures, including the piriform cortex (Pir). The densest outputs of the Me target the bed nucleus of the stria terminalis (BST) and the hypothalamus. The MeA and MePV project to key structures of the circuit involved in the defensive response against predators (medial posterointermediate BST, anterior hypothalamic area, dorsomedial aspect of the ventromedial hypothalamic nucleus), although less dense projections also innervate reproductive-related nuclei. In contrast, the MePD projects mainly to structures that control reproductive behaviors [medial posteromedial BST, medial preoptic nucleus, and ventrolateral aspect of the ventromedial hypothalamic nucleus], although less dense projections to defensive-related nuclei also exist. These results confirm and extend previous results in other rodents and suggest that the medial amygdala is anatomically and functionally compartmentalized. PMID:22933993

Differential efferent projections of the anterior, posteroventral, and posterodorsal subdivisions of the medial amygdala in mice.

PubMed

Pardo-Bellver, Cecília; Cádiz-Moretti, Bernardita; Novejarque, Amparo; Martínez-García, Fernando; Lanuza, Enrique

2012-01-01

The medial amygdaloid nucleus (Me) is a key structure in the control of sociosexual behavior in mice. It receives direct projections from the main and accessory olfactory bulbs (AOB), as well as an important hormonal input. To better understand its behavioral role, in this work we investigate the structures receiving information from the Me, by analysing the efferent projections from its anterior (MeA), posterodorsal (MePD) and posteroventral (MePV) subdivisions, using anterograde neuronal tracing with biotinylated and tetrametylrhodamine-conjugated dextranamines. The Me is strongly interconnected with the rest of the chemosensory amygdala, but shows only moderate projections to the central nucleus and light projections to the associative nuclei of the basolateral amygdaloid complex. In addition, the MeA originates a strong feedback projection to the deep mitral cell layer of the AOB, whereas the MePV projects to its granule cell layer. The Me (especially the MeA) has also moderate projections to different olfactory structures, including the piriform cortex (Pir). The densest outputs of the Me target the bed nucleus of the stria terminalis (BST) and the hypothalamus. The MeA and MePV project to key structures of the circuit involved in the defensive response against predators (medial posterointermediate BST, anterior hypothalamic area, dorsomedial aspect of the ventromedial hypothalamic nucleus), although less dense projections also innervate reproductive-related nuclei. In contrast, the MePD projects mainly to structures that control reproductive behaviors [medial posteromedial BST, medial preoptic nucleus, and ventrolateral aspect of the ventromedial hypothalamic nucleus], although less dense projections to defensive-related nuclei also exist. These results confirm and extend previous results in other rodents and suggest that the medial amygdala is anatomically and functionally compartmentalized.

The effects of a mindfulness-based lifestyle programme for adults with Parkinson's disease: protocol for a mixed methods, randomised two-group control study.

PubMed

Advocat, Jenny; Russell, Grant; Enticott, Joanne; Hassed, Craig; Hester, Jennifer; Vandenberg, Brooke

2013-10-10

Parkinson's disease (PD) is the second most common neurodegenerative disorder in developed countries. There is an increasing interest in the use of mindfulness-related interventions in the management of patients with a chronic disease. In addition, interventions that promote personal control, stress-management and other lifestyle factors, such as diet and exercise, assist in reducing disability and improving quality of life in people with chronic illnesses. There has been little research in this area for people with PD. A prospective mixed-method randomised clinical trial involving community living adults with PD aged <76 years and with moderate disease severity (Hoehn and Yahr stage 2) PD. Participants will be randomised into the ESSENCE 6-week programme or a matched wait list control group. ESSENCE is a multifaceted, healthy lifestyle and mindfulness programme designed to improve quality of life. We aim to determine whether participation in a mindfulness and lifestyle programme could improve PD-related function and explore self-management related experiences and changing attitudes towards self-management. The outcome measures will include 5 self-administered questionnaires: PD function and well-being questionnaire (PDQ39), Health Behaviours, Mental health, Multidimensional locus of control, and Freiburg mindfulness inventory. An embedded qualitative protocol will include in-depth interviews with 12 participants before and after participation in the 6-week programme and a researcher will observe the programme and take notes. Repeated measures of Analysis of Variance (ANOVA) will examine the outcome measures for any significant effects from the group allocation, age, sex, adherence score and attendance. Qualitative data will be analysed thematically. We will outline the benefits of, and barriers to, the uptake of the intervention. This protocol has received ethics approval from the Monash University Human Research Ethics Committee project number CF11/2662-2011001553. This is the first research of its kind in Australia involving a comprehensive, lifestyle-based programme for people with PD and has the potential to involve a broader range of providers than standard care. The findings will be disseminated through peer reviewed journals, primary care conferences in Australia as well as abroad and through the Parkinson's community. Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12612000440820.

The effects of a mindfulness-based lifestyle programme for adults with Parkinson’s disease: protocol for a mixed methods, randomised two-group control study

PubMed Central

Advocat, Jenny; Russell, Grant; Enticott, Joanne; Hassed, Craig; Hester, Jennifer; Vandenberg, Brooke

2013-01-01

Introduction Parkinson's disease (PD) is the second most common neurodegenerative disorder in developed countries. There is an increasing interest in the use of mindfulness-related interventions in the management of patients with a chronic disease. In addition, interventions that promote personal control, stress-management and other lifestyle factors, such as diet and exercise, assist in reducing disability and improving quality of life in people with chronic illnesses. There has been little research in this area for people with PD. Methods A prospective mixed-method randomised clinical trial involving community living adults with PD aged <76 years and with moderate disease severity (Hoehn and Yahr stage 2) PD. Participants will be randomised into the ESSENCE 6-week programme or a matched wait list control group. ESSENCE is a multifaceted, healthy lifestyle and mindfulness programme designed to improve quality of life. We aim to determine whether participation in a mindfulness and lifestyle programme could improve PD-related function and explore self-management related experiences and changing attitudes towards self-management. The outcome measures will include 5 self-administered questionnaires: PD function and well-being questionnaire (PDQ39), Health Behaviours, Mental health, Multidimensional locus of control, and Freiburg mindfulness inventory. An embedded qualitative protocol will include in-depth interviews with 12 participants before and after participation in the 6-week programme and a researcher will observe the programme and take notes. Analysis Repeated measures of Analysis of Variance (ANOVA) will examine the outcome measures for any significant effects from the group allocation, age, sex, adherence score and attendance. Qualitative data will be analysed thematically. We will outline the benefits of, and barriers to, the uptake of the intervention. Ethics This protocol has received ethics approval from the Monash University Human Research Ethics Committee project number CF11/2662–2011001553. Dissemination This is the first research of its kind in Australia involving a comprehensive, lifestyle-based programme for people with PD and has the potential to involve a broader range of providers than standard care. The findings will be disseminated through peer reviewed journals, primary care conferences in Australia as well as abroad and through the Parkinson's community. Registration details Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12612000440820. PMID:24114370

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

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

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.

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.

Developing Partnerships between Higher Education Faculty, K-12 Science Teachers, and School Administrators via MSP initiatives: The RITES Model

NASA Astrophysics Data System (ADS)

Caulkins, J. L.; Kortz, K. M.; Murray, D. P.

2011-12-01

The Rhode Island Technology Enhanced Science Project (RITES) is a NSF-funded Math and Science Partnership (MSP) project that seeks to improve science education. RITES is, at its core, a unique partnership that fosters relationships between middle and high school science teachers, district and school administrators, higher education (HE) faculty members, and science education researchers. Their common goal is to enhance scientific inquiry, increase classroom technology usage, and improve state level science test scores. In one of the more visible examples of this partnership, middle and high school science teachers work closely with HE science faculty partners to design and teach professional development (PD) workshops. The PD sessions focus on technology-enhanced scientific investigations (e.g. use of probes, online simulations, etc.), exemplify inquiry-based instruction, and relate expert content knowledge. Teachers from these sessions express substantial satisfaction in the program, report increased comfort levels in teaching the presented materials (both via post-workshop surveys), and show significant gains in content knowledge (via pre-post assessments). Other benefits to this kind of partnership, in which K-12 and HE teachers are considered equals, include: 1) K-12 teachers are empowered through interactions with HE faculty and other science teachers in the state; 2) HE instructors become more informed not only about good pedagogical practices, but also practical aspects of teaching science such as engaging students; and 3) the PD sessions tend to be much stronger than ones designed and presented solely by HE scientists, for while HE instructors provide content expertise, K-12 teachers provide expertise in K-12 classroom practice and implementation. Lastly, the partnership is mutually beneficial for the partners involved because both sides learn practical ways to teach science and inquiry at different levels. In addition to HE faculty and K-12 science teacher interactions, RITES gives district-level administrators, HE faculty and teacher-leaders the opportunity to meet and set mutual teaching goals, enhancing the partnership and a sense of ownership within it.

An intelligent training system for space shuttle flight controllers

NASA Technical Reports Server (NTRS)

Loftin, R. Bowen; Wang, Lui; Baffes, Paul; Hua, Grace

1988-01-01

An autonomous intelligent training system which integrates expert system technology with training/teaching methodologies is described. The system was designed to train Mission Control Center (MCC) Flight Dynamics Officers (FDOs) to deploy a certain type of satellite from the Space Shuttle. The Payload-assist module Deploys/Intelligent Computer-Aided Training (PD/ICAT) system consists of five components: a user interface, a domain expert, a training session manager, a trainee model, and a training scenario generator. The interface provides the trainee with information of the characteristics of the current training session and with on-line help. The domain expert (DeplEx for Deploy Expert) contains the rules and procedural knowledge needed by the FDO to carry out the satellite deploy. The DeplEx also contains mal-rules which permit the identification and diagnosis of common errors made by the trainee. The training session manager (TSM) examines the actions of the trainee and compares them with the actions of DeplEx in order to determine appropriate responses. A trainee model is developed for each individual using the system. The model includes a history of the trainee's interactions with the training system and provides evaluative data on the trainee's current skill level. A training scenario generator (TSG) designs appropriate training exercises for each trainee based on the trainee model and the training goals. All of the expert system components of PD/ICAT communicate via a common blackboard. The PD/ICAT is currently being tested. Ultimately, this project will serve as a vehicle for developing a general architecture for intelligent training systems together with a software environment for creating such systems.

An intelligent training system for space shuttle flight controllers

NASA Technical Reports Server (NTRS)

Loftin, R. Bowen; Wang, Lui; Baffles, Paul; Hua, Grace

1988-01-01

An autonomous intelligent training system which integrates expert system technology with training/teaching methodologies is described. The system was designed to train Mission Control Center (MCC) Flight Dynamics Officers (FDOs) to deploy a certain type of satellite from the Space Shuttle. The Payload-assist module Deploys/Intelligent Computer-Aided Training (PD/ICAT) system consists of five components: a user interface, a domain expert, a training session manager, a trainee model, and a training scenario generator. The interface provides the trainee with information of the characteristics of the current training session and with on-line help. The domain expert (Dep1Ex for Deploy Expert) contains the rules and procedural knowledge needed by the FDO to carry out the satellite deploy. The Dep1Ex also contains mal-rules which permit the identification and diagnosis of common errors made by the trainee. The training session manager (TSM) examines the actions of the trainee and compares them with the actions of Dep1Ex in order to determine appropriate responses. A trainee model is developed for each individual using the system. The model includes a history of the trainee's interactions with the training system and provides evaluative data on the trainee's current skill level. A training scenario generator (TSG) designs appropriate training exercises for each trainee based on the trainee model and the training goals. All of the expert system components of PD/ICAT communicate via a common blackboard. The PD/ICAT is currently being tested. Ultimately, this project will serve as a vehicle for developing a general architecture for intelligent training systems together with a software environment for creating such systems.

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.

Monitoring of ovarian activity by measurement of urinary excretion rates using the Ovarian Monitor, Part IV: the relationship of the pregnanediol glucuronide threshold to basal body temperature and cervical mucus as markers for the beginning of the post-ovulatory infertile period.

PubMed

Blackwell, Leonard F; Vigil, Pilar; Alliende, María Elena; Brown, Simon; Festin, Mario; Cooke, Delwyn G

2016-02-01

Do the basal body temperature (BBT) shift and the cervical mucus markers for the beginning of the post-ovulatory infertile phase (POIP) of a menstrual cycle agree with the corresponding urinary pregnanediol glucuronide (PdG) threshold value? Perfect agreement between the cervical mucus markers and BBT shift and the hormonal definition of the start of post-ovulatory infertility occurred for only 7-17% of the cycles. The PdG threshold of 7.0 µmol/24 h is an objective and accurate marker for the beginning of the POIP. The rise in serum progesterone also produces the BBT shift and changes in cervical mucus which determine the mucus peak. Serum progesterone and urinary PdG are closely correlated when variations in urine volume are taken into account. Individual menstrual cycle profiles of urinary PdG excretion rates for 91 fertile cycles from normally cycling women were analysed to identify the day of the beginning of the POIP. These days were compared with those determined by the day of the BBT shift +2 days, the day of the mucus peak +4 days and the later of these two indicators. The study lasted 3 years. A total of 62 women with normal menstrual cycles were recruited from three centres: Palmerston North, New Zealand; Sydney, Australia and Santiago, Chile. The cycles were displayed individually in a proprietary database program which recorded the PdG excretion rates, the BBT shift day and the cervical mucus peak day. A group of 15 women from a separate Chilean study had PdG urinary data measured as well as their day of ovulation determined by ultrasound. The BBT and cervical mucus markers differed significantly in their identification of the beginning of the POIP when compared with the PdG excretion rate of 7.0 µmol/24 h. The observation that the BBT shift day and the mucus peak day could be identified even though the PdG excretion rates were still at baseline levels in some cycles could lead to an unexpected pregnancy for women using these natural family planning (NFP) indicators. The study consisted only of fertile cycles from women with regular cycles of 20-40 days duration. All the women were intending to avoid a pregnancy during the study, thus the limits of the fertile window were not tested. The NFP signals occurring earlier than the PdG threshold day could lead to an unexpected pregnancy. The signals occurring on the same day or later than the PdG threshold would not lead to unexpected pregnancies, but would require extra abstinence that could lead to non-compliance with the NFP method. A possible improvement in reliability of NFP methods is suggested. This study (project #90905) was funded by the NDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP). D.G.C. currently works for a diagnostic development company, Science Haven Ltd. The other authors have nothing to declare. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Association of Parkinson Disease Risk Loci With Mild Parkinsonian Signs in Older Persons

PubMed Central

Shulman, Joshua M.; Yu, Lei; Buchman, Aron S.; Evans, Denis A.; Schneider, Julie A.; Bennett, David A.; De Jager, Philip L.

2014-01-01

IMPORTANCE Parkinsonian motor signs are common in the aging population and are associated with adverse health outcomes. Compared with Parkinson disease (PD), potential genetic risk factors for mild parkinsonian signs have been largely unexplored. OBJECTIVE To determine whether PD susceptibility loci are associated with parkinsonism or substantia nigra pathology in a large community-based cohort of older persons. DESIGN, SETTING, AND PARTICIPANTS Eighteen candidate single-nucleotide polymorphisms from PD genome-wide association studies were evaluated in a joint clinicopathologic cohort. Participants included 1698 individuals and a nested autopsy collection of 821 brains from the Religious Orders Study and the Rush Memory and Aging Project, 2 prospective community-based studies. MAIN OUTCOMES AND MEASURES The primary outcomes were a quantitative measure of global parkinsonism or component measures of bradykinesia, rigidity, tremor, and gait impairment that were based on the motor Unified Parkinson’s Disease Rating Scale. In secondary analyses, we examined associations with additional quantitative motor traits and postmortem indices, including substantia nigra Lewy bodies and neuronal loss. RESULTS Parkinson disease risk alleles in the MAPT (rs2942168; P = .0006) and CCDC62 (rs12817488; P = .004) loci were associated with global parkinsonism, and these associations remained after exclusion of patients with a PD diagnosis. Based on motor Unified Parkinson’s Disease Rating Scale subscores, MAPT (P = .0002) and CCDC62 (P = .003) were predominantly associated with bradykinesia, and we further discovered associations between SREBF1 (rs11868035; P = .005) and gait impairment, SNCA (rs356220; P = .04) and rigidity, and GAK (rs1564282; P = .03) and tremor. In the autopsy cohort, only NMD3 (rs34016896; P = .03) was related to nigral neuronal loss, and no associations were detected with Lewy bodies. CONCLUSIONS AND RELEVANCE In addition to the established link to PD susceptibility, our results support a broader role for several loci in the development of parkinsonian motor signs and nigral pathology in older persons. PMID:24514572

Wettability of Si and Al–12Si alloy on Pd-implanted 6H–SiC

NASA Astrophysics Data System (ADS)

Wang, Ting-Ting; Liu, Gui-Wu; Huang, Zhi-Kun; Zhang, Xiang-Zhao; Xu, Zi-Wei; Qiao, Guan-Jun

2018-04-01

Not Available Project supported by the National Natural Science Foundation of China (Grant Nos. 51572112 and 51172177), the Natural Science Foundation of Jiangsu Province, China (Grant No. BK20151340), the Six Talent Peaks Project of Jiangsu Province, China (Grant Nos. 2014-XCL-002 and TD-XCL-004), the Innovation/Entrepreneurship Program of Jiangsu Province, China (Grant No. [2015]26), and the Qing Lan Project of Jiangsu Province, China (Grant No. [2016]15).

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

SL12-GADRAS-PD2Ka Annual Report

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

Mitchell, Dean J.

2014-09-09

The GADRAS Development project comprises several elements that are all related to the Detector Response Function (DRF), which is the core of GADRAS. An ongoing activity is implementing continuous improvements in the accuracy and versatility of the DRF. The ability to perform rapid computation of the response of gammaray detectors for 3-D descriptions of source objects and their environments is a good example of a recent utilization of this versatility. The 3-D calculations, which execute several orders of magnitude faster than competing techniques, compute the response as an extension of the DRF so the radiation transport problem is never solvedmore » explicitly, thus saving considerable computational time. Maintenance of the Graphic User Interface (GUI) and extension of the GUI to enable construction of the 3-D source models is included in tasking for the GADRAS Development project. Another aspect of this project is application of the isotope identification algorithms for search applications. Specifically, SNL is tasked with development of an isotope-identification based search capability for use with the RSL-developed AVID system, which supports simultaneous operation of numerous radiation search assets. A Publically Available (PA) GADRAS-DRF application, which eliminates sensitive analysis components, will soon be available so that the DRF can be used by researchers at universities and corporations.« less

Exposure to well water and pesticides in Parkinson's disease: a case-control study in the Madrid area

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

Jimenez-Jimenez, F.J.; Mateo, D.; Gimenez-Roldan, S.

1992-01-01

Past exposure to well water and pesticides was assessed in 128 unselected Parkinson's disease (PD) patients and 256 age and sex-matched controls. All were residents in a defined urban area of Madrid, Spain. In keeping with other reports, we found that exposure to well water might be a factor associated with the likelihood of developing PD, though only prolonged exposures of 30 years or longer were significantly different between PD and controls (p less than 0.02). In contrast, past exposure to pesticides did not appear to be associated with an increased risk of developing PD. Prolonged well water drinking antedatingmore » the development of PD was not associated with early onset of the disease, nor did such cases progress to greater disability. Future case-control studies addressing prolonged well water consumption as a risk factor in PD should look for differences in the content of substances other than pesticides in the water as determined by the source of water to which patients may have been specifically exposed.« less

Future of anti-PD-1/PD-L1 applications: Combinations with other therapeutic regimens.

PubMed

Song, Mengjia; Chen, Xinfeng; Wang, Liping; Zhang, Yi

2018-04-01

Programmed cell death 1 (PD-1)/programmed cell death 1 ligand (PD-L1) blockade has shown promising effects in cancer immunotherapy. Removing the so-called " brakes" on T cell immune responses by blocking the PD-1/PD-L1 check point should boost anti-tumor immunity and provide durable tumor regression for cancer patients. However, 30%-60% of patients show no response to PD-1/PD-L1 blockade. Thus, it is urgent to explore the underlying resistance mechanisms to improve sensitivity to anti-PD-1/PD-L1 therapy. We propose that the mechanisms promoting resistance mainly include T cell exclusion or exhaustion at the tumor site, immunosuppressive factors in the tumor microenvironment (TME), and a range of tumor-intrinsic factors. This review highlights the power of studying the cellular and molecular mechanisms of resistance to improve the rational design of combination therapeutic strategies that can be translated to the clinic. Here, we briefly discuss the development of PD-1/PD-L1 blockade agents and focus on the current issues and future prospects for potential combinatorial therapeutic strategies that include anti-PD-1/PD-L1 therapy, based upon the available preclinical and clinical data.

Semicomprehensive analysis of the postnatal age-related changes in the mRNA expression of sex steroidogenic enzymes and sex steroid receptors in the male rat hippocampus.

PubMed

Kimoto, Tetsuya; Ishii, Hirotaka; Higo, Shimpei; Hojo, Yasushi; Kawato, Suguru

2010-12-01

Although sex steroids play a crucial role in the postnatal brain development, the age-related changes in the hippocampal steroidogenesis remain largely unknown. We performed comprehensive investigations for the mRNA expressions of 26 sex steroidogenic enzymes/proteins and three sex steroid receptors in the male rat hippocampus, at the ages of postnatal day (PD) 1, PD4, PD7, PD10, PD14, 4 wk, and 12 wk (adult), by RT-PCR/Southern blotting analysis. The relative expression levels of these enzymes/receptors at PD1 were Srd5a1 > Star > Ar ∼ Hsd17b4 ∼ Hsd17b1 ∼ Hsd17b7 ∼ Esr1 ∼ Srd5a2 > Hsd17b3 > Esr2 > Cyp11a1 > Cyp17a1 > Cyp19a1 ∼ Hsd17b2 > 3β-hydroxysteroid dehydrogenase I. The mRNA levels of essential enzymes for progesterone/testosterone/estradiol metabolisms (Cyp17a1, Hsd17b7, and Cyp19a1) were approximately constant between PD1 and PD14 and then declined toward the adult levels. Cyp11a1 increased during PD4-PD14 and then considerably decreased toward the adult level (∼8% of PD1). Hsd17b1, Hsd17b2, and 3β-hydroxysteroid dehydrogenase I mRNA decreased approximately monotonously. Hsd17b3 increased to approximately 200% of PD1 during PD4-PD14 and was maintained at this high level. The 5α-reductase mRNA was maintained constant (Srd5a1) or decreased monotonically (Srd5a2) toward the adult level. The Esr1 level peaked at PD4 and decreased toward the adult level, whereas Ar greatly increased during PD1-PD14 and was maintained at this high level. The Star and Hsd17b4 levels were maintained constant from neonate to adult. These results suggest that the hippocampal sex steroidogenic properties are substantially altered during the postnatal development processes, which might contribute to brain sexual maturation.

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.

Impaired embryonic development in glucose-6-phosphate dehydrogenase-deficient Caenorhabditis elegans due to abnormal redox homeostasis induced activation of calcium-independent phospholipase and alteration of glycerophospholipid metabolism.

PubMed

Chen, Tzu-Ling; Yang, Hung-Chi; Hung, Cheng-Yu; Ou, Meng-Hsin; Pan, Yi-Yun; Cheng, Mei-Ling; Stern, Arnold; Lo, Szecheng J; Chiu, Daniel Tsun-Yee

2017-01-12

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a commonly pervasive inherited disease in many parts of the world. The complete lack of G6PD activity in a mouse model causes embryonic lethality. The G6PD-deficient Caenorhabditis elegans model also shows embryonic death as indicated by a severe hatching defect. Although increased oxidative stress has been implicated in both cases as the underlying cause, the exact mechanism has not been clearly delineated. In this study with C. elegans, membrane-associated defects, including enhanced permeability, defective polarity and cytokinesis, were found in G6PD-deficient embryos. The membrane-associated abnormalities were accompanied by impaired eggshell structure as evidenced by a transmission electron microscopic study. Such loss of membrane structural integrity was associated with abnormal lipid composition as lipidomic analysis revealed that lysoglycerophospholipids were significantly increased in G6PD-deficient embryos. Abnormal glycerophospholipid metabolism leading to defective embryonic development could be attributed to the increased activity of calcium-independent phospholipase A 2 (iPLA) in G6PD-deficient embryos. This notion is further supported by the fact that the suppression of multiple iPLAs by genetic manipulation partially rescued the embryonic defects in G6PD-deficient embryos. In addition, G6PD deficiency induced disruption of redox balance as manifested by diminished NADPH and elevated lipid peroxidation in embryos. Taken together, disrupted lipid metabolism due to abnormal redox homeostasis is a major factor contributing to abnormal embryonic development in G6PD-deficient C. elegans.

Insights on How to Shape Teacher Learning Policy: The Role of Teacher Content Knowledge in Explaining Differential Effects of Professional Development

ERIC Educational Resources Information Center

Covay Minor, Elizabeth; Desimone, Laura; Caines Lee, Jade; Hochberg, Eric D.

2016-01-01

In the US, many federal, state and local school improvement policies rely on teacher professional development (PD) to foster classroom change. Past research suggests PD that has a content focus is the most effective, but that even content-focused PD varies in its effectiveness. Through in-depth interviews of teachers participating in a middle…

PD-1/PD-L1 Blockade: Have We Found the Key to Unleash the Antitumor Immune Response?

PubMed Central

Xu-Monette, Zijun Y.; Zhang, Mingzhi; Li, Jianyong; Young, Ken H.

2017-01-01

PD-1–PD-L1 interaction is known to drive T cell dysfunction, which can be blocked by anti-PD-1/PD-L1 antibodies. However, studies have also shown that the function of the PD-1–PD-L1 axis is affected by the complex immunologic regulation network, and some CD8+ T cells can enter an irreversible dysfunctional state that cannot be rescued by PD-1/PD-L1 blockade. In most advanced cancers, except Hodgkin lymphoma (which has high PD-L1/L2 expression) and melanoma (which has high tumor mutational burden), the objective response rate with anti-PD-1/PD-L1 monotherapy is only ~20%, and immune-related toxicities and hyperprogression can occur in a small subset of patients during PD-1/PD-L1 blockade therapy. The lack of efficacy in up to 80% of patients was not necessarily associated with negative PD-1 and PD-L1 expression, suggesting that the roles of PD-1/PD-L1 in immune suppression and the mechanisms of action of antibodies remain to be better defined. In addition, important immune regulatory mechanisms within or outside of the PD-1/PD-L1 network need to be discovered and targeted to increase the response rate and to reduce the toxicities of immune checkpoint blockade therapies. This paper reviews the major functional and clinical studies of PD-1/PD-L1, including those with discrepancies in the pathologic and biomarker role of PD-1 and PD-L1 and the effectiveness of PD-1/PD-L1 blockade. The goal is to improve understanding of the efficacy of PD-1/PD-L1 blockade immunotherapy, as well as enhance the development of therapeutic strategies to overcome the resistance mechanisms and unleash the antitumor immune response to combat cancer. PMID:29255458

PD-1/PD-L1 Blockade: Have We Found the Key to Unleash the Antitumor Immune Response?

PubMed

Xu-Monette, Zijun Y; Zhang, Mingzhi; Li, Jianyong; Young, Ken H

2017-01-01

PD-1-PD-L1 interaction is known to drive T cell dysfunction, which can be blocked by anti-PD-1/PD-L1 antibodies. However, studies have also shown that the function of the PD-1-PD-L1 axis is affected by the complex immunologic regulation network, and some CD8 + T cells can enter an irreversible dysfunctional state that cannot be rescued by PD-1/PD-L1 blockade. In most advanced cancers, except Hodgkin lymphoma (which has high PD-L1/L2 expression) and melanoma (which has high tumor mutational burden), the objective response rate with anti-PD-1/PD-L1 monotherapy is only ~20%, and immune-related toxicities and hyperprogression can occur in a small subset of patients during PD-1/PD-L1 blockade therapy. The lack of efficacy in up to 80% of patients was not necessarily associated with negative PD-1 and PD-L1 expression, suggesting that the roles of PD-1/PD-L1 in immune suppression and the mechanisms of action of antibodies remain to be better defined. In addition, important immune regulatory mechanisms within or outside of the PD-1/PD-L1 network need to be discovered and targeted to increase the response rate and to reduce the toxicities of immune checkpoint blockade therapies. This paper reviews the major functional and clinical studies of PD-1/PD-L1, including those with discrepancies in the pathologic and biomarker role of PD-1 and PD-L1 and the effectiveness of PD-1/PD-L1 blockade. The goal is to improve understanding of the efficacy of PD-1/PD-L1 blockade immunotherapy, as well as enhance the development of therapeutic strategies to overcome the resistance mechanisms and unleash the antitumor immune response to combat cancer.

Idiopathic REM Sleep Behavior Disorder in the development of Parkinson’s Disease

PubMed Central

Boeve, Bradley F.

2016-01-01

Summary Parkinson’s disease (PD) is a progressive neurodegenerative disorder associated with Lewy body disease (LBD) pathology in central and peripheral nervous system structures. While the etiology of PD is not fully understood, recent clinicopathologic analyses by Braak and colleagues have led to the development of a staging system of LBD pathology in the evolution of prototypical PD. This system posits a relatively predictable topography of progression of LBD pathology in the central nervous system, from olfactory structures and the medulla, which then progresses rostrally from the medulla to the pons, then midbrain/substantia nigra, then limbic, and then neocortical structures. If this topography and temporal evolution of LBD pathology indeed occur, one could hypothesize that other manifestations of LBD which reflect degeneration of olfactory and pontomedullary structures may begin many years prior to the development of prominent nigral degeneration and the associated parkinsonian features of classic PD. One such manifestation of prodromal PD is rapid eye movement (REM) sleep behavior disorder (RBD), which is a parasomnia manifested by vivid dreams associated with dream enactment behavior during REM sleep. Animal and human studies have implicated lesions or dysfunction in REM sleep and motor control circuitry in the pontomedullary structures cause RBD phenomenology, and degeneration of these structures could explain the presence of RBD years or decades prior to the onset of parkinsonism in those who develop PD. This review incorporates the rapidly growing literature on RBD and other prodromal features of PD as it pertains to the Braak staging system, and presents a framework from which many hypotheses can be (and already are being) tested. An important outcome of this framework will be to determine the natural history of RBD and associated features in the evolution to PD in the current era of no disease-modifying therapies – these natural history data will permit the development of clinical trail methodology with key measures and adequate power to detect if such therapies delay the onset or prevent the development of PD and associated morbidity. PMID:23578773

KSC-03PD-2377

NASA Technical Reports Server (NTRS)

2003-01-01

KENNEDY SPACE CENTER, FLA. Research team members take their places on one of the watercraft being utilized to conduct underwater acoustic research in the Launch Complex 39 turn basin. Several government agencies, including NASA, NOAA, the Navy, the Coast Guard, and the Florida Fish and Wildlife Commission are involved in the testing. The research involves demonstrations of passive and active sensor technologies, with applications in fields ranging from marine biological research to homeland security. The work is also serving as a pilot project to assess the cooperation between the agencies involved. Equipment under development includes a passive acoustic monitor developed by NASAs Jet Propulsion Laboratory, and mobile robotic sensors from the Navys Mobile Diving and Salvage Unit.

KSC-03PD-2369

NASA Technical Reports Server (NTRS)

2003-01-01

KENNEDY SPACE CENTER, FLA. Dr. Grant Gilmore (left), Dynamac Corp., talks to another member of the research team conducting underwater acoustic research in the Launch Complex 39 turn basin. Several government agencies, including NASA, NOAA, the Navy, the Coast Guard, and the Florida Fish and Wildlife Commission are involved in the testing. The research involves demonstrations of passive and active sensor technologies, with applications in fields ranging from marine biological research to homeland security. The work is also serving as a pilot project to assess the cooperation between the agencies involved. Equipment under development includes a passive acoustic monitor developed by NASAs Jet Propulsion Laboratory, and mobile robotic sensors from the Navys Mobile Diving and Salvage Unit.

PD-L1 inhibitors in the pipeline: Promise and progress.

PubMed

Vanella, Vito; Festino, Lucia; Strudel, Martina; Simeone, Ester; Grimaldi, Antonio M; Ascierto, Paolo A

2017-01-01

Checkpoint inhibitors have improved survival for patients with melanoma, non-small-cell lung cancer (NSCLC), bladder, head and neck and other cancers. Antibodies against PD-L1, including atezolizumab, avelumab and durvalumab, are also being developed and have been approved for various cancers. Compared with anti-CTLA-4 drugs, studies with anti-PD-1/PD-L1 agents have suggested higher response rates and improved survival. Targeting PD-L1 rather than PD-1 may also theoretically offer further benefit, with the potential for improved efficacy and reduced toxicity, although this has not been clearly shown by clinical experience to date. Anti-PD-L1 agents have shown good efficacy and manageable toxicity in several tumor types.

Low-Dimensional Palladium Nanostructures for Fast and Reliable Hydrogen Gas Detection

PubMed Central

Noh, Jin-Seo; Lee, Jun Min; Lee, Wooyoung

2011-01-01

Palladium (Pd) has received attention as an ideal hydrogen sensor material due to its properties such as high sensitivity and selectivity to hydrogen gas, fast response, and operability at room temperature. Interestingly, various Pd nanostructures that have been realized by recent developments in nanotechnologies are known to show better performance than bulk Pd. This review highlights the characteristic properties, issues, and their possible solutions of hydrogen sensors based on the low-dimensional Pd nanostructures with more emphasis on Pd thin films and Pd nanowires. The finite size effects, relative strengths and weaknesses of the respective Pd nanostructures are discussed in terms of performance, manufacturability, and practical applicability. PMID:22346605

Microstructures of Pd-containing dispersants for admixed dental amalgams.

PubMed

Chern Lin, J H; Greener, E H

1991-10-01

Blended Pd-containing dispersants were developed by the utilization of a Ag-Cu eutectic into which Pd was substituted for Ag or Cu in concentrations of up to 20 wt%. Compositions were melted either in argon-filled sealed vycor tubes or in a graphite-linked carbon crucible of an induction furnace with an argon blanket. Ingots of approximately 1.5 cm in diameter were sectioned to 0.2 cm in thickness and polished through standard metallographic polishing procedures. The possible compounds were identified by XRD. The microstructures of the alloys were examined by SEM/EDS. XRD analysis of the alloys revealed the preferential dissolution of Pd in Cu when the Pd concentration was less than or equal to 10 wt%. When the Pd concentration exceeded 20 wt%, Pd was found to be dissolved in both Ag and Pd. No Cu3Pd x-ray diffraction peaks were found for alloys with Pd concentration of up to 20 wt%. SEM/EDS analysis confirmed XRD results; lamellae of Ag and Cu-Pd were found in alloys with Pd concentration less than or equal to 10 wt%.

Sustainability of a long term professional development program

NASA Astrophysics Data System (ADS)

Ries, Christine E.

Currently, in most school districts, the main form of teacher education comes from professional development (PD) that claims to improve teaching and student achievement. School districts and teachers spend time and money trying to make sure that they are providing the best quality education for their students. Yet, educators are looking for what the most effective form of PD should look like. Utilizing the methodology of a descriptive case study a long-term PD grant, called Science Alliance was evaluated to add to the research on PD and grant program efficacy. Twelve teachers that participated in the Science Alliance grant were interviewed, observed, and given a survey to see how and to what degree they were implementing the inquiry methodology three years after the grant ended. The results were compared with previously existing data that were collected by a company that Science Alliance hired to complete external research on the effects of the PD. The findings suggest that the teachers that participated have sustained the utilization and implementation of the methodology learned during the training. School administrators and/or staff developers could utilize the findings from this study to see what effective PD may entail. Future researchers may use findings from this study when reporting about grant program evaluations and/or PD.

Subclinical dopaminergic dysfunction in asymptomatic Parkinson's disease patients' relatives with a decreased sense of smell.

PubMed

Berendse, H W; Booij, J; Francot, C M; Bergmans, P L; Hijman, R; Stoof, J C; Wolters, E C

2001-07-01

By the time a clinical diagnosis of Parkinson's disease (PD) is made, a significant loss of dopaminergic neurons has already occurred. Identifying patients in the period between the presumed onset of dopaminergic cell loss and the appearance of clinical parkinsonism may be of major importance in the development of effective neuroprotective treatment strategies. In an effort to develop a feasible strategy to detect preclinical PD, a combination of olfactory processing tasks, including odor detection, odor identification, and odor discrimination was used to select groups of hyposmic and normosmic individuals from a total of 250 relatives (parents, siblings, or children) of subjects with PD. Single photon emission computed tomography (SPECT) with [123I]beta-CIT as a dopamine transporter ligand was used to assess nigrostriatal dopaminergic function in 25 hyposmic and 23 normosmic relatives of PD patients. An abnormal reduction in striatal dopamine transporter binding was found in 4 out of 25 hyposmic relatives of PD patients, two of whom subsequently developed clinical parkinsonism, and in none of the 23 normosmic relatives. These observations demonstrate that subclinical reductions in dopamine transporter binding can be detected in asymptomatic relatives of sporadic PD patients by means of [123I]beta-CIT and SPECT. The results further indicate that olfactory deficits may precede clinical motor signs in PD.

Interference removals on Pd, Ru and Au with ICP-QQQ-MS in PGE RM

NASA Astrophysics Data System (ADS)

Nadeem Hussain Bokhari, Syed; Meisel, Thomas; Walkner, Christoph

2015-04-01

Gold and platinum group elements (PGE) are essential industrial precious metals with high world demand due to their unique properties. Struggle for natural exploration of PGE is on great pace and recycling from industrial wastes, electronics and catalytic convertor is on the rise for PGE supply chain. Along with these developments it is becoming more challenging for analytical chemists to determine gold and PGE out of complex matrix which causes severe interferences. The current state of art is online analysis coupled with chromatographic separation of interferences. The ICP-QQQ-MS Agilent 8800 has the capability of using multi tunes and mass shifts. We aim to remove interferences on Pd+ (for direct and isotope dilution analysis) Au+ and Ru+ in lieu of chemical separations. YO+, SrOH+, ZnAr+, NiAr+, ZrO+, CuAr+, MoO+ , Ru+and Cd+ are expected interferences on Pd+ while Au+ is interfered by TaO+, HfOH+, GdAr+ and 102Ru+ ,104Ru+ by 102Pd+ ,104Pd+ etc. Initial test were performed on pure solutions of 1mg/l (interfering elements): 1 ng/l (Pd, Ru & Au) respectively. The outcomes of initial tests were applied on PGE reference material (RM) WMG-1 and SARM-7 (digested with Na2O2 sintering). The results obtained show that YO+, SrOH+ interfere (104Pd,105Pd), 104 Ru+ on (104Pd), ZnAr+ has slight interference on (104Pd and106Pd), ZrO+, NiAr+, CuAr+ interferences are negligible, MoO+ has severe interference on (108Pd, 110Pd) and that Cd+ has severe isobaric interference on (106Pd,108Pd, 110Pd). These interference have been removed by formation of Pd(NH3)3+complex. The TaO+, HfOH+ and GdAr+ interferences on Au+ are best removed by formation of Au(NH3)+ and Au(NH3)2+ complexes. 102Pd+,104Pd+interference on 102Ru+ ,104Ru+ can be removed by formation of Ru(NH3)4+ and RuO+ compounds. The results obtained comply with certified values of RM. The developed method is being tested on low concentration PGE reference materials. References: Sugiyama, N. " Removal of complex spectral interferences on noble metal isotopes." Agilent 8800 ICP-QQQ Application Handbook, 2014, 42-46.

Materials Data on PdC (SG:216) by Materials Project

DOE Data Explorer

Kristin Persson

2016-09-21

Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

Materials Data on PdC (SG:225) by Materials Project

DOE Data Explorer

Kristin Persson

2016-09-21

Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

Materials Data on SnPd (SG:62) by Materials Project

DOE Data Explorer

Kristin Persson

2015-01-27

Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

Materials Data on PdN (SG:131) by Materials Project

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

Kristin Persson

2016-05-24

Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

Development and Translational Application of a Minimal Physiologically Based Pharmacokinetic Model for a Monoclonal Antibody against Interleukin 23 (IL-23) in IL-23-Induced Psoriasis-Like Mice.

PubMed

Chen, Xi; Jiang, Xiling; Doddareddy, Rajitha; Geist, Brian; McIntosh, Thomas; Jusko, William J; Zhou, Honghui; Wang, Weirong

2018-04-01

The interleukin (IL)-23/T h 17/IL-17 immune pathway has been identified to play an important role in the pathogenesis of psoriasis. Many therapeutic proteins targeting IL-23 or IL-17 are currently under development for the treatment of psoriasis. In the present study, a mechanistic pharmacokinetics (PK)/pharmacodynamics (PD) study was conducted to assess the target-binding and disposition kinetics of a monoclonal antibody (mAb), CNTO 3723, and its soluble target, mouse IL-23, in an IL-23-induced psoriasis-like mouse model. A minimal physiologically based pharmacokinetic model with target-mediated drug disposition features was developed to quantitatively assess the kinetics and interrelationship between CNTO 3723 and exogenously administered, recombinant mouse IL-23 in both serum and lesional skin site. Furthermore, translational applications of the developed model were evaluated with incorporation of human PK for ustekinumab, an anti-human IL-23/IL-12 mAb developed for treatment of psoriasis, and human disease pathophysiology information in psoriatic patients. The results agreed well with the observed clinical data for ustekinumab. Our work provides an example on how mechanism-based PK/PD modeling can be applied during early drug discovery and how preclinical data can be used for human efficacious dose projection and guide decision making during early clinical development of therapeutic proteins. Copyright © 2018 by The Author(s).

Professional Development in a Reform Context: Understanding the Design and Enactment of Learning Experiences Created by Teacher Leaders for Science Educators

NASA Astrophysics Data System (ADS)

Shafer, Laura

Teacher in-service learning about education reforms like NGSS often begin with professional development (PD) as a foundational component (Supovitz & Turner, 2000). Teacher Leaders, who are early implementers of education reform, are positioned to play a contributing role to the design of PD. As early implementers of reforms, Teacher Leaders are responsible for interpreting the purposes of reform, enacting reforms with fidelity to meet those intended goals, and are positioned to share their expertise with others. However, Teacher Leader knowledge is rarely accessed as a resource for the design of professional development programs. This study is unique in that I analyze the knowledge Teacher Leaders, who are positioned as developers of PD, bring to the design of PD around science education reform. I use the extended interconnected model of professional growth (Clarke & Hollingsworth, 2002; Coenders & Terlouw, 2015) to analyze the knowledge pathways Teacher Leaders' access as PD developers. I found that Teacher Leaders accessed knowledge pathways that cycled through their personal domain, domain of practice and domain of consequence. Additionally the findings indicated when Teacher Leaders did not have access to these knowledge domains they were unwilling to continue with PD design. These findings point to how Teacher Leaders prioritize their classroom experience to ground PD design and use their perceptions of student learning outcomes as an indicator of the success of the reform. Because professional development (PD) is viewed as an important resource for influencing teachers' knowledge and beliefs around the implementation of education reform efforts (Garet, et al., 2001; Suppovitz & Turner, 2000), I offer that Teacher Leaders, who are early implementers of reform measures, can contribute to the professional development system. The second part of this dissertation documents the instantiation of the knowledge of Teacher Leaders, who are positioned as designers and facilitators of PD. I examine the extent to which Teacher Leader knowledge is instantiated into specific resources and tasks during PD specifically for the Next Generation Science Standards (NGSS). The findings indicate that Teacher Leaders' knowledge is instantiated in tasks that promote and facilitate alignment of Teacher Leader goals for NGSS science practices-based instruction, which are framed around student learning outcomes. I offer a number of ways in which these findings can help educators and PD developers to better structure activities that present an alternative vision for science education that also provides the needed resources to shape how classroom tasks are designed and managed in ways that attend to and build on the practical knowledge of Teacher Leaders. The third part of this dissertation addresses the role Teacher Leaders play in this reform context with respect to their contributions to the professional development system. Based on the analyses of the Teacher Leaders in this study, I claim Teacher Leaders are essential contributors to the professional development system that extends beyond their typical role of participant. I argue that Teacher Leaders bring special expertise to the role of designers and facilitators of PD programs, and to the role of ambassadors for professional learning communities in a reform context. Because Teacher Leaders have a broader influence on the professional development system as pictured here, the Teacher Leaders in this study represent an essential piece of the reform puzzle.

Modeling and Validation of Sodium Plugging for Heat Exchangers in Sodium-cooled Fast Reactor Systems

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

Ferroni, Paolo; Tatli, Emre; Czerniak, Luke

The project “Modeling and Validation of Sodium Plugging for Heat Exchangers in Sodium-cooled Fast Reactor Systems” was conducted jointly by Westinghouse Electric Company (Westinghouse) and Argonne National Laboratory (ANL), over the period October 1, 2013- March 31, 2016. The project’s motivation was the need to provide designers of Sodium Fast Reactors (SFRs) with a validated, state-of-the-art computational tool for the prediction of sodium oxide (Na 2O) deposition in small-diameter sodium heat exchanger (HX) channels, such as those in the diffusion bonded HXs proposed for SFRs coupled with a supercritical CO 2 (sCO 2) Brayton cycle power conversion system. In SFRs,more » Na 2O deposition can potentially occur following accidental air ingress in the intermediate heat transport system (IHTS) sodium and simultaneous failure of the IHTS sodium cold trap. In this scenario, oxygen can travel through the IHTS loop and reach the coldest regions, represented by the cold end of the sodium channels of the HXs, where Na 2O precipitation may initiate and continue. In addition to deteriorating HX heat transfer and pressure drop performance, Na 2O deposition can lead to channel plugging especially when the size of the sodium channels is small, which is the case for diffusion bonded HXs whose sodium channel hydraulic diameter is generally below 5 mm. Sodium oxide melts at a high temperature well above the sodium melting temperature such that removal of a solid plug such as through dissolution by pure sodium could take a lengthy time. The Sodium Plugging Phenomena Loop (SPPL) was developed at ANL, prior to this project, for investigating Na 2O deposition phenomena within sodium channels that are prototypical of the diffusion bonded HX channels envisioned for SFR-sCO 2 systems. In this project, a Computational Fluid Dynamic (CFD) model capable of simulating the thermal-hydraulics of the SPPL test section and provided with Na 2O deposition prediction capabilities, was developed. This state-of-the-art computational tool incorporates a first-principles Na 2O deposition model developed by ANL, and combines it with predictive capabilities for the spatial and temporal variation of temperature, velocity, dissolved oxygen concentration, and wall temperature under flowing sodium conditions. The CFD model was validated under no-deposition conditions using experimental data collected with the SPPL, demonstrating the model’s capability to predict the thermal-hydraulics of the SPPL test section within the measurement uncertainty characterizing the SPPL instrumentation. The model’s deposition prediction capability was not, however, validated as the SPPL could not be operated under plugging conditions during the project, resulting in the lack of deposition data with adequate pedigree for a CFD model validation. Two novel diagnostic techniques to detect and characterize Na 2O deposits, i.e. Ultrasonic Time Domain Reflectometry (UTDR) and Potential Drop (PD) techniques, were developed to ultimately assist in the validation effort under plugging conditions, which can be performed once the SPPL becomes operational. This development effort consisted first in demonstrating, analytically and/or computationally, the capability of these techniques to diagnose Na 2O deposits inside of small channels (particularly the deposit’s thickness), and subsequently in the fabrication and testing of prototypical UTDR and PD instrumentation. The testing, performed on mockups of the SPPL test section, demonstrated the capability of these techniques to detect and characterize material discontinuities like those induced by sodium oxide deposition on stainless steel channel walls. Because of the mentioned impossibility to run the SPPL in a plugging mode, the developed instrumentation could not be tested in-situ, i.e. at the SPPL while deposits are being formed inside of the SPPL test section. Recommended future work includes a possible enhancement in the CFD modeling technique and installation of the developed UTDR and PD instrumentation on the test section, followed by plugging tests to be conducted with the SPPL. The installation of the UTDR and PD diagnostic instrumentation on the SPPL test section will allow collection of Na 2O deposition data after the onset of deposition to nearly complete channel plugging, which can ultimately be used for the validation of the CFD model.« less

Dual-functional Pt-on-Pd supported on reduced graphene oxide hybrids: peroxidase-mimic activity and an enhanced electrocatalytic oxidation characteristic.

PubMed

Zhang, Xiahong; Wu, Genghuang; Cai, Zhixiong; Chen, Xi

2015-03-01

In this study, a facile hydrothermal method was developed to synthesize Pt-on-Pd supported on reduced graphene oxide (Pt-on-Pd/RGO) hybrids. Because of the synergistic effect between Pt-on-Pd and RGO, the obtained Pt-on-Pd/RGO had superior peroxidase-mimic activities in H2O2 reduction and TMB oxidation. The reaction medium was optimized and a sensing approach for H2O2 was developed with a linear range from 0.98 to 130.7 μM of H2O2. In addition, the characteristic of electrocatalytic oxidation of methanol was investigated. The peak current density value, j(f), for the Pt-on-Pd/RGO hybrid (328 mA mg(Pt)(-1)) was about 1.85 fold higher than that of commercial Pt black (177 mA mg(Pt)(-1)) and, also, more durable electrocatalytic activity could be obtained. For the first time, the dual-functional Pt-on-Pd/RGO with peroxidase-mimic activity and an enhanced electrocatalytic oxidation characteristic was reported. Copyright © 2014 Elsevier B.V. All rights reserved.

Genetic characterization of Vitis germplasm collected from the southwestern US and Mexico to expedite Pierce's disease-resistance breeding.

PubMed

Riaz, S; Huerta-Acosta, K; Tenscher, A C; Walker, M A

2018-04-30

Pierce's disease (PD) limits the cultivation of Vitis vinifera grape cultivars in California, across the southern United States and into South America. Resistance has been well characterized in V. arizonica, and one resistance locus has been identified (PdR1). However, resistance is poorly characterized in most other grape species. We tested a wide range of Vitis species from the southwestern United States for resistance to PD and used nuclear and chloroplast markers to phenotypically and genetically select a diverse set of resistant accessions. Chloroplast SSR markers identified 11 maternal lineage lines within the set of 17 (14 new and three previously identified) PD resistant accessions. A total of 19 breeding populations (F1 and pseudo-BC1) were developed with the 14 PD resistant accessions, and a total of 705 seedlings were analyzed for PD resistance. Using a limited mapping approach, 12 SSR markers, linked to the PdR1 locus, were used to genotype the breeding populations and phenotypic data were analyzed. Nine accessions had a major resistance quantitative trait locus (QTL) within the genomic region containing PdR1. The phenotypic data for these three resistant accessions, ANU67, b41-13, and T03-16, did not associate with PdR1 linked markers, indicating that their resistance is located in other regions of the genome. These three accessions were identified as candidates for use in the development of framework maps with larger populations capable of detecting additional and unique loci for PD resistance breeding and the stacking of PD resistance genes.

Mechanism of the development of nonalcoholic steatohepatitis after pancreaticoduodenectomy.

PubMed

Nagaya, Tadanobu; Tanaka, Naoki; Kimura, Takefumi; Kitabatake, Hiroyuki; Fujimori, Naoyuki; Komatsu, Michiharu; Horiuchi, Akira; Yamaura, Takahiro; Umemura, Takeji; Sano, Kenji; Gonzalez, Frank J; Aoyama, Toshifumi; Tanaka, Eiji

2015-06-01

It is recognized that nonalcoholic fatty liver disease (NAFLD), including nonalcoholic steatohepatitis (NASH), may develop after pancreaticoduodenectomy (PD). However, the mechanism of NASH development remains unclear. This study aimed to examine the changes in gene expression associated with NASH occurrence following PD. The expression of genes related to fatty acid/triglyceride (FA/TG) metabolism and inflammatory signaling was examined using liver samples obtained from 7 post-PD NASH patients and compared with 6 healthy individuals and 32 conventional NASH patients. The livers of post-PD NASH patients demonstrated significant up-regulation of the genes encoding CD36, FA-binding proteins 1 and 4, acetyl-coenzyme A carboxylase α, diacylglycerol acyltransferase 2, and peroxisome proliferator-activated receptor (PPAR) γ compared with normal and conventional NASH livers. Although serum apolipoprotein B (ApoB) and TG were decreased in post-PD NASH patients, the mRNAs of ApoB and microsomal TG transfer protein were robustly increased, indicating impaired TG export from the liver as very-low-density lipoprotein (VLDL). Additionally, elevated mRNA levels of myeloid differentiation primary response 88 and superoxide dismutases in post-PD NASH livers suggested significant activation of innate immune response and augmentation of oxidative stress generation. Enhanced FA uptake into hepatocytes and lipogenesis, up-regulation of PPARγ, and disruption of VLDL excretion into the circulation are possible mechanisms of steatogenesis after PD. These results provide a basis for understanding the pathogenesis of NAFLD/NASH following PD.

TRAV7-2*02 Expressing CD8⁺ T Cells Are Responsible for Palladium Allergy.

PubMed

Takeda, Yuri; Suto, Yoshiko; Ito, Koyu; Hashimoto, Wataru; Nishiya, Tadashi; Ueda, Kyosuke; Narushima, Takayuki; Takahashi, Tetsu; Ogasawara, Kouetsu

2017-05-31

While metallic biomaterials have led to an improvement in the quality of life, metal allergies, especially to palladium (Pd), has caused a recent increase in allergic patients. Metal allergy is known to be a T cell-mediated delayed-type hypersensitivity (DTH); however, the pathogenic T cell subsets and the specific T cell receptor (TCR) have not been identified. Therefore, we attempted to identify the pathogenic T cells responsible for Pd allergy. We found that activating CD8⁺ T cells significantly increased and that the TRAV (TCRα variable) 7-2*02 chain skewed in Pd allergic mice. Furthermore, adoptive transfer experiments revealed that in vitro-cultured Pd-stimulated antigen presenting cells (APCs) function as memory APCs with recipient mice developing Pd allergy and that the frequency of TRAV7-2*02 increases the same as conventional Pd allergic mice. In contrast, neither proliferation of CD8⁺ T cells nor increasing of TRAV7-2*02 was observed in major histocompatibility complex I (MHC I)-deficient Pd-APCs transferred to mice. Taken together, we revealed that TRAV7-2*02-expressing CD8⁺ T cells are the pathogenic T cells for the development of Pd allergy. We also identified the CDR3 consensus motif of pathogenic TCRs as CAAXSGSWQLIF in TRAV7-2*02/TRAJ (TCRα junction)22*01 positive cells. These results suggest that the specific TCRs represent novel targets for the development of diagnostics and treatments for metal allergy.

TRAV7-2*02 Expressing CD8+ T Cells Are Responsible for Palladium Allergy

PubMed Central

Takeda, Yuri; Suto, Yoshiko; Ito, Koyu; Hashimoto, Wataru; Nishiya, Tadashi; Ueda, Kyosuke; Narushima, Takayuki; Takahashi, Tetsu; Ogasawara, Kouetsu

2017-01-01

While metallic biomaterials have led to an improvement in the quality of life, metal allergies, especially to palladium (Pd), has caused a recent increase in allergic patients. Metal allergy is known to be a T cell-mediated delayed-type hypersensitivity (DTH); however, the pathogenic T cell subsets and the specific T cell receptor (TCR) have not been identified. Therefore, we attempted to identify the pathogenic T cells responsible for Pd allergy. We found that activating CD8+ T cells significantly increased and that the TRAV (TCRα variable) 7-2*02 chain skewed in Pd allergic mice. Furthermore, adoptive transfer experiments revealed that in vitro-cultured Pd-stimulated antigen presenting cells (APCs) function as memory APCs with recipient mice developing Pd allergy and that the frequency of TRAV7-2*02 increases the same as conventional Pd allergic mice. In contrast, neither proliferation of CD8+ T cells nor increasing of TRAV7-2*02 was observed in major histocompatibility complex I (MHC I)-deficient Pd-APCs transferred to mice. Taken together, we revealed that TRAV7-2*02-expressing CD8+ T cells are the pathogenic T cells for the development of Pd allergy. We also identified the CDR3 consensus motif of pathogenic TCRs as CAAXSGSWQLIF in TRAV7-2*02/TRAJ (TCRα junction)22*01 positive cells. These results suggest that the specific TCRs represent novel targets for the development of diagnostics and treatments for metal allergy. PMID:28561797

Color Discrimination in Patients with Gaucher Disease and Parkinson Disease.

PubMed

Simon-Tov, Shlomi; Dinur, Tama; Giladi, Nir; Bar-Shira, Anat; Zelis, Mayaan; Zimran, Ari; Elstein, Deborah

2015-01-01

Poor color discrimination among patients with Parkinson disease (PD) has long been recognized. It has been shown that carrying one or two mutations in the β-glucocerebrosidase gene (GBA) for the autosomal disease Gaucher disease (GD), as based initially on clinical evidence, is a genetic risk factor for early-onset PD. The purpose of this study was to assess color discrimination in patients with one or two GBA mutations relative to healthy controls to ascertain whether this function is affected when persons with GD or even one GBA mutation develop PD. The Farnsworth-Munsell 100 hue test (FMHT) was evaluated among patients with GD+PD compared to patients with GD only, obligate GBA carriers with and without PD, patients with PD only, and healthy controls. FMHT outcome include computer-generated TES (Total Error Score) and values recommended by Vingrys & King-Smith. Six groups of 10 persons were tested. Significant differences were seen for male GD+PD and for age in PD. The highest mean TES was in the PD only group, the lowest in the GD only group. There was a significant difference because of PD in groups with GD and GBA carriers. GD+PD means were between GD only and PD only mean scores. These findings confirm that PD impacts color discrimination, more in males with GD+PD but nonetheless, GD+PD patients (but not GBA carriers) had better scores than PD only patients.

The Effects of a Computerized Professional Development Program on Teachers and Students with and without Disabilities in Secondary General Education Classes

ERIC Educational Resources Information Center

Schumaker, Jean B.; Fisher, Joseph B.; Walsh, Lisa D.

2010-01-01

Effects of a computerized professional development (PD) program were investigated in two studies. For each, teachers were randomly assigned to either a Virtual Workshop (VW) group that used a computerized program for PD or to an Actual Workshop (AW) group that participated in a live PD session. In Study 1, the teachers' knowledge about and…

Inhibitors of the PD-1 Pathway in Tumor Therapy

PubMed Central

LaFleur, Martin W.; Muroyama, Yuki; Drake, Charles G.; Sharpe, Arlene H.

2018-01-01

The programmed death 1 (PD-1) pathway delivers inhibitory signals that function as a brake for immune responses. This pathway limits the initiation and duration of immune responses, thereby protecting tissues from immune-mediated damage and autoimmune diseases. However, the PD-1 pathway also inhibits immune responses to tumors. The critical role of PD-1 in preventing antitumor immunity is demonstrated by the transformative effects of PD-1 pathway blockade in a broad range of cancers with the hallmark of durability of response. Despite this success, most patients do not respond to PD-1 monotherapy, and some patients experience adverse events. In this review, we discuss the functions of the PD-1 pathway and its translation to cancer immunotherapy. We also consider current challenges and opportunities for PD-1 cancer immunotherapy, including mechanisms of response and resistance, identification of biomarkers of response to PD-1 therapy, characterization and treatment of PD-1 therapy–related adverse events, and development of safe and effective combination therapies. PMID:29311378

A Cybrid Cell Model for the Assessment of the Link Between Mitochondrial Deficits and Sporadic Parkinson’s Disease

PubMed Central

Arduíno, Daniela M.; Esteves, A. Raquel; Swerdlow, Russell H.; Cardoso, Sandra M.

2015-01-01

Parkinson’s disease (PD) is a multifactorial and clinically complex age-related movement disorder. The cause of its most common form (sporadic PD, sPD) is unknown, but one prominent causal factor is mitochondrial dysfunction. Although several genetic- and toxin-based models have been developed along the last decades to mimic the pathological cascade of PD, cellular models that reliably recapitulate the pathological features of the neurons that degenerate in PD are scarce. We describe here the generation of cytoplasmic hybrid cells (or cybrids) as a cellular model of sPD. This approach consists on the fusion of platelets harboring mtDNA from sPD patients with cells in which the endogenous mtDNA has been depleted (Rho0 cells). The sPD cybrid model has been successful in recapitulating most of the hallmarks of sPD, constituting now a validated model for addressing the link between mitochondrial dysfunction and sPD pathology. PMID:25634293

A cybrid cell model for the assessment of the link between mitochondrial deficits and sporadic Parkinson's disease.

PubMed

Arduíno, Daniela M; Esteves, A Raquel; Swerdlow, Russell H; Cardoso, Sandra M

2015-01-01

Parkinson's disease (PD) is a multifactorial and clinically complex age-related movement disorder. The cause of its most common form (sporadic PD, sPD) is unknown, but one prominent causal factor is mitochondrial dysfunction. Although several genetic- and toxin-based models have been developed along the last decades to mimic the pathological cascade of PD, cellular models that reliably recapitulate the pathological features of the neurons that degenerate in PD are scarce.We describe here the generation of cytoplasmic hybrid cells (or cybrids) as a cellular model of sPD. This approach consists on the fusion of platelets harboring mtDNA from sPD patients with cells in which the endogenous mtDNA has been depleted (Rho0 cells).The sPD cybrid model has been successful in recapitulating most of the hallmarks of sPD, constituting now a validated model for addressing the link between mitochondrial dysfunction and sPD pathology.

Sex Differences in Early Postnatal Microglial Colonization of the Developing Rat Hippocampus Following a Single-Day Alcohol Exposure.

PubMed

Ruggiero, M J; Boschen, K E; Roth, T L; Klintsova, A Y

2018-06-01

Microglia are involved in various homeostatic processes in the brain, including phagocytosis, apoptosis, and synaptic pruning. Sex differences in microglia colonization of the developing brain have been reported, but have not been established following alcohol insult. Developmental alcohol exposure represents a neuroimmune challenge that may contribute to cognitive dysfunction prevalent in humans with Fetal Alcohol Spectrum Disorders (FASD) and in rodent models of FASD. Most studies have investigated neuroimmune activation following adult alcohol exposure or following multiple exposures. The current study uses a single day binge alcohol exposure model (postnatal day [PD] 4) to examine sex differences in the neuroimmune response in the developing rat hippocampus on PD5 and 8. The neuroimmune response was evaluated through measurement of microglial number and cytokine gene expression at both time points. Male pups had higher microglial number compared to females in many hippocampal subregions on PD5, but this difference disappeared by PD8, unless exposed to alcohol. Expression of pro-inflammatory marker CD11b was higher on PD5 in alcohol-exposed (AE) females compared to AE males. After alcohol exposure, C-C motif chemokine ligand 4 (CCL4) was significantly increased in female AE pups on PD5 and PD8. Tumor necrosis factor-α (TNF-α) levels were also upregulated by AE in males on PD8. The results demonstrate a clear difference between the male and female neuroimmune response to an AE challenge, which also occurs in a time-dependent manner. These findings are significant as they add to our knowledge of specific sex-dependent effects of alcohol exposure on microglia within the developing brain.

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.

Mitochondrial Dysfunction in Parkinson's Disease.

PubMed

Moon, Hyo Eun; Paek, Sun Ha

2015-06-01

Parkinson's disease (PD) is characterized by the selective loss of dopaminergic neurons of the substantia nigra pars compacta (SNc) with motor and nonmotor symptoms. Defective mitochondrial function and increased oxidative stress (OS) have been demonstrated as having an important role in PD pathogenesis, although the underlying mechanism is not clear. The etiopathogenesis of sporadic PD is complex with variable contributions of environmental factors and genetic susceptibility. Both these factors influence various mitochondrial aspects, including their life cycle, bioenergetic capacity, quality control, dynamic changes of morphology and connectivity (fusion, fission), subcellular distribution (transport), and the regulation of cell death pathways. Mitochondrial dysfunction has mainly been reported in various non-dopaminergic cells and tissue samples from human patients as well as transgenic mouse and fruit fly models of PD. Thus, the mitochondria represent a highly promising target for the development of PD biomarkers. However, the limited amount of dopaminergic neurons prevented investigation of their detailed study. For the first time, we established human telomerase reverse transcriptase (hTERT)-immortalized wild type, idiopathic and Parkin deficient mesenchymal stromal cells (MSCs) isolated from the adipose tissues of PD patients, which could be used as a good cellular model to evaluate mitochondrial dysfunction for the better understanding of PD pathology and for the development of early diagnostic markers and effective therapy targets of PD. In this review, we examine evidence for the roles of mitochondrial dysfunction and increased OS in the neuronal loss that leads to PD and discuss how this knowledge further improve the treatment for patients with PD.

Evolution of diagnostic criteria and assessments for Parkinson's disease mild cognitive impairment.

PubMed

Goldman, Jennifer G; Holden, Samantha K; Litvan, Irene; McKeith, Ian; Stebbins, Glenn T; Taylor, John-Paul

2018-04-01

Mild cognitive impairment has gained recognition as a construct and a potential prodromal stage to dementia in both Alzheimer's disease and Parkinson's disease (PD). Although mild cognitive impairment has been recognized in the Alzheimer's disease field, it is a relatively more recent topic of interest in PD. Recent advances include the development of diagnostic criteria for PD mild cognitive impairment to provide more uniform definitions for clinical and research use. Studies reveal that mild cognitive impairment in PD is frequent, but also heterogeneous, with variable clinical presentations, differences in its progression to dementia, and likely differences in underlying pathophysiology. Application of the International Parkinson and Movement Disorder Society PD Mild Cognitive Impairment Task Force diagnostic criteria has provided insights regarding cognitive measures, functional assessments, and other key topics that may require additional refinement. Furthermore, it is important to consider definitions of PD mild cognitive impairment in the landscape of other related Lewy body disorders, such as dementia with Lewy bodies, and in the context of prodromal and early-stage PD. This article examines the evolution of mild cognitive impairment in concept and definition, particularly in PD, but also in related disorders such as Alzheimer's disease and dementia with Lewy bodies; the development and application of International Parkinson and Movement Disorder Society PD Mild Cognitive Impairment diagnostic criteria; and insights and future directions for the field of PD mild cognitive impairment. © 2018 International Parkinson and Movement Disorder Society. © 2018 International Parkinson and Movement Disorder Society.

PD-L1 Expression on Retrovirus-Infected Cells Mediates Immune Escape from CD8+ T Cell Killing.

PubMed

Akhmetzyanova, Ilseyar; Drabczyk, Malgorzata; Neff, C Preston; Gibbert, Kathrin; Dietze, Kirsten K; Werner, Tanja; Liu, Jia; Chen, Lieping; Lang, Karl S; Palmer, Brent E; Dittmer, Ulf; Zelinskyy, Gennadiy

2015-10-01

Cytotoxic CD8+ T Lymphocytes (CTL) efficiently control acute virus infections but can become exhausted when a chronic infection develops. Signaling of the inhibitory receptor PD-1 is an important mechanism for the development of virus-specific CD8+ T cell dysfunction. However, it has recently been shown that during the initial phase of infection virus-specific CD8+ T cells express high levels of PD-1, but are fully competent in producing cytokines and killing virus-infected target cells. To better understand the role of the PD-1 signaling pathway in CD8+ T cell cytotoxicity during acute viral infections we analyzed the expression of the ligand on retrovirus-infected cells targeted by CTLs. We observed increased levels of PD-L1 expression after infection of cells with the murine Friend retrovirus (FV) or with HIV. In FV infected mice, virus-specific CTLs efficiently eliminated infected target cells that expressed low levels of PD-L1 or that were deficient for PD-L1 but the population of PD-L1high cells escaped elimination and formed a reservoir for chronic FV replication. Infected cells with high PD-L1 expression mediated a negative feedback on CD8+ T cells and inhibited their expansion and cytotoxic functions. These findings provide evidence for a novel immune escape mechanism during acute retroviral infection based on PD-L1 expression levels on virus infected target cells.

Development of an Agrobacterium-mediated transformation system for the cold-adapted fungi Pseudogymnoascus destructans and P. pannorum.

PubMed

Zhang, Tao; Ren, Ping; Chaturvedi, Vishnu; Chaturvedi, Sudha

2015-08-01

The mechanisms of cold adaptation by fungi remain unknown. This topic is of high interest due to the emergence of white-nose syndrome (WNS), a skin infection of hibernating bats caused by Pseudogymnoascus destructans (Pd). Recent studies indicated that apart from Pd, there is an abundance of other Pseudogymnoascus species in the hibernacula soil. We developed an Agrobacterium tumefaciens-mediated transformation (ATMT) system for Pd and a related fungus Pseudogymnoascus pannorum (Pp) to advance experimental studies. URE1 gene encoding the enzyme urease was used as an easy to screen marker to facilitate molecular genetic analyses. A Uracil-Specific Excision Reagent (USER) Friendly pRF-HU2 vector containing Pd or Pp ure1::hygromycin (HYG) disruption cassette was introduced into A. tumefaciens AGL-1 cells by electroporation and the resulting strains were co-cultivated with conidia of Pd or Pp for various durations and temperatures to optimize the ATMT system. Overall, 680 Pd (0.006%) and 1800 Pp (0.018%) transformants were obtained from plating of 10(7) conidia; their recoveries were strongly correlated with the length of the incubation period (96h for Pd; 72h for Pp) and with temperature (15-18°C for Pd; 25°C for Pp). The homologous recombination in transformants was 3.1% for Pd and 16.7% for Pp. The availability of a standardized ATMT system would allow future molecular genetic analyses of Pd and related cold-adapted fungi. Copyright © 2015. Published by Elsevier Inc.

Controlled Pd(0)/t Bu3P Catalyzed Suzuki Cross-Coupling Polymerization of AB-Type Monomers with ArPd(t Bu3P)X or Pd2(dba)3/t Bu3P/ArX as the Initiator

DOE PAGES

Zhang, Honghai; Xing, Chun-Hui; Hu, Qiao-Sheng; ...

2015-02-05

The synthesis of well-defined and functionalized conjugated polymers, which are essential in the development of efficient organic electronics, through Suzuki cross-coupling polymerizations has been a challenging task. We developed controlled Pd(0)/t-Bu3P-catalyzed Suzuki cross-coupling polymerizations of AB-type monomers via the chain-growth mechanism with a series of in situ generated ArPd(t-Bu3P)X (X = I, Br, Cl) complexes as initiators. Among them, the combinations of Pd2(dba)3/t-Bu3P/p-BrC6H4I, Pd2(dba)3/t-Bu3P/p-BrC6H4CH2OH and Pd2(dba)3/t-Bu3P/p-PhCOC6H4Br were identified as highly robust initiator systems, resulting in polymers with predictable molecular weight and narrow polydispersity (PDI~1.13-1.20). In addition, Pd2(dba)3/t-Bu3P/p-BrC6H4CH2OH and Pd2(dba)3/t-Bu3P/p-PhCOC6H4Br initiator systems afforded functional polymers with >95% fidelity. Our results pavedmore » the road to access well-defined conjugated polymers, including conjugated polymers with complex polymer architectures such as block copolymers and branch copolymers.« less

A Syllabus for Teaching Peritoneal Dialysis to Patients and Caregivers.

PubMed

Figueiredo, Ana E; Bernardini, Judith; Bowes, Elaine; Hiramatsu, Miki; Price, Valerie; Su, Chunyan; Walker, Rachael; Brunier, Gillian

Being aware of controversies and lack of evidence in peritoneal dialysis (PD) training, the Nursing Liaison Committee of the International Society for Peritoneal Dialysis (ISPD) has undertaken a review of PD training programs around the world in order to develop a syllabus for PD training. This syllabus has been developed to help PD nurses train patients and caregivers based on a consensus of training program reviews, utilizing current theories and principles of adult education. It is designed as a 5-day program of about 3 hours per day, but both duration and content may be adjusted based on the learner. After completion of our proposed PD training syllabus, the PD nurse will have provided education to a patient and/or caregiver such that the patient/caregiver has the required knowledge, skills and abilities to perform PD at home safely and effectively. The course may also be modified to move some topics to additional training times in the early weeks after the initial sessions. Extra time may be needed to introduce other concepts, such as the renal diet or healthy lifestyle, or to arrange meetings with other healthcare professionals. The syllabus includes a checklist for PD patient assessment and another for PD training. Further research will be needed to evaluate the effect of training using this syllabus, based on patient and nurse satisfaction as well as on infection rates and longevity of PD as a treatment. Copyright © 2016 International Society for Peritoneal Dialysis.

KSC-07pd3320

NASA Image and Video Library

2007-11-14

KENNEDY SPACE CENTER, FLA. -- In the Orbiter Processing Facility, one of two Materials International Space Station Experiments, or MISSE, is lowered into space shuttle Endeavour's payload bay for installation. The MISSE is part of the payload onboard Endeavour for mission STS-123. The MISSE project is a NASA/Langley Research Center-managed cooperative endeavor to fly materials and other types of space exposure experiments on the International Space Station. The objective is to develop early, low-cost, non-intrusive opportunities to conduct critical space exposure tests of space materials and components planned for use on future spacecraft. Photo credit: NASA/Kim Shiflett

KSC-07pd3321

NASA Image and Video Library

2007-11-14

KENNEDY SPACE CENTER, FLA. -- In the Orbiter Processing Facility, the second of two Materials International Space Station Experiments, or MISSE, is lowered into space shuttle Endeavour's payload bay for installation. The MISSE is part of the payload onboard Endeavour for mission STS-123. The MISSE project is a NASA/Langley Research Center-managed cooperative endeavor to fly materials and other types of space exposure experiments on the International Space Station. The objective is to develop early, low-cost, non-intrusive opportunities to conduct critical space exposure tests of space materials and components planned for use on future spacecraft. Photo credit: NASA/Kim Shiflett

KSC-07pd3319

NASA Image and Video Library

2007-11-14

KENNEDY SPACE CENTER, FLA. -- In the Orbiter Processing Facility, one of two Materials International Space Station Experiments, or MISSE, is lowered into space shuttle Endeavour's payload bay for installation. The MISSE is part of the payload onboard Endeavour for mission STS-123. The MISSE project is a NASA/Langley Research Center-managed cooperative endeavor to fly materials and other types of space exposure experiments on the International Space Station. The objective is to develop early, low-cost, non-intrusive opportunities to conduct critical space exposure tests of space materials and components planned for use on future spacecraft. Photo credit: NASA/Kim Shiflett

KSC-04pd1142

NASA Image and Video Library

2004-05-13

KENNEDY SPACE CENTER, FLA. -- Adm. Craig E. Steidle (center), NASA’s associate administrator, Office of Exploration Systems, tours the Orbiter Processing Facility on a visit to KSC. At left is Conrad Nagel, chief of the Shuttle Project Office. They are standing under the left wing and wheel well of the orbiter Discovery. The Office of Exploration Systems was established to set priorities and direct the identification, development and validation of exploration systems and related technologies to support the future space vision for America. Steidle’s visit included a tour of KSC to review the facilities and capabilities to be used to support the vision.

KSC-04pd1140

NASA Image and Video Library

2004-05-13

KENNEDY SPACE CENTER, FLA. -- Adm. Craig E. Steidle (center), NASA’s associate administrator, Office of Exploration Systems, listens to Conrad Nagel, chief of the Shuttle Project Office (right), during a tour of the Orbiter Processing Facility on a visit to KSC. They are standing under the orbiter Discovery. The Office of Exploration Systems was established to set priorities and direct the identification, development and validation of exploration systems and related technologies to support the future space vision for America. Steidle’s visit included a tour of KSC to review the facilities and capabilities to be used to support the vision.

KSC-04pd1141

NASA Image and Video Library

2004-05-13

KENNEDY SPACE CENTER, FLA. -- Adm. Craig E. Steidle (center), NASA’s associate administrator, Office of Exploration Systems, listens to Conrad Nagel, chief of the Shuttle Project Office (right), during a tour of the Orbiter Processing Facility on a visit to KSC. They are standing under the orbiter Discovery. The Office of Exploration Systems was established to set priorities and direct the identification, development and validation of exploration systems and related technologies to support the future space vision for America. Steidle’s visit included a tour of KSC to review the facilities and capabilities to be used to support the vision.

Impacts of aerosol-cloud interactions on past and future changes in tropospheric composition

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

Unger, N.; Menon, S.; Shindell, D. T.

2009-02-02

The development of effective emissions control policies that are beneficial to both climate and air quality requires a detailed understanding of all the feedbacks in the atmospheric composition and climate system. We perform sensitivity studies with a global atmospheric composition-climate model to assess the impact of aerosols on tropospheric chemistry through their modification on clouds, aerosol-cloud interactions (ACI). The model includes coupling between both tropospheric gas-phase and aerosol chemistry and aerosols and liquid-phase clouds. We investigate past impacts from preindustrial (PI) to present day (PD) and future impacts from PD to 2050 (for the moderate IPCC A1B scenario) that embracemore » a wide spectrum of precursor emission changes and consequential ACI. The aerosol indirect effect (AIE) is estimated to be -2.0 Wm{sup -2} for PD-PI and -0.6 Wm{sup -2} for 2050-PD, at the high end of current estimates. Inclusion of ACI substantially impacts changes in global mean methane lifetime across both time periods, enhancing the past and future increases by 10% and 30%, respectively. In regions where pollution emissions increase, inclusion of ACI leads to 20% enhancements in in-cloud sulfate production and {approx}10% enhancements in sulfate wet deposition that is displaced away from the immediate source regions. The enhanced in-cloud sulfate formation leads to larger increases in surface sulfate across polluted regions ({approx}10-30%). Nitric acid wet deposition is dampened by 15-20% across the industrialized regions due to ACI allowing additional re-release of reactive nitrogen that contributes to 1-2 ppbv increases in surface ozone in outflow regions. Our model findings indicate that ACI must be considered in studies of methane trends and projections of future changes to particulate matter air quality.« less

Creating Virtual Fieldwork Experiences of Geoheritage Sites as Educator Professional Development (Invited)

NASA Astrophysics Data System (ADS)

Duggan-Haas, D.

2013-12-01

Geoheritage sites are identified as such because they include excellent examples of geologic features or processes, or they have played an important role in the development of geologic understandings. These characteristics also make them excellent sites for teaching in the field, for teaching educators about the nature of fieldwork, and for making Virtual Fieldwork Experiences (VFEs, multimedia representations of field sites). Through the NSF-funded Regional and Local Earth (ReaL) Earth Inquiry Project, we have engaged educators in these practices. The nature of geoheritage sites is anomalous -- if this were not the case, the sites would not gain recognition. Anomalous features or processes can be powerful learning tools when placed into comparison with the more mundane, and the Earth system science of sites local to schools is likely to be mundane. By comparing the mundane and the extraordinary, it is hoped we can learn more about both. The professional development (PD) in ReaL Earth Inquiry begins with a face-to-face workshop within the teachers' region at a site that is interesting from an Earth system science perspective. Though we recognize and emphasize that all sites are interesting from an ESS perspective if you know how to look, the sites typically have features worthy of geoheritage designation. PD does not end with the end of the workshop but continues with online study groups where teachers work together to complete the workshop site VFE, and transition to work on VFEs of sites local to their schools. Throughout the program, participants engage in: - mentored fieldwork that pays attention to the skills and knowledge needed to lead fieldwork; - instruction in and use of a wide range of technologies for making VFEs; - study of a coherent conceptual framework connected to the project's driving question: Why does this place look the way it does? - and, use of resources for supporting all of the above The resources include templates for making VFEs and a framework summarized in the attached graphic organizer that features a series of questions that can be productively asked of any field site. By working with educators, we not only produce curriculum resources in the form of VFEs, we also engage in educator PD that produces evidence of its effectiveness, at least in terms of indications that educators are engaged in field study both at the workshop site and after they return home. Production of local VFEs sometimes involves students. The VFE Graphic Organizer, showing a series of questions that may be asked about any site, all under the project's driving question: Why does this place look the way it does?

Electronic Transitions of Palladium Monoboride and Platinum Monoboride

NASA Astrophysics Data System (ADS)

Ng, Y. W.; Pang, H. F.; Wong, Y. S.; Qian, Yue; Cheung, A. S.-C.

2012-06-01

Electronic transition spectrum of palladium monoboride (PdB) and platinum (PtB) monoboride have been studied using the technique of laser-ablation/reaction free jet expansion and laser induced fluorescence spectroscopy. The metal monoborides were produced by reacting laser ablated metal atoms and diborane ((B_2H_6) seeded in argon. Five and six vibrational bands were observed respectively for the PdB and PtB molecules. Preliminary analysis of the rotationally resolved structure showed that both molecules have X2 Σ+ ground state. Least-squares fit of the measured line positions yielded molecular constants for the electronic states involved. Molecular and electronic structures of PdB and PtB are discussed using a molecular orbital energy level diagram. Financial support from the Research Grants Council of the Hong Kong Special Administrative Region, China (Project No. HKU 701008P) is gratefully acknowledged.

Soluble PD-L1 with PD-1-binding capacity exists in the plasma of patients with non-small cell lung cancer.

PubMed

Takeuchi, Masahiro; Doi, Tomomitsu; Obayashi, Kunie; Hirai, Ayako; Yoneda, Kazue; Tanaka, Fumihiro; Iwai, Yoshiko

2018-04-01

PD-L1 is one of the important immune checkpoint molecules that can be targeted by cancer immunotherapies. PD-L1 has a soluble form (sPD-L1) and a membrane-bound form (mPD-L1). Conventional enzyme-linked immunosorbent assay (ELISA) systems can detect sPD-L1 using anti-PD-L1 capture antibody through the antigen-antibody reaction, but cannot evaluate the quality and function of sPD-L1. In this study, we developed a novel ELISA system for the detection and quantification of sPD-L1 with PD-1-binding capacity (bsPD-L1). To capture bsPD-L1 through the ligand-receptor reaction, the anti-PD-L1 capture antibody in the conventional ELISA was replaced with PD-1-Ig fusion protein in the new ELISA. The new ELISA could detect bsPD-L1 in 29 out of 75 plasma samples from patients with non-small cell lung cancer (NSCLC), with higher sensitivity and frequency than the conventional ELISA. The western blot analysis showed that sPD-L1 in the plasma was glycosylated. Treatment of the samples with glycosidase reduced the absorbance determined by the new ELISA but had no effect on the absorbance determined by the conventional ELISA. These results suggest that glycosylation of sPD-L1 is important for its binding to the immobilized PD-1 in the new ELISA. Our new ELISA system may be useful for the evaluation of functional sPD-L1 with PD-1-binding capacity in cancer patients. Copyright © 2018 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

Evaluation of taurine as an osmotic agent for peritoneal dialysis solution.

PubMed

Nishimura, Hideki; Ikehara, Osamu; Naito, Takashi; Higuchi, Chieko; Sanaka, Tsutomu

2009-01-01

The development of a glucose-free peritoneal dialysis (PD) solution is important because glucose has been associated with functional and morphological damage to the peritoneal membrane. The ultrafiltration (UF) and biocompatibility of new PD solutions containing taurine (PD-taurine) instead of glucose as an osmolite were tested in a rat PD model. To determine the solution's UF ability, different concentrations of taurine in PD solutions were compared to glucose-based PD solutions (PD-glucose) by giving single intraperitoneal injections for 2, 4, and 6 hours. To examine the biocompatibility of PD-taurine, the rats were divided into 3 groups: a 3.86% PD-glucose group, a 3.5% PD-taurine group and a not dialyzed group. The rats were given 10-mL injections of PD fluids intraperitoneally 3 times daily for 7 days. A peritoneal equilibration test (PET) was performed using a 1.9% xylitol solution at the time the rats were sacrificed. Mesothelial cell monolayers were obtained from the animals and studied based on a population analysis. The net UF of PD-taurine increased in a dose-dependent manner; the 3.5% PD-taurine solution was equivalent to the 3.86% PD-glucose solution after 4 hours. The PET showed that the drainage volume and the D(4)/D(0) ratio for xylitol after 4 hours with PD-taurine solution were significantly greater than with the PD-glucose solution (p < 0.001 and p < 0.001 respectively). Mesothelial and fibroblast-like cell proliferation was significantly less with PD-taurine than with PD-glucose (p < 0.01). These results indicate that PD-taurine resulted in net UF equivalent to that of PD-glucose and was more biocompatible than PD-glucose with respect to the peritoneal membrane.

The tumor suppressor miR-138-5p targets PD-L1 in colorectal cancer

PubMed Central

Zhao, Lian; Yu, Haibo; Yi, Shuijing; Peng, Xiaowei; Su, Peng; Xiao, Zhiming; Liu, Rui; Tang, Anliu; Li, Xiayu; Liu, Fen; Shen, Shourong

2016-01-01

microRNAs (miRNAs) play critical roles in cancer development and progression. This study investigated the effects of miR-138-5p in human colorectal cancer (CRC) development. miR-138-5p was frequently downregulated in CRC tissues and was associated with advanced clinical stage, lymph node metastasis and poor overall survival. We found that miR-138-5p decreased expression of programmed cell death ligand 1 (PD-L1) through interaction with its PD-L1 3′ untranslated region. miR-138-5p also dramatically suppressed CRC cell growth in vitro and inhibited tumorigenesis in vivo. PD-L1 and miR-138-5p levels were inversely correlated in human CRC tumors, and miR-138-5p inhibited PD-L1 expression in tumor models. These results suggest that miR-138-5p is a tumor suppressor in CRC, and its effects are exerted at least partially through PD-L1 downregulation. Low miR-138-5p and high PD-L1 levels correlated with shorter overall CRC patient survival, indicating that miR-138-5p and PD-L1 may serve as CRC biomarkers for risk group assignment, optimal therapy selection and clinical outcome prediction. Targeting PD-L1, possibly by administering miR-138-5p mimics, might be a clinically effective anti-CRC therapeutic strategy. PMID:27248318

The tumor suppressor miR-138-5p targets PD-L1 in colorectal cancer.

PubMed

Zhao, Lian; Yu, Haibo; Yi, Shuijing; Peng, Xiaowei; Su, Peng; Xiao, Zhiming; Liu, Rui; Tang, Anliu; Li, Xiayu; Liu, Fen; Shen, Shourong

2016-07-19

microRNAs (miRNAs) play critical roles in cancer development and progression. This study investigated the effects of miR-138-5p in human colorectal cancer (CRC) development. miR-138-5p was frequently downregulated in CRC tissues and was associated with advanced clinical stage, lymph node metastasis and poor overall survival. We found that miR-138-5p decreased expression of programmed cell death ligand 1 (PD-L1) through interaction with its PD-L1 3' untranslated region. miR-138-5p also dramatically suppressed CRC cell growth in vitro and inhibited tumorigenesis in vivo. PD-L1 and miR-138-5p levels were inversely correlated in human CRC tumors, and miR-138-5p inhibited PD-L1 expression in tumor models. These results suggest that miR-138-5p is a tumor suppressor in CRC, and its effects are exerted at least partially through PD-L1 downregulation. Low miR-138-5p and high PD-L1 levels correlated with shorter overall CRC patient survival, indicating that miR-138-5p and PD-L1 may serve as CRC biomarkers for risk group assignment, optimal therapy selection and clinical outcome prediction. Targeting PD-L1, possibly by administering miR-138-5p mimics, might be a clinically effective anti-CRC therapeutic strategy.

Validation of FFM PD counts for screening personality pathology and psychopathy in adolescence.

PubMed

Decuyper, Mieke; De Clercq, Barbara; De Bolle, Marleen; De Fruyt, Filip

2009-12-01

Miller and colleagues (Miller, Bagby, Pilkonis, Reynolds, & Lynam, 2005) recently developed a Five-Factor Model (FFM) personality disorder (PD) count technique for describing and diagnosing PDs and psychopathy in adulthood. This technique conceptualizes PDs relying on general trait models and uses facets from the expert-generated PD prototypes to score the FFM PDs. The present study corroborates on the study of Miller and colleagues (2005) and investigates in Study 1 whether the PD count technique shows discriminant validity to describe PDs in adolescence. Study 2 extends this objective to psychopathy. Results suggest that the FFM PD count technique is equally successful in adolescence as in adulthood to describe PD symptoms, supporting the use of this descriptive method in adolescence. The normative data and accompanying PD count benchmarks enable to use FFM scores for PD screening purposes in adolescence.

Plasmodesmata-mediated intercellular signaling during plant growth and development.

PubMed

Yadav, Shri R; Yan, Dawei; Sevilem, Iris; Helariutta, Ykä

2014-01-01

Plasmodesmata (PD) are cytoplasmic channels that connect neighboring cells for cell-to-cell communication. PD structure and function vary temporally and spatially to allow formation of symplastic domains during different stages of plant development. Reversible deposition of callose at PD plays an important role in controlling molecular trafficking through PD by regulating their size exclusion limit. Previously, we reported several semi-dominant mutants for CALLOSE SYNTHASE 3 (CALS3) gene, which overproduce callose at PD in Arabidopsis. By combining two of these mutations in a LexA-VP16-ER (XVE)-based estradiol inducible vector system, a tool known as the "icals3m system" was developed to temporally obstruct the symplastic connections in a specified spatial domain. The system has been successfully tested and used, in combination with other methods, to investigate the route for mobile signals such as the SHR protein, microRNA165/6, and cytokinins in Arabidopsis roots, and also to understand the role of symplastic domain formation during lateral root development. We envision that this tool may also be useful for identifying tissue-specific symplastic regulatory networks and to analyze symplastic movement of metabolites.

Enterprise Professional Development--Evaluating Learning

ERIC Educational Resources Information Center

Murphy, Gerald A.; Calway, Bruce A.

2010-01-01

Whilst professional development (PD) is an activity required by many regulatory authorities, the value that enterprises obtain from PD is often unknown, particularly when it involves development of knowledge. This paper discusses measurement techniques and processes and provides a review of established evaluation techniques, highlighting…

Materials Data on Ca(GePd)2 (SG:139) by Materials Project

DOE Data Explorer

Kristin Persson

2014-11-02

Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

Materials Data on Ba(AsPd)2 (SG:123) by Materials Project

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

Kristin Persson

Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

Materials Data on Pd(SCl3)2 (SG:2) by Materials Project

DOE Data Explorer

Kristin Persson

2014-11-02

Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

Materials Data on TbGaPd (SG:62) by Materials Project

DOE Data Explorer

Kristin Persson

2015-01-27

Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

Materials Data on U(SiPd)2 (SG:139) by Materials Project

DOE Data Explorer

Kristin Persson

2016-02-10

Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

Materials Data on U(GePd)2 (SG:139) by Materials Project

DOE Data Explorer

Kristin Persson

2016-02-05

Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

Materials Data on CuPdO2 (SG:53) by Materials Project

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

Kristin Persson

Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

Materials Data on KPrPdO3 (SG:12) by Materials Project

DOE Data Explorer

Kristin Persson

2016-02-05

Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

Materials Data on KNdPdO3 (SG:12) by Materials Project

DOE Data Explorer

Kristin Persson

2016-02-10

Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

Materials Data on KSmPdO3 (SG:12) by Materials Project

DOE Data Explorer

Kristin Persson

2016-02-05

Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

Materials Data on KLaPdO3 (SG:12) by Materials Project

DOE Data Explorer

Kristin Persson

2016-02-05

Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

Materials Data on KGdPdO3 (SG:12) by Materials Project

DOE Data Explorer

Kristin Persson

2014-07-09

Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

Materials Data on TePdI (SG:131) by Materials Project

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

Kristin Persson

2016-02-05

Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

Materials Data on BaIn2Pd (SG:63) by Materials Project

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

Kristin Persson

2017-05-05

Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

7 CFR 3430.58 - Prior approvals.

Code of Federal Regulations, 2011 CFR

2011-01-01

.... (b) No-cost extensions of time—(1) General. Awardees may initiate a one-time no-cost extension of the... portion(s) of the project for which the extension is being requested; and signature of the AR and the PD...

Materials Data on PdF3 (SG:167) by Materials Project

DOE Data Explorer

Kristin Persson

2015-03-07

Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

Materials Data on PdF2 (SG:136) by Materials Project

DOE Data Explorer

Kristin Persson

2015-02-09

Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

Materials Data on SrPdF4 (SG:140) by Materials Project

DOE Data Explorer

Kristin Persson

2014-11-02

Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

Materials Data on BaPdF4 (SG:140) by Materials Project

DOE Data Explorer

Kristin Persson

2014-11-02

Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

Materials Data on Y(SiPd)2 (SG:139) by Materials Project

DOE Data Explorer

Kristin Persson

2014-07-09

Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

Materials Data on MgPd5 (SG:155) by Materials Project

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

Kristin Persson

2016-08-28

Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

Materials Data on AgPdO2 (SG:47) by Materials Project

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

Kristin Persson

2016-04-21

Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

Materials Data on Pd7Se4 (SG:18) by Materials Project

DOE Data Explorer

Kristin Persson

2016-02-10

Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

Materials Data on CaSn2Pd (SG:63) by Materials Project

DOE Data Explorer

Kristin Persson

2015-02-09

Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

Materials Data on LaSn2Pd (SG:63) by Materials Project

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

Kristin Persson

2016-08-31

Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

Materials Data on YbSn2Pd (SG:63) by Materials Project

DOE Data Explorer

Kristin Persson

2015-03-08

Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

Materials Data on Sn2Pd (SG:142) by Materials Project

DOE Data Explorer

Kristin Persson

2014-11-02

Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

Materials Data on Tb(SiPd)2 (SG:139) by Materials Project

DOE Data Explorer

Kristin Persson

2014-07-09

Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

Materials Data on Tb(GePd)2 (SG:139) by Materials Project

DOE Data Explorer

Kristin Persson

2016-04-04

Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

Mathematics Professional Development: Critical Features for Developing Leadership Skills and Building Teachers' Capacity

ERIC Educational Resources Information Center

Koellner, Karen; Jacobs, Jennifer; Borko, Hilda

2011-01-01

This article focuses on three features of professional development (PD) programs that play an important role in developing leadership skills and building teachers' capacity: (1) fostering a professional learning community, (2) developing teachers' mathematical knowledge for teaching, and (3) adapting PD to support local needs and interests. We…

The times they are a-changing: Self-directed long-term services and supports and gerontological social work.

PubMed

Sciegaj, Mark; Hooyman, Nancy R; Mahoney, Kevin J; DeLuca, Casey

2018-03-05

The Partnerships for Person-Centered (PC) and Participant-Directed (PD) Long-Term Services and Supports (LTSS) Project (Partnerships Project) was a three-year effort funded by the New York Community Trust to develop and implement social work curriculum that would better prepare students for the changing practice demands of the aging and disability services network for self-directed LTSS (SD-LTSS). This article first describes the growth of SD-LTSS and the need for trained social workers on this service delivery model. The paper then describes the Partnerships Project that involved schools of social work along and aging and disability network organization partners in nine states. This description includes the major activities of the project including the creation of SD-LTSS competencies for social work education, the infusion of these competencies in beginning and advanced social work classes, and student assessment of their attainment of these competencies. This article then discusses the challenges to institutionalizing such curricular changes within social work programs and the need for a national strategy to train social workers for the demands of SD-LTSS.

Reaction-Based Reactive Transport Modeling of Iron Reduction and Uranium Immobilization at Area 2 of the NABIR Field Research Center

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

Burgos, W.D.

2009-09-02

This report summarizes research conducted in conjunction with a project entitled “Reaction-Based Reactive Transport Modeling of Iron Reduction and Uranium Immobilization at Area 2 of the NABIR Field Research Center”, which was funded through the Integrative Studies Element of the former NABIR Program (now the Environmental Remediation Sciences Program) within the Office of Biological and Environmental Research. Dr. William Burgos (The Pennsylvania State University) was the overall PI/PD for the project, which included Brian Dempsey (Penn State), Gour-Tsyh (George) Yeh (Central Florida University), and Eric Roden (formerly at The University of Alabama, now at the University of Wisconsin) as separately-fundedmore » co-PIs. The project focused on development of a mechanistic understanding and quantitative models of coupled Fe(III)/U(VI) reduction in FRC Area 2 sediments. The work builds on our previous studies of microbial Fe(III) and U(VI) reduction, and was directly aligned with the Scheibe et al. ORNL FRC Field Project at Area 2.« less

KSC-06pd0547

NASA Image and Video Library

2006-03-24

KENNEDY SPACE CENTER, FLA. -- With the ribbon-cutting ceremony, the new Operations Support Building II is officially in business. Participating in the event are (left to right) Aris Garcia, vice president of the architecture firm Wolfgang Alvarez; Mark Nappi, associate program manager of Ground Operations for United Space Alliance; Donald Minderman, NASA project manager; Scott Kerr, director of Engineering Development at Kennedy; Bill Parsons, deputy director of Kennedy Space Center; Miguel Morales, with NASA Engineering Development; Mike Wetmore, director of Shuttle Processing; and Tim Clancy, president of the construction firm Clancy & Theys. The Operations Support Building II is an Agency safety and health initiative project to replace 198,466 square feet of substandard modular housing and trailers in the Launch Complex 39 area at Kennedy Space Center. The five-story building, which sits south of the Vehicle Assembly Building and faces the launch pads, includes 960 office spaces, 16 training rooms, computer and multimedia conference rooms, a Mission Conference Center with an observation deck, technical libraries, an Exchange store, storage, break areas, and parking. Photo credit: NASA/George Shelton

Glutamate Neonatal Excitotoxicity Modifies VEGF-A, VEGF-B, VEGFR-1 and VEGFR-2 Protein Expression Profiles During Postnatal Development of the Cerebral Cortex and Hippocampus of Male Rats.

PubMed

Castañeda-Cabral, Jose Luis; Beas-Zarate, Carlos; Gudiño-Cabrera, Graciela; Ureña-Guerrero, Monica E

2017-09-01

Vascular endothelial growth factor (VEGF) exerts both neuroprotective and proinflammatory effects in the brain, depending on the VEGF (A-E) and VEGF receptor (VEGFR1-3) types involved. Neonatal monosodium glutamate (MSG) treatment triggers an excitotoxic degenerative process associated with several neuropathological conditions, and VEGF messenger RNA (mRNA) expression is increased at postnatal day (PD) 14 in rat hippocampus (Hp) following the treatment. The aim of this work was to establish the changes in immunoreactivity to VEGF-A, VEGF-B, VEGFR-1 and VEGFR-2 proteins induced by neonatal MSG treatment (4 g/kg, subcutaneous, at PD1, 3, 5 and 7) in the cerebral motor cortex (CMC) and Hp. Samples collected from PD2 to PD60 from control and MSG-treated male Wistar rats were assessed by western blotting for each protein. Considering that immunoreactivity measured by western blotting is related to the protein expression level, we found that each protein in each cerebral region has a specific expression profile throughout the studied ages, and all profiles were differentially modified by MSG. Specifically, neonatal MSG treatment significantly increased the immunoreactivity to the following: (1) VEGF-A at PD8-PD10 in the CMC and at PD6-PD8 in the Hp; (2) VEGF-B at PD2, PD6 and PD10 in the CMC and at PD8-PD9 in the Hp; and (3) VEGFR-2 at PD6-PD8 in the CMC and at PD21-PD60 in the Hp. Also, MSG significantly reduced the immunoreactivity to the following: (1) VEGF-B at PD8-PD9 and PD45-PD60 in the CMC; and (2) VEGFR-1 at PD4-PD6 and PD14-PD21 in the CMC and at PD4, PD9-PD10 and PD60 in the Hp. Our results indicate that VEGF-mediated signalling is involved in the excitotoxic process triggered by neonatal MSG treatment and should be further characterized.

Agonistic TAM-163 antibody targeting tyrosine kinase receptor-B: applying mechanistic modeling to enable preclinical to clinical translation and guide clinical trial design.

PubMed

Vugmeyster, Yulia; Rohde, Cynthia; Perreault, Mylene; Gimeno, Ruth E; Singh, Pratap

2013-01-01

TAM-163, an agonist monoclonal antibody targeting tyrosine receptor kinase-B (TrkB), is currently being investigated as a potential body weight modulatory agent in humans. To support the selection of the dose range for the first-in-human (FIH) trial of TAM-163, we conducted a mechanistic analysis of the pharmacokinetic (PK) and pharmacodynamic (PD) data (e.g., body weight gain) obtained in lean cynomolgus and obese rhesus monkeys following single doses ranging from 0.3 to 60 mg/kg. A target-mediated drug disposition (TMDD) model was used to describe the observed nonlinear PK and Emax approach was used to describe the observed dose-dependent PD effect. The TMDD model development was supported by the experimental determination of the binding affinity constant (9.4 nM) and internalization rate of the drug-target complex (2.08 h(-1)). These mechanistic analyses enabled linking of exposure, target (TrkB) coverage, and pharmacological activity (e.g., PD) in monkeys, and indicated that ≥ 38% target coverage (time-average) was required to achieve significant body weight gain in monkeys. Based on the scaling of the TMDD model from monkeys to humans and assuming similar relationship between the target coverage and pharmacological activity between monkey and humans, subcutaneous (SC) doses of 1 and 15 mg/kg in humans were projected to be the minimally and the fully pharmacologically active doses, respectively. Based on the minimal anticipated biological effect level (MABEL) approach for starting dose selection, the dose of 0.05 mg/kg (3 mg for a 60 kg human) SC was recommended as the starting dose for FIH trials, because at this dose level<10% target coverage was projected at Cmax (and all other time points). This study illustrates a rational mechanistic approach for the selection of FIH dose range for a therapeutic protein with a complex model of action.

Development and Validation of Personality Disorder Spectra Scales for the MMPI-2-RF.

PubMed

Sellbom, Martin; Waugh, Mark H; Hopwood, Christopher J

2018-01-01

The purpose of this study was to develop and validate a set of MMPI-2-RF (Ben-Porath & Tellegen, 2008/2011) personality disorder (PD) spectra scales. These scales could serve the purpose of assisting with DSM-5 PD diagnosis and help link categorical and dimensional conceptions of personality pathology within the MMPI-2-RF. We developed and provided initial validity results for scales corresponding to the 10 PD constructs listed in the DSM-5 using data from student, community, clinical, and correctional samples. Initial validation efforts indicated good support for criterion validity with an external PD measure as well as with dimensional personality traits included in the DSM-5 alternative model for PDs. Construct validity results using psychosocial history and therapists' ratings in a large clinical sample were generally supportive as well. Overall, these brief scales provide clinicians using MMPI-2-RF data with estimates of DSM-5 PD constructs that can support cross-model connections between categorical and dimensional assessment approaches.

In vitro pharmacokinetic/pharmacodynamic models in anti-infective drug development: focus on TB

PubMed Central

Vaddady, Pavan K; Lee, Richard E; Meibohm, Bernd

2011-01-01

For rapid anti-tuberculosis (TB) drug development in vitro pharmacokinetic/pharmacodynamic (PK/PD) models are useful in evaluating the direct interaction between the drug and the bacteria, thereby guiding the selection of candidate compounds and the optimization of their dosing regimens. Utilizing in vivo drug-clearance profiles from animal and/or human studies and simulating them in an in vitro PK/PD model allows the in-depth characterization of antibiotic activity of new and existing antibacterials by generating time–kill data. These data capture the dynamic interplay between mycobacterial growth and changing drug concentration as encountered during prolonged drug therapy. This review focuses on important PK/PD parameters relevant to anti-TB drug development, provides an overview of in vitro PK/PD models used to evaluate the efficacy of agents against mycobacteria and discusses the related mathematical modeling approaches of time–kill data. Overall, it provides an introduction to in vitro PK/PD models and their application as critical tools in evaluating anti-TB drugs. PMID:21359155

Graphene-based plasmonic photodetector for photonic integrated circuits.

PubMed

Kim, Jin Tae; Yu, Young-Jun; Choi, Hongkyw; Choi, Choon-Gi

2014-01-13

We developed a planar-type graphene-based plasmonic photodetector (PD) for the development of all-graphene photonic-integrated-circuits (PICs). By configuring the graphene plasmonic waveguide and PD structure all-in-one, the proposed graphene PD detects horizontally incident light. The photocurrent profile with opposite polarity is the maximum at graphene-electrode interfaces due to a Schottky-like barrier effect at the interface. The photocurrent amplitude increases with an increase of the graphene-metal interface length. Obtaining time constants of less than 39.7 ms for the time response, we concluded that the proposed graphene PD could be exploited further for application in all graphene-based PICs.

Holistic Approach to Secondary Earth Science Teacher Professional Development: the Triad of Project-based Instruction, Earth Science Content, and GIS Technology

NASA Astrophysics Data System (ADS)

Rubino-Hare, L.; Sample, J. C.; Fredrickson, K.; Claesgens, J.; Bloom, N.; Henderson-Dahms, C.; Manone, M.

2011-12-01

We have provided two years of professional development for secondary and middle school teachers with a focus on project-based instruction (PBI) using GIS. The EYE-POD project (funded by NSF-ITEST) involved pairs of teachers from Arizona and the surrounding region in two-week institutes during Summer, 2010, and an advanced institute in Summer, 2011. The NAz-POD project (funded by Arizona Department of Education and administered by Science Foundation Arizona) provided similar PD experiences, but the institutes occurred during weekends in the academic year. The institutes were led by a team with expertise in Earth science content, professional development and pedagogy, and GIS. The teachers developed learning modules using the project based learning instructional model. Pedagogy, content, and GIS skills were combined throughout the professional development activities. Academic year follow up by NAU personnel included classroom observations and technical support. For assessing student work we provided a rubric, but learned that teachers were not prepared to assess GIS products in order to determine the level of student understanding. In year two of the project we incorporated strategies for assessment of student products into the professional development. Teacher-participants and their students completed several pre- and post- assessments. Teacher assessments included a geospatial performance assessment, classroom observations, and content tests. Student data collection included attitude and efficacy questionnaires, content tests, and authentic assessments including products using GIS. Content tests were the same for teachers and students and included spatial reasoning, data analysis, and Earth science content. Data was also collected on teacher perception of professional development delivery and self-reported confidence in teaching with PBI and geospatial technology. Student assessments show that improvement occurred in all areas on the content test. Possible factors resulting in this improvement will be shared, and placed in the context of other assessment results.

Thioureas as ligands in the pd-catalyzed intramolecular Pauson-Khand reaction.

PubMed

Tang, Yefeng; Deng, Lujiang; Zhang, Yangdong; Dong, Guangbin; Chen, Jiahua; Yang, Zhen

2005-04-14

[reaction: see text] The thiourea-Pd complex was established as a novel type of catalyst in the PKR of allylpropargylamine, and the demonstrated chemistry may prove to be valuable for developing thiuorea as a ligand for the Pd-catalyzed Pauson-Khand reaction.

Safinamide: first global approval.

PubMed

Deeks, Emma D

2015-04-01

Safinamide (Xadago(®)) is an oral α-aminoamide derivative developed by Newron for the treatment of Parkinson's disease (PD). The drug has both dopaminergic properties (highly selective and reversible inhibition of monoamine oxidase-B) and non-dopaminergic properties (selective sodium channel blockade and calcium channel modulation, with consequent inhibition of excessive glutamate release). Safinamide is approved in the EU, Iceland, Lichtenstein and Norway, as an add-on therapy to stable-dose levodopa, alone or in combination with other PD therapies in mid- to late-stage fluctuating PD patients; regulatory submissions have also been filed in the USA and Switzerland for its use in this indication. Additional submissions have been made in the USA, Iceland, Lichtenstein, Norway and Switzerland for early-stage PD. Safinamide has also undergone phase II investigation in PD patients with drug-induced dyskinesia (France, Germany, Austria, Canada and South Africa) or cognitive impairment (USA and Spain). This article summarizes the milestones in the development of safinamide leading to its first approval for PD.

Silver and palladium alloy nanoparticle catalysts: reductive coupling of nitrobenzene through light irradiation.

PubMed

Peiris, Sunari; Sarina, Sarina; Han, Chenhui; Xiao, Qi; Zhu, Huai-Yong

2017-08-15

Silver-palladium (Ag-Pd) alloy nanoparticles strongly absorb visible light and exhibit significantly higher photocatalytic activity compared to both pure palladium (Pd) and silver (Ag) nanoparticles. Photocatalysts of Ag-Pd alloy nanoparticles on ZrO 2 and Al 2 O 3 supports are developed to catalyze the nitroaromatic coupling to the corresponding azo compounds under visible light irradiation. Ag-Pd alloy NP/ZrO 2 exhibited the highest photocatalytic activity for nitrobenzene coupling to azobenzene (yield of ∼80% in 3 hours). The photocatalytic efficiency could be optimized by altering the Ag : Pd ratio of the alloy nanoparticles, irradiation light intensity, temperature and wavelength. The rate of the reaction depends on the population and energy of the excited electrons, which can be improved by increasing the light intensity or by using a shorter wavelength. The knowledge developed in this study may inspire further studies on Ag alloy photocatalysts and organic syntheses using Ag-Pd nanoparticle catalysts driven under visible light Irradiation.

Panic disorder among African Americans, Caribbean blacks and non-Hispanic whites

PubMed Central

Himle, Joseph A.; Taylor, Robert Joseph; Abelson, Jamie M.; Matusko, Niki; Muroff, Jordana; Jackson, James

2014-01-01

Introduction This study investigated co-morbidities, level of disability, service utilization and demographic correlates of panic disorder (PD) among African Americans, Caribbean blacks and non-Hispanic white Americans. Methods Data are from the National Survey of American Life (NSAL) and the National Comorbidity Survey-Replication (NCS-R). Results Non-Hispanic whites are the most likely to develop PD across the lifespan compared to the black subgroups. Caribbean blacks were found to experience higher levels of functional impairment. There were no gender differences found in prevalence of PD in Caribbean blacks, indicating that existing knowledge about who is at risk for developing PD (generally more prevalent in women) may not be true among this subpopulation. Furthermore, Caribbean blacks with PD were least likely to use mental health services compared to African Americans and non-Hispanic whites. Conclusion This study demonstrates that PD may affect black ethnic subgroups differently, which has important implications for understanding the nature and etiology of the disorder. PMID:22983664

Using Effective Professional Development Sessions to Implement Change in Curriculum and Classroom Practices: My Story as a Teacher at Exmouth District High School, WA's Remotest District High

ERIC Educational Resources Information Center

Bedford, Susie

2005-01-01

Teaching in a remote town has its drawbacks with regard to Professional Development (PD), which becomes extremely costly, so each staff member is probably limited to one decent PD once a year. This means choosing PD extremely carefully to ensure "value for money" and hopefully that it will provide the teacher concerned with…

Dysphagia in Parkinson's Disease.

PubMed

Suttrup, Inga; Warnecke, Tobias

2016-02-01

More than 80 % of patients with Parkinson's disease (PD) develop dysphagia during the course of their disease. Swallowing impairment reduces quality of life, complicates medication intake and leads to malnutrition and aspiration pneumonia, which is a major cause of death in PD. Although the underlying pathophysiology is poorly understood, it has been shown that dopaminergic and non-dopaminergic mechanisms are involved in the development of dysphagia in PD. Clinical assessment of dysphagia in PD patients is challenging and often delivers unreliable results. A modified water test assessing maximum swallowing volume is recommended to uncover oropharyngeal dysphagia in PD. PD-specific questionnaires may also be useful to identify patients at risk for swallowing impairment. Fiberoptic endoscopic evaluation of swallowing and videofluoroscopic swallowing study are both considered to be the gold standard for evaluation of PD-related dysphagia. In addition, high-resolution manometry may be a helpful tool. These instrumental methods allow a reliable detection of aspiration events. Furthermore, typical patterns of impairment during the oral, pharyngeal and/or esophageal swallowing phase of PD patients can be identified. Therapy of dysphagia in PD consists of pharmacological interventions and swallowing treatment by speech and language therapists (SLTs). Fluctuating dysphagia with deterioration during the off-state should be treated by optimizing dopaminergic medication. The methods used during swallowing treatment by SLTs shall be selected according to the individual dysphagia pattern of each PD patient. A promising novel method is an intensive training of expiratory muscle strength. Deep brain stimulation does not seem to have a clinical relevant effect on swallowing function in PD. The goal of this review is giving an overview on current stages of epidemiology, pathophysiology, diagnosis, and treatment of PD-associated dysphagia, which might be helpful for neurologists, speech-language therapists, and other clinicians in their daily work with PD patients and associated swallowing difficulties. Furthermore areas with an urgent need for future clinical research are identified.

Senescent cells re-engineered to express soluble programmed death receptor-1 for inhibiting programmed death receptor-1/programmed death ligand-1 as a vaccination approach against breast cancer.

PubMed

Chen, Zehong; Hu, Kang; Feng, Lieting; Su, Ruxiong; Lai, Nan; Yang, Zike; Kang, Shijun

2018-06-01

Various types of vaccines have been proposed as approaches for prevention or delay of the onset of cancer by boosting the endogenous immune system. We previously developed a senescent-cell-based vaccine, induced by radiation and veliparib, as a preventive and therapeutic tool against triple-negative breast cancer. However, the programmed death receptor-1/programmed death ligand-1 (PD-1/PD-L1) pathway was found to play an important role in vaccine failure. Hence, we further developed soluble programmed death receptor-1 (sPD1)-expressing senescent cells to overcome PD-L1/PD-1-mediated immune suppression while vaccinating to promote dendritic cell (DC) maturity, thereby amplifying T-cell activation. In the present study, sPD1-expressing senescent cells showed a particularly active status characterized by growth arrest and modified immunostimulatory cytokine secretion in vitro. As expected, sPD1-expressing senescent tumor cell vaccine (STCV/sPD-1) treatment attracted more mature DC and fewer exhausted-PD1 + T cells in vivo. During the course of the vaccine studies, we observed greater safety and efficacy for STCV/sPD-1 than for control treatments. STCV/sPD-1 pre-injections provided complete protection from 4T1 tumor challenge in mice. Additionally, the in vivo therapeutic study of mice with s.c. 4T1 tumor showed that STCV/sPD-1 vaccination delayed tumorigenesis and suppressed tumor progression at early stages. These results showed that STCV/sPD-1 effectively induced a strong antitumor immune response against cancer and suggested that it might be a potential strategy for TNBC prevention. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Trends in Professional Development for and Collaboration by Health Education Teachers—41 States, 2000–2010

PubMed Central

Brener, Nancy D.; McManus, Tim; Wechsler, Howell; Kann, Laura

2015-01-01

BACKGROUND Professional development (PD) and collaboration help ensure the quality of school health education. The purpose of this study was to examine trends in the percentage of lead health education teachers (LHETs) receiving PD on health topics and collaborating with other school staff on health education activities. METHODS This study analyzed representative data from 41 states participating in School Health Profiles surveys between 2000 and 2010. Logistic regression examined linear trends in the percentage of LHETs who received PD on 12 topics and who collaborated on health education activities. RESULTS Significant increases in the percentage of LHETs receiving PD on nutrition and physical activity and significant decreases in the percentage of LHETs receiving PD on alcohol- and other drug-use prevention and human immunodeficiency virus prevention were seen. Significant increases in the percentage of LHETs who collaborated with physical education staff and nutrition services staff were seen in 29 and 39 states, respectively. CONCLUSIONS Although 10-year increases in PD and collaboration in the areas of nutrition and physical activity are encouraging, PD and collaboration in other topic areas still need improvement. These results will help states target more resources toward PD and collaboration in areas where they have been decreasing. PMID:24020688

Intranasal gene delivery for treating Parkinson's disease: overcoming the blood-brain barrier.

PubMed

Aly, Amirah E-E; Waszczak, Barbara L

2015-01-01

Developing a disease-modifying gene therapy for Parkinson's disease (PD) has been a high priority for over a decade. However, due to the inability of large biomolecules to cross the blood-brain barrier (BBB), the only means of delivery to the brain has been intracerebral infusion. Intranasal administration offers a non-surgical means of bypassing the BBB to deliver neurotrophic factors, and the genes encoding them, directly to the brain. This review summarizes: i) evidence demonstrating intranasal delivery to the brain of a number of biomolecules having therapeutic potential for various CNS disorders; and ii) evidence demonstrating neuroprotective efficacy of a subset of biomolecules specifically for PD. The intersection of these two spheres represents the area of opportunity for development of new intranasal gene therapies for PD. To that end, our laboratory showed that intranasal administration of glial cell line-derived neurotrophic factor (GDNF), or plasmid DNA nanoparticles encoding GDNF, provides neuroprotection in a rat model of PD, and that the cells transfected by the nanoparticle vector are likely to be pericytes. A number of genes encoding neurotrophic factors have therapeutic potential for PD, but few have been tested by the intranasal route and shown to be neuroprotective in a model of PD. Intranasal delivery provides a largely unexplored, promising approach for development of a non-invasive gene therapy for PD.

Polymer monolithic capillary microextraction on-line coupled with inductively coupled plasma-mass spectrometry for the determination of trace Au and Pd in biological samples

NASA Astrophysics Data System (ADS)

Liu, Xiaolan; He, Man; Chen, Beibei; Hu, Bin

2014-11-01

A novel method based on on-line polymer monolithic capillary microextraction (CME)-inductively coupled plasma mass spectrometry (ICP-MS) was developed for the determination of trace Au and Pd in biological samples. For this purpose, poly(glycidyl methacrylate-ethylene dimethacrylate) monolith was prepared and functionalized with mercapto groups. The prepared monolith exhibited good selectivity to Au and Pd, and good resistance to strong acid with a long life span. Factors affecting the extraction efficiency of CME, such as sample acidity, sample flow rate, eluent conditions and coexisting ion interference were investigated in detail. Under the optimal conditions, the limits of detection (LODs, 3σ) were 5.9 ng L- 1 for Au and 8.3 ng L- 1 for Pd, and the relative standard deviations (RSDs, c = 50 ng L-1, n = 7) were 6.5% for Au and 1.1% for Pd, respectively. The developed method was successfully applied to the determination of Au and Pd in human urine and serum samples with the recovery in the range of 84-118% for spiked samples. The developed on-line polymer monolithic CME-ICP-MS method has the advantages of rapidity, simplicity, low sample/reagent consumption, high sensitivity and is suitable for the determination of trace Au and Pd in biological samples with limited amount available and complex matrix.

C/EBPα is dispensable for the ontogeny of PD-1+ CD4+ memory T cells but restricts their expansion in an age-dependent manner.

PubMed

Norrie, Ida Christine; Ohlsson, Ewa; Nielsen, Olaf; Hasemann, Marie Sigurd; Porse, Bo T

2014-01-01

Ageing and cancer is often associated with altered T cell distributions and this phenomenon has been suggested to be the main driver in the development of immunosenescence. Memory phenotype PD-1+ CD4+ T cells accumulate with age and during leukemic development, and they might account for the attenuated T cell response in elderly or diseased individuals. The transcription factor C/EBPα has been suggested to be responsible for the accumulation as well as for the senescent features of these cells including impaired TCR signaling and decreased proliferation. Thus modulating the activity of C/EBPα could potentially target PD-1+ CD4+ T cells and consequently, impede the development of immunosenescence. To exploit this possibility we tested the importance of C/EBPα for the development of age-dependent PD-1+ CD4+ T cells as well as its role in the accumulation of PD-1+ CD4+ T cells during leukemic progression. In contrast to earlier suggestions, we find that loss of C/EBPα expression in the lymphoid compartment led to an increase of PD-1+ CD4+ T cells specifically in old mice, suggesting that C/EBPα repress the accumulation of these cells in elderly by inhibiting their proliferation. Furthermore, C/EBPα-deficiency in the lymphoid compartment had no effect on leukemic development and did not affect the accumulation of PD-1+ CD4+ T cells. Thus, in addition to contradict earlier suggestions of a role for C/EBPα in immunosenescence, these findings efficiently discard the potential of using C/EBPα as a target for the alleviation of ageing/cancer-associated immunosenescence.

C/EBPα Is Dispensable for the Ontogeny of PD-1+ CD4+ Memory T Cells but Restricts Their Expansion in an Age-Dependent Manner

PubMed Central

Norrie, Ida Christine; Ohlsson, Ewa; Nielsen, Olaf

2014-01-01

Ageing and cancer is often associated with altered T cell distributions and this phenomenon has been suggested to be the main driver in the development of immunosenescence. Memory phenotype PD-1+ CD4+ T cells accumulate with age and during leukemic development, and they might account for the attenuated T cell response in elderly or diseased individuals. The transcription factor C/EBPα has been suggested to be responsible for the accumulation as well as for the senescent features of these cells including impaired TCR signaling and decreased proliferation. Thus modulating the activity of C/EBPα could potentially target PD-1+ CD4+ T cells and consequently, impede the development of immunosenescence. To exploit this possibility we tested the importance of C/EBPα for the development of age-dependent PD-1+ CD4+ T cells as well as its role in the accumulation of PD-1+ CD4+ T cells during leukemic progression. In contrast to earlier suggestions, we find that loss of C/EBPα expression in the lymphoid compartment led to an increase of PD-1+ CD4+ T cells specifically in old mice, suggesting that C/EBPα repress the accumulation of these cells in elderly by inhibiting their proliferation. Furthermore, C/EBPα-deficiency in the lymphoid compartment had no effect on leukemic development and did not affect the accumulation of PD-1+ CD4+ T cells. Thus, in addition to contradict earlier suggestions of a role for C/EBPα in immunosenescence, these findings efficiently discard the potential of using C/EBPα as a target for the alleviation of ageing/cancer-associated immunosenescence. PMID:24404186

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.

Developing xylem-preferential expression of PdGA20ox1, a gibberellin 20-oxidase 1 from Pinus densiflora, improves woody biomass production in a hybrid poplar.

PubMed

Jeon, Hyung-Woo; Cho, Jin-Seong; Park, Eung-Jun; Han, Kyung-Hwan; Choi, Young-Im; Ko, Jae-Heung

2016-04-01

Woody biomass has gained popularity as an environmentally friendly, renewable and sustainable resource for liquid fuel production. Here, we demonstrate biotechnological improvement of the quantity and quality of woody biomass by employing developing xylem (DX)-preferential production of gibberellin (GA), a phytohormone that positively regulates stem growth. First, for the proof of concept experiment, we produced transgenic Arabidopsis plants expressing GA20-oxidase, a key enzyme in the production of bioactive GAs, from Pinus densiflora (PdGA20ox1) under the control of either a constitutive 35S promoter, designated 35S::PdGA20ox1, or a DX-specific promoter (originated from poplar), designated DX15::PdGA20ox1. As we hypothesized, both transgenic Arabidopsis plants (35S::PdGA20ox1 and DX15::PdGA20ox1) exhibited an accelerated stem growth that resulted in a large increase of biomass, up to 300% compared to wild-type control plants, together with increased secondary wall thickening and elongation of fibre cells. Next, we applied our concept to the production of transgenic poplar trees. Both transgenic poplar trees (35S::PdGA20ox1 and DX15::PdGA20ox1) showed dramatic increases in biomass, up to 300%, with accelerated stem growth and xylem differentiation. Cell wall monosaccharide composition analysis revealed that in both Arabidopsis and poplar, glucose and xylose contents were significantly increased. However, undesirable phenotypes of 35S::PdGA20ox1 poplar, including poor root growth and leaf development, were found. Interestingly, DX15::PdGA20ox1 poplar resulted in a reduction of undesirable phenotypes. Our results indicate that the controlled production of GAs through a tissue-specific promoter can be utilized as an efficient biotechnological tool for producing enhanced plant biomass, minimizing unwanted effects. © 2015 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

Breast percent density estimation from 3D reconstructed digital breast tomosynthesis images

NASA Astrophysics Data System (ADS)

Bakic, Predrag R.; Kontos, Despina; Carton, Ann-Katherine; Maidment, Andrew D. A.

2008-03-01

Breast density is an independent factor of breast cancer risk. In mammograms breast density is quantitatively measured as percent density (PD), the percentage of dense (non-fatty) tissue. To date, clinical estimates of PD have varied significantly, in part due to the projective nature of mammography. Digital breast tomosynthesis (DBT) is a 3D imaging modality in which cross-sectional images are reconstructed from a small number of projections acquired at different x-ray tube angles. Preliminary studies suggest that DBT is superior to mammography in tissue visualization, since superimposed anatomical structures present in mammograms are filtered out. We hypothesize that DBT could also provide a more accurate breast density estimation. In this paper, we propose to estimate PD from reconstructed DBT images using a semi-automated thresholding technique. Preprocessing is performed to exclude the image background and the area of the pectoral muscle. Threshold values are selected manually from a small number of reconstructed slices; a combination of these thresholds is applied to each slice throughout the entire reconstructed DBT volume. The proposed method was validated using images of women with recently detected abnormalities or with biopsy-proven cancers; only contralateral breasts were analyzed. The Pearson correlation and kappa coefficients between the breast density estimates from DBT and the corresponding digital mammogram indicate moderate agreement between the two modalities, comparable with our previous results from 2D DBT projections. Percent density appears to be a robust measure for breast density assessment in both 2D and 3D x-ray breast imaging modalities using thresholding.

CD4 T cells promote rather than control tuberculosis in the absence of PD-1-mediated inhibition.

PubMed

Barber, Daniel L; Mayer-Barber, Katrin D; Feng, Carl G; Sharpe, Arlene H; Sher, Alan

2011-02-01

Although CD4 T cells are required for host resistance to Mycobacterium tuberculosis, they may also contribute to pathology. In this study, we examine the role of the inhibitory receptor PD-1 and its ligand PD-L1 during M. tuberculosis infection. After aerosol exposure, PD-1 knockout (KO) mice develop high numbers of M. tuberculosis-specific CD4 T cells but display markedly increased susceptibility to infection. Importantly, we show that CD4 T cells themselves drive the increased bacterial loads and pathology seen in infected PD-1 KO mice, and PD-1 deficiency in CD4 T cells is sufficient to trigger early mortality. PD-L1 KO mice also display enhanced albeit less severe susceptibility, indicating that T cells are regulated by multiple PD ligands during M. tuberculosis infection. M. tuberculosis-specific CD8 T cell responses were normal in PD-1 KO mice, and CD8 T cells only had a minor contribution to the exacerbated disease in the M. tuberculosis-infected PD-1 KO and PD-L1 KO mice. Thus, in the absence of the PD-1 pathway, M. tuberculosis benefits from CD4 T cell responses, and host resistance requires inhibition by PD-1 to prevent T cell-driven exacerbation of the infection.

Nanoscale PdO Catalyst Functionalized Co3O4 Hollow Nanocages Using MOF Templates for Selective Detection of Acetone Molecules in Exhaled Breath.

PubMed

Koo, Won-Tae; Yu, Sunmoon; Choi, Seon-Jin; Jang, Ji-Soo; Cheong, Jun Young; Kim, Il-Doo

2017-03-08

The increase of surface area and the functionalization of catalyst are crucial to development of high-performance semiconductor metal oxide (SMO) based chemiresistive gas sensors. Herein, nanoscale catalyst loaded Co 3 O 4 hollow nanocages (HNCs) by using metal-organic framework (MOF) templates have been developed as a new sensing platform. Nanoscale Pd nanoparticles (NPs) were easily loaded on the cavity of Co based zeolite imidazole framework (ZIF-67). The porous structure of ZIF-67 can restrict the size of Pd NPs (2-3 nm) and separate Pd NPs from each other. Subsequently, the calcination of Pd loaded ZIF-67 produced the catalytic PdO NPs functionalized Co 3 O 4 HNCs (PdO-Co 3 O 4 HNCs). The ultrasmall PdO NPs (3-4 nm) are well-distributed in the wall of Co 3 O 4 HNCs, the unique structure of which can provide high surface area and high catalytic activity. As a result, the PdO-Co 3 O 4 HNCs exhibited improved acetone sensing response (R gas /R air = 2.51-5 ppm) compared to PdO-Co 3 O 4 powders (R gas /R air = 1.98), Co 3 O 4 HNCs (R gas /R air = 1.96), and Co 3 O 4 powders (R gas /R air = 1.45). In addition, the PdO-Co 3 O 4 HNCs showed high acetone selectivity against other interfering gases. Moreover, the sensor array clearly distinguished simulated exhaled breath of diabetics from healthy people's breath. These results confirmed the novel synthesis of MOF templated nanoscale catalyst loaded SMO HNCs for high performance gas sensors.

Composite biomarkers defined by multiparametric immunofluorescence analysis identify ALK-positive adenocarcinoma as a potential target for immunotherapy

PubMed Central

Roussel, Hélène; De Guillebon, Eléonore; Biard, Lucie; Mandavit, Marion; Gibault, Laure; Fabre, Elisabeth; Antoine, Martine; Hofman, Paul; Beau-Faller, Michèle; Blons, Hélène; Danel, Claire; Barthes, Françoise Le Pimpec; Gey, Alain; Granier, Clémence; Wislez, Marie; Laurent-Puig, Pierre; Oudard, Stéphane; Bruneval, Patrick; Badoual, Cécile; Cadranel, Jacques; Tartour, Eric

2017-01-01

ABSTRACT Anaplastic lymphoma kinase (ALK) inhibitors have been successfully developed for non-small cell lung carcinoma (NSCLC) displaying chromosomal rearrangements of the ALK gene, but unfortunately resistance invariably occurs. Blockade of the PD-1-PD-L1/2 inhibitory pathway constitutes a breakthrough for the treatment of NSCLC. Some predictive biomarkers of clinical response to this therapy are starting to emerge, such as PD-L1 expression by tumor/stromal cells and infiltration by CD8+ T cells expressing PD-1. To more effectively integrate all of these potential biomarkers of clinical response to immunotherapy, we have developed a multiparametric immunofluorescence technique with automated immune cell counting to comprehensively analyze the tumor microenvironment of ALK-positive adenocarcinoma (ADC). When analyzed as either a continuous or a dichotomous variable, the mean number of tumor cells expressing PD-L1 (p = 0.012) and the percentage of tumor cells expressing PD-L1 were higher in ALK-positive ADC than in EGFR-mutated ADC or WT (non-EGFR-mutated and non-KRAS-mutated) NSCLC. A very strong correlation between PD-L1 expression on tumor cells and intratumoral infiltration by CD8+ T cells was observed, suggesting that an adaptive mechanism may partly regulate this expression. A higher frequency of tumors combining positive PD-L1 expression and infiltration by intratumoral CD8+ T cells or PD-1+CD8+ T cells was also observed in ALK-positive lung cancer patients compared with EGFR-mutated (p = 0.03) or WT patients (p = 0.012). These results strongly suggest that a subgroup of ALK-positive lung cancer patients may constitute good candidates for anti-PD-1/-PD-L1 therapies. PMID:28507793

Photodeposited Pd Nanoparticles with Disordered Structure for Phenylacetylene Semihydrogenation

PubMed Central

Fan, Qining; He, Sha; Hao, Lin; Liu, Xin; Zhu, Yue; Xu, Sailong; Zhang, Fazhi

2017-01-01

Developing effective heterogeneous metal catalysts with high selectivity and satisfactory activity for chemoselective hydrogenation of alkyne to alkene is of great importance in the chemical industry. Herein, we report our efforts to fabricate TiO2-supported Pd catalysts by a photodeposition method at room temperature for phenylacetylene semihydrogenation to styrene. The resulting Pd/TiO2 catalyst, possessing smaller Pd ensembles with ambiguous lattice fringes and more low coordination Pd sites, exhibits higher styrene selectivity compared to two contrastive Pd/TiO2 samples with larger ensembles and well-organized crystal structure fabricated by deposition-precipitation or photodeposition with subsequent thermal treatment at 300 °C. The sample derived from photodeposition exhibits greatly slow styrene hydrogenation in kinetic evaluation because the disordered structure of Pd particles in photodeposited Pd/TiO2 may prevent the formation of β-hydride phases and probably produce more surface H atoms, which may favor high styrene selectivity. PMID:28176843

Photodeposited Pd Nanoparticles with Disordered Structure for Phenylacetylene Semihydrogenation

NASA Astrophysics Data System (ADS)

Fan, Qining; He, Sha; Hao, Lin; Liu, Xin; Zhu, Yue; Xu, Sailong; Zhang, Fazhi

2017-02-01

Developing effective heterogeneous metal catalysts with high selectivity and satisfactory activity for chemoselective hydrogenation of alkyne to alkene is of great importance in the chemical industry. Herein, we report our efforts to fabricate TiO2-supported Pd catalysts by a photodeposition method at room temperature for phenylacetylene semihydrogenation to styrene. The resulting Pd/TiO2 catalyst, possessing smaller Pd ensembles with ambiguous lattice fringes and more low coordination Pd sites, exhibits higher styrene selectivity compared to two contrastive Pd/TiO2 samples with larger ensembles and well-organized crystal structure fabricated by deposition-precipitation or photodeposition with subsequent thermal treatment at 300 °C. The sample derived from photodeposition exhibits greatly slow styrene hydrogenation in kinetic evaluation because the disordered structure of Pd particles in photodeposited Pd/TiO2 may prevent the formation of β-hydride phases and probably produce more surface H atoms, which may favor high styrene selectivity.

cDNA cloning and expression analysis of two distinct Sox8 genes in Paramisgurnus dabryanus (Cypriniformes).

PubMed

Xia, Xiaohua; Zhao, Jie; Du, Qiyan; Chang, Zhongjie

2010-08-01

The Sox9 gene attracts a lot of attention because of its connection with gonadal development and differentiation. However, Sox8, belonging to the same subgroup SoxE, has rarely been studied. To investigate the function as well as the evolutionary origin of SOXE subgroup, we amplified the genomic DNA of Paramisgurnus dabryanu using a pair of degenerate primers. Using rapid amplification of the cDNA ends (RACE), it was discovered that P. dabryanu has two duplicates: Sox8a and Sox8b. Each has an intron of different length in the conserved HMG-box region. The overall sequence similarity of the deduced amino acid of PdSox8a and PdSox8b was 46.26%, and only two amino acids changed in the HMG-box. This is the first evidence showing that there are two distinct duplications of Sox8 genes in Cypriniformes. Southern blot analysis showed only one hybrid band, with lengths 7.4 or 9.2 kb. Both semi-quantitative RT-PCR and real-time quantitative PCR assay displayed that both PdSox8a and PdSox8b are downregulated during early embryonic development. In adult tissues, the two Sox8 genes expressed ubiquitously, and expression levels are particularly high in the gonads and brain. In gonads, both PdSox8a and PdSox8b are expressed at a higher level in the tesis than in the ovary. PdSox8a and PdSox8b may have functional overlaps and are essential for the neuronal development and differentiation of gonads.

Relationship Between Gender, Age, and Weight and the Serum Ionized Calcium Variations in Dog Periodontal Disease Evolution.

PubMed

Carreira, L Miguel; Dias, Daniela; Azevedo, Pedro

2015-06-01

To analyze the relationships between gender, age, weight, and variations in the levels of serum ionized calcium ([iCa(2+)]) during periodontal disease (PD) evolution. In this study, dogs (n = 50) were divided into 5 groups according to the stage of PD: G0 (no PD), G1 (gingivitis), G2 (initial periodontitis), G3 (moderate periodontitis), and G4 (severe periodontitis). Statistically significant correlations were observed between age, [iCa(2+)] levels, and PD stage. Older dogs had lower [iCa(2+)] levels and more advanced PD stages (high positive correlation), and their body weight decreased as PD developed (negative correlation). Lower [iCa(2+)] values were associated with more severe PD. Copyright © 2015 Elsevier Inc. All rights reserved.

Materials Data on Y5(In2Pd)2 (SG:55) by Materials Project

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

Kristin Persson

2016-02-11

Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

Materials Data on Pd(SeBr3)2 (SG:2) by Materials Project

DOE Data Explorer

Kristin Persson

2014-11-02

Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

Materials Data on U(PdS2)2 (SG:88) by Materials Project

DOE Data Explorer

Kristin Persson

2016-02-10

Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

Materials Data on K2PdF4 (SG:12) by Materials Project

DOE Data Explorer

Kristin Persson

2014-11-02

Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

Materials Data on Na17Pd15F48 (SG:1) by Materials Project

DOE Data Explorer

Kristin Persson

2014-07-09

Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

Materials Data on Li2PdO3 (SG:1) by Materials Project

DOE Data Explorer

Kristin Persson

2014-07-09

Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

Materials Data on Y(PdO2)2 (SG:88) by Materials Project

DOE Data Explorer

Kristin Persson

2015-03-07

Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

Materials Data on U2PdS4 (SG:43) by Materials Project

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

Kristin Persson

Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

Effects of alloying element on stabilities, electronic structures, and mechanical properties of Pd-based superalloys

NASA Astrophysics Data System (ADS)

Yan, Pei; Chong, Xiao-Yu; Jiang, Ye-Hua; Feng, Jing

2017-12-01

Not Available Project supported by the Young-Talent Support Programs of Kunming University of Science and Technology, China (Grant No. 11504146) and the National Natural Science Foundation of China (Grant No. 51762028).

Effects of the root bark of Paeonia suffruticosa on mitochondria-mediated neuroprotection in an MPTP-induced model of Parkinson's disease.

PubMed

Kim, Hyo Geun; Park, Gunhyuk; Piao, Ying; Kang, Min Seo; Pak, Youngmi Kim; Hong, Seon-Pyo; Oh, Myung Sook

2014-03-01

Parkinson's disease (PD) is generally characterized by the progressive loss of dopaminergic neurons projecting from the substantia nigra pars compacta (SNpc) to the striatum that results in movement dysfunction, but also entails mitochondrial dysfunction. The purpose of this study is to evaluate the protective effects of Moutan Cortex Radicis (MCE, Moutan peony) on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD-like symptoms and to elucidate the underlying mechanisms of action, with a focus on mitochondrial function. In a rat primary mesencephalic culture system, MCE significantly protected dopaminergic neurons from the neurotoxic effects of 1-methyl-4-phenylpyridinium (MPP(+)), an active form of MPTP. Additionally, in a subacute mouse model of MPTP-induced PD, MCE resulted in enhanced recovery from PD-like motor symptoms, including increased locomotor activity and reduced bradykinesia. MCE increased dopamine availability and protected against MPTP-induced dopaminergic neuronal damage. Moreover, MCE inhibited MPTP-induced mitochondrial dysfunction and resulted in increased expression of phosphorylated Akt, ND9, mitochondrial transcription factor A, and H2AX in the SNpc. Mitochondria-mediated apoptosis was also inhibited, via the regulation of B-cell lymphoma family proteins and the inhibition of cytochrome C release and caspase-3 activation. These results indicate that MCE has neuroprotective effects in PD models and may be useful for preventing or treating PD. Copyright © 2014 Elsevier Ltd. All rights reserved.

A Theoretical Investigation on CO Oxidation by Single-Atom Catalysts M1/γ-Al2O3 (M=Pd, Fe, Co, and Ni).

PubMed

Yang, Tao; Fukuda, Ryoichi; Hosokawa, Saburo; Tanaka, Tsunehiro; Sakaki, Shigeyoshi; Ehara, Masahiro

2017-04-07

Single-atom catalysts have attracted much interest recently because of their excellent stability, high catalytic activity, and remarkable atom efficiency. Inspired by the recent experimental discovery of a highly efficient single-atom catalyst Pd 1 /γ-Al 2 O 3 , we conducted a comprehensive DFT study on geometries, stabilities and CO oxidation catalytic activities of M 1 /γ-Al 2 O 3 (M=Pd, Fe, Co, and Ni) by using slab-model. One of the most important results here is that Ni 1 /Al 2 O 3 catalyst exhibits higher activity in CO oxidation than Pd 1 /Al 2 O 3 . The CO oxidation occurs through the Mars van Krevelen mechanism, the rate-determining step of which is the generation of CO 2 from CO through abstraction of surface oxygen. The projected density of states (PDOS) of 2 p orbitals of the surface O, the structure of CO-adsorbed surface, charge polarization of CO and charge transfer from CO to surface are important factors for these catalysts. Although the binding energies of Fe and Co with Al 2 O 3 are very large, those of Pd and Ni are small, indicating that the neighboring O atom is not strongly bound to Pd and Ni, which leads to an enhancement of the reactivity of the O atom toward CO. The metal oxidation state is suggested to be one of the crucial factors for the observed catalytic activity.

[Development of a pre-dehydration assessment sheet: Research among elderly individuals who regularly visited an elderly-care institution].

PubMed

Taniguchi, Hideki; Akiyama, Masako; Gomi, Ikuko; Kimura, Mamiko

2015-01-01

In the present study, we defined the state of pre-dehydration (PD) as the suspected loss of body fluids, not accompanied by subjective symptoms, where the serum osmotic pressure ranges from 292 to 300 mOsm/kg・H2O. The goal of this study was to develop a PD assessment sheet based on the results of sensitivity and specificity testing among elderly individuals. We evaluated the serum osmotic pressure in 70 subjects >65 years of age who regularly visited an elderly-care institution. We then determined the associations between the serum osmotic pressure and various dehydration-related diagnostic factors identified in our previous study. Risk factors for dehydration were evaluated using a logistic regression analysis and allotted points according to the odds ratio. PD was confirmed in 15 subjects (21.4%) using measurements of the serum osmotic pressure. We developed a PD assessment sheet that consisted of six items: (1) Female gender (4 points), (2) BMI≥25 kg/m2 (5 points), (3) Diuretics (6 points), (4) Laxatives (2 points), (5) Dry skin (2 points) and (6) A desire to consume cold drinks or foods (2 points). The cutoff value at which the risk of PD was high was set at 9 points (total of 21 points) (sensitivity 0.73, specificity 0.82; P<0.001). In this study, we found that 21.4% of the elderly subjects had PD. Using these data, we developed an effective noninvasive tool for detecting PD among elderly individuals.

The Norwegian Computerized Adaptive Test of Personality Disorder-Static Form (CAT-PD-SF): Reliability, Factor Structure, and Relationships With Personality Functioning.

PubMed

Thimm, Jens C

2017-12-01

The Computerized Adaptive Test of Personality Disorder-Static Form (CAT-PD-SF) is a self-report inventory developed to assess pathological personality traits. The current study explored the reliability and higher order factor structure of the Norwegian version of the CAT-PD-SF and the relationships between the CAT-PD traits and domains of personality functioning in an undergraduate student sample ( N = 375). In addition to the CAT-PD-SF, the short form of the Severity Indices of Personality Problems and the Brief Symptom Inventory were administered. The results showed that the Norwegian CAT-PD-SF has good score reliability. Factor analysis of the CAT-PD-SF scales indicated five superordinate factors that correspond to the trait domains of the alternative DSM-5 model for personality disorders. The CAT-PD traits were highly predictive of impaired personality functioning after controlling for psychological distress. It is concluded that the CAT-PD-SF is a promising tool for the assessment of personality disorder traits.

Ordered PdCu-Based Nanoparticles as Bifunctional Oxygen-Reduction and Ethanol-Oxidation Electrocatalysts

DOE PAGES

Jiang, Kezhu; Wang, Pengtang; Guo, Shaojun; ...

2016-06-02

Here, the development of superior non-platinum electrocatalysts for enhancing the electrocatalytic activity and stability for the oxygen-reduction reaction (ORR) and liquid fuel oxidation reaction is very important for the commercialization of fuel cells,but still agreat challenge.Herein, we demonstrate a new colloidal chemistry technique for making structurally ordered PdCu-based nanoparticles (NPs) with composition control from PdCu to PdCuNi and PtCuCo.Under the dual tuning on the composition and intermetallic phase,the ordered PdCuCo NPs exhibit better activity and much enhanced stability for ORR and ethanol-oxidation reaction (EOR)than those of disordered PdCuM NPs,the commercial Pt/Cand Pd/C catalysts.The density functional theory (DFT)calculations reveal that themore » improved ORR activity on the PdCuM NPs stems from the catalytically active hollow sites arising from the ligand effect and the compressive strain on thePd surface owing to the smaller atomic size of Cu, Co,and Ni.« less

Financial implications to Medicare from changing the dialysis modality mix under the bundled prospective payment system.

PubMed

Liu, Frank X; Walton, Surrey M; Leipold, Robert; Isbell, Deborah; Golper, Thomas A

2014-01-01

The economic burden of treating end-stage renal disease (ESRD) continues to grow. As one response, effective January 1, 2011, Medicare implemented a bundled prospective payment system (PPS, including injectable drugs) for dialysis patients. This study investigated the 5-year budget impact on Medicare under the new PPS of changes in the distribution of patients undergoing peritoneal dialysis (PD), in-center hemodialysis (ICHD), and home hemodialysis (HHD). An Excel-based budget impact model was created to assess dialysis-associated Medicare costs. The model accounted for dialysis access establishment, the current monthly capitation physician payment for ESRD, Medicare dialysis payments (including start-up costs), training, oral drug costs, and the costs and probabilities of adverse events including access failure, hospitalization for access infection, pneumonia, septicemia, and cardiovascular events. United States Renal Data System (USRDS) data were used to project the US Medicare dialysis patient population across time. The baseline scenario assumed a stable distribution of PD (7.7%), HHD (1.3%) and ICHD (91.0%) over 5 years. Three comparison scenarios raised the proportions of PD and HHD by (1) 1% and 0.5%, (2) 2% and 0.75%, and (3) 3% and 1% each year; a fourth scenario held HHD constant and lowered PD by 1% per year. Under the bundled PPS, scenarios that increased PD and HHD from 7.7% and 1.3% over 5 years resulted in cumulative savings to Medicare of $114.8M (Scenario 1, 11.7% PD and 3.3% HHD at year 5), $232.9M (Scenario 2, 15.7% PD and 4.3% HHD at year 5), and $350.9M (Scenario 3, 19.7% PD and 5.3% HHD at year 5). When the PD population was decreased from 7.7% in 2013 to 3.7% by 2017 with a constant HHD population, the total Medicare payment for dialysis patients increased by over $121.2M. Under Medicare bundled PPS, increasing the proportion of patients on PD and HHD vs ICHD could generate substantial savings in dialysis-associated costs to Medicare. Copyright © 2014 International Society for Peritoneal Dialysis.

Modulating PD-L1 expression in multiple myeloma: an alternative strategy to target the PD-1/PD-L1 pathway.

PubMed

Tremblay-LeMay, Rosemarie; Rastgoo, Nasrin; Chang, Hong

2018-03-27

Even with recent advances in therapy regimen, multiple myeloma patients commonly develop drug resistance and relapse. The relevance of targeting the PD-1/PD-L1 axis has been demonstrated in pre-clinical models. Monotherapy with PD-1 inhibitors produced disappointing results, but combinations with other drugs used in the treatment of multiple myeloma seemed promising, and clinical trials are ongoing. However, there have recently been concerns about the safety of PD-1 and PD-L1 inhibitors combined with immunomodulators in the treatment of multiple myeloma, and several trials have been suspended. There is therefore a need for alternative combinations of drugs or different approaches to target this pathway. Protein expression of PD-L1 on cancer cells, including in multiple myeloma, has been associated with intrinsic aggressive features independent of immune evasion mechanisms, thereby providing a rationale for the adoption of new strategies directly targeting PD-L1 protein expression. Drugs modulating the transcriptional and post-transcriptional regulation of PD-L1 could represent new therapeutic strategies for the treatment of multiple myeloma, help potentiate the action of other drugs or be combined to PD-1/PD-L1 inhibitors in order to avoid the potentially problematic combination with immunomodulators. This review will focus on the pathophysiology of PD-L1 expression in multiple myeloma and drugs that have been shown to modulate this expression.

The Concept of Prodromal Parkinson’s Disease

PubMed Central

Mahlknecht, Philipp; Seppi, Klaus; Poewe, Werner

2015-01-01

Parkinson’s disease (PD) is currently clinically defined by a set of cardinal motor features centred on the presence of bradykinesia and at least one additional motor symptom out of tremor, rigidity or postural instability. However, converging evidence from clinical, neuropathological, and imaging research suggests initiation of PD-specific pathology prior to appearance of these classical motor signs. This latent phase of neurodegeneration in PD is of particular relevance in relation to the development of disease-modifying or neuroprotective therapies which would require intervention at the earliest stages of disease. A key challenge in PD research, therefore, is to identify and validate markers for the preclinical and prodromal stages of the illness. Currently, several nonmotor symptoms have been associated with an increased risk to develop PD in otherwise healthy individuals and ongoing research is aimed at validating a variety of candidate PD biomarkers based on imaging, genetic, proteomic, or metabolomic signatures, supplemented by work on tissue markers accessible to minimally invasive biopsies. In fact, the recently defined MDS research criteria for prodromal PD have included combinations of risk and prodromal markers allowing to define target populations of future disease modification trials. PMID:26485429

Genetic Testing and Parkinson Disease: Assessment of Patient Knowledge, Attitudes, and Interest

PubMed Central

Wood, Elisabeth McCarty; Xie, Sharon X.; Siderowf, Andrew; Van Deerlin, Vivianna M.

2012-01-01

The most common genetic contributor to late-onset Parkinson disease (PD) is the LRRK2 gene. In order to effectively integrate LRRK2 genetic testing into clinical practice, a strategy tailored to the PD population must be developed. We assessed 168 individuals with PD for baseline knowledge of genetics, perceived risk, and interest and opinions regarding genetic counseling and testing. Most participants felt that they were familiar with general genetics terms but overall knowledge levels were low, with an average score of 55%. The majority of participants thought it was likely they inherited a PD gene (72%), believed genetic testing for PD would be useful (86%), and were interested in genetic testing (59%) and genetic counseling (56%). However, only a few participants had heard of any genetic tests for PD (29%) or LRRK2 (10%). There appears to be a significant level of interest in genetics and genetic testing within the PD population, but a considerable deficit in genetics knowledge and an over-estimation of risk. Genetic education and counseling tools to address these needs were developed to provide patients with the ability to make informed and knowledgeable genetic testing decisions. PMID:21476119

PD-1 suppresses development of humoral responses that protect against Tn-bearing tumors

PubMed Central

Haro, Marcela A.; Littrell, Chad A.; Yin, Zhaojun; Huang, Xuefei; Haas, Karen M.

2017-01-01

Tn is a carbohydrate antigen uniquely exposed on tumor mucins and thus, an ideal target for immunotherapy. However, it has been difficult to elicit protective antibody responses against Tn antigen and other tumor associated carbohydrate antigens. Our study demonstrates this can be attributed to PD-1 immuno-inhibition. Our data show a major role for PD-1 in suppressing mucin- and Tn-specific B-cell activation, expansion, and antibody production important for protection against Tn-bearing tumor cells. These Tn/mucin-specific B cells belong to the innate-like B-1b cell subset typically responsible for T cell–independent antibody responses. Interestingly, PD-1–mediated regulation is B cell–intrinsic and CD4+ cells play a key role in supporting Tn/mucin-specific B cell antibody production in the context of PD-1 deficiency. Mucin-reactive antibodies produced in the absence of PD-1 inhibition largely belong to the IgM subclass and elicit potent antitumor effects via a complement-dependent mechanism. The identification of this role for PD-1 in regulating B cell–dependent antitumor immunity to Tn antigen highlights an opportunity to develop new therapeutic strategies targeting tumor associated carbohydrate antigens. PMID:27856425

Factors associated with peritoneal dialysis catheter complications in children.

PubMed

Stewart, Camille L; Acker, Shannon N; Pyle, Laura L; Kulungowski, Ann; Cadnapaphornchai, Melissa; Bruny, Jennifer L; Karrer, Frederick

2016-01-01

Peritoneal dialysis (PD) is a common method of renal replacement therapy for children. However, placement of PD catheters has risk, and some are never used. We conducted a retrospective chart review of children with a PD catheter placed between 2000 and 2014. Logistic regression analyses were used to identify covariates associated with complications. We identified 175 children with PD catheters. 110 complications developed in 80 children (45.7%). Complications including unexpected return to the operating room and peritonitis increased as the length of time a catheter was in place increased. Children who weighed <12.4 kg had 3.2 times greater odds of developing a leak (95% CI 1.21-8.63, p=0.02). Twelve children never used their PD catheters, 9 with acute kidney injury (AKI) who recovered from their disease more quickly than expected. No covariate was associated with nonuse. Complications with PD catheters are common and increase the longer catheters are in place. Lower weight children are at greater risk of PD catheter leak. Decreased initial volumes of dialysate in smaller children may mitigate this risk. Nonuse may be reduced if dialysis is permitted the day of placement for children with AKI. Copyright © 2016 Elsevier Inc. All rights reserved.

Mass Spectrometric Methodologies for Investigating the Metabolic Signatures of Parkinson's Disease: Current Progress and Future Perspectives.

PubMed

Gill, Emily L; Koelmel, Jeremy P; Yost, Richard A; Okun, Michael S; Vedam-Mai, Vinata; Garrett, Timothy J

2018-03-06

Parkinson's disease (PD) is a neurodegenerative disorder resulting from the loss of dopaminergic neurons of the substantia nigra as well as degeneration of motor and nonmotor basal ganglia circuitries. Typically known for classical motor deficits (tremor, rigidity, bradykinesia), early stages of the disease are associated with a large nonmotor component (depression, anxiety, apathy, etc.). Currently, there are no definitive biomarkers of PD, and the measurement of dopamine metabolites does not allow for detection of prodromal PD nor does it aid in long-term monitoring of disease progression. Given that PD is increasingly recognized as complex and heterogeneous, involving several neurotransmitters and proteins, it is of importance that we advance interdisciplinary studies to further our knowledge of the molecular and cellular pathways that are affected in PD. This approach will possibly yield useful biomarkers for early diagnosis and may assist in the development of disease-modifying therapies. Here, we discuss preanalytical factors associated with metabolomics studies, summarize current mass spectrometric methodologies used to evaluate the metabolic signature of PD, and provide future perspectives of the rapidly developing field of MS in the context of PD.

The rise of practice development with/in reformed bureaucracy: discourse, power and the government of nursing.

PubMed

Rudge, Trudy; Holmes, Dave; Perron, Amélie

2011-10-01

Using a neo-Foucauldian approach, a critique of texts explicitly dealing with the definitional work for practice development (PD) was undertaken. PD has been taken up by many organizations as a way of focusing on nurses' practices to benefit patients and the organization. Literature pertaining to the PD phenomenon was examined and the present study explores those texts accomplishing definitional work. The discourse corpus collected together articles in nursing journals, book chapters and textbooks. The corpus was analysed using the discourse analysis method. PD uses and manipulates its location in a network of managerialism, evidence-based nursing, safety and quality discourses in healthcare to verify (and confirm) its definition and its position as central to progress in nursing practice. We argue that while PD is portrayed as 'emancipatory' and transforming, nurses bear the responsibility for the system and its failures in a web of intricate power relations. The present study offers a review of the PD ideology in nursing where a critical perspective has yet to be found. Nursing managers should understand that PD is not a panacea for improving patient care. © 2011 Blackwell Publishing Ltd.

Facile synthesis of hierarchical dendritic PtPd nanogarlands supported on reduced graphene oxide with enhanced electrocatalytic properties

NASA Astrophysics Data System (ADS)

Li, Shan-Shan; Zheng, Jie-Ning; Ma, Xiaohong; Hu, Yuan-Yuan; Wang, Ai-Jun; Chen, Jian-Rong; Feng, Jiu-Ju

2014-05-01

A simple and facile method is developed for one-pot preparation of hierarchical dendritic PtPd nanogarlands supported on reduced graphene oxide (PtPd/RGO) at room temperature, without using any seed, organic solvent, or complex apparatus. It is found that octylphenoxypolyethoxyethanol (NP-40) as a soft template and its amount are critical to the formation of PtPd garlands. The as-prepared nanocomposites are further applied to methanol and ethanol oxidation with significantly enhanced electrocatalytic activity and better stability in alkaline media.A simple and facile method is developed for one-pot preparation of hierarchical dendritic PtPd nanogarlands supported on reduced graphene oxide (PtPd/RGO) at room temperature, without using any seed, organic solvent, or complex apparatus. It is found that octylphenoxypolyethoxyethanol (NP-40) as a soft template and its amount are critical to the formation of PtPd garlands. The as-prepared nanocomposites are further applied to methanol and ethanol oxidation with significantly enhanced electrocatalytic activity and better stability in alkaline media. Electronic supplementary information (ESI) available: Experimental section, Fig. S1-S12 and Tables S1 and S2. See DOI: 10.1039/c3nr06808k

Facile synthesis of palladium nanoparticles supported on multi-walled carbon nanotube for efficient hydrogenation of biomass-derived levulinic acid

NASA Astrophysics Data System (ADS)

Yan, Kai; Lafleur, Todd; Liao, Jiayou

2013-09-01

Different loading of palladium (Pd) nanoparticles were successfully fabricated on multi-walled carbon nanotubes using Pd acetylacetonate as the precursor via a simple liquid impregnation method. The crystal phase, morphology, textural structure and the chemical state of the resulting Pd nanoparticles (Pd/CNT) catalysts were studied and the characterization results indicated that the uniform dispersion of small Pd nanoparticles with the size range of 1.0-4.5 nm was achieved. The synthesized Pd/CNT catalysts exhibited efficient performance for the catalytic hydrogenation of biomass-derived levulinic acid into biofuel γ-valerolactone. In comparison with the commercial 5 wt% Pd/C and the 5 wt% Pd/CNT catalyst prepared by Pd nitrate precursor, much higher activities were achieved, whereas the biofuel γ-valerolactone was highly produced with 56.3 % yield at 57.6 % conversion of levulinic acid on the 5 wt% Pd/CNT catalyst under mild conditions. The catalyst developed in this work may be a good candidate for the wide applications in the hydrogenation.

A motif for infinite metal atom wires.

PubMed

Yin, Xi; Warren, Steven A; Pan, Yung-Tin; Tsao, Kai-Chieh; Gray, Danielle L; Bertke, Jeffery; Yang, Hong

2014-12-15

A new motif for infinite metal atom wires with tunable compositions and properties is developed based on the connection between metal paddlewheel and square planar complex moieties. Two infinite Pd chain compounds, [Pd4(CO)4(OAc)4Pd(acac)2] 1 and [Pd4(CO)4(TFA)4Pd(acac)2] 2, and an infinite Pd-Pt heterometallic chain compound, [Pd4(CO)4(OAc)4Pt(acac)2] 3, are identified by single-crystal X-ray diffraction analysis. In these new structures, the paddlewheel moiety is a Pd four-membered ring coordinated by bridging carboxylic ligands and μ2 carbonyl ligands. The planar moiety is either Pd(acac)2 or Pt(acac)2 (acac = acetylacetonate). These moieties are connected by metallophilic interactions. The results showed that these one-dimensional metal wire compounds have photoluminescent properties that are tunable by changing ligands and metal ions. 3 can also serve as a single source precursor for making Pd4Pt bimetallic nanostructures with precise control of metal composition. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Professional development for science teachers.

PubMed

Wilson, Suzanne M

2013-04-19

The Next Generation Science Standards will require large-scale professional development (PD) for all science teachers. Existing research on effective teacher PD suggests factors that are associated with substantial changes in teacher knowledge and practice, as well as students' science achievement. But the complexity of the U.S. educational system continues to thwart the search for a straightforward answer to the question of how to support teachers. Interventions that take a systemic approach to reform hold promise for improving PD effectiveness.

Interference from retrieval cues in Parkinson's disease.

PubMed

Crescentini, Cristiano; Marin, Dario; Del Missier, Fabio; Biasutti, Emanuele; Shallice, Tim

2011-11-01

Existing studies on memory interference in Parkinson's disease (PD) patients have provided mixed results and it is unknown whether PD patients have problems in overcoming interference from retrieval cues. We investigated this issue by using a part-list cuing paradigm. In this paradigm, after the study of a list of items, the presentation of some of these items as retrieval cues hinders the recall of the remaining ones. We tested PD patients' (n = 19) and control participants' (n = 16) episodic memory in the presence and absence of part-list cues, using initial-letter probes, and following either weak or strong serial associative encoding of list items. Both PD patients and control participants showed a comparable and significant part-list cuing effect after weak associative encoding (13% vs. 12% decrease in retrieval in part-list cuing vs. no part-list cuing -control- conditions in PD patients and control participants, respectively), denoting a similar effect of cue-driven interference in the two populations when a serial retrieval strategy is hard to develop. However, only PD patients showed a significant part-list cuing effect after strong associative encoding (20% vs. 5% decrease in retrieval in patients and controls, respectively). When encoding promotes the development of an effective serial retrieval strategy, the presentation of part-list cues has a specifically disruptive effect in PD patients. This indicates problems in strategic retrieval, probably related to PD patients' increased tendency to rely on external cues. Findings in control conditions suggest that less effective encoding may have contributed to PD patients' memory performance.

Altered Pharyngeal Muscles in Parkinson Disease

PubMed Central

Mu, Liancai; Sobotka, Stanislaw; Chen, Jingming; Su, Hungxi; Sanders, Ira; Adler, Charles H.; Shill, Holly A.; Caviness, John N.; Samanta, Johan E.; Beach, Thomas G.

2012-01-01

Dysphagia (impaired swallowing) is common in Parkinson disease (PD) patients and is related to aspiration pneumonia, the primary cause of death in PD. Therapies that ameliorate the limb motor symptoms of PD are ineffective for dysphagia. This suggests that the pathophysiology of PD dysphagia may differ from that affecting limb muscles but little is known about potential neuromuscular abnormalities in the swallowing muscles in PD. This study examined the fiber histochemistry of pharyngeal constrictor (PC) and cricopharyngeal (CP) sphincter muscles in postmortem specimens from 8 PD and 4 age-matched control patients. Pharyngeal muscles in PD patients exhibited many atrophic fibers, fiber type grouping, and fast-to-slow myosin heavy chain transformation. These alterations indicate that the pharyngeal muscles experienced neural degeneration and regeneration over the course of PD. Notably, the PD patients with dysphagia had a higher percentage of atrophic myofibers vs. with those without dysphagia and controls. The fast-to-slow fiber type transition is consistent with abnormalities in swallowing, slow movement of food and increased tone in the CP sphincter in PD patients. The alterations in the pharyngeal muscles may play a pathogenic role in the development of dysphagia in PD patients. PMID:22588389

Altered pharyngeal muscles in Parkinson disease.

PubMed

Mu, Liancai; Sobotka, Stanislaw; Chen, Jingming; Su, Hungxi; Sanders, Ira; Adler, Charles H; Shill, Holly A; Caviness, John N; Samanta, Johan E; Beach, Thomas G

2012-06-01

Dysphagia (impaired swallowing) is common in patients with Parkinson disease (PD) and is related to aspiration pneumonia, the primary cause of death in PD. Therapies that ameliorate the limb motor symptoms of PD are ineffective for dysphagia. This suggests that the pathophysiology of PD dysphagia may differ from that affecting limb muscles, but little is known about potential neuromuscular abnormalities in the swallowing muscles in PD. This study examined the fiber histochemistry of pharyngeal constrictor and cricopharyngeal sphincter muscles in postmortem specimens from 8 subjects with PD and 4 age-matched control subjects. Pharyngeal muscles in subjects with PD exhibited many atrophic fibers, fiber type grouping, and fast-to-slow myosin heavy chain transformation. These alterations indicate that the pharyngeal muscles experienced neural degeneration and regeneration over the course of PD. Notably, subjects with PD with dysphagia had a higher percentage of atrophic myofibers versus with those without dysphagia and controls. The fast-to-slow fiber-type transition is consistent with abnormalities in swallowing, slow movement of food, and increased tone in the cricopharyngeal sphincter in subjects with PD. The alterations in the pharyngeal muscles may play a pathogenic role in the development of dysphagia in subjects with PD.

Combinatorial high-throughput optical screening of high performance Pd alloy cathode for hybrid Li-air battery.

PubMed

Jun, Young Jin; Park, Sung Hyeon; Woo, Seong Ihl

2014-12-08

Combinatorial high-throughput optical screening method was developed to find the optimum composition of highly active Pd-based catalysts at the cathode of the hybrid Li-air battery. Pd alone, which is one-third the cost of Pt, has difficulty in replacing Pt; therefore, the integration of other metals was investigated to improve its performance toward oxygen reduction reaction (ORR). Among the binary Pd-based catalysts, the composition of Pd-Ir derived catalysts had higher performance toward ORR compared to other Pd-based binary combinations. The composition at 88:12 at. % (Pd: Ir) showed the highest activity toward ORR at the cathode of the hybrid Li-air battery. The prepared Pd(88)Ir(12)/C catalyst showed a current density of -2.58 mA cm(-2) at 0.8 V (vs RHE), which was around 30% higher compared to that of Pd/C (-1.97 mA cm(-2)). When the prepared Pd(88)Ir(12)/C catalyst was applied to the hybrid Li-air battery, the polarization of the cell was reduced and the energy efficiency of the cell was about 30% higher than that of the cell with Pd/C.

Selective hydrodechlorination of 1,2-dichloroethane catalyzed by trace Pd decorated Ag/Al2O3 catalysts prepared by galvanic replacement

NASA Astrophysics Data System (ADS)

Sun, Jingya; Han, Yuxiang; Fu, Heyun; Wan, Haiqin; Xu, Zhaoyi; Zheng, Shourong

2018-01-01

Ag catalysts decorated by trace Pd supported on γ-Al2O3 with different structure and chemical properties were prepared using a combined impregnation and galvanic replacement method. For comparison, monometallic Ag/γ-Al2O3 and Pd/γ-Al2O3 catalysts were prepared using the impregnation method. Gas-phase catalytic hydrodechlorination of 1,2-dichloroethane to ethylene was investigated on those catalysts. The structures and chemical compositions of bimetallic Pd-Ag particles in the catalysts were controlled by adjusting Pd replacement amount. The as-prepared catalysts were characterized by X-ray diffraction, transmission electron microscopy, UV-vis diffuse reflectance spectroscopy, X-ray photoelectron spectroscopy, and in-situ FTIR spectroscopy of CO adsorption. The results demonstrated that contiguous Pd sites dominated in the monometallic Pd/γ-Al2O3 catalyst, while Pd atoms were separately decorated on the surface of Ag particles in the bimetallic Pd-Ag/γ-Al2O3 catalysts when Pd replacement amount was below 0.30 wt.%. At Pd replacement amount of 0.30 wt.%, Pd ensembles with contiguous Pd sites developed in the bimetallic catalyst. Thus, monometallic Pd/γ-Al2O3 catalyst displayed negligible ethylene selectivity toward the catalytic hydrodechlorination of 1,2-dichloroethane, while bimetallic Pd-Ag/γ-Al2O3 catalyst with a Pd replacement amount of 0.13 wt.% exhibited 94.6% of ethylene selectivity. Furthermore, selectivity to incompletely dechlorinated byproduct chloroethylene decreased with Pd replacement amount, due to the enhanced decoration effect of Pd on large Ag ensembles. Findings in this work provide a promising bimetallic catalyst prepared by galvanic replacement for the selective catalytic hydrodechlorination of 1,2-dichloroethane.

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.

"We Always Want to Get Better": Teachers' Voices on Professional Development

ERIC Educational Resources Information Center

Parise, Leigh M.; Finkelstein, Carla; Alterman, Emma

2015-01-01

Through the Innovative Professional Development (iPD) Challenge, the Bill & Melinda Gates Foundation has invested in helping school districts and networks redesign their professional development systems to serve educators better and improve student performance. MDRC's evaluation of the iPD Challenge involves case studies and multiple rounds of…

The role of the amygdala in the pathophysiology of panic disorder: evidence from neuroimaging studies

PubMed Central

2012-01-01

Although the neurobiological mechanisms underlying panic disorder (PD) are not yet clearly understood, increasing amount of evidence from animal and human studies suggests that the amygdala, which plays a pivotal role in neural network of fear and anxiety, has an important role in the pathogenesis of PD. This article aims to (1) review the findings of structural, chemical, and functional neuroimaging studies on PD, (2) relate the amygdala to panic attacks and PD development, (3) discuss the possible causes of amygdalar abnormalities in PD, (4) and suggest directions for future research. PMID:23168129

Person-Centered Care in the Home Setting for Parkinson's Disease: Operation House Call Quality of Care Pilot Study.

PubMed

Hack, Nawaz; Akbar, Umer; Monari, Erin H; Eilers, Amanda; Thompson-Avila, Amanda; Hwynn, Nelson H; Sriram, Ashok; Haq, Ihtsham; Hardwick, Angela; Malaty, Irene A; Okun, Michael S

2015-01-01

Objective. (1) To evaluate the feasibility of implementing and evaluating a home visit program for persons with Parkinson's disease (PD) in a rural setting. (2) To have movement disorders fellows coordinate and manage health care delivery. Background. The University of Florida, Center for Movement Disorders and Neurorestoration established Operation House Call to serve patients with PD who could not otherwise afford to travel to an expert center or to pay for medical care. PD is known to lead to significant disability, frequent hospitalization, early nursing home placement, and morbidity. Methods. This was designed as a quality improvement project. Movement disorders fellows travelled to the home(s) of underserved PD patients and coordinated their clinical care. The diagnosis of Parkinson's disease was confirmed using standardized criteria, and the Unified Parkinson's Disease Rating Scale was performed and best treatment practices were delivered. Results. All seven patients have been followed up longitudinally every 3 to 6 months in the home setting, and they remain functional and independent. None of the patients have been hospitalized for PD related complications. Each patient has a new updatable electronic medical record. All Operation House Call cases are presented during video rounds for the interdisciplinary PD team to make recommendations for care (neurology, neurosurgery, neuropsychology, psychiatry, physical therapy, occupational therapy, speech therapy, and social work). One Operation House Call patient has successfully received deep brain stimulation (DBS). Conclusion. This program is a pilot program that has demonstrated that it is possible to provide person-centered care in the home setting for PD patients. This program could provide a proof of concept for the construction of a larger visiting physician or nurse program.

Are hospitalized Parkinson's disease patients more likely to carry a do-not-resuscitate order?

PubMed

Mahajan, Abhimanyu; Patel, Achint; Nadkarni, Girish; Sidiropoulos, Christos

2017-03-01

While DNR utilization is a complex subjective phenomenon, the effect of such a decision can collectively influence attitudes of care. The role of palliative care in advanced PD has been under appreciated. We reviewed the Healthcare Cost and Utilization Project's National Inpatient Sample (NIS) database from 2012 for all hospitalizations ⩾65years. We identified PD by using ICD-9-CM code 332.0 and DNR status with ICD code - V49.86 entered during the same admission as a secondary diagnosis. We estimated risk of mortality by the 3M™ All Patient Refined DRG (APR DRG) classification System and generated multivariate regression models to assess associations between DNR and PD after adjusting for confounders. Finally, we tested for interaction by risk of mortality. We analyzed 12,700,000 hospitalizations with age ⩾65years in 2012, of which 246625 (1.94%) pts had PD. Proportion of DNR utilization was higher among PD patients vs. those without, 20895 (8.47%) vs. 723090 (5.8%) (p<0.01). In multivariable regression analysis, PD patients were associated with higher odds of DNR utilization [Adjusted Odds ratio (aOR): 1.26, 95% CI: 1.21, 1.30, p<0.001]. Finally, the odds of DNR utilization increased significantly with APR-DRG stage [aOR: 1 vs. 1.61 (Stage 2) vs. 2.46 (Stage 3) vs. 3.61 (Stage 4); p<0.0001]. PD patients have higher odds of DNR utilization than the general population, which worsens with increasing objective risk of mortality. This is likely correlated with perception of end of life and importance of QOL with increasing severity of overall illness. Copyright © 2016 Elsevier Ltd. All rights reserved.

Alterations of immune response of non-small cell lung cancer with Azacytidine

PubMed Central

Easwaran, Hariharan; Mohammad, Helai P.; Vendetti, Frank; VanCriekinge, Wim; DeMeyer, Tim; Du, Zhengzong; Parsana, Princy; Rodgers, Kristen; Yen, Ray-Whay; Zahnow, Cynthia A.; Taube, Janis M.; Brahmer, Julie R.; Tykodi, Scott S.; Easton, Keith; Carvajal, Richard D.; Jones, Peter A.; Laird, Peter W.; Weisenberger, Daniel J.; Tsai, Salina; Juergens, Rosalyn A.; Topalian, Suzanne L.; Rudin, Charles M.; Brock, Malcolm V.; Pardoll, Drew; Baylin, Stephen B.

2013-01-01

Innovative therapies are needed for advanced Non-Small Cell Lung Cancer (NSCLC). We have undertaken a genomics based, hypothesis driving, approach to query an emerging potential that epigenetic therapy may sensitize to immune checkpoint therapy targeting PD-L1/PD-1 interaction. NSCLC cell lines were treated with the DNA hypomethylating agent azacytidine (AZA – Vidaza) and genes and pathways altered were mapped by genome-wide expression and DNA methylation analyses. AZA-induced pathways were analyzed in The Cancer Genome Atlas (TCGA) project by mapping the derived gene signatures in hundreds of lung adeno (LUAD) and squamous cell carcinoma (LUSC) samples. AZA up-regulates genes and pathways related to both innate and adaptive immunity and genes related to immune evasion in a several NSCLC lines. DNA hypermethylation and low expression of IRF7, an interferon transcription factor, tracks with this signature particularly in LUSC. In concert with these events, AZA up-regulates PD-L1 transcripts and protein, a key ligand-mediator of immune tolerance. Analysis of TCGA samples demonstrates that a significant proportion of primary NSCLC have low expression of AZA-induced immune genes, including PD-L1. We hypothesize that epigenetic therapy combined with blockade of immune checkpoints – in particular the PD-1/PD-L1 pathway – may augment response of NSCLC by shifting the balance between immune activation and immune inhibition, particularly in a subset of NSCLC with low expression of these pathways. Our studies define a biomarker strategy for response in a recently initiated trial to examine the potential of epigenetic therapy to sensitize patients with NSCLC to PD-1 immune checkpoint blockade. PMID:24162015

Common variant rs356182 near SNCA defines a Parkinson's disease endophenotype.

PubMed

Cooper, Christine A; Jain, Nimansha; Gallagher, Michael D; Weintraub, Daniel; Xie, Sharon X; Berlyand, Yosef; Espay, Alberto J; Quinn, Joseph; Edwards, Karen L; Montine, Thomas; Van Deerlin, Vivianna M; Trojanowski, John; Zabetian, Cyrus P; Chen-Plotkin, Alice S

2017-01-01

Parkinson's disease (PD) presents clinically with several motor subtypes that exhibit variable treatment response and prognosis. Here, we investigated genetic variants for their potential association with PD motor phenotype and progression. We screened 10 SNPs, previously associated with PD risk, for association with tremor-dominant (TD) versus postural-instability gait disorder (PIGD) motor subtypes. SNPs that correlated with the TD/PIGD ratio in a discovery cohort of 251 PD patients were then evaluated in a multi-site replication cohort of 559 PD patients. SNPs associated with motor phenotype in both cross-sectional cohorts were next evaluated for association with (1) rates of motor progression in a longitudinal subgroup of 230 PD patients and (2) brain alpha-synuclein ( SNCA ) expression in the GTEx (Genotype-Tissue Expression project) consortium database. Genotype at rs356182, near SNCA , correlated with the TD/PIGD ratio in both the discovery (Bonferroni-corrected P = 0.04) and replication cohorts ( P = 0.02). The rs356182 GG genotype was associated with a more tremor-predominant phenotype and predicted a slower rate of motor progression (1-point difference in annual rate of UPDRS-III motor score change, P = 0.01). The rs356182 genotype was associated with SNCA expression in the cerebellum ( P = 0.005). Our study demonstrates that the GG genotype at rs356182 provides molecular definition for a clinically important endophenotype associated with (1) more tremor-predominant motor phenomenology, (2) slower rates of motor progression, and (3) decreased brain expression of SNCA . Such molecularly defined endophenotyping in PD may benefit both clinical trial design and tailoring of clinical care as we enter the era of precision medicine.

Cerebellar Influence on Motor Cortex Plasticity: Behavioral Implications for Parkinson’s Disease

PubMed Central

Kishore, Asha; Meunier, Sabine; Popa, Traian

2014-01-01

Normal motor behavior involves the creation of appropriate activity patterns across motor networks, enabling firing synchrony, synaptic integration, and normal functioning of these networks. Strong topography-specific connections among the basal ganglia, cerebellum, and their projections to overlapping areas in the motor cortices suggest that these networks could influence each other’s plastic responses and functions. The defective striatal signaling in Parkinson’s disease (PD) could therefore lead to abnormal oscillatory activity and aberrant plasticity at multiple levels within the interlinked motor networks. Normal striatal dopaminergic signaling and cerebellar sensory processing functions influence the scaling and topographic specificity of M1 plasticity. Both these functions are abnormal in PD and appear to contribute to the abnormal M1 plasticity. Defective motor map plasticity and topographic specificity within M1 could lead to incorrect muscle synergies, which could manifest as abnormal or undesired movements, and as abnormal motor learning in PD. We propose that the loss of M1 plasticity in PD reflects a loss of co-ordination among the basal ganglia, cerebellar, and cortical inputs which translates to an abnormal plasticity of motor maps within M1 and eventually to some of the motor signs of PD. The initial benefits of dopamine replacement therapy on M1 plasticity and motor signs are lost during the progressive course of disease. Levodopa-induced dyskinesias in patients with advanced PD is linked to a loss of M1 sensorimotor plasticity and the attenuation of dyskinesias by cerebellar inhibitory stimulation is associated with restoration of M1 plasticity. Complimentary interventions should target reestablishing physiological communication between the striatal and cerebellar circuits, and within striato-cerebellar loop. This may facilitate correct motor synergies and reduce abnormal movements in PD. PMID:24834063

Person-Centered Care in the Home Setting for Parkinson's Disease: Operation House Call Quality of Care Pilot Study

PubMed Central

Akbar, Umer; Eilers, Amanda; Thompson-Avila, Amanda; Malaty, Irene A.; Okun, Michael S.

2015-01-01

Objective. (1) To evaluate the feasibility of implementing and evaluating a home visit program for persons with Parkinson's disease (PD) in a rural setting. (2) To have movement disorders fellows coordinate and manage health care delivery. Background. The University of Florida, Center for Movement Disorders and Neurorestoration established Operation House Call to serve patients with PD who could not otherwise afford to travel to an expert center or to pay for medical care. PD is known to lead to significant disability, frequent hospitalization, early nursing home placement, and morbidity. Methods. This was designed as a quality improvement project. Movement disorders fellows travelled to the home(s) of underserved PD patients and coordinated their clinical care. The diagnosis of Parkinson's disease was confirmed using standardized criteria, and the Unified Parkinson's Disease Rating Scale was performed and best treatment practices were delivered. Results. All seven patients have been followed up longitudinally every 3 to 6 months in the home setting, and they remain functional and independent. None of the patients have been hospitalized for PD related complications. Each patient has a new updatable electronic medical record. All Operation House Call cases are presented during video rounds for the interdisciplinary PD team to make recommendations for care (neurology, neurosurgery, neuropsychology, psychiatry, physical therapy, occupational therapy, speech therapy, and social work). One Operation House Call patient has successfully received deep brain stimulation (DBS). Conclusion. This program is a pilot program that has demonstrated that it is possible to provide person-centered care in the home setting for PD patients. This program could provide a proof of concept for the construction of a larger visiting physician or nurse program. PMID:26078912

Evaluation of PD/PID controller for insulin control on blood glucose regulation in a Type-I diabetes

NASA Astrophysics Data System (ADS)

Mahmud, Farhanahani; Isse, Nadir Hussien; Daud, Nur Atikah Mohd; Morsin, Marlia

2017-01-01

This project introduces a simulation of Proportional-Derivative (PD) and Proportional-Integral-Derivative (PID) controller based on a virtual Type 1 Diabetes Mellitus (T1DM) patient: Hovorka diabetic model using MATLAB-Simulink software. The results of these simulations are based on three tuning responses for each controller which are fast, slow and oscillation responses. The main purpose of this simulation is to achieve an acceptable stability and fastness response towards the regulation of glucose concentration using PD and PID controller response with insulin infusion rate. Therefore, in order to analyze and compare the responses of both controller performances, one-day simulations of the insulin-glucose dynamic have been conducted using a typical day meal plan that contains five meals of different bolus size. It is found that the PID closed-loop control with a short rise time is required to retrieve a satisfactory glucose regulation.

Towards the Rational Design of Nanoparticle Catalysts

NASA Astrophysics Data System (ADS)

Dash, Priyabrat

This research is focused on development of routes towards the rational design of nanoparticle catalysts. Primarily, it is focused on two main projects; (1) the use of imidazolium-based ionic liquids (ILs) as greener media for the design of quasi-homogeneous nanoparticle catalysts and (2) the rational design of heterogeneous-supported nanoparticle catalysts from structured nanoparticle precursors. Each project has different studies associated with the main objective of the design of nanoparticle catalysts. In the first project, imidazolium-based ionic liquids have been used for the synthesis of nanoparticle catalysts. In particular, studies on recyclability, reuse, mode-of-stability, and long-term stability of these ionic-liquid supported nanoparticle catalysts have been done; all of which are important factors in determining the overall "greenness" of such synthetic routes. Three papers have been published/submitted for this project. In the first publication, highly stable polymer-stabilized Au, Pd and bimetallic Au-Pd nanoparticle catalysts have been synthesized in imidazolium-based 1-butyl-3-methylimidazolium hexafluorophosphate ([BMIM]PF6) ionic liquid (Journal of Molecular Catalysis A: Chemical, 2008, 286, 114). The resulting nanoparticles were found to be effective and selective quasi-homogeneous catalysts towards a wide-range of hydrogenation reactions and the catalyst solution was reused for further catalytic reactions with minimal loss in activity. The synthesis of very pure and clean ILs has allowed a platform to study the effects of impurities in the imidazolium ILs on nanoparticle stability. In a later study, a new mode of stabilization was postulated where the presence of low amounts of 1-methylimidazole has substantial effects on the resulting stability of Au and Pd-Au nanoparticles in these ILs (Chemical Communications, 2009, 812). In further continuation of this study, a comparative study involving four stabilization protocols for nanoparticle stabilization in BMIMPF6 IL is described, and have shown that nanoparticle stability and catalytic activity of nanoparticles is dependent on the overall stability of the nanoparticles towards aggregation (manuscript submitted). The second major project is focused on synthesizing structurally well-defined supported catalysts by incorporating the nanoparticle precursors (both alloy and core shell) into oxide frameworks (TiO2 and Al2O 3), and examining their structure-property relationships and catalytic activity. a full article has been published on this project (Journal of Physical Chemistry C, 2009, 113, 12719) in which a route to rationally design supported catalysts from structured nanoparticle precursors with precise control over size, composition, and internal structure of the nanoparticles has been shown. In a continuation of this methodology for the synthesis of heterogeneous catalysts, efforts were carried out to apply the same methodology in imidazolium-based ILs as a one-pot media for the synthesis of supported-nanoparticle heterogeneous catalysts via the trapping of pre-synthesized nanoparticles into porous inorganic oxide materials. Nanoparticle catalysts in highly porous titania supports were synthesized using this methodology (manuscript to be submitted).

Heterogeneous Electrocatalyst of Palladium-Cobalt-Phosphorus on Carbon Support for Oxygen Reduction Reaction in High Temperature Proton Exchange Membrane Fuel Cells.

PubMed

You, Dae Jong; Pak, Chanho; Jin, Seon-Ah; Lee, Kang Hee; Kwon, Kyungjung; Choi, Kyoung Hwan; Heo, Pil Won; Jang, Hongchul; Kim, Jun Young; Kim, Ji Man

2016-05-01

Palladium-cobalt-phosphorus (PdCoP) catalysts supported on carbon (Ketjen Black) were investigated as a cathode catalyst for oxygen reduction reaction (ORR) in high temperature proton exchange membrane fuel cells (HT-PEMFCs). The PdCoP catalyst was synthesized via a modified polyol process in teflon-sealed reactor by microwave-heating. From X-ray diffraction and transmission electron microscopic analysis, the PdCoP catalyst exhibits a face-centered cubic structure, similar to palladium (Pd), which is attributed to form a good solid solution of Co atoms and P atoms in the Pd lattice. The PdCoP nanoparticles with average diameter of 2.3 nm were uniformly distributed on the carbon support. The electrochemical surface area (ECSA) and ORR activity of PdP, PdCo and PdCoP catalysts were measured using a rotating disk electrode technique with cyclic voltammetry and the linear sweep method. The PdCoP catalysts showed the highest performances for ECSA and ORR, which might be attributed both to formation of small nanoparticle by phosphorus atom and to change in lattice constant of Pd by cobalt atom. Furthermore, The HT-PEMFCs single cell performance employing PdCoP catalyst exhibited an enhanced cell performance compared to a single cell using the PdP and PdCo catalysts. This result indicates the importance of electric and geometric control of Pd alloy nanoparticles that can improve the catalytic activity. This synergistic combination of Co and P with Pd could provide the direction of development of non-Pt catalyst for fuel cell system.

Eyeblink conditioning in the developing rabbit

PubMed Central

Brown, Kevin L.; Woodruff-Pak, Diana S.

2011-01-01

Eyeblink classical conditioning in pre-weanling rabbits was examined in the present study. Using a custom lightweight headpiece and restrainer, New Zealand white littermates were trained once daily in 400 ms delay eyeblink classical conditioning from postnatal days (PD) 17–21 or PD 24–28. These ages were chosen because eyeblink conditioning emerges gradually over PD 17–24 in rats (Stanton, Freeman, & Skelton, 1992), another altricial species with neurodevelopmental features similar to those of rabbits. Consistent with well-established findings in rats, rabbits trained from PD 24–28 showed greater conditioning relative to littermates trained from PD 17–21. Both age groups displayed poor retention of eyeblink conditioning at retraining one month after acquisition. These findings are the first to demonstrate eyeblink conditioning in the developing rabbit. With further characterization of optimal conditioning parameters, this preparation may have applications to neurodevelopmental disease models as well as research exploring the ontogeny of memory. PMID:21953433

Best Practices. Premiere PD

ERIC Educational Resources Information Center

Brown, Ryan; Ernst, Jeremy; Clark, Aaron; DeLuca, Bill; Kelly, Daniel

2017-01-01

Educators who engage in best practices utilize a variety of instructional delivery methods to assist all learners in achieving success in concept mastery. Best practices help educators set expectations for completing activities/lessons/projects/units, differentiate instruction, integrate curricula, and provide active learning opportunities for…

Materials Data on Li15Bi4(PdO10)2 (SG:1) by Materials Project

DOE Data Explorer

Kristin Persson

2016-03-27

Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

Mitochondria: A Common Target for Genetic Mutations and Environmental Toxicants in Parkinson’s Disease

PubMed Central

Helley, Martin P.; Pinnell, Jennifer; Sportelli, Carolina; Tieu, Kim

2017-01-01

Parkinson’s disease (PD) is a devastating neurological movement disorder. Since its first discovery 200 years ago, genetic and environmental factors have been identified to play a role in PD development and progression. Although genetic studies have been the predominant driving force in PD research over the last few decades, currently only a small fraction of PD cases can be directly linked to monogenic mutations. The remaining cases have been attributed to other risk associated genes, environmental exposures and gene–environment interactions, making PD a multifactorial disorder with a complex etiology. However, enormous efforts from global research have yielded significant insights into pathogenic mechanisms and potential therapeutic targets for PD. This review will highlight mitochondrial dysfunction as a common pathway involved in both genetic mutations and environmental toxicants linked to PD. PMID:29204154

Measurement of benzenethiol adsorption to nanostructured Pt, Pd, and PtPd films using Raman spectroelectrochemistry.

PubMed

Pomfret, Michael B; Pietron, Jeremy J; Owrutsky, Jeffrey C

2010-05-04

Raman spectroscopy and electrochemical methods were used to study the behavior of the model adsorbate benzenethiol (BT) on nanostructured Pt, Pd, and PtPd electrodes as a function of applied potential. Benzenethiol adsorbs out of ethanolic solutions as the corresponding thiolate, and voltammetric stripping data reveal that BT is oxidatively removed from all of the nanostructured metals upon repeated oxidative and reductive cycling. Oxidative stripping potentials for BT increase in the order Pt < PtPd < Pd, indicating that BT adsorbs most strongly to nanoscale Pd. Yet, BT Raman scattering intensities, measured in situ over time scales of minutes to hours, are most persistent on the film of nanostructured Pt. Raman spectra indicate that adsorbed BT desorbs from nanoscale Pt at oxidizing potentials via cleavage of the Pt-S bond. In contrast, on nanoscale Pd and PtPd, BT is irreversibly lost due to cleavage of BT C-S bonds at oxidizing potentials, which leaves adsorbed sulfur oxides on Pd and PtPd films and effects the desulfurization of BT. While Pd and PtPd films are less sulfur-resistant than Pt films, palladium oxides, which form at higher potentials than Pt oxides, oxidatively desulfurize BT. In situ spectroelectrochemical Raman spectroscopy provides real-time, chemically specific information that complements the cyclic voltammetric data. The combination of these techniques affords a powerful and convenient method for guiding the development of sulfur-tolerant PEMFC catalysts.

Selective hydrogenation of phenol to cyclohexanone in water over Pd@N-doped carbons derived from ZIF-67: Role of dicyandiamide

NASA Astrophysics Data System (ADS)

Ding, Shuaishuai; Zhang, Chunhua; Liu, Yefei; Jiang, Hong; Chen, Rizhi

2017-12-01

Highly efficient Pd@CN catalysts for selective hydrogenation of phenol to cyclohexanone in water were successfully fabricated by loading Pd nanoparticles (NPs) in N-doped carbons (CN) derived from ZIF-67 with dicyandiamide (DICY) as the additional nitrogen source. For comparison, polyvinylpyrrolidone (PVP) was also used as the additional nitrogen source during the ZIF-67 synthesis. The results showed that the PVP and DICY had significantly different impacts on the microstructures of as-obtained CN materials and the catalytic performance of Pd@CN catalysts in the phenol hydrogenation. The addition of DICY had the positive promotion effect on the surface area of the obtained CN materials. Moreover, the introduction of DICY could increase the nitrogen content of CN and then prevent the re-oxidation of Pd NPs during air contact, resulting in higher Pd0 ratio. In comparison with PVP, the DICY was more suitable as the additional nitrogen source for the formation of CN and Pd@CN (Pd@CND, Pd@CNP). The Pd@CND exhibited superior catalytic activity as compared to Pd@CNP (phenol conversion 96.9% vs. 67.4%). More importantly, the as-prepared Pd@CND catalyst could be reused for four times without catalytic performance reduction. The work would aid the development of Pd@CN catalysts with superior catalytic properties.

Dissecting plasmodesmata molecular composition by mass spectrometry-based proteomics.

PubMed

Salmon, Magali S; Bayer, Emmanuelle M F

2012-01-01

In plants, the intercellular communication through the membranous channels called plasmodesmata (PD; singular plasmodesma) plays pivotal roles in the orchestration of development, defence responses, and viral propagation. PD are dynamic structures embedded in the plant cell wall that are defined by specialized domains of the endoplasmic reticulum (ER) and the plasma membrane (PM). PD structure and unique functions are guaranteed by their particular molecular composition. Yet, up to recent years and despite numerous approaches such as mutant screens, immunolocalization, or screening of random cDNAs, only few PD proteins had been conclusively identified and characterized. A clear breakthrough in the search of PD constituents came from mass-spectrometry-based proteomic approaches coupled with subcellular fractionation strategies. Due to their position, firmly anchored in the extracellular matrix, PD are notoriously difficult to isolate for biochemical analysis. Proteomic-based approaches have therefore first relied on the use of cell wall fractions containing embedded PD then on "free" PD fractions whereby PD membranes were released from the walls by enzymatic degradation. To discriminate between likely contaminants and PD protein candidates, bioinformatics tools have often been used in combination with proteomic approaches. GFP fusion proteins of selected candidates have confirmed the PD association of several protein families. Here we review the accomplishments and limitations of the proteomic-based strategies to unravel the functional and structural complexity of PD. We also discuss the role of the identified PD-associated proteins.

Severe Alterations in Lipid Composition of Frontal Cortex Lipid Rafts from Parkinson’s Disease and Incidental Parkinson’s Disease

PubMed Central

Fabelo, Noemí; Martín, Virginia; Santpere, Gabriel; Marín, Raquel; Torrent, Laia; Ferrer, Isidre; Díaz, Mario

2011-01-01

Lipid rafts are cholesterol- and sphingomyelin-enriched microdomains that provide a highly saturated and viscous physicochemical microenvironment to promote protein–lipid and protein–protein interactions. We purified lipid rafts from human frontal cortex from normal, early motor stages of Parkinson’s disease (PD) and incidental Parkinson’s disease (iPD) subjects and analyzed their lipid composition. We observed that lipid rafts from PD and iPD cortices exhibit dramatic reductions in their contents of n-3 and n-6 long-chain polyunsaturated fatty acids, especially docosahexaenoic acid (22:6-n3) and arachidonic acid (20:4n-6). Also, saturated fatty acids (16:0 and 18:0) were significantly higher than in control brains. Paralleling these findings, unsaturation and peroxidability indices were considerably reduced in PD and iPD lipid rafts. Lipid classes were also affected in PD and iPD lipid rafts. Thus, phosphatidylserine and phosphatidylinositol were increased in PD and iPD, whereas cerebrosides and sulfatides and plasmalogen levels were considerably diminished. Our data pinpoint a dramatic increase in lipid raft order due to the aberrant biochemical structure in PD and iPD and indicate that these abnormalities of lipid rafts in the frontal cortex occur at early stages of PD pathology. The findings correlate with abnormal lipid raft signaling and cognitive decline observed during the development of these neurodegenerative disorders. PMID:21717034

Development of low cost contacts to silicon solar cells

NASA Technical Reports Server (NTRS)

Tanner, D. P.

1980-01-01

The results of the second phase of the program of developing low cost contacts to silicon solar cells using copper are presented. Phase 1 yielded the development of a plated Pd-Cr-Cu contact system. This process produced cells with shunting problems when they were heated to 400 C for 5 minutes. Means of stopping the identified copper diffusion which caused the shunting were investigated. A contact heat treatment study was conducted with Pd-Ag, Ci-Ag, Pd-Cu, Cu-Cr, and Ci-Ni-Cu. Nickel is shown to be an effective diffusion barrier to copper.

Emerging preclinical pharmacological targets for Parkinson's disease

PubMed Central

More, Sandeep Vasant; Choi, Dong-Kug

2016-01-01

Parkinson's disease (PD) is a progressive neurological condition caused by the degeneration of dopaminergic neurons in the basal ganglia. It is the most prevalent form of Parkinsonism, categorized by cardinal features such as bradykinesia, rigidity, tremors, and postural instability. Due to the multicentric pathology of PD involving inflammation, oxidative stress, excitotoxicity, apoptosis, and protein aggregation, it has become difficult to pin-point a single therapeutic target and evaluate its potential application. Currently available drugs for treating PD provide only symptomatic relief and do not decrease or avert disease progression resulting in poor patient satisfaction and compliance. Significant amount of understanding concerning the pathophysiology of PD has offered a range of potential targets for PD. Several emerging targets including AAV-hAADC gene therapy, phosphodiesterase-4, potassium channels, myeloperoxidase, acetylcholinesterase, MAO-B, dopamine, A2A, mGlu5, and 5-HT-1A/1B receptors are in different stages of clinical development. Additionally, alternative interventions such as deep brain stimulation, thalamotomy, transcranial magnetic stimulation, and gamma knife surgery, are also being developed for patients with advanced PD. As much as these therapeutic targets hold potential to delay the onset and reverse the disease, more targets and alternative interventions need to be examined in different stages of PD. In this review, we discuss various emerging preclinical pharmacological targets that may serve as a new promising neuroprotective strategy that could actually help alleviate PD and its symptoms. PMID:26988916

Brief exposure to methamphetamine (METH) and phencyclidine (PCP) during late development leads to long-term learning deficits in rats.

PubMed

White, Ilsun M; Minamoto, Takehiro; Odell, Joseph R; Mayhorn, Joseph; White, Wesley

2009-04-17

Exposure to methamphetamine (METH) and phencyclidine (PCP) during early development is thought to produce later behavioral deficits. We postulated that exposure to METH and PCP during later development would produce similar behavioral deficits, particularly learning deficits in adulthood. Wistar rats were treated with METH (9 mg/kg), PCP (9 mg/kg), or saline during later development, postnatal days (PD) 50-51, and subsequent behavioral changes were examined including: locomotor activity during the acute drug state (PD 50-51) and the post-drug phase (PD 50-80); social interaction on PD 54-80; and spatial discrimination and reversal in adulthood (after PD 90). METH and PCP differentially affected locomotion during the acute state, but not during the post-drug phase. METH decreased social interaction throughout tests two weeks after drug treatment, whereas PCP decreased social interaction only during the first 8 min of tests. Neither METH nor PCP impaired initial acquisition of spatial discrimination. However, reversal was significantly impaired by PCP, whereas METH produced a mild deficit, compared to controls. Our data provide evidence that exposure to PCP and METH during later development lead to enduring cognitive deficits in adulthood. Selective impairment of reversal may reflect neurological damage in the prefrontal cortex due to early exposure to drugs.

A Physical Model of Human Skin and Its Application for Search and Rescue

DTIC Science & Technology

2009-12-01

allow iv for the development of skin detection algorithms with a high probability of detection (PD) and a low probability of false alarm ( PFA ). The...various skin colors were collected. The skin detection algorithm developed in this work had a PD as high as 0.95 with a PFA of 0.006. Skin...threshold 0 < γ < 1. . . . . . . . . . . . . 103 63. Top: Detection Image with NDSI threshold γ = 0.314 with PD = 0.95 and corresponding PFA = 0.0156

Impaired glutamatergic projection from the motor cortex to the subthalamic nucleus in 6-hydroxydopamine-lesioned hemi-parkinsonian rats.

PubMed

Wang, Yan-Yan; Wang, Yong; Jiang, Hai-Fei; Liu, Jun-Hua; Jia, Jun; Wang, Ke; Zhao, Fei; Luo, Min-Hua; Luo, Min-Min; Wang, Xiao-Min

2018-02-01

The glutamatergic projection from the motor cortex to the subthalamic nucleus (STN) constitutes the cortico-basal ganglia circuit and plays a critical role in the control of movement. Emerging evidence shows that the cortico-STN pathway is susceptible to dopamine depletion. Specifically in Parkinson's disease (PD), abnormal electrophysiological activities were observed in the motor cortex and STN, while the STN serves as a key target of deep brain stimulation for PD therapy. However, direct morphological changes in the cortico-STN connectivity in response to PD progress are poorly understood at present. In the present study, we used a trans-synaptic anterograde tracing method with herpes simplex virus-green fluorescent protein (HSV-GFP) to monitor the cortico-STN connectivity in a rat model of PD. We found that the connectivity from the primary motor cortex (M1) to the STN was impaired in parkinsonian rats as manifested by a marked decrease in trans-synaptic infection of HSV-GFP from M1 neurons to STN neurons in unilateral 6-hydroxydopamine (6-OHDA)-lesioned rats. Ultrastructural analysis with electron microscopy revealed that excitatory synapses in the STN were also impaired in parkinsonian rats. Glutamatergic terminals identified by a specific marker (vesicular glutamate transporter 1) were reduced in the STN, while glutamatergic neurons showed an insignificant change in their total number in both the M1 and STN regions. These results indicate that the M1-STN glutamatergic connectivity is downregulated in parkinsonian rats. This downregulation is mediated probably via a mechanism involving the impairments of excitatory terminals and synapses in the STN. Copyright © 2017. Published by Elsevier Inc.

Concomitant development of hypersexuality and delusional jealousy in patients with Parkinson's disease: a case series.

PubMed

Poletti, Michele; Lucetti, Claudio; Baldacci, Filippo; Del Dotto, Paolo; Bonuccelli, Ubaldo

2014-11-01

Both impulse-control disorders and delusional jealousy (DJ) may be considered non-motor side-effects of dopamine agonist therapy in Parkinson's disease (PD). We aimed to investigate the possible concomitant development of these features in PD and their clinical correlates. We performed a cross-sectional investigation in 1063 consecutive PD patients with the Questionnaire for Impulsive Compulsive Disorders in Parkinson's disease and the Parkinson's Psychosis Questionnaire. 81 patients presented ICDs (prevalence 7.61%) and 23 patients presented DJ (17 males, 6 females; prevalence 2.16%). 9 male PD patients presented both DJ and ICDs (39.13% of patients with DJ, 11.11% of patients with ICDs; prevalence of 0.84% in the whole PD sample), with a concomitant onset of delusional jealousy and hypersexuality in 8 cases and a concomitant onset of delusional jealousy and pathological gambling in 2 cases. Hypersexuality and delusional jealousy may occur independently in PD patients "on" dopamine agonist therapy, but may develop together probably reflecting a common alteration of sexuality (sexual arousal and jealousy) The presence of both of these clinical features and sexuality more in general should be investigated when features of either one of them appear. Further confirmation is needed in larger samples of patients. Copyright © 2014. Published by Elsevier Ltd.

A Developmental Framework for Complex Plasmodesmata Formation Revealed by Large-Scale Imaging of the Arabidopsis Leaf Epidermis[W

PubMed Central

Fitzgibbon, Jessica; Beck, Martina; Zhou, Ji; Faulkner, Christine; Robatzek, Silke; Oparka, Karl

2013-01-01

Plasmodesmata (PD) form tubular connections that function as intercellular communication channels. They are essential for transporting nutrients and for coordinating development. During cytokinesis, simple PDs are inserted into the developing cell plate, while during wall extension, more complex (branched) forms of PD are laid down. We show that complex PDs are derived from existing simple PDs in a pattern that is accelerated when leaves undergo the sink–source transition. Complex PDs are inserted initially at the three-way junctions between epidermal cells but develop most rapidly in the anisocytic complexes around stomata. For a quantitative analysis of complex PD formation, we established a high-throughput imaging platform and constructed PDQUANT, a custom algorithm that detected cell boundaries and PD numbers in different wall faces. For anticlinal walls, the number of complex PDs increased with increasing cell size, while for periclinal walls, the number of PDs decreased. Complex PD insertion was accelerated by up to threefold in response to salicylic acid treatment and challenges with mannitol. In a single 30-min run, we could derive data for up to 11k PDs from 3k epidermal cells. This facile approach opens the door to a large-scale analysis of the endogenous and exogenous factors that influence PD formation. PMID:23371949

Interdiffusion and stress development in single-crystalline Pd/Ag bilayers

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

Noah, Martin A., E-mail: m.noah@is.mpg.de; Flötotto, David; Wang, Zumin

Interdiffusion and stress evolution in single-crystalline Pd/single-crystalline Ag thin films were investigated by Auger electron spectroscopy sputter-depth profiling and in-situ X-ray diffraction, respectively. The concentration-dependent chemical diffusion coefficient, as well as the impurity diffusion coefficient of Ag in Pd could be determined in the low temperature range of 356 °C–455 °C. As a consequence of the similarity of the strong concentration-dependences of the intrinsic diffusion coefficients, the chemical diffusion coefficient varies only over three orders of magnitude over the whole composition range, despite the large difference of six orders of magnitude of the self-diffusion coefficients of Ag in Ag and Pd inmore » Pd. It is shown that the Darken-Manning treatment should be adopted for interpretation of the experimental data; the Nernst-Planck treatment yielded physically unreasonable results. Apart from the development of compressive thermal stress, the development of stress in both sublayers separately could be ascribed to compositional stress (tensile in the Ag sublayer and compressive in the Pd sublayer) and dominant relaxation processes, especially in the Ag sublayer. The effect of these internal stresses on the values determined for the diffusion coefficients is shown to be negligible.« 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

Concave Pd-Ru nanocubes bounded with high active area for boosting ethylene glycol electrooxidation

NASA Astrophysics Data System (ADS)

Xiong, Zhiping; Xu, Hui; Li, Shumin; Gu, Zhulan; Yan, Bo; Guo, Jun; Du, Yukou

2018-01-01

This paper reported our extensive efforts in the design of concave PdRu nanocubes via a facile wet-chemical strategy. Different from the previously reported PdRu nanostructures, the as-prepared concave PdRu nanocubes combined the advantages of fascinating nanocube structure, synergistic and electronic effect as well as high surface area. All of these beneficial terms endow them to exhibit superior electrocatalytic activity and long-term stability towards ethylene glycol oxidation as compared with commercial Pd/C. Our work highlights the significance of shape-controlled of PdRu nanostructures over the electrocatalytic performances towards the electrooxidation of ethylene glycol (EG), which will pave up a new strategy for boosting the development of renewable and clean energy technology.

Parkinson's Disease Therapeutics: New Developments and Challenges Since the Introduction of Levodopa

PubMed Central

Smith, Yoland; Wichmann, Thomas; Factor, Stewart A; DeLong, Mahlon R

2012-01-01

The demonstration that dopamine loss is the key pathological feature of Parkinson's disease (PD), and the subsequent introduction of levodopa have revolutionalized the field of PD therapeutics. This review will discuss the significant progress that has been made in the development of new pharmacological and surgical tools to treat PD motor symptoms since this major breakthrough in the 1960s. However, we will also highlight some of the challenges the field of PD therapeutics has been struggling with during the past decades. The lack of neuroprotective therapies and the limited treatment strategies for the nonmotor symptoms of the disease (ie, cognitive impairments, autonomic dysfunctions, psychiatric disorders, etc.) are among the most pressing issues to be addressed in the years to come. It appears that the combination of early PD nonmotor symptoms with imaging of the nigrostriatal dopaminergic system offers a promising path toward the identification of PD biomarkers, which, once characterized, will set the stage for efficient use of neuroprotective agents that could slow down and alter the course of the disease. PMID:21956442

Humanized mouse model of glucose 6-phosphate dehydrogenase deficiency for in vivo assessment of hemolytic toxicity.

PubMed

Rochford, Rosemary; Ohrt, Colin; Baresel, Paul C; Campo, Brice; Sampath, Aruna; Magill, Alan J; Tekwani, Babu L; Walker, Larry A

2013-10-22

Individuals with glucose 6-phosphate dehydrogenase (G6PD) deficiency are at risk for the development of hemolytic anemia when given 8-aminoquinolines (8-AQs), an important class of antimalarial/antiinfective therapeutics. However, there is no suitable animal model that can predict the clinical hemolytic potential of drugs. We developed and validated a human (hu)RBC-SCID mouse model by giving nonobese diabetic/SCID mice daily transfusions of huRBCs from G6PD-deficient donors. Treatment of SCID mice engrafted with G6PD-deficient huRBCs with primaquine, an 8-AQ, resulted in a dose-dependent selective loss of huRBCs. To validate the specificity of this model, we tested known nonhemolytic antimalarial drugs: mefloquine, chloroquine, doxycycline, and pyrimethamine. No significant loss of G6PD-deficient huRBCs was observed. Treatment with drugs known to cause hemolytic toxicity (pamaquine, sitamaquine, tafenoquine, and dapsone) resulted in loss of G6PD-deficient huRBCs comparable to primaquine. This mouse model provides an important tool to test drugs for their potential to cause hemolytic toxicity in G6PD-deficient populations.

Personality disorders in early adolescence and the development of later substance use disorders in the general population

PubMed Central

Cohen, Patricia; Chen, Henian; Crawford, Thomas N.; Brook, Judith S.; Gordon, Kathy

2007-01-01

Assessments of personality disorder (PD) and conduct disorder (CD) in a random community sample at mean age 13 were employed to predict subsequent substance abuse disorder (SUD), trajectories of symptoms of abuse or dependence on alcohol, marijuana, or other illicit substances, and hazard of initiating marijuana use over the subsequent decade. Personality disorders and conduct disorder were associated with diagnoses and symptoms of SUDs in every model and their effects were independent of correlated family risks, participant sex, and other Axis I disorders. Specific elevated PD symptoms in early adolescence were also associated with differential trajectories of already initiated SUD symptoms as well as elevated risk for future onset of SUD symptoms. For several models the greatest of these effects were shown for borderline PD and for conduct disorder, the predecessor of adult antisocial PD. Passive-aggressive PD also showed independent elevation effects on substance use symptoms for alcohol and marijuana. Analyses over 30 years suggest that Cluster B PD (borderline, histrionic, narcissistic) are independent risks for development of SUD and warrant clinical attention. PMID:17227697

Personality disorders in early adolescence and the development of later substance use disorders in the general population.

PubMed

Cohen, Patricia; Chen, Henian; Crawford, Thomas N; Brook, Judith S; Gordon, Kathy

2007-04-01

Assessments of personality disorder (PD) and conduct disorder (CD) in a random community sample at mean age 13 were employed to predict subsequent substance abuse disorder (SUD), trajectories of symptoms of abuse or dependence on alcohol, marijuana, or other illicit substances, and hazard of initiating marijuana use over the subsequent decade. Personality disorders and conduct disorder were associated with diagnoses and symptoms of SUDs in every model and their effects were independent of correlated family risks, participant sex, and other Axis I disorders. Specific elevated PD symptoms in early adolescence were also associated with differential trajectories of already initiated SUD symptoms as well as elevated risk for future onset of SUD symptoms. For several models the greatest of these effects were shown for borderline PD and for conduct disorder, the predecessor of adult antisocial PD. Passive-aggressive PD also showed independent elevation effects on substance use symptoms for alcohol and marijuana. Analyses over 30 years suggest that Cluster B PD (borderline, histrionic, narcissistic) are independent risks for development of SUD and warrant clinical attention.

Cerebrospinal fluid biomarkers of central dopamine deficiency predict Parkinson's disease.

PubMed

Goldstein, David S; Holmes, Courtney; Lopez, Grisel J; Wu, Tianxia; Sharabi, Yehonatan

2018-05-01

Consistent with nigrostriatal dopamine depletion, low cerebrospinal fluid (CSF) concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC), the main neuronal metabolite of dopamine, characterize Parkinson's disease (PD) even in recently diagnosed patients. Whether low CSF levels of DOPAC or DOPA, the precursor of dopamine, identify pre-clinical PD in at-risk healthy individuals has been unknown. Participants in the intramural NINDS PDRisk study entered information about family history of PD, olfactory dysfunction, dream enactment behavior, and orthostatic hypotension at a protocol-specific website. After at least 3 risk factors were confirmed by on-site screening, 26 subjects had CSF sampled for levels of catechols and were followed for at least 3 years. Of 26 PDRisk subjects, 4 were diagnosed with PD (Pre-Clinical PD group); 22 risk-matched (mean 3.2 risk factors) subjects remained disease-free after a median of 3.7 years (No-PD group). The Pre-Clinical PD group had lower initial DOPA and DOPAC levels than did the No-PD group (p = 0.0302, p = 0.0190). All 3 subjects with both low DOPA (<2.63 pmol/mL) and low DOPAC (<1.22 pmol/mL) levels, based on optimum cut-off points using the minimum distance method, developed PD, whereas none of 14 subjects with both normal DOPA and DOPAC levels did so (75% sensitivity at 100% specificity, p = 0.0015 by 2-tailed Fisher's exact test). In people with multiple PD risk factors, those with low CSF DOPA and low CSF DOPAC levels develop clinical disease during follow-up. We suggest that neurochemical biomarkers of central dopamine deficiency identify the disease in a pre-clinical phase. Published by Elsevier Ltd.

Nonoverlapping roles of PD-1 and FoxP3 in maintaining immune tolerance in a novel autoimmune pancreatitis mouse model.

PubMed

Zhang, Baihao; Chikuma, Shunsuke; Hori, Shohei; Fagarasan, Sidonia; Honjo, Tasuku

2016-07-26

PD-1 (programmed-death 1), an immune-inhibitory receptor required for immune self-tolerance whose deficiency causes autoimmunity with variable severity and tissue specificity depending on other genetic factors, is expressed on activated T cells, including the transcription factor FoxP3(+) Treg cells known to play critical roles in maintaining immune tolerance. However, whether PD-1 expression by the Treg cells is required for their immune regulatory function, especially in autoimmune settings, is still unclear. We found that mice with partial FoxP3 insufficiency developed early-onset lympho-proliferation and lethal autoimmune pancreatitis only when PD-1 is absent. The autoimmune phenotype was rescued by the transfer of FoxP3-sufficient T cells, regardless of whether they were derived from WT or PD-1-deficient mice, indicating that Treg cells dominantly protect against development of spontaneous autoimmunity without intrinsic expression of PD-1. The absence of PD-1 combined with partial FoxP3 insufficiency, however, led to generation of ex-FoxP3 T cells with proinflammatory properties and expansion of effector/memory T cells that contributed to the autoimmune destruction of target tissues. Altogether, the results suggest that PD-1 and FoxP3 work collaboratively in maintaining immune tolerance mostly through nonoverlapping pathways. Thus, PD-1 is modulating the activation threshold and maintaining the balance between regulatory and effector T cells, whereas FoxP3 is sufficient for dominant regulation through maintaining the integrity of the Treg function. We suggest that genetic or environmental factors that even moderately affect the expression of both PD-1 and FoxP3 can cause life-threatening autoimmune diseases by disrupting the T-cell homeostasis.

CSF biomarkers associated with disease heterogeneity in early Parkinson’s disease: the Parkinson’s Progression Markers Initiative study

PubMed Central

Kang, Ju-Hee; Mollenhauer, Brit; Coffey, Christopher S.; Toledo, Jon B.; Weintraub, Daniel; Galasko, Douglas R.; Irwin, David J.; Van Deerlin, Vivianna; Chen-Plotkin, Alice S.; Caspell-Garcia, Chelsea; Waligórska, Teresa; Taylor, Peggy; Shah, Nirali; Pan, Sarah; Zero, Pawel; Frasier, Mark; Marek, Kenneth; Kieburtz, Karl; Jennings, Danna; Tanner, Caroline M.; Simuni, Tanya; Singleton, Andrew; Toga, Arthur W.; Chowdhury, Sohini; Trojanowski, John Q.; Shaw, Leslie M.

2016-01-01

The development of biomarkers to predict the progression of Parkinson’s disease (PD) from its earliest stage through its heterogeneous course is critical for research and therapeutic development. The Parkinson’s Progression Markers Initiative (PPMI) study is an ongoing international multicenter, prospective study to validate biomarkers in drug-naïve PD patients and matched healthy controls (HC). We quantified cerebrospinal fluid (CSF) alpha-synuclein (α-syn), amyloid-beta1–42 (Aβ1–42), total tau (t-tau), and tau phosphorylated at Thr181 (p-tau) in 660 PPMI subjects at baseline, and correlated these data with measures of the clinical features of these subjects. We found that CSF α-syn, t-tau and p-tau levels, but not Aβ1–42, were significantly lower in PD compared with HC, while the diagnostic value of the individual CSF biomarkers for PD diagnosis was limited due to large overlap. The level of α-syn, but not other biomarkers, was significantly lower in PD patients with non-tremor-dominant phenotype compared with tremor-dominant phenotype. In addition, in PD patients the lowest Aβ1–42, or highest t-tau/Aβ1–42 and t-tau/α-syn quintile in PD patients were associated with more severe non-motor dysfunction compared with the highest or lowest quintiles, respectively. In a multivariate regression model, lower α-syn was significantly associated with worse cognitive test performance. APOE ε4 genotype was associated with lower levels of Aβ1–42, but neither with PD diagnosis nor cognition. Our data suggest that the measurement of CSF biomarkers in early-stage PD patients may relate to disease heterogeneity seen in PD. Longitudinal observations in PPMI subjects are needed to define their prognostic performance. PMID:27021906

Nonoverlapping roles of PD-1 and FoxP3 in maintaining immune tolerance in a novel autoimmune pancreatitis mouse model

PubMed Central

Zhang, Baihao; Chikuma, Shunsuke; Hori, Shohei; Fagarasan, Sidonia; Honjo, Tasuku

2016-01-01

PD-1 (programmed-death 1), an immune-inhibitory receptor required for immune self-tolerance whose deficiency causes autoimmunity with variable severity and tissue specificity depending on other genetic factors, is expressed on activated T cells, including the transcription factor FoxP3+ Treg cells known to play critical roles in maintaining immune tolerance. However, whether PD-1 expression by the Treg cells is required for their immune regulatory function, especially in autoimmune settings, is still unclear. We found that mice with partial FoxP3 insufficiency developed early-onset lympho-proliferation and lethal autoimmune pancreatitis only when PD-1 is absent. The autoimmune phenotype was rescued by the transfer of FoxP3-sufficient T cells, regardless of whether they were derived from WT or PD-1–deficient mice, indicating that Treg cells dominantly protect against development of spontaneous autoimmunity without intrinsic expression of PD-1. The absence of PD-1 combined with partial FoxP3 insufficiency, however, led to generation of ex-FoxP3 T cells with proinflammatory properties and expansion of effector/memory T cells that contributed to the autoimmune destruction of target tissues. Altogether, the results suggest that PD-1 and FoxP3 work collaboratively in maintaining immune tolerance mostly through nonoverlapping pathways. Thus, PD-1 is modulating the activation threshold and maintaining the balance between regulatory and effector T cells, whereas FoxP3 is sufficient for dominant regulation through maintaining the integrity of the Treg function. We suggest that genetic or environmental factors that even moderately affect the expression of both PD-1 and FoxP3 can cause life-threatening autoimmune diseases by disrupting the T-cell homeostasis. PMID:27410049

Peyronie's disease intervention trials: methodological challenges and issues.

PubMed

Müller, Alexander; Mulhall, John P

2009-03-01

Peyronie's Disease (PD) has been studied for more than 260 years since Francois de la Peyronie's description in 1743. Based on the current literature, the prevalence of PD seems 3-9% with an average age of onset in the fifth life decade. Much effort has been spent on developing nonsurgical treatment options to cure or at least prevent disease progression. The recent examination of drug trials for erectile dysfunction has led us to assess PD trial methodology more closely. An Iinternet search on PubMed was performed using MeSH words PD, clinical trials, oral, transdermal, intralesional and shock wave therapy focusing on 26 representing studies published over the last 15 years. Mean Outcome Measures. A comprehensive review of the current literature on nonsurgical treatment options for PD was conducted to address methodological issues and challenges in PD trials highlighting trial design, patient population, and symptom and sign assessment. The majority of the reviewed studies are underpowered and the heterogeneity in the methodological approach and patient assessment between the studies is one of the remarkable findings from our review. Studies should use a uniform means of defining the degree and type of penile deformity and a large enough cohort of patients should be studied for adequate study power. An ideally designed PD intervention trial should comprise: (i) a randomized, placebo-controlled design; (ii) with a PD patient set representative of the general PD population; and (iii) a comprehensive symptom and sign assessment before and at the end of treatment which includes an assessment of at least deformity, pain, and sexual function. A number of challenges exist for the design of PD intervention trials and deciphering the data generated from them. The field would benefit greatly from a consensus statement or guidelines development on the design and conduct of such trials.

Development and validation of a yoga module for Parkinson disease.

PubMed

Kakde, Noopur; Metri, Kashinath G; Varambally, Shivarama; Nagaratna, Raghuram; Nagendra, H R

2017-03-25

Background Parkinson's disease (PD), a progressive neurodegenerative disease, affects motor and nonmotor functions, leading to severe debility and poor quality of life. Studies have reported the beneficial role of yoga in alleviating the symptoms of PD; however, a validated yoga module for PD is unavailable. This study developed and validated an integrated yoga module(IYM) for PD. Methods The IYM was prepared after a thorough review of classical yoga texts and previous findings. Twenty experienced yoga experts, who fulfilled the inclusion criteria, were selected validating the content of the IYM. A total of 28 practices were included in the IYM, and each practice was discussed and rated as (i) not essential, (ii) useful but not essential, and (iii) essential; the content validity ratio (CVR) was calculated using Lawshe's formula. Results Data analysis revealed that of the 28 IYM practices, 21 exhibited significant content validity (cut-off value: 0.42, as calculated by applying Lawshe's formula for the CVR). Conclusions The IYM is valid for PD, with good content validity. However, future studies must determine the feasibility and efficacy of the developed module.

Gene Expression Differences in Peripheral Blood of Parkinson’s Disease Patients with Distinct Progression Profiles

PubMed Central

Soreq, Lilach; Lobo, Patrícia P.; Mestre, Tiago; Coelho, Miguel; Rosa, Mário M.; Gonçalves, Nilza; Wales, Pauline; Mendes, Tiago; Gerhardt, Ellen; Fahlbusch, Christiane; Bonifati, Vincenzo; Bonin, Michael; Miltenberger-Miltényi, Gabriel; Borovecki, Fran; Soreq, Hermona; Ferreira, Joaquim J.; F. Outeiro, Tiago

2016-01-01

The prognosis of neurodegenerative disorders is clinically challenging due to the inexistence of established biomarkers for predicting disease progression. Here, we performed an exploratory cross-sectional, case-control study aimed at determining whether gene expression differences in peripheral blood may be used as a signature of Parkinson’s disease (PD) progression, thereby shedding light into potential molecular mechanisms underlying disease development. We compared transcriptional profiles in the blood from 34 PD patients who developed postural instability within ten years with those of 33 patients who did not develop postural instability within this time frame. Our study identified >200 differentially expressed genes between the two groups. The expression of several of the genes identified was previously found deregulated in animal models of PD and in PD patients. Relevant genes were selected for validation by real-time PCR in a subset of patients. The genes validated were linked to nucleic acid metabolism, mitochondria, immune response and intracellular-transport. Interestingly, we also found deregulation of these genes in a dopaminergic cell model of PD, a simple paradigm that can now be used to further dissect the role of these molecular players on dopaminergic cell loss. Altogether, our study provides preliminary evidence that expression changes in specific groups of genes and pathways, detected in peripheral blood samples, may be correlated with differential PD progression. Our exploratory study suggests that peripheral gene expression profiling may prove valuable for assisting in prediction of PD prognosis, and identifies novel culprits possibly involved in dopaminergic cell death. Given the exploratory nature of our study, further investigations using independent, well-characterized cohorts will be essential in order to validate our candidates as predictors of PD prognosis and to definitively confirm the value of gene expression analysis in aiding patient stratification and therapeutic intervention. PMID:27322389

Assessing cognitive dysfunction in Parkinson's disease: An online tool to detect visuo‐perceptual deficits

PubMed Central

Schwarzkopf, Dietrich S.; Bahrami, Bahador; Fleming, Stephen M.; Jackson, Ben M.; Goch, Tristam J. C.; Saygin, Ayse P.; Miller, Luke E.; Pappa, Katerina; Pavisic, Ivanna; Schade, Rachel N.; Noyce, Alastair J.; Crutch, Sebastian J.; O'Keeffe, Aidan G.; Schrag, Anette E.; Morris, Huw R.

2018-01-01

ABSTRACT Background: People with Parkinson's disease (PD) who develop visuo‐perceptual deficits are at higher risk of dementia, but we lack tests that detect subtle visuo‐perceptual deficits and can be performed by untrained personnel. Hallucinations are associated with cognitive impairment and typically involve perception of complex objects. Changes in object perception may therefore be a sensitive marker of visuo‐perceptual deficits in PD. Objective: We developed an online platform to test visuo‐perceptual function. We hypothesised that (1) visuo‐perceptual deficits in PD could be detected using online tests, (2) object perception would be preferentially affected, and (3) these deficits would be caused by changes in perception rather than response bias. Methods: We assessed 91 people with PD and 275 controls. Performance was compared using classical frequentist statistics. We then fitted a hierarchical Bayesian signal detection theory model to a subset of tasks. Results: People with PD were worse than controls at object recognition, showing no deficits in other visuo‐perceptual tests. Specifically, they were worse at identifying skewed images (P < .0001); at detecting hidden objects (P = .0039); at identifying objects in peripheral vision (P < .0001); and at detecting biological motion (P = .0065). In contrast, people with PD were not worse at mental rotation or subjective size perception. Using signal detection modelling, we found this effect was driven by change in perceptual sensitivity rather than response bias. Conclusions: Online tests can detect visuo‐perceptual deficits in people with PD, with object recognition particularly affected. Ultimately, visuo‐perceptual tests may be developed to identify at‐risk patients for clinical trials to slow PD dementia. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society. PMID:29473691

Closing the science achievement gap for ninth grade English learners through standards- and inquiry-based science instruction

NASA Astrophysics Data System (ADS)

Estrada, Myrna Hipol

In light of the need to close the achievement gap among our culturally and linguistically diverse students, more specifically the Hispanics and the Hispanic English Learners (ELs), the effects of teacher professional development (2 year PD vs. 1 Year PD vs. no PD) on the implementation of a standards-aligned and inquiry-based science curriculum program---the Integrated Coordinated Science for the 21st Century published by It's About Time, Inc. (ICS-IAT)---on the LAUSD ninth graders science scores were examined. Participants included 8,937 9th grade students (7,356 Hispanics). The primary outcome measurement was scaled scores from the California Standard Test (CST) in Integrated Coordinated Science (CST_ICS1). Correlations between California English Language Development Test (CELDT) component subscores (reading, listening and speaking) and CST scores were also examined. Results indicated that the science scores of the students of teachers who participated in two year PD were significantly higher compared to the scores of students of the one year PD group and the control group. The results show that all ethnic groups benefited from two years of teacher PD, except the African American group. Among Hispanics, students classified as IFEP, RFEP and EO gained from the teachers having two years of professional development. But the target population, ELs did not benefit from two years of teacher PD. The correlations between the CELDT and CST_ELA were much higher than the CELDT and CST_ICS1 correlations. This finding validates Abedi's claim (2004) that EL students are disadvantaged because of their language handicap on tests that have a greater language load. Two year PD participation significantly enhanced the accessibility of science to the ninth graders. The essential features in the PD were classroom simulation of all the activities identified in the storyboard with the actual and correct use of needed equipment and materials; creation and presentation of sample or model Chapter Challenges; practice on the use of the storyboard; facilitation of activity debriefs using a debrief template; and the use and practice of identified strategies and scaffoldings targeting ELs. Three innovations developed by the LAUSD-ICS Leadership Team also were introduced in the PD sessions. They are the storyboard, "cartoon analysis" and debrief template.