Power Extension Package (PEP) system definition extension, orbital service module systems analysis study. Volume 12: PEP data item descriptions

NASA Technical Reports Server (NTRS)

1979-01-01

Contractor information requirements necessary to support the power extension package project of the space shuttle program are specified for the following categories of data: project management; configuration management; systems engineering and test; manufacturing; reliability, quality assurance and safety; logistics; training; and operations.

Project FIRES. Volume 1: Program Overview and Summary, Phase 1B

NASA Technical Reports Server (NTRS)

Abeles, F. J.

1980-01-01

Overall performance requirements and evaluation methods for firefighters protective equipment were established and published as the Protective Ensemble Performance Standards (PEPS). Current firefighters protective equipment was tested and evaluated against the PEPS requirements, and the preliminary design of a prototype protective ensemble was performed. In phase 1B, the design of the prototype ensemble was finalized. Prototype ensembles were fabricated and then subjected to a series of qualification tests which were based upon the PEPS requirements. Engineering drawings and purchase specifications were prepared for the new protective ensemble.

Minority Engineering Program Pipeline: A Proposal to Increase Minority Student Enrollment and Retention in Engineering

NASA Technical Reports Server (NTRS)

Charity, Pamela C.; Klein, Paul B.; Wadhwa, Bhushan

1995-01-01

The Cleveland State University Minority Engineering Program Pipeline consist of programs which foster engineering career awareness, academic enrichment, and professional development for historically underrepresented minority studies. The programs involved are the Access to Careers in Engineering (ACE) Program for high school pre-engineering students: the LINK Program for undergraduate students pursuing degree which include engineering; and the PEP (Pre-calculus Enrichment Program) and EPIC (Enrichment Program in Calculus) mathematics programs for undergraduate academic enrichment. The pipeline is such that high school graduates from the ACE Program who enroll at Cleveland State University in pursuit of engineering degrees are admitted to the LINK Program for undergraduate level support. LINK Program students are among the minority participants who receive mathematics enrichment through the PEP and EPIC Programs for successful completion of their engineering required math courses. THese programs are interdependent and share the goal of preparing minority students for engineering careers by enabling them to achieve academically and obtain college degree and career related experience.

A reduced graphene oxide-based fluorescence resonance energy transfer sensor for highly sensitive detection of matrix metalloproteinase 2.

PubMed

Xi, Gaina; Wang, Xiaoping; Chen, Tongsheng

2016-01-01

A novel fluorescence nanoprobe (reduced nano-graphene oxide [nrGO]/fluorescein isothiocyanate-labeled peptide [Pep-FITC]) for ultrasensitive detection of matrix metalloproteinase 2 (MMP2) has been developed by engineering the Pep-FITC comprising the specific MMP2 substrate domain (PLGVR) onto the surface of nrGO particles through non-covalent linkage. The nrGO was obtained by water bathing nano-graphene oxide under 90°C for 4 hours. After mixing the nrGO and Pep-FITC for 30 seconds, the fluorescence from Pep-FITC was almost completely quenched due to the fluorescence resonance energy transfer between fluorescein isothiocyanate (FITC) and nrGO. Upon cleavage of the amide bond between Leu and Gly in the Pep-FITC by protease-MMP2, the FITC bound to nrGO was separated from nrGO surface, disrupting the fluorescence resonance energy transfer process and resulting in fluorescence recovery of FITC. Under optimal conditions, the fluorescence recovery of nrGO/Pep-FITC was found to be directly proportional to the concentration of MMP2 within 0.02-0.1 nM. The detection limit of the nrGO/Pep-FITC was determined to be 3 pM, which is approximately tenfold lower than that of the unreduced carboxylated nano-graphene oxide/Pep-FITC probe.

Space platforms - A cost effective evolution of Spacelab operation

NASA Technical Reports Server (NTRS)

Stofan, A. J.

1981-01-01

The capabilities added to the Shuttle/Spacelab configuration by the addition of the Power Extension Package (PEP), the Power System (PS), and the Science and Applications Space Platforms (SASP) are reviewed with an emphasis on SASP. SASP are intended for placement in orbit by the Shuttle to test new instruments and systems, for clustering of instrumentation, and for servicing, refurbishment, repair, or augmentation by the Shuttle. The PEP permits extended stays in orbit (30 days), and the PS is an orbital solar array and energy storage system acting as a free flying spacecraft. The Shuttle can deliver payloads to the PS or attach to it for extension of the Spacelab operations. Applications of SASP for long term space-based biological experiments are outlined, and the fact that SASP do not increase the required Shuttle in-orbit time is stressed.

Chemical addressability of potato virus X for its applications in bio/nanotechnology.

PubMed

Le, Duc H T; Hu, He; Commandeur, Ulrich; Steinmetz, Nicole F

2017-12-01

Potato virus X (PVX), a type member of the plant virus potexvirus group, offers a unique nanotechnology platform based on its high aspect ratio and flexible filamentous shape. The PVX platform has already been engineered and studied for its uses in imaging, drug delivery, and immunotherapies. While genetic engineering procedures are well established for PVX, there is limited information about chemical conjugation strategies for functionalizing PVX, partly due to the lack of structural information of PVX at high resolution. To overcome these challenges, we built a structural model of the PVX particle based on the available structures from pepino mosaic virus (PepMV), a close cousin of PVX. Using the model and a series of chemical conjugation experiments, we identified and probed the addressability of cysteine side chains. Chemical reactivity of cysteines was confirmed using Michael-addition and thiol-selective probes, including fluorescent dyes and biotin tags. LC/MS/MS was used to map Cys 121 as having the highest selectivity for modification. Finally, building on the availability of two reactive groups, the newly identified Cys and previously established Lys side chains, we prepared multifunctional PVX nanoparticles by conjugating Gd-DOTA for magnetic resonance imaging (MRI) to lysines and fluorescent dyes for optical imaging to cysteines. The resulting functionalized nanofilament could have applications in dual-modal optical-MRI imaging applications. These results further extend the understanding of the chemical properties of PVX and enable development of novel multifunctional platforms in bio/nanotechnology. Copyright © 2017 Elsevier Inc. All rights reserved.

The combined transduction of copper, zinc-superoxide dismutase and catalase mediated by cell-penetrating peptide, PEP-1, to protect myocardium from ischemia-reperfusion injury.

PubMed

Huang, Guang-Qing; Wang, Jia-Ning; Tang, Jun-Ming; Zhang, Lei; Zheng, Fei; Yang, Jian-Ye; Guo, Ling-Yun; Kong, Xia; Huang, Yong-Zhang; Liu, Yong; Chen, Shi-You

2011-05-21

Our previous studies indicate that either PEP-1-superoxide dismutase 1 (SOD1) or PEP-1-catalase (CAT) fusion proteins protects myocardium from ischemia-reperfusion-induced injury in rats. The aim of this study is to explore whether combined use of PEP-1-SOD1 and PEP-1-CAT enhances their protective effects. SOD1, PEP-1-SOD1, CAT or PEP-1-CAT fusion proteins were prepared and purified by genetic engineering. In vitro and in vivo effects of these proteins on cell apoptosis and the protection of myocardium after ischemia-reperfusion injury were measured. Embryo cardiac myocyte H9c2 cells were used for the in vitro studies. In vitro cellular injury was determined by the expression of lactate dehydrogenase (LDH). Cell apoptosis was quantitatively assessed with Annexin V and PI double staining by Flow cytometry. In vivo, rat left anterior descending coronary artery (LAD) was ligated for one hour followed by two hours of reperfusion. Hemodynamics was then measured. Myocardial infarct size was evaluated by TTC staining. Serum levels of myocardial markers, creatine kinase-MB (CK-MB) and cTnT were quantified by ELISA. Bcl-2 and Bax expression in left ventricle myocardium were analyzed by western blot. In vitro, PEP-1-SOD1 or PEP-1-CAT inhibited LDH release and apoptosis rate of H9c2 cells. Combined transduction of PEP-1-SOD1 and PEP-1-CAT, however, further reduced the LDH level and apoptosis rate. In vivo, combined usage of PEP-1-SOD1 and PEP-1-CAT produced a greater effect than individual proteins on the reduction of CK-MB, cTnT, apoptosis rate, lipoxidation end product malondialdehyde, and the infarct size of myocardium. Functionally, the combination of these two proteins further increased left ventricle systolic pressure, but decreased left ventricle end-diastolic pressure. This study provided a basis for the treatment or prevention of myocardial ischemia-reperfusion injury with the combined usage of PEP-1-SOD1 and PEP-1-CAT fusion proteins.

A reduced graphene oxide-based fluorescence resonance energy transfer sensor for highly sensitive detection of matrix metalloproteinase 2

PubMed Central

Xi, Gaina; Wang, Xiaoping; Chen, Tongsheng

2016-01-01

A novel fluorescence nanoprobe (reduced nano-graphene oxide [nrGO]/fluorescein isothiocyanate-labeled peptide [Pep-FITC]) for ultrasensitive detection of matrix metalloproteinase 2 (MMP2) has been developed by engineering the Pep-FITC comprising the specific MMP2 substrate domain (PLGVR) onto the surface of nrGO particles through non-covalent linkage. The nrGO was obtained by water bathing nano-graphene oxide under 90°C for 4 hours. After mixing the nrGO and Pep-FITC for 30 seconds, the fluorescence from Pep-FITC was almost completely quenched due to the fluorescence resonance energy transfer between fluorescein isothiocyanate (FITC) and nrGO. Upon cleavage of the amide bond between Leu and Gly in the Pep-FITC by protease-MMP2, the FITC bound to nrGO was separated from nrGO surface, disrupting the fluorescence resonance energy transfer process and resulting in fluorescence recovery of FITC. Under optimal conditions, the fluorescence recovery of nrGO/Pep-FITC was found to be directly proportional to the concentration of MMP2 within 0.02–0.1 nM. The detection limit of the nrGO/Pep-FITC was determined to be 3 pM, which is approximately tenfold lower than that of the unreduced carboxylated nano-graphene oxide/Pep-FITC probe. PMID:27143876

Novel role of Engrailed 1 as a prosurvival transcription factor in basal-like breast cancer and engineering of interference peptides block its oncogenic function

PubMed Central

Beltran, A S; Graves, L M; Blancafort, P

2014-01-01

Basal-like breast tumors are aggressive cancers associated with high proliferation and metastasis. Chemotherapy is currently the only treatment option; however, resistance often occurs resulting in recurrence and patient death. Some extremely aggressive cancers are also associated with hypoxia, inflammation and high leukocyte infiltration. Herein, we discovered that the neural-specific transcription factor, Engrailed 1 (EN1), is exclusively overexpressed in these tumors. Short hairpin RNA (shRNA)-mediated knockdown of EN1 triggered potent and selective cell death. In contrast, ectopic overexpression of EN1 in normal cells activated survival pathways and conferred resistance to chemotherapeutic agents. Exogenous expression of EN1 cDNA reprogrammed the breast epithelial cells toward a long-lived, neural-like phenotype displaying dopaminergic markers. Gene expression microarrays demonstrated that the EN1 cDNA altered transcription of a high number of inflammatory molecules, notably chemokines and chemokine receptors, which could mediate prosurvival pathways. To block EN1 function, we engineered synthetic interference peptides (iPeps) comprising the EN1-specific sequences that mediate essential protein-protein interactions necessary for EN1 function and an N-terminal cell-penetrating peptide/nuclear localization sequence. These EN1-iPeps rapidly mediated a strong apoptotic response in tumor cells overexpressing EN1, with no toxicity to normal or non EN1-expressing cells. Delivery of EN1-iPeps into basal-like cancer cells significantly decreased the fifty percent inhibitory concentrations (IC50) of chemotherapeutic drugs routinely used to treat breast cancer. Lastly, matrix-assisted laser desorption/ionization-time of flight mass spectrometry and immunoprecipitation assays demonstrated that EN1-iPeps captured targets involved in transcriptional and post-transcriptional regulation. Importantly, the EN1-iPeps bound the glutamyl-prolyl tRNA synthetase (EPRS) target, which has been associated with the transcript-specific translational control of inflammatory proteins and activation of amino-acid stress pathways. This work unveils EN1 as an activator of intrinsic inflammatory pathways associated with prosurvival in basal-like breast cancer. We further build upon these results and describe the engineering of iPeps targeting EN1 (EN1-iPeps) as a novel and selective therapeutic strategy to combat these lethal forms of breast cancer. PMID:24141779

BMP-2 Derived Peptide and Dexamethasone Incorporated Mesoporous Silica Nanoparticles for Enhanced Osteogenic Differentiation of Bone Mesenchymal Stem Cells.

PubMed

Zhou, Xiaojun; Feng, Wei; Qiu, Kexin; Chen, Liang; Wang, Weizhong; Nie, Wei; Mo, Xiumei; He, Chuanglong

2015-07-29

Bone morphogenetic protein-2 (BMP-2), a growth factor that induces osteoblast differentiation and promotes bone regeneration, has been extensively investigated in bone tissue engineering. The peptides of bioactive domains, corresponding to residues 73-92 of BMP-2 become an alternative to reduce adverse side effects caused by the use of high doses of BMP-2 protein. In this study, BMP-2 peptide functionalized mesoporous silica nanoparticles (MSNs-pep) were synthesized by covalently grafting BMP-2 peptide on the surface of nanoparticles via an aminosilane linker, and dexamethasone (DEX) was then loaded into the channel of MSNs to construct nanoparticulate osteogenic delivery systems (DEX@MSNs-pep). The in vitro cell viability of MSNs-pep was tested with bone mesenchymal stem cells (BMSCs) exposure to different particle concentrations, revealing that the functionalized MSNs had better cytocompatibility than their bare counterparts, and the cellular uptake efficiency of MSNs-pep was remarkably larger than that of bare MSNs. The in vitro results also show that the MSNs-pep promoted osteogenic differentiation of BMSCs in terms of the levels of alkaline phosphatase (ALP) activity, calcium deposition, and expression of bone-related protein. Moreover, the osteogenic differentiation of BMSCs can be further enhanced by incorporating of DEX into MSNs-pep. After intramuscular implantation in rats for 3 weeks, the computed tomography (CT) images and histological examination indicate that this nanoparticulate osteogenic delivery system induces effective osteoblast differentiation and bone regeneration in vivo. Collectively, the BMP-2 peptide and DEX incorporated MSNs can act synergistically to enhance osteogenic differentiation of BMSCs, which have potential applications in bone tissue engineering.

The Woods Hole Partnership Education Program (PEP): Broadening Participation in the Geosciences

NASA Astrophysics Data System (ADS)

Scott, O.; Jearld, A., Jr.; Liles, G.; Gutierrez, B.

2015-12-01

In March 2009, the Woods Hole Diversity Initiative launched the Partnership Education Program (PEP), a multi-institutional effort to increase diversity in the student population (and ultimately the work force) in the Woods Hole science community. PEP, a summer research internship program, is open to students of all backgrounds but is designed especially to provide opportunities for URM in science, technology, engineering, and mathematics (STEM). PEP is a 10-week program which provides intensive mentored research, a credit-bearing course and supplemental career and professional development activities. Students have opportunities to work in various research areas of geosciences. PEP is emerging as an effective and sustainable approach to bringing students into the STEM research community. PEP is carefully structured to provide critical support for students as they complete their undergraduate experience and prepare for geosciences careers and/or graduate school. The PEP experience is intended to provide students with an entry into the Woods Hole science community, one of the most vibrant marine and environmental research communities in the world. The program aims to provide a first-hand introduction to emerging issues and real-world training in the research skills that students need to advance in science, either as graduate students or bachelors-level working scientists. This is a long-recognized need and efforts are being made to ensure that the students begin to acquire skills and aptitudes that position them to take advantage of a wide range of opportunities. Of note is that the PEP is transitioning into a two year program where students are participating in a second year as a research intern or employee. Since 2013, at least four partner institutions have invited PEP alumni to participate in their respective programs as research assistants and/or full-time technicians.

Effects of intratracheally instilled laser printer-emitted engineered nanoparticles in a mouse model: A case study of toxicological implications from nanomaterials released during consumer use

PubMed Central

Pirela, Sandra V.; Lu, Xiaoyan; Miousse, Isabelle; Sisler, Jennifer D.; Qian, Yong; Guo, Nancy; Koturbash, Igor; Castranova, Vincent; Thomas, Treye; Godleski, John; Demokritou, Philip

2016-01-01

Incorporation of engineered nanomaterials (ENMs) into toners used in laser printers has led to countless quality and performance improvements. However, the release of ENMs during printing (consumer use) has raised concerns about their potential adverse health effects. The aim of this study was to use “real world” printer-emitted particles (PEPs), rather than raw toner powder, and assess the pulmonary responses following exposure by intratracheal instillation. Nine-week old male Balb/c mice were exposed to various doses of PEPs (0.5, 2.5 and 5 mg/kg body weight) by intratracheal instillation. These exposure doses are comparable to real world human inhalation exposures ranging from 13.7 to 141.9 h of printing. Toxicological parameters reflecting distinct mechanisms of action were evaluated, including lung membrane integrity, inflammation and regulation of DNA methylation patterns. Results from this in vivo toxicological analysis showed that while intratracheal instillation of PEPs caused no changes in the lung membrane integrity, there was a pulmonary immune response, indicated by an elevation in neutrophil and macrophage percentage over the vehicle control and low dose PEPs groups. Additionally, exposure to PEPs upregulated expression of the Ccl5 (Rantes), Nos1 and Ucp2 genes in the murine lung tissue and modified components of the DNA methylation machinery (Dnmt3a) and expression of transposable element (TE) LINE-1 compared to the control group. These genes are involved in both the repair process from oxidative damage and the initiation of immune responses to foreign pathogens. The results are in agreement with findings from previous in vitro cellular studies and suggest that PEPs may cause immune responses in addition to modifications in gene expression in the murine lung at doses that can be comparable to real world exposure scenarios, thereby raising concerns of deleterious health effects. PMID:26989787

Consumer exposures to laser printer-emitted engineered nanoparticles: A case study of life-cycle implications from nano-enabled products.

PubMed

Pirela, Sandra V; Sotiriou, Georgios A; Bello, Dhimiter; Shafer, Martin; Bunker, Kristin Lee; Castranova, Vincent; Thomas, Treye; Demokritou, Philip

2015-01-01

It is well established that printers emit nanoparticles during their operation. To-date, however, the physicochemical and toxicological characterization of "real world" printer-emitted nanoparticles (PEPs) remains incomplete, hampering proper risk assessment efforts. Here, we investigate our earlier hypothesis that engineered nanomaterials (ENMs) are used in toners and ENMs are released during printing (consumer use). Furthermore, we conduct a detailed physicochemical and morphological characterization of PEPs in support of ongoing toxicological assessment. A comprehensive suite of state of the art analytical methods and tools was employed for the physicochemical and morphological characterization of 11 toners widely utilized in printers from major printer manufacturers and their PEPs. We confirmed that a number of ENMs incorporated into toner formulations (e.g. silica, alumina, titania, iron oxide, zinc oxide, copper oxide, cerium oxide, carbon black among others) and released into the air during printing. All evaluated toners contained large amounts of organic carbon (OC, 42-89%), metals/metal oxides (1-33%), and some elemental carbon (EC, 0.33-12%). The PEPs possess a composition similar to that of toner and contained 50-90% OC, 0.001-0.5% EC and 1-3% metals. While the chemistry of the PEPs generally reflected that of their toners, considerable differences are documented indicative of potential transformations taking place during consumer use (printing). We conclude that: (i) Routine incorporation of ENMs in toners classifies them as nano-enabled products (NEPs); (ii) These ENMs become airborne during printing; (iii) The chemistry of PEPs is complex and it reflects that of the toner and paper. This work highlights the importance of understanding life-cycle (LC) nano-EHS implications of NEPs and assessing real world exposures and associated toxicological properties rather than focusing on "raw" materials used in the synthesis of an NEP.

Consumer exposures to laser printer-emitted engineered nanoparticles: A case study of life-cycle implications from nano-enabled products

PubMed Central

Pirela, Sandra V.; Sotiriou, Georgios A.; Bello, Dhimiter; Shafer, Martin; Bunker, Kristin Lee; Castranova, Vincent; Thomas, Treye; Demokritou, Philip

2015-01-01

It is well established that printers emit nanoparticles during their operation. To-date, however, the physicochemical and toxicological characterization of “real world” printer-emitted nanoparticles (PEPs) remains incomplete, hampering proper risk assessment efforts. Here, we investigate our earlier hypothesis that engineered nanomaterials (ENMs) are used in toners and ENMs are released during printing (consumer use). Furthermore, we conduct a detailed physicochemical and morphological characterization of PEPs in support of ongoing toxicological assessment. A comprehensive suite of state of the art analytical methods and tools was employed for the physicochemical and morphological characterization of 11 toners widely utilized in printers from major printer manufacturers and their PEPs. We confirmed that a number of ENMs incorporated into toner formulations (e.g., silica, alumina, titania, iron oxide, zinc oxide, copper oxide, cerium oxide, carbon black among others) and released into the air during printing. All evaluated toners contained large amounts of organic carbon (OC, 42–89%), metals/metal oxides (1–33%), and some elemental carbon (EC, 0.33–12%). The PEPs possess a composition similar to that of toner and contained 50–90% OC, 0.001–0.5% EC and 1–3% metals. While the chemistry of the PEPs generally reflected that of their toners, considerable differences are documented indicative of potential transformations taking place during consumer use (printing). We conclude that: (i) Routine incorporation of ENMs in toners classifies them as nano-enabled products (NEPs); (ii) These ENMs become airborne during printing; (iii) The chemistry of PEPs is complex and it reflects that of the toner and paper. This work highlights the importance of understanding life-cycle (LC) nano-EHS implications of NEPs and assessing real world exposures and associated toxicological properties rather than focusing on “raw” materials used in the synthesis of an NEP. PMID:25387251

Diversifying a Famous Science Community One Cohort at a Time: The Woods Hole Partnership Education Program (PEP)

NASA Astrophysics Data System (ADS)

Scott, O.; Jearld, A.

2012-12-01

In March 2009, the Woods Hole Diversity Initiative launched the Partnership Education Program (PEP), a multi-institutional effort to increase diversity in the student population (and ultimately the work force) in the Woods Hole science community. PEP, a summer research internship program, is open to students of all backgrounds but is designed especially to provide opportunities for individuals from populations under-represented in science, technology, engineering, and mathematics (STEM) and who otherwise would not have had the opportunity to come to Woods Hole to study or do research. To date, 60 students from 39 colleges and universities have participated and there is evidence that PEP students are being retained and continuing on the path towards completing STEM degrees and pursuing careers in marine and environmental science. PEP alumni are enrolled in graduate programs and employed in STEM-related jobs. They have availed themselves to other experiential learning and career development opportunities in the Woods Hole community and beyond. They have published papers with their PEP research mentors, and have won awards from presentations at professional conferences. During the PEP summer program, students gain a range of skills and knowledge as well as acquire the dispositions, attitudes and behaviors that are essential to their educational and career success. These run the gamut and include areas such as content and technical research knowledge related to the marine and environmental sciences, next step education and career transitions, and key competencies related to educational and career progression in STEM fields. As an evidence-based, promising practice for retaining students in STEM, the PEP model is emerging as an effective and sustainable approach. Beyond Woods Hole, PEP is gaining national recognition as information about PEP is disseminated via multiple channels, both electronic and non electronic. PEP's applicant pool has increased from 24 in Year 1 to 70 in Year 4. As a collaborative, partnership initiative, PEP has established a critical mass of underrepresented students participating in the Woods Hole scientific communities who, through their research, are contributing to advancing knowledge in the marine and environmental sciences. PEP's instrumental role in supporting students as they pursue STEM education and careers and helping them maintain a positive trajectory is invaluable as a sustainable approach that features institutions that pool resources to accomplish a common goal.

Operation and Performance Measurement on Engines in Sea Level Test Facilities

DTIC Science & Technology

1984-03-01

progressively larger collector to ’:7.. *: capture the efflux, but secondary airflow increases rapidly as collector area .-- increases. Therefore...1 + Dbm + Dc + Dts + Dbt - WeVe + (Pe - P 2 )Ae where the terms above and to follow are defined as Fa - measured thrust from load cell Pn - net thrust...Dbt - buoyancy (boat-tail) drag on exhaust nozzle. Considering that . (Pe-P" 2 )Ae + WeVe - (Pe-P..)Ae + (P-1-P- 2 )Ae + WeVe and .. .* Pg (Pe-PŖ)Ae

Disentangling the Disabling Process: Insights From the Precipitating Events Project

PubMed Central

Gill, Thomas M.

2014-01-01

Among older persons, disability in activities of daily living is common and highly morbid. The Precipitating Events Project (PEP Study), an ongoing longitudinal study of 754 initially nondisabled, community-living persons, aged 70 or older, was designed to further elucidate the epidemiology of disability, with the goal of informing the development of effective interventions to maintain and restore independent function. Over the past 16 years, participants have completed comprehensive, home-based assessments at 18-month intervals and have been interviewed monthly to reassess their functional status and ascertain intervening events, other health care utilization, and deaths. Findings from the PEP Study have demonstrated that the disabling process for many older persons is characterized by multiple and possibly interrelated disability episodes, even over relatively short periods of time, and that disability often results when an intervening event is superimposed upon a vulnerable host. Given the frequency of assessments, long duration of follow-up, and recent linkage to Medicare data, the PEP Study will continue to be an outstanding platform for disability research in older persons. In addition, as the number of decedents accrues, the PEP Study will increasingly become a valuable resource for investigating symptoms, function, and health care utilization at the end of life. PMID:25035454

GRC-2005-C-01066

NASA Image and Video Library

2001-07-28

Photographic documentation of the High Power Engine Propulsion HiPEP after a duration test. Also photographed are the instrumentation and installation articles to reveal post test conditions such as corrosion and pitting.

GRC-2005-C-01076

NASA Image and Video Library

2001-07-28

Photographic documentation of the High Power Engine Propulsion HiPEP after a duration test. Also photographed are the instrumentation and installation articles to reveal post test conditions such as corrosion and pitting.

GRC-2005-C-01036

NASA Image and Video Library

2001-07-28

Photographic documentation of the High Power Engine Propulsion HiPEP after a duration test. Also photographed are the instrumentation and installation articles to reveal post test conditions such as corrosion and pitting.

SpirPep: an in silico digestion-based platform to assist bioactive peptides discovery from a genome-wide database.

PubMed

Anekthanakul, Krittima; Hongsthong, Apiradee; Senachak, Jittisak; Ruengjitchatchawalya, Marasri

2018-04-20

Bioactive peptides, including biological sources-derived peptides with different biological activities, are protein fragments that influence the functions or conditions of organisms, in particular humans and animals. Conventional methods of identifying bioactive peptides are time-consuming and costly. To quicken the processes, several bioinformatics tools are recently used to facilitate screening of the potential peptides prior their activity assessment in vitro and/or in vivo. In this study, we developed an efficient computational method, SpirPep, which offers many advantages over the currently available tools. The SpirPep web application tool is a one-stop analysis and visualization facility to assist bioactive peptide discovery. The tool is equipped with 15 customized enzymes and 1-3 miscleavage options, which allows in silico digestion of protein sequences encoded by protein-coding genes from single, multiple, or genome-wide scaling, and then directly classifies the peptides by bioactivity using an in-house database that contains bioactive peptides collected from 13 public databases. With this tool, the resulting peptides are categorized by each selected enzyme, and shown in a tabular format where the peptide sequences can be tracked back to their original proteins. The developed tool and webpages are coded in PHP and HTML with CSS/JavaScript. Moreover, the tool allows protein-peptide alignment visualization by Generic Genome Browser (GBrowse) to display the region and details of the proteins and peptides within each parameter, while considering digestion design for the desirable bioactivity. SpirPep is efficient; it takes less than 20 min to digest 3000 proteins (751,860 amino acids) with 15 enzymes and three miscleavages for each enzyme, and only a few seconds for single enzyme digestion. Obviously, the tool identified more bioactive peptides than that of the benchmarked tool; an example of validated pentapeptide (FLPIL) from LC-MS/MS was demonstrated. The web and database server are available at http://spirpepapp.sbi.kmutt.ac.th . SpirPep, a web-based bioactive peptide discovery application, is an in silico-based tool with an overview of the results. The platform is a one-stop analysis and visualization facility; and offers advantages over the currently available tools. This tool may be useful for further bioactivity analysis and the quantitative discovery of desirable peptides.

Updated US Public Health Service guidelines for the management of occupational exposures to human immunodeficiency virus and recommendations for postexposure prophylaxis.

PubMed

Kuhar, David T; Henderson, David K; Struble, Kimberly A; Heneine, Walid; Thomas, Vasavi; Cheever, Laura W; Gomaa, Ahmed; Panlilio, Adelisa L

2013-09-01

This report updates US Public Health Service recommendations for the management of healthcare personnel (HCP) who experience occupational exposure to blood and/or other body fluids that might contain human immunodeficiency virus (HIV). Although the principles of exposure management remain unchanged, recommended HIV postexposure prophylaxis (PEP) regimens and the duration of HIV follow-up testing for exposed personnel have been updated. This report emphasizes the importance of primary prevention strategies, the prompt reporting and management of occupational exposures, adherence to recommended HIV PEP regimens when indicated for an exposure, expert consultation in management of exposures, follow-up of exposed HCP to improve adherence to PEP, and careful monitoring for adverse events related to treatment, as well as for virologic, immunologic, and serologic signs of infection. To ensure timely postexposure management and administration of HIV PEP, clinicians should consider occupational exposures as urgent medical concerns, and institutions should take steps to ensure that staff are aware of both the importance of and the institutional mechanisms available for reporting and seeking care for such exposures. The following is a summary of recommendations: (1) PEP is recommended when occupational exposures to HIV occur; (2) the HIV status of the exposure source patient should be determined, if possible, to guide need for HIV PEP; (3) PEP medication regimens should be started as soon as possible after occupational exposure to HIV, and they should be continued for a 4-week duration; (4) new recommendation-PEP medication regimens should contain 3 (or more) antiretroviral drugs (listed in Appendix A ) for all occupational exposures to HIV; (5) expert consultation is recommended for any occupational exposures to HIV and at a minimum for situations described in Box 1 ; (6) close follow-up for exposed personnel ( Box 2 ) should be provided that includes counseling, baseline and follow-up HIV testing, and monitoring for drug toxicity; follow-up appointments should begin within 72 hours of an HIV exposure; and (7) new recommendation-if a newer fourth-generation combination HIV p24 antigen-HIV antibody test is utilized for follow-up HIV testing of exposed HCP, HIV testing may be concluded 4 months after exposure ( Box 2 ); if a newer testing platform is not available, follow-up HIV testing is typically concluded 6 months after an HIV exposure.

Engineering an Affinity-Enhanced Peptide through Optimization of Cyclization Chemistry.

PubMed

Ngambenjawong, Chayanon; Pineda, Julio Marco B; Pun, Suzie H

2016-12-21

Peptide cyclization is a strategy used to improve stability and activity of peptides. The most commonly used cyclization method is disulfide bridge formation of cysteine-containing peptides, as is typically found in nature. Over the years, an increasing number of alternative chemistries for peptide cyclization with improved efficiency, kinetics, orthogonality, and stability have been reported. However, there has been less appreciation for the opportunity to fine-tune peptide activity via the diverse chemical entities introduced at the site of linkage by different cyclization strategies. Here, we demonstrate how cyclization optimization of an M2 "anti-inflammatory" macrophage-binding peptide (M2pep) resulted in a significant increase in binding affinity of the optimized analog to M2 macrophages while maintaining binding selectivity compared to M1 "pro-inflammatory" macrophages. In this study, we report synthesis and evaluation of four cyclic M2pep(RY) analogs with diverse cyclization strategies: (1) Asp-[amide]-Lys, (2) azido-Lys-[triazole(copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC))]-propargyl-Gly, (3) Cys-[decafluorobiphenyl (DFBP)]-Cys, and (4) Cys-[decafluorobiphenyl sulfone (DFS)]-Cys, whereby the chemical entity or linker at the linkage site is shown in the square bracket and is between the residues involved in cyclization. These peptides are compared to a disulfide-cyclized M2pep(RY) that we previously reported as a serum-stable, affinity-enhanced analog to the original linear M2pep. DFBP-cyclized M2pep(RY) exhibits the highest binding activity to M2 macrophages with apparent dissociation constant (K D ) about 2.03 μM compared to 36.3 μM for the original disulfide-cyclized M2pep(RY) and 220 μM for the original linear peptide. DFS-cyclized M2pep(RY) also binds more strongly than the original cyclized analog, whereas amide- and triazole-cyclized M2pep(RY) analogs bind less strongly. We verified that DFBP alone has negligible binding to M2 macrophages and the incorporation of diphenylalanine to the original sequence improves binding activity at the expense of solubility and increased toxicity. In conclusion, we report development of cyclic M2pep(RY) analogs with diverse cyclization strategies leading to the discovery of DFBP-cyclized M2pep(RY) with enhanced M2 macrophage-binding activity.

Dendrimer-conjugated peptide vaccine enhances clearance of Chlamydia trachomatis genital infection.

PubMed

Ganda, Ingrid S; Zhong, Qian; Hali, Mirabela; Albuquerque, Ricardo L C; Padilha, Francine F; da Rocha, Sandro R P; Whittum-Hudson, Judith A

2017-07-15

Peptide-based vaccines have emerged in recent years as promising candidates in the prevention of infectious diseases. However, there are many challenges to maintaining in vivo peptide stability and enhancement of peptide immunogenicity to generate protective immunity which enhances clearance of infections. Here, a dendrimer-based carrier system is proposed for peptide-based vaccine delivery, and shows its anti-microbial feasibility in a mouse model of Chlamydia trachomatis. Chlamydiae are the most prevalent sexually transmitted bacteria worldwide, and also the causal agent of trachoma, the leading cause of preventable infectious blindness. In spite of the prevalence of this infectious agent and the many previous vaccine-related studies, there is no vaccine commercially available. The carrier system proposed consists of generation 4, hydroxyl-terminated, polyamidoamine (PAMAM) dendrimers (G4OH), to which a peptide mimic of a chlamydial glycolipid antigen-Peptide 4 (Pep4, AFPQFRSATLLL) was conjugated through an ester bond. The ester bond between G4OH and Pep4 is expected to break down mainly in the intracellular environment for antigen presentation. Pep4 conjugated to dendrimer induced Chlamydia-specific serum antibodies after subcutaneous immunizations. Further, this new vaccine formulation significantly protected immunized animals from vaginal challenge with infectious Chlamydia trachomatis, and it reduced infectious loads and tissue (genital tract) damage. Pep4 conjugated to G4OH or only mixed with peptide provided enhanced protection compared to Pep4 and adjuvant (i.e. alum), suggesting a potential adjuvant effect of the PAMAM dendrimer. Combined, these results demonstrate that hydroxyl-terminated PAMAM dendrimer is a promising polymeric nanocarrier platform for the delivery of peptide vaccines and this approach has potential to be expanded to other infectious intracellular bacteria and viruses of public health significance. Copyright © 2017 Elsevier B.V. All rights reserved.

Turn-on fluorescence sensor based on single-walled-carbon-nanohorn-peptide complex for the detection of thrombin.

PubMed

Zhu, Shuyun; Liu, Zhongyuan; Hu, Lianzhe; Yuan, Yali; Xu, Guobao

2012-12-14

Proteases play a central role in several widespread diseases. Thus, there is a great need for the fast and sensitive detection of various proteolytic enzymes. Herein, we have developed a carbon nanotube (CNT)-based protease biosensing platform that uses peptides as a fluorescence probe for the first time. Single-walled carbon nanohorns (SWCNHs) and thrombin were used to demonstrate this detection strategy. SWCNHs can adsorb a fluorescein-based dye (FAM)-labeled peptide (FAM-pep) and quench the fluorescence of FAM. In contrast, thrombin can cleave FAM-pep on SWCNHs and recover the fluorescence of FAM, which allows the sensitive detection of thrombin. This biosensor has a high sensitivity and selectivity toward thrombin, with a detection limit of 100 pM. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Stanford Synchrotron Radiation Laboratory activity report for 1986

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

Cantwell, K.

1987-12-31

1986 was another year of major advances for SSRL as the ultimate capabilities of PEP as a synchrotron radiation source became more apparent and a second PEP beam line was initiated, while effective development and utilization of SPEAR proceeded. Given these various PEP developments, SSRL abandoned its plans for a separate diffraction limited ring, as they abandoned their plans for a 6--7 GeV ring of the APS type last year. It has become increasingly apparent that SSRL should concentrate on developing SPEAR and PEP as synchrotron radiation sources. Consequently, initial planning for a 3 GeV booster synchrotron injector for SPEARmore » was performed in 1986, with a proposal to the Department of Energy resulting. As described in Chapter 2, the New Rings Group and the Machine Physics Group were combined into one Accelerator Physics Group. This group is focusing mainly on the improvement of SPEAR`s operating conditions and on planning for the conversion of PEP into a fourth generation x-ray source. Considerable emphasis is also being given to the training of accelerator physics graduate students. At the same time, several improvements of SSRL`s existing facilities were made. These are described in Chapter 3. Chapter 4 describes new SSRL beam lines being commissioned. Chapter 5 discusses SSRL`s present construction projects. Chapter 6 discusses a number of projects presently underway in the engineering division. Chapter 7 describes SSRL`s advisory panels while Chapter 8 discusses SSRL`s overall organization. Chapter 9 describes the experimental progress reports.« less

[Construction and prokaryotic expression of recombinant gene EGFRvIII HBcAg and immunogenicity analysis of the fusion protein].

PubMed

Duan, Xiao-yi; Wang, Jian-sheng; Guo, You-min; Han, Jun-li; Wang, Quan-ying; Yang, Guang-xiao

2007-01-01

To construct recombinant prokaryotic expression plasmid pET28a(+)/c-PEP-3-c and evaluate the immunogenicity of the fusion protein. cDNA fragment encoding PEP-3 was obtained from pGEM-T Easy/PEP-3 and inserted into recombinant plasmid pGEMEX/HBcAg. Then it was subcloned in prokaryotic expression vector and transformed into E.coli BL21(DE3). The fusion protein was expressed by inducing IPTG and purified by Ni(2+)-NTA affinity chromatography. BALB/c mice were immunized with fusion protein and the antibody titre was determined by indirect ELISA. The recombinant gene was confirmed to be correct by restriction enzyme digestion and DNA sequencing. After prokaryotic expression, fusion protein existed in sediment and accounted for 56% of all bacterial lysate. The purified product accounted for 92% of all protein and its concentration was 8 g/L. The antibody titre in blood serum reached 1:16 000 after the fourth immunization and reached 1:2.56x10(5) after the sixth immunization. The titre of anti-PEP-3 antibody reached 1:1.28x10(5) and the titre of anti-HBcAg antibody was less than 1:4x10(3). Fusion gene PEP-3-HBcAg is highly expressed in E.coli BL21. The expressed fusion protein can induce neutralizing antibody with high titer and specificity, which lays a foundation for the study of genetically engineering vaccine for malignant tumors with the high expression of EGFRvIII.

OAO-3 end of mission tests report

NASA Technical Reports Server (NTRS)

Kalil, F.; Kull, F. J.; Mcintosh, R.; Ollendorf, S.; Margolies, D. L.; Gemmell, J.; Tasevoli, C. M.; Polidan, R. S.; Kochevar, H.; Chapman, C.

1981-01-01

Twelve engineering type tests were performed on several subsystems and experiment(s) of the OAO 3 spacecraft near its end of mission. The systems tested include: Princeton experiment package (PEP), fine error system guidance, inertial reference unit, star trackers, heat pipes, thermal control coatings, command and data handling, solar array; batteries, and onboard processor/power boost regulator. Generally, the systems performed well for the 8 1/2 years life of OAO 3, although some degradation was noted in the sensitivity of PEP and in the absorptivity of the skin coatings. Battery life was prolonged during the life of the mission in large part by carefully monitoring the charge-discharge cycle with careful attention not to overcharge.

Feasibility Study for an Asymmetric B Factory Based on PEP

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

Chattapadhyay, A.; Hitlin, D.; Porter, F.

This report addresses the feasibility of designing and constructing an asymmetric B-factory based on the PEP storage ring at SLAC that can ultimately reach a luminosity of 1 X 10{sup 34} cm{sup -2}s{sup -1}. Such a facility, operating at the {gamma}(4S) resonance, could be used to study mixing, rate decays, and CP violation in the B{bar B} system, and could also study tau and charm physics. The essential accelerator physics, engineering, and technology issues that must be addressed to successfully build this exciting and challenging facility are identified, and possible solutions, or R and D that will reasonable lead tomore » such solutions, are described.« less

Towards an integrative model of C4 photosynthetic subtypes: insights from comparative transcriptome analysis of NAD-ME, NADP-ME, and PEP-CK C4 species

PubMed Central

Bräutigam, Andrea; Schliesky, Simon; Külahoglu, Canan; Osborne, Colin P.; Weber, Andreas P.M.

2014-01-01

C4 photosynthesis affords higher photosynthetic carbon conversion efficiency than C3 photosynthesis and it therefore represents an attractive target for engineering efforts aiming to improve crop productivity. To this end, blueprints are required that reflect C4 metabolism as closely as possible. Such blueprints have been derived from comparative transcriptome analyses of C3 species with related C4 species belonging to the NAD-malic enzyme (NAD-ME) and NADP-ME subgroups of C4 photosynthesis. However, a comparison between C3 and the phosphoenolpyruvate carboxykinase (PEP-CK) subtype of C4 photosynthesis is still missing. An integrative analysis of all three C4 subtypes has also not been possible to date, since no comparison has been available for closely related C3 and PEP-CK C4 species. To generate the data, the guinea grass Megathyrsus maximus, which represents a PEP-CK species, was analysed in comparison with a closely related C3 sister species, Dichanthelium clandestinum, and with publicly available sets of RNA-Seq data from C4 species belonging to the NAD-ME and NADP-ME subgroups. The data indicate that the core C4 cycle of the PEP-CK grass M. maximus is quite similar to that of NAD-ME species with only a few exceptions, such as the subcellular location of transfer acid production and the degree and pattern of up-regulation of genes encoding C4 enzymes. One additional mitochondrial transporter protein was associated with the core cycle. The broad comparison identified sucrose and starch synthesis, as well as the prevention of leakage of C4 cycle intermediates to other metabolic pathways, as critical components of C4 metabolism. Estimation of intercellular transport fluxes indicated that flux between cells is increased by at least two orders of magnitude in C4 species compared with C3 species. In contrast to NAD-ME and NADP-ME species, the transcription of photosynthetic electron transfer proteins was unchanged in PEP-CK. In summary, the PEP-CK blueprint of M. maximus appears to be simpler than those of NAD-ME and NADP-ME plants. PMID:24642845

Improvement of succinate production by release of end-product inhibition in Corynebacterium glutamicum.

PubMed

Chung, Soon-Chun; Park, Joon-Song; Yun, Jiae; Park, Jin Hwan

2017-03-01

Succinate is a renewable-based platform chemical that may be used to produce a wide range of chemicals including 1,4-butanediol, tetrahydrofurane, and γ-butyrolactone. However, industrial fermentation of organic acids is often subject to end-product inhibition, which significantly retards cell growth and limits metabolic activities and final productivity. In this study, we report the development of metabolically engineered Corynebacterium glutamicum for high production of succinate by release of end-product inhibition coupled with an increase of key metabolic flux. It was found that the rates of glucose consumption and succinate production were significantly reduced by extracellular succinate in an engineered strain, S003. To understand the mechanism underlying the inhibition by succinate, comparative transcriptome analysis was performed. Among the downregulated genes, overexpression of the NCgl0275 gene was found to suppress the inhibition of glucose consumption and succinate production, resulting in a 37.7% increase in succinate production up to 55.4g/L in fed-batch fermentation. Further improvement was achieved by increasing the metabolic flux from PEP to OAA. The final engineered strain was able to produce 152.2g/L succinate, the highest production reported to date, with a yield of 1.1g/g glucose under anaerobic condition. These results suggest that the release of end-product inhibition coupled with an increase in key metabolic flux is a promising strategy for enhancing production of succinate. Copyright © 2017. Published by Elsevier Inc.

Producibility Engineering and Planning (PEP)

DTIC Science & Technology

1977-01-01

Materiel System, May 1976. c. Cesare Raimondi, "Estimating Drafting Time - Art , Science , Guess- work", Machine Design, 7 September 1972. d. Current Wage...Comprehensive 8 16 24 32 40 86 45 70 90 80 1/ Cesare Raimondi, "Estimating Drafting Time- Art , Science , Guesswork," Machine Design, September

Project fires. Volume 2: Protective ensemble performance standards, phase 1B

NASA Astrophysics Data System (ADS)

Abeles, F. J.

1980-05-01

The design of the prototype protective ensemble was finalized. Prototype ensembles were fabricated and then subjected to a series of qualification tests which were based upon the protective ensemble performance standards PEPS requirements. Engineering drawings and purchase specifications were prepared for the new protective ensemble.

Genetic engineering of Escherichia coli to improve L-phenylalanine production.

PubMed

Liu, Yongfei; Xu, Yiran; Ding, Dongqin; Wen, Jianping; Zhu, Beiwei; Zhang, Dawei

2018-01-30

L-phenylalanine (L-Phe) is an essential amino acid for mammals and applications expand into human health and nutritional products. In this study, a system level engineering was conducted to enhance L-Phe biosynthesis in Escherichia coli. We inactivated the PTS system and recruited glucose uptake via combinatorial modulation of galP and glk to increase PEP supply in the Xllp01 strain. In addition, the HTH domain of the transcription factor TyrR was engineered to decrease the repression on the transcriptional levels of L-Phe pathway enzymes. Finally, proteomics analysis demonstrated the third step of the SHIK pathway (catalyzed via AroD) as the rate-limiting step for L-Phe production. After optimization of the aroD promoter strength, the titer of L-Phe increased by 13.3%. Analysis of the transcriptional level of genes involved in the central metabolic pathways and L-Phe biosynthesis via RT-PCR showed that the recombinant L-Phe producer exhibited a great capability in the glucose utilization and precursor (PEP and E4P) generation. Via systems level engineering, the L-Phe titer of Xllp21 strain reached 72.9 g/L in a 5 L fermenter under the non-optimized fermentation conditions, which was 1.62-times that of the original strain Xllp01. The metabolic engineering strategy reported here can be broadly employed for developing genetically defined organisms for the efficient production of other aromatic amino acids and derived compounds.

Characterization of a New M13 Metallopeptidase from Deep-Sea Shewanella sp. E525-6 and Mechanistic Insight into Its Catalysis

PubMed Central

Yang, Jin-Yu; Wang, Peng; Li, Chun-Yang; Dong, Sheng; Song, Xiao-Yan; Zhang, Xi-Ying; Xie, Bin-Bin; Zhou, Bai-Cheng; Zhang, Yu-Zhong; Chen, Xiu-Lan

2016-01-01

Bacterial extracellular peptidases are important for bacterial nutrition and organic nitrogen degradation in the ocean. While many peptidases of the M13 family from terrestrial animals and bacteria are studied, there has been no report on M13 peptidases from marine bacteria. Here, we characterized an M13 peptidase, PepS, from the deep-sea sedimentary strain Shewanella sp. E525-6, and investigated its substrate specificity and catalytic mechanism. The gene pepS cloned from strain E525-6 contains 2085 bp and encodes an M13 metallopeptidase. PepS was expressed in Escherichia coli and purified. Among the characterized M13 peptidases, PepS shares the highest sequence identity (47%) with Zmp1 from Mycobacterium tuberculosis, indicating that PepS is a new member of the M13 family. PepS had the highest activity at 30°C and pH 8.0. It retained 15% activity at 0°C. Its half life at 40°C was only 4 min. These properties indicate that PepS is a cold-adapted enzyme. The smallest substrate for PepS is pentapeptide, and it is probably unable to cleave peptides of more than 30 residues. PepS prefers to hydrolyze peptide bonds with P1′ hydrophobic residues. Structural and mutational analyses suggested that His531, His535 and Glu592 coordinate the catalytic zinc ion in PepS, Glu532 acts as a nucleophile, and His654 is probably involved in the transition state stabilization. Asp538 and Asp596 can stablize the orientations of His531 and His535, and Arg660 can stablize the orientation of Asp596. These results help in understanding marine bacterial peptidases and organic nitrogen degradation. PMID:26779153

Characterization of a New M13 Metallopeptidase from Deep-Sea Shewanella sp. E525-6 and Mechanistic Insight into Its Catalysis.

PubMed

Yang, Jin-Yu; Wang, Peng; Li, Chun-Yang; Dong, Sheng; Song, Xiao-Yan; Zhang, Xi-Ying; Xie, Bin-Bin; Zhou, Bai-Cheng; Zhang, Yu-Zhong; Chen, Xiu-Lan

2015-01-01

Bacterial extracellular peptidases are important for bacterial nutrition and organic nitrogen degradation in the ocean. While many peptidases of the M13 family from terrestrial animals and bacteria are studied, there has been no report on M13 peptidases from marine bacteria. Here, we characterized an M13 peptidase, PepS, from the deep-sea sedimentary strain Shewanella sp. E525-6, and investigated its substrate specificity and catalytic mechanism. The gene pepS cloned from strain E525-6 contains 2085 bp and encodes an M13 metallopeptidase. PepS was expressed in Escherichia coli and purified. Among the characterized M13 peptidases, PepS shares the highest sequence identity (47%) with Zmp1 from Mycobacterium tuberculosis, indicating that PepS is a new member of the M13 family. PepS had the highest activity at 30°C and pH 8.0. It retained 15% activity at 0°C. Its half life at 40°C was only 4 min. These properties indicate that PepS is a cold-adapted enzyme. The smallest substrate for PepS is pentapeptide, and it is probably unable to cleave peptides of more than 30 residues. PepS prefers to hydrolyze peptide bonds with P1' hydrophobic residues. Structural and mutational analyses suggested that His531, His535 and Glu592 coordinate the catalytic zinc ion in PepS, Glu532 acts as a nucleophile, and His654 is probably involved in the transition state stabilization. Asp538 and Asp596 can stablize the orientations of His531 and His535, and Arg660 can stablize the orientation of Asp596. These results help in understanding marine bacterial peptidases and organic nitrogen degradation.

Floor Plans Engine Removal Platform, Hold Down Arm Platform, ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Floor Plans - Engine Removal Platform, Hold Down Arm Platform, Hydraulic Equipment Platforms, Isometric Cutaway of Engine Removal Platform, Isometric Cutaway of Hold Down Arm Platform, Isometric Cutaway of Hydraulic Platforms and Engine Support System Access - Marshall Space Flight Center, Saturn V S-IC Static Test Facility, West Test Area, Huntsville, Madison County, AL

Expression of six peptidases from Lactobacillus helveticus in Lactococcus lactis.

PubMed

Luoma, S; Peltoniemi, K; Joutsjoki, V; Rantanen, T; Tamminen, M; Heikkinen, I; Palva, A

2001-03-01

For development of novel starter strains with improved proteolytic properties, the ability of Lactococcus lactis to produce Lactobacillus helveticus aminopeptidase N (PepN), aminopeptidase C (PepC), X-prolyl dipeptidyl aminopeptidase (PepX), proline iminopeptidase (PepI), prolinase (PepR), and dipeptidase (PepD) was studied by introducing the genes encoding these enzymes into L. lactis MG1363 and its derivatives. According to Northern analyses and enzyme activity measurements, the L. helveticus aminopeptidase genes pepN, pepC, and pepX are expressed under the control of their own promoters in L. lactis. The highest expression level, using a low-copy-number vector, was obtained with the L. helveticus pepN gene, which resulted in a 25-fold increase in PepN activity compared to that of wild-type L. lactis. The L. helveticus pepI gene, residing as a third gene in an operon in its host, was expressed in L. lactis under the control of the L. helveticus pepX promoter. The genetic background of the L. lactis derivatives tested did not affect the expression level of any of the L. helveticus peptidases studied. However, the growth medium used affected both the recombinant peptidase profiles in transformant strains and the resident peptidase activities. The levels of expression of the L. helveticus pepD and pepR clones under the control of their own promoters were below the detection limit in L. lactis. However, substantial amounts of recombinant pepD and PepR activities were obtained in L. lactis when pepD and pepR were expressed under the control of the inducible lactococcal nisA promoter at an optimized nisin concentration.

Expression of Six Peptidases from Lactobacillus helveticus in Lactococcus lactis

PubMed Central

Luoma, Susanna; Peltoniemi, Kirsi; Joutsjoki, Vesa; Rantanen, Terhi; Tamminen, Marja; Heikkinen, Inka; Palva, Airi

2001-01-01

For development of novel starter strains with improved proteolytic properties, the ability of Lactococcus lactis to produce Lactobacillus helveticus aminopeptidase N (PepN), aminopeptidase C (PepC), X-prolyl dipeptidyl aminopeptidase (PepX), proline iminopeptidase (PepI), prolinase (PepR), and dipeptidase (PepD) was studied by introducing the genes encoding these enzymes into L. lactis MG1363 and its derivatives. According to Northern analyses and enzyme activity measurements, the L. helveticus aminopeptidase genes pepN, pepC, and pepX are expressed under the control of their own promoters in L. lactis. The highest expression level, using a low-copy-number vector, was obtained with the L. helveticus pepN gene, which resulted in a 25-fold increase in PepN activity compared to that of wild-type L. lactis. The L. helveticus pepI gene, residing as a third gene in an operon in its host, was expressed in L. lactis under the control of the L. helveticus pepX promoter. The genetic background of the L. lactis derivatives tested did not affect the expression level of any of the L. helveticus peptidases studied. However, the growth medium used affected both the recombinant peptidase profiles in transformant strains and the resident peptidase activities. The levels of expression of the L. helveticus pepD and pepR clones under the control of their own promoters were below the detection limit in L. lactis. However, substantial amounts of recombinant pepD and PepR activities were obtained in L. lactis when pepD and pepR were expressed under the control of the inducible lactococcal nisA promoter at an optimized nisin concentration. PMID:11229915

The structure and outcomes of a HIV postexposure prophylaxis program in a high HIV prevalence setup in western Kenya.

PubMed

Siika, Abraham M; Nyandiko, Winston M; Mwangi, Ann; Waxman, Michael; Sidle, John E; Kimaiyo, Sylvester N; Wools-Kaloustian, Kara

2009-05-01

In 2001, HIV postexposure prophylaxis (PEP) was initiated in western Kenya. Design, implementation, and evolution of the PEP program are described. Patient data were analyzed for reasons, time to initiation, and PEP outcome. Occupational PEP was initiated first followed by nonoccupational PEP (nPEP). Antiretroviral regimens were based upon national PEP guidelines, affordability and availability, and prevailing HIV prevalence. Emerging side effects data and cost improvements influenced regimen changes. Between November 2001 and December 2006, 446 patients sought PEP. Occupational exposure: 91 patients: 51 males; 72 accepted HIV testing; 48 of 52 source patients were HIV infected; median exposure-PEP time 3 hours (range: 0.3-96 hours). Of 72 HIV-negative patients receiving PEP, 3 discontinued, 69 completed, and 23 performed post-PEP HIV RNA polymerase chain reaction (all negative). Eleven follow-up HIV enzyme-linked immunosorbent assay tests have all turned negative. Nonoccupational exposure: 355 patients; 285 females; 90 children; 300 accepted HIV testing; median exposure-nPEP time 19 hours (range: 1-672 hours). Of 296 HIV-negative patients on nPEP, 1 died, 15 discontinued, 104 are on record having completed PEP, and 129 returned for 6-week HIV RNA polymerase chain reaction (1 patient tested positive). Eighty-seven follow-up HIV enzyme-linked immunosorbent assay tests have all turned negative. It is feasible to provide PEP and nPEP in resource-constrained settings.

Towards an integrative model of C4 photosynthetic subtypes: insights from comparative transcriptome analysis of NAD-ME, NADP-ME, and PEP-CK C4 species.

PubMed

Bräutigam, Andrea; Schliesky, Simon; Külahoglu, Canan; Osborne, Colin P; Weber, Andreas P M

2014-07-01

C4 photosynthesis affords higher photosynthetic carbon conversion efficiency than C3 photosynthesis and it therefore represents an attractive target for engineering efforts aiming to improve crop productivity. To this end, blueprints are required that reflect C4 metabolism as closely as possible. Such blueprints have been derived from comparative transcriptome analyses of C3 species with related C4 species belonging to the NAD-malic enzyme (NAD-ME) and NADP-ME subgroups of C4 photosynthesis. However, a comparison between C3 and the phosphoenolpyruvate carboxykinase (PEP-CK) subtype of C4 photosynthesis is still missing. An integrative analysis of all three C4 subtypes has also not been possible to date, since no comparison has been available for closely related C3 and PEP-CK C4 species. To generate the data, the guinea grass Megathyrsus maximus, which represents a PEP-CK species, was analysed in comparison with a closely related C3 sister species, Dichanthelium clandestinum, and with publicly available sets of RNA-Seq data from C4 species belonging to the NAD-ME and NADP-ME subgroups. The data indicate that the core C4 cycle of the PEP-CK grass M. maximus is quite similar to that of NAD-ME species with only a few exceptions, such as the subcellular location of transfer acid production and the degree and pattern of up-regulation of genes encoding C4 enzymes. One additional mitochondrial transporter protein was associated with the core cycle. The broad comparison identified sucrose and starch synthesis, as well as the prevention of leakage of C4 cycle intermediates to other metabolic pathways, as critical components of C4 metabolism. Estimation of intercellular transport fluxes indicated that flux between cells is increased by at least two orders of magnitude in C4 species compared with C3 species. In contrast to NAD-ME and NADP-ME species, the transcription of photosynthetic electron transfer proteins was unchanged in PEP-CK. In summary, the PEP-CK blueprint of M. maximus appears to be simpler than those of NAD-ME and NADP-ME plants. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology.

High activity and stability of codon-optimized phosphoenolpyruvate carboxylase from Photobacterium profundum SS9 at low temperatures and its application for in vitro production of oxaloacetate.

PubMed

Park, Soohyun; Hong, Soohye; Pack, Seung Pil; Lee, Jinwon

2014-02-01

Phosphoenolpyruvate carboxylase (PEPC) of Photobacterium profundum SS9 can be expressed and purified using the Escherichia coli expression system. In this study, a codon-optimized PEPC gene (OPPP) was used to increase expression levels. We confirmed OPPP expression and purified it from extracts of recombinant E. coli SGJS117 harboring the OPPP gene. The purified OPPP showed a specific activity value of 80.3 U/mg protein. The OPPP was stable under low temperature (5-30 °C) and weakly basic conditions (pH 8.5-10). The enzymatic ability of OPPP was investigated for in vitro production of oxaloacetate using phosphoenolpyruvate (PEP) and bicarbonate. Only samples containing the OPPP, PEP, and bicarbonate resulted in oxaloacetate production. OPPP production system using E. coli could be a platform technology to produce high yields of heterogeneous gene and provide the PEPC enzyme, which has high enzyme activity.

Project FIRES [Firefighters' Integrated Response Equipment System]. Volume 2: Protective Ensemble Performance Standards, Phase 1B

NASA Technical Reports Server (NTRS)

Abeles, F. J.

1980-01-01

The design of the prototype protective ensemble was finalized. Prototype ensembles were fabricated and then subjected to a series of qualification tests which were based upon the protective ensemble performance standards PEPS requirements. Engineering drawings and purchase specifications were prepared for the new protective ensemble.

Methods for Measuring Characteristics of Night Vision Goggles

DTIC Science & Technology

1993-10-01

TA 18 6. AUTHOR(S) WU 07 Harry L. Task Peter L. Marasco Richard T. Hartman, Capt Annette R. Zobel 7. PEP.FORMING...DTIC S SELECTE T Harry L. Task 3 MR 16 1994 R Richard T. Hartman 0 Peter L. Mardsco F N CREW SYSTEMS DIRECTORATE G HUMAN ENGINEERING DIVX[SIONWRIGHT-PAT

Propulsion and Energetics Panel Working Group 15 on the Uniform Engine Test Programme

DTIC Science & Technology

1990-02-01

earlier test of uniform aerodynamic models in wind tunnels under the auspices of the Fluid Dynamics Panel. A formal proposal was presented to the...this major new effort and members of the engine test community throughout AGARD were selected to serve on Working Group 15 along with PEP...STPA/MO 4 Mr J.R.Bednarsk; 4 Avenue de Ia Porte d’lssy PE-63 75015 Paris Naval Air Propulsion Center PO Box 7176 GERMANY Trenton. New Jersey 08628

Chemical characterization of Pleurotus eryngii polysaccharide and its tumor-inhibitory effects against human hepatoblastoma HepG-2 cells.

PubMed

Ren, Daoyuan; Wang, Ning; Guo, Jianjun; Yuan, Li; Yang, Xingbin

2016-03-15

This study was designed to investigate the chemical characterization and antitumor effects of Pleurotus eryngii polysaccharides (PEP). The crude PEP was fractionated into two fractions, namely PEP-1 and PEP-2. HPLC analysis showed that PEP-1 and PEP-2 were heteropolysaccharides mainly composed of glucose with the average molecular weights of 2.54×10(4)Da (PEP-1) and 4.63×10(5)Da (PEP-2), respectively. High molecular mass PEP-2 was shown to exhibit stronger growth inhibition against human hepatoblastoma HepG-2 cells in comparison with PEP-1. Flow cytometric analysis showed that PEP-2 exerted a stimulatory effect on apoptosis of HepG-2 cells, and induced the cell-cycle arrest at the S-phase, with the observation of intracellular ROS production. These findings suggest that the polysaccharides, especially PEP-2, are very important nutritional ingredients responsible for the anticancer health benefits of P. eryngii. Copyright © 2015 Elsevier Ltd. All rights reserved.

Post-exposure Prophylaxis Awareness, Knowledge, Access and Use Among Three Populations in New York City, 2016-17.

PubMed

Koblin, Beryl A; Usher, DaShawn; Nandi, Vijay; Tieu, Hong-Van; Bravo, Eddie; Lucy, Debbie; Miles, London; Ortiz, Geneva; Kindlon, Marcia J; Parisi, Donna M; Frye, Victoria

2018-06-01

Post-exposure prophylaxis (PEP) is a cost-effective, but underused HIV prevention strategy. PEP awareness, knowledge, access, and usage was assessed among young men of color who have sex with men (YMSMOC; n = 177), transgender women (TW; n = 182), and cisgender women of color (CWOC; n = 170) in New York City. 59% were aware of PEP: 80% among YMSMOC, 63% among TW and 34% among CWOC (p < 0.001). 13% had ever used PEP. PEP awareness was higher among YMSMOC with a recent HIV test and lower among those with ≥ 4 partners. PEP awareness was lower among TW who anticipated stigma and reported barriers to taking PEP, and higher among TW who exchanged sex for resources. Among CWOC, more barriers to taking PEP reduced the odds of PEP awareness. PEP education and outreach needs to be deliberate about population-specific campaigns, with a need to focus on reducing PEP stigma and other barriers which impede PEP access.

Reversibly Switchable, pH-Dependent Peptide Ligand Binding via 3,5-Diiodotyrosine Substitutions.

PubMed

Ngambenjawong, Chayanon; Sylvestre, Meilyn; Gustafson, Heather H; Pineda, Julio Marco B; Pun, Suzie H

2018-04-20

Cell type-specific targeting ligands utilized in drug delivery applications typically recognize receptors that are overexpressed on the cells of interest. Nonetheless, these receptors may also be expressed, to varying extents, on off-target cells, contributing to unintended side effects. For the selectivity profile of targeting ligands in cancer therapy to be improved, stimuli-responsive masking of these ligands with acid-, redox-, or enzyme-cleavable molecules has been reported, whereby the targeting ligands are exposed in specific environments, e.g., acidic tumor hypoxia. One possible drawback of these systems lies in their one-time, permanent trigger, which enables the "demasked" ligands to bind off-target cells if released back into the systemic circulation. A promising strategy to address the aforementioned problem is to design ligands that show selective binding based on ionization state, which may be microenvironment-dependent. In this study, we report a systematic strategy to engineer low pH-selective targeting peptides using an M2 macrophage-targeting peptide (M2pep) as an example. 3,5-Diiodotyrosine mutagenesis into native tyrosine residues of M2pep confers pH-dependent binding behavior specific to acidic environment (pH 6) when the amino acid is protonated into the native tyrosine-like state. At physiological pH of 7.4, the hydroxyl group of 3,5-diiodotyrosine on the peptide is deprotonated leading to interruption of the peptide native binding property. Our engineered pH-responsive M2pep (Ac-Y-Î-Î) binds target M2 macrophages more selectively at pH 6 than at pH 7.4. In addition, 3,5-diiodotyrosine substitutions also improve serum stability of the peptide. Finally, we demonstrate pH-dependent reversibility in target binding via a postbinding peptide elution study. The strategy presented here should be applicable for engineering pH-dependent functionality of other targeting peptides with potential applications in physiology-dependent in vivo targeting applications (e.g., targeting hypoxic tumor/inflammation) or in in vitro receptor identification.

Enhancing the water dispersibility of paclitaxel by complexation with hydrophobic peptides.

PubMed

Inada, Asuka; Oshima, Tatsuya; Baba, Yoshinari

2015-11-01

The complex between paclitaxel (Ptx) and a peptide mixture (Pep) was prepared to enhance of the water-dispersibility of Ptx. Pep was prepared by enzymatic hydrolysis of casein, followed by fractionation using ammonium sulfate precipitation and ultrafiltration. The Ptx and Pep complex (Ptx-Pep) was prepared by mixing an ethanol solution of Ptx and an aqueous solution of Pep followed by lyophilization. The water dispersibility test of Ptx-Pep prepared using different fractions of Pep demonstrated that a fraction (Pep-A), containing relatively hydrophobic peptides with high molecular weights, was effective in enhancing the water dispersibility of Ptx. The sequences of the major peptides in Pep-A were identified by matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometry with "LIFT" technique. The water dispersibility of the complex between Ptx and Pep-A (Ptx-Pep-A) was independent of pH, even though it is positively or negatively charged under strongly acidic and neutral conditions. As the particle size of Ptx-Pep-A in aqueous media was 147-215 nm, Ptx-Pep-A was present as a hydrocolloidal material in aqueous media. Copyright © 2015 Elsevier B.V. All rights reserved.

Peptidase-3 (Pep-3), dipeptidase variant in the rat homologous to mouse pep-3 (Dip-1) and human PEP-c.

PubMed

Womack, J E; Cramer, D V

1980-10-01

Starch gel electrophoresis and histochemical staining with L-leucyl-L-tyrosine have revealed genetic variation for dipeptidase in Rattus norvegicus. The tissue distribution, substrate specificity, and heterozygous expression as a monmeric protein suggest homology of the variant peptidase to human PEP-C and mouse Pep-3 (Dip-1). We propose Peptidase-3 (Pep-3) as a name for this autosomal locus in the rat. The allele responsible for slower (less anodal) electrophoretic migration is designated Pep-3a and is characteristic of strain ACI/Pit. A faster (more anodal) electrophoretic mobility is the product of the Pep-3b allele in strain F344/Pit. Twenty-five additional inbred strains carry Pep-3a and 16 others carry Pep-3b. Wild rats trapped in Pittsburgh were polymorphic for this locus. Alleles at Pep-3 segregated independently of c (linkage group I), a (linkage group IV), RT2 and Es-1 (linkage group V), h (linkage group VI), and RTI (linkage group VIII).

PEP: patient-supported esthetic protocol.

PubMed

Gebhard-Achilles, Walter

2013-01-01

Nowadays, materials and process engineering, especially digital-based techniques, are becoming more and more important for esthetic dentistry. Digital communication is also increasing, which is accompanied by a change from a personal contact to a more technocratic and less emotional and empathic communication. Sometimes our personal experiences and perceptions, based on dental, empirical knowledge, collide with this development. It also happens very often, that the patients - with their perceptions, concerns and not least their esthetic preferences - feel neglected by the treatment team. Patient's wishes often cannot be described adequately. The patient-supported esthetic protocol (PEP) described in this article is a simple tool with which the patients are involved in the esthetic concerns of their treatment. The patient feels to be more perceived, respected, and their wishes implemented, without affecting the medical therapy. At the same time, PEP is used for communication within the health care team, such as the dentist and the dental technician. Because of the clear record it is easy to recognize the changes the patient desires, and the suggestions a teammate developed with the patient, without having been present at the session. Furthermore, the protocol can be attached to the patient's medical history and, therefore, could be a tool for quality management.

Evidence that the rabbit proton-peptide co-transporter PepT1 is a multimer when expressed in Xenopus laevis oocytes.

PubMed

Panitsas, Konstantinos-E; Boyd, C A R; Meredith, David

2006-04-01

To test whether the rabbit proton-coupled peptide transporter PepT1 is a multimer, we have employed a combination of transport assays, luminometry and site-directed mutagenesis. A functional epitope-tagged PepT1 construct (PepT1-FLAG) was co-expressed in Xenopus laevis oocytes with a non-functional but normally trafficked mutant form of the same transporter (W294F-PepT1). The amount of PepT1-FLAG cRNA injected into the oocytes was kept constant, while the amount of W294F-PepT1 cRNA was increased over the mole fraction range of 0 to 1. The uptake of [(3)H]-D: -Phe-L: -Gln into the oocytes was measured at pH(out) 5.5, and the surface expression of PepT1-FLAG was quantified by luminometry. As the mole fraction of injected W294F-PepT1 increased, the uptake of D: -Phe-L: -Gln decreased. This occurred despite the surface expression of PepT1-FLAG remaining constant, and so we can conclude that PepT1 must be a multimer. Assuming that PepT1 acts as a homomultimer, the best fit for the modelling suggests that PepT1 could be a tetramer, with a minimum requirement of two functional subunits in each protein complex. Western blotting also showed the presence of higher-order complexes of PepT1-FLAG in oocyte membranes. It should be noted that we cannot formally exclude the possibility that PepT1 interacts with unidentified Xenopus protein(s). The finding that PepT1 is a multimer has important implications for the molecular modelling of this protein.

Materiel Acquisition Management Guide

DTIC Science & Technology

1980-02-11

Ii-n manager and his staff, hiqhlighted by the specific de - tails provided in tabbea one-sheet descriptions. • Part III - Areas of Aco-uisition...support program requirements? Support and Test Equipment (S/TE)? Spares Support (SS)? Storage and transportation ? training? o Have test and...PACKAGES PROCUREMENT PLANNING/ PROCUREMENT pLANS TEST AND EVALUATION - PLANNING PRODUCIBILITY ENGINEERING AND TRAINING PLANNING (PEP) TRANSPORTABILITY

Environmental Containment Property Estimation Using QSARs in an Expert System

DTIC Science & Technology

1993-01-15

2 megabytes of memory (RAM), with 1000 kBytes of memory allocated for HyperCard. PEP overview The PEP system currently consists of four HyperCard...BCF Universel I ’ mI Figure 6. TSA module card from PEP The TSA module is also designed to accept files generated by other hardware/software... allocated to 1500 MB. * Installation of PEP PEP is typically shipped on one 3.5 inch 1.44 Megabyte floppy disk. To install PEP: 1. Insert the PEP disk into

Cell killing mode of liblomycin (NK313), a novel dose-survival relationship different from bleomycins.

PubMed

Kuramochi-Motegi, A; Kuramochi, H; Takahashi, K; Takeuchi, T

1991-04-01

Liblomycin (NK313) is a novel derivative of bleomycin (BLM) and peplomycin (PEP). The cell kill kinetics of NK313 on rat ascites hepatoma AH66 were compared with those of PEP. NK313 induced intracellular DNA cleavage and arrested cell cycle progression at the G2 phase similarly to PEP. The cytocidal effect of NK313, however, was found to be different from that of PEP as described below: 1) The dose-survival curve for cells exposed to PEP for 1 hour was upward concave, whereas in case of NK313, the survival curve was linear. PEP was more effective to AH66 than NK313 at lower concentration, but at higher concentration, NK313 was much more effective. 2) The time-survival curve for cells treated with either NK313 or PEP was biphasic. NK313, however, did not induce temporary resistance of AH66 cells to NK313, while PEP induced resistance to PEP. 3) NK313 was effective against the cells which became temporarily resistant to PEP by the treatment of PEP. These differences suggest that NK313 might be of value to treat PEP-insensitive tumor cells.

Development and Validation of the Pride in Eating Pathology Scale (PEP-S).

PubMed

Faija, Cintia L; Fox, John R E; Tierney, Stephanie; Peters, Sarah; Gooding, Patricia A

2017-01-01

There is a growing body of theoretical and clinical literature highlighting the role of pride in maintaining eating disordered behaviours. Despite its clinical importance, there are no measures to assess feelings of pride associated with eating psychopathology. This study describes the development and validation of the Pride in Eating Pathology Scale (PEP-S), a self-report questionnaire that examines feelings of pride towards eating disordered symptoms (e.g., pride in food restriction, thinness and weight loss). Participants were 390 females, recruited from university and community populations, whose mean age was 26.99 years. Respondents rated pride in eating pathology on a 7-point Likert-scale. Principal Component Analysis indicated that the 60-item scale comprised a four component structure: (1) pride in weight loss, food control and thinness, (2) pride in healthy weight and healthy eating, (3) pride in outperforming others and social recognition and (4) pride in capturing other people's attention due to extreme thinness. These four components explained a total of 65.31% of the variance. The PEP-S demonstrated very good internal reliability (α ranging from 0.88 to 0.98) and very good test-retest reliability over a 3-week time-span (r ranging from 0.81 to 0.93). The PEP-S also showed excellent convergent and discriminant validity. Furthermore, the scale discriminated between women with high and low levels of eating psychopathology. The PEP-S is a psychometrically robust measure of pride in eating pathology. It has the potential to advance theoretical understanding and may also be clinically useful. Copyright © 2015 John Wiley & Sons, Ltd. The PEP-S is a valid, reliable, quick and easy to administer self-report questionnaire that measures pride related to eating pathology. The PEP-S assesses four clinically relevant dimensions: (1) pride in weight loss, food control and thinness, (2) pride in healthy weight and healthy eating, (3) pride in outperforming others and social recognition and (4) pride in capturing other people's attention due to extreme thinness. The PEP-S has very good internal and test-retest reliability, and very good convergent and discriminant validity. The PEP-S distinguishes between women with higher and lower levels of eating psychopathology. The PEP-S makes an important contribution to understanding pride in eating psychopathology, which is essential from both clinical and theoretical perspectives. Copyright © 2015 John Wiley & Sons, Ltd.

DNA sequence analysis, expression, distribution, and physiological role of the Xaa-prolyldipeptidyl aminopeptidase gene from Lactobacillus helveticus CNRZ32.

PubMed

Yüksel, G U; Steele, J L

1996-02-01

Lactobacillus helveticus CNRZ32 possesses an Xaa-prolyldipeptidyl aminopeptidase (PepX), which releases amino-terminal dipeptides from peptides containing proline residues in the penultimate position. The PepX gene, designated pepX, from Lb. helveticus CNRZ32 was sequenced. Analysis of the sequence identified a putative 2379-bp pepX open-reading frame, which encodes a polypeptide of 793 amino acid residues with a deduced molecular mass of 88,111 Da. The gene shows significant sequence identity with sequenced pepX genes from lactic acid bacteria. The product of the gene contains a motif that is almost identical with the active-site motif of the serine-dependent PepX from lactococci. The introduction of pepX into Lactococcus lactis LM0230 on either pGK12 (a low-copy-number plasmid vector) or pIL253 (a high-copy-number plasmid vector) did not result in a significant increase in PepX activity, while the introduction of pepX into CNRZ32 on pGK12 resulted in a four-fold increase in PepX activity. Southern hybridization experiments revealed that the pepX gene from CNRZ32 is well conserved in lactobacilli, pediococci and streptococci. The physiological role of PepX during growth in lactobacillus MRS (a rich medium containing protein hydrolysates along with other ingredients) and milk was examined by comparing growth of CNRZ32 and a CNRZ32 PepX-negative derivative. No difference in growth rate or acid production was observed between CNRZ32 and its PepX-negative derivative in MRS. However, the CNRZ32 PepX-negative derivative grew in milk at a reduced specific growth rate when compared to wild-type CNRZ32. Introduction of the cloned PepX determinant into the CNRZ32 PepX-negative derivative resulted in a construct with a specific growth rate similar to that of wild-type CNRZ32.

A Novel Glutamyl (Aspartyl)-Specific Aminopeptidase A from Lactobacillus delbrueckii with Promising Properties for Application

PubMed Central

Stressler, Timo; Ewert, Jacob; Merz, Michael; Funk, Joshua; Claaßen, Wolfgang; Lutz-Wahl, Sabine; Schmidt, Herbert; Kuhn, Andreas; Fischer, Lutz

2016-01-01

Lactic acid bacteria (LAB) are auxotrophic for a number of amino acids. Thus, LAB have one of the strongest proteolytic systems to acquit their amino acid requirements. One of the intracellular exopeptidases present in LAB is the glutamyl (aspartyl) specific aminopeptidase (PepA; EC 3.4.11.7). Most of the PepA enzymes characterized yet, belonged to Lactococcus lactis sp., but no PepA from a Lactobacillus sp. has been characterized so far. In this study, we cloned a putative pepA gene from Lb. delbrueckii ssp. lactis DSM 20072 and characterized it after purification. For comparison, we also cloned, purified and characterized PepA from Lc. lactis ssp. lactis DSM 20481. Due to the low homology between both enzymes (30%), differences between the biochemical characteristics were very likely. This was confirmed, for example, by the more acidic optimum pH value of 6.0 for Lb-PepA compared to pH 8.0 for Lc-PepA. In addition, although the optimum temperature is quite similar for both enzymes (Lb-PepA: 60°C; Lc-PepA: 65°C), the temperature stability after three days, 20°C below the optimum temperature, was higher for Lb-PepA (60% residual activity) than for Lc-PepA (2% residual activity). EDTA inhibited both enzymes and the strongest activation was found for CoCl2, indicating that both enzymes are metallopeptidases. In contrast to Lc-PepA, disulfide bond-reducing agents such as dithiothreitol did not inhibit Lb-PepA. Finally, Lb-PepA was not product-inhibited by L-Glu, whereas Lc-PepA showed an inhibition. PMID:27003449

A Novel Glutamyl (Aspartyl)-Specific Aminopeptidase A from Lactobacillus delbrueckii with Promising Properties for Application.

PubMed

Stressler, Timo; Ewert, Jacob; Merz, Michael; Funk, Joshua; Claaßen, Wolfgang; Lutz-Wahl, Sabine; Schmidt, Herbert; Kuhn, Andreas; Fischer, Lutz

2016-01-01

Lactic acid bacteria (LAB) are auxotrophic for a number of amino acids. Thus, LAB have one of the strongest proteolytic systems to acquit their amino acid requirements. One of the intracellular exopeptidases present in LAB is the glutamyl (aspartyl) specific aminopeptidase (PepA; EC 3.4.11.7). Most of the PepA enzymes characterized yet, belonged to Lactococcus lactis sp., but no PepA from a Lactobacillus sp. has been characterized so far. In this study, we cloned a putative pepA gene from Lb. delbrueckii ssp. lactis DSM 20072 and characterized it after purification. For comparison, we also cloned, purified and characterized PepA from Lc. lactis ssp. lactis DSM 20481. Due to the low homology between both enzymes (30%), differences between the biochemical characteristics were very likely. This was confirmed, for example, by the more acidic optimum pH value of 6.0 for Lb-PepA compared to pH 8.0 for Lc-PepA. In addition, although the optimum temperature is quite similar for both enzymes (Lb-PepA: 60°C; Lc-PepA: 65°C), the temperature stability after three days, 20°C below the optimum temperature, was higher for Lb-PepA (60% residual activity) than for Lc-PepA (2% residual activity). EDTA inhibited both enzymes and the strongest activation was found for CoCl2, indicating that both enzymes are metallopeptidases. In contrast to Lc-PepA, disulfide bond-reducing agents such as dithiothreitol did not inhibit Lb-PepA. Finally, Lb-PepA was not product-inhibited by L-Glu, whereas Lc-PepA showed an inhibition.

The Danish PEP Registry: Experience with the use of post-exposure prophylaxis following blood exposure to HIV from 1999-2012.

PubMed

Lunding, Suzanne; Katzenstein, Terese L; Kronborg, Gitte; Storgaard, Merete; Pedersen, Court; Mørn, Birgitte; Lindberg, Jens Å; Kronborg, Thit M; Jensen, Janne

2016-01-01

The risk of occupational exposures to blood cannot be eliminated completely and access to post-exposure prophylaxis (PEP) to prevent HIV transmission is important. However, PEP administration has been associated with frequent adverse effects, low compliance and difficulties to ensure a proper risk assessment. This nationwide study describes 14 years of experience with the use of PEP following blood exposure in Denmark. A descriptive study of all PEP cases following non-sexual exposure to HIV in Denmark from 1999-2012. A total of 411 cases of PEP were described. There was a mean of 29.4 cases/year, increasing from 23 cases in 1999 to 49 cases in 2005 and then decreasing to 16 cases in 2012. Overall 67.2% of source patients were known to be HIV-positive at the time of PEP initiation, with no significant change over time. The median time to initiation of PEP was 2.5 h (0.15-28.5) following occupational exposure. Adverse effects were reported by 50.9% with no significant difference according to PEP regimen. In 85.1% of cases with available data, either a full course of PEP was completed or PEP was stopped because the source was tested HIV-negative. Only 6.6% stopped PEP early due to adverse effects. PEP in Denmark is generally prescribed according to the guidelines and the annual number of cases has declined since 2005. Adverse effects were common regardless of PEP regimens used and new drug regimens should be considered.

Structural Basis of Glyphosate Resistance Resulting from the Double Mutation Thr97 → Ile and Pro101 → Ser in 5-Enolpyruvylshikimate-3-phosphate Synthase from Escherichia coli*S⃞

PubMed Central

Funke, Todd; Yang, Yan; Han, Huijong; Healy-Fried, Martha; Olesen, Sanne; Becker, Andreas; Schönbrunn, Ernst

2009-01-01

The shikimate pathway enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) is the target of the broad spectrum herbicide glyphosate. The genetic engineering of EPSPS led to the introduction of glyphosate-resistant crops worldwide. The genetically engineered corn lines NK603 and GA21 carry distinct EPSPS enzymes. CP4 EPSPS, expressed in NK603 corn and transgenic soybean, cotton, and canola, belongs to class II EPSPS, glyphosate-insensitive variants of this enzyme isolated from certain Gram-positive bacteria. GA21 corn, on the other hand, was created by point mutations of class I EPSPS, such as the enzymes from Zea mays or Escherichia coli, which are sensitive to low glyphosate concentrations. The structural basis of the glyphosate resistance resulting from these point mutations has remained obscure. We studied the kinetic and structural effects of the T97I/P101S double mutation, the molecular basis for GA21 corn, using EPSPS from E. coli. The T97I/P101S enzyme is essentially insensitive to glyphosate (Ki = 2.4 mm) but maintains high affinity for the substrate phosphoenolpyruvate (PEP) (Km = 0.1 mm). The crystal structure at 1.7-Å resolution revealed that the dual mutation causes a shift of residue Gly96 toward the glyphosate binding site, impairing efficient binding of glyphosate, while the side chain of Ile97 points away from the substrate binding site, facilitating PEP utilization. The single site T97I mutation renders the enzyme sensitive to glyphosate and causes a substantial decrease in the affinity for PEP. Thus, only the concomitant mutations of Thr97 and Pro101 induce the conformational changes necessary to produce catalytically efficient, glyphosate-resistant class I EPSPS. PMID:19211556

Structural basis of glyphosate resistance resulting from the double mutation Thr97 -> Ile and Pro101 -> Ser in 5-enolpyruvylshikimate-3-phosphate synthase from Escherichia coli.

PubMed

Funke, Todd; Yang, Yan; Han, Huijong; Healy-Fried, Martha; Olesen, Sanne; Becker, Andreas; Schönbrunn, Ernst

2009-04-10

The shikimate pathway enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) is the target of the broad spectrum herbicide glyphosate. The genetic engineering of EPSPS led to the introduction of glyphosate-resistant crops worldwide. The genetically engineered corn lines NK603 and GA21 carry distinct EPSPS enzymes. CP4 EPSPS, expressed in NK603 corn and transgenic soybean, cotton, and canola, belongs to class II EPSPS, glyphosate-insensitive variants of this enzyme isolated from certain Gram-positive bacteria. GA21 corn, on the other hand, was created by point mutations of class I EPSPS, such as the enzymes from Zea mays or Escherichia coli, which are sensitive to low glyphosate concentrations. The structural basis of the glyphosate resistance resulting from these point mutations has remained obscure. We studied the kinetic and structural effects of the T97I/P101S double mutation, the molecular basis for GA21 corn, using EPSPS from E. coli. The T97I/P101S enzyme is essentially insensitive to glyphosate (K(i) = 2.4 mm) but maintains high affinity for the substrate phosphoenolpyruvate (PEP) (K(m) = 0.1 mm). The crystal structure at 1.7-A resolution revealed that the dual mutation causes a shift of residue Gly(96) toward the glyphosate binding site, impairing efficient binding of glyphosate, while the side chain of Ile(97) points away from the substrate binding site, facilitating PEP utilization. The single site T97I mutation renders the enzyme sensitive to glyphosate and causes a substantial decrease in the affinity for PEP. Thus, only the concomitant mutations of Thr(97) and Pro(101) induce the conformational changes necessary to produce catalytically efficient, glyphosate-resistant class I EPSPS.

Risk models for post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP): smoking and chronic liver disease are predictors of protection against PEP.

PubMed

DiMagno, Matthew J; Spaete, Joshua P; Ballard, Darren D; Wamsteker, Erik-Jan; Saini, Sameer D

2013-08-01

We investigated which variables independently associated with protection against or development of postendoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) and severity of PEP. Subsequently, we derived predictive risk models for PEP. In a case-control design, 6505 patients had 8264 ERCPs, 211 patients had PEP, and 22 patients had severe PEP. We randomly selected 348 non-PEP controls. We examined 7 established- and 9 investigational variables. In univariate analysis, 7 variables predicted PEP: younger age, female sex, suspected sphincter of Oddi dysfunction (SOD), pancreatic sphincterotomy, moderate-difficult cannulation (MDC), pancreatic stent placement, and lower Charlson score. Protective variables were current smoking, former drinking, diabetes, and chronic liver disease (CLD, biliary/transplant complications). Multivariate analysis identified seven independent variables for PEP, three protective (current smoking, CLD-biliary, CLD-transplant/hepatectomy complications) and 4 predictive (younger age, suspected SOD, pancreatic sphincterotomy, MDC). Pre- and post-ERCP risk models of 7 variables have a C-statistic of 0.74. Removing age (seventh variable) did not significantly affect the predictive value (C-statistic of 0.73) and reduced model complexity. Severity of PEP did not associate with any variables by multivariate analysis. By using the newly identified protective variables with 3 predictive variables, we derived 2 risk models with a higher predictive value for PEP compared to prior studies.

Uptake and Repeat Use of Postexposure Prophylaxis in a Community-Based Clinic in Los Angeles, California

PubMed Central

Bolan, Robert K.; Flynn, Risa P.; Kerrone, Dustin R.; Pieribone, David L.; Kulkarni, Sonali P.; Stitt, Jackelyn C.; Mejia, Everardo; Landovitz, Raphael J.

2014-01-01

Abstract Postexposure prophylaxis (PEP) has become an important tool for HIV prevention in the men who have sex with men (MSM) communities within Los Angeles County. However, it is unclear as to whether the most sexually at-risk MSM populations are accessing PEP services. Furthermore, it is unclear what behavioral risk factors differentiate individuals who utilize PEP once (single PEP) versus those who utilize it multiple times (re-PEP). Data were collected between May 2011 and December 2012 on all clients enrolled in the Los Angeles LGBT Center's (the Center) PEP-LA program as well as on all sexually transmitted infection (STI) screening clients visiting the Center. Multivariate logistic regression models were used to analyze results. PEP clients had greater odds of having a history of gonorrhea in the past year when compared to high-risk, non-PEP clients (OR: 1.71; CI: 1.25–2.35). Furthermore, they had greater odds of using methamphetamines (OR: 1.71; CI: 1.30–2.24) and inhaled nitrates (OR: 1.62; CI: 1.30–2.01) in the past 12 months when compared to high-risk, non-PEP clients. Re-PEP clients had greater odds of methamphetamine use than single PEP clients (OR: 2.80; CI: 1.65–4.75). There were no significant differences by race/ethnicity between high-risk, non-PEP clients and PEP clients in either the entire cohort or MSM only sample. However, African Americans made up 8.5% of persons accessing PEP services but 16.7% of persons who tested HIV positive. Similar proportions of PEP use by race/ethnicity are problematic considering the disproportionate burden of HIV infections in the African American community. Although uptake among the highest risk populations has been brisk (n=649), inequities based upon race/ethnicity suggest the need for increased outreach. PMID:24970113

Power Extension Package (PEP) system definition extension, orbital service module systems analysis study. Volume 2: PEP

NASA Technical Reports Server (NTRS)

1979-01-01

User power, duration, and orbit requirements, which were the prime factors influencing power extension package (PEP) design, are discussed. A representative configuration of the PEP concept is presented and the major elements of the system are described as well as the PEP-to-Orbiter and remote manipulator interface provisions.

PEPR2 is a second receptor for the Pep1 and Pep2 peptides and contributes to defense responses in arabidopsis

USDA-ARS?s Scientific Manuscript database

A 23-amino acid peptide, AtPep1, and its homologues are endogenous elicitors in Arabidopsis, inducing defense related genes. AtPep1 enhances resistance to a root pathogen, Pythium irregulare, through the salicylic acid, jasmonic acid, ethylene, and reactive oxygen species signaling pathways. AtPep...

The impact of cognitive behavioral therapy on post event processing among those with social anxiety disorder.

PubMed

Price, Matthew; Anderson, Page L

2011-02-01

Individuals with social anxiety are prone to engage in post event processing (PEP), a post mortem review of a social interaction that focuses on negative elements. The extent that PEP is impacted by cognitive behavioral therapy (CBT) and the relation between PEP and change during treatment has yet to be evaluated in a controlled study. The current study used multilevel modeling to determine if PEP decreased as a result of treatment and if PEP limits treatment response for two types of cognitive behavioral treatments, a group-based cognitive behavioral intervention and individually based virtual reality exposure. These hypotheses were evaluated using 91 participants diagnosed with social anxiety disorder. The findings suggested that PEP decreased as a result of treatment, and that social anxiety symptoms for individuals reporting greater levels of PEP improved at a slower rate than those with lower levels of PEP. Further research is needed to understand why PEP attenuates response to treatment. Copyright © 2010 Elsevier Ltd. All rights reserved.

PepPat, a pattern-based oligopeptide homology search method and the identification of a novel tachykinin-like peptide.

PubMed

Jiang, Ying; Gao, Ge; Fang, Gang; Gustafson, Eric L; Laverty, Maureen; Yin, Yanbin; Zhang, Yong; Luo, Jingchu; Greene, Jonathan R; Bayne, Marvin L; Hedrick, Joseph A; Murgolo, Nicholas J

2003-05-01

PepPat, a hybrid method that combines pattern matching with similarity scoring, is described. We also report PepPat's application in the identification of a novel tachykinin-like peptide. PepPat takes as input a query peptide and a user-specified regular expression pattern within the peptide. It first performs a database pattern match and then ranks candidates on the basis of their similarity to the query peptide. PepPat calculates similarity over the pattern spanning region, enhancing PepPat's sensitivity for short query peptides. PepPat can also search for a user-specified number of occurrences of a repeated pattern within the target sequence. We illustrate PepPat's application in short peptide ligand mining. As a validation example, we report the identification of a novel tachykinin-like peptide, C14TKL-1, and show it is an NK1 (neuokinin receptor 1) agonist whose message is widely expressed in human periphery. PepPat is offered online at: http://peppat.cbi.pku.edu.cn.

General in-situation safety behaviors are uniquely associated with post-event processing.

PubMed

Mitchell, Melissa A; Schmidt, Norman B

2014-06-01

Research suggests that state anxiety and in-situation safety behaviors are associated with post-event processing (PEP) in social anxiety. Past research has obtained mixed results on whether one or both factors contribute to PEP. The current investigation evaluated state anxiety and in-situation safety behaviors (including subtypes of in-situation safety behaviors) simultaneously to determine their relative contributions to PEP. A prospective study assessed social anxiety, state anxiety, in-situation safety behaviors, PEP, and depression in the context of a speech stressor. Consistent with theory, in-situation safety behaviors were uniquely associated with greater PEP. State anxiety was not uniquely associated with PEP. Furthermore, restricting and active subtypes of in-situation safety behaviors showed specificity to PEP. Limitations of the present study include the use of a nonclinical analog sample and retrospective reporting of PEP. These findings highlight the importance of research on in-situation safety behaviors as a potential contributor to PEP. Published by Elsevier Ltd.

The Impact of Cognitive Behavioral Therapy on Post Event Processing Among Those with Social Anxiety Disorder

PubMed Central

Price, Matthew; Anderson, Page L.

2011-01-01

Individuals with social anxiety are prone to engage in post event processing (PEP), a post mortem review of a social interaction that focuses on negative elements. The extent that PEP is impacted by cognitive behavioral therapy (CBT) and the relation between PEP and change during treatment has yet to be evaluated in a controlled study. The current study used multilevel modeling to determine if PEP decreased as a result of treatment and if PEP limits treatment response for two types of cognitive behavioral treatments, a group-based cognitive behavioral intervention and individually based virtual reality exposure. These hypotheses were evaluated using 91 participants diagnosed with social anxiety disorder. The findings suggested that PEP decreased as a result of treatment, and that social anxiety symptoms for individuals reporting greater levels of PEP improved at a slower rate than those with lower levels of PEP. Further research is needed to understand why PEP attenuates response to treatment. PMID:21159328

Influence of the metal ion on the enzyme activity and kinetics of PepA from Lactobacillus delbrueckii.

PubMed

Ewert, Jacob; Glück, Claudia; Strasdeit, Henry; Fischer, Lutz; Stressler, Timo

2018-03-01

The aminopeptidase A (PepA; EC 3.4.11.7) belongs to the group of metallopeptidases with two bound metal ions per subunit (M1M2(PepA)) and is specific for the cleavage of N-terminal glutamic (Glu) and aspartic acid (Asp) and, in low amounts, serine (Ser) residues. Our group recently characterized the first PepA from a Lactobacillus strain. However, the characterization was performed using synthetic para-nitroaniline substrates and not original peptide substrates, as was done in the current study. Prior to the characterization using original peptide substrates, the PepA purified was converted to its inactive apo-form and eight different metal ions were tested to restore its activity. It was found that five of the metal ions were able to reactivate apo-PepA: Co 2+ , Cu 2+ , Mn 2+ , Ni 2+ and Zn 2+ . Interestingly, depending on the metal ion used for reactivation, the activity and the pH and temperature profile differed. Exemplarily, MnMn(PepA), NiNi(PepA) and ZnZn(PepA) had an activity optimum using MES buffer (50mM, pH 6.0) and 60°C, whereas the activity optimum changed to Na/K-phosphate-buffer (50mM, pH 7.0) and 55°C for CuCu(PepA). However, more important than the changes in optimum pH and temperature, the kinetic properties of PepA were affected by the metal ion used. While all PepA variants could release N-terminal Glu or Asp, only CoCo(PepA), NiNi(PepA) and CuCu(PepA) could release Ser from the particular peptide substrate. In addition, it was found that the enzyme efficiency (V max /K M ) and catalytic mechanism (positive cooperative binding (Hill coefficent; n), substrate inhibition (K IS )) were influenced by the metal ion. Exemplarily, a high cooperativity (n>2),K IS value >20mM and preference for N-terminal Glu were detected for CuCu(PepA). In summary, the results suggested that an exchange of the metal ion can be used for tailoring the properties of PepA for specific hydrolysis requirements. Copyright © 2017 Elsevier Inc. All rights reserved.

VizieR Online Data Catalog: PACS Evolutionary Probe (PEP-DR1) catalogs (Lutz+, 2011)

NASA Astrophysics Data System (ADS)

Lutz, D.; Poglitsch, A.; Altieri, B.; Andreani, P.; Aussel, H.; Berta, S.; Bongiovanni, A.; Brisbin, D.; Cava, A.; Cepa, J.; Cimatti, A.; Daddi, E.; Dominguez-Sanchez, H.; Elbaz, D.; Foerster Schreiber, N. M.; Genzel, R.; Grazian, A.; Gruppioni, C.; Harwit, M.; Le Floc'h, E.; Magdis, G.; Magnelli, B.; Maiolino, R.; Nordon, R.; Perez Garcia, A. M.; Popesso, P.; Pozzi, F.; Riguccini, L.; Rodighiero, G.; Saintonge, A.; Sanchez Portal, M.; Santini, P.; Shao, L.; Sturm, E.; Tacconi, L. J.; Valtchanov, I.; Wetzstein, M.; Wieprecht, E.

2013-11-01

PACS catalogs built by the PEP team, with key contributions by Stefano Berta, Benjamin Magnelli, Paola Popesso, Dieter Lutz, Francesca Pozzi, Bruno Altieri, Herve Aussel, Hoseong Hwang, Emeric Le Floc'h, Georgios Magdis, Raanan Nordon, Albrecht Poglitsch, Laurie Riguccini, Amelie Saintonge, Li Shao. For more details, please refer to Lutz et al. (2011A&A...532A..90L) and to the PDF documentation associated to the release. Data and catalogs can be retrieved from the web page http://www.mpe.mpg.de/ir/Research/PEP/publicdatareleases.php See the PDF documentation associated to the PEP DR1 release, http://www.mpe.mpg.de/resources/PEP/DR1tarballs/readmePEP_global.pdf and http://www.mpe.mpg.de/resources/PEP/DR1tarballs/readmePEP_SPIRE.pdf for more details. (69 data files).

Introduction of Peptidase Genes from Lactobacillus delbrueckii subsp. lactis into Lactococcus lactis and Controlled Expression

PubMed Central

Wegmann, U.; Klein, J. R.; Drumm, I.; Kuipers, O. P.; Henrich, B.

1999-01-01

Peptidases PepI, PepL, PepW, and PepG from Lactobacillus delbrueckii subsp. lactis, which have no counterparts in Lactococcus lactis, and peptidase PepQ were examined to determine their potential to confer new peptidolytic properties to lactococci. Controllable expression of the corresponding genes (pep genes) was achieved by constructing translational fusions with the promoter of the nisA gene (PnisA). A suitable host strain, UKLc10, was constructed by chromosomal integration of the genes encoding the NisRK two-component system into the fivefold peptidase-deficient mutant IM16 of L. lactis. Recombinants of this strain were used to analyze growth, peptidase activities, peptide utilization, and intracellular protein cleavage products. After nisin induction of PnisA::pep fusions, all of the peptidases were visible as distinct bands in protein gels. Despite the fact that identical transcription and translation signals were used to express the pep genes, the relative amounts of individual peptidases varied considerably. All of the peptidases exhibited activities in extracts of recombinant UKLc10 clones, but only PepL and PepG allowed the clones to utilize specific peptide substrates as sources of essential amino acids. In milk medium, induction of pepG and induction of pepW resulted in growth acceleration. The activities of all five peptidases during growth in milk medium were revealed by high-performance liquid chromatography analyses of intracellular amino acid and peptide pools. PMID:10543778

A genetic study of various enzyme polymorphisms in Pleurodeles waltlii (Urodele Amphibian). II. Peptidases: demonstration of sex linkage.

PubMed

Ferrier, V; Gasser, F; Jaylet, A; Cayrol, C

1983-06-01

The existence of four peptidases was demonstrated by starch gel electrophoresis in Pleurodeles waltlii: PEP-1, PEP-2, PEP-3, and PEP-4. Peptidases-3 and -4 are monomorphic, and peptidases-1 and -2 are polymorphic. The heredity of the polymorphisms was studied using individuals arising from crosses or of gynogenetic origin. Peptidase-1 is dimeric; its polymorphism depends on a pair of codominant alleles, Pep-1A and Pep-1B, which are situated on the Z and W sex chromosomes, respectively, in close proximity to, or even within, the sex differential segment. As the differential segment is very close to the centromere, the PEP-1 locus therefore also appears to be closely linked to it. Expression of the PEP-1 locus was shown to be independent of the sex hormone environment. This locus is the first case reported in amphibians of an enzyme marker linked to the genetic sex. It allows the sex of PLeurodeles to be determined before they reach sexual maturity. Peptidase-2 is monomeric. Its polymorphism depends on a pair of codominant alleles on an autosomal PEP-2 locus. The high proportion of heterozygous animals in the gynogenetic offspring of females heterozygous for the PEP-2 locus indicates segregation which is independent of the centromere. Analysis of the offspring of doubly heterozygous females (i.e., for two of the loci--LDH-B, G6PDH, PEP-1, and PEP-2) shows that the four loci are independent.

SPECT imaging of fibrin using fibrin-binding peptides.

PubMed

Starmans, Lucas W E; van Duijnhoven, Sander M J; Rossin, Raffaella; Aime, Silvio; Daemen, Mat J A P; Nicolay, Klaas; Grüll, Holger

2013-01-01

Noninvasive detection of fibrin in vivo using diagnostic imaging modalities may improve clinical decision-making on possible therapeutic options in atherosclerosis, cancer and thrombus-related pathologies such as pulmonary embolism and deep venous thrombosis. The aim of this study was to assess the potential of a novel (111)In-labeled fibrin-binding peptide (FibPep) to visualize thrombi in mice noninvasively using single-photon emission computed tomography (SPECT). FibPep and a negative control peptide (NCFibPep) were synthesized and their fibrin-binding properties were assessed in vitro. FibPep showed enhanced binding compared with NCFibPep to both fibrin and blood clots. FibPep bound to fibrin with a dissociation constant (K(d)) of 0.8 μ m, whereas NCFibPep displayed at least a 100-fold lower affinity towards fibrin. A FeCl3 -injury carotid artery thrombosis mouse model was used to evaluate the peptides in vivo. FibPep and NCFibPep displayed rapid blood clearance and were eliminated via the renal pathway. In vivo SPECT imaging using FibPep allowed clear visualization of thrombi. Ex vivo biodistribution showed significantly increased uptake of FibPep in the thrombus-containing carotid in comparison to the noninjured carotid (5.7 ± 0.7 and 0.6 ± 0.4% injected dose per gram (%ID g(-1)), respectively; p < 0.01; n = 4), whereas nonspecific NCFibPep did not (0.4 ± 0.2 and 0.3 ± 0.0%ID g(-1), respectively; n = 4). In conclusion, FibPep displayed high affinity towards fibrin in vitro and rapid blood clearance in vivo, and allowed sensitive detection of thrombi using SPECT imaging. Therefore, this particular imaging approach may provide a new tool to diagnose and monitor diseases such as atherosclerosis and cancer. Copyright © 2013 John Wiley & Sons, Ltd.

Species differences in the pharmacokinetics of cefadroxil as determined in wildtype and humanized PepT1 mice.

PubMed

Hu, Yongjun; Smith, David E

2016-05-01

PepT1 (SLC15A1) is a high-capacity low-affinity transporter that is important in the absorption of digested di/tripeptides from dietary protein in the small intestine. PepT1 is also crucial for the intestinal uptake and absorption of therapeutic agents such as the β-lactam aminocephalosporins and antiviral prodrugs. Species differences, however, have been observed in PepT1-mediated intestinal absorption and pharmacokinetics, thereby, making it more difficult to predict systemic drug exposure. In the present study, we evaluated the in situ intestinal permeability of the PepT1 substrate cefadroxil in wildtype and humanized PepT1 (huPepT1) mice, and the in vivo absorption and disposition of drug after escalating oral doses. The in situ perfusions indicated that cefadroxil had a twofold higher affinity (i.e., twofold lower Km) for jejunal PepT1 in huPepT1 mice, lower but substantial permeability in all regions of the small intestine, and low but measureable permeability in the colon as compared to wildtype animals. The in vivo experiments indicated almost superimposable pharmacokinetic profiles between the two genotypes after intravenous bolus dosing of cefadroxil. In contrast, after oral dose escalation, the systemic exposure of cefadroxil was reduced in huPepT1 mice as compared to wildtype animals. Moreover, the AUC and Cmax versus dose relationships were nonlinear for huPepT1 but not wildtype mice, and similar to that observed from human subjects. In conclusion, our findings indicate that huPepT1 mice may provide a valuable tool in the drug discovery process by better predicting the oral pharmacokinetic profiles of PepT1 substrates in humans. Copyright © 2016 Elsevier Inc. All rights reserved.

Iron Oxide Nanoparticle-Micelles (ION-Micelles) for Sensitive (Molecular) Magnetic Particle Imaging and Magnetic Resonance Imaging

PubMed Central

Starmans, Lucas W. E.; Burdinski, Dirk; Haex, Nicole P. M.; Moonen, Rik P. M.; Strijkers, Gustav J.; Nicolay, Klaas; Grüll, Holger

2013-01-01

Background Iron oxide nanoparticles (IONs) are a promising nanoplatform for contrast-enhanced MRI. Recently, magnetic particle imaging (MPI) was introduced as a new imaging modality, which is able to directly visualize magnetic particles and could serve as a more sensitive and quantitative alternative to MRI. However, MPI requires magnetic particles with specific magnetic properties for optimal use. Current commercially available iron oxide formulations perform suboptimal in MPI, which is triggering research into optimized synthesis strategies. Most synthesis procedures aim at size control of iron oxide nanoparticles rather than control over the magnetic properties. In this study, we report on the synthesis, characterization and application of a novel ION platform for sensitive MPI and MRI. Methods and Results IONs were synthesized using a thermal-decomposition method and subsequently phase-transferred by encapsulation into lipidic micelles (ION-Micelles). Next, the material and magnetic properties of the ION-Micelles were analyzed. Most notably, vibrating sample magnetometry measurements showed that the effective magnetic core size of the IONs is 16 nm. In addition, magnetic particle spectrometry (MPS) measurements were performed. MPS is essentially zero-dimensional MPI and therefore allows to probe the potential of iron oxide formulations for MPI. ION-Micelles induced up to 200 times higher signal in MPS measurements than commercially available iron oxide formulations (Endorem, Resovist and Sinerem) and thus likely allow for significantly more sensitive MPI. In addition, the potential of the ION-Micelle platform for molecular MPI and MRI was showcased by MPS and MRI measurements of fibrin-binding peptide functionalized ION-Micelles (FibPep-ION-Micelles) bound to blood clots. Conclusions The presented data underlines the potential of the ION-Micelle nanoplatform for sensitive (molecular) MPI and warrants further investigation of the FibPep-ION-Micelle platform for in vivo, non-invasive imaging of fibrin in preclinical disease models of thrombus-related pathologies and atherosclerosis. PMID:23437371

Iron oxide nanoparticle-micelles (ION-micelles) for sensitive (molecular) magnetic particle imaging and magnetic resonance imaging.

PubMed

Starmans, Lucas W E; Burdinski, Dirk; Haex, Nicole P M; Moonen, Rik P M; Strijkers, Gustav J; Nicolay, Klaas; Grüll, Holger

2013-01-01

Iron oxide nanoparticles (IONs) are a promising nanoplatform for contrast-enhanced MRI. Recently, magnetic particle imaging (MPI) was introduced as a new imaging modality, which is able to directly visualize magnetic particles and could serve as a more sensitive and quantitative alternative to MRI. However, MPI requires magnetic particles with specific magnetic properties for optimal use. Current commercially available iron oxide formulations perform suboptimal in MPI, which is triggering research into optimized synthesis strategies. Most synthesis procedures aim at size control of iron oxide nanoparticles rather than control over the magnetic properties. In this study, we report on the synthesis, characterization and application of a novel ION platform for sensitive MPI and MRI. IONs were synthesized using a thermal-decomposition method and subsequently phase-transferred by encapsulation into lipidic micelles (ION-Micelles). Next, the material and magnetic properties of the ION-Micelles were analyzed. Most notably, vibrating sample magnetometry measurements showed that the effective magnetic core size of the IONs is 16 nm. In addition, magnetic particle spectrometry (MPS) measurements were performed. MPS is essentially zero-dimensional MPI and therefore allows to probe the potential of iron oxide formulations for MPI. ION-Micelles induced up to 200 times higher signal in MPS measurements than commercially available iron oxide formulations (Endorem, Resovist and Sinerem) and thus likely allow for significantly more sensitive MPI. In addition, the potential of the ION-Micelle platform for molecular MPI and MRI was showcased by MPS and MRI measurements of fibrin-binding peptide functionalized ION-Micelles (FibPep-ION-Micelles) bound to blood clots. The presented data underlines the potential of the ION-Micelle nanoplatform for sensitive (molecular) MPI and warrants further investigation of the FibPep-ION-Micelle platform for in vivo, non-invasive imaging of fibrin in preclinical disease models of thrombus-related pathologies and atherosclerosis.

Is there an optimal level of positive expiratory pressure (PEP) to improve walking tolerance in patients with severe COPD?

PubMed

Russo, Davide; Simonelli, Carla; Paneroni, Mara; Saleri, Manuela; Piroddi, Ines Maria Grazia; Cardinale, Francesco; Vitacca, Michele; Nicolini, Antonello

2016-07-01

The application of positive expiratory pressure (PEP) devices during exercise had been proposed in order to counteract the pulmonary hyperinflation, reduce the dyspnea and thus increase the exercise tolerance in patients with severe chronic obstructive pulmonary disease (COPD). This randomized controlled crossover trial investigated the effect of two different levels of PEP (1 cmH2O and 10 cmH2O) on distance covered at 6minute walk test (6MWT) in patients with severe COPD. Secondary outcomes were the evaluation of PEP effects on physiological and pulmonary function variables. Seventy-two severe COPD patients, referred to our hospitals as in and out patients, were recruited. A basal 6MWT without devices was performed on the first day, and then repeated with PEP 1 cmH2O (PEP1) and 10 cmH2O (PEP10), with a randomized crossover design. Slow and forced spirometries, including the inspiratory capacity measure, were repeated before and after each 6MWT. 50 patients (average age 69,92 year, mean FEV1 41,42% of predicted) concluded the trial. The 6MWT improved significantly among both PEP levels and baseline (323,8 mt at baseline vs. 337,8 PEP1 and 341,8 PEP10; p<.002 and p<.018, respectively). The difference between PEP10 and PEP1 did not reach the significance. No improvements were found in pulmonary function, symptoms and physiological variables after the 6MWT. In patients with severe COPD, the application of 1 cmH2O of PEP seems to improve the exercise tolerance as 10 cmH2O, with similar dyspnea. Further studies should investigate the effects of low levels of PEP on aerobic training programs. Copyright © 2016 SEPAR. Published by Elsevier Espana. All rights reserved.

Estimated protective effectiveness of intramuscular immune serum globulin post-exposure prophylaxis during a measles outbreak in British Columbia, Canada, 2014.

PubMed

Bigham, Mark; Murti, Michelle; Fung, Christina; Hemming, Felicity; Loadman, Susan; Stam, Robert; Van Buynder, Paul; Lem, Marcus

2017-05-09

Intramuscular Immune Serum Globulin (IM ISG) is recommended as post-measles exposure prophylaxis (PEP) when administered within 6days of initial exposure, with variable effectiveness in preventing measles disease. Effectiveness of IM ISG PEP in preventing clinical measles was assessed during a 2014 measles outbreak among a religious-affiliated community in British Columbia, Canada. Fifty-five self-reporting measles susceptible contacts were offered exclusively IM ISG PEP within an eligibility period best surmised to be within 6days of initial measles case exposure. Clinical outcome of IM ISG PEP recipients was determined by selective active surveillance and case self-reporting. IM ISG PEP failure was defined as onset of a measles-like rash 8-21days post-IM ISG PEP. Post-IM ISG PEP measles IgG antibody level was tested in 8 recipients. Factors associated with measles disease were analyzed. Seventeen of 55 IM ISG PEP recipients developed clinically consistent measles in the following 8-21days, corresponding to an estimated crude protective effectiveness of 69%. In school aged children 5-18years, among whom potential exposure intensity and immune status confounders were considered less likely, estimated IM ISG PEP protective effectiveness was 50%. Age <25years was significantly associated with breakthrough clinical measles in bivariate analysis (p=0.0217). Among 8 tested contacts of 17 considered IM ISG PEP failures, post-IM ISG PEP measles IgG antibody levels (mean 16.3days (range 16-17days) post-PEP) were all <150mIU/ml. The estimated crude IM ISG PEP protective effectiveness against measles disease within 8-21days post-ISG administration was 69%. Accuracy of this estimated protective effectiveness is vulnerable to assumptions and uncertainties in ascertaining exposure details and pre-exposure immune status. Increasing the Canadian recommended measles IM ISG PEP dose from 0.25 to 0.5ml/kg (up to 15ml maximum volume) may increase protective effectiveness. Copyright © 2017 Elsevier Ltd. All rights reserved.

Transduction of PEP-1-heme oxygenase-1 into insulin-producing INS-1 cells protects them against cytokine-induced cell death

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

Lee, Su Jin; Kang, Hyung Kyung; Song, Dong Keun

Pro-inflammatory cytokines play a crucial role in the destruction of pancreatic β-cells, thereby triggering the development of autoimmune diabetes mellitus. We recently developed a cell-permeable fusion protein, PEP-1-heme oxygenase-1 (PEP-1-HO-1) and investigated the anti-inflammatory effects in macrophage cells. In this study, we transduced PEP-1-HO-1 into INS-1 insulinoma cells and examined its protective effect against cytokine-induced cell death. PEP-1-HO-1 was successfully delivered into INS-1 cells in time- and dose-dependent manner and was maintained within the cells for at least 48 h. Pre-treatment with PEP-1-HO-1 increased the survival of INS-1 cells exposed to cytokine mixture (IL-1β, IFN-γ, and TNF-α) in a dose-dependent manner.more » PEP-1-HO-1 markedly decreased cytokine-induced production of reactive oxygen species (ROS), nitric oxide (NO), and malondialdehyde (MDA). These protective effects of PEP-1-HO-1 against cytokines were correlated with the changes in the levels of signaling mediators of inflammation (iNOS and COX-2) and cell apoptosis/survival (Bcl-2, Bax, caspase-3, PARP, JNK, and Akt). These results showed that the transduced PEP-1-HO-1 efficiently prevented cytokine-induced cell death of INS-1 cells by alleviating oxidative/nitrosative stresses and inflammation. Further, these results suggested that PEP-1-mediated HO-1 transduction may be a potential therapeutic strategy to prevent β-cell destruction in patients with autoimmune diabetes mellitus. - Highlights: • We showed that PEP-1-HO-1 was efficiently delivered into INS-1 cells. • Transduced PEP-1-HO-1 exerted a protective effect against cytokine-induced cell death. • Transduced PEP-1-HO-1 inhibited cytokine-induced ROS and NO accumulation. • PEP-1-HO-1 suppressed cytokine-induced expression of iNOS, COX-2, and Bax. • PEP-1-HO-1 transduction may be an efficient tool to prevent β-cell destruction.« less

Channel modelling for free-space optical inter-HAP links using adaptive ARQ transmission

NASA Astrophysics Data System (ADS)

Parthasarathy, S.; Giggenbach, D.; Kirstädter, A.

2014-10-01

Free-space optical (FSO) communication systems have seen significant developments in recent years due to growing need for very high data rates and tap-proof communication. The operation of an FSO link is suited to diverse variety of applications such as satellites, High Altitude Platforms (HAPs), Unmanned Aerial Vehicles (UAVs), aircrafts, ground stations and other areas involving both civil and military situations. FSO communication systems face challenges due to different effects of the atmospheric channel. FSO channel primarily suffers from scintillation effects due to Index of Refraction Turbulence (IRT). In addition, acquisition and pointing becomes more difficult because of the high directivity of the transmitted beam: Miss-pointing of the transmitted beam and tracking errors at the receiver generate additional fading of the optical signal. High Altitude Platforms (HAPs) are quasi-stationary vehicles operating in the stratosphere. The slowly varying but precisely determined time-of-flight of the Inter-HAP channel adds to its characteristics. To propose a suitable ARQ scheme, proper theoretical understanding of the optical atmospheric propagation and modeling of a specific scenario FSO channel is required. In this paper, a bi-directional symmetrical Inter-HAP link has been selected and modeled. The Inter-HAP channel model is then investigated via simulations in terms of optical scintillation induced by IRT and in presence of pointing error. The performance characteristic of the model is then quantified in terms of fading statistics from which the Packet Error Probability (PEP) is calculated. Based on the PEP characteristics, we propose suitable ARQ schemes.

Web-Based Psychoeducation Program for Caregivers of First-Episode of Psychosis: An Experience of Chinese Population in Hong Kong.

PubMed

Chan, Sherry K W; Tse, Samson; Sit, Harrison Long Tin; Hui, Christy L M; Lee, Edwin H M; Chang, Wing C; Chen, Eric Y H

2016-01-01

Caregivers of patients with first-episode psychosis are often with little knowledge about the illness and experience more burden of care. Psychoeducation to caregivers has shown to be effective in improving outcomes of patients and possibly reduce stress of the caregivers. This has been recommended as one of the key psychosocial interventions for specific early intervention for psychosis service. However, the accessibility of the service, high case load of the health care professionals and self-stigma of caregivers are often the barriers of implementation of these programs in the real world. Incorporating the convenience of information access via internet and the concept of self-management approach, an interactive internet-based self-help psychoeducation program (iPEP) (www.ipep.hk) for the caregivers of patients with psychosis was established targeting the caregivers of patients with psychosis at early stage in Hong Kong. It provides a comprehensive online resource center in both written and video format on knowledge about psychosis, skills of care, and information of local resources. It also has a forum facilitate information exchange between healthcare professionals and the caregivers, allowing for self-management. Over 800 caregivers have joined the program as members. The evaluation of the subset of the members/users of the iPEP suggested that the iPEP program has been well received and appreciated by the caregivers of patients with first episode psychosis locally. It can potentially serve as a platform for future development of specific manual-based psychoeducation program for caregivers targeting at the needs of different groups.

Web-Based Psychoeducation Program for Caregivers of First-Episode of Psychosis: An Experience of Chinese Population in Hong Kong

PubMed Central

Chan, Sherry K. W.; Tse, Samson; Sit, Harrison Long Tin; Hui, Christy L. M.; Lee, Edwin H. M.; Chang, Wing C.; Chen, Eric Y. H.

2016-01-01

Caregivers of patients with first-episode psychosis are often with little knowledge about the illness and experience more burden of care. Psychoeducation to caregivers has shown to be effective in improving outcomes of patients and possibly reduce stress of the caregivers. This has been recommended as one of the key psychosocial interventions for specific early intervention for psychosis service. However, the accessibility of the service, high case load of the health care professionals and self-stigma of caregivers are often the barriers of implementation of these programs in the real world. Incorporating the convenience of information access via internet and the concept of self-management approach, an interactive internet-based self-help psychoeducation program (iPEP) (www.ipep.hk) for the caregivers of patients with psychosis was established targeting the caregivers of patients with psychosis at early stage in Hong Kong. It provides a comprehensive online resource center in both written and video format on knowledge about psychosis, skills of care, and information of local resources. It also has a forum facilitate information exchange between healthcare professionals and the caregivers, allowing for self-management. Over 800 caregivers have joined the program as members. The evaluation of the subset of the members/users of the iPEP suggested that the iPEP program has been well received and appreciated by the caregivers of patients with first episode psychosis locally. It can potentially serve as a platform for future development of specific manual-based psychoeducation program for caregivers targeting at the needs of different groups. PMID:28082935

Genes Required for Vacuolar Acidity in Saccharomyces Cerevisiae

PubMed Central

Preston, R. A.; Reinagel, P. S.; Jones, E. W.

1992-01-01

Mutations that cause loss of acidity in the vacuole (lysosome) of Saccharomyces cerevisiae were identified by screening colonies labeled with the fluorescent, pH-sensitive, vacuolar labeling agent, 6-carboxyfluorescein. Thirty nine vacuolar pH (Vph(-)) mutants were identified. Four of these contained mutant alleles of the previously described PEP3, PEP5, PEP6 and PEP7 genes. The remaining mutants defined eight complementation groups of vph mutations. No alleles of the VAT2 or TFP1 genes (known to encode subunits of the vacuolar H(+)-ATPase) were identified in the Vph(-) screen. Strains bearing mutations in any of six of the VPH genes failed to grow on medium buffered at neutral pH; otherwise, none of the vph mutations caused notable growth inhibition on standard yeast media. Expression of the vacuolar protease, carboxypeptidase Y, was defective in strains bearing vph4 mutations but was apparently normal in strains bearing any of the other vph mutations. Defects in vacuolar morphology at the light microscope level were evident in all Vph(-) mutants. Strains that contained representative mutant alleles of the 17 previously described PEP genes were assayed for vacuolar pH; mutations in seven of the PEP genes (including PEP3, PEP5, PEP6 and PEP7) caused loss of vacuolar acidity. PMID:1628805

Factors associated with post-ERCP pancreatitis and the effect of pancreatic duct stenting in a pediatric population.

PubMed

Troendle, David M; Abraham, Omana; Huang, Rong; Barth, Bradley A

2015-01-01

Risk factors for the development of post-ERCP pancreatitis (PEP) have not been identified in the pediatric population. It remains unclear what constitutes appropriate prophylaxis in this patient population. To assess the prevalence and severity of PEP in the pediatric population and identify factors associated with developing PEP and to evaluate the effect of prophylactic pancreatic duct stenting in high-risk patients. Retrospective analysis of an ERCP database at a single large pediatric center. Academic center. A total of 432 ERCPs performed on 313 patients younger than 19 years of age from January 2004 to October 2013. ERCP for any indication. Rates and severity of PEP, preprocedural and procedural risk factors for the development of PEP, and the effect of pancreatic stents on preventing PEP in high-risk patients. PEP occurred after 47 procedures (prevalence, 10.9%). Thirty-four cases were mild, 9 were moderate, and 4 were severe. There was no mortality. On multiple logistic analysis, pancreatic duct injection (P<.0001; odds ratio 30.8; 95% confidence interval [CI], 9.1-103.9) and pancreatic sphincterotomy (P<.01; OR 3.8; 95% CI, 1.6-9.8) were positively associated with PEP. A history of chronic pancreatitis was negatively associated with PEP (P<.05; OR 0.37; 95% CI, 0.15-0.93). On subset analysis, placing a prophylactic pancreatic stent was associated with significantly increased rates of PEP in patients with pancreatic duct injection compared with those who had no attempt at stent placement (P<.01). Two patients with severe pancreatitis had prophylactic pancreatic stents in place. Retrospective investigation. In the pediatric population, pancreatic duct injection and pancreatic sphincterotomy are associated with significantly increased rates of PEP, whereas a history of chronic pancreatitis is negatively associated. Prophylactic pancreatic stenting is associated with higher rates of PEP in high-risk patients and does not eliminate severe PEP. Copyright © 2015 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

Transport of Phosphoenolpyruvate by Chloroplasts from Mesembryanthemum crystallinum L. Exhibiting Crassulacean Acid Metabolism 1

PubMed Central

Neuhaus, H. Ekkehard; Holtum, Joseph A. M.; Latzko, Erwin

1988-01-01

Chloroplasts from CAM-Mesembryanthemum crystallinum can transport phosphoenolpyruvate (PEP) across the envelope. The initial velocities of PEP uptake in the dark at 4°C exhibited saturation kinetics with increasing external PEP concentration. PEP uptake had a Vmax of 6.46 (±0.05) micromoles per milligram chlorophyll per hour and an apparent Kmpep of 0.148 (±0.004) millimolar. The uptake was competitively inhibited by Pi (apparent Ki = 0.19 millimolar), by glycerate 3-phosphate (apparent Ki = 0.13 millimolar), and by dihydroxyacetone phosphate, but malate and pyruvate were without effect. The chloroplasts were able to synthesize PEP when presented with pyruvate. PEP synthesis was light dependent. The prolonged synthesis and export of PEP from the chloroplasts required the presence of Pi or glycerate 3-phosphate in the external medium. It is suggested that the transport of pyruvate and PEP across the chloroplasts envelope is required during the gluconeogenic conversion of carbon from malate to storage carbohydrate in the light. PMID:16666128

Quercetin Protects Yeast Saccharomyces cerevisiae pep4 Mutant from Oxidative and Apoptotic Stress and Extends Chronological Lifespan.

PubMed

Alugoju, Phaniendra; Janardhanshetty, Sudharshan Setra; Subaramanian, Subasri; Periyasamy, Latha; Dyavaiah, Madhu

2018-05-01

The yeast Saccharomyces cerevisiae PEP4 gene encodes vacuolar endopeptidase proteinase A (Pep4p), which is a homolog of the human CTSD gene that encodes cathepsin D. Mutation of CTSD gene in human resulted in a number of neurodegenerative diseases. In this study, we have shown that yeast pep4 mutant cells are highly sensitive to oxidative and apoptotic stress induced by hydrogen peroxide and acetic acid, respectively. pep4∆ cells also showed accumulation of reactive oxygen species (ROS), apoptotic markers, and reduced chronological lifespan. In contrast, quercetin pretreatment protected the pep4 mutant from oxidative and apoptotic stress-induced sensitivity by scavenging ROS and reducing apoptotic markers. The percentage viability of quercetin-treated pep4∆ cells was more pronounced and increased stress resistance against oxidant, apoptotic, and heat stress during chronological aging. From our experimental results, we concluded that quercetin protects yeast pep4 mutant cells from oxidative stress and apoptosis, thereby increasing viability during chronological aging.

Isolation of prolyl endopeptidase inhibitory peptides from a sodium caseinate hydrolysate.

PubMed

Hsieh, Cheng-Hong; Wang, Tzu-Yuan; Hung, Chuan-Chuan; Hsieh, You-Liang; Hsu, Kuo-Chiang

2016-01-01

Prolyl endopeptidase (PEP) has been associated with neurodegenerative disorders, and the PEP inhibitors can restore the memory loss caused by amnesic compounds. In this study, we investigated the PEP inhibitory activity of the enzymatic hydrolysates from various food protein sources, and isolated and identified the PEP inhibitory peptides. The hydrolysate obtained from sodium caseinate using bromelain (SC/BML) displayed the highest inhibitory activity of 86.8% at 5 mg mL(-1) in the present study, and its IC50 value against PEP was 0.77 mg mL(-1). The F-5 fraction by RP-HPLC (reversed-phase high performance liquid chromatography) from SC/BML showed the highest PEP inhibition rate of 88.4%, and 9 peptide sequences were identified. The synthetic peptides (1245.63-1787.94 Da) showed dose-dependent inhibition effects on PEP as competitive inhibitors with IC50 values between 29.8 and 650.5 μM. The results suggest that the peptides derived from sodium caseinate have the potential to be PEP inhibitors.

Incidence and risk factors for post-ERCP pancreatitis in chronic pancreatitis.

PubMed

Zhao, Zhen-Hua; Hu, Liang-Hao; Ren, Hong-Bo; Zhao, An-Jing; Qian, Yang-Yang; Sun, Xiao-Tian; Su, Song; Zhu, Shu-Guang; Yu, Jin; Zou, Wen-Bin; Guo, Xiao-Rong; Wang, Lei; Li, Zhao-Shen; Liao, Zhuan

2017-09-01

Almost all studies on post-ERCP pancreatitis (PEP) have mainly involved patients with biliary diseases rather than chronic pancreatitis (CP), and the concept that CP seems to be a protective factor associated with PEP has not been studied in detail. The aim of this study was to determine the incidence of PEP in patients with CP at different clinical stages and to identify the predictive and protective factors of PEP in a large cohort. In this observational cohort study, medical records of patients with CP (CP group) and biliary diseases (BD group) in a tertiary hospital from January 2011 to May 2015 were examined. The difference in the incidence of PEP between CP group and BD group and the risk of PEP at different clinical stages of CP were calculated by the χ 2 test or the Fisher exact test. The predictive and protective factors for PEP were investigated by univariate and multivariate analysis. In total, 2028 ERCP procedures were performed in 1301 patients with CP and 2000 procedures in 1655 patients with BD. The overall incidence of PEP in CP group (4.5%) was similar to that in the BD group (4.8%; P = .747). However, CP patients had significantly lower rates of moderate and severe attacks (0% vs 1.3%, P < .01). According to the M-ANNHEIM classification, the PEP incidences of CP at stages 0, I, II, III, and IV were 4.4%, 5.1%, 3.8%, 2.0%, and 2.0%, respectively. CP patients at stage Ia had the highest PEP incidence (8.0%) among all CP patients, significantly higher than that at stages Ib + Ic (3.9%) and II (3.8%). Female gender, history of acute pancreatitis, and prior PEP were independent risk factors of PEP, whereas extracorporeal shock wave lithotripsy was a protective factor. Compared with BD patients, CP patients had similar incidence of PEP overall but lower grades of severity. The incidence of PEP in CP patients decreased significantly with disease progression. (Clinical trial registration number: NCT02781987.). Copyright © 2017 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

Physiological and Transcriptional Characterization of Escherichia Coli Strains Lacking Interconversion of Phosphoenolpyruvate and Pyruvate When Glucose and Acetate are Coutilized

PubMed Central

Sabido, Andrea; Sigala, Juan Carlos; Hernández-Chávez, Georgina; Flores, Noemí; Gosset, Guillermo; Bolívar, Francisco

2013-01-01

Phosphoenolpyruvate (PEP) is a precursor involved in the biosynthesis of aromatics and other valuable compounds in Escherichia coli. The PEP:carbohydrate phosphotransferase system (PTS) is the major glucose transport system and the largest PEP consumer. To increase intracellular PEP availability for aromatics production purposes, mutant strains of E. coli JM101 devoid of the ptsHIcrr operon (PB11 strain) have been previously generated. In this derivative, transport and growth rate on glucose decreased significantly. A laboratory evolved strain derived from PB11 that partially recovered its growth capacity on glucose was named PB12. In the present study, we blocked carbon skeletons interchange between PEP and pyruvate (PYR) in these ptsHIcrr− strains by deleting the pykA, pykF, and ppsA genes. The PB11 pykAF− ppsA− strain exhibited no growth on glucose or acetate alone, but it was viable when both substrates were consumed simultaneously. In contrast, the PB12 pykAF− ppsA− strain displayed a low growth rate on glucose or acetate alone, but in the mixture, growth was significantly improved. RT-qPCR expression analysis of PB11 pykAF− ppsA− growing with both carbon sources showed a downregulation of all central metabolic pathways compared with its parental PB11 strain. Under the same conditions, transcription of most of the genes in PB12 pykAF− ppsA− did not change, and few like aceBAK, sfcA, and poxB were overexpressed compared with PB12. We explored the aromatics production capabilities of both ptsHIcrr− pykAF− ppsA− strains and the engineered PB12 pykAF− ppsA− tyrR− pheAev2+/pJLBaroGfbrtktA enhanced the yield of aromatic compounds when coutilizing glucose and acetate compared with the control strain PB12 tyrR− pheAev2+/pJLBaroGfbrtktA. Biotechnol. Bioeng. 2014;111: 1150–1160. © 2013 The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals, Inc. PMID:24375081

A Pyrophosphate Based Energy Generating Module

DTIC Science & Technology

2008-12-01

OMB control number. 1. REPORT DATE DEC 2008 2 . REPORT TYPE N/A 3 . DATES COVERED - 4. TITLE AND SUBTITLE A Pyrophosphate Based Energy...for each substrate (PPi, PEP, and AMP) using double reciprocal Lineweaver-Burk plots of saturation data. 10| 2 10| 3 10|4 10|5 10|6 10|7 10-11 10- 10...Partitioning 1 2 3 4 Bilayer - + + + α-Hemolysin - - + + Upper Reservoir +PPi, +PEP +PPi, +PEP +PPi, +PEP +PPi, +PEP, +Luc Lower Reservoir +AMP

The Ustilago maydis Effector Pep1 Suppresses Plant Immunity by Inhibition of Host Peroxidase Activity

PubMed Central

Zechmann, Bernd; Hillmer, Morten; Doehlemann, Gunther

2012-01-01

The corn smut Ustilago maydis establishes a biotrophic interaction with its host plant maize. This interaction requires efficient suppression of plant immune responses, which is attributed to secreted effector proteins. Previously we identified Pep1 (Protein essential during penetration-1) as a secreted effector with an essential role for U. maydis virulence. pep1 deletion mutants induce strong defense responses leading to an early block in pathogenic development of the fungus. Using cytological and functional assays we show that Pep1 functions as an inhibitor of plant peroxidases. At sites of Δpep1 mutant penetrations, H2O2 strongly accumulated in the cell walls, coinciding with a transcriptional induction of the secreted maize peroxidase POX12. Pep1 protein effectively inhibited the peroxidase driven oxidative burst and thereby suppresses the early immune responses of maize. Moreover, Pep1 directly inhibits peroxidases in vitro in a concentration-dependent manner. Using fluorescence complementation assays, we observed a direct interaction of Pep1 and the maize peroxidase POX12 in vivo. Functional relevance of this interaction was demonstrated by partial complementation of the Δpep1 mutant defect by virus induced gene silencing of maize POX12. We conclude that Pep1 acts as a potent suppressor of early plant defenses by inhibition of peroxidase activity. Thus, it represents a novel strategy for establishing a biotrophic interaction. PMID:22589719

Utility of the Psychoeducational Profile-3 for assessing cognitive and language skills of children with autism spectrum disorders.

PubMed

Fulton, Mandy L; D'Entremont, Barbara

2013-10-01

The Psychoeducational Profile-3's (PEP-3) ability to estimate cognitive and language skills of 136 children (20-75 months) with autism spectrum disorders (ASDs) across a range of functioning, and the association between the PEP-3 and ASD symptomatology was examined using retrospective data. PEP-3 cognitive and language measures were positively correlated with similar measures on the Child Development Inventory, the Merrill-Palmer Revised, and the Vineland Adaptive Behaviour Scale-2. The PEP-3 sometimes provided higher or lower estimates than other measures. Significant differences were found between diagnostic groups on PEP-3 cognitive and language measures. PEP-3 cognitive scores correlated positively with scores on the Autism Diagnostic Observation Schedule. Findings support the use of the PEP-3 to measure cognition and language in children with ASDs.

Pathogenic bacteria induce colonic PepT1 expression: an implication in host defense response

PubMed Central

Nguyen, Hang Thi Thu; Dalmasso, Guillaume; Powell, Kimberly R.; Yan, Yutao; Bhatt, Shantanu; Kalman, Daniel; Sitaraman, Shanthi; Merlin, Didier

2009-01-01

Background & Aims Expression of the di/tripeptide transporter PepT1 has been observed in the colon under inflammatory conditions, however, the inducing factors and underlying mechanisms remain unknown. Here, we address the effects of pathogenic bacteria on colonic PepT1 expression together with its functional consequences. Methods Human colonic HT29-Cl.19A cells were infected with the attaching and effacing (A/E) enteropathogenic E. coli (EPEC). Wild-type and PepT1 transgenic mice or cultured colonic tissues derived from these mice were infected with Citrobacter rodentium, a murine A/E pathogen related to EPEC. Results EPEC induced PepT1 expression and activity in HT29-Cl.19A cells by intimately attaching to host cells through lipid rafts. Induction of PepT1 expression by EPEC required the transcription factor Cdx2. PepT1 expression reduced binding of EPEC to lipid rafts, as well as activation of NF-κB and MAP kinase and production of IL-8. Accordingly, ex vivo and in vivo experiments revealed that C. rodentium induced colonic PepT1 expression and that, compared to their wild-type counterparts, PepT1 transgenic mice infected with C. rodentium exhibited decreased bacterial colonization, production of pro-inflammatory cytokines, and neutrophil infiltration into the colon. Conclusions Our findings demonstrate a molecular mechanism underlying the regulation of colonic PepT1 expression under pathological conditions and reveal a novel role for PepT1 in host defense via its capacity to modulate bacterial-epithelial interactions and intestinal inflammation. PMID:19549526

Experiences of HIV postexposure prophylaxis (PEP) among highly exposed men who have sex with men (MSM).

PubMed

Palich, Romain; Martin-Blondel, Guillaume; Cuzin, Lise; Le Talec, Jean-Yves; Boyer, Pierre; Massip, Patrice; Delobel, Pierre

2017-11-01

HIV postexposure prophylaxis (PEP) is indicated after sexual exposure with high risk of transmission. Men who have sex with men (MSM) are the main target of PEP. The aim of our study was to investigate the experience and shortcomings of PEP among people with a high risk of HIV exposure. Subjects with ongoing follow-up for HIV infection and PEP history were selected for the qualitative study. Semistructured interviews were conducted at the patients' homes. They were audio-recorded, transcribed and deidentified before data analysis, double coding and thematic analysis with an inductive approach. Twenty-three patients were eligible for the qualitative study. Thirteen interviews were carried out. All patients were 20-60-year-old MSM. The median time between PEP and HIV diagnosis was 3.3 years (interquartile range (IQR) 25-75 =0.9-4.9). Many participants reported negative PEP experiences: awkward access to the PEP clinic, uneasiness and shame in the hospital setting, unpleasant interaction and moral disapprobation from the medical staff, treatment intolerance and prevention messages that were 'inconsistent with real life' CONCLUSION: Our data highlight PEP management failures among its target population that may have compromised any subsequent attempts to seek out PEP. Practitioners should be more aware of MSM sexual contexts and practices. PEP consultations should provide the opportunity to discuss prevention strategies with highly exposed HIV-negative subjects, which may include pre-exposure prophylaxis. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Crystal structure and mutational analysis of aminoacylhistidine dipeptidase from Vibrio alginolyticus reveal a new architecture of M20 metallopeptidases.

PubMed

Chang, Chin-Yuan; Hsieh, Yin-Cheng; Wang, Ting-Yi; Chen, Yi-Chin; Wang, Yu-Kuo; Chiang, Ting-Wei; Chen, Yi-Ju; Chang, Cheng-Hsiang; Chen, Chun-Jung; Wu, Tung-Kung

2010-12-10

Aminoacylhistidine dipeptidases (PepD, EC 3.4.13.3) belong to the family of M20 metallopeptidases from the metallopeptidase H clan that catalyze a broad range of dipeptide and tripeptide substrates, including L-carnosine and L-homocarnosine. Homocarnosine has been suggested as a precursor for the neurotransmitter γ-aminobutyric acid (GABA) and may mediate the antiseizure effects of GABAergic therapies. Here, we report the crystal structure of PepD from Vibrio alginolyticus and the results of mutational analysis of substrate-binding residues in the C-terminal as well as substrate specificity of the PepD catalytic domain-alone truncated protein PepD(CAT). The structure of PepD was found to exist as a homodimer, in which each monomer comprises a catalytic domain containing two zinc ions at the active site center for its hydrolytic function and a lid domain utilizing hydrogen bonds between helices to form the dimer interface. Although the PepD is structurally similar to PepV, which exists as a monomer, putative substrate-binding residues reside in different topological regions of the polypeptide chain. In addition, the lid domain of the PepD contains an "extra" domain not observed in related M20 family metallopeptidases with a dimeric structure. Mutational assays confirmed both the putative di-zinc allocations and the architecture of substrate recognition. In addition, the catalytic domain-alone truncated PepD(CAT) exhibited substrate specificity to l-homocarnosine compared with that of the wild-type PepD, indicating a potential value in applications of PepD(CAT) for GABAergic therapies or neuroprotection.

Creating the City: An Interview with Antonia Darder and Pepón Osorio

ERIC Educational Resources Information Center

Herman, David, Jr.; Kraehe, Amelia; Bartholomee, Lucy; Lewis, Tyson

2017-01-01

Today there is a lot of discussion about creative economies and how cities are the engines driving growth in a variety of industries. But cities are not merely rows of buildings, or sets of laws, such as zoning ordinances or parking regulations. A city is, rather, a set of dynamic experiences that we all participate in as co(labor)ators. As a way…

47 CFR 11.14 - Primary Entry Point (PEP) System.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 1 2010-10-01 2010-10-01 false Primary Entry Point (PEP) System. 11.14 Section 11.14 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL EMERGENCY ALERT SYSTEM (EAS) General § 11.14 Primary Entry Point (PEP) System. The PEP system is a nationwide network of broadcast...

PEP Up Your PE Program: Writing and Implementing a PEP Grant

ERIC Educational Resources Information Center

McCollum, Starla; Elliott, Steven M.; Burke, Michelle M.; Civalier, Aimee; Pruitt, Wayne; Palmer, Scott

2005-01-01

Physical Education for Progress grants, otherwise known as PEP grants, are part of the Carol M. White Physical Education Program administered by the federal government. PEP grants are available to local educational agencies and community-based organizations to initiate, expand, or improve physical education programs, including after-school…

47 CFR 11.14 - Primary Entry Point (PEP) System.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 1 2011-10-01 2011-10-01 false Primary Entry Point (PEP) System. 11.14 Section 11.14 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL EMERGENCY ALERT SYSTEM (EAS) General § 11.14 Primary Entry Point (PEP) System. The PEP system is a nationwide network of broadcast...

Metabolic engineering to guide evolution - Creating a novel mode for L-valine production with Corynebacterium glutamicum.

PubMed

Schwentner, Andreas; Feith, André; Münch, Eugenia; Busche, Tobias; Rückert, Christian; Kalinowski, Jörn; Takors, Ralf; Blombach, Bastian

2018-03-06

Evolutionary approaches are often undirected and mutagen-based yielding numerous mutations, which need elaborate screenings to identify relevant targets. We here apply Metabolic engineering to Guide Evolution (MGE), an evolutionary approach evolving and identifying new targets to improve microbial producer strains. MGE is based on the idea to impair the cell's metabolism by metabolic engineering, thereby generating guided evolutionary pressure. It consists of three distinct phases: (i) metabolic engineering to create the evolutionary pressure on the applied strain followed by (ii) a cultivation phase with growth as straightforward screening indicator for the evolutionary event, and (iii) comparative whole genome sequencing (WGS), to identify mutations in the evolved strains, which are eventually re-engineered for verification. Applying MGE, we evolved the PEP and pyruvate carboxylase-deficient strain C. glutamicum Δppc Δpyc to grow on glucose as substrate with rates up to 0.31 ± 0.02 h -1 which corresponds to 80% of the growth rate of the wildtype strain. The intersection of the mutations identified by WGS revealed isocitrate dehydrogenase (ICD) as consistent target in three independently evolved mutants. Upon re-engineering in C. glutamicum Δppc Δpyc, the identified mutations led to diminished ICD activities and activated the glyoxylate shunt replenishing oxaloacetate required for growth. Intracellular relative quantitative metabolome analysis showed that the pools of citrate, isocitrate, cis-aconitate, and L-valine were significantly higher compared to the WT control. As an alternative to existing L-valine producer strains based on inactivated or attenuated pyruvate dehydrogenase complex, we finally engineered the PEP and pyruvate carboxylase-deficient C. glutamicum strains with identified ICD mutations for L-valine production by overexpression of the L-valine biosynthesis genes. Among them, C. glutamicum Δppc Δpyc ICD G407S (pJC4ilvBNCE) produced up to 8.9 ± 0.4 g L-valine L -1 , with a product yield of 0.22 ± 0.01 g L-valine per g glucose. Copyright © 2018 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

Five-year cost-effectiveness of the Patient Empowerment Programme (PEP) for type 2 diabetes mellitus in primary care.

PubMed

Lian, Jinxiao; McGhee, Sarah M; So, Ching; Chau, June; Wong, Carlos K H; Wong, William C W; Lam, Cindy L K

2017-09-01

This study evaluated the short-term cost-effectiveness of the Patient Empowerment Programme (PEP) for diabetes mellitus (DM) in Hong Kong. Propensity score matching was used to select a matched group of PEP and non-PEP subjects. A societal perspective was adopted to estimate the cost of PEP. Outcome measures were the cumulative incidence of all-cause mortality and diabetic complication over a 5-year follow-up period and the number needed to treat (NNT) to avoid 1 event. The incremental cost-effectiveness ratio (ICER) of cost per event avoided was calculated using the PEP cost per subject multiplied by the NNT. The PEP cost per subject from the societal perspective was US$247. There was a significantly lower cumulative incidence of all-cause mortality (2.9% vs 4.6%, P < .001), any DM complication (9.5% vs 10.8%, P = .001) and CVD events (6.8% vs 7.6%, P = .018), in the PEP group. The costs per death from any cause, DM complication or case of CVD avoided were US$14 465, US$19 617 and US$30 796, respectively. The extra amount allocated to managing PEP was small and it appears cost-effective in the short-term as an addition to RAMP. © 2017 John Wiley & Sons Ltd.

Is post-event processing a social anxiety specific or transdiagnostic cognitive process in the anxiety spectrum?

PubMed

Laposa, Judith M; Collimore, Kelsey C; Rector, Neil A

2014-11-01

Research on post-event processing (PEP), where individuals conduct a post-mortem evaluation of a social situation, has focused primarily on its relationship with social anxiety. The current study examined: 1) levels of PEP for a standardized event in different anxiety disorders; 2) the relationship between peak anxiety levels during this event and subsequent PEP; and 3) the relationship between PEP and disorder-specific symptom severity. Participants with primary DSM-IV diagnoses of social anxiety disorder (SAD), obsessive compulsive disorder (OCD), panic disorder with/without agoraphobia (PD/A), or generalized anxiety disorder (GAD) completed diagnosis specific symptom measures before attending group cognitive behavioural therapy (CBT) specific to their diagnosis. Participants rated their peak anxiety level during the first group therapy session, and one week later rated PEP in the context of CBT. The results indicated that all anxiety disorder groups showed heightened and equivalent PEP ratings. Peak state anxiety during the first CBT session predicted subsequent level of PEP, irrespective of diagnostic group. PEP ratings were found to be associated with disorder-specific symptom severity in SAD, GAD, and PD/A, but not in OCD. PEP may be a transdiagnostic process with relevance to a broad range of anxiety disorders, not just SAD.

Post-Event Processing across Multiple Anxiety Presentations: Is it Specific to Social Anxiety Disorder?

PubMed

Perera, Stefan; Rowa, Karen; McCabe, Randi E

2016-09-01

Post-event processing (PEP) occurs when individuals engage in cognitive rumination following an event or interaction. Although the relation between PEP and social anxiety has been clearly demonstrated, it remains unclear whether PEP is limited to individuals with elevated social anxiety, or if it is also problematic among people with other anxiety presentations. The present study assessed PEP after the first session of group cognitive behavioural therapy (CBT) in individuals with a variety of anxiety presentations. Participants with a principal diagnosis of SAD (N = 25), those diagnosed with a principal other anxiety disorder with comorbid SAD (N = 18), and those with principal other anxiety diagnoses with no SAD (N = 43) completed baseline measures of social anxiety severity and state anxiety at their first session of CBT and measures of PEP one week later. Participants with a principal diagnosis of SAD experienced the most PEP in the week following the first CBT session, while those with no comorbid SAD experienced the least. Those with comorbid SAD experienced intermediate levels of PEP. The strongest predictor of PEP was state anxiety during the first session. Results suggest that PEP is more problematic for clients with SAD as part of their clinical presentation. Clinical and theoretical implications are discussed.

Letting go of yesterday: Effect of distraction on post-event processing and anticipatory anxiety in a socially anxious sample.

PubMed

Blackie, Rebecca A; Kocovski, Nancy L

2016-01-01

According to cognitive models, post-event processing (PEP) is a key factor in the maintenance of social anxiety. Given that decreasing PEP can be challenging for socially anxious individuals, it is important to identify potentially useful strategies. Although distraction may help to decrease PEP, the findings have been equivocal. The primary purpose of this study was to examine whether a brief distraction period immediately following a speech would lead to less PEP the next day. The secondary aim was to examine the effect of distraction following an initial speech on anticipatory anxiety for a second speech, via reductions in PEP. Participants (N = 77 undergraduates with elevated social anxiety; 67.53% female) delivered a speech and were randomly assigned to a distraction, rumination, or control condition. The following day, participants reported levels of PEP in relation to the first speech, as well as anxiety regarding a second, upcoming speech. As expected, those in the distraction condition reported less PEP than those in the rumination and control conditions. Additionally, distraction following the first speech was indirectly related to anticipatory anxiety for the second speech, via PEP. Distraction may represent a potentially useful strategy for reducing PEP and other maladaptive processes that may maintain social anxiety.

Structural Organization of Baculovirus Occlusion Bodies and Protective Role of Multilayered Polyhedron Envelope Protein.

PubMed

Sajjan, Dayanand B; Hinchigeri, Shivayogeppa B

2016-03-01

Baculoviruses are the ingenious insect pathogens. Outside the host, baculovirus occlusion bodies (OB) provide stability to occlusion-derived viruses (ODV) embedded within. The OB is an organized structure, chiefly composed of proteins namely polyhedrin, polyhedron envelope protein (PEP) and P10. Currently, the structural organization of OB is poorly understood and the role of OB proteins in conferring the stability to ODV is unknown. Here we have shown that the assembly of polyhedrin unit cells into an OB is a rapid process; the PEP forms in multiple layers; the PEP layers predominantly contribute to ODV viability. Full-grown OBs (n = 36) were found to be 4.0 ± 1.0 µm in diameter and possessed a peculiar geometry of a truncated rhombic dodecahedron. The atomic force microscopy (AFM) study on the structure of OBs at different stages of growth in insect cells revealed polyhedrin assembly and thickness of PEP layers. The thickness of PEP layers at 53 h post-transfection (hpt) ranged from 56 to 80 nm. Mature PEP layers filled up approximately one third of the OB volume. The size of ODV nucleocapsid was found to be 433 ± 10 nm in length. The zeta potential and particle size distribution study of viruses revealed the protective role of PEP layers. The presence of a multilayered PEP confers a viable advantage to the baculoviruses compared to single-layered PEP. Thus, these findings may help in developing PEP layer-based biopolymers for protein-based nanodevices, nanoelectrodes and more stable biopesticides.

Trichome density of main stem is tightly linked to PepMoV resistance in chili pepper (Capsicum annuum L.).

PubMed

Kim, Hyun Jung; Han, Jung-Heon; Kim, Seungill; Lee, Heung Ryul; Shin, Jun-Sung; Kim, Jeong-Ho; Cho, Juok; Kim, Young Ho; Lee, Hee Jae; Kim, Byung-Dong; Choi, Doil

2011-04-01

A relationship between pepper trichome and pepper mottle virus (PepMoV) resistance was examined. In an intraspecific F(2) mapping population from the cross between Capsicum annuum CM334 (trichome-bearing and PepMoV resistant) and Chilsungcho (glabrous and PepMoV susceptible), major QTLs for both traits were identified by composite interval mapping in linkage group (LG) 24 corresponding a telomere region on pepper chromosome 10. Ptel1 of putative trichome enhancing locus was a common major QTL for trichome density on the main stem and calyx. Ptel1 apart from HpmsE031 at a 1.03 cM interval was specifically associated to the trichome density on the main stem, whereas Ptel2 near m104 marker on LG2 was specific for the calyx trichome. Epistatic analysis indicated that Ptel1 engaged in controlling the trichome density by mutual interactions with the organ-specific QTLs. For PepMoV resistance, two QTLs (Pep1 and Pep2) were identified on the LG 24. Pep1 was located with Ptel1 in the R-gene cluster (RGC) for potyvirus resistance including Pvr4 with broad spectrum resistance to potyviruses. Pep1 flanking TG420 marker seemed to be the major factors determining correlation with PepMoV resistance. These results indicate that the level of trichome density on pepper main stem can be used as a morphological marker for Pvr4 in pepper breeding.

Cost-effectiveness analysis of varicella vaccine as post-exposure prophylaxis in Hong Kong.

PubMed

Chui, Ka-Sing; Wu, Hiu-Lok; You, Joyce H S

2014-01-01

The varicella vaccine is an effective post-exposure prophylaxis (PEP) for chickenpox. This study aimed to analyze the cost-effectiveness of PEP using varicella vaccine for pediatric patients from the perspective of the public healthcare provider in Hong Kong. A decision tree was designed to compare cost and clinical outcomes of PEP with varicella vaccine versus no PEP in pediatric patients (aged 1-18 y) susceptible to chickenpox with household exposure. Two tiers of outcome were simulated: (1) total direct medical cost per subject exposed, and (2) the quality-adjusted life-year (QALY) loss associated with chickenpox per subject exposed. Model inputs were retrieved from local epidemiology and the medical literature. A sensitivity analysis was performed on all parameters to test the robustness of model results. The base-case analysis showed PEP with varicella vaccine to be less costly (expected cost USD 320 vs USD 731) with lower QALY loss (0.00423 QALY vs 0.01122 QALY) when compared to no PEP. The sensitivity analysis showed that PEP with varicella vaccine was less costly if PEP effectiveness was > 6.2% or the chickenpox infection rate without PEP was > 8.6%. In 10,000 Monte Carlo simulations, PEP with vaccine was cost-effective over 99% of the time, with a mean cost saving of USD 611 per patient (95% confidence interval USD 602-620; p < 0.001) and lower mean QALY loss of 0.00809 QALY (95% confidence interval 0.00802-0.00816 QALY; p < 0.001). Using varicella vaccine as PEP appears to be a cost-saving strategy to avert QALY loss in susceptible pediatric patients exposed to chickenpox in Hong Kong.

Streptococcus pyogenes Endopeptidase O Contributes to Evasion from Complement-mediated Bacteriolysis via Binding to Human Complement Factor C1q*

PubMed Central

Honda-Ogawa, Mariko; Sumitomo, Tomoko; Mori, Yasushi; Hamd, Dalia Talat; Ogawa, Taiji; Yamaguchi, Masaya; Nakata, Masanobu; Kawabata, Shigetada

2017-01-01

Streptococcus pyogenes secretes various virulence factors for evasion from complement-mediated bacteriolysis. However, full understanding of the molecules possessed by this organism that interact with complement C1q, an initiator of the classical complement pathway, remains elusive. In this study, we identified an endopeptidase of S. pyogenes, PepO, as an interacting molecule, and investigated its effects on complement immunity and pathogenesis. Enzyme-linked immunosorbent assay and surface plasmon resonance analysis findings revealed that S. pyogenes recombinant PepO bound to human C1q in a concentration-dependent manner under physiological conditions. Sites of inflammation are known to have decreased pH levels, thus the effects of PepO on bacterial evasion from complement immunity was analyzed in a low pH condition. Notably, under low pH conditions, PepO exhibited a higher affinity for C1q as compared with IgG, and PepO inhibited the binding of IgG to C1q. In addition, pepO deletion rendered S. pyogenes more susceptible to the bacteriocidal activity of human serum. Also, observations of the morphological features of the pepO mutant strain (ΔpepO) showed damaged irregular surfaces as compared with the wild-type strain (WT). WT-infected tissues exhibited greater severity and lower complement activity as compared with those infected by ΔpepO in a mouse skin infection model. Furthermore, WT infection resulted in a larger accumulation of C1q than that with ΔpepO. Our results suggest that interaction of S. pyogenes PepO with C1q interferes with the complement pathway, which enables S. pyogenes to evade complement-mediated bacteriolysis under acidic conditions, such as seen in inflammatory sites. PMID:28154192

Simple purification method for a recombinantly expressed native His-tag-free aminopeptidase A from Lactobacillus delbrueckii.

PubMed

Stressler, Timo; Tanzer, Coralie; Ewert, Jacob; Claaßen, Wolfgang; Fischer, Lutz

2017-03-01

The aminopeptidase A (PepA; EC 3.4.11.7) is an intracellular exopeptidase present in lactic acid bacteria. The PepA cleaves glutamyl/aspartyl residues from the N-terminal end of peptides and can, therefore, be applied for the production of protein hydrolysates with an increased amount of these amino acids, which results in a savory taste (umami). The first PepA from a lactobacilli strain was recombinantly expressed in Escherichia coli in a recently published study and harbored a C-terminal His 6 -tag for easier purification. Due to the fact that a His-tag might influence the properties of an enzyme, a simple purification method for the non-His-tagged PepA was required. Surprisingly, the PepA precipitated at a very low ammonium sulfate concentration of 5%. Unusual for a precipitating step, the purity of PepA was over 95% and the obtained activity yield was 110%. The high purity allows biochemical characterization and kinetic investigation. As a result, the optimum pH (6.0-6.5) and temperature (60-65 °C) were comparable to the His 6 -tag harboring PepA; the K M value was at 0.79 mM slightly lower compared to 1.21 mM, respectively. Since PepA is a homo dodecamer, it has a high molecular mass of approximately 480 kDa. Therefore, a subsequent preparative size-exclusion chromatography (SEC) step seemed promising. The PepA after SEC was purified to homogeneity. In summary, the simple two-step purification method presented can be applied to purify high amounts of PepA that will allow the performance of experiments in the future to crystalize PepA for the first time. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of pergolide mesylate on transduction efficiency of PEP-1-catalase protein

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

Sohn, Eun Jeong; Kim, Dae Won; Kim, Young Nam

2011-03-18

Research highlights: {yields} We studied effects of pergolide mesylate (PM) on in vitro and in vivo transduction of PEP-1-catalase. {yields} PEP-1-catatase inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation. {yields} PM enhanced the transduction of PEP-1-catalase into HaCaT cells and skin tissue. {yields} PM increased anti-inflammatory activity of PEP-1-catalase. {yields} PM stimulated therapeutic action of anti-oxidant enzyme catalase in oxidative-related diseases. -- Abstract: The low transduction efficiency of various proteins is an obstacle to their therapeutic application. However, protein transduction domains (PTDs) are well-known for a highly effective tool for exogenous protein delivery to cells. We examined the effects of pergolide mesylate (PM) onmore » the transduction of PEP-1-catalase into HaCaT human keratinocytes and mice skin and on the anti-inflammatory activity of PEP-1-catatase against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation using Western blot and histological analysis. PM enhanced the time- and dose-dependent transduction of PEP-1-catalase into HaCaT cells without affecting the cellular toxicity. In a mouse edema model, PEP-1-catalase inhibited the increased expressions of inflammatory mediators and cytokines such as cyclooxygenase-2, inducible nitric oxide synthase, interleukin-6 and -1{beta}, and tumor necrosis factor-{alpha} induced by TPA. On the other hand, PM alone failed to exert any significant anti-inflammatory effects. However, the anti-inflammatory effect of co-treatment with PEP-1-catalase and PM was more potent than that of PEP-1-catalase alone. Our results indicate that PM may enhance the delivery of PTDs fusion therapeutic proteins to target cells and tissues and has potential to increase their therapeutic effects of such drugs against various diseases.« less

Guidelines "PEP," Peer Evaluation Program. A Systematic Approach for Evaluating Educational Programs, 1973-1974.

ERIC Educational Resources Information Center

Grotsky, Jeffery N.; And Others

The Peer Evaluation Program (PEP) has been instituted by the Division of Special Education, Pennsylvania State Department of Education, to allow intermediate units an opportunity to continuously improve their programs. The advantages of the PEP system are: (1) it is a self-improvememt system of program development; (2) PEP allows local autonomy as…

Preschool Children's Performance on Profiling Elements of Prosody in Speech-Communication (PEPS-C)

ERIC Educational Resources Information Center

Gibbon, Fiona E.; Smyth, Heather

2013-01-01

Profiling Elements of Prosody in Speech-Communication (PEPS-C) has not been used widely to assess prosodic abilities of preschool children. This study was therefore aimed at investigating typically developing 4-year-olds' performance on PEPS-C. PEPS-C was presented to 30 typically developing 4-year-olds recruited in southern Ireland. Children were…

PEP-on-DEP: A competitive peptide-based disposable electrochemical aptasensor for renin diagnostics.

PubMed

Biyani, Manish; Kawai, Keiko; Kitamura, Koichiro; Chikae, Miyuki; Biyani, Madhu; Ushijima, Hiromi; Tamiya, Eiichi; Yoneda, Takashi; Takamura, Yuzuru

2016-10-15

Antibody-based immunosensors are relatively less accessible to a wide variety of unreachable targets, such as low-molecular-weight biomarkers that represent a rich untapped source of disease-specific diagnostic information. Here, we present a peptide aptamer-based electrochemical sensor technology called 'PEP-on-DEP' to detect less accessible target molecules, such as renin, and to improve the quality of life. Peptide-based aptamers represent a relatively smart class of affinity binders and show great promise in biosensor development. Renin is involved in the regulation of arterial blood pressure and is an emerging biomarker protein for predicting cardiovascular risk and prognosis. To our knowledge, no studies have described aptamer molecules that can be used as new potent probes for renin. Here, we describe a portable electrochemical biosensor platform based on the newly identified peptide aptamer molecules for renin. We constructed a randomized octapeptide library pool with diversified sequences and selected renin specific peptide aptamers using cDNA display technology. We identified a few peptide aptamer sequences with a KD in the µM binding affinity range for renin. Next, we grafted the selected peptide aptamers onto gold nanoparticles and detected renin in a one-step competitive assay using our originally developed DEP (Disposable Electrochemical Printed) chip and a USB powered portable potentiostat system. We successfully detected renin in as little as 300ngmL(-1) using the PEP-on-DEP method. Thus, the generation and characterization of novel probes for unreachable target molecules by merging a newly identified peptide aptamer with electrochemical transduction allowed for the development of a more practical biosensor that, in principle, can be adapted to develop a portable, low-cost and mass-producible biosensor for point-of-care applications. Copyright © 2015 Elsevier B.V. All rights reserved.

Lateral flow assay for rapid detection of white spot syndrome virus (WSSV) using a phage-displayed peptide as bio-recognition probe.

PubMed

Kulabhusan, Prabir Kumar; Rajwade, Jyutika M; Sahul Hameed, A S; Paknikar, Kishore M

2017-06-01

White spot disease caused by the white spot syndrome virus (WSSV) has a major socio-economic impact on shrimp farming in India. It has been realized that a field-usable diagnostic capable of rapid detection of WSSV can prevent huge economic losses in disease outbreaks. In this work, we explored the possibility of using a peptide as bio-recognition probe in a field-usable device for the detection of WSSV from infected shrimps and prawns. A commercially available random phage-display library was screened against rVP28 (a major structural protein of WSSV, expressed as a recombinant protein in Escherichia coli). A bacteriophage clone VP28-4L was obtained, and its binding to purified rVP28 protein as well as WSSV from infected shrimp Litopaeneus vannamei tissue was confirmed by ELISA and western blot. The apparent equilibrium dissociation constant (K d ,app) was calculated to be 810 nM. VP28-4L did not show cross-reactivity with any other shrimp viruses. A 12-mer peptide (pep28, with the sequence 'TFQAFDLSPFPS') displayed on the VP28-4L was synthesized, and its diagnostic potential was evaluated in a lateral flow assay (LFA). Visual detection of WSSV could be achieved using biotinylated-pep28 and streptavidin-conjugated gold nanoparticles. In LFA, 12.5 μg/mL of the virus could be detected from L. vannamei gill tissue homogenate within 20 min. Pep28 thus becomes an attractive candidate in bio-recognition of WSSV in field-usable diagnostic platforms benefitting the aquaculture sector.

p53 in pure epithelioid PEComa: an immunohistochemistry study and gene mutation analysis.

PubMed

Bing, Zhanyong; Yao, Yuan; Pasha, Theresa; Tomaszewski, John E; Zhang, Paul J

2012-04-01

Pure epithelioid PEComa (PEP; so-called epithelioid angiomyolipoma) is rare and is more often associated with aggressive behaviors. The pathogenesis of PEP has been poorly understood. The authors studied p53 expression and gene mutation in PEPs by immunohistochemistry, single-strand conformation polymorphism, and direct sequencing in paraffin material from 8 PEPs. A group of classic angiomyolipomas (AMLs) were also analyzed for comparison. Five PEPs were from kidneys and 1 each from the heart, the liver, and the uterus. PEPs showed much stronger p53 nuclear staining (Allred score 6.4 ± 2.5) than the classic AML (2.3 ± 2.9) (P < .01). There was no p53 single-strand conformation polymorphism identified in either the PEPs or the 8 classic AMLs. p53 mutation analyses by direct sequencing of exons 5 to 9 showed 4 mutations in 3 of 8 PEPs but none in any of the 8 classic AMLs. The mutations included 2 missense mutations in a hepatic PEComa and 2 silent mutations in 2 renal PEPs. Both the missense mutations in the hepatic PEComa involved the exon 5, one involving codon 165, with change from CAG to CAC (coding amino acid changed from glutamine to histidine), and the other involving codon 182, with change from TGC to TAC (coding amino acid changed from cysteine to tyrosine). The finding of stronger p53 expression and mutations in epithelioid angiomyolipomas might have contributed to their less predictable behavior. However, the abnormal p53 expression cannot be entirely explained by p53 mutations in the exons examined in the PEPs.

Developmental contributions to macronutrient selection: a randomized controlled trial in adult survivors of malnutrition

PubMed Central

Campbell, Claudia P.; Raubenheimer, David; Badaloo, Asha V.; Gluckman, Peter D.; Martinez, Claudia; Gosby, Alison; Simpson, Stephen J.; Osmond, Clive; Boyne, Michael S.

2016-01-01

Abstract Background and objectives: Birthweight differences between kwashiorkor and marasmus suggest that intrauterine factors influence the development of these syndromes of malnutrition and may modulate risk of obesity through dietary intake. We tested the hypotheses that the target protein intake in adulthood is associated with birthweight, and that protein leveraging to maintain this target protein intake would influence energy intake (EI) and body weight in adult survivors of malnutrition. Methodology: Sixty-three adult survivors of marasmus and kwashiorkor could freely compose a diet from foods containing 10, 15 and 25 percentage energy from protein (percentage of energy derived from protein (PEP); Phase 1) for 3 days. Participants were then randomized in Phase 2 (5 days) to diets with PEP fixed at 10%, 15% or 25%. Results: Self-selected PEP was similar in both groups. In the groups combined, selected PEP was 14.7, which differed significantly (P < 0.0001) from the null expectation (16.7%) of no selection. Self-selected PEP was inversely related to birthweight, the effect disappearing after adjusting for sex and current body weight. In Phase 2, PEP correlated inversely with EI (P = 0.002) and weight change from Phase 1 to 2 (P = 0.002). Protein intake increased with increasing PEP, but to a lesser extent than energy increased with decreasing PEP. Conclusions and implications: Macronutrient intakes were not independently related to birthweight or diagnosis. In a free-choice situation (Phase 1), subjects selected a dietary PEP significantly lower than random. Lower PEP diets induce increased energy and decreased protein intake, and are associated with weight gain. PMID:26817484

Diclofenac Does Not Reduce the Risk of Post-endoscopic Retrograde Cholangiopancreatography Pancreatitis in Low-Risk Units.

PubMed

Rainio, Mia; Lindström, Outi; Udd, Marianne; Louhimo, Johanna; Kylänpää, Leena

2017-08-01

Nonsteroidal anti-inflammatory drugs have an inhibitory role in pathogenesis of pancreatitis. Guidelines from the European Society of Gastrointestinal Endoscopy recommend routine rectal administration of 100 mg of diclofenac or indomethacin immediately before or after ERCP for all patients without contraindications. Our aim was to evaluate the effect of diclofenac in preventing post-ERCP pancreatitis (PEP) in a high-volume, low-PEP-risk ERCP unit. The rate and severity of PEP were compared in groups of 1000 historical controls prior to the routine use of diclofenac and in 1000 patients receiving 100 mg diclofenac before ERCP. PEP occurred in 56 (2.8%) of the 2000 patients, and the rate of the pancreatitis was 2.8% in control group and 2.8% in diclofenac group (p = 1.000). The PEP rate among the native papilla patients was 3.9% in control group and 3.6% in diclofenac group (p = 0.803). In subgroup analysis of patients with a high risk of PEP, diclofenac neither prevented PEP nor made its course milder. In an unselected patient population in a center with a low incidence of PEP, diclofenac seems to have no beneficial effect.

The relationship of post-event processing to self-evaluation of performance in social anxiety.

PubMed

Brozovich, Faith; Heimberg, Richard G

2011-06-01

Socially anxious and control participants engaged in a social interaction with a confederate and then wrote about themselves or the other person (i.e., self-focused post-event processing [SF-PEP] vs. other-focused post-event processing [OF-PEP]) and completed several questionnaires. One week later, participants completed measures concerning their evaluation of their performance in the social interaction and the degree to which they engaged in post-event processing (PEP) during the week. Socially anxious individuals evaluated their performance in the social interaction more poorly than control participants, both immediately after and 1 week later. Socially anxious individuals assigned to the SF-PEP condition displayed fewer positive feelings about their performance compared to the socially anxious individuals in the OF-PEP condition as well as controls in either condition. Also, the trait tendency to engage in PEP moderated the effect of social anxiety on participants' evaluation of their performance in the interaction, such that high socially anxious individuals with high trait PEP scores evaluated themselves in the interaction more negatively at the later assessment. These results suggest that PEP and other self-evaluative processes may perpetuate the cycle of social anxiety. Copyright © 2011. Published by Elsevier Ltd.

Positive expiratory pressure therapy versus other airway clearance techniques for bronchiectasis.

PubMed

Lee, Annemarie L; Burge, Angela T; Holland, Anne E

2017-09-27

People with bronchiectasis experience chronic cough and sputum production and require the prescription of airway clearance techniques (ACTs). A common type of ACT prescribed is positive expiratory pressure (PEP) therapy. A previous review has suggested that ACTs including PEP therapy are beneficial compared to no treatment in people with bronchiectasis. However, the efficacy of PEP therapy in a stable clinical state or during an acute exacerbation compared to other ACTs in bronchiectasis is unknown. The primary aim of this review was to determine the effects of PEP therapy compared with other ACTs on health-related quality of life (HRQOL), rate of acute exacerbations, and incidence of hospitalisation in individuals with stable or an acute exacerbation of bronchiectasis.Secondary aims included determining the effects of PEP therapy upon physiological outcomes and clinical signs and symptoms compared with other ACTs in individuals with stable or an acute exacerbation of bronchiectasis. We searched the Cochrane Airways Group Specialised Register of Trials, PEDro and clinical trials registries from inception to February 2017 and we handsearched relevant journals. Randomised controlled parallel and cross-over trials that compared PEP therapy versus other ACTs in participants with bronchiectasis. We used standard methodological procedures as outlined by Cochrane. Nine studies involving 213 participants met the inclusion criteria, of which seven were cross-over in design. All studies included adults with bronchiectasis, with eight including participants in a stable clinical state and one including participants experiencing an acute exacerbation. Eight studies used oscillatory PEP therapy, using either a Flutter or Acapella device and one study used Minimal PEP therapy. The comparison intervention differed between studies. The methodological quality of studies was poor, with cross-over studies including suboptimal or no washout period, and a lack of blinding of participants, therapists or personnel for outcome measure assessment in most studies. Clinical heterogeneity between studies limited meta-analysis.Daily use of oscillatory PEP therapy for four weeks was associated with improved general health according to the Short-Form 36 questionnaire compared to the active cycle of breathing technique (ACBT). When applied for three sessions over one week, minimal PEP therapy resulted in similar improvement in cough-related quality of life as autogenic drainage (AD) and L'expiration Lente Totale Glotte Ouverte en Decubitus Lateral (ELTGOL). Oscillatory PEP therapy twice daily for four weeks had similar effects on disease-specific HRQOL (MD -0.09, 95% CI -0.37 to 0.19; low-quality evidence). Data were not available to determine the incidence of hospitalisation or rate of exacerbation in clinically stable participants.Two studies of a single session comparison of oscillatory PEP therapy and gravity-assisted drainage (GAD) with ACBT had contrasting findings. One study found a similar sputum weight produced with both techniques (SMD 0.54g (-0.38 to 1.46; 20 participants); the other found greater sputum expectoration with GAD and ACBT (SMD 5.6 g (95% CI 2.91 to 8.29: 36 participants). There was no difference in sputum weight yielded between oscillatory PEP therapy and ACBT with GAD when applied daily for four weeks or during an acute exacerbation. Although a single session of oscillatory PEP therapy was associated with less sputum compared to AD (median difference 3.1 g (95% CI 1.5 to 4.8 g; one study, 31 participants), no difference between oscillatory PEP therapy and seated ACBT was evident. PEP therapy had a similar effect on dynamic and static measures of lung volumes and gas exchange as all other ACTs. A single session of oscillatory PEP therapy (Flutter) generated a similar level of fatigue as ACBT with GAD, but greater fatigue was noted with oscillatory PEP therapy compared to ACBT alone. The degree of breathlessness experienced with PEP therapy did not differ from other techniques. Among studies exploring adverse events, only one study reported nausea with use of oscillatory PEP therapy. PEP therapy appears to have similar effects on HRQOL, symptoms of breathlessness, sputum expectoration, and lung volumes compared to other ACTs when prescribed within a stable clinical state or during an acute exacerbation. The number of studies and the overall quality of the evidence were both low. In view of the chronic nature of bronchiectasis, additional information is needed to establish the long-term clinical effects of PEP therapy over other ACTs for outcomes that are important to people with bronchiectasis and on clinical parameters which impact on disease progression and patient morbidity in individuals with stable bronchiectasis. In addition, the role of PEP therapy during an acute exacerbation requires further exploration. This information is necessary to provide further guidance for prescription of PEP therapy for people with bronchiectasis.

GroEL actively stimulates folding of the endogenous substrate protein PepQ.

PubMed

Weaver, Jeremy; Jiang, Mengqiu; Roth, Andrew; Puchalla, Jason; Zhang, Junjie; Rye, Hays S

2017-06-30

Many essential proteins cannot fold without help from chaperonins, like the GroELS system of Escherichia coli. How chaperonins accelerate protein folding remains controversial. Here we test key predictions of both passive and active models of GroELS-stimulated folding, using the endogenous E. coli metalloprotease PepQ. While GroELS increases the folding rate of PepQ by over 15-fold, we demonstrate that slow spontaneous folding of PepQ is not caused by aggregation. Fluorescence measurements suggest that, when folding inside the GroEL-GroES cavity, PepQ populates conformations not observed during spontaneous folding in free solution. Using cryo-electron microscopy, we show that the GroEL C-termini make physical contact with the PepQ folding intermediate and help retain it deep within the GroEL cavity, resulting in reduced compactness of the PepQ monomer. Our findings strongly support an active model of chaperonin-mediated protein folding, where partial unfolding of misfolded intermediates plays a key role.

Factors Associated with Forensic Nurses Offering HIV nPEP status-post Sexual Assault

PubMed Central

Draughon, Jessica E.; Hauda, William E.; Price, Bonnie; Rotolo, Sue; Austin, Kim Wieczorek; Sheridan, Daniel J.

2014-01-01

Non-occupational post-exposure prophylaxis (nPEP) for Human Immunodeficiency Virus (HIV) is offered inconsistently to patients who have been sexually assaulted. This may be due to Forensic Nurse Examiner (FNE) programs utilizing diverse nPEP protocols and HIV risk assessment algorithms. This study examines factors associated with FNEs offering nPEP to patients following sexual assault at two FNE programs in urban settings. Offering nPEP is mostly driven by site-specific protocol. At Site 1 in addition to open anal or open genital wounds, the presence of injury to the head or face was associated with FNEs offering nPEP (AOR 64.15, 95%CI [2.12 – 1942.37]). At Site 2, patients assaulted by someone of other race/ethnicity (non-White, non-African American) were 86% less likely to be offered nPEP (AOR 0.14, 95%CI [.03-.72]) than patients assaulted by Whites. In addition to following site specific protocols, future research should further explore the mechanisms influencing clinician decision making. PMID:24733232

Short-term exposure to engineered nanomaterials affects cellular epigenome

PubMed Central

Lu, Xiaoyan; Miousse, Isabelle R.; Pirela, Sandra V.; Melnyk, Stepan; Koturbash, Igor; Demokritou, Philip

2015-01-01

Extensive incorporation of engineered nanomaterials (ENMs) into industrial and biomedical applications increases the risks of exposure to these potentially hazardous materials. While the geno- and cytotoxic effects of ENMs have been investigated, the potential of ENMs to target the cellular epigenome remains largely unknown. Our goal was to determine whether or not industry relevant ENMs can affect the epigenome at low cytotoxic doses. A panel of cells relevant to inhalation exposures such as human and murine macrophages (THP-1 and RAW264.7, respectively) and human small airway epithelial cells (SAEC) were exposed to printer-emitted engineered nanoparticles (PEPs), mild steel welding fumes (MS-WF), copper oxide (CuO), and titanium dioxide (TiO2) nanoparticles. Toxicological effects, including cytotoxicity, oxidative stress, and inflammatory responses were assessed, taking into consideration in-vitro dosimetry. The effects of ENMs on cellular epigenome were determined by addressing the global and transposable elements (TEs)-associated DNA methylation and expression of DNA methylation machinery and TEs. The percentage of ENMs-induced cytotoxicity for all cell lines was in the range of 0-15%. Oxidative stress was evident in SAEC after exposure to PEPs and in THP-1 when exposed to CuO. Additionally, exposure to ENMs resulted in modest alterations in DNA methylation of two most abundant TEs in mammalian genomes, LINE-1 and Alu/SINE, their transcriptional reactivation, and decreased expression of DNA methylation machinery in a cell-, dose-, and ENM-dependent manner. These results indicate that exposure to ENMs at environmentally relevant concentrations, aside from the geno- and cytotoxic effects, can also affect the epigenome of target cells. PMID:25938281

Differential effect of a patient-education transition intervention in adolescents with IBD vs. diabetes.

PubMed

Schmidt, Silke; Markwart, Henriette; Bomba, Franziska; Muehlan, Holger; Findeisen, Annette; Kohl, Martina; Menrath, Ingo; Thyen, Ute

2018-04-01

Patient education programs (PEPs) to improve disease management are part of standard and regular treatment in adolescents with diabetes. In Germany, youth with inflammatory bowel disease (IBD) receive individual counseling but not PEPs in group settings. Generic PEPs have been developed in order to improve transition from child-centered to adolescent health services. The aim of the study was to investigate the effects of a transition-oriented PEP on quality of life (QoL) and self-management in young patients with IBD (PEP naive), compared to patients with diabetes (familiar with PEPs). A 2-day transition workshop was oriented at improving psychosocial skills and addressed both generic as well as specific aspects of the condition. A controlled trial on the outcomes of a generic transition-oriented PEP was conducted in 14- to 20-year-old patients with IBD (n = 99) and diabetes (n = 153). Transition competence and QoL were assessed at baseline and 6-month follow-up. Results show that the intervention lead to a significant increase in QoL only in patients with IBD. The PEP significantly improved transition competence in both groups, however to a higher extent in subjects with IBD. Transition-oriented PEPs can have differential effects in different patient groups. However, this needs further longitudinal investigations. What is Known: • To date, evidence has accumulated concerning the effectiveness of patient education programs (PEPs) in pediatric health care for chronic conditions such as type 1 diabetes, asthma, atopic dermatitis, or obesity but is less documented in inflammatory bowel disease (IBD). In particular, PEPs in the transition period have not been investigated in youth with IBD. • The current study focuses on evaluating a PEP for transition preparation and management designed to be generically used across different chronic conditions since many aspects of managing chronic conditions share commonalities across conditions. The 2-day workshop included condition-specific modules adapted to the specific medical needs but was otherwise similar in quality and organization among different conditions. What is New: • The transition-oriented PEP was effective in enhancing self-management and transition management skills in both patients with IBD and diabetes; however, effects were higher in youth with IBD. A significant impact of the intervention on patients' QoL compared to the control group was only identified in youth with IBD. • We recommend that patients with IBD have access to PEP as a standard treatment as well as to a transition program during the course of illness.

Randomized controlled trial of the tolerability and completion of maraviroc compared with Kaletra® in combination with Truvada® for HIV post-exposure prophylaxis (MiPEP Trial).

PubMed

Milinkovic, Ana; Benn, Paul; Arenas-Pinto, Alejandro; Brima, Nataliya; Copas, Andrew; Clarke, Amanda; Fisher, Martin; Schembri, Gabriel; Hawkins, David; Williams, Andy; Gilson, Richard

2017-06-01

Post-exposure prophylaxis (PEP) for HIV is often poorly tolerated and not completed. Alternative PEP regimens may improve adherence and completion, aiding HIV prevention. We conducted a randomized controlled trial of a maraviroc-based PEP regimen compared with a standard-of-care regimen using ritonavir-boosted lopinavir. Patients meeting criteria for PEP were randomized to tenofovir disoproxil/emtricitabine (200/245 mg) once daily plus ritonavir-boosted lopinavir (Kaletra ® 400/100 mg) or maraviroc 300 mg twice daily. The composite primary endpoint was completion of 28 days of the allocated PEP regimen without grade 3 or 4 clinical or laboratory adverse events (AEs) related to the PEP medication. Two hundred and thirteen individuals were randomized (107 to maraviroc; 106 to Kaletra ® arm). Follow-up rates were high in both groups. There was no difference in the primary endpoint; 70 (71%) in the maraviroc and 64 (65%) in the Kaletra ® arm ( P  =   0.36) completed PEP without grade 3 or 4 AEs. Discontinuation of PEP was the same (18%) in both groups. There were no grade 3 or 4 clinical AEs in either arm, but more grade 1 or 2 clinical AEs in the Kaletra ® arm (91% versus 70%; P  < 0.001). Antidiarrhoeal medication use was higher in the Kaletra ® arm (67% versus 25%; P  < 0.001). There were no HIV seroconversions in the study period. The completion rate in the absence of grade 3 or 4 AEs was similar with both regimens. Maraviroc-based PEP was better tolerated, supporting its use as an option for non-occupational PEP. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Knowledge and attitudes of non-occupational HIV post-exposure prophylaxis amongst first- and second-year medical students at Stellenbosch University in South Africa

PubMed Central

Meintjes, Willem A.J.; Chola, Lumbwe

2014-01-01

Abstract Background Human immunodeficiency virus (HIV) infection is a worldwide problem, with 68% of infected people residing in sub-Saharan Africa. Antiretroviral therapy is used as post-exposure prophylaxis (PEP) to prevent infection in cases of occupational exposure, and use has recently been expanded to non-occupational exposure. Studies have demonstrated a lack of awareness of non-occupational PEP (NO-PEP) in the general population. Aim The aim of this study was to evaluate knowledge and attitudes towards availability of, access to and use of NO-PEP amongst first- and second-year medical students. Setting Participants were medical undergraduates of Stellenbosch University in the Western Cape of South Africa who were registered in 2013. Methods A descriptive cross-sectional study of 169 students was performed. Data were collected using self-administered questionnaires handed out in a classroom in August 2013. Self-reported knowledge and attitudes towards NO-PEP and barriers to access to and use of NO-PEP were analysed using frequency tables. Associations between self-reported and objective knowledge of NO-PEP were analysed by odds ratios. Results Over 90% of students had good knowledge on HIV transmission, and about 75% knew how it can be prevented. Twenty eight per cent (n = 47) of students reported knowledge of NO-PEP; 67% reported hearing about it from lecturers, whilst 1% reported hearing about it from their partner. Students who knew the correct procedure to take when a dose is forgotten were 2.4 times more likely to report knowledge of NO-PEP than those who did not know what to do when a dose is forgotten (p = 0.029). No other associations were statistically significant. Conclusion Students had positive attitudes towards the use of NO-PEP and also identified barriers to its use. Despite good knowledge of HIV prevention and transmission, knowledge on NO-PEP was poor. PMID:26245421

Psychometrics and utility of Psycho-Educational Profile-Revised as a developmental quotient measure among children with the dual disability of intellectual disability and autism.

PubMed

Alwinesh, Merlin Thanka Jemi; Joseph, Rachel Beulah Jansirani; Daniel, Anna; Abel, Julie Sandra; Shankar, Satya Raj; Mammen, Priya; Russell, Sushila; Russell, Paul Swamidhas Sudhakar

2012-09-01

There is no agreement about the measure to quantify the intellectual/developmental level in children with the dual disability of intellectual disability and autism. Therefore, we studied the psychometric properties and utility of Psycho-Educational Profile-Revised (PEP-R) as a developmental test in this population. We identified 116 children with dual disability from the day care and inpatient database of a specialised Autism Clinic. Scale and domain level scores of PEP-R were collected and analyzed. We examined the internal consistency, domain-total correlation of PEP-R and concurrent validity of PEP-R against Gesell's Developmental Schedule, inter-rater and test-retest reliability and utility of PEP-R among children with dual disability in different ages, functional level and severity of autism. Besides the adequate face and content validity, PEP-R demonstrates a good internal consistency (Cronbach's α ranging from 0.91 to 0.93) and domain-total correlation (ranging from 0.75 to 0.90). The inter-rater reliability (intraclass correlation coefficient, ICC = 0.96) and test-retest reliability (ICC = 0.87) for PEP-R is good. There is moderate-to-high concurrent validity with GDS (r ranging from 0.61 to 0.82; all Ps = 0.001). The utility of PEP-R as a developmental measure was good with infants, toddlers, pre-school and primary school children. The ability of PEP-R to measure the developmental age was good, irrespective of the severity of autism but was better with high-functioning children. The PEP-R as an intellectual/developmental test has strong psychometric properties in children with dual disability. It could be used in children with different age groups and severity of autism. PEP-R should be used with caution as a developmental test in children with dual disability who are low functioning.

PLGA nanoparticles loaded with beta-lactoglobulin-derived peptides modulate mucosal immunity and may facilitate cow's milk allergy prevention.

PubMed

Kostadinova, Atanaska I; Middelburg, Jim; Ciulla, Michele; Garssen, Johan; Hennink, Wim E; Knippels, Leon M J; van Nostrum, Cornelus F; Willemsen, Linette E M

2018-01-05

Beta-lactoglobulin (BLG)-derived peptides may facilitate oral tolerance to whey and prevent cow's milk allergy (CMA). Loading of BLG-peptides in poly(lactic-co-glycolic acid) (PLGA) nanoparticles (Pep-NP) may improve this. Here we studied the uptake of NP and the capacity of NP and Pep-NP to activate bone marrow dendritic cells (BMDC). Furthermore, CMA prevention was evaluated by orally exposing three-week-old female C3H/HeOuJ mice to Pep-NP, NP or free peptides (PepMix) for 6 days before oral sensitization with whole whey protein and effects on the spleen and small intestine lamina propria (SI-LP) were studied. In BMDC, NP and Pep-NP enhanced CD40 expression and IL-6 and TNF-α secretion, while tended to decrease CD80 expression and prevented PepMix-induced IL-12 secretion. In vivo, oral exposure to Pep-NP, but not NP or PepMix, prior to whey sensitization tended to partially prevent the acute allergic skin response to whole whey protein. Splenocytes of NP-pre-exposed mice secreted increased levels of whey-specific IL-6, but this was silenced in Pep-NP-pre-exposed mice which also showed reduced TNF-α and IFN-γ secretion. In the SI-LP, Pep-NP pre-exposure reduced the CD4 + T cell frequency in CMA mice compared to PBS pre-exposure. In addition, while NP increased whey-specific IL-6 secretion in the SI-LP, Pep-NP did not and maintained regulatory TGF-β secretion. This study presents a proof-of-concept that PLGA nanoparticles facilitate the capacity of BLG peptides to suppress the allergic response to whole whey protein. Hence, PLGA nanoparticles may be further developed as an adjunct strategy for BLG-peptide-based oral tolerance induction and CMA prevention. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Construction, characterization and evaluation of the protective efficacy of the Streptococcus suis double mutant strain ΔSsPep/ΔSsPspC as a live vaccine candidate in mice.

PubMed

Hu, Jin; You, Wujin; Wang, Bin; Hu, Xueying; Tan, Chen; Liu, Jinlin; Chen, Huanchun; Bei, Weicheng

2015-01-01

Streptococcus suis serotype 2 (S. suis 2) causes sepsis and meningitis in piglets and humans, and results in one of the most serious bacterial diseases affecting the production of commercial pigs around the world. Due to the failure of the current inactivated vaccine to protect against the disease, development of a new attenuated live vaccine against S. suis 2 by deleting essential virulence factors is urgently needed. We have previously reported the construction and characterization of an SsPep single gene deletion mutant strain ΔSsPep based on S. suis 2. Our previous results have shown that SsPep plays a critical role in the pathogenesis of S. suis 2. In this study, a precisely defined double-deletion mutant ΔSsPep/ΔSsPspC of S. suis 2 without antibiotic-resistance markers was constructed based on ΔSsPep, and the levels of virulence of the wild-type (WT) and ΔSsPep/ΔSsPspC were compared in a mouse experimental infection model. We demonstrated that the double mutant ΔSsPep/ΔSsPspC was less virulent than the WT, and could induce a noticeable antibody response. Analysis of IgG subclasses (IgG1 and IgG2a) indicated that both Th1 and Th2 responses were induced by ΔSsPep/ΔSsPspC, although the IgG2a (Th1) response predominated over the IgG1 (Th2) response. Moreover, ΔSsPep/ΔSsPspC could confer 90% protective efficacy against challenge with a lethal dose of fully virulent S. suis 2. Taken together, these data demonstrate that ΔSsPep/ΔSsPspC can be used as an effective live vaccine and provide a novel strategy against infection of S. suis 2. Copyright © 2014 Elsevier GmbH. All rights reserved.

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

Kwon, Soon Won; Sohn, Eun Jeong; Kim, Dae Won

Highlights: {yields} Recombinant PEP-1 heme oxygenase-1 expression vector was constructed and overexpressed. {yields} We investigated transduction efficiency of PEP-1-HO-1 protein in Raw 264.7 cells. {yields} PEP-1-HO-1 was efficiently transduced into Raw 264.7 cells in a dose and time dependent manner. {yields} PEP-1-HO-1 exerted anti-inflammatory activity in Raw 264.7 cells and in a mice edema model. {yields} PEP-1-HO-1 could be used as a therapeutic drug against inflammatory diseases. -- Abstract: Heme oxygenase-1 (HO-1), which catalyzes the degradation of free heme to biliverdin, carbon monoxide (CO), and free iron (Fe{sup 2+}), is up-regulated by several cellular stress and cell injuries, including inflammation,more » ischemia and hypoxia. In this study, we examined whether fusion of HO-1 with PEP-1, a protein transduction domain that is able to deliver exogenous molecules to living cells or tissues, would facilitate HO-1 delivery to target cells and tissues, and thereby effectively exert a therapeutically useful response against inflammation. Western blot analysis demonstrated that PEP-1-HO-1 fusion proteins were transduced into Raw 264.7 cells in time- and dose-dependent manners, and were stably maintained in the cells for about 60 h. In addition, fluorescence analysis revealed that only PEP-1-HO-1 fusion proteins were significantly transduced into the cytoplasm of cells, while HO-1 proteins failed to be transduced. In lipopolysaccharide (LPS)-stimulated Raw 264.7 cells and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse edema model, transduced PEP-1-HO-1 fusion proteins effectively inhibited the overexpression of pro-inflammatory mediators and cytokines. Also, histological analysis demonstrated that PEP-1-HO-1 remarkably suppressed ear edema. The results suggest that the PEP-1-HO-1 fusion protein can be used as a therapeutic molecule against reactive oxygen species-related inflammatory diseases.« less

Streptococcus pyogenes Endopeptidase O Contributes to Evasion from Complement-mediated Bacteriolysis via Binding to Human Complement Factor C1q.

PubMed

Honda-Ogawa, Mariko; Sumitomo, Tomoko; Mori, Yasushi; Hamd, Dalia Talat; Ogawa, Taiji; Yamaguchi, Masaya; Nakata, Masanobu; Kawabata, Shigetada

2017-03-10

Streptococcus pyogenes secretes various virulence factors for evasion from complement-mediated bacteriolysis. However, full understanding of the molecules possessed by this organism that interact with complement C1q, an initiator of the classical complement pathway, remains elusive. In this study, we identified an endopeptidase of S. pyogenes , PepO, as an interacting molecule, and investigated its effects on complement immunity and pathogenesis. Enzyme-linked immunosorbent assay and surface plasmon resonance analysis findings revealed that S. pyogenes recombinant PepO bound to human C1q in a concentration-dependent manner under physiological conditions. Sites of inflammation are known to have decreased pH levels, thus the effects of PepO on bacterial evasion from complement immunity was analyzed in a low pH condition. Notably, under low pH conditions, PepO exhibited a higher affinity for C1q as compared with IgG, and PepO inhibited the binding of IgG to C1q. In addition, pepO deletion rendered S. pyogenes more susceptible to the bacteriocidal activity of human serum. Also, observations of the morphological features of the pepO mutant strain (Δ pepO ) showed damaged irregular surfaces as compared with the wild-type strain (WT). WT-infected tissues exhibited greater severity and lower complement activity as compared with those infected by Δ pepO in a mouse skin infection model. Furthermore, WT infection resulted in a larger accumulation of C1q than that with Δ pepO. Our results suggest that interaction of S. pyogenes PepO with C1q interferes with the complement pathway, which enables S. pyogenes to evade complement-mediated bacteriolysis under acidic conditions, such as seen in inflammatory sites. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

The Financial Burden of Public Health Responses to Hepatitis A Cases Among Food Handlers, 2012-2014.

PubMed

Morey, Rebecca J; Collier, Melissa G; Nelson, Noele P

When food handlers become ill with hepatitis A virus (HAV) infection, state and local health departments must assess the risk of HAV transmission through prepared food and recommend or provide postexposure prophylaxis (PEP) for those at risk for HAV infection. Providing PEP (eg, hepatitis A [HepA] vaccine or immunoglobulin), however, is costly. To describe the burden of these responses on state and local health departments, we determined the number of public health responses to HAV infections among food handlers by reviewing public internet sources of media articles. We then contacted each health department to collect data on whether PEP was recommended to food handlers or restaurant patrons, the number of PEP doses given, the number of HepA vaccine or immunoglobulin doses given as PEP, and the mean number of health department person-hours required for the response. Of 32 public health responses identified from Twitter, HealthMap, and Google alerts from January 1, 2012, to December 31, 2014, a total of 27 (84%) recommended PEP for other food handlers or restaurant patrons or both. Per public health response, the mean cost per dose of the HepA vaccine or immunoglobulin was $34 139; the mean personnel cost per response was $7329; and the total mean cost of each response was $41 468. PEP is expensive. Less aggressive approaches to PEP, such as limiting PEP to fellow food handlers in nonoutbreak situations, should be considered in the postvaccination era. HepA vaccine for PEP provides long-term immunity and can be used when immunoglobulin is unavailable or cannot be administered within 14 days of exposure to HAV.

Developmental contributions to macronutrient selection: a randomized controlled trial in adult survivors of malnutrition.

PubMed

Campbell, Claudia P; Raubenheimer, David; Badaloo, Asha V; Gluckman, Peter D; Martinez, Claudia; Gosby, Alison; Simpson, Stephen J; Osmond, Clive; Boyne, Michael S; Forrester, Terrence E

2016-01-01

Birthweight differences between kwashiorkor and marasmus suggest that intrauterine factors influence the development of these syndromes of malnutrition and may modulate risk of obesity through dietary intake. We tested the hypotheses that the target protein intake in adulthood is associated with birthweight, and that protein leveraging to maintain this target protein intake would influence energy intake (EI) and body weight in adult survivors of malnutrition. Sixty-three adult survivors of marasmus and kwashiorkor could freely compose a diet from foods containing 10, 15 and 25 percentage energy from protein (percentage of energy derived from protein (PEP); Phase 1) for 3 days. Participants were then randomized in Phase 2 (5 days) to diets with PEP fixed at 10%, 15% or 25%. Self-selected PEP was similar in both groups. In the groups combined, selected PEP was 14.7, which differed significantly (P < 0.0001) from the null expectation (16.7%) of no selection. Self-selected PEP was inversely related to birthweight, the effect disappearing after adjusting for sex and current body weight. In Phase 2, PEP correlated inversely with EI (P = 0.002) and weight change from Phase 1 to 2 (P = 0.002). Protein intake increased with increasing PEP, but to a lesser extent than energy increased with decreasing PEP. Macronutrient intakes were not independently related to birthweight or diagnosis. In a free-choice situation (Phase 1), subjects selected a dietary PEP significantly lower than random. Lower PEP diets induce increased energy and decreased protein intake, and are associated with weight gain. © The Author(s) 2015. Published by Oxford University Press on behalf of the Foundation for Evolution, Medicine, and Public Health.

High specificity ZnO quantum dots for diagnosis and treatment in bacterial infection

NASA Astrophysics Data System (ADS)

Zhang, Min; Qian, Zhiyu; Gu, Yueqing

2016-03-01

Early diagnosis and effective treatment of bacterial infection has become increasingly important. Herein, we developed a fluorescent nano-probe MPA@ZnO-PEP by conjugating SiO2-stabilized ZnO quantum dot (ZnO@SiO2) with bacteria-targeting peptide PEP, which was encapsulated with MPA, a near infrared (NIR) dye. The nanoprobe MPA@ZnO-PEP showed excellent fluorescence property and could specifically distinguish bacterial infection from sterile inflammation both in vitro and in vivo. The favorable biocompatability of MPA@ZnO-PEP was verified by MTT assay. This probe was further modified with antibiotic methicillin to form the theranostic nanoparticle MPA/Met@ZnO-PEP with amplified antibacterial activity. These results promised the great potential of MPA@ZnO-PEP for efficient non-invasive early diagnosis of bacterial infections and effective bacterial-targeting therapy.

Light-chain residue 95 is critical for antigen binding and multispecificity of monoclonal antibody G2.

PubMed

Usui, Daiki; Inaba, Satomi; Kamatari, Yuji O; Ishiguro, Naotaka; Oda, Masayuki

2017-09-02

The monoclonal antibody, G2, specifically binds to the immunogen peptide derived from the chicken prion protein, Pep18mer, and two chicken proteins derived peptides, Pep8 and Pep395; G2 binds with equal affinity to Pep18mer. The amino acid sequences of the three peptides are completely different, and so the recognition mechanism of G2 is unique and interesting. We generated a single-chain Fv (scFv) antibody of G2, and demonstrated its correct folding with an antigen binding function similar to intact G2 antibody. We also generated a Pro containing mutant of G2 scFv at residue 95 of the light chain, and analyzed its antigen binding using a surface plasmon biosensor. The mutant lost its binding ability to Pep18mer, but remained those to Pep8 and Pep395. The results clearly indicate residue 95 as being critical for multispecific antigen binding of G2 at the site generated from the junctional diversity introduced at the joints between the V and J gene segments. Copyright © 2017 Elsevier Inc. All rights reserved.

Efficient post-exposure prophylaxis against rabies by applying a four-dose DNA vaccine intranasally.

PubMed

Tesoro Cruz, Emiliano; Feria Romero, Iris Angélica; López Mendoza, Juan Gabriel; Orozco Suárez, Sandra; Hernández González, Rafael; Favela, Francisco Blanco; Pérez Torres, Armando; José Alvaro Aguilar Setién

2008-12-09

We tested two post-exposure prophylaxes (PEPs) for rabies in laboratory animals; one was a traditional antirabies vaccine for humans via intramuscular route (IM), and the other was a DNA vaccine administered by intranasal route (IN). In contrast to The World Health Organization's recommended five-dose PEP, we gave only four doses without hyper-immune antirabies sera, making the PEP more rigorous. All animals were challenged with challenge virus strain (CVS); 16h later, PEP was applied. All animals that received the PEP with DNA/IN survived, and 87% of the rabbits and 80% of the mice that received the PEP with traditional antirabies vaccine/IM survived. Negative controls succumbed to infection. The expression of G protein was detected in the NALT, cerebellum, cerebral cortex (neocortex), cerebellum and hippocampus, mainly in the glial cells (microglia) and microvessels. On the other hand, plasmid construct was detected in brain and its mRNA expression in medium and posterior encephalon. The efficiency of this DNA/IN PEP is probably due to the early expression of the antigen in the brain stimulating the immune system locally.

The validity of ACT-PEP test scores for predicting academic performance of registered nurses in BSN programs.

PubMed

Yang, J C; Noble, J

1990-01-01

This study investigated the validity of three American College Testing-Proficiency Examination Program (ACT-PEP) tests (Maternal and Child Nursing, Psychiatric/Mental Health Nursing, Adult Nursing) for predicting the academic performance of registered nurses (RNs) enrolled in bachelor's degree BSN programs nationwide. This study also examined RN students' performance on the ACT-PEP tests by their demographic characteristics: student's age, sex, race, student status (full- or part-time), and employment status (full- or part-time). The total sample for the three tests comprised 2,600 students from eight institutions nationwide. The median correlation coefficients between the three ACT-PEP tests and the semester grade point averages ranged from .36 to .56. Median correlation coefficients increased over time, supporting the stability of ACT-PEP test scores for predicting academic performance over time. The relative importance of selected independent variables for predicting academic performance was also examined; the most important variable for predicting academic performance was typically the ACT-PEP test score. Across the institutions, student demographic characteristics did not contribute significantly to explaining academic performance, over and above ACT-PEP scores.

Covalent modification of a ten-residue cationic antimicrobial peptide with levofloxacin

NASA Astrophysics Data System (ADS)

Rodriguez, Carlos; Papanastasiou, Emilios; Juba, Melanie; Bishop, Barney

2014-09-01

The rampant spread of antibiotic resistant bacteria has spurred interest in alternative strategies for developing next-generation antibacterial therapies. As such, there has been growing interest in cationic antimicrobial peptides (CAMPs) and their therapeutic applications. Modification of CAMPs via conjugation to auxiliary compounds, including small molecule drugs, is a new approach to developing effective, broad-spectrum antibacterial agents with novel physicochemical properties and versatile antibacterial mechanisms. Here, we’ve explored design parameters for engineering CAMPs conjugated to small molecules with favorable physicochemical and antibacterial properties by covalently affixing a fluoroquinolone antibiotic, levofloxacin, to the ten-residue CAMP Pep-4. Relative to the unmodified Pep-4, the conjugate was found to demonstrate substantially increased antibacterial potency under high salt concentrations. Historically, it has been observed that most CAMPs lose antibacterial effectiveness in such high ionic strength environments, a fact that has presented a challenge to their development as therapeutics. Physicochemical studies revealed that P4LC was more hydrophobic than Pep-4, while mechanistic findings indicated that the conjugate was more effective at disrupting bacterial membrane integrity. Although the inherent antibacterial effect of the incorporated levofloxacin molecules did not appear to be substantially realized in this conjugate, these findings nevertheless suggest that covalent attachment of small molecule antibiotics with favorable physicochemical properties to CAMPs could be a promising strategy for enhancing peptide performance and overall therapeutic potential. These results have broader applicability to the development of future CAMP-antibiotic conjugates for potential therapeutic applications.

X-Prolyl Dipeptidyl Aminopeptidase Gene (pepX) Is Part of the glnRA Operon in Lactobacillus rhamnosus

PubMed Central

Varmanen, Pekka; Savijoki, Kirsi; Åvall, Silja; Palva, Airi; Tynkkynen, Soile

2000-01-01

A peptidase gene expressing X-prolyl dipeptidyl aminopeptidase (PepX) activity was cloned from Lactobacillus rhamnosus 1/6 by using the chromogenic substrate l-glycyl-l-prolyl-β-naphthylamide for screening of a genomic library in Escherichia coli. The nucleotide sequence of a 3.5-kb HindIII fragment expressing the peptidase activity revealed one complete open reading frame (ORF) of 2,391 nucleotides. The 797-amino-acid protein encoded by this ORF was shown to be 40, 39, and 36% identical with PepXs from Lactobacillus helveticus, Lactobacillus delbrueckii, and Lactococcus lactis, respectively. By Northern analysis with a pepX-specific probe, transcripts of 4.5 and 7.0 kb were detected, indicating that pepX is part of a polycistronic operon in L. rhamnosus. Cloning and sequencing of the upstream region of pepX revealed the presence of two ORFs of 360 and 1,338 bp that were shown to be able to encode proteins with high homology to GlnR and GlnA proteins, respectively. By multiple primer extension analyses, the only functional promoter in the pepX region was located 25 nucleotides upstream of glnR. Northern analysis with glnA- and pepX-specific probes indicated that transcription from glnR promoter results in a 2.0-kb dicistronic glnR-glnA transcript and also in a longer read-through polycistronic transcript of 7.0 kb that was detected with both probes in samples from cells in exponential growth phase. The glnA gene was disrupted by a single-crossover recombinant event using a nonreplicative plasmid carrying an internal part of glnA. In the disruption mutant, glnRA-specific transcription was derepressed 10-fold compared to the wild type, but the 7.0-kb transcript was no longer detectable with either the glnA- or pepX-specific probe, demonstrating that pepX is indeed part of glnRA operon in L. rhamnosus. Reverse transcription-PCR analysis further supported this operon structure. An extended stem-loop structure was identified immediately upstream of pepX in the glnA-pepX intergenic region, a sequence that showed homology to a 23S-5S intergenic spacer and to several other L. rhamnosus-related entries in data banks. PMID:10613874

X-prolyl dipeptidyl aminopeptidase gene (pepX) is part of the glnRA operon in Lactobacillus rhamnosus.

PubMed

Varmanen, P; Savijoki, K; Avall, S; Palva, A; Tynkkynen, S

2000-01-01

A peptidase gene expressing X-prolyl dipeptidyl aminopeptidase (PepX) activity was cloned from Lactobacillus rhamnosus 1/6 by using the chromogenic substrate L-glycyl-L-prolyl-beta-naphthylamide for screening of a genomic library in Escherichia coli. The nucleotide sequence of a 3.5-kb HindIII fragment expressing the peptidase activity revealed one complete open reading frame (ORF) of 2,391 nucleotides. The 797-amino-acid protein encoded by this ORF was shown to be 40, 39, and 36% identical with PepXs from Lactobacillus helveticus, Lactobacillus delbrueckii, and Lactococcus lactis, respectively. By Northern analysis with a pepX-specific probe, transcripts of 4.5 and 7.0 kb were detected, indicating that pepX is part of a polycistronic operon in L. rhamnosus. Cloning and sequencing of the upstream region of pepX revealed the presence of two ORFs of 360 and 1,338 bp that were shown to be able to encode proteins with high homology to GlnR and GlnA proteins, respectively. By multiple primer extension analyses, the only functional promoter in the pepX region was located 25 nucleotides upstream of glnR. Northern analysis with glnA- and pepX-specific probes indicated that transcription from glnR promoter results in a 2.0-kb dicistronic glnR-glnA transcript and also in a longer read-through polycistronic transcript of 7.0 kb that was detected with both probes in samples from cells in exponential growth phase. The glnA gene was disrupted by a single-crossover recombinant event using a nonreplicative plasmid carrying an internal part of glnA. In the disruption mutant, glnRA-specific transcription was derepressed 10-fold compared to the wild type, but the 7.0-kb transcript was no longer detectable with either the glnA- or pepX-specific probe, demonstrating that pepX is indeed part of glnRA operon in L. rhamnosus. Reverse transcription-PCR analysis further supported this operon structure. An extended stem-loop structure was identified immediately upstream of pepX in the glnA-pepX intergenic region, a sequence that showed homology to a 23S-5S intergenic spacer and to several other L. rhamnosus-related entries in data banks.

PEP-1-SIRT2-induced matrix metalloproteinase-1 and -13 modulates type II collagen expression via ERK signaling in rabbit articular chondrocytes.

PubMed

Eo, Seong-Hui; Choi, Soo Young; Kim, Song Ja

2016-11-01

Matrix metalloproteinases (MMPs) are critical for the degradation of the extracellular matrix (ECM), which includes cartilage-specific collagen types I, II and XI. We previously found that PEP-1-sirtuin (SIRT)2 could induce dedifferentiation of articular chondrocytes; however, the underlying mechanisms remains unclear. We addressed this in the present study by examining the association between PEP-1-SIRT2 and the expression of MMP-1 and MMP-13 and type II collagen in rabbit articular chondrocytes. We found that PEP-1-SIRT2 increased MMP-1 and -13 expression in a dose- and time-dependent manner, as determined by western blotting. A similar trend in MMP-1 and -13 levels was observed in cultures during expansion to four passages. Pharmacological inhibition of MMP-1 and -13 blocked the PEP-1-SIRT2-induced decrease in type II collagen level. Phosphorylation of extracellular regulated kinase (ERK) was increased by PEP-1-SIRT2; however, treatment with the mitogen-activated protein kinase inhibitor PD98059 suppressed PEP-1-SIRT2-induced MMP-1 and -13 expression and dedifferentiation while restoring type II collagen expression in passage 2 cells. These results suggest that PEP-1-SIRT2 promotes MMP-induced dedifferentiation via ERK signaling in articular chondrocytes. Copyright © 2016 Elsevier Inc. All rights reserved.

A Colletotrichum gloeosporioides-induced esterase gene of nonclimacteric pepper (Capsicum annuum) fruit during ripening plays a role in resistance against fungal infection.

PubMed

Ko, Moon Kyung; Jeon, Woong Bae; Kim, Kwang Sang; Lee, Hyun Hwa; Seo, Hyo Hyoun; Kim, Young Soon; Oh, Boung-Jun

2005-07-01

Ripe fruits of pepper (Capsicum annuum) are resistant to the anthracnose fungus, Colletotrichum gloeosporioides, whereas unripe-mature fruits are susceptible. A pepper esterase gene (PepEST) that is highly expressed during an incompatible interaction between the ripe fruit of pepper and C. gloeosporioides was previously cloned. Deduced amino acid sequence of PepEST cDNA showed homology to both esterases and lipases, and contained -HGGGF- and -GXSXG- motifs and a catalytic triad. Inhibition of PepEST activity by a specific inhibitor of serine hydrolase demonstrated that a serine residue is critical for the enzyme activity. Expression of PepEST gene was fruit-specific in response to C. gloeosporioides inoculation, and up-regulated by wounding or jasmonic acid treatment during ripening. PepEST mRNA and protein was differentially accumulated in ripe vs. unripe fruit from 24 h after inoculation when C. gloeosporioides is invading into fruits. Immunochemical examination revealed that PepEST accumulation was localized in epidermal and cortical cell layers in infected ripe fruit, but rarely even in epidermal cells in infected unripe one. Over-expression of PepEST in transgenic Arabidopsis plants caused restriction of Alternaria brassicicola colonization by inhibition of spore production, resulting in enhanced resistance against A.brassicicola. These results suggest that PepEST is involved in the resistance of ripe fruit against C.gloeosporioides infection.

An operon from Lactobacillus helveticus composed of a proline iminopeptidase gene (pepI) and two genes coding for putative members of the ABC transporter family of proteins.

PubMed

Varmanen, P; Rantanen, T; Palva, A

1996-12-01

A proline iminopeptidase gene (pepI) of an industrial Lactobacillus helveticus strain was cloned and found to be organized in an operon-like structure of three open reading frames (ORF1, ORF2 and ORF3). ORF1 was preceded by a typical prokaryotic promoter region, and a putative transcription terminator was found downstream of ORF3, identified as the pepI gene. Using primer-extension analyses, only one transcription start site, upstream of ORF1, was identifiable in the predicted operon. Although the size of mRNA could not be judged by Northern analysis either with ORF1-, ORF2- or pepI-specific probes, reverse transcription-PCR analyses further supported the operon structure of the three genes. ORF1, ORF2 and ORF3 had coding capacities for 50.7, 24.5 and 33.8 kDa proteins, respectively. The ORF3-encoded PepI protein showed 65% identity with the PepI proteins from Lactobacillus delbrueckii subsp. bulgaricus and Lactobacillus delbrueckii subsp. lactis. The ORF1-encoded protein had significant homology with several members of the ABC transporter family but, with two distinct putative ATP-binding sites, it would represent an unusual type among the bacterial ABC transporters. ORF2 encoded a putative integral membrane protein also characteristic of the ABC transporter family. The pepI gene was overexpressed in Escherichia coli. Purified PepI hydrolysed only di and tripeptides with proline in the first position. Optimum PepI activity was observed at pH 7.5 and 40 degrees C. A gel filtration analysis indicated that PepI is a dimer of M(r) 53,000. PepI was shown to be a metal-independent serine peptidase having thiol groups at or near the active site. Kinetic studies with proline-p-nitroanilide as substrate revealed Km and Vmax values of 0.8 mM and 350 mmol min-1 mg-1, respectively, and a very high turnover number of 135,000 s-1.

The Premature Ejaculation Profile: validation of self-reported outcome measures for research and practice.

PubMed

Patrick, Donald L; Giuliano, François; Ho, Kai Fai; Gagnon, Dennis D; McNulty, Pauline; Rothman, Margaret

2009-02-01

To evaluate the reliability and validity of the Premature Ejaculation Profile (PEP), a self-reported outcome instrument for evaluating domains of PE and its treatment, comprised of four single-item measures, a profile, and an index score. Data were from men participating in observational studies in the USA (PE, 207 men; non-PE, 1380) and Europe (PE, 201; non-PE, 914) and from men with PE (1238) participating in a phase III randomized, placebo-controlled clinical trial of dapoxetine. The PEP contains four measures: perceived control over ejaculation, personal distress related to ejaculation, satisfaction with sexual intercourse, and interpersonal difficulty related to ejaculation, each assessed on five-point response scales. Test-retest reliability, known-groups validity, and ability to detect a patient-reported global impression of change (PGI) in condition were evaluated for the individual PEP measures and a PEP index score (the mean of all four measures). Profile analysis was conducted using multivariate analysis of variance. All PEP measures showed acceptable reliability (intraclass correlation coefficients ranged from 0.66 to 0.83) and mean scores for all measures differed significantly between PE and non-PE groups (P < 0.001). Men who reported a reduction in PE with treatment in the phase III trial had significantly greater scores on each of the four measures. The PEP profiles of men with and without PE differed significantly (P < 0.001) in both observational studies; higher levels of PGI were associated with higher PEP profiles (P < 0.001). The PEP index score also showed acceptable reliability and was significantly different between the PE and non-PE groups (P < 0.001). Men who reported an improvement in PE with treatment in the phase III trial had significantly greater PEP index scores. In the phase III trial, nausea was the most common adverse event with dapoxetine. The PEP provides a reliable, valid, and interpretable measure for use in monitoring outcomes of men with PE.

Treatment of new-onset type 1 diabetes with peptide DiaPep277 is safe and associated with preserved beta-cell function: extension of a randomized, double-blind, phase II trial.

PubMed

Raz, I; Avron, A; Tamir, M; Metzger, M; Symer, L; Eldor, R; Cohen, I R; Elias, D

2007-05-01

Treatment with DiaPep277, a peptide derived from HSP60, has been shown to preserve beta-cell function in non-obese diabetic mouse (NOD) mice and in a trial with newly diagnosed human patients with type 1 diabetes treated over a 10-month period. This article extends the clinical trial observations to a total of 20 months of treatment to determine the safety and the effects of repeated doses of DiaPep277 on endogenous insulin secretion, metabolic control, and exogenous insulin requirements. Thirty-five male patients (aged 16-58) with a basal C-peptide greater than 0.1 nmol/L were assigned to periodic treatment with DiaPep277 (1 mg) or placebo for a 12-month treatment and 18-month observation protocol, later extended to an additional year of treatment. Stimulated C-peptide, HbA1c, and an exogenous insulin dose were the clinical endpoints. At 18 months, stimulated C-peptide concentrations had fallen in the placebo group (p = 0.0005) but were maintained in the DiaPep277 group. The need for exogenous insulin was higher in the placebo group than in the DiaPep277 group. Mean HbA1c concentrations were similar in both groups. After extension of the study, patients continuing treatment with DiaPep277 and those switched from placebo to DiaPep277 manifested a trend towards a greater preservation of beta-cell function compared to patients maintained on or switched to placebo. The safety profile of DiaPep277 was similar between the treatment and placebo groups, and no drug-related adverse events occurred. Periodic treatment of subjects with DiaPep277 over 2 years was safe and associated preservation of endogenous insulin secretion up to 18 months was observed. Copyright 2007 John Wiley & Sons, Ltd.

Performance of a bedside test for tetanus immunity: results of a cross-sectional study among three EDs in the Netherlands in 2012-2013.

PubMed

van der Maas, N At; Donken, R; Te Wierik, M J M; Swaan, C M; Hahne, S J M; de Melker, H E

2016-11-01

Despite sustained high vaccination coverage and a national guideline by the Health Council (HC-guideline) on tetanus postexposure prophylaxis (T-PEP), tetanus sporadically occurs in the Netherlands. This study aims to assess the added value of a bedside test for tetanus immunity (Tetanos Quick Stick (TQS); Ingen BioSciences Group, France), in the context of routine T-PEP in two adult cohorts: those born before introduction of tetanus toxoid vaccination in the National Immunization Programme (NIP) in 1957 (pre-NIP-cohort; n=196) and those born after (NIP-cohort; n=405). Adults included at the time of visiting one of three participating EDs received T-PEP as per routine recommendations. Subsequently, a nurse performed the TQS and filled in a questionnaire. We compared the indication for T-PEP based on TQS results with those based on the HC-guideline and with actually administration of T-PEP, stratified by cohort. Among the pre-NIP and NIP-cohort, 16% and 9%, respectively, received T-PEP, while this was not indicated based on the HC-guideline. Furthermore, 8% and 7%, respectively, did not get T-PEP, although it was indicated by the guideline. Comparing the indication derived from the HC-guideline with TQS result found that 22% (pre-NIP-cohort) and 8% (NIP-cohort) were not eligible for T-PEP according to the HC-guideline but had a negative TQS. Conversely, 36% (pre-NIP-cohort) and 73% (NIP-cohort) were eligible for T-PEP according to the HC-guideline but had positive TQS, indicating sufficient tetanus protection. Use of the TQS would allow better targeting of T-PEP. Furthermore, stricter adherence to the HC-guideline can prevent overimmunisation and decrease the risk of tetanus. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Cost Description and Comparative Cost Efficiency of Post-Exposure Prophylaxis and Canine Mass Vaccination against Rabies in N'Djamena, Chad.

PubMed

Mindekem, Rolande; Lechenne, Monique Sarah; Naissengar, Kemdongarti Service; Oussiguéré, Assandi; Kebkiba, Bidjeh; Moto, Daugla Doumagoum; Alfaroukh, Idriss Oumar; Ouedraogo, Laurent Tinoanga; Salifou, Sahidou; Zinsstag, Jakob

2017-01-01

Rabies claims approximately 59,000 human lives annually and is a potential risk to 3.3 billion people in over 100 countries worldwide. Despite being fatal in almost 100% of cases, human rabies can be prevented by vaccinating dogs, the most common vector, and the timely administration of post-exposure prophylaxis (PEP) to exposed victims. For the control and prevention of human rabies in N'Djamena, the capital city of Chad, a free mass vaccination campaign for dogs was organized in 2012 and 2013. The campaigns were monitored by parallel studies on the incidence of canine rabies based on diagnostic testing of suspect animals and the incidence of human bite exposure recorded at selected health facilities. Based on the cost description of the campaign and the need for PEP registered in health centers, three cost scenarios were compared: cumulative cost-efficiency of (1) PEP alone, (2) dog mass vaccination and PEP, (3) dog mass vaccination, PEP, and maximal communication between human health and veterinary workers (One Health communication). Assuming ideal One Health communication, the cumulative prospective cost of dog vaccination and PEP break even with the cumulative prospective cost of PEP alone in the 10th year from the start of the calculation (2012). The cost efficiency expressed in cost per human exposure averted is much higher with canine vaccination and One Health communication than with PEP alone. As shown in other studies, our cost-effectiveness analysis highlights that canine vaccination is financially the best option for animal rabies control and rabies prevention in humans. This study also provides evidence of the beneficial effect of One Health communication. Only with close communication between the human and animal health sectors will the decrease in animal rabies incidence be translated into a decline for PEP. An efficiently applied One Health concept would largely reduce the cost of PEP in resource poor countries and should be implemented for zoonosis control in general.

Cost Description and Comparative Cost Efficiency of Post-Exposure Prophylaxis and Canine Mass Vaccination against Rabies in N’Djamena, Chad

PubMed Central

Mindekem, Rolande; Lechenne, Monique Sarah; Naissengar, Kemdongarti Service; Oussiguéré, Assandi; Kebkiba, Bidjeh; Moto, Daugla Doumagoum; Alfaroukh, Idriss Oumar; Ouedraogo, Laurent Tinoanga; Salifou, Sahidou; Zinsstag, Jakob

2017-01-01

Rabies claims approximately 59,000 human lives annually and is a potential risk to 3.3 billion people in over 100 countries worldwide. Despite being fatal in almost 100% of cases, human rabies can be prevented by vaccinating dogs, the most common vector, and the timely administration of post-exposure prophylaxis (PEP) to exposed victims. For the control and prevention of human rabies in N’Djamena, the capital city of Chad, a free mass vaccination campaign for dogs was organized in 2012 and 2013. The campaigns were monitored by parallel studies on the incidence of canine rabies based on diagnostic testing of suspect animals and the incidence of human bite exposure recorded at selected health facilities. Based on the cost description of the campaign and the need for PEP registered in health centers, three cost scenarios were compared: cumulative cost-efficiency of (1) PEP alone, (2) dog mass vaccination and PEP, (3) dog mass vaccination, PEP, and maximal communication between human health and veterinary workers (One Health communication). Assuming ideal One Health communication, the cumulative prospective cost of dog vaccination and PEP break even with the cumulative prospective cost of PEP alone in the 10th year from the start of the calculation (2012). The cost efficiency expressed in cost per human exposure averted is much higher with canine vaccination and One Health communication than with PEP alone. As shown in other studies, our cost-effectiveness analysis highlights that canine vaccination is financially the best option for animal rabies control and rabies prevention in humans. This study also provides evidence of the beneficial effect of One Health communication. Only with close communication between the human and animal health sectors will the decrease in animal rabies incidence be translated into a decline for PEP. An efficiently applied One Health concept would largely reduce the cost of PEP in resource poor countries and should be implemented for zoonosis control in general. PMID:28421186

A preliminary attempt to experimentally induce post event processing in social anxiety disorder.

PubMed

Rowa, Karen; Antony, Martin M; Swinson, Richard P; McCabe, Randi E

2014-03-01

Post event processing (PEP) in social anxiety disorder involves rumination about social events after the fact, and is thought to be a crucial feature of the maintenance of the disorder. The current experiment aimed to manipulate the use of PEP in individuals with social anxiety disorder. Forty-one individuals with social anxiety disorder completed a videotaped speech. Anxiety ratings and degree of PEP were measured after the task as well as the day following the experiment. Individuals in the distract group reported a greater decrease in anxiety from baseline to post-experimental task than those asked to focus. Individuals in the distract group also reported higher PEP about the task than those instructed to complete a focus task, which appeared to be partially accounted for by baseline differences in symptom severity and state anxiety. Degree of PEP was positively correlated with anxiety ratings, both after the experimental task as well as 24 hours later. These findings suggest that naturalistic PEP is problematic for individuals with social anxiety disorder, especially for those with more severe symptoms. A distraction task, even with breakthrough PEP, appears to have useful short-term effects on anxiety reduction as compared to focus instructions.

Pharmacokinetic Effects of Cinnamic Acid, Amygdalin, Glycyrrhizic Acid and Liquiritin on Ephedra Alkaloids in Rats.

PubMed

Tang, Yinghong; Zheng, Mengkai; Chen, Yu-Lin; Chen, Jianzhen; He, Yu

2017-06-01

Ephedra alkaloids, including ephedrine (EP), pseudoephedrine (PEP) and methylephedrine (MEP), are sympathomimetic compounds with known toxicities but many Ephedra (Ephedrae herba) preparations, such as Ephedra decoction, have been clinically applied for centuries. In order to explore the possible detoxification mechanism of Ephedra alkaloids, four representative compounds in Ephedra decoction (cinnamic acid, amygdalin, glycyrrhizic acid and liquiritin) were studied for their pharmacokinetic effects on Ephedra alkaloids in Sprague-Dawley rats. Animals were randomly divided into six groups, with six rats in each. Rats were treated orally with EP-PEP-MEP (20 mg/kg EP + 20 mg/kg PEP + 20 mg/kg MEP) and different combinations of cinnamic acid (3.03 mg/kg), amygdalin (56.97 mg/kg), glycyrrhizic acid (12.42 mg/kg), liquiritin (3.79 mg/kg) with EP-PEP-MEP, and 20 mg/kg EP + 20 mg/kg PEP + 20 mg/kg MEP + 3.03 mg/kg cinnamic acid + 56.97 mg/kg amygdalin + 12.42 mg/kg glycyrrhizic acid + 3.79 mg/kg liquiritin. Blood samples (0.5 mL) were taken from the orbital sinus venous plexus into heparinized tubes at 5, 10, 20, 30, 45, 60, 90, 120, 180, 240, 300 and 360 min (6 rats per time point in each group) following single administration. The concentrations of Ephedra alkaloids in rat plasma were determined using a validated high performance liquid chromatography method. Area under the concentration-time curve from 0 to 360 min (AUC 0-t ) of EP, PEP and MEP were 666.99, 650.76 and 632.37 µg·min/mL, respectively. Maximum plasma concentration (C max ) of EP, PEP and MEP were 4.15, 4.08 and 3.59 μg/mL, respectively. Mean residence time (MRT) of EP, PEP and MEP were 197.00, 173.97 and 183.87 min, respectively, when the rats were treated with EP-PEP-MEP. Cinnamic acid increased the AUC 0-t of EP while decreased C max of EP, amygdalin and glycyrrhizic acid increased C max and AUC 0-t of EP and PEP, while liquiritin decreased AUC 0-t of EP and PEP. The four representative compounds reduced MRT of EP, PEP and MEP, four compounds decreased AUC 0-t of MEP. The EP-PEP-MEP + cinnamic acid + amygdalin + glycyrrhizic acid + liquiritin group increased AUC 0-t of EP while decreased MRT of EP, increased MRT of PEP while decreased AUC 0-t of PEP. The EP-PEP-MEP + cinnamic acid + amygdalin + glycyrrhizic acid + liquiritin group decreased MRT, AUC 0-t and C max of MEP. Significant changes in pharmacokinetic parameters of EP, PEP and MEP were observed after oral administration with different combinations. The pharmacokinetic results reported here might provide reference for clinical usage of Ephedra alkaloids.

Evaluation of tetravalent and conserved synthetic peptides vaccines derived from Dengue virus Envelope domain I and II.

PubMed

Rocha, Raissa Prado; Livonesi, Márcia Cristina; Fumagalli, Marcilio Jorge; Rodrigues, Naiara Ferreira; da Costa, Lauro César Felipe; Dos Santos, Michelle Cristina Silva Gomes; de Oliveira Rocha, Eliseu Soares; Kroon, Erna Geessien; Malaquias, Luiz Cosme Cotta; Coelho, Luiz Felipe Leomil

2014-08-08

Dengue is a major worldwide public health problem, especially in the tropical and subtropical regions of the world. Primary infection with a single Dengue virus (DENV) serotype causes a mild, self-limiting febrile illness called dengue fever. However, a subset of patients experiencing a secondary infection with a different serotype progress to the severe form of the disease, called dengue hemorrhagic fever. In this study, the vaccine potential of three tetravalent and conserved synthetic peptides derived from DENV envelope domain I (named Pep01) and II (named Pep02 and Pep03) was evaluated. Human dengue IgM/IgG positive serum (n=16) showed reactivity against Pep01, Pep02 and Pep03 in different degrees. Mice immunization experiments showed that these peptides were able to induce a humoral response characterized by antibodies with low neutralizing activity. The spleen cells derived from mice immunized with the peptides showed a significant cytotoxic activity (only for Pep02 and Pep03), a high expression of IL-10 (P<0.01) and a reduced expression of TNF-α and IFN-gamma (P<0.001) compared to DENV-1 infected splenocytes. Thus these peptides, and specially the Pep03, can induce a humoral response characterized by antibodies with low neutralizing activities and probably a T cell response that could be beneficial to induce an effective immune response against all DENV serotypes and do not contributed to the immunopathogenesis. However, further studies in peptide sequence will be required to induce the production of neutralizing antibodies against all four DENV serotypes and also to improve immunogenicity of these peptides. Copyright © 2014 Elsevier B.V. All rights reserved.

Characterization of PgPepO, a bacterial homologue of endothelin-converting enzyme-1.

PubMed

Carson, Julie A; Ansai, Toshihiro; Awano, Shuji; Yu, Weixian; Takehara, Tadamichi; Turner, Anthony J

2002-08-01

PgPepO is a homologue of endothelin-converting enzyme-1 (ECE-1), with which it shares 31% identity. PgPepO was isolated from the periodontal pathogen Porphyromonas gingivalis. Recent studies have suggested a link between periodontal and cardiovascular disease, and several groups have suggested that bacterial and viral infections may contribute to the latter. P. gingivalis possesses the ability to invade, and multiply within, aortic endothelial cells and has been localized to atherosclerotic plaques. PgPepO was expressed and purified to homogeneity and we have begun detailed functional analysis, in terms of substrate preference and inhibitor specificity, in order to provide active-site comparisons with other members of the neprilysin (NEP)/ECE family. PgPepO possesses similar substrate specificity to ECE-1 and has been shown to cleave big endothelin-1 (big ET-1), big ET-2 and big ET-3, converting the substrates into their respective mature endothelin peptides. Substance P, angiotensin I, angiotensin II and neurotensin are all cleaved at multiple sites by PgPepO and the kinetics of these reactions have been compared. The potent vasoconstrictor urotensin II is not hydrolysed by PgPepO. Cleavage of bradykinin by PgPepO occurs at the Pro(7)-Phe(8) bond and is inhibited by the NEP and ECE-1 inhibitor phosphoramidon in a pH-dependent fashion (IC(50) =10 microM at pH 7.0) but not by thiorphan, an NEP-specific inhibitor. PgPepO activity is completely inhibited by EDTA. Characterization of this enzyme is important in elucidating possible links between periodontal pathogens and cardiovascular disorders such as atherosclerosis, and provides an opportunity to gain structural information on a bacterial protein with striking similarity to human ECE-1.

The effect of positive expiratory pressure (PEP) therapy on symptoms, quality of life and incidence of re-exacerbation in patients with acute exacerbations of chronic obstructive pulmonary disease: a multicentre, randomised controlled trial.

PubMed

Osadnik, Christian R; McDonald, Christine F; Miller, Belinda R; Hill, Catherine J; Tarrant, Ben; Steward, Ranjana; Chao, Caroline; Stodden, Nicole; Oliveira, Cristino C; Gagliardi, Nadia; Holland, Anne E

2014-02-01

Positive expiratory pressure (PEP) is a technique used to enhance sputum clearance during acute exacerbations of chronic obstructive pulmonary disease (AECOPD). The impact of PEP therapy during acute exacerbations on clinically important outcomes is not clear. This study sought to determine the effect of PEP therapy on symptoms, quality of life and future exacerbations in patients with AECOPD. 90 inpatients (58 men; mean age 68.6 years, FEV(1) 40.8% predicted) with AECOPD and sputum expectoration were randomised to receive usual care (including physical exercise)±PEP therapy. The Breathlessness, Cough and Sputum Scale (BCSS), St George's Respiratory Questionnaire (SGRQ) and BODE index (Body mass index, airflow Obstruction, Dyspnoea, Exercise tolerance) were measured at discharge, 8 weeks and 6 months following discharge, and analysed via linear mixed models. Exacerbations and hospitalisations were recorded using home diaries. There were no significant between-group differences over time for BCSS score [mean (SE) at discharge 5.2 (0.4) vs 5.0 (0.4) for PEP and control group, respectively; p=0.978] or SGRQ total score [41.6 (2.6) vs 40.8 (2.8) at 8 weeks, p=0.872]. Dyspnoea improved more rapidly in the PEP group over the first 8 weeks (p=0.006), however these benefits were not observed at 6 months. Exacerbations (p=0.986) and hospitalisations (p=0.359) did not differ between groups. We found no evidence that PEP therapy during AECOPD improves important short-term or long-term outcomes. There does not appear to be a routine role for PEP therapy in the management of such individuals.

Differentiating Nonoccupational Postexposure Prophylaxis Seroconverters and Non-Seroconverters in a Community-Based Clinic in Los Angeles, California

PubMed Central

Weiss, Robert E.; Bolan, Robert K.; Kofron, Ryan M.; Flynn, Risa P.; Pieribone, David L.; Kulkarni, Sonali P.; Landovitz, Raphael J.

2017-01-01

Abstract Background. Nonoccupational postexposure prophylaxis (nPEP) is a 28-day regimen of antiretroviral medications taken within 72 hours of human immunodeficiency virus (HIV) exposure to prevent HIV acquisition. Although nPEP has been recommended since 1998, few studies have analyzed the characteristics that distinguish nPEP failures (seroconverters) and successes (non-seroconverters). Methods. This retrospective study analyzed all nPEP courses prompted by sexual exposure that were prescribed at the Los Angeles LGBT Center between March 2010 and July 2014. Fisher exact tests and logistic regressions were used to determine characteristics that distinguished nPEP seroconverters from non-seroconverters. Results. Of the nPEP courses administered, 1744 had a follow-up visit for HIV testing within 24 weeks of exposure and 17 individuals seroconverted. Seven reported a known re-exposure, 8 self-reported only condom-protected sex subsequent to the initial exposure, and 2 reported abstinence since the exposure. In multivariable analyses, seroconverters were more likely than non-seroconverters to report methamphetamine use, incomplete medication adherence, and nPEP initiation later in the 72-hour window. Conclusions. Nonoccupational postexposure prophylaxis is an important emergency tool for HIV prevention. Our findings corroborate that timing of the initial nPEP dose is an important predictor of seroconversion. Although the current study did not offer the initial nPEP dose at the beginning of the visit, use of this fast-track dosing schedule will ensure that the first dose is taken as early as possible postexposure and may lower the likelihood for seroconversion. Furthermore, we recommend systematic screening for substance use because these individuals may be well suited for pre-exposure prophylaxis given their sustained risk. PMID:28596981

Effects of breathing exercises on breathing patterns in obese and non-obese subjects.

PubMed

Olsén, M F; Lönroth, H; Bake, B

1999-05-01

Chest physiotherapy in connection with abdominal surgery includes different deep-breathing exercises to prevent post-operative pulmonary complications. The therapy is effective in preventing pulmonary complications, especially in high-risk patients such as obese persons. The mechanisms behind the effect is unclear, but part of the effect may be explained by the changes in breathing patterns. The aim of this study was therefore to describe and to analyse the breathing patterns in obese and non-obese subjects during three different breathing techniques frequently used in the treatment of post-operative patients. Twenty-one severely obese [body mass index (BMI) > 40] and 21 non-obese (BMI 19-25) subjects were studied. All persons denied having any lung disease and were non-smokers. The breathing techniques investigated were: deep breaths without any resistance (DB), positive expiratory pressure (PEP) with an airway resistance of approximately +15 cmH2O (1.5 kPa) during expiration, inspiratory resistance positive expiratory pressure (IR-PEP) with a pressure of approximately -10 cmH2O (-1.0 kPa) during inspiration. Expiratory resistance as for PEP. Volume against time was monitored while the subjects were sitting in a body plethysmograph. Variables for volume and flow during the breathing cycle were determined. Tidal volume and alveolar ventilation were highest during DB, and peak inspiratory volume was significantly higher than during PEP and IR-PEP in the group of obese subjects. The breathing cycles were prolonged in all techniques but were most prolonged in PEP and IR-PEP. The functional residual capacity (FRC) was significantly lower during DB than during PEP and IR-PEP in the group of obese subjects. FRC as determined within 2 min of finishing each breathing technique was identical to before the breathing manoeuvres.

New Tethered Phospholipid Bilayers Integrating Functional G-Protein-Coupled Receptor Membrane Proteins.

PubMed

Chadli, Meriem; Rebaud, Samuel; Maniti, Ofelia; Tillier, Bruno; Cortès, Sandra; Girard-Egrot, Agnès

2017-10-03

Membrane proteins exhibiting extra- and intracellular domains require an adequate near-native lipid platform for their functional reconstitution. With this aim, we developed a new technology enabling the formation of a peptide-tethered bilayer lipid membrane (pep-tBLM), a lipid bilayer grafted onto peptide spacers, by way of a metal-chelate interaction. To this end, we designed an original peptide spacer derived from the natural α-laminin thiopeptide (P19) possessing a cysteine residue in the N-terminal extremity for grafting onto gold and a C-terminal extremity modified by four histidine residues (P19-4H). In the presence of nickel, the use of this anchor allowed us to bind liposomes of variable compositions containing a 2% molar ratio of a chelating lipid, 1,2-dioleoyl-sn-glycero-3-[(N-(5-amino-1-carboxypentyl)iminodiacetic acid)succinyl] so-called DOGS-NTA, and to form the planar bilayer by triggering liposome fusion by an α-helical (AH) peptide derived from the N-terminus of the hepatitis C virus NS5A protein. The formation of pep-tBLMs was characterized by surface plasmon resonance imaging (SPRi), and their continuity, fluidity, and homogeneity were demonstrated by fluorescence recovery after photobleaching (FRAP), with a diffusion coefficient of 2.5 × 10 -7 cm 2 /s, and atomic force microscopy (AFM). By using variable lipid compositions including phosphatidylcholine (PC), phosphatidylserine (PS), phosphatidylethanolamine (PE), phosphatidylinositol 4,5-bisphosphate (PIP 2 ), sphingomyelin (SM), phosphatidic acid (PA), and cholesterol (Chol) in various ratios, we show that the membrane can be formed independently from the lipid composition. We made the most of this advantage to reincorporate a transmembrane protein in an adapted complex lipid composition to ensure its functional reinsertion. For this purpose, a cell-free expression system was used to produce proteoliposomes expressing the functional C-X-C motif chemokine receptor 4 (CXCR4), a seven-transmembrane protein belonging to the large superfamily of G-protein-coupled receptors (GPCRs). We succeeded in reinserting CXCR4 in pep-tBLMs formed on P19-4H by the fusion of tethered proteoliposomes. AFM and FRAP characterization allowed us to show that pep-tBLMs inserting CXCR4 remained fluid, homogeneous, and continuous. The value of the diffusion coefficient determined in the presence of reinserted CXCR4 was 2 × 10 -7 cm 2 /s. Ligand binding assays using a synthetic CXCR4 antagonist, T22 ([Tyr5,12, Lys7]-polyphemusin II), revealed that CXCR4 can be reinserted in pep-tBLMs with functional folding and orientation. This new approach represents a method of choice for investigating membrane protein reincorporation and a promising way of creating a new generation of membrane biochips adapted for screening agonists or antagonists of transmembrane proteins.

Psychoeducation and Problem Solving (PEPS) Therapy for Adults With Personality Disorder: A Pragmatic Randomized-Controlled Trial.

PubMed

McMurran, Mary; Day, Florence; Reilly, Joseph; Delport, Juan; McCrone, Paul; Whitham, Diane; Tan, Wei; Duggan, Conor; Montgomery, Alan A; Williams, Hywel C; Adams, Clive E; Jin, Huajie; Moran, Paul; Crawford, Mike J

2017-12-01

We compared psychoeducation and problem solving (PEPS) therapy against usual treatment in a multisite randomized-controlled trial. The primary outcome was social functioning. We aimed to recruit 444 community-dwelling adults with personality disorder; however, safety concerns led to an early cessation of recruitment. A total of 154 people were randomized to PEPS and 152 to usual treatment. Follow-up at 72 weeks was completed for 68%. PEPS therapy was no more effective than usual treatment for improving social functioning (adjusted difference in mean Social Functioning Questionnaire scores = -0.73; 95% CI [-1.83, 0.38]; p = 0.19). PEPS therapy is not an effective treatment for improving social functioning of adults with personality disorder living in the community.

Effects of UPR and ERAD pathway on the prolyl endopeptidase production in Pichia pastoris by controlling of nitrogen source.

PubMed

Wang, Xiao-Dong; Jiang, Ting; Yu, Xiao-Wei; Xu, Yan

2017-07-01

Prolyl endopeptidase (PEP) is very useful in various industries, while the high cost of enzyme production remains a major obstacle for its industrial applications. Pichia pastoris has been used for the PEP production; however, the fermentation process has not be investigated and little is known about the impact of excessive PEP production on the host cell physiology. Here, we optimized the nitrogen source to improve the PEP expression level and further evaluated the cellular response including UPR and ERAD. During methanol induction phase the PEP activity (1583 U/L) was increased by 1.48-fold under the optimized nitrogen concentration of NH 4 + (300 mmol/L) and casamino acids [1.0% (w/v)] in a 3-L bioreactor. Evaluated by RT-PCR the UPR and ERAD pathways were confirmed to be activated. Furthermore, a strong decrease of ERAD-related gene transcription was observed with the addition of nitrogen source, which contributed to a higher PEP expression level.

Hepatitis A Cases Among Food Handlers: A Local Health Department Response-New York City, 2013.

PubMed

Ridpath, Alison; Reddy, Vasudha; Layton, Marcelle; Misener, Mark; Scaccia, Allison; Starr, David; Stavinsky, Faina; Varma, Jay K; Waechter, HaeNa; Zucker, Jane R; Balter, Sharon

During 2013, the New York City Department of Health and Mental Hygiene (DOHMH) received reports of 6 hepatitis A cases among food handlers. We describe our decision-making process for public notification, type of postexposure prophylaxis (PEP) offered, and lessons learned. For 3 cases, public notification was issued and DOHMH offered only hepatitis A vaccine as PEP. Subsequent outbreaks resulted from 1 case for which no public notification was issued or PEP offered, and 1 for which public notification was issued and PEP was offered too late. DOHMH continues to use environmental assessments to guide public notification decisions and offer only hepatitis A vaccine as PEP after public notification but recognizes the need to evaluate each situation individually. The PEP strategy employed by DOHMH should be considered because hepatitis A vaccine is immunogenic in all age groups, can be obtained by local jurisdictions more quickly, and is logistically easier to administer in mass clinics than immunoglobulin.

ComplexQuant: high-throughput computational pipeline for the global quantitative analysis of endogenous soluble protein complexes using high resolution protein HPLC and precision label-free LC/MS/MS.

PubMed

Wan, Cuihong; Liu, Jian; Fong, Vincent; Lugowski, Andrew; Stoilova, Snejana; Bethune-Waddell, Dylan; Borgeson, Blake; Havugimana, Pierre C; Marcotte, Edward M; Emili, Andrew

2013-04-09

The experimental isolation and characterization of stable multi-protein complexes are essential to understanding the molecular systems biology of a cell. To this end, we have developed a high-throughput proteomic platform for the systematic identification of native protein complexes based on extensive fractionation of soluble protein extracts by multi-bed ion exchange high performance liquid chromatography (IEX-HPLC) combined with exhaustive label-free LC/MS/MS shotgun profiling. To support these studies, we have built a companion data analysis software pipeline, termed ComplexQuant. Proteins present in the hundreds of fractions typically collected per experiment are first identified by exhaustively interrogating MS/MS spectra using multiple database search engines within an integrative probabilistic framework, while accounting for possible post-translation modifications. Protein abundance is then measured across the fractions based on normalized total spectral counts and precursor ion intensities using a dedicated tool, PepQuant. This analysis allows co-complex membership to be inferred based on the similarity of extracted protein co-elution profiles. Each computational step has been optimized for processing large-scale biochemical fractionation datasets, and the reliability of the integrated pipeline has been benchmarked extensively. This article is part of a Special Issue entitled: From protein structures to clinical applications. Copyright © 2012 Elsevier B.V. All rights reserved.

Rape and HIV post-exposure prophylaxis: addressing the dual epidemics in South Africa.

PubMed

Kim, Julia C; Martin, Lorna J; Denny, Lynette

2003-11-01

In South Africa, a country notable for both a rapidly escalating AIDS epidemic and high levels of sexual violence, the issue of HIV post-exposure prophylaxis (PEP) following rape has recently come to the fore, and a policy supporting provision of PEP has been approved by the national government. This paper compares the conditions for providing PEP in Europe and North America with the conditions faced by two initiatives in South Africa, one serving a primarily rural base, and one urban. It is based on a review of the literature on sexual violence in South Africa and use of PEP following occupational and non-occupational exposure. It incorporates perspectives from in-depth interviews in 2000 with 18 key informants, including survivors of sexual violence, gender and HIV activists, domestic violence NGOs, rape crisis centres, physicians, lawyers, researchers and HIV/AIDS advisors in the Department of Health. The paper argues that given the scientific evidence for PEP, and the nature of the dual epidemics of HIV and sexual violence in South Africa, the public health and social justice rationale for implementing PEP equals and indeed exceeds that put forward in industrialised countries. However, delays in accessing PEP caused by the public justice system and lack of training for service providers constitute significant obstacles to effective implementation. In this respect, provision of PEP presents an opportunity to reform and strengthen existing services for post-rape care and to link attention to the epidemic of sexual violence to HIV/AIDS prevention.

Development of an HIV Postexposure Prophylaxis (PEP) Protocol for Trainees Engaging in Academic Global Health Experiences.

PubMed

Arora, Gitanjli; Hoffman, Risa M

2017-11-01

Global health (GH) education programs have become increasingly common in U.S. medical schools and graduate medical education programs, with growing numbers of medical students, residents, and fellows participating in clinical experiences in settings with high HIV prevalence and limited resources. However, there are no guidelines for provision of HIV postexposure prophylaxis (PEP) to trainees engaging in these academic GH experiences. Faculty of the Global Health Education Programs (GHEP) at the David Geffen School of Medicine at UCLA and GH partner institutions recognized the need for PEP access for trainees engaged in GH experiences. In 2013-2014, key UCLA faculty collaborated in the development of the UCLA GHEP PEP Protocol, which includes provision of PEP medications to trainees prior to departure, an on-call infectious disease/HIV specialist to advise trainees who have exposures, and a system for following up with exposed trainees while on the GH rotation and after their return. Between February 2014 and September 2016, 112 medical students and 110 residents received education on the PEP protocol during their predeparture orientation. The protocol was used for 28 exposures (27 occupational, 1 nonoccupational), with PEP recommended in 3 occupational cases (all needlesticks) and the single nonoccupational case. There were no reported HIV seroconversions. The authors plan to formally evaluate the PEP protocol, conduct a qualitative assessment with trainees and both UCLA and GH partner faculty, and discuss best practices with institutions across the United States and with GH partners.

Reducing adverse self-medication behaviors in older adults with the Next Generation Personal Education Program (PEP-NG): Design and methodology

PubMed Central

Neafsey, Patricia J; Anderson, Elizabeth; Coleman, Craig; Lin, Carolyn A; M’lan, Cyr E; Walsh, Stephen

2009-01-01

A randomized controlled efficacy trial targeting older adults with hypertension is providing a tailored education intervention with a Next Generation Personal Education Program (PEP-NG) in primary care practices in New England. Ten participating advanced practice registered nurses (APRNs) completed online knowledge and self-efficacy measures pre-onsite training and twice more after completing a continuing education program. Patient participants self-refer in response to study recruitment brochures and posters. Twenty-four participants from each APRN practice (total N = 240) are randomly assigned by the PEP-NG software to either control (data collection and four routine APRN visits) or tailored intervention (PEP-NG interface and four focused APRN visits) conditions. Patients access the PEP-NG interface via wireless tablet and use a stylus to answer demographic, knowledge, and self-efficacy questions as well as prescription and over-the-counter self-medication practice questions. The PEP-NG analyzes patient-reported information and delivers tailored educational content. Patients’ outcome measures are self-reported antihypertensive medication adherence, blood pressure, knowledge and self-efficacy concerning potential adverse self-medication practices, adverse self-medication behavior “risk” score and satisfaction with the PEP-NG and APRN provider relationship. APRN outcome measures are knowledge and self-efficacy concerning adverse self-medication practices, self-efficacy for communicating with older adults and satisfaction with the PEP-NG. Time–motion and cost–benefit analyses will be conducted. PMID:20016796

Heterologous expression and characterisation of the Aspergillus aspartic protease involved in the hydrolysis and decolorisation of red-pigmented proteins.

PubMed

Takenaka, Shinji; Umeda, Mayo; Senba, Hisanori; Koyama, Dai; Tanaka, Kosei; Yoshida, Ken-Ichi; Doi, Mikiharu

2017-01-01

Aspergillus repens strain MK82 produces an aspartic protease (PepA_MK82) that efficiently decolorises red-pigmented proteins during dried bonito fermentation. However, further expansion of the industrial applications of PepA_MK82 requires the high-level production and efficient preparation of the recombinant enzyme. The genomic DNA and cDNA fragments encoding the protease were cloned from strain MK82 and sequenced. Phylogenetic analysis of PepA_MK82 and comparisons with previously reported fungal aspartic proteases showed that PepA_MK 82 clusters with different groups of these enzymes. Heterologous expression of PepA_MK82 in Pichia pastoris yielded preparations of higher purity than obtained with an Escherichia coli expression system. Total protease activity in a 100-mL culture of the P. pastoris transformant was 14 times higher than that from an equivalent culture of A. repense MK82. The recombinant PepA_MK82 was easily obtained via acetone precipitation; the final recovery was 83%. PepA_MK82 and its recombinant had similar characteristics in terms of their optimal pH, thermostability, and decolorisation activity. The recombinant was also able to decolorise flaked, dried bonito and to bleach a blood-stained cloth. Given its ability to hydrolyse and decolorise red-pigmented proteins, recombinant PepA_MK8 can be exploited in the food industry and as a stain-removal agent in laundry applications. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

RFID-Based Multidisciplinary Educational Platform to Improve the Engineering and Technology Curriculums

ERIC Educational Resources Information Center

Yelamarthi, Kumar

2012-01-01

Multidisciplinary projects involving electrical engineering (EE), mechanical engineering (ME), and computer engineering (CE) students are both exciting and difficult to conceptualize. Answering this challenge, this paper presents a multidisciplinary educational platform on radio frequency identification-based assistive devices. The combination of…

Anti-retroviral Therapy Based HIV Prevention Among a Sample of Men Who Have Sex with Men in Cape Town, South Africa: Use of Post-exposure Prophylaxis and Knowledge on Pre-exposure Prophylaxis.

PubMed

Hugo, J M; Stall, R D; Rebe, K; Egan, J E; De Swardt, G; Struthers, H; McIntyre, J A

2016-12-01

Men who have Sex with Men (MSM) have been affected disproportionately by the global HIV pandemic. Rates of consistent condom-use are low and there is a need for further biomedical prevention interventions to prevent new HIV infections. Post exposure prophylaxis (PEP) can reduce the risk of HIV, but uptake among MSM is low. Pre-exposure prophylaxis (PrEP), an innovative anti-retroviral-based HIV prevention tool might be an appropriate intervention for MSM who have recently accessed PEP that involves HIV negative individuals taking daily tenofovir+emtricitabine for HIV prevention. 44 MSM, attending a primary health-care level MSM-focused sexual health clinic in Cape Town, South Africa, who had initiated PEP were enrolled in this study. Participants were followed up after 2, 4 and 12 weeks. Self-administered electronic surveys were completed at the initial, 4 and 12 week visit. Barriers and facilitators to accessing PEP and remaining adherent were examined, as was knowledge about PrEP. Thirty-two participants (80 %) were <40 years of age (range 20-65 years). 35 % of the participants reported their reason for requiring PEP as condomless receptive anal intercourse. A further 20 % required PEP following condomless penetrative anal intercourse; 27.5 % required PEP due to a broken condom during receptive anal sex and 2 participants during insertive anal sex. Three participants did not complete 28 days of PEP or were lost to follow up. Over half (58.5 %) of the participants reported being completely adherent to their regime; under a third (31.7 %) reported missing one PEP dose; and 9.8 % reported missing more than one dose. 36/40 (90 %) had heard of PrEP and 30/40 (75 %) indicated that they would use PrEP if it were accessible to them. That we enrolled 44 MSM who accessed PEP from a Department of Health affiliated clinic over 12 months, speaks to the low uptake by MSM of PEP services in South Africa. Adherence was high and demonstrates that adherence support is feasible from a state health clinic. Reported risk behaviors in some high-risk participants did not change over time, demonstrating the need for additional longer-term HIV preventions such as PrEP. PEP users could conceivably be transitioned from PEP to PrEP.

Power Extension Package (PEP) system definition extension, orbital service module systems analysis study. Volume 9: PEP design, development and test plans

NASA Technical Reports Server (NTRS)

1979-01-01

A plan for the production of two PEP flight systems is defined. The task's milestones are described. Provisions for the development and assembly of new ground support equipment required for both testing and launch operations are included.

77 FR 54570 - Notice of Submission for OMB Review; Office of Planning, Evaluation and Policy Development...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-05

.... White Physical Education Program (PEP) is authorized by the Elementary and Secondary Education Act of 1965, as amended. In establishing PEP, Congress acknowledged the critical need to improve physical... of what PEP projects experience related to two new program competitive preference priorities: The...

Power Extension Package (PEP) system definition extension, orbital service module systems analysis study. Volume 3: PEP analysis and tradeoffs

NASA Technical Reports Server (NTRS)

1979-01-01

The objectives, conclusions, and approaches for accomplishing 19 specific design and analysis activities related to the installation of the power extension package (PEP) into the Orbiter cargo bay are described as well as those related to its deployment, extension, and retraction. The proposed cable handling system designed to transmit power from PEP to the Orbiter by way of the shuttle remote manipulator system is described and a preliminary specification for the gimbal assembly, solar array drive is included.

Increased prolyl endopeptidase activity in human neoplasia.

PubMed

Larrinaga, Gorka; Perez, Itxaro; Blanco, Lorena; López, José I; Andrés, Leire; Etxezarraga, Carmen; Santaolalla, Francisco; Zabala, Aitor; Varona, Adolfo; Irazusta, Jon

2010-08-09

Prolyl endopeptidase (EC 3.4.21.26) (PEP) is a serine peptidase that converts several biologically active peptides. This enzyme has been linked to several neurological, digestive, cardiovascular and infectous disorders. However, little is known about its involvement in neoplastic processes. This study analyzes fluorimetrically cytosolic and membrane-bound PEP activity in a large series (n=122) of normal and neoplastic tissues from the kidney, colon, oral cavity, larynx, thyroid gland and testis. Cytosolic PEP activity significantly increased in clear cell renal cell carcinoma, urothelial carcinoma of the renal pelvis and head and neck squamous cell carcinoma. Both cytosolic and membrane-bound PEP activity were also increased in colorectal adenomatous polyps. These data suggest the involvement of PEP in some mechanisms that underlie neoplastic processes. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Self-focused attention affects subsequent processing of positive (but not negative) performance appraisals.

PubMed

Holzman, Jacob B; Valentiner, David P

2016-03-01

Cognitive-behavioral models highlight the conjoint roles of self-focused attention (SFA), post-event processing (PEP), and performance appraisals in the maintenance of social anxiety. SFA, PEP, and biased performance appraisals are related to social anxiety; however, limited research has examined how SFA affects information-processing following social events. The current study examined whether SFA affects the relationships between performance appraisals and PEP following a social event.. 137 participants with high (n = 72) or low (n = 65) social anxiety were randomly assigned to conditions of high SFA or low SFA while engaging in a standardized social performance. Subsequent performance appraisals and PEP were measured. Immediate performance appraisals were not affected by SFA. High levels of SFA led to a stronger, inverse relationship between immediate positive performance appraisals and subsequent negative PEP. High levels of SFA also led to a stronger, inverse relationship between negative PEP and changes in positive performance appraisals.. Future research should examine whether the current findings, which involved a standardized social performance event, extend to interaction events as well as in a clinical sample. These findings suggest that SFA affects the processing of positive information following a social performance event. SFA is particularly important for understanding how negative PEP undermines positive performance appraisals.. Published by Elsevier Ltd.

Estimated preejection period (PEP) based on the detection of the R-wave and dZ/dt-min peaks in ECG and ICG

NASA Astrophysics Data System (ADS)

van Lien, René; Schutte, Nienke M.; Meijer, Jan H.; de Geus, Eco J. C.

2013-04-01

The validity of estimating the PEP from a fixed value for the Q-wave onset to the R-wave peak (QR) interval and from the R-wave peak to the dZ/dt-min peak (ISTI) interval is evaluated. Ninety-one subjects participated in a laboratory experiment in which a variety of physical and mental stressors were presented and 31 further subjects participated in a sequence of structured ambulatory activities in which large variation in posture and physical activity was induced. PEP, QR interval, and ISTI were scored. Across the diverse laboratory and ambulatory conditions the QR interval could be approximated by a fixed interval of 40 ms but 95% confidence intervals were large (25 to 54 ms). Multilevel analysis showed that 79% to 81% of the within and between-subject variation in the RB interval could be predicted by the ISTI. However, the optimal intercept and slope values varied significantly across subjects and study setting. Bland-Altman plots revealed a large discrepancy between the estimated PEP and the actual PEP based on the Q-wave onset and B-point. It is concluded that the estimated PEP can be a useful tool but cannot replace the actual PEP to index cardiac sympathetic control.

Social Anxiety and Post-Event Processing: The Impact of Race

PubMed Central

Buckner, Julia D.; Dean, Kimberlye E.

2016-01-01

Background Social anxiety is among the most prevalent psychiatric conditions, yet little attention has been paid to whether putative cognitive vulnerability factors related to social anxiety in predominantly White samples are related to social anxiety among historically underrepresented groups. Design We tested whether one such vulnerability factor, post-event processing (PEP; detailed review of social event that can increase state social anxiety) was related to social anxiety among African American (AA; n=127) persons, who comprise one of the largest underrepresented racial groups in the U.S. Secondarily, we tested whether AA participants differed from non-Hispanic White participants (n=127) on PEP and social anxiety and whether race moderated the relation between PEP and social anxiety. Method Data were collected online among undergraduates. Results PEP was positively correlated with social anxiety among AA participants, even after controlling for depression and income, pr=.30, p=.001. AA and White participants did not differ on social anxiety or PEP, β=−1.57, 95% C.I.: −5.11, 1.96. The relation of PEP to social anxiety did not vary as a function of race, β=0.00, 95% C.I.: −0.02, 0.02. Conclusions PEP may be an important cognitive vulnerability factor related to social anxiety among AA persons suffering from social anxiety. PMID:27576610

Chest physiotherapy with positive expiratory pressure breathing after abdominal and thoracic surgery: a systematic review.

PubMed

Orman, J; Westerdahl, E

2010-03-01

A variety of chest physiotherapy techniques are used following abdominal and thoracic surgery to prevent or reduce post-operative complications. Breathing techniques with a positive expiratory pressure (PEP) are used to increase airway pressure and improve pulmonary function. No systematic review of the effects of PEP in surgery patients has been performed previously. The purpose of this systematic review was to determine the effect of PEP breathing after an open upper abdominal or thoracic surgery. A literature search of randomised-controlled trials (RCT) was performed in five databases. The trials included were systematically reviewed by two independent observers and critically assessed for methodological quality. We selected six RCT evaluating the PEP technique performed with a mechanical device in spontaneously breathing adult patients after abdominal or thoracic surgery via thoracotomy. The methodological quality score varied between 4 and 6 on the Physiotherapy Evidence Database score. The studies were published between 1979 and 1993. Only one of the included trials showed any positive effects of PEP compared to other breathing techniques. Today, there is scarce scientific evidence that PEP treatment is better than other physiotherapy breathing techniques in patients undergoing abdominal or thoracic surgery. There is a lack of studies investigating the effect of PEP over placebo or no physiotherapy treatment.

Social anxiety and post-event processing among African-American individuals.

PubMed

Buckner, Julia D; Dean, Kimberlye E

2017-03-01

Social anxiety is among the most prevalent psychiatric conditions, yet little attention has been paid to whether putative cognitive vulnerability factors related to social anxiety in predominantly White samples are related to social anxiety among historically underrepresented groups. We tested whether one such vulnerability factor, post-event processing (PEP; detailed review of social event that can increase state social anxiety) was related to social anxiety among African-American (AA; n = 127) persons, who comprise one of the largest underrepresented racial groups in the U.S. Secondarily, we tested whether AA participants differed from non-Hispanic White participants (n = 127) on PEP and social anxiety and whether race moderated the relation between PEP and social anxiety. Data were collected online among undergraduates. PEP was positively correlated with social anxiety among AA participants, even after controlling for depression and income, pr = .30, p = .001. AA and White participants did not differ on social anxiety or PEP, β = -1.57, 95% CI: -5.11, 1.96. The relation of PEP to social anxiety did not vary as a function of race, β = 0.00, 95% CI: -0.02, 0.02. PEP may be an important cognitive vulnerability factor related to social anxiety among AA persons suffering from social anxiety.

Effects of a psycho-educational programme on health-related quality of life in patients treated for colorectal and anal cancer: A feasibility trial.

PubMed

Ohlsson-Nevo, Emma; Karlsson, Jan; Nilsson, Ulrica

2016-04-01

Colorectal cancer (CRC) may have a negative impact on a person's quality of life. Psycho-educational interventions for patients with CRC are rarely studied. The purpose of this feasibility trial was to evaluate the effect of a psycho-educational programme (PEP) on the health-related quality of life (HRQL) of patients treated for CRC and anal cancer. Patients with CRC and anal cancer were randomly assigned to a PEP (n = 47) or standard treatment (n = 39). The PEP included informative lectures, discussion, and reflection. HRQL was evaluated using the SF-36 at baseline and 1, 6, and 12 months after the end of the PEP. Patients in the PEP group had significantly better Mental Health scores after 1 month and significantly better Bodily Pain scores after 6 months compared with patients who received standard care. The results of this study indicate that a PEP can have a short-term effect on the mental health and bodily pain of patients treated for CRC and anal cancer when comparing with a control group. The article discusses the methodological difficulties of evaluating an intervention such as this PEP in a clinical setting. Copyright © 2015. Published by Elsevier Ltd.

Sustainability of an HIV PEP Program for Sexual Assault Survivors: “Lessons Learned” from Health Care Providers

PubMed Central

Du Mont, Janice; Macdonald, Sheila; Myhr, Terri; Loutfy, Mona R

2011-01-01

This study explored challenges to continuing an HIV post-exposure prophylaxis (PEP) program of care provided to sexual assault survivors in the province of Ontario, Canada. Data were collected as part of an implementation and evaluation of a universal offering of HIV PEP (known as the HIV PEP Program) at 24 of 34 provincial hospital-based sexual assault treatment centres. Experienced health care providers were surveyed (n = 132) and interviewed in four focus groups (n = 26) about their perceptions of what, if any, factors threatened their ability to maintain the HIV PEP Program. All focus groups were audio-recorded and the recordings transcribed. The transcriptions and open-ended survey responses were analyzed using content analysis. Administrator, nurse, physician, social worker, and pharmacist respondents perceived important barriers to sustainability of the HIV PEP Program. Eight constructs were identified within four broad themes: resources (inadequate funds, overworked and unacknowledged staff), expertise (insufficient external supports, insufficiently trained and knowledgeable staff), commitment (lack of institutional support, physician resistance to offering HIV PEP), and accommodation (lack of flexibility in addressing specific client and community needs, inaccessibility and lack of clarity of tools). We discuss the implications of these findings and the actions that were taken to address the challenges. PMID:22216082

Polysaccharides from Enteromorpha prolifera Improve Glucose Metabolism in Diabetic Rats

PubMed Central

Lin, Wenting; Wang, Wenxiang; Liao, Dongdong; Chen, Damiao; Zhu, Pingping; Cai, Guoxi; Kiyoshi, Aoyagi

2015-01-01

This study investigated the effects of polysaccharides from Enteromorpha prolifera (PEP) on glucose metabolism in a rat model of diabetes mellitus (DM). PEP (0, 150, 300, and 600 mg/kg) was administered intragastrically to rats for four weeks. After treatment, fasting blood glucose (FBG) and insulin (INS) levels were measured, and the insulin sensitivity index (ISI) was calculated. The morphopathological changes in the pancreas were observed. Serum samples were collected to measure the oxidant-antioxidant status. The mRNA expression levels of glucokinase (GCK) and insulin receptor (InsR) in liver tissue and glucose transporter type 4 (GLUT-4) and adiponectin (APN) in adipose tissue were determined. Compared with the model group, the FBG and INS levels were lower, the ISI was higher, and the number of islet β-cells was significantly increased in all the PEP groups. In the medium- and high-dose PEP groups, MDA levels decreased, and the enzymatic activities of SOD and GSH-Px increased. The mRNA expression of InsR and GCK increased in all the PEP groups; APN mRNA expression increased in the high-dose PEP group, and GLUT-4 mRNA expression increased in adipose tissue. These findings suggest that PEP is a potential therapeutic agent that can be utilized to treat DM. PMID:26347892

Post-event processing in social anxiety disorder: Examining the mediating roles of positive metacognitive beliefs and perceptions of performance.

PubMed

Gavric, Dubravka; Moscovitch, David A; Rowa, Karen; McCabe, Randi E

2017-04-01

Post-event processing (PEP) is defined as repetitive negative thinking following anxiety provoking social events. PEP is thought to maintain anxiety symptoms in Social Anxiety Disorder (SAD) but little is known about the specific factors that contribute to the maintenance of PEP. The current study investigated how perceptions of performance and positive metacognitive beliefs might contribute to the persistence of PEP. Participants with SAD (n = 24) as well as anxious (n = 24) and healthy (n = 25) control participants completed a standardized social performance task in the lab. Their engagement in PEP and perceptions of performance were assessed in the week that followed. Immediately following the social task, individuals with SAD rated their performance more negatively and endorsed a greater number of positive metacognitive beliefs about PEP than did participants in both control groups. Importantly, both metacognitive beliefs and initial negative self-ratings of performance mediated the relationship between group status and PEP in the days following the event. These results are consistent with cognitive and metacognitive models of SAD and enhance our understanding of the cognitive processes which may function to initiate and maintain negative thinking patterns in SAD. Copyright © 2017 Elsevier Ltd. All rights reserved.

Awareness and knowledge of human immunodeficiency virus post exposure prophylaxis among Nigerian Family Physicians.

PubMed

Agaba, Patricia A; Agaba, Emmanuel I; Ocheke, Amaka N; Daniyam, Comfort A; Akanbi, Maxwell O; Okeke, Edith N

2012-07-01

To determine the level of awareness and knowledge of HIV postexposure prophylaxis (HIV PEP) and determinants of adequate knowledge among Family Physicians in Nigeria. This was a cross-sectional questionnaire-based survey conducted among 175 Family Physicians at two national conferences. Majority (97.7%) of the respondents was aware of the concept of HIV PEP and 99.4% believed it was effective in preventing HIV transmission. Over two third of our respondents had been exposed to NSI; however, less than 25% of those exposed received PEP. There was high level of knowledge of the various high-risk body fluids as well as types of high-risk exposures. 93.9% of our respondents knew that HIV PEP should commence within 1 h of exposure, 83.3% knew the correct duration of HIV PEP, but only 57.0% knew the ideal PEP regimen for high-risk exposures. The total mean score for our respondents was 17.8±2.9 with 79.4% having an adequate score. Being a junior doctor and male sex were associated with adequate knowledge. This study shows that despite high levels of awareness and knowledge of HIV PEP, access to its use among family physicians in Nigeria is still sub-optimal.

A Cyclin D2-derived peptide acts on specific cell cycle phases by activating ERK1/2 to cause the death of breast cancer cells.

PubMed

Russo, Lilian C; Araujo, Christiane B; Iwai, Leo K; Ferro, Emer S; Forti, Fabio L

2017-01-16

Protein degradation by the proteasome generates functional intracellular peptides. Pep5, a peptide derived from Cyclin D2, induces cell death in tumor cell lines and reduces the volume of rat C6 glioblastoma tumors in vivo. Here, we chose the human MDA-MB-231 breast cancer cells to evaluate the mechanism of cell death induced by pep5 in different phases of the cell cycle. Fluorescently labeled pep5, monitored by real time confocal microscopy, entered the MDA-MB-231 cells 3min after application and localized to the nucleus and cytoplasm. Pep5-induced cell death was increased when the MDA-MB-231 cell population was arrested at the G1/S transition or in S phase compared to asynchronous cells. Pep5 induced permanent extracellular signal-regulated kinase (ERK1/2) phosphorylation in MDA-MB-231 cells synchronized in G1/S or S phase. Affinity chromatography followed by mass spectrometry identified CLIC1 and Plectin as the only two proteins that interacted with pep5 in both asynchronous and synchronized MDA-MB-231 cells. These interactions could explain the long-lasting ERK1/2 phosphorylation and the cytoskeleton perturbations in the MDA-MB-231 cells, in which the stress fibers' integrity is affected by pep5 treatments. These data suggest that pep5 has potential therapeutic properties for treating specific types of cancers, such as breast cancer cells. Pep5, a natural intracellular peptide formed by the degradation of Cyclin D2 through the ubiquitin-proteasome system, induces cell death when reintroduced into MDA-MB-231 breast cancer cells, which express low levels of Cyclin D2, specifically in G1/S arrested cells or in cells that are passing through S phase. Under these conditions, pep5 is able to interact with different intracellular proteins, primarily cytoskeleton and proteasome components, which can lead to cellular apoptosis. Together, our data suggest that pep5 is an intracellular peptide with therapeutic potential for treating specific types of tumors with low expression of Cyclin D2 by inhibiting cell proliferation. Copyright © 2016 Elsevier B.V. All rights reserved.

DeNovoGUI: An Open Source Graphical User Interface for de Novo Sequencing of Tandem Mass Spectra

PubMed Central

2013-01-01

De novo sequencing is a popular technique in proteomics for identifying peptides from tandem mass spectra without having to rely on a protein sequence database. Despite the strong potential of de novo sequencing algorithms, their adoption threshold remains quite high. We here present a user-friendly and lightweight graphical user interface called DeNovoGUI for running parallelized versions of the freely available de novo sequencing software PepNovo+, greatly simplifying the use of de novo sequencing in proteomics. Our platform-independent software is freely available under the permissible Apache2 open source license. Source code, binaries, and additional documentation are available at http://denovogui.googlecode.com. PMID:24295440

DeNovoGUI: an open source graphical user interface for de novo sequencing of tandem mass spectra.

PubMed

Muth, Thilo; Weilnböck, Lisa; Rapp, Erdmann; Huber, Christian G; Martens, Lennart; Vaudel, Marc; Barsnes, Harald

2014-02-07

De novo sequencing is a popular technique in proteomics for identifying peptides from tandem mass spectra without having to rely on a protein sequence database. Despite the strong potential of de novo sequencing algorithms, their adoption threshold remains quite high. We here present a user-friendly and lightweight graphical user interface called DeNovoGUI for running parallelized versions of the freely available de novo sequencing software PepNovo+, greatly simplifying the use of de novo sequencing in proteomics. Our platform-independent software is freely available under the permissible Apache2 open source license. Source code, binaries, and additional documentation are available at http://denovogui.googlecode.com .

Investigating the strategies for microbial production of trehalose from lignocellulosic sugars.

PubMed

Wu, Yifei; Wang, Jian; Shen, Xiaolin; Wang, Jia; Chen, Zhenya; Sun, Xinxiao; Yuan, Qipeng; Yan, Yajun

2018-03-01

Trehalose, a multi-functional and value-added disaccharide, can be efficiently biosynthesized from glucose by using a synergetic carbon utilization mechanism (SynCar) which coupled phosphoenolpyruvate (PEP) generation from the second carbon source with PEP-dependent phosphotransferase system (PTS) to promote non-catabolic use of glucose. Considering glucose and xylose present in large amounts in lignocellulosic sugars, we explored new strategies for conversion of both sugars into trehalose. Herein, we first attempted trehalose production from xylose directly, based on which, synergetic utilization of glucose, and xylose prompted by SynCar was implemented in engineered Escherichia coli. As the results, the final titer of trehalose reached 5.55 g/L in shake flask experiments. The conversion ratio or utilization efficiency of glucose or xylose to trehalose was around fourfold higher than that of the original strain (YW-3). This work not only demonstrated the possibility of directly converting xylose (C5 sugar) into trehalose (C12 disaccharide), but also suggested a promising strategy for trehalose production from lignocellulosic sugars for the first time. © 2017 Wiley Periodicals, Inc.

Introducing WISDEM:An Integrated System Modeling for Wind Turbines and Plant (Presentation)

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

Dykes, K.; Graf, P.; Scott, G.

2015-01-01

The National Wind Technology Center wind energy systems engineering initiative has developed an analysis platform to leverage its research capabilities toward integrating wind energy engineering and cost models across wind plants. This Wind-Plant Integrated System Design & Engineering Model (WISDEM) platform captures the important interactions between various subsystems to achieve a better National Wind Technology Center wind energy systems engineering initiative has developed an analysis platform to leverage its research capabilities toward integrating wind energy engineering and cost models across wind plants. This Wind-Plant Integrated System Design & Engineering Model (WISDEM) platform captures the important interactions between various subsystems tomore » achieve a better understanding of how to improve system-level performance and achieve system-level cost reductions. This work illustrates a few case studies with WISDEM that focus on the design and analysis of wind turbines and plants at different system levels.« less

Mitochondria-acting hexokinase II peptides carried by short-length carbon nanotubes with increased cellular uptake, endosomal evasion, and enhanced bioactivity against cancer cells

NASA Astrophysics Data System (ADS)

Yoong, Sia Lee; Lau, Wei Liang; Liu, Ang Yu; Prendergast, D'arcy; Ho, Han Kiat; Yu, Victor Chun Kong; Lee, Chengkuo; Ang, Wee Han; Pastorin, Giorgia

2015-08-01

Type II hexokinase (HKII) has emerged as a viable therapeutic target due to its involvement in metabolic reprogramming and also apoptosis prevention. The peptide derived from the fifteen amino acid sequence in the HKII N-terminal region [HKII(pep)] can compete with endogenous proteins for binding on mitochondria and trigger apoptosis. However, this peptide is not cell-permeable. In this study, multi-walled carbon nanotubes (MWCNTs) were used to effectively deliver HKII(pep) across cellular barriers without compromising their bioactivity. The peptide was conjugated on either oxidized MWCNTs or 2,2'-(ethylenedioxy)bis(ethylamine)-functionalized MWCNTs, yielding MWCNT-HKII(pep) and MWCNT-TEG-HKII(pep), respectively. Both conjugates were shown to be internalized by breast cancer MCF-7 cells using confocal microscopy. Moreover, these nanoconjugates seemed to have escaped from endosomes and be in the vicinity of mitochondria. The WST-1 cytotoxicity assay conducted on MCF-7 and colon carcinoma HCT116 cells revealed that MWCNT-peptide conjugates were significantly more effective in curbing cancer cell growth compared to a commercially available cell permeable HKII fusion peptide. In addition, both nanoconjugates displayed an enhanced ability in eliciting apoptosis and depleting the ATP level in HCT116 cells compared to the mere HKII peptide. Importantly, hexokinase II release from mitochondria was demonstrated in MWCNT-HKII(pep) and MWCNT-TEG-HKII(pep) treated cells, highlighting that the structure and bioactivity of HKII(pep) were not compromised after covalent conjugation to MWCNTs.Type II hexokinase (HKII) has emerged as a viable therapeutic target due to its involvement in metabolic reprogramming and also apoptosis prevention. The peptide derived from the fifteen amino acid sequence in the HKII N-terminal region [HKII(pep)] can compete with endogenous proteins for binding on mitochondria and trigger apoptosis. However, this peptide is not cell-permeable. In this study, multi-walled carbon nanotubes (MWCNTs) were used to effectively deliver HKII(pep) across cellular barriers without compromising their bioactivity. The peptide was conjugated on either oxidized MWCNTs or 2,2'-(ethylenedioxy)bis(ethylamine)-functionalized MWCNTs, yielding MWCNT-HKII(pep) and MWCNT-TEG-HKII(pep), respectively. Both conjugates were shown to be internalized by breast cancer MCF-7 cells using confocal microscopy. Moreover, these nanoconjugates seemed to have escaped from endosomes and be in the vicinity of mitochondria. The WST-1 cytotoxicity assay conducted on MCF-7 and colon carcinoma HCT116 cells revealed that MWCNT-peptide conjugates were significantly more effective in curbing cancer cell growth compared to a commercially available cell permeable HKII fusion peptide. In addition, both nanoconjugates displayed an enhanced ability in eliciting apoptosis and depleting the ATP level in HCT116 cells compared to the mere HKII peptide. Importantly, hexokinase II release from mitochondria was demonstrated in MWCNT-HKII(pep) and MWCNT-TEG-HKII(pep) treated cells, highlighting that the structure and bioactivity of HKII(pep) were not compromised after covalent conjugation to MWCNTs. Electronic supplementary information (ESI) available: Additional TEM images, UV-Vis scanning characterisation, WST-1 assay results, and immunoblotting of HKII in the total cell lysate. See DOI: 10.1039/c5nr00980d

Pulse Oximeter Plethysmograph Estimate of Pulsus Paradoxus as a Measure of Acute Asthma Exacerbation Severity and Response to Treatment.

PubMed

Arnold, Donald H; Wang, Li; Hartert, Tina V

2016-03-01

Pulsus paradoxus is one of the few objective bedside measures of acute asthma exacerbation severity but is difficult to measure in tachypneic and tachycardic patients and in noisy clinical environments. Our primary objective was to examine whether pulse oximeter plethysmograph estimate of pulsus paradoxus (PEP) is associated with physiologic and symptom measures of acute exacerbation severity (airway resistance by impulse oscillometry [%IOS] and the Acute Asthma Intensity Research Score [AAIRS]). Secondary objectives were to validate the previous association of PEP with percent predicted forced expiratory volume in 1 second (%FEV1 ) and to examine associations of change of PEP with change of these outcomes after 2 hours of treatment. This was a secondary analysis of data from a prospective observational study of patients aged 5-17 years with acute asthma exacerbations. The predictor variable, PEP, was measured using a dedicated pulse oximeter and waveform analysis program. Outcome measures included the AAIRS, %IOS, and %FEV1 at baseline and after 2 hours of treatment. We examined associations of PEP with %IOS and the AAIRS at baseline using multiple linear regression models adjusted for age, sex, and race. As secondary analyses we similarly examined the association of PEP with %FEV1 at baseline and change of PEP with change of %IOS, the AAIRS, and %FEV1 after 2 hours of treatment using multiple linear regression models adjusted for the baseline value of the outcome measure and the AAIRS. Among 684 participants (61% males; 61% African American) there were associations of baseline PEP with %IOS, the AAIRS, and %FEV1 (p < 0.001). Change of PEP after 2 hours of treatment was associated with change of %FEV1 (p < 0.001) and change of the AAIRS (p = 0.01) but not with change of %IOS (p = 0.60). PEP demonstrates criterion validity in predicting baseline %IOS, the AAIRS, and %FEV1 , and responsiveness to change of the AAIRS and %FEV1 . Data contained in the oximeter plethysmograph waveform might be utilized as a continuous, objective measure of acute asthma exacerbation severity and real-time response to treatment. © 2016 by the Society for Academic Emergency Medicine.

Plant elicitor peptides are conserved signals regulating direct and indirect antiherbivore defense

PubMed Central

Huffaker, Alisa; Pearce, Gregory; Veyrat, Nathalie; Erb, Matthias; Turlings, Ted C. J.; Sartor, Ryan; Shen, Zhouxin; Briggs, Steven P.; Vaughan, Martha M.; Alborn, Hans T.; Teal, Peter E. A.; Schmelz, Eric A.

2013-01-01

Insect-induced defenses occur in nearly all plants and are regulated by conserved signaling pathways. As the first described plant peptide signal, systemin regulates antiherbivore defenses in the Solanaceae, but in other plant families, peptides with analogous activity have remained elusive. In the current study, we demonstrate that a member of the maize (Zea mays) plant elicitor peptide (Pep) family, ZmPep3, regulates responses against herbivores. Consistent with being a signal, expression of the ZmPROPEP3 precursor gene is rapidly induced by Spodoptera exigua oral secretions. At concentrations starting at 5 pmol per leaf, ZmPep3 stimulates production of jasmonic acid, ethylene, and increased expression of genes encoding proteins associated with herbivory defense. These include proteinase inhibitors and biosynthetic enzymes for production of volatile terpenes and benzoxazinoids. In accordance with gene expression data, plants treated with ZmPep3 emit volatiles similar to those from plants subjected to herbivory. ZmPep3-treated plants also exhibit induced accumulation of the benzoxazinoid phytoalexin 2-hydroxy-4,7-dimethoxy-1,4-benzoxazin-3-one glucoside. Direct and indirect defenses induced by ZmPep3 contribute to resistance against S. exigua through significant reduction of larval growth and attraction of Cotesia marginiventris parasitoids. ZmPep3 activity is specific to Poaceous species; however, peptides derived from PROPEP orthologs identified in Solanaceous and Fabaceous plants also induce herbivory-associated volatiles in their respective species. These studies demonstrate that Peps are conserved signals across diverse plant families regulating antiherbivore defenses and are likely to be the missing functional homologs of systemin outside of the Solanaceae. PMID:23509266

The use of HIV post-exposure prophylaxis in forensic medicine following incidents of sexual violence in Hamburg, Germany: a retrospective study.

PubMed

Ebert, Julia; Sperhake, Jan Peter; Degen, Olaf; Schröder, Ann Sophie

2018-05-18

In Hamburg, Germany, the initiation of HIV post-exposure prophylaxis (HIV PEP) in cases of sexual violence is often carried out by forensic medical specialists (FMS) using the city's unique Hamburg Model. FMS-provided three-day HIV PEP starter packs include a combination of raltegravir and emtricitabine/tenofovir. This study aimed to investigate the practice of offering HIV PEP, reasons for discontinuing treatment, patient compliance, and whether or not potential perpetrators were tested for HIV. We conducted a retrospective study of forensic clinical examinations carried out by the Hamburg Department of Legal Medicine following incidents of sexual violence from 2009 to 2016. One thousand two hundred eighteen incidents of sexual violence were reviewed. In 18% of these cases, HIV PEP was initially prescribed by the FMS. HIV PEP indication depended on the examination occurring within 24 h after the incident, no/unknown condom use, the occurrence of ejaculation, the presence of any injury, and the perpetrator being from population at high risk for HIV. Half of the HIV PEP recipients returned for a reevaluation of the HIV PEP indication by an infectious disease specialist, and just 16% completed the full month of treatment. Only 131 potential perpetrators were tested for HIV, with one found to be HIV positive. No HIV seroconversion was registered among the study sample. Provision of HIV PEP by an FMS after sexual assault ensures appropriate and prompt care for victims. However, patient compliance and completion rates are low. HIV testing of perpetrators must be carried out much more rigorously.

Pancreatits after endoscopic retrograde cholangio-pancreatography

PubMed Central

Abdel Aziz, Ayman M; Lehman, Glen A

2007-01-01

Pancreatitis is the most common complication after endoscopic retrograde cholangio-pancreatography (ERCP); the reported incidence of this complication varies from less than 1% to 40%, but a rate of 4%-8% is reported in most prospective studies involving non-selected patients. Differences in criteria for defining pancreatitis, methods of data collection, and patient populations (i.e. number of high-risk patients included in the published series) are factors that are likely to affect the varying rates of post-ERCP pancreatitis. The severity of post-ERCP pancreatitis (PEP) can range from a minor inconvenience with one or two days of added hospitalization with full recovery to a devastating illness with pancreatic necrosis, multiorgan failure, permanent disability, and even death. Although, most episodes of PEP are mild (about 90%), a small percentage of patients (about 10%) develop moderate or severe pancreatitis. In the past, PEP was often viewed as an unpredictable and unavoidable complication, with no realistic strategy for its avoidance. New data have aided in stratification of patients into PEP risk categories and new measures have been introduced to decrease the risk of PEP. As most ERCPs are performed on an outpatient basis, the majority of patients will not develop PEP and can be discharged. Alternatively, early detection of those patients who will go on to develop PEP can guide decisions regarding hospital admission and aggressive management. In the last decade, great efforts have been addressed toward prevention of this complication. Points of emphasis have included technical measures, pharmacological prophylaxis, and patient selection. This review provides a comprehensive, evidence-based assessment of published data on PEP and current suggestions for its avoidance. PMID:17569133

AtPep3 is a hormone-like peptide that plays a role in the salinity stress tolerance of plants.

PubMed

Nakaminami, Kentaro; Okamoto, Masanori; Higuchi-Takeuchi, Mieko; Yoshizumi, Takeshi; Yamaguchi, Yube; Fukao, Yoichiro; Shimizu, Minami; Ohashi, Chihiro; Tanaka, Maho; Matsui, Minami; Shinozaki, Kazuo; Seki, Motoaki; Hanada, Kousuke

2018-05-29

Peptides encoded by small coding genes play an important role in plant development, acting in a similar manner as phytohormones. Few hormone-like peptides, however, have been shown to play a role in abiotic stress tolerance. In the current study, 17 Arabidopsis genes coding for small peptides were found to be up-regulated in response to salinity stress. To identify peptides leading salinity stress tolerance, we generated transgenic Arabidopsis plants overexpressing these small coding genes and assessed survivability and root growth under salinity stress conditions. Results indicated that 4 of the 17 overexpressed genes increased salinity stress tolerance. Further studies focused on AtPROPEP3 , which was the most highly up-regulated gene under salinity stress. Treatment of plants with synthetic peptides encoded by AtPROPEP3 revealed that a C-terminal peptide fragment (AtPep3) inhibited the salt-induced bleaching of chlorophyll in seedlings. Conversely, knockdown AtPROPEP3 transgenic plants exhibited a hypersensitive phenotype under salinity stress, which was complemented by the AtPep3 peptide. This functional AtPep3 peptide region overlaps with an AtPep3 elicitor peptide that is related to the immune response of plants. Functional analyses with a receptor mutant of AtPep3 revealed that AtPep3 was recognized by the PEPR1 receptor and that it functions to increase salinity stress tolerance in plants. Collectively, these data indicate that AtPep3 plays a significant role in both salinity stress tolerance and immune response in Arabidopsis .

PEP725 Pan European Phenological Database

NASA Astrophysics Data System (ADS)

Koch, E.; Lipa, W.; Ungersböck, M.; Zach-Hermann, S.

2012-04-01

PEP725 is a 5 years project with the main object to promote and facilitate phenological research by delivering a pan European phenological database with an open, unrestricted data access for science, research and education. PEP725 is funded by EUMETNET (the network of European meteorological services), ZAMG and the Austrian ministry for science & research bm:w_f. So far 16 European national meteorological services and 7 partners from different nati-onal phenological network operators have joined PEP725. The data access is very easy via web-access from the homepage www.pep725.eu. Ha-ving accepted the PEP725 data policy and registry the data download can be done by different criteria as for instance the selection of a specific plant or all data from one country. At present more than 300 000 new records are available in the PEP725 data-base coming from 31 European countries and from 8150 stations. For some more sta-tions (154) META data (location and data holder) are provided. Links to the network operators and data owners are also on the webpage in case you have more sophisticated questions about the data. Another objective of PEP725 is to bring together network-operators and scientists by organizing workshops. In April 2012 the second of these workshops will take place on the premises of ZAMG. Invited speakers will give presentations spanning the whole study area of phenology starting from observations to modelling. Quality checking is also a big issue. At the moment we study the literature to find ap-propriate methods.

Into Our Hoods: Where Critical Performance Pedagogy Births Resistance

ERIC Educational Resources Information Center

Tintiangco-Cubales, Allyson; Daus-Magbual, Arlene; Desai, Maharaj; Sabac, Aldrich; Von Torres, Maynard

2016-01-01

This study focuses on Pin@y Educational Partnerships (PEP), an Ethnic Studies educational pipeline that the five authors have been part of. PEP is in direct opposition to neoliberalism by providing an educational experience for youth to positively transform themselves and their communities. As part of PEP's transformative curriculum, we employ…

Evaluation and Validation: A Look at the Program Effectiveness Panel.

ERIC Educational Resources Information Center

Cook, Nancy R.; And Others

The work of the Program Effectiveness Panel (PEP) of the United States Department of Education was examined. The PEP is the Department of Education's primary means of certifying or validating the effectiveness of educational programs. Thirty-three educational programs were validated by the PEP between January 1988 and December 1990. Over time,…

Workload, Job Satisfaction and Perceptions of Role Preparation of Principal Educational Psychologists in England.

ERIC Educational Resources Information Center

Male, Dawn B.; Male, Trevor

2003-01-01

Describes the results of a study which investigated workload, job satisfaction and perceptions of role preparation of Principal Educational Psychologists (PEPs) in England. Results indicated that PEPs have a generally positive attitude to the profession and express overall job satisfaction. Despite the overall satisfaction, PEPs found the job…

Converting a Staphylococcus aureus toxin into effective cyclic pseudopeptide antibiotics.

PubMed

Solecki, Olivia; Mosbah, Amor; Baudy Floc'h, Michèle; Felden, Brice

2015-03-19

Staphylococcus aureus produces peptide toxins that it uses to respond to environmental cues. We previously characterized PepA1, a peptide toxin from S. aureus, that induces lytic cell death of both bacterial and host cells. That led us to suggest that PepA1 has an antibacterial activity. Here, we demonstrate that exogenously provided PepA1 has activity against both Gram-positive and Gram-negative bacteria. We also see that PepA1 is significantly hemolytic, thus limiting its use as an antibacterial agent. To overcome these limitations, we converted PepA1 into nonhemolytic derivatives. Our most promising derivative is a cyclic heptapseudopeptide with inconsequential toxicity to human cells, enhanced stability in human sera, and sharp antibacterial activity. Mechanistically, linear and helical PepA1 derivatives form pores at the bacterial and erythrocyte surfaces, while the cyclic peptide induces bacterial envelope reorganization, with insignificant action on the erythrocytes. Our work demonstrates that bacterial toxins might be an attractive starting point for antibacterial drug development. Copyright © 2015 Elsevier Ltd. All rights reserved.

The effects of PEP-1-FK506BP on dry eye disease in a rat model.

PubMed

Kim, Dae Won; Lee, Sung Ho; Ku, Sae Kwang; Lee, Ji Eun; Cha, Hyun Ju; Youn, Jong Kyu; Kwon, Hyeok Yil; Park, Jong Hoon; Park, Eun Young; Cho, Sung-Woo; Han, Kyu Hyung; Park, Jinseu; Eum, Won Sik; Choi, Soo Young

2015-03-01

As FK506 binding proteins (FK506BPs) are known to play an important role in the regulation of a variety of biological processes related to cell survival, this study was designed to examined the protective effects of FK506 binding protein 12 (FK506BP) on low humidity air flow induced dry eye in a rat model using transduced PEP-1-FK506BP. After the topical application of PEP-1-FK506BP, tear volumes were markedly increased and significant prevention of cornea damage was observed compared with dry eye rats. Further, immunohistochemical analysis demonstrated that PEP-1-FK506BP markedly prevented damage to the cornea, the bulbar conjunctiva, and the palpebral conjunctiva epithelial lining compared with dry eye rats. In addition, caspase-3 and PARP expression levels were found to be decreased. These results demonstrated that topical application of PEP-1-FK506BP significantly ameliorates dry eye injury in an animal model. Thus, we suggest that PEP-1-FK506BP can be developed as a new ophthalmic drop to treat dry eye diseases.

Executive summary of the consensus document on post-exposure prophylaxis against HIV, HBV and HCV in adults and children.

PubMed

Polo Rodriguez, Rosa; Lozano, Fernando; González de Castro, Pedro; Jiménez, Ma Alonso; Miró, Oscar; Ramón Blanco, Jose; Moreno, David; Dueñas, Carlos; Muñoz Platón, Enriqueta; Fernández Escribano, Marina; Sanz Sanz, Jesús; Fumaz, Carmina; Santos, Ignacio; García, Federico; Téllez, Ma Jesús; González Montero, Raúl; Vals Jimenez, Ma Victoria; Losa, Juan Emilio; Valle Robles, Ma Luisa; Iribarren, Jose Antonio; Ortega, Enrique

2016-02-01

Post-exposure prophylaxis (PEP) can be a secondary measure to prevent infection by human immunodeficiency virus (HIV) when primary prevention has failed. PEP is advised for people with sporadic and exceptional risk exposure to HIV. This consensus document about occupational and non-occupational PEP recommendations aims to be a technical document for healthcare professionals. Its main objective is to facilitate the appropriate use of PEP. To this end, some recommendations have been established to assess the risk of transmission in different types of exposure, situations where PEP should be recommended, special circumstances to take into account, antiretroviral (ARV) guidelines including start and end of the treatment, early monitoring of tolerance and adherence to the treatment, subsequent monitoring of people exposed, independently of having received PEP or not, and need of psychological support. This document is intended for all professionals who work in clinical practice in the field of HIV infection. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Positive benefits: preventive impact of post-exposure prophylaxis awareness among those with diagnosed HIV.

PubMed

Dodds, C

2008-04-01

To consider the extent to which those presenting for post-exposure prophylaxis (PEP) after sexual risk had been encouraged to do so by their PEP-aware partners with (diagnosed) HIV. Thirty men who had completed the 2005 UK Gay Men's Sex Survey who said they had ever tried to get PEP took part in a 30 minute telephone interview. Fifteen men in the sample described a sexual exposure incident where they had knowledge that their partner was diagnosed with having HIV. Of these, only five knew about their partner's HIV diagnosis prior to sexual contact. The remaining 10 sought PEP because their sexual partner revealed his positive status following potential sexual exposure. Our analysis revealed that word of mouth from friends, sexual partners and health professionals played a key role in men's knowledge about the existence of PEP. It is important for HIV and sexual health specialists to ensure that PEP information is not only targeted at those who are tested negative for HIV or are untested but also to people with diagnosed HIV.

An interactive technology approach to educate older adults about drug interactions arising from over-the-counter self-medication practices.

PubMed

Neafsey, Patricia J; Strickler, Zoe; Shellman, Juliette; Chartier, Virginia

2002-01-01

An interactive computer program (Personal Education Program [PEP]) designed for the learning styles and psychomotor skills of older adults was used to teach older adults about potential drug interactions that can result from self-medication with over-the-counter (OTC) agents and alcohol. Subjects used the PEP on notebook computers equipped with infrared sensitive touchscreens. Subjects were recruited from senior centers. Those who met age, vision, literacy, independence, and medication use criteria were randomly assigned to one of three groups: (1) PEP plus information booklet; (2) information booklet only; or (3) control. A repeated measures (three time periods 2 weeks apart), three-group design was used. Users of PEP had significantly greater knowledge and self-efficacy scores than both the conventional and control groups at all three time points. The PEP group reported fewer adverse self-medication behaviors over time. Reported self-medication behaviors did not change over time for either the conventional or control groups. Subjects indicated a high degree of satisfaction with the PEP and reported their intent to make specific changes in self-medication behaviors.

Evaluation of Pressure Generated by Resistors From Different Positive Expiratory Pressure Devices.

PubMed

Fagevik Olsén, Monika; Carlsson, Maria; Olsén, Erik; Westerdahl, Elisabeth

2015-10-01

Breathing exercises with positive expiratory pressure (PEP) are used to improve pulmonary function and airway clearance. Different PEP devices are available, but there have been no studies that describe the pressure generated by different resistors. The purpose of this study was to compare pressures generated from the proprietary resistor components of 4 commercial flow-dependent PEP valves with all other parameters kept constant. Resistors from 4 flow-regulated PEP devices (Pep/Rmt system, Wellspect HealthCare; Pipe P breathing exerciser, Koo Medical Equipment; Mini-PEP, Philips Respironics [including resistors by Rüsch]; and 15-mm endo-adapter, VBM Medizintechnik) were tested randomly by a blinded tester at constant flows of 10 and 18 L/min from an external gas system. All resistors were tested 3 times. Resistors with a similar diameter produced statistically significant different pressures at the same flow. The differences were smaller when the flow was 10 L/min compared with 18 L/min. The differences were also smaller when the diameter of the resistor was increased. The pressures produced by the 4 resistors of the same size were all significantly different when measuring 1.5- and 2.0-mm resistors at a flow of 10 L/min and 2.0-mm resistors at a flow of 18 L/min (P < .001). There were no significant differences between any of the resistors when testing sizes of 4.5 and 5.0 mm at either flow. The Mini-PEP and adapter resistors gave the highest pressures. Pressures generated by the different proprietary resistor components of 4 commercial PEP devices were not comparable, even though the diameter of the resistors is reported to be the same. The pressures generated were significantly different, particularly when using small-diameter resistors at a high flow. Therefore, the resistors may not be interchangeable. This is important information for clinicians, particularly when considering PEP for patients who do not tolerate higher pressures. Copyright © 2015 by Daedalus Enterprises.

The Pan European Phenological Database PEP725: Data Content and Data Quality Control Procedures

NASA Astrophysics Data System (ADS)

Jurkovic, Anita; Hübner, Thomas; Koch, Elisabeth; Lipa, Wolfgang; Scheifinger, Helfried; Ungersböck, Markus; Zach-Hermann, Susanne

2014-05-01

Phenology - the study of the timing of recurring biological events in the animal and plant world - has become an important approach for climate change impact studies in recent years. It is therefore a "conditio sine qua non" to collect, archive, digitize, control and update phenological datasets. Thus and with regard to cross-border cooperation and activities it was necessary to establish, operate and promote a pan European phenological database (PEP725). Such a database - designed and tested under cost action 725 in 2004 and further developed and maintained in the framework of the EUMETNET program PEP725 - collects data from different European governmental and nongovernmental institutions and thus offers a unique compilation of plant phenological observations. The data follows the same classification scheme - the so called BBCH coding system - that makes datasets comparable. Europe had a long tradition in the observation of phenological events: the history of collecting phenological data and their usage in climatology began in 1751. The first datasets in PEP725 date back to 1868. However, there are only a few observations available until 1950. From 1951 onwards, the phenological networks all over Europe developed rapidly: Currently, PEP725 provides about 9 million records from 23 European countries (covering approximately 50% of Europe). To supply the data in a good and uniform quality it is essential and worthwhile to establish and develop data quality control procedures. Consequently, one of the main tasks within PEP725 is the conception of a multi-stage-quality control. Currently the tests are stepwise composed: completeness -, plausibility -, time consistency -, climatological - and statistical checks. In a nutshell: The poster exemplifies the status quo of the data content of the PEP725 database and incipient stages of used and planned quality controls, respectively. For more details, we would also like to promote and refer to the PEP725 website (http://www.pep725.eu) and invite additional institutions and regional services to join our program.

Molecular cloning and functional expression of atlantic salmon peptide transporter 1 in Xenopus oocytes reveals efficient intestinal uptake of lysine-containing and other bioactive di- and tripeptides in teleost fish.

PubMed

Rønnestad, Ivar; Murashita, Koji; Kottra, Gabor; Jordal, Ann-Elise; Narawane, Shailesh; Jolly, Cecile; Daniel, Hannelore; Verri, Tiziano

2010-05-01

Atlantic salmon (Salmo salar L.) is one of the most economically important cultured fish and also a key model species in fish nutrition. During digestion, dietary proteins are enzymatically cleaved and a fraction of degradation products in the form of di- and tripeptides translocates from the intestinal lumen into the enterocyte via the Peptide Transporter 1 (PepT1). With this in mind, a full-length cDNA encoding the Atlantic salmon PepT1 (asPepT1) was cloned and functionally characterized. When overexpressed in Xenopus laevis oocytes, asPepT1 operated as a low-affinity/high-capacity transport system, and its maximal transport activity slightly increased as external proton concentration decreased (varying extracellular pH from 6.5 to 8.5). A total of 19 tested di- and tripeptides, some with acknowledged bioactive properties, some containing lysine, which is conditionally growth limiting in fish, were identified as well transported substrates, with affinities ranging between approximately 0.5 and approximately 1.5 mmol/L. Analysis of body tissue distribution showed the highest levels of asPepT1 mRNA in the digestive tract. In particular, asPepT1 mRNA was present in all segments after the stomach, with higher levels in the pyloric caeca and midgut region and lower levels in the hindgut. Depriving salmon of food for 6 d resulted in a approximately 70% reduction of intestinal PepT1 mRNA levels. asPepT1 will allow systematic in vitro analysis of transport of selected di- and tripeptides that may be generated in Atlantic salmon intestine during gastrointestinal transit. Also, asPepT1 will be useful as a marker to estimate protein absorption function along the intestine under various physiological and pathological conditions.

Evaluation of a postexposure rabies prophylaxis protocol for domestic animals in Texas: 2000-2009.

PubMed

Wilson, Pamela J; Oertli, Ernest H; Hunt, Patrick R; Sidwa, Thomas J

2010-12-15

To determine whether postexposure rabies prophylaxis (PEP) in domestic animals, as mandated in Texas, has continued to be effective and to evaluate preexposure or postexposure vaccination failures from 2000 through 2009. Retrospective case series. 1,014 unvaccinated domestic animals (769 dogs, 126 cats, 72 horses, 39 cattle, 3 sheep, 4 goats, and 1 llama) that received PEP and 12 vaccinated domestic animals (7 dogs and 5 cats) with possible failure of protection. Zoonotic incident reports from 2000 through 2009 were reviewed for information regarding unvaccinated domestic animals that received PEP in accordance with the state protocol after exposure to a laboratory-confirmed rabid animal; reports also were reviewed for any preexposure or postexposure vaccination failures. The state-required PEP protocol was as follows: immediately vaccinate the animal against rabies, isolate the animal for 90 days, and administer booster vaccinations during the third and eighth weeks of the isolation period. From 2000 through 2009, 1,014 animals received PEP; no failures were recorded. One preexposure vaccination failure was recorded. The Texas PEP protocol was used during the 10-year period. Results indicated that an effective PEP protocol for unvaccinated domestic animals exposed to rabies was immediate vaccination against rabies, a strict isolation period of 90 days, and administration of booster vaccinations during the third and eighth weeks of the isolation period.

Orgyia pseudotsugata baculovirus p10 and polyhedron envelope protein genes: analysis of their relative expression levels and role in polyhedron structure.

PubMed

Gross, C H; Russell, R L; Rohrmann, G F

1994-05-01

To investigate the regulation of p10 and polyhedron envelope protein (PEP) gene expression and their role in polyhedron development, Orgyia pseudotsugata multinucleocapsid nuclear polyhedrosis viruses lacking these genes were constructed. Recombinant viruses were produced, in which the p10 gene, the PEP gene or both genes were disrupted with the beta-glucuronidase (GUS) or beta-galactosidase (lacZ) genes. GUS activity under the control of the PEP protein promoter was observed later in infection and its maximal expression was less than 10% the level for p10 promoter-GUS constructs. Tissues from O. pseudotsugata larvae infected with these recombinants were examined by electron microscopy. Cells from insects infected with the p10- viruses lacked p10-associated fibrillar structures, but fragments of polyhedron envelope-like structures were observed on the surface of some polyhedra. Immunogold labelling of cells infected with the p10-GUS+ virus with an antibody directed against PEP showed that the PEP was concentrated at the surface of polyhedra. Although polyhedra produced by p10 and PEP gene deletion mutants demonstrated what appeared to be a polyhedron envelope by transmission electron microscopy, scanning electron microscopy showed that they had irregular, pitted surfaces that were different from wild-type polyhedra. These data suggested that both p10 and PEP are important for the proper formation of the periphery of polyhedra.

The effectiveness of a squash eyewear promotion strategy

PubMed Central

Eime, R; Finch, C; Wolfe, R; Owen, N; McCarty, C

2005-01-01

Objective: To evaluate the protective eyewear promotion (PEP) project, which was a comprehensive educational strategy to increase the use of appropriate protective eyewear by squash players. Methods: An ecological study design was used. Four squash venues in one playing association were randomly chosen to receive PEP and four in another association maintained usual practice and hence formed a control group. The primary evaluation measurements were surveys of cross sectional samples of players carried out before and after the intervention. The surveys investigated players' knowledge, behaviours, and attitudes associated with the use of protective eyewear. The survey carried out after the intervention also determined players' exposure to PEP. Univariate and multivariate analyses were undertaken to describe differences at PEP venues from pre- to post-intervention and to compare these with the control venues. Results: The PEP players had 2.4 times the odds (95% confidence interval, 1.3 to 4.2) of wearing appropriate eyewear compared with control group players post-intervention, relative to the groups' pre-intervention baselines. Components of PEP, such as stickers and posters and the availability and prominent positioning of the project eyewear, were found to contribute to players adopting favourable eyewear behaviours. Conclusions: Components of the PEP intervention were shown to be effective. The true success will be the sustainability and dissemination of the project, favourable eyewear behaviours, and evidence of the prevention of eye injuries long into the future. PMID:16118310

Exploring the Potential of (99m)Tc(CO)3-Labeled Triazolyl Peptides for Tumor Diagnosis.

PubMed

Gaonkar, Raghuvir H; Ganguly, Soumya; Baishya, Rinku; Dewanjee, Saikat; Sinha, Samarendu; Gupta, Amit; Ganguly, Shantanu; Debnath, Mita C

2016-04-01

In recent years the authors have reported on (99m)Tc(CO)3-labeled peptides that serve as carriers for biomolecules or radiopharmaceuticals to the tumors. In continuation of that work they report the synthesis of a pentapeptide (Met-Phe-Phe-Gly-His; pep-1), a hexapeptide (Met-Phe-Phe-Asp-Gly-His; pep-2), and a tetrapeptide (Asp-Gly-Arg-His; pep-3) and the attachment of 3-amino-1,2,4-triazole to the β carboxylic function of the aspartic acid unit of pep-2 and pep-3. The pharmacophores were radiolabeled in high yields with [(99m)Tc(CO)3(H2O)3](+) metal aqua ion, characterized for their stability in serum and saline, as well as in His solution, and found to be substantially stable. B16F10 cell line binding studies showed favorable uptake and internalization. In vivo behavior of the radiolabeled triazolyl peptides was assessed in mice bearing induced tumor. The (99m)Tc(CO)3-triazolyl pep-3 demonstrated rapid urinary clearance and comparatively better tumor uptake. Imaging studies showed visualization of the tumor using (99m)Tc(CO)3-triazolyl pep-3, but due to high abdominal background, low delineation occurred. Based on the results further experiments will be carried out for targeting tumor with triazolyl peptides.

The Prison Education Project

NASA Astrophysics Data System (ADS)

Reese, Renford

2017-12-01

This article briefly compares the prison system in the United States with progressive correctional systems in the world, before pivoting to discuss the lessons learned from the author's development of the Prison Education Project (PEP). PEP has expanded educational opportunities for inmates in 12 Californian correctional facilities. With the assistance of 800 university student and faculty volunteers, PEP has serviced approximately 5,000 inmates in these facilities since 2011. By providing academic, life skills and career development programming, PEP aims to educate, empower and transform the lives of incarcerated individuals. This article is a summary of the development of PEP, examining programme outcomes and highlighting implementation, fundraising and branding strategies. The robust spirit of volunteerism is also a central component of the discussion, with the phenomenon of "reciprocal reflex" at the heart of the PEP volunteer experience. This reflex ignites the passion and gratitude of both volunteers and inmates. The volunteers learn just as much as they teach, and the inmates teach just as much as they learn. The fact that each group shows deep gratitude to the other for the learning experience creates an exciting symbiotic loop and an esprit de corps which inspires and empowers all involved. The "reciprocal reflex" leads to lifelong learning. This article captures the intricate dynamics of how PEP has evolved into the largest volunteer-based prison education programme of its kind in the United States.

The pepATTRACT web server for blind, large-scale peptide-protein docking.

PubMed

de Vries, Sjoerd J; Rey, Julien; Schindler, Christina E M; Zacharias, Martin; Tuffery, Pierre

2017-07-03

Peptide-protein interactions are ubiquitous in the cell and form an important part of the interactome. Computational docking methods can complement experimental characterization of these complexes, but current protocols are not applicable on the proteome scale. pepATTRACT is a novel docking protocol that is fully blind, i.e. it does not require any information about the binding site. In various stages of its development, pepATTRACT has participated in CAPRI, making successful predictions for five out of seven protein-peptide targets. Its performance is similar or better than state-of-the-art local docking protocols that do require binding site information. Here we present a novel web server that carries out the rigid-body stage of pepATTRACT. On the peptiDB benchmark, the web server generates a correct model in the top 50 in 34% of the cases. Compared to the full pepATTRACT protocol, this leads to some loss of performance, but the computation time is reduced from ∼18 h to ∼10 min. Combined with the fact that it is fully blind, this makes the web server well-suited for large-scale in silico protein-peptide docking experiments. The rigid-body pepATTRACT server is freely available at http://bioserv.rpbs.univ-paris-diderot.fr/services/pepATTRACT. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

75 FR 33748 - Amateur Radio Use of the Allocation at 5 MHz

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-15

... envelope power (PEP). 3. The existing amateur radio use of the 60 meter band represents a balancing of... Comment Filing System (ECFS), (2) the Federal Government's eRulemaking Portal, or (3) by filing paper... transmitter output power in modern amateur radio transceivers is 100 W PEP, and that the present 50 W PEP...

Diblock Terpolymers Are Tunable and pH Responsive Vehicles To Increase Hydrophobic Drug Solubility for Oral Administration.

PubMed

Tale, Swapnil; Purchel, Anatolii A; Dalsin, Molly C; Reineke, Theresa M

2017-11-06

Synthetic polymers offer tunable platforms to create new oral drug delivery vehicles (excipients) to increase solubility, supersaturation maintenance, and bioavailability of poorly aqueous soluble pharmaceutical candidates. Five well-defined diblock terpolymers were synthesized via reversible addition-fragmentation chain transfer polymerization (RAFT) and consist of a first block of either poly(ethylene-alt-propylene) (PEP), poly(N-isopropylacrylamide) (PNIPAm), or poly(N,N-diethylaminoethyl methacrylate) (PDEAEMA) and a second hydrophilic block consisting of a gradient copolymer of N,N-dimethylacrylamide (DMA) and 2-methacrylamidotrehalose (MAT). This family of diblock terpolymers offers hydrophobic, hydrophilic, or H-bonding functionalities to serve as noncovalent sites of drug binding. Drug-polymer spray dried dispersions (SDDs) were created with a model drug, probucol, and characterized by differential scanning calorimetry (DSC). These studies revealed that probucol crystallinity decreased with increasing H-bonding sites available in the polymer. The PNIPAm-b-P(DMA-grad-MAT) systems revealed the best performance at pH 6.5, where immediate probucol release and effective maintenance of 100% supersaturation was found, which is important for facilitating drug solubility in more neutral conditions (intestinal environment). However, the PDEAEMA-b-P(DMA-grad-MAT) system revealed poor probucol dissolution at pH 6.5 and 5.1. Alternatively, at an acidic pH of 3.1, a rapid and high dissolution profile and effective supersaturation maintenance of up to 90% of the drug was found, which could be useful for triggering drug release in acidic environments (stomach). The PEP-b-P(DMA-grad-MAT) system showed poor performance (only ∼20% of drug solubility at pH 6.5), which was attributed to the low solubility of the polymers in the dissolution media. This work demonstrates the utility of diblock terpolymers as a potential new excipient platform to optimize design parameters for triggered release and solubilizing hydrophobic drug candidates for oral delivery.

Cloning of oligopeptide transport carrier PepT1 and comparative analysis of PepT1 messenger ribonucleic acid expression in response to dietary nitrogen levels in yak () and indigenous cattle () on the Qinghai-Tibetan plateau.

PubMed

Wang, H C; Shi, F Y; Hou, M J; Fu, X Y; Long, R J

2016-08-01

The gastrointestinal lumen can directly absorb all di- and tripeptide protein degradation products, and oligopeptide absorption depends on the specific peptide transport carriers, which are located in gastrointestinal epithelial cells on the brush border membrane. Yak () use N more efficiently than cattle do, which implies that yak have a specific mechanism of nonprotein utilization including a peptide absorption mechanism. However, this mechanism has not been clarified. Our objective was to explore whether yak possess any adaptive mechanisms of peptide absorption to survive in the harsh foraging environment of the Qinghai-Tibetan plateau. Twelve castrated males of each of 2 genotypes, yak () and indigenous cattle (), were fed diets of various N levels. The yak PepT1 (yPepT1) cDNA was cloned in omasum epithelial tissue. Our results showed that the full-length yPepT1 cDNA contains 2,805 bp, and a 2,121-bp open reading frame encodes a putative protein of 707 AA residues. The yPepT1 AA sequence identified 5 putative extracellular N-glycosylation sites (Asn, Asn, Asn, Asn, and Asn), 2 putative intracellular protein kinase A sites (Ser and Thr), and 3 intracellular putative protein kinase C sites (Ser, Ser, and Ser). The yPepT1 AA sequence was 99, 95, 86, and 83% identical to PepT1 from cattle (), sheep (), pigs (), and humans (), respectively. The relative PepT1 mRNA expression for indigenous cattle was greater than yak in the rumen, omasum, duodenum, ileum, and liver ( < 0.001); however, it was lower in jejunum tissue ( < 0.01). The relative PepT1 mRNA expression in response to increasing dietary N for both genotypes were linear in the rumen and jejunum ( < 0.10); quadratic or cubic in the reticulum ( < 0.01); linear or quadratic in the duodenum, ileum, and liver ( ≤ 0.01); and linear, quadratic, or cubic in the omasum ( < 0.001). Moreover, there were significant interactions between genotype and dietary N in rumen, reticulum, omasum, duodenum, jejunum, ileum, and liver tissues. In conclusion, the PepT1 profile and expression in gastrointestinal epithelial cells of yak varied from those of cattle, implying that yak have evolved a peptide transport mechanism to adapt the environment of the Qinghai-Tibetan plateau.

Cost-effectiveness of rabies post exposure prophylaxis in Iran.

PubMed

Hatam, Nahid; Esmaelzade, Firooz; Mirahmadizadeh, Alireza; Keshavarz, Khosro; Rajabi, Abdolhalim; Afsar Kazerooni, Parvin; Ataollahi, Marzieh

2014-01-01

The rabies is one of the most important officially-known viral zoonotic diseases for its global distribution, outbreak, high human and veterinary costs, and high death rate and causes high economic costs in different countries of the world every year. The rabies is the deadliest disease and if the symptoms break out in a person, one will certainly die. However, the deaths resulting from rabies can be prevented by post-exposure prophylaxis. To do so, in Iran and most of the countries in the world, all the people who are exposed to animal bite receive Post-Exposure Prophylaxis (PEP) treatment. The present survey aimed to investigate the cost-effectiveness of PEP in southern Iran. The present study estimated the PEP costs from the government`s Perspective with step-down method for the people exposed to animal bite, estimated the number of DALYs prevented by PEP in the individuals using decision Tree model, and computed the Incremental cost-effectiveness Ratio. The information collected of all reported animal bite cases (n=7111) in Fars Province, who referred rabies registries in urban and rural health centers to receive active care. Performing the PEP program cost estimated 1,052,756.1 USD for one  year and the estimated cost for the treatment of each animal bite case and each prevented death was 148.04 and 5945.42 USD, respectively. Likewise 4,509.82 DALYs were prevented in southern Iran in 2011 by PEP program. The incremental cost-effectiveness ratio for each DALY was estimated to be 233.43 USD. In addition to its full effectiveness in prophylaxis from rabies, PEP program saves the financial resources of the society, as well. This study showed performing PEP to be more cost-effective.

Efficient delivery of cell impermeable phosphopeptides by a cyclic peptide amphiphile containing tryptophan and arginine.

PubMed

Nasrolahi Shirazi, Amir; Tiwari, Rakesh Kumar; Oh, Donghoon; Banerjee, Antara; Yadav, Arpita; Parang, Keykavous

2013-05-06

Phosphopeptides are valuable reagent probes for studying protein-protein and protein-ligand interactions. The cellular delivery of phosphopeptides is challenging because of the presence of the negatively charged phosphate group. The cellular uptake of a number of fluorescent-labeled phosphopeptides, including F'-GpYLPQTV, F'-NEpYTARQ, F'-AEEEIYGEFEAKKKK, F'-PEpYLGLD, F'-pYVNVQN-NH2, and F'-GpYEEI (F' = fluorescein), was evaluated in the presence or absence of a [WR]4, a cyclic peptide containing alternative arginine (R) and tryptophan (W) residues, in human leukemia cells (CCRF-CEM) after 2 h incubation using flow cytometry. [WR]4 improved significantly the cellular uptake of all phosphopeptides. PEpYLGLD is a sequence that mimics the pTyr1246 of ErbB2 that is responsible for binding to the Chk SH2 domain. The cellular uptake of F'-PEpYLGLD was enhanced dramatically by 27-fold in the presence of [WR]4 and was found to be time-dependent. Confocal microscopy of a mixture of F'-PEpYLGLD and [WR]4 in live cells exhibited intracellular localization and significantly higher cellular uptake compared to that of F'-PEpYLGLD alone. Transmission electron microscopy (TEM) and isothermal calorimetry (ITC) were used to study the interaction of PEpYLGLD and [WR]4. TEM results showed that the mixture of PEpYLGLD and [WR]4 formed noncircular nanosized structures with width and height of 125 and 60 nm, respectively. ITC binding studies confirmed the interaction between [WR]4 and PEpYLGLD. The binding isotherm curves, derived from sequential binding models, showed an exothermic interaction driven by entropy. These studies suggest that amphiphilic peptide [WR]4 can be used as a cellular delivery tool of cell-impermeable negatively charged phosphopeptides.

Post-exposure prophylaxis use and recurrent exposure to HIV among men who have sex with men who use crystal methamphetamine

PubMed Central

Oldenburg, Catherine E.; Jain, Sachin; Mayer, Kenneth H.; Mimiaga, Matthew J.

2014-01-01

Background Men who have sex with men (MSM) who use crystal methamphetamine (CM) are at increased risk for HIV infection. Post-exposure prophylaxis (PEP) is a useful HIV prevention strategy if individuals are able to identify high-risk exposures and seek timely care, however to date there has been limited data on the use of PEP by CM users. Methods A retrospective cohort study of all PEP prescriptions (N=1,130 prescriptions among 788 MSM) at Fenway Community Health in Boston, MA was undertaken. Multivariable models were used to assess the association between CM use during exposure (7.4% used CM during exposure) and chronically (7.4% of MSM were chronic CM users) and individual-level and event-level outcomes among MSM who used PEP at least once. Results Compared to those who had not used CM, MSM PEP users who used CM more frequently returned for repeat PEP (aOR 5.13, 95%CI 2.82 to 9.34) and were significantly more likely to seroconvert over the follow-up period (aHR 3.61, 95%CI 1.51 to 8.60). MSM who used CM had increased odds of unprotected anal intercourse as the source of exposure (aOR 2.12, 95%CI 1.16 to 3.87) and knowing that their partner was HIV infected (aOR 2.27, 95%CI 1.42 to 3.64). Conclusions While MSM who use CM may have challenges accessing ART in general, these data highlight the fact that those who were able to access PEP subsequently remained at increased risk of HIV seroconversion Counseling and/or substance use interventions during the PEP course should be considered for CM-using MSM. PMID:25482500

Large Energetic Particle Pressures in Solar Cycles 23 and 24

NASA Astrophysics Data System (ADS)

Lario, D.; Decker, R. B.; Roelof, E. C.; Viñas, A. F.; Wimmer-Schweingruber, R. F.; Berger, L.

2017-09-01

We study periods of elevated energetic particle intensities observed at the L1 Sun-Earth Lagrangian point when the partial energy density associated with energetic (≥80 keV) particles (PEP) dominates that of the local magnetic field (PB) and thermal plasma populations (PPLS). These periods are not uncommon and are frequently observed prior to the passage of interplanetary (IP) shocks. Because of the significant decreases in key solar wind parameters observed during solar cycle 24 [e.g., 1], we were motivated to perform a comparative statistical analysis to determine if the occurrence rate of periods when PEP exceeded PB or PPLS, or both, differed between solar cycles 23 and 24. We find that the general decrease of PB and PPLS in solar cycle 24 was also accompanied by a general decrease of periods with elevated PEP. The result is that solar cycle 24 showed a lower number of time intervals dominated by PEP. We analyze whether these differences can be related to the properties of the IP shocks observed at L1. Incomplete datasets of shock parameters do not show significant differences between solar cycles 23 and 24 that would allow us to explain the difference in the number of periods with PEP>PB and PEP>PPLS. We analyze then the averaged plasma parameters measured in the upstream region of the shocks and find significantly lower solar wind proton temperatures and magnetic field magnitude upstream of IP shocks in solar cycle 24 compared with those in solar cycle 23. These factors, together with the lower level of solar activity, may explain the lower particle intensities in solar cycle 24 and hence the fewer events with PEP>PB and PEP>PPLS.

Transferrin receptor-targeted pH-sensitive micellar system for diminution of drug resistance and targetable delivery in multidrug-resistant breast cancer

PubMed Central

Gao, Wei; Ye, Guihua; Duan, Xiaochuan; Yang, Xiaoying; Yang, Victor C

2017-01-01

The emergence of drug resistance is partially associated with overproduction of transferrin receptor (TfR). To overcome multidrug resistance (MDR) and achieve tumor target delivery, we designed a novel biodegradable pH-sensitive micellar system modified with HAIYPRH, a TfR ligand (7pep). First, the polymers poly(l-histidine)-coupled polyethylene glycol-2000 (PHIS-PEG2000) and 7pep-modified 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-polyethylene glycol-2000 (7pep-DSPE-PEG2000) were synthesized, and the mixed micelles were prepared by blending of PHIS-PEG2000 and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-polyethylene glycol-2000 (DSPE-PEG2000) or 7pep-DSPE-PEG2000 (7-pep HD micelles). The micelles exhibited good size uniformity, high encapsulation efficiency, and a low critical micelle concentration. By changing the polymer ratio in the micellar formulation, the pH response range was specially tailored to pH ~6.0. When loaded with antitumor drug doxorubicin (DOX), the micelle showed an acid pH-triggering drug release profile. The cellular uptake and cytotoxicity study demonstrated that 7-pep HD micelles could significantly enhance the intracellular level and antitumor efficacy of DOX in multidrug-resistant cells (MCF-7/Adr), which attributed to the synergistic effect of poly(l-histidine)-triggered endolysosom escape and TfR-mediated endocytosis. Most importantly, the in vivo imaging study confirmed the target-ability of 7-pep HD micelles to MDR tumor. These findings indicated that 7-pep HD micelles would be a promising drug delivery system in the treatment of drug-resistant tumors. PMID:28223798

Molecular biology of C4 phosphoenolpyruvate carboxylase: Structure, regulation and genetic engineering.

PubMed

Rajagopalan, A V; Devi, M T; Raghavendra, A S

1994-02-01

Three to four families of nuclear genes encode different isoforms of phosphoenolpyruvate (PEP) carboxylase (PEPC): C4-specific, C3 or etiolated, CAM and root forms. C4 leaf PEPC is encoded by a single gene (ppc) in sorghum and maize, but multiple genes in the C4-dicot Flaveria trinervia. Selective expression of ppc in only C4-mesophyll cells is proposed to be due to nuclear factors, DNA methylation and a distinct gene promoter. Deduced amino acid sequences of C4-PEPC pinpoint the phosphorylatable serine near the N-terminus, C4-specific valine and serine residues near the C-terminus, conserved cysteine, lysine and histidine residues and PEP binding/catalytic sites. During the PEPC reaction, PEP and bicarbonate are first converted into carboxyphosphate and the enolate of pyruvate. Carboxyphosphate decomposes within the active site into Pi and CO2, the latter combining with the enolate to form oxalacetate. Besides carboxylation, PEPC catalyzes a HCO3 (-)-dependent hydrolysis of PEP to yield pyruvate and Pi. Post-translational regulation of PEPC occurs by a phosphorylation/dephosphorylation cascade in vivo and by reversible enzyme oligomerization in vitro. The interrelation between phosphorylation and oligomerization of the enzyme is not clear. PEPC-protein kinase (PEPC-PK), the enzyme responsible for phosphorylation of PEPC, has been studied extensively while only limited information is available on the protein phosphatase 2A capable of dephosphorylating PEPC. The C4 ppc was cloned and expressed in Escherichia coli as well as tobacco. The transformed E. coli produced a functional/phosphorylatable C4 PEPC and the transgenic tobacco plants expressed both C3 and C4 isoforms. Site-directed mutagenesis of ppc indicates the importance of His(138), His(579) and Arg(587) in catalysis and/or substrate-binding by the E. coli enzyme, Ser(8) in the regulation of sorghum PEPC. Important areas for further research on C4 PEPC are: mechanism of transduction of light signal during photoactivation of PEPC-PK and PEPC in leaves, extensive use of site-directed mutagenesis to precisely identify other key amino acid residues, changes in quarternary structure of PEPC in vivo, a high-resolution crystal structure, and hormonal regulation of PEPC expression.

One-year study of occupational human immunodeficiency virus postexposure prophylaxis.

PubMed

Garb, James Robert

2002-03-01

A 12-month experience with human immunodeficiency virus (HIV) postexposure prophylaxis (PEP) in a tertiary care center was evaluated for timeliness of treatment and adherence to treatment recommendations. Forty-six health care workers were started on HIV PEP. Risk status of the source patient, rather than type of exposure, was a significant determinant for both initiating and completing treatment. Of those exposed to HIV-positive sources, 79% completed the full 28 days of therapy. Only 22% of all health care workers who started PEP discontinued treatment because of adverse effects. Excluding three cases with significant delays in reporting and one in which treatment was controversial, the mean time from exposure to first dose of PEP was 1 hour and 46 minutes. The use of a defined treatment protocol, with supporting educational material and PEP medication immediately available, is an effective way of managing HIV exposures.

Validation of PEP-II Resonantly Excited Turn-by-Turn BPM Data

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

Yan, Yiton T.; Cai, Yunhai; Colocho, William.

2007-06-28

For optics measurement and modeling of the PEP-II electron (HER) and position (LER) storage rings, we have been doing well with MIA [1] which requires analyzing turn-by-turn Beam Position Monitor (BPM) data that are resonantly excited at the horizontal, vertical, and longitudinal tunes. However, in anticipation that certain BPM buttons and even pins in the PEP-II IR region would be missing for the run starting in January 2007, we had been developing a data validation process to reduce the effect due to the reduced BPM data accuracy on PEP-II optics measurement and modeling. Besides the routine process for ranking BPMmore » noise level through data correlation among BPMs with a singular-value decomposition (SVD), we could also check BPM data symplecticity by comparing the invariant ratios. Results from PEP-II measurement will be presented.« less

Genetic Characterization and Physiological Role of Endopeptidase O from Lactobacillus helveticus CNRZ32

PubMed Central

Chen, Yo-Shen; Steele, James L.

1998-01-01

A previously identified insert expressing an endopeptidase from a Lactobacillus helveticus CNRZ32 genomic library was characterized. Nucleotide sequence analysis revealed an open reading frame of 1,941 bp encoding a putative protein of 71.2 kDa which contained a zinc-protease motif. Protein homology searches revealed that this enzyme has 40% similarity with endopeptidase O (PepO) from Lactococcus lactis P8-2-47. Northern hybridization revealed that pepO is monocistronic and is expressed throughout the growth phase. CNRZ32 derivatives lacking PepO activity were constructed via gene replacement. Enzyme assays revealed that the PepO mutant had significantly reduced endopeptidase activity when compared to CNRZ32 with two of the three substrates examined. Growth studies indicated that PepO has no detectable effect on growth rate or acid production by Lactobacillus helveticus CNRZ32 in amino acid defined or skim milk medium. PMID:9726890

Acute effects of MDMA on autonomic cardiac activity and their relation to subjective prosocial and stimulant effects.

PubMed

Clark, Christine M; Frye, Charles G; Wardle, Margaret C; Norman, Greg J; de Wit, Harriet

2015-03-01

MDMA is a stimulant with unique "prosocial" effects, the physiological and pharmacological mechanisms of which are unknown. Here, we examine the relationship of measures of parasympathetic and sympathetic nervous system activity to the prosocial effects of MDMA. Parasympathetic activity was measured using respiratory sinus arrhythmia (RSA) and sympathetic activity using pre-ejection period (PEP). Over three sessions, 33 healthy volunteers received placebo, 0.75 mg/kg, and 1.5 mg/kg MDMA under counterbalanced, double-blind conditions, while we measured subjective feelings, RSA, and PEP. RSA and PEP data were available for 26 and 21 participants, respectively. MDMA increased prosocial and stimulated feelings, decreased RSA, and decreased PEP. At 1.5 mg/kg, subjective prosocial effects correlated with stimulated feelings and PEP, but not RSA. This suggests sympathetic, rather than parasympathetic, effects relate to the prosocial effects of MDMA. © 2014 Society for Psychophysiological Research.

Further Empirical Data on the Psychoeducational Profile-Revised (PEP-R): Reliability and Validation with the Vineland Adaptive Behavior Scales

ERIC Educational Resources Information Center

Villa, Susanna; Micheli, Enrico; Villa, Laura; Pastore, Valentina; Crippa, Alessandro; Molteni, Massimo

2010-01-01

The PEP-R (psychoeducational profile revised) is an instrument that has been used in many countries to assess abilities and formulate treatment programs for children with autism and related developmental disorders. To the end to provide further information on the PEP-R's psychometric properties, a large sample (N = 137) of children presenting…

Parenting for Literacy Development and Educational Success: An Examination of the Parent Education Profile. Research Brief #3

ERIC Educational Resources Information Center

Prins, Esther; Toso, Blaire Willson

2008-01-01

The Parent Education Profile (PEP) is an instrument that rates parents' support for children's literacy development. This study examined how the PEP portrays the ideal parent, its assumptions about parenting and education, and the values and ideals it promotes. In sum, many aspects of the PEP evaluate parents by the mainstream (White,…

75 FR 27580 - Notice of Lodging of Consent Decree Under the Clean Air Act

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-17

... given that on May 10, 2010, a proposed Consent Decree (``Decree'') in United States v. The Pep Boys... (``CAA'') against The Pep Boys--Manny, Moe & Jack, and Baja, Inc., for violations of the mobile source.... The Pep Boys--Manny, Moe & Jack, and Baja, Inc., Civil Action No. 10-cv-00745, (D.D.C.), D.J. Ref. 90...

Expression of PEP carboxylase from Escherichia coli complements the phenotypic effects of pyruvate carboxylase mutations in Saccharomyces cerevisiae.

PubMed

Flores, C L; Gancedo, C

1997-08-04

We investigated the effects of the expression of the Escherichia coli ppc gene encoding PEP carboxylase in Saccharomyces cerevisiae mutants devoid of pyruvate carboxylase. Functional expression of the ppc gene restored the ability of the yeast mutants to grow in glucose-ammonium medium. Growth yield in this medium was the same in the transformed yeast than in the wild type although the growth rate of the transformed yeast was slower. Growth in pyruvate was slowed down in the transformed strain, likely due to a futile cycle produced by the simultaneous action of PEP carboxykinase and PEP carboxylase.

RNA-dependent RNA polymerase (NIb) of the potyviruses is an avirulence factor for the broad-spectrum resistance gene Pvr4 in Capsicum annuum cv. CM334.

PubMed

Kim, Saet-Byul; Lee, Hye-Young; Seo, Seungyeon; Lee, Joo Hyun; Choi, Doil

2015-01-01

Potyviruses are one of the most destructive viral pathogens of Solanaceae plants. In Capsicum annuum landrace CM334, a broad-spectrum gene, Pvr4 is known to be involved in resistance against multiple potyviruses, including Pepper mottle virus (PepMoV), Pepper severe mosaic virus (PepSMV), and Potato virus Y (PVY). However, a potyvirus avirulence factor against Pvr4 has not been identified. To identify the avirulence factor corresponding to Pvr4 in potyviruses, we performed Agrobacterium-mediated transient expressions of potyvirus protein coding regions in potyvirus-resistant (Pvr4) and -susceptible (pvr4) pepper plants. Hypersensitive response (HR) was observed only when a RNA-dependent RNA polymerase (NIb) of PepMoV, PepSMV, or PVY was expressed in Pvr4-bearing pepper leaves in a genotype-specific manner. In contrast, HR was not observed when the NIb of Tobacco etch virus (TEV), a virulent potyvirus, was expressed in Pvr4-bearing pepper leaves. Our results clearly demonstrate that NIbs of PepMoV, PepSMV, and PVY serve as avirulence factors for Pvr4 in pepper plants.

Overexpression of the PepF Oligopeptidase Inhibits Sporulation Initiation in Bacillus subtilis†

PubMed Central

Kanamaru, Kyoko; Stephenson, Sophie; Perego, Marta

2002-01-01

The yjbG gene encoding the homologue of the PepF1 and PepF2 oligoendopeptidases of Lactococcus lactis (Monnet et al., J. Biol. Chem. 269:32070–32076, 1994; Nardi et al., J. Bacteriol. 179:4164–4171, 1997) has been identified in Bacillus subtilis as an inhibitor of sporulation initiation when present in the cells on a multicopy plasmid. Genetic analysis suggested that the inhibitory effect is due to hydrolysis of the PhrA peptide in a form as small as the pentapeptide (ARNQT). Inactivation of PhrA results in deregulation of the RapA phosphatase and thus dephosphorylation of the Spo0F∼∼P response regulator component of the phosphorelay for sporulation initiation. When overexpressed, the B. subtilis PepF is most likely hydrolyzing additional peptides of the Phr family, as is the case for PhrC involved in control of competence development. Chromosomal inactivation of the yjbG/pepF gene did not give rise to any detectable phenotype. The function of PepF in B. subtilis remains unknown. Limited experiments with a yjbG paralogue called yusX indicated that a frameshift is present, making the corresponding gene product inactive. PMID:11741842

Performance perceptions and self-focused attention predict post-event processing after a real-life social performance situation.

PubMed

Helbig-Lang, Sylvia; Poels, Vanja; Lincoln, Tania M

2016-11-01

Cognitive approaches to social anxiety suggest that an excessive brooding about one's performance in a social situation (post-event processing; PEP) is involved in the maintenance of anxiety. To date, most studies investigating PEP were conducted in laboratory settings. The present study sought to replicate previous findings on predictors of PEP after a naturalistic social performance situation. Sixty-five students, who had to give an evaluated presentation for credits, completed measures of trait social anxiety. Immediately after their presentation, participants rated state anxiety and attentional focus during the presentation, and provided an overall evaluation of their performance. One week after the presentation, they rated PEP during the preceding week, and reappraised their performance. Regression analyses demonstrated that the performance ratings after and self-focused attention during the presentation were unique predictors of PEP over and above the effects of trait and state anxiety. There was no evidence that PEP was associated with a biased recall of individual performance evaluations. The results support cognitive theories that emphasize the importance of negative self-perceptions in the development of social anxiety and related processes, and underline self-focused attention and self-evaluative processes as important targets during treatment.

Development and validation of the trait and state versions of the Post-Event Processing Inventory.

PubMed

Blackie, Rebecca A; Kocovski, Nancy L

2017-03-01

Post-event processing (PEP) refers to negative and prolonged rumination following anxiety-provoking social situations. Although there are scales to assess PEP, they are situation-specific, some targeting only public-speaking situations. Furthermore, there are no trait measures to assess the tendency to engage in PEP. The purpose of this research was to create a new measure of PEP, the Post-Event Processing Inventory (PEPI), which can be employed following all types of social situations and includes both trait and state forms. Over two studies (study 1, N = 220; study 2, N = 199), we explored and confirmed the factor structure of the scale with student samples. For each form of the scale, we found and confirmed that a higher-order, general PEP factor could be inferred from three sub-domains (intensity, frequency, and self-judgment). We also found preliminary evidence for the convergent, concurrent, discriminant/divergent, incremental, and predictive validity for each version of the scale. Both forms of the scale demonstrated excellent internal consistency and the trait form had excellent two-week test-retest reliability. Given the utility and versatility of the scale, the PEPI may provide a useful alternative to existing measures of PEP and rumination.

Evaluation of 111In-labeled EPep and FibPep as tracers for fibrin SPECT imaging.

PubMed

Starmans, Lucas W E; van Duijnhoven, Sander M J; Rossin, Raffaella; Berben, Monique; Aime, Silvio; Daemen, Mat J A P; Nicolay, Klaas; Grüll, Holger

2013-11-04

Fibrin targeting is an attractive strategy for nuclear imaging of thrombosis, atherosclerosis and cancer. Recently, FibPep, an (111)In-labeled fibrin-binding peptide, was established as a tracer for fibrin SPECT imaging and was reported to allow sensitive detection of minute thrombi in mice using SPECT. In this study, we developed EPep, a novel (111)In-labeled fibrin-binding peptide containing the fibrin-binding domain of the clinically verified EP-2104R peptide, and sought to compare the potential of EPep and FibPep as tracers for fibrin SPECT imaging. In vitro, both EPep and FibPep showed high stability in serum, but were less stable in liver and kidney homogenate assays. Both peptide probes displayed comparable affinities toward human and mouse derived fibrin (Kd ≈ 1 μM), and similarly to FibPep, EPep showed fast blood clearance, low nontarget uptake and high thrombus uptake (6.8 ± 1.2% ID g(-1)) in a mouse carotid artery thrombosis model. Furthermore, EPep showed a similar affinity toward rat derived fibrin (Kd ≈ 1 μM), displayed high thrombus uptake in a rat carotid artery thrombosis model (0.74 ± 0.39% ID g(-1)), and allowed sensitive detection of thrombosis in rats using SPECT. In contrast, FibPep displayed a significantly lower affinity toward rat derived fibrin (Kd ≈ 14 μM) and low uptake in rat thrombi (0.06 ± 0.02% ID g(-1)) and did not allow clear visualization of carotid artery thrombosis in rats using SPECT. These results were confirmed ex vivo by autoradiography, which showed a 7-fold higher ratio of activity in the thrombus over the contralateral carotid artery for EPep in comparison to FibPep. These findings suggest that the FibPep binding fibrin epitope is not fully homologous between humans and rats, and that preclinical rat models of disease should not be employed to gauge the clinical potential of FibPep. In conclusion, both peptides showed approximately similar metabolic stability and affinity toward human and mouse derived fibrin, and displayed high thrombus uptake in a mouse carotid artery thrombosis model. Therefore, both EPep and FibPep are promising fibrin targeted tracers for translation into clinical settings to serve as novel tools for molecular imaging of fibrin.

Methods/Labor Standards Application Program - Phase IV

DTIC Science & Technology

1985-01-01

Engine Platform a. Pressure switch b. Compressor motor c. Voltage regulator d. Open and clean generator exciter and main windings S3 . Main Collector...clean motors b. Slip rings Gantry #3 Annual: S2. Engine Platform a. Pressure switch b. Compressor motor Voltage regulator d. Open and clean generator...Travel Motors Open and clean motorsa. b. Slip rings Gantry #4 S2 . S3. S4 . S5 . Engine Platform a. Pressure switch b. Compressor motor Voltage regulator

PEGylated Polyamidoamine dendrimer conjugated with tumor homing peptide as a potential targeted delivery system for glioma.

PubMed

Jiang, Yan; Lv, Lingyan; Shi, Huihui; Hua, Yabing; Lv, Wei; Wang, Xiuzhen; Xin, Hongliang; Xu, Qunwei

2016-11-01

Glioblastoma multiforme (GBM) is the most common and aggressive primary central nervous system (CNS) tumor with a short survival time. The failure of chemotherapy is ascribed to the low transport of chemotherapeutics across the Blood Brain Tumor Barrier (BBTB) and poor penetration into tumor tissue. In order to overcome the two barriers, small nanoparticles with active targeted capability are urgently needed for GBM drug delivery. In this study, we proposed PEGylated Polyamidoamine (PAMAM) dendrimer nanoparticles conjugated with glioma homing peptides (Pep-1) as potential glioma targeting delivery system (Pep-PEG-PAMAM), where PEGylated PAMAM dendrimer nanoparticle was utilized as carrier due to its small size and perfect penetration into tumor and Pep-1 was used to overcome BBTB via interleukin 13 receptor α2 (IL-13Rα2) mediated endocytosis. The preliminary availability and safety of Pep-PEG-PAMAM as a nanocarrier for glioma was evaluated. In vitro results indicated that a significantly higher amount of Pep-PEG-PAMAM was endocytosed by U87 MG cells. In vivo fluorescence imaging of U87MG tumor-bearing mice confirmed that the fluorescence intensity at glioma site of targeted group was 2.02 folds higher than that of untargeted group (**p<0.01), and glioma distribution experiment further revealed that Pep-PEG-PAMAM exhibited a significantly enhanced accumulation and improved penetration at tumor site. In conclusion, Pep-1 modified PAMAM was a promising nanocarrier for targeted delivery of brain glioma. Copyright © 2016 Elsevier B.V. All rights reserved.

A case study for integrated STEM outreach in an urban setting using a do-it-yourself vertical jump measurement platform.

PubMed

Drazan, John F; Danielsen, Heather; Vercelletto, Matthew; Loya, Amy; Davis, James; Eglash, Ron

2016-08-01

The purpose of this study was to develop and deploy a low cost vertical jump platform using readily available materials for Science, Technology, Engineering, and Mathematics (STEM) education and outreach in the inner city. The platform was used to measure the jumping ability of participants to introduce students to the collection and analysis of scientific data in an engaging, accessible manner. This system was designed and fabricated by a student team of engineers as part of a socially informed engineering and design class. The vertical jump platform has been utilized in 10 classroom lectures in physics and biology. The system was also used in an after school program in which high school volunteers prepared a basketball based STEM outreach program, and at a community outreach events with over 100 participants. At present, the same group of high school students are now building their own set of vertical jump platform under the mentorship of engineering undergraduates. The construction and usage of the vertical jump platform provides an accessible introduction to the STEM fields within the urban community.

Coaching Science Stars. Pep Talk and Play Book for Real-World Problem Solving.

ERIC Educational Resources Information Center

Barkman, Robert C.

This manual adapts the pedagogy used on the playing field, the studio, and the stage to the classroom. This method, called "Pep Talk," encourages teachers to: (1) create a need to know; (2) challenge students to know; (3) show how to know; (4) apply know-how; and (5) know how to inspire cooperation. Pep talk is the method coaches use when they…

PEP solar array definition study

NASA Technical Reports Server (NTRS)

1979-01-01

The power extension package (PEP) is a solar array system that will be used on the space transportation system to augment the power of the Orbiter vehicle and to extend the time the vehicle may stay in orbit. The baseline configuration of the PEP is reviewed. The programmatic aspects of the design covering the development plan, the manufacturing facility plan and the estimated costs and risks are presented.

Perceptions of the Impact of a PEP Grant on Elementary Physical Education Programs in One School District

ERIC Educational Resources Information Center

Elliott, Steven; McCollum, Starla; Colquitt, Gavin; Pritchard, Tony

2013-01-01

A school district received a Physical Education for Progress grant (PEP). PEP grants are part of the Carol M. White Program and are administered by the U.S. Department of Education. These grants are available to local educational agencies to initiate, expand, or improve physical education (PE) programs. The purpose of this study was to determine…

Utility of the Psychoeducational Profile-3 for Assessing Cognitive and Language Skills of Children with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Fulton, Mandy L.; D'Entremont, Barbara

2013-01-01

The Psychoeducational Profile-3's (PEP-3) ability to estimate cognitive and language skills of 136 children (20-75 months) with autism spectrum disorders (ASDs) across a range of functioning, and the association between the PEP-3 and ASD symptomatology was examined using retrospective data. PEP-3 cognitive and language measures were positively…

47 CFR 97.313 - Transmitter power standards.

Code of Federal Regulations, 2010 CFR

2010-10-01

... station may transmit with a transmitter power exceeding 1.5 kW PEP. (c) No station may transmit with a transmitter power output exceeding 200 W PEP: (1) On the 10.10-10.15 MHz segment; (2) On the 3.525-3.60 MHz, 7... within ITU Regions 1 or 3. (d) No station may transmit with a transmitter power exceeding 25 W PEP on the...

47 CFR 97.313 - Transmitter power standards.

Code of Federal Regulations, 2013 CFR

2013-10-01

... station may transmit with a transmitter power exceeding 1.5 kW PEP. (c) No station may transmit with a transmitter power output exceeding 200 W PEP: (1) On the 10.10-10.15 MHz segment; (2) On the 3.525-3.60 MHz, 7... Regions 1 or 3. (d) No station may transmit with a transmitter power exceeding 25 W PEP on the VHF 1.25 m...

47 CFR 97.313 - Transmitter power standards.

Code of Federal Regulations, 2014 CFR

2014-10-01

... station may transmit with a transmitter power exceeding 1.5 kW PEP. (c) No station may transmit with a transmitter power output exceeding 200 W PEP: (1) On the 10.10-10.15 MHz segment; (2) On the 3.525-3.60 MHz, 7... Regions 1 or 3. (d) No station may transmit with a transmitter power exceeding 25 W PEP on the VHF 1.25 m...

40 CFR Appendix A to Part 58 - Quality Assurance Requirements for SLAMS, SPMs and PSD Air Monitoring

Code of Federal Regulations, 2011 CFR

2011-07-01

... in section 4.3.1 of this appendix. 3.2.7PM2.5 Performance Evaluation Program (PEP) Procedures. The... evaluation audit means that both the primary monitor and PEP audit concentrations are valid and above 3 µg/m3... Evaluation Program (PEP) Procedures. Each year, one performance evaluation audit, as described in section 3.2...

47 CFR 97.313 - Transmitter power standards.

Code of Federal Regulations, 2011 CFR

2011-10-01

... station may transmit with a transmitter power exceeding 1.5 kW PEP. (c) No station may transmit with a transmitter power output exceeding 200 W PEP: (1) On the 10.10-10.15 MHz segment; (2) On the 3.525-3.60 MHz, 7... Regions 1 or 3. (d) No station may transmit with a transmitter power exceeding 25 W PEP on the VHF 1.25 m...

40 CFR Appendix A to Part 58 - Quality Assurance Requirements for SLAMS, SPMs and PSD Air Monitoring

Code of Federal Regulations, 2012 CFR

2012-07-01

... in section 4.3.1 of this appendix. 3.2.7PM2.5 Performance Evaluation Program (PEP) Procedures. The... evaluation audit means that both the primary monitor and PEP audit concentrations are valid and above 3 µg/m3... Evaluation Program (PEP) Procedures. Each year, one performance evaluation audit, as described in section 3.2...

47 CFR 97.313 - Transmitter power standards.

Code of Federal Regulations, 2012 CFR

2012-10-01

... station may transmit with a transmitter power exceeding 1.5 kW PEP. (c) No station may transmit with a transmitter power output exceeding 200 W PEP: (1) On the 10.10-10.15 MHz segment; (2) On the 3.525-3.60 MHz, 7... Regions 1 or 3. (d) No station may transmit with a transmitter power exceeding 25 W PEP on the VHF 1.25 m...

Engineer Company Force Structure Force Modularization in Support of Decisive Action. Does the Corps of Engineers Need to Re-Structure Engineer Construction Companies Again in order to Support Decisive Actions?

DTIC Science & Technology

2012-05-16

Regional Command RCP Route Clearance Platoon RSOI Reception, Staging, Onward Movement, Integration SBCT Stryker Brigade Combat Team TOE Table of...Point (ASPs), and field hospital platforms; prepare river crossing sites; and support port repair due to Hydraulic Excavator (HYEX), provides force...platforms, FARPS, supply routes, roads, control points, fire bases, tank ditches, ASPs, and field hospital platforms; prepare river crossing sites; and

Genes involved in protein metabolism of the probiotic lactic acid bacterium Lactobacillus delbrueckii UFV H2b20.

PubMed

Do Carmo, A P; da Silva, D F; De Oliveira, M N V; Borges, A C; De Carvalho, A F; De Moraes, C A

2011-09-01

A basic requirement for the prediction of the potential use of lactic acid bacteria (LAB) in the dairy industry is the identification of specific genes involved in flavour-forming pathways. The probiotic Lactobacillus delbrueckii UFV H2b20 was submitted to a genetic characterisation and phylogenetic analysis of genes involved in protein catabolism. Eight genes belonging to this system were identified, which possess a closely phylogenetic relationship to NCFM strains representative, as it was demonstrated for oppC and oppBII, encoding oligopeptide transport system components. PepC, PepN, and PepX might be essential for growth of LAB, probiotic or not, since the correspondent genes are always present, including in L. delbrueckii UFV H2b20 genome. For pepX gene, a probable link between carbohydrate catabolism and PepX expression may exists, where it is regulated by PepR1/CcpA-like, a common feature between Lactobacillus strains and also in L. delbrueckii UFV H2b20. The well conserved evolutionary history of the ilvE gene is evidence that the pathways leading to branched-chain amino acid degradation, such as isoleucine and valine, are similar among L. delbrueckii subsp. bulgaricus strains and L. delbrueckii UFV H2b20. Thus, the involvement of succinate in flavour formation can be attributed to IlvE activity. The presence of aminopeptidase G in L. delbrueckii UFV H2b20 genome, which is absent in several strains, might improve the proteolytic activity and effectiveness. The nucleotide sequence encoding PepG revealed that it is a cysteine endopeptidase, belonging to Peptidase C1 superfamily; sequence analysis showed 99% identity with L. delbrueckii subsp. bulgaricus ATCC 11842 pepG, whereas protein sequence analysis revealed 100% similarity with PepG from the same organism. The present study proposes a schematic model to explain how the proteolytic system of the probiotic L. delbrueckii UFV H2b20 works, based on the components identified so far.

Should travellers to rabies-endemic countries be pre-exposure vaccinated? An assessment of post-exposure prophylaxis and pre-exposure prophylaxis given to Danes travelling to rabies-endemic countries 2000-12.

PubMed

Christiansen, Annette H; Rodriguez, Anna B; Nielsen, Jens; Cowan, Susan A

2016-04-01

Since 2000, a steady increase of vaccines used for both rabies Post-exposure prophylaxis (PEP) and rabies Pre-exposure prophylaxis (PrEP) given to Danish travellers was observed. This study aims to evaluate whether the increase of PEP and PrEP was due to increased travelling, increased awareness of the need for PrEP, or more animal bites per travel, leading to more PEP being administered, in order to assess the need for changing the recommendations. We also described in which countries Danish travelers most frequently reported possible exposure to rabies, and evaluated the timeliness of rabies PEP, including rabies immunoglobulin (RIG). We included all Danes reported to the National Database for Rabies Treatment as having started rabies PEP either abroad or after returning to Denmark, between 2000 and 2012. Data on the yearly number of Danish travelers from 2004 to 2012 to Thailand were collected to calculate the incidence of animal bites at this destination. We also included data on rabies vaccines sold for PrEP or for booster vaccination in Denmark. PEP after possible exposure to rabies abroad increased yearly by 8.8 %. Likewise vaccines sold for PrEP increased by 8.2% annually. The number of Danish travelers to Thailand increased by 7.3% per year, resulting in a stable incidence of animal bites per 100,000 travelers. Seventy-five % started PEP in the country of exposure, while only 10 % received RIG. The yearly increase in PEP and PrEP are parallel to the yearly increase in number of travelers, and can thus be explained by the increased rate of traveling, and not by a rise in awareness of rabies risk or more bites per traveler.Even short term travelers should be given the option of including PrEP in their travel immunisation program, as PEP and especially RIG is not always available in rabies-endemic countries. © International Society of Travel Medicine, 2016. All rights reserved. Published by Oxford University Press. For permissions, please e-mail: journals.permissions@oup.com.

Rabies Situation in Cambodia

PubMed Central

Ly, Sowath; Buchy, Philippe; Heng, Nay Yim; Ong, Sivuth; Chhor, Nareth; Bourhy, Hervé; Vong, Sirenda

2009-01-01

Background Rabies, a fatal but preventable zoonosis, is a major public health problem in developing countries. In Cambodia the disease burden is largely underestimated because patients with encephalitis following dog bites are rarely hospitalized and die at home. Since 1998 Institut Pasteur in Cambodia (IPC), Phnom Penh has been the only source of free post-exposure prophylaxis (PEP) and post-mortem diagnosis. Methods The 1998–2007 data compiled by IPC was analyzed to describe all treated patients for PEP, results of human testing and confirmed rabies cases, and results of animal testing. From dog bites' characteristics, we defined a suspected rabid dog bite injury (SRDBI) in humans as a bite that was unprovoked, from a dog that died spontaneously, or from a dog that was reported sick. We applied a deterministic probability model to estimate 2007 rabies human mortality nationwide from the estimated incidence of rabid dog bites, the body distribution of bite wounds, and the probability of PEP access. Results During 1998–2007, 124,749 patients received PEP at IPC (average 12,470; range 8,907–14,475), and 63 fatal human cases presenting with encephalitis following a dog bite were reported, in which 73% were confirmed positive for rabies by direct immunofluorescence assay or by reverse-transcriptase polymerase chain reaction. During 1998–2007, IPC tested 1,255 animal brain samples; 1,214 (97%) were from dogs including 610 (49%) positive samples. In 2007, 14,475 patients received PEP (100 PEP/100,000 people in Cambodia) including 95% who resided in Phnom Penh (615 PEP/100,000) or five neighboring provinces. The predictive model estimated 810 human rabies deaths would occur in 2007 (95%confidence interval [CI] 394–1,607), an incidence of 5.8/100,000 (95% CI 2.8–11.5). Conclusions Access to PEP is only sufficient for Phnom Penh residents. In 2007, the estimated rabies related mortality exceeded that of malaria and that of dengue. A national rabies control program is needed to improve surveillance and access to PEP, and to initiate vaccination campaigns in dogs. PMID:19907631

Receptor-mediated cytotoxicity of alpha-MSH fragments containing melphalan in a human melanoma cell line.

PubMed

Morandini, R; Süli-Vargha, H; Libert, A; Loir, B; Botyánszki, J; Medzihradszky, K; Ghanem, G

1994-01-02

Four alpha-MSH drug conjugates have been synthesized, 2 C-terminal (Pep 3 and 4) and 2 central fragments (Pep 1 and 2), the latter being the 4-10 sequence known to be the main alpha-MSH-receptor-recognition site. Melphalan was introduced into each sequence at different locations. Their ability to recognize alpha-MSH receptors as well as their cytotoxic effects were compared in 3 cell lines: melanoma, carcinoma and fibroblast cells. Pep 1 and 2 were able to specifically bind to MSH receptors on melanoma cells by displacing labelled alpha-MSH from its binding sites at concentrations similar to the 4-10 heptapeptide sequence known to contain the main receptor-recognition site. They subsequently penetrate the cell, most probably by a receptor internalization mechanism, since about half of their effect could be inhibited by competition at the receptor level. Significant and selective cytotoxic effects to melanoma cells could be observed after only 2 hr exposure to the drug conjugates. Interestingly, these 2 conjugates, differing only in melphalan position, showed completely different cytotoxicity in terms of IC50 values, Pep 1 being 24 times more toxic to all cells; but the 2 were equally specific to melanoma cells. However, they both were less toxic to all cells than melphalan itself. Furthermore, Pep 1 and 2 were able to block the receptor and, unlike Pep 3 and 4, their cytotoxic effect could be significantly inhibited by an alpha-MSH agonist. Pep 3 and 4 were 5 to 10 times less toxic than melphalan to melanoma and carcinoma cells and 50 times less to fibroblast cells, and did not show any cell-type selectivity. They were less toxic than Pep 1 to melanoma and carcinoma cells by a factor of 2, but equally toxic to fibroblasts. In contrast, they were more toxic than Pep 2 to fibroblasts, melanoma and carcinoma by a factor of 3, 10 and 24 respectively. Our data strongly suggest a receptor-mediated cytotoxicity mechanism occurring with alpha-MSH central fragments in human melanoma cells due to the presence of alpha-MSH-specific receptors. This mechanism appeared to be both peptide- and cell-type-specific.

Consumption of gluten with gluten-degrading enzyme by celiac patients: A pilot-study

PubMed Central

Tack, Greetje J; van de Water, Jolanda MW; Bruins, Maaike J; Kooy-Winkelaar, Engelina MC; van Bergen, Jeroen; Bonnet, Petra; Vreugdenhil, Anita CE; Korponay-Szabo, Ilma; Edens, Luppo; von Blomberg, B Mary E; Schreurs, Marco WJ; Mulder, Chris J; Koning, Frits

2013-01-01

AIM: To assesses the safety and efficacy of Aspergillus niger prolyl endoprotease (AN-PEP) to mitigate the immunogenic effects of gluten in celiac patients. METHODS: Patients with initial diagnosis of celiac disease as confirmed by positive serology with subtotal or total villous atrophy on duodenal biopsies who adhere to a strict gluten-free diet (GFD) resulting in normalised antibodies and mucosal healing classified as Marsh 0 or I were included. In a randomised double-blind placebo-controlled pilot study, patients consumed toast (approximately 7 g/d gluten) with AN-PEP for 2 wk (safety phase). After a 2-wk washout period with adherence of the usual GFD, 14 patients were randomised to gluten intake with either AN-PEP or placebo for 2 wk (efficacy phase). Measurements at baseline included complaints, quality-of-life, serum antibodies, immunophenotyping of T-cells and duodenal mucosa immunohistology. Furthermore, serum and quality of life questionnaires were collected during and after the safety, washout and efficacy phase. Duodenal biopsies were collected after the safety phase and after the efficacy phase. A change in histological evaluation according to the modified Marsh classification was the primary endpoint. RESULTS: In total, 16 adults were enrolled in the study. No serious adverse events occurred during the trial and no patients withdrew during the trial. The mean score for the gastrointestinal subcategory of the celiac disease quality (CDQ) was relatively high throughout the study, indicating that AN-PEP was well tolerated. In the efficacy phase, the CDQ scores of patients consuming gluten with placebo or gluten with AN-PEP did not significantly deteriorate and moreover no differences between the groups were observed. During the efficacy phase, neither the placebo nor the AN-PEP group developed significant antibody titers. The IgA-EM concentrations remained negative in both groups. Two patients were excluded from entering the efficacy phase as their mucosa showed an increase of two Marsh steps after the safety phase, yet with undetectable serum antibodies, while 14 patients were considered histologically stable on gluten with AN-PEP. Also after the efficacy phase, no significant deterioration was observed regarding immunohistological and flow cytometric evaluation in the group consuming placebo compared to the group receiving AN-PEP. Furthermore, IgA-tTG deposit staining increased after 2 wk of gluten compared to baseline in four out of seven patients on placebo. In the seven patients receiving AN-PEP, one patient showed increased and one showed decreased IgA-tTG deposits. CONCLUSION: AN-PEP appears to be well tolerated. However, the primary endpoint was not met due to lack of clinical deterioration upon placebo, impeding an effect of AN-PEP. PMID:24124328

A Multicenter, Prospective, Randomized Controlled Trial Evaluating the Efficacy of Rectal Diclofenac and Sublingual Nitroglycerin as a Combined Prophylactic Treatment for Post-ERCP Pancreatitis.

PubMed

Tomoda, Takeshi; Kato, Hironari; Mizukawa, Sho; Muro, Shinichiro; Akimoto, Yutaka; Uchida, Daisuke; Matsumoto, Kazuyuki; Yamamoto, Naoki; Horiguchi, Shigeru; Tsutsumi, Koichiro; Okada, Hiroyuki

2016-01-01

Acute pancreatitis is the major complication of endoscopic retrograde cholangiopancreatography (ERCP). A preliminary research suggested that the administration of nonsteroidal anti-inflammatory drugs (NSAIDs) with nitroglycerin might reduce the incidence of post-ERCP pancreatitis (PEP) more effectively than NSAIDs alone. We conduct a two-arm, multicenter, prospective, randomized, superiority trial to evaluate the additional effect of nitroglycerin for prevention of PEP. A total of 900 patients randomly receive 50 mg diclofenac suppository either alone or with 5 mg isosorbide dinitrate sublingual tablet. The primary endpoint is the occurrence of PEP. This study will clarify whether NSAIDs plus nitroglycerin can prevent PEP.

Responsiveness of the psychoeducational profile-third edition for children with autism spectrum disorders.

PubMed

Chen, Kuan-Lin; Chiang, Fu-Mei; Tseng, Mei-Hui; Fu, Chung-Pei; Hsieh, Ching-Lin

2011-12-01

The aim of this study was to examine the responsiveness of the Psychoeducational Profile-third edition (PEP-3) in children with Autism Spectrum Disorders (ASD). We investigated the responsiveness in terms of three types of scores (i.e., raw scores, developmental ages, and percentile ranks) of the subtests and composites of the PEP-3 and three methods of analysis were used: effect size, standardized response mean, and paired t test. The findings generally support the use of the PEP-3 as an outcome measure. We suggest using the raw scores and developmental ages of the PEP-3 when evaluating program effectiveness and developmental changes for children with ASD.

An Open-Source Automated Peptide Synthesizer Based on Arduino and Python.

PubMed

Gali, Hariprasad

2017-10-01

The development of the first open-source automated peptide synthesizer, PepSy, using Arduino UNO and readily available components is reported. PepSy was primarily designed to synthesize small peptides in a relatively small scale (<100 µmol). Scripts to operate PepSy in a fully automatic or manual mode were written in Python. Fully automatic script includes functions to carry out resin swelling, resin washing, single coupling, double coupling, Fmoc deprotection, ivDde deprotection, on-resin oxidation, end capping, and amino acid/reagent line cleaning. Several small peptides and peptide conjugates were successfully synthesized on PepSy with reasonably good yields and purity depending on the complexity of the peptide.

Recombinant glucose uptake system

DOEpatents

Ingrahm, Lonnie O.; Snoep, Jacob L.; Arfman, Nico

1997-01-01

Recombinant organisms are disclosed that contain a pathway for glucose uptake other than the pathway normally utilized by the host cell. In particular, the host cell is one in which glucose transport into the cell normally is coupled to PEP production. This host cell is transformed so that it uses an alternative pathway for glucose transport that is not coupled to PEP production. In a preferred embodiment, the host cell is a bacterium other than Z. mobilis that has been transformed to contain the glf and glk genes of Z. mobilis. By uncoupling glucose transport into the cell from PEP utilization, more PEP is produced for synthesis of products of commercial importance from a given quantity of biomass supplied to the host cells.

Floor Plans Rolling Platform, Tech Systems Platform, and Load ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Floor Plans - Rolling Platform, Tech Systems Platform, and Load Platform Plans - Marshall Space Flight Center, F-1 Engine Static Test Stand, On Route 565 between Huntsville and Decatur, Huntsville, Madison County, AL

Transduced human copper chaperone for Cu,Zn-SOD (PEP-1-CCS) protects against neuronal cell death.

PubMed

Choi, Soo Hyun; Kim, Dae Won; Kim, So Young; An, Jae Jin; Lee, Sun Hwa; Choi, Hee Soon; Sohn, Eun Jung; Hwang, Seok-Il; Won, Moo Ho; Kang, Tae-Cheon; Kwon, Hyung Joo; Kang, Jung Hoon; Cho, Sung-Woo; Park, Jinseu; Eum, Won Sik; Choi, Soo Young

2005-12-31

Reactive oxygen species (ROS) contribute to the development of various human diseases. Cu,Zn-superoxide dismutase (SOD) is one of the major means by which cells counteract the deleterious effects of ROS. SOD activity is dependent upon bound copper ions supplied by its partner metallochaperone protein, copper chaperone for SOD (CCS). In the present study, we investigated the protective effects of PEP-1-CCS against neuronal cell death and ischemic insults. When PEP-1-CCS was added to the culture medium of neuronal cells, it rapidly entered the cells and protected them against paraquat-induced cell death. Moreover, transduced PEP-1-CCS markedly increased endogenous SOD activity in the cells. Immunohistochemical analysis revealed that it prevented neuronal cell death in the hippocampus in response to transient forebrain ischemia. These results suggest that CCS is essential to activate SOD, and that transduction of PEP-1-CCS provides a potential strategy for therapeutic delivery in various human diseases including stroke related to SOD or ROS.

Mumps Postexposure Prophylaxis with a Third Dose of Measles-Mumps-Rubella Vaccine, Orange County, New York, USA

PubMed Central

Lawler, Jacqueline; Curns, Aaron T.; Brandeburg, Christina; Wallace, Gregory S.

2013-01-01

Although the measles-mumps-rubella (MMR) vaccine is not recommended for mumps postexposure prophylaxis (PEP), data on its effectiveness are limited. During the 2009–2010 mumps outbreak in the northeastern United States, we assessed effectiveness of PEP with a third dose of MMR vaccine among contacts in Orthodox Jewish households who were given a third dose within 5 days of mumps onset in the household’s index patient. We compared mumps attack rates between persons who received a third MMR dose during the first incubation period after onset in the index patient and 2-dose vaccinated persons who had not. Twenty-eight (11.7%) of 239 eligible household members received a third MMR dose as PEP. Mumps attack rates were 0% among third-dose recipients versus 5.2% among 2-dose recipients without PEP (p = 0.57). Although a third MMR dose administered as PEP did not have a significant effect, it may offer some benefits in specific outbreak contexts. PMID:23965729

Effects of a Proline Endopeptidase on the Detection and Quantitation of Gluten by Antibody-Based Methods during the Fermentation of a Model Sorghum Beer.

PubMed

Panda, Rakhi; Fiedler, Katherine L; Cho, Chung Y; Cheng, Raymond; Stutts, Whitney L; Jackson, Lauren S; Garber, Eric A E

2015-12-09

The effectiveness of a proline endopeptidase (PEP) in hydrolyzing gluten and its putative immunopathogenic sequences was examined using antibody-based methods and mass spectrometry (MS). Based on the results of the antibody-based methods, fermentation of wheat gluten containing sorghum beer resulted in a reduction in the detectable gluten concentration. The addition of PEP further reduced the gluten concentration. Only one sandwich ELISA was able to detect the apparent low levels of gluten present in the beers. A competitive ELISA using a pepsin-trypsin hydrolysate calibrant was unreliable because the peptide profiles of the beers were inconsistent with that of the hydrolysate calibrant. Analysis by MS indicated that PEP enhanced the loss of a fragment of an immunopathogenic 33-mer peptide in the beer. However, Western blot results indicated partial resistance of the high molecular weight (HMW) glutenins to the action of PEP, questioning the ability of PEP in digesting all immunopathogenic sequences present in gluten.

Biological studies on the degradation products of 3-[(S)-1'-phenylethylamino]propylaminobleomycin: a novel analog (pepleomycin).

PubMed

Takahashi, K; Ekimoto, H; Aoyagi, S; Koyu, A; Kuramochi, H; Yoshioka, O; Matsuda, A; Fujii, A; Umezawa, H

1979-01-01

Pepleomycin (PEP), 3-[(S)-1'-phenylethylamino]propylaminobleomycin has potent activity and is less pulmonary toxic than bleomycin (BLM). Biological activity and toxicity of the following degradation products of PEP have been studied in detail: the product of carbamoyl migration (ISO), the product of decarbamylation (DC), the product of ring closure of the side chain on the pyrimidine moiety (RC), the depyruvamide product (DP) and the product of an enzymatic inactivation (DA). These degradation products showed much lower activity than PEP in vitro: antimicrobial and anti-HeLa activities, inhibition of DNA synthesis in AH66 cells and the DNA strand cleavage. Acute toxicity and pulmonary toxicity were tested in mice. Results indicated much lower acute toxicity corresponding to the decreased in vitro activity when compared to PEP. DP and RC did not cause lung fibrosis in mice, while ISO and DC showed 1/2.6 and 1/5.7 degree of pulmonary toxicity, respectively, in comparison with PEP.

National guidelines on management of occupational exposure to HIV.

PubMed

Rewari, B B; Negi, Shivi

2009-05-01

During patient care, the healthcare personnel are at risk of infection of blood-borne pathogens (HIV, HBV, HCV) which is referred to as occupational exposure. Exposure to blood, semen, vaginal secretions, CSF, synovial, pleural, peritoneal, pericardial fluid, amniotic fluid and other body fluids contaminated with visible blood can lead to infection. Steps which are to be followed after occupational exposure are: (1) Step I : First aid following the exposure. (2) Step 2: Establish eligibility for postexposure prophylaxis (PEP). (3) Step 3: Counselling for PEP. (4) Step 4: Prescribe PEP. (5) HIV chemoprophylaxis. (6) Step 6: Follow-up of an exposed person. In order to get timely prophylactic therapy, PEP drugs should be kept available round-the-clock in at least three locations, casualty, ICU and labour room. Every hospital should have a written protocol and SOP for handling occupational exposure. NACO is in the process of launching a national HIV PEP Registry for capturing the cases of occupational exposure to HIV more effectively.

Preschool children's performance on Profiling Elements of Prosody in Speech-Communication (PEPS-C).

PubMed

Gibbon, Fiona E; Smyth, Heather

2013-07-01

Profiling Elements of Prosody in Speech-Communication (PEPS-C) has not been used widely to assess prosodic abilities of preschool children. This study was therefore aimed at investigating typically developing 4-year-olds' performance on PEPS-C. PEPS-C was presented to 30 typically developing 4-year-olds recruited in southern Ireland. Children were judged to have completed the test if they produced analysable responses to >95% of the items. The children's scores were compared with data from typically developing 5-6-year-olds. The majority (83%) of 4-year-olds were able to complete the test. The children scored at chance or weak ability levels on all subtests. The 4-year-olds had lower scores than 5-6-year-olds in all subtests, apart from one, with the difference reaching statistical significance in 8 out of 12 subtests. The results indicate that PEPS-C could be a valuable tool for assessing prosody in young children with typical development and some groups of young children with communication disorders.

Can PEP-3 Provide a Cognitive Profile in Children with ASD? A Comparison between the Developmental Ages of PEP-3 and IQ of Leiter-R

ERIC Educational Resources Information Center

De Giacomo, Andrea; Craig, Francesco; Cristella, Arcangelo; Terenzio, Vanessa; Buttiglione, Maura; Margari, Lucia

2016-01-01

Background: The assessment of the intelligence quotient (IQ) in children with autism spectrum disorder (ASD) is important to plan a detailed therapeutic-educative programme. The aim of the study was to evaluate the usefulness of the Psychoeducational Profile-third edition (PEP-3) to estimate the general cognitive development of children with ASD.…

Storage rings, internal targets and PEP

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

Spencer, J.E.

Storage rings with internal targets are described, using PEP as an example. The difference between electrons and heavier particles such as protons, antiprotons, and heavy ions is also discussed because it raises possibilities of bypass insertions for more exotic experiments. PEP is compared to other rings in various contexts to verify the assertion that it is an ideal ring for many fundamental and practical applications that can be carried on simultaneously. (LEW)

Lessons Learned from Developing a Patient Engagement Panel: An OCHIN Report.

PubMed

Arkind, Jill; Likumahuwa-Ackman, Sonja; Warren, Nate; Dickerson, Kay; Robbins, Lynn; Norman, Kathy; DeVoe, Jennifer E

2015-01-01

There is renewed interest in patient engagement in clinical and research settings, creating a need for documenting and publishing lessons learned from efforts to meaningfully engage patients. This article describes early lessons learned from the development of OCHIN's Patient Engagement Panel (PEP). OCHIN supports a national network of more than 300 community health centers (CHCs) and other primary care settings that serve over 1.5 million patients annually across nearly 20 states. The PEP was conceived in 2009 to harness the CHC tradition of patient engagement in this new era of patient-centered outcomes research and to ensure that patients were engaged throughout the life cycle of our research projects, from conception to dissemination. Developed by clinicians and researchers within our practice-based research network, recruitment of patients to serve as PEP members began in early 2012. The PEP currently has a membership of 18 patients from 3 states. Over the past 24 months, the PEP has been involved with 12 projects. We describe developing the PEP and challenges and lessons learned (eg, recruitment, funding model, creating value for patient partners, compensation). These lessons learned are relevant not only for research but also for patient engagement in quality improvement efforts and other clinical initiatives. © Copyright 2015 by the American Board of Family Medicine.

High sensitivity test of the Pauli Exclusion Principle for electrons with X-ray spectroscopy (VIP2)

NASA Astrophysics Data System (ADS)

Marton, Johann; VIP2 Collaboration

2015-10-01

The Pauli Exclusion Principle (PEP) is one of the most fundamental rules in physics and it has various important consequences ranging from atomic and subatomic systems to the stability of matter and stellar objects like neutron stars. Due to many observations This rule must be valid to an extremely high degree and consequently no violations were found so far. On the other hand a simple explanation of PEP is still missing. Many experimental investigations based on different assumptions were performed to search for a tiny PEP violation in various systems. The experiment VIP2 at the Gran Sasso underground laboratory (LNGS of INFN) is designed to test the PEP for electrons with high sensitivity by searching for forbidden X-ray transitions in copper atoms. This experiment aims to improve the PEP violation limit obtained with our preceding experiment VIP by orders of magnitude. The experimental method, comparison of the VIP result with different PEP searches and the present status of the VIP2 experiment will be presented. We acknowledge the support from the: HadronPhysics FP6 (506078), HadronPhysics2 FP7 (227431), HadronPhysics3 (283286) projects, EU COST Action 1006 (Fundamental Problems in Quantum Physics) and the Austrian Science Fund (FWF).

PepMapper: a collaborative web tool for mapping epitopes from affinity-selected peptides.

PubMed

Chen, Wenhan; Guo, William W; Huang, Yanxin; Ma, Zhiqiang

2012-01-01

Epitope mapping from affinity-selected peptides has become popular in epitope prediction, and correspondingly many Web-based tools have been developed in recent years. However, the performance of these tools varies in different circumstances. To address this problem, we employed an ensemble approach to incorporate two popular Web tools, MimoPro and Pep-3D-Search, together for taking advantages offered by both methods so as to give users more options for their specific purposes of epitope-peptide mapping. The combined operation of Union finds as many associated peptides as possible from both methods, which increases sensitivity in finding potential epitopic regions on a given antigen surface. The combined operation of Intersection achieves to some extent the mutual verification by the two methods and hence increases the likelihood of locating the genuine epitopic region on a given antigen in relation to the interacting peptides. The Consistency between Intersection and Union is an indirect sufficient condition to assess the likelihood of successful peptide-epitope mapping. On average from 27 tests, the combined operations of PepMapper outperformed either MimoPro or Pep-3D-Search alone. Therefore, PepMapper is another multipurpose mapping tool for epitope prediction from affinity-selected peptides. The Web server can be freely accessed at: http://informatics.nenu.edu.cn/PepMapper/

The Effectiveness of the Rectal Administration of Low-dose Diclofenac for the Prevention of Post-endoscopic Retrograde Cholangiopancreatography Pancreatitis.

PubMed

Okuno, Mitsuru; Shiroko, Junko; Taguchi, Daisuke; Yamaguchi, Kimihiro; Takada, Jun; Imai, Susumu; Sato, Hiroyuki; Thanabashi, Shinobu

2018-03-30

Objective A 50-100-mg rectal dose of nonsteroidal anti-inflammatory drugs (NSAIDs; diclofenac or indomethacin) has been shown to prevent post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). However, this is higher than the recommended 25-mg dose that is commonly administered to Japanese patients. The objective of this study was to evaluate the safety and efficacy of 25-mg rectal dose of diclofenac in preventing PEP. Methods Between January 2016 and March 2017, a total of 147 patients underwent ERCP with or without the rectal administration of diclofenac (25 mg) 20 min before the procedure. A retrospective analysis was conducted to evaluate the efficacy and safety of this dose in preventing PEP. Results Thirteen patients (8.8%) developed PEP: 3 patients (4.1%) in the diclofenac group and 10 (13.7%) in the control group (p=0.0460). After ERCP, there were no cases of gastrointestinal hemorrhage, ulceration, acute renal failure, or death. A multivariate logistic regression analysis revealed that the non-administration of rectal diclofenac was a risk factor for PEP (odds ratio=3.530; 95% confidence interval=1.017-16.35; p=0.0468). Conclusions A 25-mg rectal dose of diclofenac might prevent PEP.

Cannabis-Related Problems and Social Anxiety: The Mediational Role of Post-Event Processing.

PubMed

Ecker, Anthony H; Buckner, Julia D

2018-01-02

Cannabis is the most commonly used illicit drug in the US, and is associated with a range of psychological, social, and physical health-related problems. Individuals who endorse elevated levels of social anxiety are especially at risk for experiencing cannabis-related problems, including cannabis use disorder, despite not using cannabis more often than those with more normative social anxiety. Identification of mechanisms that underlie the relationship between social anxiety and cannabis-related problems may inform treatment and prevention efforts. Post-event processing (PEP, i.e., cognitively reviewing past social interactions/performances) is a social anxiety-related phenomenon that may be one such mechanism. The current study sought to test PEP as a mediator of the relationship between social anxiety and cannabis-related problems, adjusting for cannabis use frequency. Cannabis-using (past 3-month) undergraduate students recruited in 2015 (N = 244; 76.2% female; 74.2% Non-Hispanic Caucasian) completed an online survey of cannabis use, cannabis-related problems, social anxiety, and PEP. Bootstrap estimate of the indirect effect of social anxiety through PEP was significant, suggesting PEP is a mediator of the social anxiety-cannabis-related problems relationship. Conclusions/Importance: Treatment and prevention efforts may benefit from targeting PEP among individuals with elevated social anxiety and cannabis-related problems.

Review. The mammalian proton-coupled peptide cotransporter PepT1: sitting on the transporter-channel fence?

PubMed

Meredith, David

2009-01-27

The proton-coupled di- and tripeptide transporter PepT1 (SLC15a1) is the major route by which dietary nitrogen is taken up from the small intestine, as well as being the route of entry for important therapeutic (pro)drugs such as the beta-lactam antibiotics, angiotensin-converting enzyme inhibitors and antiviral and anti-cancer agents. PepT1 is a member of the major facilitator superfamily of 12 transmembrane domain transporter proteins. Expression studies in Xenopus laevis on rabbit PepT1 that had undergone site-directed mutagenesis of a conserved arginine residue (arginine282 in transmembrane domain 7) to a glutamate revealed that this residue played a role in the coupling of proton and peptide transport and prevented the movement of non-coupled ions during the transporter cycle. Mutations of arginine282 to other non-positive residues did not uncouple proton-peptide cotransport, but did allow additional ion movements when substrate was added. By contrast, mutations to positive residues appeared to function the same as wild-type. These findings are discussed in relation to the functional role that arginine282 may play in the way PepT1 operates, together with structural information from the homology model of PepT1 based on the Escherichia coli lactose permease crystal structure.

Cultivating engineering innovation ability based on optoelectronic experimental platform

NASA Astrophysics Data System (ADS)

Li, Dangjuan; Wu, Shenjiang

2017-08-01

As the supporting experimental platform of the Xi'an Technological University education reform experimental class, "optical technological innovation experimental platform" integrated the design and comprehensive experiments of the optical multi-class courses. On the basis of summing up the past two years teaching experience, platform pilot projects were improve. It has played a good role by making the use of an open teaching model in the cultivating engineering innovation spirit and scientific thinking of the students.

A pepper mottle virus-based vector enables systemic expression of endoglucanase D in non-transgenic plants.

PubMed

Song, Eun Gyeong; Ryu, Ki Hyun

2017-12-01

Plant-virus-based expression vectors have been used as an alternative to the creation of transgenic plants. Using a virus-based vector, we investigated the feasibility of producing the endoglucanase D (EngD) from Clostridium cellulovorans in Nicotiana benthamiana. This protein has endoglucanase, xylanase, and exoglucanase activities and may be of value for cellulose digestion in the generation of biofuels from plant biomass. The EngD gene was cloned between the nuclear inclusion b (NIb)- and coat protein (CP)-encoding sequences of pSP6PepMoV-Vb1. In vitro transcripts derived from the clone (pSP6PepMoV-Vb1/EngD) were infectious in N. benthamiana but caused milder symptoms than wild-type PepMoV-Vb1. RT-PCR amplification of total RNA from non-inoculated upper leaves infected with PepMoV-Vb1/EngD produced the target band for the CP, partial NIb and EngD-CP regions of PepMoV-V1/EngD, in addition to nonspecific bands. Western blot analysis showed the CP target bands of PepMoV-Vb1/EngD as well as non-target bands. EngD enzymatic activity in infected plants was detected using a glucose assay. The plant leaves showed increased senescence compared with healthy and PepMoV-Vb1-infected plants. Our study suggests the feasibility of using a viral vector for systemic infection of plants for expression of heterologous engD for the purpose of digesting a cellulose substrate in plant cells for biomass production.

Can Rectal Diclofenac Prevent Post Endoscopic Retrograde Cholangiopancreatography Pancreatitis?

PubMed

Lua, Guan Way; Muthukaruppan, Raman; Menon, Jayaram

2015-10-01

Non steroidal anti-inflammatory drugs (NSAIDs) have been shown to reduce the incidence of post endoscopic retrograde cholangiopancreatography pancreatitis (PEP). There were various trials using different routes and dosages of NSAIDs but meta-analysis revealed inconsistent results. The aims of this study were to determine the efficacy of rectal diclofenac in preventing PEP and to evaluate any adverse events. This was a randomized, open-label, two-arm, prospective clinical trial. Only patients at high risk of developing PEP were recruited. They received 100 mg rectal diclofenac or no intervention immediately after ERCP. The patients were reviewed 30 days after discharge to evaluate any adverse event. Among 144 recruited patients, 69 (47.9%) received diclofenac and 75 (52.1%) had no intervention. Eleven patients (7.6%) developed PEP, in which seven were from the diclofenac group and four were in the control group. Eight cases of PEP (5.5%) were mild and three cases (2.1%) were moderate. The differences in pancreatitis incidence and severity between both groups were not statistically significant. There were 11 adverse events reported. Clinically significant bleeding happened in four patients (2.8%): one from the diclofenac group and three from the control group. Other events included cholangitis: two patients (2.9%) from the diclofenac group and four (5.3%) from the control group. One patient from the diclofenac group (1.4%) had a perforation which was treated conservatively. In summary, prophylactic rectal diclofenac did not significantly decrease the incidence of PEP among patients at high risk for developing PEP. However, the administration of diclofenac was fairly safe with few clinical adverse events.

Cu, Zn-Superoxide Dismutase Increases the Therapeutic Potential of Adipose-derived Mesenchymal Stem Cells by Maintaining Antioxidant Enzyme Levels.

PubMed

Yoo, Dae Young; Kim, Dae Won; Chung, Jin Young; Jung, Hyo Young; Kim, Jong Whi; Yoon, Yeo Sung; Hwang, In Koo; Choi, Jung Hoon; Choi, Goang-Min; Choi, Soo Young; Moon, Seung Myung

2016-12-01

In the present study, we investigated the ability of Cu, Zn-superoxide dismutase (SOD1) to improve the therapeutic potential of adipose tissue-derived mesenchymal stem cells (Ad-MSCs) against ischemic damage in the spinal cord. Animals were divided into four groups: the control group, vehicle (PEP-1 peptide and artificial cerebrospinal fluid)-treated group, Ad-MSC alone group, and Ad-MSC-treated group with PEP-1-SOD1. The abdominal aorta of the rabbit was occluded for 30 min in the subrenal region to induce ischemic damage, and immediately after reperfusion, artificial cerebrospinal fluid or Ad-MSCs (2 × 10 5 ) were administered intrathecally. In addition, PEP-1 or 0.5 mg/kg PEP-1-SOD1 was administered intraperitoneally to the Ad-MSC-treated rabbits. Motor behaviors and NeuN-immunoreactive neurons were significantly decreased in the vehicle-treated group after ischemia/reperfusion. Administration of Ad-MSCs significantly ameliorated the changes in motor behavior and NeuN-immunoreactive neuronal survival. In addition, the combination of PEP-1-SOD1 and Ad-MSCs further increased the ameliorative effects of Ad-MSCs in the spinal cord after ischemia. Furthermore, the administration of Ad-MSCs with PEP-1-SOD1 decreased lipid peroxidation and maintained levels of antioxidants such as SOD1 and glutathione peroxidase compared to the Ad-MSC alone group. These results suggest that combination therapy using Ad-MSCs and PEP-1-SOD1 strongly protects neurons from ischemic damage by modulating the balance of lipid peroxidation and antioxidants.

Identification of peptide sequences that target to the brain using in vivo phage display.

PubMed

Li, Jingwei; Zhang, Qizhi; Pang, Zhiqing; Wang, Yuchen; Liu, Qingfeng; Guo, Liangran; Jiang, Xinguo

2012-06-01

Phage display technology could provide a rapid means for the discovery of novel peptides. To find peptide ligands specific for the brain vascular receptors, we performed a modified phage display method. Phages were recovered from mice brain parenchyma after administrated with a random 7-mer peptide library intravenously. A longer circulation time was arranged according to the biodistributive brain/blood ratios of phage particles. Following sequential rounds of isolation, a number of phages were sequenced and a peptide sequence (CTSTSAPYC, denoted as PepC7) was identified. Clone 7-1, which encodes PepC7, exhibited translocation efficiency about 41-fold higher than the random library phage. Immunofluorescence analysis revealed that Clone 7-1 had a significant superiority on transport efficiency into the brain compared with native M13 phage. Clone 7-1 was inhibited from homing to the brain in a dose-dependent fashion when cyclic peptides of the same sequence were present in a competition assay. Interestingly, the linear peptide (ATSTSAPYA, Pep7) and a scrambled control peptide PepSC7 (CSPATSYTC) did not compete with the phage at the same tested concentration (0.2-200 pg). Labeled by Cy5.5, PepC7 exhibited significant brain-targeting capability in in vivo optical imaging analysis. The cyclic conformation of PepC7 formed by disulfide bond, and the correct structure itself play a critical role in maintaining the selectivity and affinity for the brain. In conclusion, PepC7 is a promising brain-target motif never been reported before and it could be applied to targeted drug delivery into the brain.

Gabexate in the prophylaxis of post-ERCP pancreatitis: a meta-analysis of randomized controlled trials.

PubMed

Zheng, Minghua; Chen, Yongping; Yang, Xinjun; Li, Ji; Zhang, Youcai; Zeng, Qiqiang

2007-02-12

Acute pancreatitis is a common complication of endoscopic retrograde cholangiopancreatography and the benefit of its pharmacological treatment is unclear. Although prophylactic use of gabexate for the reduction of pancreatic injury after ERCP has been evaluated, the discrepancy about gabexate's beneficial effect on pancreatic injury still exists. This study aimed to evaluate the effectiveness and safety of gabexate in the prophylaxis of post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP). We employed the method recommended by the Cochrane Collaboration to perform a meta-analysis of randomized controlled trials (RCTs) of gabexate in the prevention of post-ERCP pancreatitis (PEP) including three RCTs conducted in Italy and one in China. All of the four RCTs were of high quality. When the RCTs were analyzed, odds ratios (OR) for gabexate mesilate were 0.67 [95% CI (0.31 to approximately 1.47), p = 0.32] for PEP, 3.78 [95% CI (0.62 to approximately 22.98), p = 0.15] for severe PEP, 0.68 [95% CI (0.19 to approximately 2.43), p = 0.56] for the case-fatality of PEP, 0.88 [95% CI (0.72 to approximately 1.07), p = 0.20] for post-ERCP hyperamylasemia, 0.69 [95% CI (0.39 to approximately 1.21), p = 0.19] for post-ERCP abdominal pain, thus indicating no beneficial effects of gabexate on acute pancreatitis, the death rate of PEP, hyperamylasemia and abdominal pain. No evidence of publication bias was found. Gabexate mesilate can not prevent the pancreatic injury after ERCP. It is not recommended for the use of gabexate mesilate in the prophylaxis of PEP.

Pathway optimization by re-design of untranslated regions for L-tyrosine production in Escherichia coli

PubMed Central

Cheol Kim, Seong; Eun Min, Byung; Gyu Hwang, Hyun; Woo Seo, Sang; Yeol Jung, Gyoo

2015-01-01

L-tyrosine is a commercially important compound in the food, pharmaceutical, chemical, and cosmetic industries. Although several attempts have been made to improve L-tyrosine production, translation-level expression control and carbon flux rebalancing around phosphoenolpyruvate (PEP) node still remain to be achieved for optimizing the pathway. Here, we demonstrate pathway optimization by altering gene expression levels for L-tyrosine production in Escherichia coli. To optimize the L-tyrosine biosynthetic pathway, a synthetic constitutive promoter and a synthetic 5′-untranslated region (5′-UTR) were introduced for each gene of interest to allow for control at both transcription and translation levels. Carbon flux rebalancing was achieved by controlling the expression level of PEP synthetase using UTR Designer. The L-tyrosine productivity of the engineered E. coli strain was increased through pathway optimization resulting in 3.0 g/L of L-tyrosine titer, 0.0354 g L-tyrosine/h/g DCW of productivity, and 0.102 g L-tyrosine/g glucose yield. Thus, this work demonstrates that pathway optimization by 5′-UTR redesign is an effective strategy for the development of efficient L-tyrosine-producing bacteria. PMID:26346938

Post-exposure prophylaxis against Ebola virus disease with experimental antiviral agents: a case-series of health-care workers.

PubMed

Jacobs, Michael; Aarons, Emma; Bhagani, Sanjay; Buchanan, Ruaridh; Cropley, Ian; Hopkins, Susan; Lester, Rebecca; Martin, Daniel; Marshall, Neal; Mepham, Stephen; Warren, Simon; Rodger, Alison

2015-11-01

Although a few international health-care workers who have assisted in the current Ebola outbreak in west Africa have been medically evacuated for treatment of Ebola virus disease, more commonly they were evacuated after potential accidental exposure to Ebola virus. An urgent need exists for a consensus about the risk assessment of Ebola virus transmission after accidental exposure, and to investigate the use of post-exposure prophylaxis (PEP). Experimental vaccines have occasionally been used for Ebola PEP, but newly developed experimental antiviral agents have potential advantages. Here, we describe a new method for risk assessment and management of health-care workers potentially exposed to Ebola virus and report the use of experimental antiviral therapies for Ebola PEP in people. We devised a risk assessment and management algorithm for health-care workers potentially exposed to Ebola virus and applied this to eight consecutive individuals who were medically evacuated to the UK from west Africa between January, and March, 2015. PEP with antiviral agents was given to health-care workers assessed to have had substantial risk exposures to Ebola virus. Participants were followed up for 42 days after potential exposure. Four of eight health-care workers were classified as having had low risk exposures and managed by watchful waiting in the community. None of these health-care workers developed Ebola virus disease. The other four health-care workers had intermediate or maximum risk exposures and were given PEP with antiviral agents. PEP was well tolerated with no serious adverse effects. None of these four health-care workers, including two with maximum risk exposures from penetrating injuries with freshly used hollow-bore needles, developed Ebola virus disease. Standardised risk assessment should be adopted and consensus guidelines developed to systematically study the efficacy and safety of PEP with experimental agents. New experimental antiviral treatments are a viable option for PEP against Ebola. Royal Free London NHS Foundation Trust. Copyright © 2015 Elsevier Ltd. All rights reserved.

Particle Environment Package (PEP) for the ESA JUICE mission

NASA Astrophysics Data System (ADS)

Barabash, Stas; Brandt, Pontus; Wurz, Peter; PEP Team

2016-10-01

PEP is a suite of six (6) sensors arranged in 4 units to measure charged and neutral particles in the Jupiter magnetospheres and at the moons to answer four overarching science questions:1. How does the corotating magnetosphere of Jupiter interact with the complex and diverse environment of Ganymede?2. How does the rapidly rotating magnetosphere of Jupiter interact with the seemingly inert Callisto?3. What are the governing mechanisms and their global impacts of release of material into the Jovian magnetosphere from seemingly inert Europa and active Io?4. How do internal and solar wind drivers cause such energetic, time variable and multi-scale phenomena in the steadily rotating giant magnetosphere of Jupiter?PEP measures positive and negative ions, electrons, exospheric neutral gas, thermal plasma and energetic neutral atoms present in all domains of the Jupiter system over nine decades of energy from < 0.001 eV to > 1 MeV with full angular coverage.PEP provides instantaneous measurements of 3D flow of the ion plasma and composition to understand the magnetosphere and magnetosphere-moon interactions. It also measures instantaneously 3D electron plasma to investigate auroral processes at the moon and Jupiter. Measurements of the angular distributions of energetic electrons at sub-second resolution probe the acceleration mechanisms and magnetic field topology and boundaries.PEP combines global imaging via remote sensing using energetic neutral atoms (ENA) with in-situ measurements and performs global imaging of Europa/Io tori and magnetosphere combined with energetic ion measurements. Using low energy ENAs originating from the particle - surface interaction PEP investigate space weathering of the icy moons by precipitation particles. PEP will first-ever directly sample of the exospheres of Europa, Ganymede, and Callisto with extremely high mass resolution (M/ΔM > 1100).The PEP sensors are (1) an ion mass analyzer, (2) an electron spectrometer, (3) a low energy ENA imager, (4) a high energy ENA and energetic ions imager, (5) an energetic electron sensor, and (6) a neutral gas and ions mass spectrometer.

Treatment of recent-onset type 1 diabetic patients with DiaPep277: results of a double-blind, placebo-controlled, randomized phase 3 trial.

PubMed

Raz, Itamar; Ziegler, Anette G; Linn, Thomas; Schernthaner, Guntram; Bonnici, Francois; Distiller, Larry A; Giordano, Carla; Giorgino, Francesco; de Vries, Liat; Mauricio, Didac; Procházka, Vlastimil; Wainstein, Julio; Elias, Dana; Avron, Ann; Tamir, Merana; Eren, Rachel; Peled, Dana; Dagan, Shlomo; Cohen, Irun R; Pozzilli, Paolo

2014-01-01

To evaluate safety and efficacy of DiaPep277 in preserving β-cell function in type 1 diabetic patients. DIA-AID 1 is a multinational, phase 3, balanced-randomized, double-blind, placebo-controlled, parallel-group clinical study. Newly diagnosed patients (N = 457, aged 16-45 years) were randomized to subcutaneous injections of DiaPep277 or placebo quarterly for 2 years. The primary efficacy end point was the change from baseline in the area under the glucagon-stimulated C-peptide curve. Secondary end points were the change from baseline in mixed-meal stimulated C-peptide secretion and in fasting C-peptide and achieving target HbA1c ≤7% (≤53 mmol/mol). Partial remission (target HbA1c on insulin ≤0.5 units/kg/day) and hypoglycemic event rate were exploratory end points. DiaPep277 was safe and well tolerated. Significant preservation of C-peptide secretion was observed in the DiaPep277-treated group compared with the placebo (relative treatment effects of 23.4%, P = 0.037, and 29.2%, P = 0.011, in the modified intent-to-treat [mITT] and per-protocol [PP] populations, respectively). The mixed-meal stimulation failed to distinguish between the groups. There was a trend toward efficacy in fasting C-peptide levels, though not statistically significant. Significantly more DiaPep277-treated than placebo-treated patients maintained target HbA1c (mITT 56% versus 44%, P = 0.03; PP 60% versus 45%, P = 0.0082) and entered partial remission (mITT 38% versus 29%, P = 0.08; PP 42% versus 30%, P = 0.035). DiaPep277 treatment reduced the relative hypoglycemic event risk (mITT by 20%; PP by 28%). DiaPep277 safely contributes to preservation of β-cell function and to improved glycemic control in patients with type 1 diabetes.

Epidermal growth factor receptor VIII peptide vaccination is efficacious against established intracerebral tumors.

PubMed

Heimberger, Amy B; Crotty, Laura E; Archer, Gary E; Hess, Kenneth R; Wikstrand, Carol J; Friedman, Allan H; Friedman, Henry S; Bigner, Darell D; Sampson, John H

2003-09-15

The epidermal growth factor receptor (EGFR) is often amplified and structurally rearranged in malignant gliomas and other tumors such as breast and lung, with the most common mutation being EGFRvIII. In the study described here, we tested in mouse models a vaccine consisting of a peptide encompassing the tumor-specific mutated segment of EGFRvIII (PEP-3) conjugated to keyhole limpet hemocyanin [KLH (PEP-3-KLH)]. C57BL/6J or C3H mice were vaccinated with PEP-3-KLH and subsequently challenged either s.c. or intracerebrally with a syngeneic melanoma cell line stably transfected with a murine homologue of EGFRvIII. Control mice were vaccinated with KLH. To test its effect on established tumors, C3H mice were also challenged intracerebrally and subsequently vaccinated with PEP-3-KLH. S.c. tumors developed in all of the C57BL/6J mice vaccinated with KLH in Freund's adjuvant, and there were no long-term survivors. Palpable tumors never developed in 70% of the PEP-3-KLH-vaccinated mice. In the C57BL/6J mice receiving the PEP-3-KLH vaccine, the tumors that did develop were significantly smaller than those in the control group (P < 0.05). PEP-3-KLH vaccination did not result in significant cytotoxic responses in standard cytotoxicity assays; however, antibody titers against PEP-3 were enhanced. The passive transfer of sera from the immunized mice to nonimmunized mice protected 31% of the mice from tumor development (P < 0.05). In vivo depletion studies showed that the effector cell population was natural killer and CD8+ T cells, and in vitro assays showed that macrophages could lyse target tumor cells with serum from the PEP-3-KLH-vaccinated mice. Peptide vaccination was also sufficiently potent to have marked efficacy against intracerebral tumors, resulting in a >173% increase in median survival time, with 80% of the C3H mice achieving long-term survival (P = 0.014). In addition, C3H mice with established intracerebral tumor that received a single treatment of PEP-3-KLH showed a 26% increase in median survival time, with 40% long-term survival (P = 0.007). Vaccination with an EGFRvIII-specific peptide is efficacious against both s.c. and established intracerebral tumors. The therapeutic effect of peptide vaccination may be mediated, in part, by antibody-dependent cellular cytotoxicity.

Suppository naproxen reduces incidence and severity of post-endoscopic retrograde cholangiopancreatography pancreatitis: Randomized controlled trial.

PubMed

Mansour-Ghanaei, Fariborz; Joukar, Farahnaz; Taherzadeh, Zahra; Sokhanvar, Homayoon; Hasandokht, Tolou

2016-06-07

To determine the efficacy of rectally administered naproxen for the prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). This double-blind randomized control trial conducted from January 2013 to April 2014 at the Gastrointestinal and Liver Diseases Research Center in Rasht, Iran. A total of 324 patients were selected from candidates for diagnostic or therapeutic ERCP by using the simple sampling method. Patients received a single dose of Naproxen (500 mg; n = 162) or a placebo (n = 162) per rectum immediately before ERCP. The overall incidence of PEP, incidence of mild to severe PEP, serum amylase levels and adverse effects were measured. The primary outcome measure was the development of pancreatitis onset of pain in the upper abdomen and elevation of the serum amylase level to > 3 × the upper normal limit (60-100 IU/L) within 24 h after ERCP. The severity of PEP was classified according to the duration of therapeutic intervention for PEP: mild, 2-3 d; moderate 4-10 d; and severe, > 10 d and/or necessitated surgical or intensive treatment, or contributed to death. PEP occurred in 12% (40/324) of participants, and was significantly more frequent in the placebo group compared to the naproxen group (P < 0.01). Of the participants, 25.9% (84/324) developed hyperamylasemia within 2 h of procedure completion, among whom only 35 cases belonged to the naproxen group (P < 0.01). The incidence of PEP was significantly higher in female sex, in patients receiving pancreatic duct injection, more than 3 times pancreatic duct cannulations, and ERCP duration more than 40 min (Ps < 0.01). There were no statistically significant differences between the groups regarding the procedures or factors that might increase the risk of PEP, sphincterotomy, precut requirement, biliary duct injection and number of pancreatic duct cannulations. In the subgroup of patients with pancreatic duct injection, the rate of pancreatitis in the naproxen group was significantly lower than that in the placebo (6 patients vs 23 patients, P < 0.01, RRR = 12%, AR = 0.3, 95%CI: 0.2-0.6). Naproxen reduced the PEP in patients with ≥ 3 pancreatic cannulations (P < 0.01, RRR = 25%, AR = 0.1, 95%CI: 0.1-0.4) and an ERCP duration > 40 min (P < 0.01, RRR = 20%, AR = 0.9, 95%CI: 0.4-1.2). Single dose of suppository naproxen administered immediately before ERCP reduces the incidence of PEP.

Evaluation of Game Engines for Cross-Platform Development of Mobile Serious Games for Health.

PubMed

Kleinschmidt, Carina; Haag, Martin

2016-01-01

Studies have shown that serious games for health can improve patient compliance and help to increase the quality of medical education. Due to a growing availability of mobile devices, especially the development of cross-platform mobile apps is helpful for improving healthcare. As the development can be highly time-consuming and expensive, an alternative development process is needed. Game engines are expected to simplify this process. Therefore, this article examines the question whether using game engines for cross-platform serious games for health can simplify the development compared to the development of a plain HTML5 app. At first, a systematic review of the literature was conducted in different databases (MEDLINE, ACM and IEEE). Afterwards three different game engines were chosen, evaluated in different categories and compared to the development of a HTML5 app. This was realized by implementing a prototypical application in the different engines and conducting a utility analysis. The evaluation shows that the Marmalade engine is the best choice for development in this scenario. Furthermore, it is obvious that the game engines have great benefits against plain HTML5 development as they provide components for graphics, physics, sounds, etc. The authors recommend to use the Marmalade Engine for a cross-platform mobile Serious Game for Health.

A silk-based scaffold platform with tunable architecture for engineering critically-sized tissue constructs.

PubMed

Wray, Lindsay S; Rnjak-Kovacina, Jelena; Mandal, Biman B; Schmidt, Daniel F; Gil, Eun Seok; Kaplan, David L

2012-12-01

In the field of tissue engineering and regenerative medicine there is significant unmet need for critically-sized, fully degradable biomaterial scaffold systems with tunable properties for optimizing tissue formation in vitro and tissue regeneration in vivo. To address this need, we have developed a silk-based scaffold platform that has tunable material properties, including localized and bioactive functionalization, degradation rate, and mechanical properties and that provides arrays of linear hollow channels for delivery of oxygen and nutrients throughout the scaffold bulk. The scaffolds can be assembled with dimensions that range from millimeters to centimeters, addressing the need for a critically-sized platform for tissue formation. We demonstrate that the hollow channel arrays support localized and confluent endothelialization. This new platform offers a unique and versatile tool for engineering 'tailored' scaffolds for a range of tissue engineering and regenerative medicine needs. Copyright © 2012 Elsevier Ltd. All rights reserved.

Public health management of invasive meningococcal disease in Baden-Wuerttemberg, Germany, 2012: adherence to guidance and estimation of resources required as determined in a survey of local health authorities.

PubMed

Murajda, Lukas; Aichinger, Elisabeth; Pfaff, Guenter; Hellenbrand, Wiebke

2015-04-12

Invasive meningococcal disease (IMD) incidence in Germany is low, but management of contacts to prevent subsequent cases still requires resources. Local public health authorities (LHA) advise antibiotic post-exposure prophylaxis (PEP) and vaccination to close contacts as defined in national guidance. We aimed to audit implementation of recommendations for IMD public health management in the state of Baden-Wuerttemberg, Germany, and to estimate associated costs. We surveyed all 38 LHAs in Baden-Wuerttemberg to evaluate knowledge of national guidance and implementation of IMD contact management using standardized questionnaires. For IMD cases notified in 2012, we requested numbers of household and other contacts ascertained, including advice given regarding PEP and post-exposure vaccination, plus staff time required for their management. We estimated costs for advised antibiotics, LHA staff time and visits to emergency departments according to published sources. The cost of preventing a subsequent case was estimated based on the number of household contacts that received PEP per IMD case and on the previous finding that ~284 household contacts must receive PEP to prevent one subsequent IMD case. Although LHAs were familiar with national recommendations, they did not advise PEP to 4% of household contacts, while 72% and 100% of school and health provider contacts, respectively, were advised PEP. Only 25% of household contacts of a case with a vaccine-preventable serogroup were advised post-exposure vaccination. A mean of 11.0 contacts/IMD case (range 0-51), of which 3.6 were household contacts, were recommended PEP. Per IMD case, mean costs for LHA staff were estimated at €440.86, for antibiotics at €219.14 and for emergency department visits to obtain PEP at €161.70 - a total of €821.17/IMD case. Preventing a subsequent IMD case would cost ~ €65,000. Our results provide insight into costs of IMD public health management in Germany. We identified marked underuse of post-exposure vaccination in household contacts and overuse of PEP in school and health care contacts. In view of an estimated 3-6 quality-adjusted life years lost per case of IMD, our estimated cost of €65,000 for preventing a subsequent case seems justifiable.

Knowledge, Attitudes and Beliefs regarding Post Exposure Prophylaxis among South African Men who have Sex with Men.

PubMed

Hugo, J M; Stall, R D; Rebe, K; Egan, J E; Jobson, G; De Swardt, G; Struthers, H; McIntyre, J A

2016-12-01

The Soweto Men's Study (2008), demonstrated an overall HIV prevalence rate of 13.2 %, with 10.1 % among straight-identified Men-who-have-sex-with-men (MSM), 6.4 % among bisexual-identified MSM and 33.9 % among gay-identified MSM. Behavioral interventions are imperative, but insufficient to prevent new HIV infections. Biomedical prevention of HIV offers a variety of combination prevention tools, including Post-exposure prophylaxis (PEP). PEP studies amongst MSM have been conducted in Amsterdam, Brazil and San Francisco, but never before in Africa. A cross-sectional, Internet-based survey was initiated to measure knowledge, attitudes and beliefs regarding PEP among South African MSM. Recruitment commenced in June 2014 and ran until October 2015. Participants were recruited through banner advertisements on Facebook.com and mambaonline.com, advertisements in the local gay media and at Health4Men (H4M) MSM-targeted clinics. Outreach workers distributed flyers advertising the study in their local communities. The survey was also made available on a computer at the H4M clinics in Cape Town and Johannesburg to reach MSM who may not have Internet access. A total of 408 men completed the survey. The majority of these men were under the age of 40, identified as gay/homosexual and were employed; 51 % (208/408) self-identified as black or of mixed race. In multivariate analysis participants who identified as gay had greater odds of having previously heard of PEP (AOR 1.91, 95 % CI 1.04, 3.51; p = 0.036), as did those who reported their HIV status as positive (AOR 2.59, 95 % CI 1.47, 4.45; p = 0.001). Participants with medical insurance had greater odds of having used PEP previously (AOR 2.67, 95 % CI 1.11, 6.43; p = 0.029). Bivariate analysis showed that condomless sex in the past 6 months was not significantly associated with PEP knowledge (p = 0.75) or uptake (p = 0.56) of PEP. Our findings suggest a lack of PEP knowledge and uptake among non-gay identified, HIV negative and un-insured MSM. Focusing PEP programs on these men may potentially increase uptake. Increased knowledge needs to be provided to MSM who engage in risky sexual behaviors.

The neuropeptide-12 improves recognition memory and neuronal plasticity of the limbic system in old rats.

PubMed

Hernández-Hernández, Elizabeth Monserrat; Caporal Hernandez, Karen; Vázquez-Roque, Rubén Antonio; Díaz, Alfonso; de la Cruz, Fidel; Florán, Benjamin; Flores, Gonzalo

2018-08-01

Aging is a stage of life where cognitive and motor functions are impaired. This is because oxidative and inflammatory processes exacerbate neurodegeneration, which affects dendritic morphology and neuronal communication of limbic regions with memory loss. Recently, the use of trophic substances has been proposed to prevent neuronal deterioration. The neuropeptide-12 (N-PEP-12) has been evaluated in elderly patients with dementia, showing improvements in cognitive tasks due to acts as a neurotrophic factor. In the present work, we evaluated the effect of N-PEP-12 on motor activity and recognition memory, as well as its effects on dendritic morphology and the immunoreactivity of GFAP, Synaptophysin (SYP), and BDNF in neurons of the prefrontal cortex (PFC), dorsal hippocampus (DH) and nucleus accumbens (NAcc) of aged rats. The results show that N-PEP-12 improved the recognition memory, but the motor activity was not modified compared to the control animals. N-PEP-12 increases the density of dendritic spines and the total dendritic length in neurons of the PFC (layers 3 and 5) and in DH (CA1 and CA3). Interestingly NAcc neurons showed a reduction in the number of dendritic spines. In the N-PEP-12 animals, when evaluating the immunoreactivity for SYP and BDNF, there was an increase in the three brain regions, while the mark for GFAP decreased significantly. Our results suggest that N-PEP-12 promotes neuronal plasticity in the limbic system of aged animals, which contributes to improving recognition memory. In this sense, N-PEP-12 can be considered as a pharmacological alternative to prevent or delay brain aging and control senile dementias. © 2018 Wiley Periodicals, Inc.

Relationship between β-cell function, metabolic control, and microvascular complications in type 2 diabetes mellitus.

PubMed

Zhao, Lihua; Ma, Jing; Wang, Shaoxin; Xie, Yun

2015-01-01

This study investigated the relationship among β-cell function, metabolic control, and diabetic microvascular complications in patients with type 2 diabetes mellitus (T2DM). In total, 885 patients with type 2 diabetes mellitus (DM) were recruited from January 2012 to January 2014 and grouped into three groups according to the area under the curve of C-peptide [AUC(C-pep)] during the 75-g oral glucose tolerance test. Logistic regression analyses were used to evaluate the association between C-peptide and microvascular complications. The prevalence of diabetic microvascular complications decreased from the first to the third AUC(C-pep) tertile (P < 0.01 for all), whereas the rates of nonalcoholic fatty liver disease (NAFLD) was positively associated with AUC(C-pep) values. Patients with lower AUC(C-pep) tertile exhibited higher levels of glycosylated hemoglobin and high-density lipoprotein cholesterol and longer duration of DM; however, levels of triglycerides, fasting C-peptide, 2-h C-peptide, body mass index, and homeostasis model assessment of insulin resistance index were lower compared with the third tertile. Comparison among patients with a similar DM duration showed a higher level of AUC(C-pep) was inversely associated with prevalence of microvascular complications. The odds ratios for nephropathy, retinopathy, and neuropathy in the lowest versus the highest AUC(C-pep) tertile were 3.10 (95% confidence interval, 2.01-4.78), 2.83 (1.73-4.64), and 2.04 (1.37-3.04) after adjustment for confounding factors. Higher AUC(C-pep) levels were associated with a decreased prevalence of microvascular complications and a good level of glycemic control, whereas higher endogenous insulin levels were linked to the components of metabolic syndrome and increased rates of NAFLD.

Fine Mapping of the Dominant Potyvirus Resistance Gene Pvr7 Reveals a Relationship with Pvr4 in Capsicum annuum.

PubMed

Venkatesh, Jelli; An, Jeongtak; Kang, Won-Hee; Jahn, Molly; Kang, Byoung-Cheorl

2018-01-01

Pepper mottle virus (PepMoV) is the most common potyvirus infection of pepper plants and causes significant yield losses. The Pvr7 gene from Capsicum chinense PI159236 and the Pvr4 gene from C. annuum CM334 both have been reported to confer dominant resistance to PepMoV. The Pvr7 locus conferring resistance to PepMoV in C. annuum '9093' was previously mapped to chromosome 10. To develop a high-resolution map of the Pvr7 locus in 9093, we constructed an intraspecific F 2 mapping population consisting of 916 individuals by crossing PepMoV-resistant C. annuum '9093' and the PepMoV-susceptible C. annuum 'Jeju'. To delimit the Pvr7 target region, single-nucleotide polymorphism (SNP) markers derived from the Pvr4 region were used for genotyping the F 2 population. Molecular mapping delimited the Pvr7 locus to a physical interval of 258 kb, which was the same region as Pvr4 on chromosome 10. Three SNP markers derived from Pvr4 mapping perfectly cosegregated with PepMoV resistance. Sequencing analyses of the Pvr7 flanking markers and the Pvr4-specific gene indicated that Pvr7 and Pvr4 are the same gene. Resistance spectrum analysis of 9093 against pepper potyviruses showed that 9093 has a resistance spectrum similar to that of cultivar CM334. These combined results demonstrate that, unlike previously thought, the dominant PepMoV resistance in 9093 could be derived from C. annuum 'CM334', and that Pvr4 and Pvr7 should be considered as the same locus.

Ovule identity mediated by pre-mRNA processing in Arabidopsis

PubMed Central

Rodríguez-Cazorla, Encarnación; Candela, Héctor; Bailey-Steinitz, Lindsay J.; Yanofsky, Martin F.; Martínez-Laborda, Antonio

2018-01-01

Ovules are fundamental for plant reproduction and crop yield as they are the precursors of seeds. Therefore, ovule specification is a critical developmental program. In Arabidopsis thaliana, ovule identity is redundantly conferred by the homeotic D-class genes SHATTERPROOF1 (SHP1), SHP2 and SEEDSTICK (STK), phylogenetically related to the MADS-domain regulatory gene AGAMOUS (AG), essential in floral organ specification. Previous studies have shown that the HUA-PEP activity, comprised of a suite of RNA-binding protein (RBP) encoding genes, regulates AG pre-mRNA processing and thus flower patterning and organ identity. Here, we report that the HUA-PEP activity additionally governs ovule morphogenesis. Accordingly, in severe hua-pep backgrounds ovules transform into flower organ-like structures. These homeotic transformations are most likely due to the dramatic reduction in SHP1, SHP2 and STK activity. Our molecular and genome-wide profiling strategies revealed the accumulation of prematurely terminated transcripts of D-class genes in hua-pep mutants and reduced amounts of their respective functional messengers, which points to pre-mRNA processing misregulation as the origin of the ovule developmental defects in such backgrounds. RNA processing and transcription are coordinated by the RNA polymerase II (RNAPII) carboxyl-terminal domain (CTD). Our results show that HUA-PEP activity members can interact with the CTD regulator C-TERMINAL DOMAIN PHOSPHATASE-LIKE1 (CPL1), supporting a co-transcriptional mode of action for the HUA-PEP activity. Our findings expand the portfolio of reproductive developmental programs in which HUA-PEP activity participates, and further substantiates the importance of RNA regulatory mechanisms (pre-mRNA co-transcriptional regulation) for correct gene expression during plant morphogenesis. PMID:29329291

The cell wall components peptidoglycan and lipoteichoic acid from Staphylococcus aureus act in synergy to cause shock and multiple organ failure.

PubMed Central

De Kimpe, S J; Kengatharan, M; Thiemermann, C; Vane, J R

1995-01-01

Although the incidence of Gram-positive sepsis has risen strongly, it is unclear how Gram-positive organisms (without endotoxin) initiate septic shock. We investigated whether two cell wall components from Staphylococcus aureus, peptidoglycan (PepG) and lipoteichoic acid (LTA), can induce the inflammatory response and multiple organ dysfunction syndrome (MODS) associated with septic shock caused by Gram-positive organisms. In cultured macrophages, LTA (10 micrograms/ml), but not PepG (100 micrograms/ml), induces the release of nitric oxide measured as nitrite. PepG, however, caused a 4-fold increase in the production of nitrite elicited by LTA. Furthermore, PepG antibodies inhibited the release of nitrite elicited by killed S. aureus. Administration of both PepG (10 mg/kg; i.v.) and LTA (3 mg/kg; i.v.) in anesthetized rats resulted in the release of tumor necrosis factor alpha and interferon gamma and MODS, as indicated by a decrease in arterial oxygen pressure (lung) and an increase in plasma concentrations of bilirubin and alanine aminotransferase (liver), creatinine and urea (kidney), lipase (pancreas), and creatine kinase (heart or skeletal muscle). There was also the expression of inducible nitric oxide synthase in these organs, circulatory failure, and 50% mortality. These effects were not observed after administration of PepG or LTA alone. Even a high dose of LTA (10 mg/kg) causes only circulatory failure but no MODS. Thus, our results demonstrate that the two bacterial wall components, PepG and LTA, work together to cause systemic inflammation and multiple systems failure associated with Gram-positive organisms. Images Fig. 2 PMID:7479784

Experimental Percutaneous Extrahepatic Portacaval Shunt Creation by Transjugular Approach in Swine

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

Seong, Chang Kyu; Pavcnik, Dusan, E-mail: pavcnikd@ohsu.edu; Uchida, Barry T.

2005-06-15

The purpose of the study was to evaluate the feasibility of the creation of a percutaneous extrahepatic portacaval shunt (PEPS) in swine by a transjugular approach and to find a suitable stent-graft to use in PEPS. In 12 swine, the extrahepatic portal vein (PV) was entered from the inferior vena cava (IVC) by a needle system introduced from the transjugular approach. A catheter introduced through the transhepatic approach served as a target. Five types of stent-graft consisting of homemade Z stents and a polytetrafluoethylene cover were explored for PEPS creation. Eight animals had follow-up venograms up to 6 weeks ormore » until the shunt became severely stenotic. Gross and histologic examinations were performed after the final follow-up venography. The PV punctures and stent-graft placement were difficult, but the PEPS was established in all animals. In four animals, the stent-graft failed to adequately cover the tract, causing severe hemorrhage. Only two shunts remained patent up to 6 weeks. The other shunts exhibited severe stenosis or occlusion. At gross examination, all shunts traversed the liver parenchyma of the caudate lobe surrounding the IVC. The extravascular PEPS portion was 4 mm to 2 cm long. All shunts entered the PV close to the splenomesenteric junction and exhibited neointimal formation. Shunt stenoses were caused by neointimal hyperplasia and occlusions by a superimposed thrombus. PEPS can be created by the transjugular approach in swine, but only the PV shunt entrance is extrahepatic. None of the tested rigid stent-grafts were suitable for PEPS creation. A short flexible stent-graft with flanged ends is suggested for further exploration.« less

Can protein-fortified pasta serve as a meat substitute?

PubMed

Bingham, C J; Tsay, R; Babayan, V K; Blackburn, G L

1982-01-01

A seventeen-day metabolic balance study was conducted with 13 healthy adult subjects to test the protein utilization of a meat-based diet and a protein-fortified pasta diet in an isonitrogenous, isocaloric inpatient study (averaging 112 gm of protein, and 2,500 cal). Intakes of calories, protein, fat, and carbohydrates, as well as ratios of meat protein or protein-fortified pasta protein (PEP), were controlled throughout the diets. The study was comprised of three experimental periods: a seven-day meat-protein control period, representing the typical american diet (TAD), averaging 18% protein, 40% fat, and 42% carbohydrate, a seven-day protein-enriched pasta control period (PEP), averaging 18% protein, 29% fat, and 53% carbohydrates, and a three-day PEP period composed of varied recipes, averaging 18% protein, 29% fat, and 53% carbohydrates. The subjects who consumed both the TAD and PEP diets achieved nitrogen balance (2.5 gN +/- 0.7 on the TAD, 2 gN +/- 0 on PEP with the PEP diet resulting in a decrease in plasma cholesterol (32 mg/dl, P less than .005), and a decrease in systolic (5.25 mm/Hg P less than .025) and diastolic blood pressure (5 mm/Hg, P less than .05), which was associated with an increase in urinary sodium excretion (19 +/- 17 mEq/day, P less than .025). In this study, it was determined that protein-fortified pasta may serve as a meat alternative. The PEP diet, which includes a beneficial change in fat/carbohydrate ratio, can alter lipid profiles, blood pressure, and sodium excretion, thus leading to improved health status and a decrease in cardiac risk factors.

Peptide drug stability: The anti-inflammatory drugs Pep19-2.5 and Pep19-4LF in cream formulation.

PubMed

Kuhlmann, Nicole; Heinbockel, Lena; Correa, Wilmar; Gutsmann, Thomas; Goldmann, Torsten; Englisch, Uwe; Brandenburg, Klaus

2018-03-30

In previous years, we developed anti-infective drugs based on antimicrobial peptides (AMPs), which have been shown to effectively block severe infections and inflammation in vitro as well as in vivo. Besides systemic application, the occurrence of severe local infections necessitates a topical application for example in the case of severe skin and soft tissue infections (SSTI). Recent investigations show that the synthetic anti-lipopolysaccharide peptide (SALP) Pep19-2.5 (Aspidasept® I) and a variant called Pep19-4LF (Aspidasept® II) are able to supress inflammation reactions also in keratinocytes, Langerhans cells, and dendritic cells from the skin. For topical application, a possible formulation represents the drug dispersed into a pharmaceutical cream (DAC base cream). Here, we present investigations on the stability of the peptides using this formulation in dependence on time, which includes the evaluation of the extraction procedure, the quantitative analysis of the peptides after extraction, its sensitivity to protease degradation and its ability to maintain activity against LPS-induced inflammation in vitro. We have developed an extraction procedure for the peptides with an optimum yield and showed that Pep19-2.5 is present as a dimer after extraction from the cream, whereas Pep19-4LF retains its monomeric form. Both peptides show no degradation by chymotrypsin after extraction for at least 1 h, which is indicative for an attachment of constituents of the base cream, inhibiting the cutting into peptidic part structures. The extracted peptides and in particular the dimeric Pep19-2.5 are still able to inhibit the LPS-induced inflammation reaction in human mononuclear cells. Copyright © 2018 Elsevier B.V. All rights reserved.

Resting sympathetic arousal moderates the association between parasympathetic reactivity and working memory performance in adults reporting high levels of life stress.

PubMed

Giuliano, Ryan J; Gatzke-Kopp, Lisa M; Roos, Leslie E; Skowron, Elizabeth A

2017-08-01

The neurovisceral integration model stipulates that autonomic function plays a critical role in the regulation of higher-order cognitive processes, yet most work to date has examined parasympathetic function in isolation from sympathetic function. Furthermore, the majority of work has been conducted on normative samples, which typically demonstrate parasympathetic withdrawal to increase arousal needed to complete cognitive tasks. Little is known about how autonomic regulation supports cognitive function in populations exposed to high levels of stress, which is critical given that chronic stress exposure alters autonomic function. To address this, we sought to characterize how parasympathetic (high-frequency heart rate variability, HF-HRV) and sympathetic (preejection period, PEP) measures of cardiac function contribute to individual differences in working memory (WM) capacity in a sample of high-risk women. HF-HRV and PEP were measured at rest and during a visual change detection measure of WM. Multilevel modeling was used to examine within-person fluctuations in WM performance throughout the task concurrently with HF-HRV and PEP, as well as between-person differences as a function of resting HF-HRV and PEP levels. Results indicate that resting PEP moderated the association between HF-HRV reactivity and WM capacity. Increases in WM capacity across the task were associated with increases in parasympathetic activity, but only among individuals with longer resting PEP (lower sympathetic arousal). Follow-up analyses showed that shorter resting PEP was associated with greater cumulative risk exposure. These results support the autonomic space framework, in that the relationship between behavior and parasympathetic function appears dependent on resting sympathetic activation. © 2017 Society for Psychophysiological Research.

A LC-MS/MS method to monitor the concentration of HYD-PEP06, a RGD-modified Endostar mimetic peptide in rat blood.

PubMed

Dong, Xiaona; Zhang, Yiwei; Meng, Zhiyun; Zhu, Xiaoxia; Gan, Hui; Gu, Ruolan; Wu, Zhuona; Li, Jian; Zheng, Ying; Yang, Baofeng; Dou, Guifang

2018-05-29

HYD-PEP06 is a novel RGD-modified Endostar mimetic peptide with 30 amino acids that is intended to suppress the formation of neoplasm vessels. This assay was developed and validated to monitor the level of the peptide HYD-PEP06 in rat blood, using liquid chromatography tandem mass spectrometry (LC-MS/MS). HYD-PEP10, another peptide similar to the analyte, was used as an internal standard (IS). A triple quadrupole mass spectrometry in Multiple Reaction Monitoring (MRM) mode and an electrospray interface (ESI) in the positive mode were used for MS analysis. The analysis was optimized with addition of 0.3% formic acid (FA) into the mobile phase as well as with a needle washing solution to overcome the carryover effect. In addition, the carryover was reduced by optimizing the mobile phase gradient. Methanol was used as a diluent of working solutions to avoid any adsorption. Methanol:acetonitrile (1:1, v:v) containing 0.3% FA was employed to precipitate the blood samples. Unknown blood samples must be placed in ice bath immediately, and precipitating agents should be added within 30 min to ensure the stability of blood samples. The assay was established and validated. This method showed a good linear relationship for the HYD-PEP06 in the range of 10 ng·mL -1 to 2000 ng·mL -1 , with R > 0.99. HYD-PEP06 was determined with accuracy values (RE%) of -5.06%-8.54%, intra- and inter-day precisions (RSD%) of 3.13%-4.87% and 4.81%-9.42%. The method was successfully in monitoring the concentration of HYD-PEP06 in rat blood. Copyright © 2018 Elsevier B.V. All rights reserved.

Bile Acid-regulated Peroxisome Proliferator-activated Receptor-α (PPARα) Activity Underlies Circadian Expression of Intestinal Peptide Absorption Transporter PepT1/Slc15a1*

PubMed Central

Okamura, Ayako; Koyanagi, Satoru; Dilxiat, Adila; Kusunose, Naoki; Chen, Jia Jun; Matsunaga, Naoya; Shibata, Shigenobu; Ohdo, Shigehiro

2014-01-01

Digested proteins are mainly absorbed as small peptides composed of two or three amino acids. The intestinal absorption of small peptides is mediated via only one transport system: the proton-coupled peptide transporter-1 (PepT1) encoded from the soluble carrier protein Slc15a1. In mammals, intestinal expression of PepT1/Slc15a1 oscillates during the daily feeding cycle. Although the oscillation in the intestinal expression of PepT1/Slc15a1 is suggested to be controlled by molecular components of circadian clock, we demonstrated here that bile acids regulated the oscillation of PepT1/Slc15a1 expression through modulating the activity of peroxisome proliferator-activated receptor α (PPARα). Nocturnally active mice mainly consumed their food during the dark phase. PPARα activated the intestinal expression of Slc15a1 mRNA during the light period, and protein levels of PepT1 peaked before the start of the dark phase. After food intake, bile acids accumulated in intestinal epithelial cells. Intestinal accumulated bile acids interfered with recruitment of co-transcriptional activator CREB-binding protein/p300 on the promoter region of Slc15a1 gene, thereby suppressing PPARα-mediated transactivation of Slc15a1. The time-dependent suppression of PPARα-mediated transactivation by bile acids caused an oscillation in the intestinal expression of PepT1/Slc15a1 during the daily feeding cycle that led to circadian changes in the intestinal absorption of small peptides. These findings suggest a molecular clock-independent mechanism by which bile acid-regulated PPARα activity governs the circadian expression of intestinal peptide transporter. PMID:25016014

Kisspeptin Antagonists Reveal Kisspeptin 1 and Kisspeptin 2 Differential Regulation of Reproduction in the Teleost, Morone saxatilis.

PubMed

Zmora, Nilli; Stubblefield, John David; Wong, Ten-Tsao; Levavi-Sivan, Berta; Millar, Robert Peter; Zohar, Yonathan

2015-09-01

The importance of kisspeptin in regulating vertebrate reproduction has been well established, but the exact mechanism continues to unfold. Unlike mammals, many lower vertebrates possess a dual kisspeptin system, Kiss1 and Kiss2. To decipher the roles of the kisspeptins in fish, we identified two potential kisspeptin antagonists, pep 234 and pep 359, by screening analogs for their ability to inactivate striped bass Kiss1 and Kiss2 receptors expressed in COS7 cells. Pep 234 (a mammalian KISS1 antagonist) antagonizes Kiss1r signaling activated by Kiss1 and Kiss2, and pep 359 (a novel analog) antagonizes Kiss2 activation of both receptors. In vitro studies using brain slices demonstrated that only Kiss2 can upregulate the expression of the hypophysiotropic gnrh1, which was subsequently diminished by pep 234 and pep 359. In primary pituitary cell cultures, the two antagonists revealed a complex network of putative endogenous and exogenous regulation by kisspeptin. While both kisspeptins stimulate Fsh expression and secretion, Kiss2 predominately induces Lh secretion. Pep 234 and 359 treatment of spawning males hindered sperm production. This effect was accompanied with decreased brain gnrh1 and gnrh2 mRNA levels and peptide content in the pituitary, and increased levels of pituitary Lh, probably due to attenuation of Lh release. Strikingly, the mRNA levels of arginine-vasotocin, the neurons of which in the preoptic area coexpress kiss2r, were dramatically reduced by the antagonists. Our results demonstrate differential actions of Kiss1 and Kiss2 systems along the hypothalamic-pituitary axis and interactions with other neuropeptides, and further reinforce the importance of kisspeptin in the execution of spawning. © 2015 by the Society for the Study of Reproduction, Inc.

Resting sympathetic arousal moderates the association between parasympathetic reactivity and working memory performance in adults reporting high levels of life stress

PubMed Central

Giuliano, Ryan J.; Gatzke-Kopp, Lisa M.; Roos, Leslie E.; Skowron, Elizabeth A.

2017-01-01

The neurovisceral integration model stipulates that autonomic function plays a critical role in the regulation of higher-order cognitive processes, yet most work to date has examined parasympathetic function in isolation from sympathetic function. Furthermore, the majority of work has been conducted on normative samples, which typically demonstrate parasympathetic withdrawal to increase arousal needed to complete cognitive tasks. Little is known about how autonomic regulation supports cognitive function in populations exposed to high levels of stress, which is critical given that chronic stress exposure alters autonomic function. To address this, we sought to characterize how parasympathetic (high-frequency heart rate variability, HF-HRV) and sympathetic (preejection period, PEP) measures of cardiac function contribute to individual differences in working memory (WM) capacity in a sample of high-risk women. HF-HRV and PEP were measured at rest and during a visual change detection measure of WM. Multilevel modeling was used to examine within-person fluctuations in WM performance throughout the task concurrently with HF-HRV and PEP, as well as between-person differences as a function of resting HF-HRV and PEP levels. Results indicate that resting PEP moderated the association between HF-HRV reactivity and WM capacity. Increases in WM capacity across the task were associated with increases in parasympathetic activity, but only among individuals with longer resting PEP (lower sympathetic arousal). Follow-up analyses showed that shorter resting PEP was associated with greater cumulative risk exposure. These results support the autonomic space framework, in that the relationship between behavior and parasympathetic function appears dependent on resting sympathetic activation. PMID:28449242

Intra-Beam Scattering, Impedance, and Instabilities in Ultimate Storage Rings

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

Bane, Karl; /SLAC

We have investigated collective effects in an ultimate storage ring, i.e. one with diffraction limited emittances in both planes, using PEP-X as an example. In an ultimate ring intra-beam scattering (IBS) sets the limit of current that can be stored. In PEP-X, a 4.5 GeV ring running round beams at 200 mA in 3300 bunches, IBS doubles the emittances to 11.5 pm at the design current. The Touschek lifetime is 11 hours. Impedance driven collective effects tend not to be important since the beam current is relatively low. We have investigated collective effects in PEP-X, an ultimate storage ring, i.e.more » one with diffraction limited emittances (at one angstrom wavelength) in both planes. In an ultimate ring intra-beam scattering (IBS) sets the limit of current that can be stored. In PEP-X, IBS doubles the emittances to 11.5 pm at the design current of 200 mA, assuming round beams. The Touschek lifetime is quite large in PEP-X, 11.6 hours, and - near the operating point - increases with decreasing emittance. It is, however, a very sensitive function of momentum acceptance. In an ultimate ring like PEP-X impedance driven collective effects tend not to be important since the beam current is relatively low. Before ultimate PEP-X can be realized, the question of how to run a machine with round beams needs serious study. For example, in this report we assumed that the vertical emittance is coupling dominated. It may turn out that using vertical dispersion is a preferable way to generate round beams. The choice will affect IBS and the Touschek effect.« less

Effects of nasal positive expiratory pressure on dynamic hyperinflation and 6-minute walk test in patients with COPD.

PubMed

Wibmer, Thomas; Rüdiger, Stefan; Heitner, Claudia; Kropf-Sanchen, Cornelia; Blanta, Ioanna; Stoiber, Kathrin M; Rottbauer, Wolfgang; Schumann, Christian

2014-05-01

Dynamic hyperinflation is an important target in the treatment of COPD. There is increasing evidence that positive expiratory pressure (PEP) could reduce dynamic hyperinflation during exercise. PEP application through a nasal mask and a flow resistance device might have the potential to be used during daily physical activities as an auxiliary strategy of ventilatory assistance. The aim of this study was to determine the effects of nasal PEP on lung volumes during physical exercise in patients with COPD. Twenty subjects (mean ± SD age 69.4 ± 6.4 years) with stable mild-to-severe COPD were randomized to undergo physical exercise with nasal PEP breathing, followed by physical exercise with habitual breathing, or vice versa. Physical exercise was induced by a standard 6-min walk test (6 MWT) protocol. PEP was applied by means of a silicone nasal mask loaded with a fixed-orifice flow resistor. Body plethysmography was performed immediately pre-exercise and post-exercise. Differences in mean pre- to post-exercise changes in total lung capacity (-0.63 ± 0.80 L, P = .002), functional residual capacity (-0.48 ± 0.86 L, P = .021), residual volume (-0.56 ± 0.75 L, P = .004), S(pO2) (-1.7 ± 3.4%, P = .041), and 6 MWT distance (-30.8 ± 30.0 m, P = .001) were statistically significant between the experimental and the control interventions. The use of flow-dependent expiratory pressure, applied with a nasal mask and a PEP device, might promote significant reduction of dynamic hyperinflation during walking exercise. Further studies are warranted addressing improvements in endurance performance under regular application of nasal PEP during physical activities.

Background sources at PEP

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

Lynch, H.; Schwitters, R.F.; Toner, W.T.

Important sources of background for PEP experiments are studied. Background particles originate from high-energy electrons and positrons which have been lost from stable orbits, ..gamma..-rays emitted by the primary beams through bremsstrahlung in the residual gas, and synchrotron radiation x-rays. The effect of these processes on the beam lifetime are calculated and estimates of background rates at the interaction region are given. Recommendations for the PEP design, aimed at minimizing background are presented. 7 figs., 4 tabs.

Engineering of Surface Chemistry for Enhanced Sensitivity in Nanoporous Interferometric Sensing Platforms.

PubMed

Law, Cheryl Suwen; Sylvia, Georgina M; Nemati, Madieh; Yu, Jingxian; Losic, Dusan; Abell, Andrew D; Santos, Abel

2017-03-15

We explore new approaches to engineering the surface chemistry of interferometric sensing platforms based on nanoporous anodic alumina (NAA) and reflectometric interference spectroscopy (RIfS). Two surface engineering strategies are presented, namely (i) selective chemical functionalization of the inner surface of NAA pores with amine-terminated thiol molecules and (ii) selective chemical functionalization of the top surface of NAA with dithiol molecules. The strong molecular interaction of Au 3+ ions with thiol-containing functional molecules of alkane chain or peptide character provides a model sensing system with which to assess the sensitivity of these NAA platforms by both molecular feature and surface engineering. Changes in the effective optical thickness of the functionalized NAA photonic films (i.e., sensing principle), in response to gold ions, are monitored in real-time by RIfS. 6-Amino-1-hexanethiol (inner surface) and 1,6-hexanedithiol (top surface), the most sensitive functional molecules from approaches i and ii, respectively, were combined into a third sensing strategy whereby the NAA platforms are functionalized on both the top and inner surfaces concurrently. Engineering of the surface according to this approach resulted in an additive enhancement in sensitivity of up to 5-fold compared to previously reported systems. This study advances the rational engineering of surface chemistry for interferometric sensing on nanoporous platforms with potential applications for real-time monitoring of multiple analytes in dynamic environments.

Is ESR Important for Predicting Post-ERCP Pancreatitis?

PubMed

Mohammad Alizadeh, Amir Houshang; Afzali, Esmaeil Shamsi; Behzad, Catherine; Mousavi, Mirhadi; Mirsattari, Dariush; Doagoo, Siavash Zafar; Zali, Mohammad Reza

2015-01-01

Pancreatitis remains the most common complication of endoscopic retrograde cholangiopancreatography (ERCP), resulting in substantial morbidity and occasional mortality. There are notable controversies and conflicting reports about risk factors of post-ERCP pancreatitis (PEP). To evaluate the potential risk factors for PEP at a referral tertiary center, as a sample of the Iranian population. Baseline characteristics and clinical as well as paraclinical information of 780 patients undergoing diagnostic and therapeutic ERCP at Taleghani hospital in Tehran between 2008 and 2012 were reviewed. Data were collected prior to the ERCP, at the time of the procedure, and 24-72 hours after discharge. PEP was diagnosed according to consensus criteria. Of the 780 patients who underwent diagnostic ERCP, pancreatitis developed in 26 patients (3.3%). In the multivariable risk model, significant risk factors with adjusted odds ratios (ORs) were age <65 years (OR = 10.647, P = 0.023) and erythrocyte sedimentation rate (ESR) >30 (OR = 6.414, P < 0.001). Female gender, history of recurrent pancreatitis, pre-ERCP hyperamylasemia, and difficult or failed cannulation could not predict PEP. There was no significant difference in the rate of PEP in wire-guided cannulation versus biliary cannulation using a sphincterotome and contrast injection as the conventional method. Performing ERCP may be safer in the elderly. Patients with high ESR may be at greater risk of PEP, which warrants close observation of these patients for signs of pancreatitis after ERCP.

Rabies Vaccine Hesitancy and Deaths Among Pregnant and Breastfeeding Women - Vietnam, 2015-2016.

PubMed

Nguyen, Huong T T; Tran, Cuc H; Dang, Anh D; Tran, Huong G T; Vu, Thiem D; Pham, Thach N; Nguyen, Hoang V; Nguyen, Anh N K; Pieracci, Emily G; Tran, Duong N

2018-03-02

Human rabies deaths are preventable through prompt administration of postexposure prophylaxis (PEP) with rabies immune globulin and rabies vaccine after exposure to a rabid animal (1); there are no known contraindications to receiving PEP (1,2). Despite widespread availability of PEP in Vietnam, in 2015 the Ministry of Health (MoH) received reports of pregnant and breastfeeding women with clinically diagnosed rabies. MoH investigated factors associated with these rabies cases. MoH found that, during 2015-2016, among 169 cases reported in Vietnam, two probable cases of rabies were reported in breastfeeding mothers and four in pregnant women, all of whom had been bitten by dogs. All six patients died. Three of the four pregnant women had cesarean deliveries. One of the three newborns died from complications believed to be unrelated to rabies; the fourth pregnant woman contracted rabies too early in pregnancy for the fetus to be viable. Two of the patients sought care from a medical provider or traditional healer; however, none sought PEP after being bitten. In each case, families reported the patient's fear of risk to the fetus or breastfed child as the primary barrier to receiving PEP. These findings highlight the need for public health messaging about the safety and effectiveness of PEP in preventing rabies among all persons with exposures, including pregnant and breastfeeding women.

StraPep: a structure database of bioactive peptides

PubMed Central

Wang, Jian; Yin, Tailang; Xiao, Xuwen; He, Dan; Xue, Zhidong; Jiang, Xinnong; Wang, Yan

2018-01-01

Abstract Bioactive peptides, with a variety of biological activities and wide distribution in nature, have attracted great research interest in biological and medical fields, especially in pharmaceutical industry. The structural information of bioactive peptide is important for the development of peptide-based drugs. Many databases have been developed cataloguing bioactive peptides. However, to our knowledge, database dedicated to collect all the bioactive peptides with known structure is not available yet. Thus, we developed StraPep, a structure database of bioactive peptides. StraPep holds 3791 bioactive peptide structures, which belong to 1312 unique bioactive peptide sequences. About 905 out of 1312 (68%) bioactive peptides in StraPep contain disulfide bonds, which is significantly higher than that (21%) of PDB. Interestingly, 150 out of 616 (24%) bioactive peptides with three or more disulfide bonds form a structural motif known as cystine knot, which confers considerable structural stability on proteins and is an attractive scaffold for drug design. Detailed information of each peptide, including the experimental structure, the location of disulfide bonds, secondary structure, classification, post-translational modification and so on, has been provided. A wide range of user-friendly tools, such as browsing, sequence and structure-based searching and so on, has been incorporated into StraPep. We hope that this database will be helpful for the research community. Database URL: http://isyslab.info/StraPep PMID:29688386

Metabolic networks to generate pyruvate, PEP and ATP from glycerol in Pseudomonas fluorescens.

PubMed

Alhasawi, Azhar; Thomas, Sean C; Appanna, Vasu D

2016-04-01

Glycerol is a major by-product of the biodiesel industry. In this study we report on the metabolic networks involved in its transformation into pyruvate, phosphoenolpyruvate (PEP) and ATP. When the nutritionally-versatile Pseudomonas fluorescens was exposed to hydrogen peroxide (H2O2) in a mineral medium with glycerol as the sole carbon source, the microbe reconfigured its metabolism to generate adenosine triphosphate (ATP) primarily via substrate-level phosphorylation (SLP). This alternative ATP-producing stratagem resulted in the synthesis of copious amounts of PEP and pyruvate. The production of these metabolites was mediated via the enhanced activities of such enzymes as pyruvate carboxylase (PC) and phosphoenolpyruvate carboxylase (PEPC). The high energy PEP was subsequently converted into ATP with the aid of pyruvate phosphate dikinase (PPDK), phosphoenolpyruvate synthase (PEPS) and pyruvate kinase (PK) with the concomitant formation of pyruvate. The participation of the phospho-transfer enzymes like adenylate kinase (AK) and acetate kinase (ACK) ensured the efficiency of this O2-independent energy-generating machinery. The increased activity of glycerol dehydrogenase (GDH) in the stressed bacteria provided the necessary precursors to fuel this process. This H2O2-induced anaerobic life-style fortuitously evokes metabolic networks to an effective pathway that can be harnessed into the synthesis of ATP, PEP and pyruvate. The bioconversion of glycerol to pyruvate will offer interesting economic benefit. Copyright © 2016 Elsevier Inc. All rights reserved.

Perspectives on HIV Pre- and Post-Exposure Prophylaxes (PrEP and PEP) Among Female and Male Sex Workers in Mombasa, Kenya: Implications for Integrating Biomedical Prevention into Sexual Health Services.

PubMed

Restar, Arjee J; Tocco, Jack Ume; Mantell, Joanne E; Lafort, Yves; Gichangi, Peter; Masvawure, Tsitsi B; Chabeda, Sophie Vusha; Sandfort, Theo G M

2017-04-01

Pre- and post-exposure prophylaxes (PrEP and PEP) can reduce the risk of HIV acquisition, yet often are inaccessible to and underutilized by most-vulnerable populations, including sex workers in sub-Saharan Africa. Based on in-depth interviews with 21 female and 23 male HIV-negative sex workers in Mombasa, Kenya, we found that awareness and knowledge of PrEP and PEP were low, although willingness to use both was high. Participants felt PrEP would be empowering and give added protection against infection, although some expressed concerns about side effects. Despite PEP's availability, few knew about it and even fewer had used it, but most who had would use it again. Sex workers valued confidentiality, privacy, trustworthiness, and convenient location in health services and wanted thorough HIV/STI assessments. These findings suggest the importance of situating PrEP and PEP within sex worker-friendly health services and conducting outreach to promote these biomedical prevention methods for Kenyan sex workers.

The isolated, twenty-three-residue-long, N-terminal region of the glutamine synthetase inactivating factor binds to its target.

PubMed

Neira, José L; Florencio, Francisco J; Muro-Pastor, M Isabel

2017-09-01

Glutamine synthetase (GS) catalyzes the ATP-dependent formation of glutamine from glutamate and ammonia. The activity of Synechocystis sp. PCC 6803 GS type I is regulated by protein-protein interactions with a 65-residue-long protein (IF7). IF7 binds initially to GS through residues at its N terminus. In this work, we studied the conformational preferences of the N-terminal region of IF7 (IF7pep, residues Ala7-Ala29), its binding to GS and its functional properties. Isolated IF7pep populated a nascent helix in aqueous solution. IF7pep was bound to GS with an affinity constant of 0.4μM, and a 1:1 stoichiometry. IF7pep did not inactivate GS, suggesting that there were other IF7 regions important to carry out the inactivating function. Binding of IF7pep to GS was electrostatically-driven and it did not follow a kinetic two-state model. Copyright © 2017 Elsevier B.V. All rights reserved.

Application of photon detectors in the VIP2 experiment to test the Pauli Exclusion Principle

NASA Astrophysics Data System (ADS)

Pichler, A.; Bartalucci, S.; Bazzi, M.; Bertolucci, S.; Berucci, C.; Bragadireanu, M.; Cargnelli, M.; Clozza, A.; Curceanu, C.; De Paolis, L.; Di Matteo, S.; D'Ufflzi, A.; Egger, J.-P.; Guaraldo, C.; Iliescu, M.; Ishiwatari, T.; Laubenstein, M.; Marton, J.; Milotti, E.; Pietreanu, D.; Piscicchia, K.; Ponta, T.; Sbardella, E.; Scordo, A.; Shi, H.; Sirghi, D.; Sirghi, F.; Sperandio, L.; Vazquez-Doce, O.; Widmann, E.; Zmeskal, J.

2016-05-01

The Pauli Exclusion Principle (PEP) was introduced by the austrian physicist Wolfgang Pauli in 1925. Since then, several experiments have checked its validity. From 2006 until 2010, the VIP (Violation of the Pauli Principle) experiment took data at the LNGS underground laboratory to test the PEP. This experiment looked for electronic 2p to Is transitions in copper, where 2 electrons are in the Is state before the transition happens. These transitions violate the PEP. The lack of detection of X-ray photons coming from these transitions resulted in a preliminary upper limit for the violation of the PEP of 4.7 × 10-29. Currently, the successor experiment VIP2 is under preparation. The main improvements are, on one side, the use of Silicon Drift Detectors (SDDs) as X-ray photon detectors. On the other side an active shielding is implemented, which consists of plastic scintillator bars read by Silicon Photomultipliers (SiPMs). The employment of these detectors will improve the upper limit for the violation of the PEP by around 2 orders of magnitude.

The effect of vacuum packaging on histamine changes of milkfish sticks at various storage temperatures.

PubMed

Kung, Hsien-Feng; Lee, Yi-Chen; Lin, Chiang-Wei; Huang, Yu-Ru; Cheng, Chao-An; Lin, Chia-Min; Tsai, Yung-Hsiang

2017-10-01

The effects of polyethylene packaging (PEP) (in air) and vacuum packaging (VP) on the histamine related quality of milkfish sticks stored at different temperatures (-20°C, 4°C, 15°C, and 25°C) were studied. The results showed that the aerobic plate count (APC), pH, total volatile basic nitrogen (TVBN), and histamine contents increased as storage time increased when the PEP and VP samples were stored at 25°C. At below 15°C, the APC, TVBN, pH, and histamine levels in PEP and VP samples were retarded, but the VP samples had considerably lower levels of APC, TVBN, and histamine than PEP samples. Once the frozen fish samples stored at -20°C for 2 months were thawed and stored at 25°C, VP retarded the increase of histamine in milkfish sticks as compared to PEP. In summary, this result suggested the milkfish sticks packed with VP and stored below 4°C could prevent deterioration of product quality and extend shelf-life. Copyright © 2017. Published by Elsevier B.V.

Perspectives on HIV Pre- and Post- Exposure Prophylaxes (PrEP and PEP) among Female and Male Sex Workers in Mombasa, Kenya: Implications for Integrating Biomedical Prevention into Sexual Health Services

PubMed Central

Restar, Arjee J.; Tocco, Jack Ume; Mantell, Joanne E.; Lafort, Yves; Gichangi, Peter; Masvawure, Tsitsi B; Chabeda, Sophie Vusha; Sandfort, Theo G. M.

2017-01-01

Pre- and post-exposure prophylaxis (PrEP and PEP) can reduce the risk of HIV acquisition, yet often are inaccessible to and underutilized by most-vulnerable populations, including sex workers in sub-Saharan Africa. Based on in-depth interviews with 21 female and 23 male HIV-negative sex workers in Mombasa, Kenya, we found that awareness and knowledge of PrEP and PEP were low, although willingness to use both was high. Participants felt PrEP would be empowering and give added protection against infection, although some expressed concerns about side effects. Despite its availability, few knew about PEP and even fewer had used it, but most who had would use it again. Sex workers valued confidentiality, privacy, trustworthiness, and convenient location in health services and wanted thorough HIV/STI assessments. These findings suggest the importance of situating PrEP and PEP within sex worker-friendly health services and conducting outreach to promote these biomedical prevention methods for Kenyan sex workers. PMID:28467163

Calorimetric and spectroscopic investigation of the interaction between the C-terminal domain of Enzyme I and its ligands

PubMed Central

Yun, Young-Joo; Suh, Jeong-Yong

2012-01-01

Enzyme I initiates a series of phosphotransfer reactions during sugar uptake in the bacterial phosphotransferase system. Here, we have isolated a stable recombinant C-terminal domain of Enzyme I (EIC) of Escherichia coli and characterized its interaction with the N-terminal domain of Enzyme I (EIN) and also with various ligands. EIC can phosphorylate EIN, but their binding is transient regardless of the presence of phosphoenolpyruvate (PEP). Circular dichroism and NMR indicate that ligand binding to EIC induces changes near aromatic groups but not in the secondary structure of EIC. Binding of PEP to EIC is an endothermic reaction with the equilibrium dissociation constant (KD) of 0.28 mM, whereas binding of the inhibitor oxalate is an exothermic reaction with KD of 0.66 mM from calorimetry. The binding thermodynamics of EIC and PEP compared to that of Enzyme I (EI) and PEP reveals that domain–domain motion in EI can contribute as large as ∼−3.2 kcal/mol toward PEP binding. PMID:22936614

Post-event Processing Predicts Impaired Cortisol Recovery Following Social Stressor: The Moderating Role of Social Anxiety.

PubMed

Maeda, Shunta; Sato, Tomoya; Shimada, Hironori; Tsumura, Hideki

2017-01-01

There is growing evidence that individuals with social anxiety show impaired cortisol recovery after experiencing social evaluative stressors. Yet, little is known regarding the cognitive processes underlying such impaired cortisol recovery. The present study examined the effect of post-event processing (PEP), referred to as repetitive thinking about social situations, on cortisol recovery following a social stressor. Forty-two non-clinical university students (23 women, 19 men, mean age = 22.0 ± 2.0 years) completed the Trier Social Stress Test (TSST), followed by a thought sampling procedure which assessed the frequency of PEP reflecting the TSST. A growth curve model showed PEP and social anxiety interactively predicted cortisol recovery. In particular, PEP predicted impaired cortisol recovery in those with low levels of social anxiety but not in those with high levels of social anxiety, which contradicted the initial hypothesis. These findings suggest that PEP is differentially associated with cortisol recovery depending on levels of social anxiety. The possible mechanisms underlying these findings were discussed in terms of protective inhibition framework.

Delivering health information about self-medication to older adults: use of touchscreen-equipped notebook computers.

PubMed

Neafsey, P J; Strickler, Z; Shellman, J; Padula, A T

2001-11-01

Preventing Drug Interactions in Active Older Adults is an educational intervention to prevent prescription and over-the-counter (OTC) drug and alcohol interactions in active, community-living older adults. The objectives of the program are to increase older adults' knowledge of potential interactions of prescription medications with OTC drugs and alcohol and to increase their confidence (self-efficacy) about how to avoid such interactions. An interactive multimedia computer software program (Personal Education Program or PEP) was designed for the learning styles and psychomotor skills of older adults. Focus groups of older adults evaluated PEP components in a formative manner during development. The program content dealing with antacids, calcium supplements, and acid reducers was pilot tested with 60 older adults recruited from local senior centers. Participants used the PEP on notebook computers equipped with infrared-sensitive touchscreens. Users of PEP had greater knowledge and self-efficacy scores than controls. Participants indicated a high degree of satisfaction with the PEP and reported their intent to make specific changes in self-medication behaviors.

Pep19 drives epitope spreading in periodontitis and periodontitis-associated autoimmune diseases.

PubMed

Kwon, E-Y; Cha, G S; Jeong, E; Lee, J-Y; Kim, S-J; Surh, C D; Choi, J

2016-06-01

Epitope spreading is one of valid mechanisms operating in immunopathological processes of infection-induced autoimmune diseases. We hypothesized that the peptide 19 from Porphyromonas gingivalis heat shock protein (HSP) 60 (Pep19) may be the dominant epitope from which epitope-specific immune response to subdominant epitopes may diversify sequentially into autoimmune responses directed at human neoepitopes in P. gingivalis-induced periodontitis and autoimmune diseases. However, the exact feature and mechanism on how Pep19 may drive epitope spreading into human autoantigens in chronic periodontitis or P. gingivalis-induced experimental periodontitis has not been clarified. The present study was performed with the following specific aims: (i) to delineate retrospectively the features of epitope spreading by human cross-sectional analysis; (ii) to demonstrate prospectively the epitope spreading into new antigenic determinants in an ordered, predictable and sequential manner in experimental periodontitis; and (iii) to clarify the mechanism on how immunization with Pep19 may mobilize helper T cells or elicit B-cell responses to human autoantigens and neoantigen. The study was devised for two independent investigations - a cross-sectional analysis on clinical subjects and a prospective analysis on experimental periodontitis - each being subdivided further into two additional independent observations. Cross-sectional dot immunoblot pattern against a panel of peptides of P. gingivalis HSP60 and human HSP60 was performed among age-dependent healthy subjects and between healthy subjects, patients with chronic periodontitis and patients with autoimmune disease, to identify epitope spreading. A peptide-specific T-cell line was established for phenotype analysis and for proliferation assay to an array of identical peptides. An identical prospective analysis was performed in P. gingivalis-induced experimental periodontitis or in Pep19-immunized mice. Cross-reactivity of anti-Pep19 monoclonal antibody was also investigated. A dominant immune response exclusively to Pep19 prevailed in healthy human subjects (before the age of 40) and mice that persisted in chronic periodontitis and autoimmune diseases without being replaced further by subsequent subdominant epitopes. A sequential epitope spreading provoked by Pep19 to subdominant autoantigen peptide 19 from human HSP60 (Hu19) in most healthy human subjects and mice, and to autoantigen peptide 9 from human HSP60 (Hu9) and neoantigen oxidized low-density lipoprotein (ox-LDL) in P. gingivalis-induced chronic periodontitis and autoimmune diseases could be demonstrated in a reproducible and predictable manner. T-cell proliferative activity to multiple autoantigens Hu19, Hu9 and ox-LDL, and cross-reactivity of anti-Pep19 monoclonal antibody to these epitopes may be proposed as cellular and molecular mechanisms responsible for the phenomenon. Moreover, the predictive value of Pep19 for Hu9 increased remarkably in the disease group when compared with that of the healthy group. Taken together, epitope spreading to Hu19, Hu9 and ox-LDL provoked by Pep19 could be proposed as a solid phenomenon observed in P. gingivalis-induced chronic periodontitis and infection-induced autoimmune diseases in a reproducible and predictable manner. T-cell proliferative activity to these peptides and cross-reactivity of anti-Pep19 antibodies to multiple human autoantigens could be proposed as cellular and molecular mechanisms responsible for this phenomenon. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Encouraging the pursuit of advanced degrees in science and engineering: Top-down and bottom-up methodologies

NASA Technical Reports Server (NTRS)

Maddox, Anthony B.; Smith-Maddox, Renee P.; Penick, Benson E.

1989-01-01

The MassPEP/NASA Graduate Research Development Program (GRDP) whose objective is to encourage Black Americans, Mexican Americans, American Indians, Puerto Ricans, and Pacific Islanders to pursue graduate degrees in science and engineering is described. The GRDP employs a top-down or goal driven methodology through five modules which focus on research, graduate school climate, technical writing, standardized examinations, and electronic networking. These modules are designed to develop and reinforce some of the skills necessary to seriously consider the goal of completing a graduate education. The GRDP is a community-based program which seeks to recruit twenty participants from a pool of Boston-area undergraduates enrolled in engineering and science curriculums and recent graduates with engineering and science degrees. The program emphasizes that with sufficient information, its participants can overcome most of the barriers perceived as preventing them from obtaining graduate science and engineering degrees. Experience has shown that the top-down modules may be complemented by a more bottom-up or event-driven methodology. This approach considers events in the academic and professional experiences of participants in order to develop the personal and leadership skills necessary for graduate school and similar endeavors.

Radiofrequency treatment enhances the catalytic function of an immobilized nanobiohybrid catalyst

NASA Astrophysics Data System (ADS)

San, Boi Hoa; Ha, Eun-Ju; Paik, Hyun-Jong; Kim, Kyeong Kyu

2014-05-01

Biocatalysis, the use of enzymes in chemical transformation, has undergone intensive development for a wide range of applications. As such, maximizing the functionality of enzymes for biocatalysis is a major priority to enable industrial use. To date, many innovative technologies have been developed to address the future demand of enzymes for these purposes, but maximizing the catalytic activity of enzymes remains a challenge. In this study, we demonstrated that the functionality of a nanobiocatalyst could be enhanced by combining immobilization and radiofrequency (RF) treatment. Aminopeptidase PepA-encapsulating 2 nm platinum nanoparticles (PepA-PtNPs) with the catalytic activities of hydrolysis and hydrogenation were employed as multifunctional nanobiocatalysts. Immobilizing the nanobiocatalysts in a hydrogel using metal chelation significantly enhanced their functionalities, including catalytic power, thermal-stability, pH tolerance, organic solvent tolerance, and reusability. Most importantly, RF treatment of the hydrogel-immobilized PepA-PtNPs increased their catalytic power by 2.5 fold greater than the immobilized PepA. Our findings indicate that the catalytic activities and functionalities of PepA-PtNPs are greatly enhanced by the combination of hydrogel-immobilization and RF treatment. Based on our findings, we propose that RF treatment of nanobiohybrid catalysts immobilized on the bulk hydrogel represents a new strategy for achieving efficient biocatalysis.Biocatalysis, the use of enzymes in chemical transformation, has undergone intensive development for a wide range of applications. As such, maximizing the functionality of enzymes for biocatalysis is a major priority to enable industrial use. To date, many innovative technologies have been developed to address the future demand of enzymes for these purposes, but maximizing the catalytic activity of enzymes remains a challenge. In this study, we demonstrated that the functionality of a nanobiocatalyst could be enhanced by combining immobilization and radiofrequency (RF) treatment. Aminopeptidase PepA-encapsulating 2 nm platinum nanoparticles (PepA-PtNPs) with the catalytic activities of hydrolysis and hydrogenation were employed as multifunctional nanobiocatalysts. Immobilizing the nanobiocatalysts in a hydrogel using metal chelation significantly enhanced their functionalities, including catalytic power, thermal-stability, pH tolerance, organic solvent tolerance, and reusability. Most importantly, RF treatment of the hydrogel-immobilized PepA-PtNPs increased their catalytic power by 2.5 fold greater than the immobilized PepA. Our findings indicate that the catalytic activities and functionalities of PepA-PtNPs are greatly enhanced by the combination of hydrogel-immobilization and RF treatment. Based on our findings, we propose that RF treatment of nanobiohybrid catalysts immobilized on the bulk hydrogel represents a new strategy for achieving efficient biocatalysis. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr00407h

WarpEngine, a Flexible Platform for Distributed Computing Implemented in the VEGA Program and Specially Targeted for Virtual Screening Studies.

PubMed

Pedretti, Alessandro; Mazzolari, Angelica; Vistoli, Giulio

2018-05-21

The manuscript describes WarpEngine, a novel platform implemented within the VEGA ZZ suite of software for performing distributed simulations both in local and wide area networks. Despite being tailored for structure-based virtual screening campaigns, WarpEngine possesses the required flexibility to carry out distributed calculations utilizing various pieces of software, which can be easily encapsulated within this platform without changing their source codes. WarpEngine takes advantages of all cheminformatics features implemented in the VEGA ZZ program as well as of its largely customizable scripting architecture thus allowing an efficient distribution of various time-demanding simulations. To offer an example of the WarpEngine potentials, the manuscript includes a set of virtual screening campaigns based on the ACE data set of the DUD-E collections using PLANTS as the docking application. Benchmarking analyses revealed a satisfactory linearity of the WarpEngine performances, the speed-up values being roughly equal to the number of utilized cores. Again, the computed scalability values emphasized that a vast majority (i.e., >90%) of the performed simulations benefit from the distributed platform presented here. WarpEngine can be freely downloaded along with the VEGA ZZ program at www.vegazz.net .

SLS Booster Engine Service Platforms Delivery

NASA Image and Video Library

2017-07-31

A flatbed truck carrying one of two new service platforms for NASA's Space Launch System booster engines nears the Vehicle Assembly Building (VAB) at the agency's Kennedy Space Center in Florida. The platforms were transported from fabricator Met-Con Inc. in Cocoa, Florida. They will be delivered to the VAB, where they will be stored and used for processing and checkout of the engines for the rocket's twin five-segment solid rocket boosters for Exploration Mission-1. EM-1 will launch an uncrewed Orion spacecraft to a stable orbit beyond the Moon and bring it back to Earth for a splashdown in the Pacific Ocean.

Booster Engine Service Platforms Delivered to VAB

NASA Image and Video Library

2018-04-17

A new service platform for NASA's Space Launch System booster engines is being prepared for the move into the Vehicle Assembly Building (VAB) at the agency's Kennedy Space Center in Florida. The platform was transported from fabricator Met-Con Inc. in Cocoa, Florida. It will be stored in the VAB, and used for processing and checkout of the engines for the rocket's twin five-segment solid rocket boosters for Exploration Mission-1. EM-1 will launch an uncrewed Orion spacecraft to a stable orbit beyond the Moon and bring it back to Earth for a splashdown in the Pacific Ocean.

SLS Booster Engine Service Platforms Delivery

NASA Image and Video Library

2017-07-31

A flatbed truck carrying one of two new service platforms for NASA's Space Launch System booster engines backs up inside the Vehicle Assembly Building (VAB) at the agency's Kennedy Space Center in Florida. The platforms were transported from fabricator Met-Con Inc. in Cocoa, Florida. They will be stored in the VAB, where they will be used for processing and checkout of the engines for the rocket's twin five-segment solid rocket boosters for Exploration Mission-1. EM-1 will launch an uncrewed Orion spacecraft to a stable orbit beyond the Moon and bring it back to Earth for a splashdown in the Pacific Ocean.

SLS Booster Engine Service Platforms Delivery

NASA Image and Video Library

2017-07-31

A flatbed truck carrying one of two new service platforms for NASA's Space Launch System booster engines backs in to the Vehicle Assembly Building (VAB) at the agency's Kennedy Space Center in Florida. The platforms were transported from fabricator Met-Con Inc. in Cocoa, Florida. They will be stored in the VAB, where they will be used for processing and checkout of the engines for the rocket's twin five-segment solid rocket boosters for Exploration Mission-1. EM-1 will launch an uncrewed Orion spacecraft to a stable orbit beyond the Moon and bring it back to Earth for a splashdown in the Pacific Ocean.

SLS Booster Engine Service Platforms Delivery

NASA Image and Video Library

2017-07-31

A flatbed truck carrying one of two new service platforms for NASA's Space Launch System booster engines arrives inside the Vehicle Assembly Building (VAB) at the agency's Kennedy Space Center in Florida. The platforms were transported from fabricator Met-Con Inc. in Cocoa, Florida. They will be stored in the VAB, where they will be used for processing and checkout of the engines for the rocket's twin five-segment solid rocket boosters for Exploration Mission-1. EM-1 will launch an uncrewed Orion spacecraft to a stable orbit beyond the Moon and bring it back to Earth for a splashdown in the Pacific Ocean.

SLS Booster Engine Service Platforms Delivery

NASA Image and Video Library

2017-07-31

A flatbed truck carrying one of two new service platforms for NASA's Space Launch System booster engines arrives at the Vehicle Assembly Building (VAB) at the agency's Kennedy Space Center in Florida. The platforms were transported from fabricator Met-Con Inc. in Cocoa, Florida. They will be stored in the VAB, where they will be used for processing and checkout of the engines for the rocket's twin five-segment solid rocket boosters for Exploration Mission-1. EM-1 will launch an uncrewed Orion spacecraft to a stable orbit beyond the Moon and bring it back to Earth for a splashdown in the Pacific Ocean.

SLS Booster Engine Service Platforms Delivery

NASA Image and Video Library

2017-07-31

New service platforms for NASA's Space Launch System booster engines, secured on two flatbed trucks, are on their way to the agency's Kennedy Space Center in Florida. They are being transported from fabricator Met-Con Inc. in Cocoa, Florida. The platforms will be delivered to the Vehicle Assembly Building, where they will be stored and used for processing and checkout of the engines for the rocket's twin five-segment solid rocket boosters for Exploration Mission-1. EM-1 will launch an uncrewed Orion spacecraft to a stable orbit beyond the Moon and bring it back to Earth for a splashdown in the Pacific Ocean.

SLS Booster Engine Service Platforms Delivery

NASA Image and Video Library

2017-07-31

One of two new work platforms for NASA's Space Launch System booster engines is secured on dunnage inside the Vehicle Assembly Building (VAB) at the agency's Kennedy Space Center in Florida. The platforms were transported from fabricator Met-Con Inc. in Cocoa, Florida. They will be stored in the VAB, where they will be used for processing and checkout of the engines for the rocket's twin five-segment solid rocket boosters for Exploration Mission-1. EM-1 will launch an uncrewed Orion spacecraft to a stable orbit beyond the Moon and bring it back to Earth for a splashdown in the Pacific Ocean.

Implementing Ethernet Services on the Payload Executive Processor (PEP)

NASA Technical Reports Server (NTRS)

Pruett, David; Guyette, Greg

2016-01-01

The Ethernet interface is more common and easier interface to implement for payload developers already familiar with Ethernet protocol in their labs. The Ethernet interface allows for a more distributed payload architecture. Connections can be placed in locations not serviced by the PEP 1553 bus. The Ethernet interface provides a new access port into the PEP so as to use the already existing services. Initial capability will include a subset of services with a plan to expand services later.

Evolving S Boxes with Reduced Differential Power Analysis Susceptibiltiy

DTIC Science & Technology

2016-12-02

coefficient [PEB+14,PPE+14]. Note that in the 4-bit case they could simultaneously maximize both cryptanalytic and side channel prop- erties [ PEP +14]. When its... PEP +14, PMMB15]; which makes sense for criteria of similar types, or when carefully weighting an understood trade-off. Work that combined...cryptanalytic and side channel properties failed to explore the trade- off [PEB+14,PPE+14, PEP +14,PMMB15], other than to provide loose bounds [MMS13]. Instead, it

Impact of food processing and simulated gastrointestinal digestion on gliadin immunoreactivity in rolls.

PubMed

Brzozowski, Bartosz

2018-07-01

The enzymatic modification of wheat proteins during dough fermentation and its digestion as supported by peptidases of microbiological origin can result in the degradation of important peptides in the pathogenesis of coeliac disease. However, baking bread and the high temperature associated with this could change the physicochemical and immunological properties of proteins. Thermal changes in the spatial structure of proteins and their hydrolysis can lead to a masking or degrading of immunoreactive peptides. The addition of prolyl endopeptidase (PEP), comprising peptidases isolated from Lactobacillus acidophilus 5e2 (LA) or transglutaminase (TG) in the course of fermentation, decreases its immunoreactivity by 83.9%, 51.9% and 18.5%, respectively. An analysis of the fractional composition of gliadins revealed that γ- and ω-gliadins are the proteins most susceptible to enzymatic modification. Hydrolysis of wheat storage proteins with PEP and LA reduces the content of αβ-, γ- and ω-gliadins by 13.7%, 60.2% and 41.9% for PEP and by 22.1%, 43.5% and 36.9% for LA, respectively. Cross-linking of proteins with TG or their hydrolysis by PEP and LA peptidases during the process of forming wheat dough, followed by digesting bread samples with PEP and LA peptidases, decreases the immunoreactivity of bread hydrolysates from 2.4% to 0.02%. The content of peptide detected in polypeptide sequences is 263.4 ± 3.3, 30.9 ± 1.5 and 7.9 ± 0.4 mg kg -1 in samples of hydrolysates of bread digested with PEP, as produced from dough modified by TG, PEP and LA, respectively. Enzymatic pre-modification of proteins during the process of dough fermentation decreases their immunoreactive potential, such that fewer peptides recognised by R5 antibodies are released during the digestion process from the bread matrix. Immunoreactive peptides are degraded more effectively when digestive enzymes are supported by the addition of PEP. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

PEP725: real time monitoring of phenological events in Austria, Germany, Sweden and Switzerland

NASA Astrophysics Data System (ADS)

Ungersboeck, Markus; Bolmgren, Kjell; Huebner, Thomas; Kaspar, Frank; Langvall, Ola; Paul, Anita; Pietragalla, Barbara; Scheifinger, Helfried; Koch, Elisabeth

2017-04-01

The main objective of PEP725 (Pan European Phenological database; http://www.pep725.eu/) is to promote and facilitate phenological research by delivering a pan European phenological database with an open, unrestricted data access for science, research and education. The first datasets in PEP725 date back to 1868; however, there are only a few observations available until 1950. From 1951 onwards, the phenological networks all over Europe developed rapidly. So far more than 11 923 489 of observations of 121 different plants are now available in the PEP725 database. Approximately 40 % of all data are flowering records, 10 % are fruit ripeness observations and also 10 % are leaf unfolding observations. The PEP725 database is updated annually. But since recently Deutscher Wetterdienst and MeteoSwiss offer their observers to upload their observations via web in real time mode, ZAMG introduced this web-based feature already in 2007 (phenowatch.at) and the observers of SWE-NPN (the Swedish National Phenology Network) can submit their observations through the web application naturenskalender.se since the start in 2008. Since spring 2016 one you can find a real time animated monitoring tool showing how the "green wave" in spring is moving from 46° northern latitude up to the Arctic Circle and the "brown wave" in autumn in the opposite direction. In 2015 the "green wave" speeds up from app. 4.4 days/degree latitude for hazel flowering to 2.9 days/ degree latitude for willow flowering and 2.25 days/degree latitude for birch leaf unfolding. There are other European countries as for instance Italy, The Netherlands, UK that have been doing visualizations of ground phenology in real time for some years, but these efforts always end at the national borders. PEP725 is funded by ZAMG, the Austrian ministry of science, research and economy and EUMETNET, the network of European meteorological services. So far 21 European meteorological services and 7 partners from different phenological network operators have joined PEP725.

Effectiveness of a patient education programme in heart failure with preserved ejection fraction: Results from the ODIN cohort study using propensity score matching.

PubMed

Agrinier, Nelly; Schockmel, Matthieu; Thilly, Nathalie; Laborde-Castérot, Hervé; Jourdain, Patrick; Alla, François; Leclercq, Christophe; Dany, François; Druelle, Justine; Drouet, Emilie; Mulak, Geneviève; Juillière, Yves

2018-01-01

Patient education programmes (PEP) are recommended for patients with heart failure but have not been specifically assessed in heart failure with preserved ejection fraction (HFpEF). To assess the effectiveness of a structured PEP in reducing all-cause mortality in patients with HFpEF. Patients with HFpEF were selected from the ODIN cohort, designed to assess PEP effectiveness in patients with HF whatever their ejection fraction, included from 2007 to 2010, and followed up until 2013. Baseline sociodemographic, clinical, biological and therapeutic characteristics were collected. At inclusion, patients were invited to participate in the PEP, which consisted of educational diagnosis, education sessions and final evaluation. Education focused on HF pathophysiology and medication, symptoms of worsening HF, dietary recommendations and management of exercise. Propensity score matching and Cox models were performed. Of 849 patients with HFpEF, 572 (67.4%) participated in the PEP and 277 (32.6%) did not. Patients who participated in the PEP were younger (67.0±13.1 vs 76.1±13.2 years; standardized difference [StDiff] =-54.6%), less often women (39.7% vs 48.4%; StDiff =-17.6%) and presented more often with hypercholesterolaemia (55.2% vs 35.2%; StDiff 41.2%), smoking (35.1% vs 28.7%; StDiff 13.8%), alcohol abuse (14.1% vs 8.9%; StDiff 16.5%) and ischaemic HF (38.7% vs 29.2%; StDiff 20.0%) than those who did not; they also presented with better clinical cardiovascular variables. After propensity score matching, baseline characteristics were balanced, except hypertension (postmatch StDiff 19.1%). The PEP was associated with lower all-cause mortality (pooled hazard ratio 0.70, 95% confidence interval 0.49-0.99; P=0.042). This association remained significant after adjustment for hypertension (adjusted pooled hazard ratio 0.68, 95% confidence interval 0.48-0.97; P=0.036). In this investigation, a structured PEP was associated with lower all-cause mortality. Patient education might be considered an effective treatment in patients with HFpEF. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Identification of the Calmodulin-Binding Domains of Fas Death Receptor

PubMed Central

Chang, Bliss J.; Samal, Alexandra B.; Vlach, Jiri; Fernandez, Timothy F.; Brooke, Dewey; Prevelige, Peter E.; Saad, Jamil S.

2016-01-01

The extrinsic apoptotic pathway is initiated by binding of a Fas ligand to the ectodomain of the surface death receptor Fas protein. Subsequently, the intracellular death domain of Fas (FasDD) and that of the Fas-associated protein (FADD) interact to form the core of the death-inducing signaling complex (DISC), a crucial step for activation of caspases that induce cell death. Previous studies have shown that calmodulin (CaM) is recruited into the DISC in cholangiocarcinoma cells and specifically interacts with FasDD to regulate the apoptotic/survival signaling pathway. Inhibition of CaM activity in DISC stimulates apoptosis significantly. We have recently shown that CaM forms a ternary complex with FasDD (2:1 CaM:FasDD). However, the molecular mechanism by which CaM binds to two distinct FasDD motifs is not fully understood. Here, we employed mass spectrometry, nuclear magnetic resonance (NMR), biophysical, and biochemical methods to identify the binding regions of FasDD and provide a molecular basis for the role of CaM in Fas–mediated apoptosis. Proteolytic digestion and mass spectrometry data revealed that peptides spanning residues 209–239 (Fas-Pep1) and 251–288 (Fas-Pep2) constitute the two CaM-binding regions of FasDD. To determine the molecular mechanism of interaction, we have characterized the binding of recombinant/synthetic Fas-Pep1 and Fas-Pep2 peptides with CaM. Our data show that both peptides engage the N- and C-terminal lobes of CaM simultaneously. Binding of Fas-Pep1 to CaM is entropically driven while that of Fas-Pep2 to CaM is enthalpically driven, indicating that a combination of electrostatic and hydrophobic forces contribute to the stabilization of the FasDD–CaM complex. Our data suggest that because Fas-Pep1 and Fas-Pep2 are involved in extensive intermolecular contacts with the death domain of FADD, binding of CaM to these regions may hinder its ability to bind to FADD, thus greatly inhibiting the initiation of apoptotic signaling pathway. PMID:26735300

A web-based online collaboration platform for formulating engineering design projects

NASA Astrophysics Data System (ADS)

Varikuti, Sainath

Effective communication and collaboration among students, faculty and industrial sponsors play a vital role while formulating and solving engineering design projects. With the advent in the web technology, online platforms and systems have been proposed to facilitate interactions and collaboration among different stakeholders in the context of senior design projects. However, there are noticeable gaps in the literature with respect to understanding the effects of online collaboration platforms for formulating engineering design projects. Most of the existing literature is focused on exploring the utility of online platforms on activities after the problem is defined and teams are formed. Also, there is a lack of mechanisms and tools to guide the project formation phase in senior design projects, which makes it challenging for students and faculty to collaboratively develop and refine project ideas and to establish appropriate teams. In this thesis a web-based online collaboration platform is designed and implemented to share, discuss and obtain feedback on project ideas and to facilitate collaboration among students and faculty prior to the start of the semester. The goal of this thesis is to understand the impact of an online collaboration platform for formulating engineering design projects, and how a web-based online collaboration platform affects the amount of interactions among stakeholders during the early phases of design process. A survey measuring the amount of interactions among students and faculty is administered. Initial findings show a marked improvement in the students' ability to share project ideas and form teams with other students and faculty. Students found the online platform simple to use. The suggestions for improving the tool generally included features that were not necessarily design specific, indicating that the underlying concept of this collaborative platform provides a strong basis and can be extended for future online platforms. Although the platform was designed to promote collaboration, adoption of the collaborative platform by students and faculty has been slow. While the platform appears to be very useful for collaboration, more time is required for it to be widely used by all the stakeholders and to fully convert from email communication to the use of the online collaboration platform.

Versatile Cas9-Driven Subpopulation Selection Toolbox for Lactococcus lactis.

PubMed

van der Els, Simon; James, Jennelle K; Kleerebezem, Michiel; Bron, Peter A

2018-04-15

CRISPR-Cas9 technology has been exploited for the removal or replacement of genetic elements in a wide range of prokaryotes and eukaryotes. Here, we describe the extension of the Cas9 application toolbox to the industrially important dairy species Lactococcus lactis The Cas9 expression vector pLABTarget, encoding the Streptocccus pyogenes Cas9 under the control of a constitutive promoter, was constructed, allowing plug and play introduction of short guide RNA (sgRNA) sequences to target specific genetic loci. Introduction of a pepN -targeting derivative of pLABTarget into L. lactis strain MG1363 led to a strong reduction in the number of transformants obtained, which did not occur in a pepN deletion derivative of the same strain, demonstrating the specificity and lethality of the Cas9-mediated double-strand breaks in the lactococcal chromosome. Moreover, the same pLABTarget derivative allowed the selection of a pepN deletion subpopulation from its corresponding single-crossover plasmid integrant precursor, accelerating the construction and selection of gene-specific deletion derivatives in L. lactis Finally, pLABTarget, which contained sgRNAs designed to target mobile genetic elements, allowed the effective curing of plasmids, prophages, and integrative conjugative elements (ICEs). These results establish that pLABTarget enables the effective exploitation of Cas9 targeting in L. lactis , while the broad-host-range vector used suggests that this toolbox could readily be expanded to other Gram-positive bacteria. IMPORTANCE Mobile genetic elements in Lactococcus lactis and other lactic acid bacteria (LAB) play an important role in dairy fermentation, having both positive and detrimental effects during the production of fermented dairy products. The pLABTarget vector offers an efficient cloning platform for Cas9 application in lactic acid bacteria. Targeting Cas9 toward mobile genetic elements enabled their effective curing, which is of particular interest in the context of potentially problematic prophages present in a strain. Moreover, Cas9 targeting of other mobile genetic elements enables the deciphering of their contribution to dairy fermentation processes and further establishment of their importance for product characteristics. Copyright © 2018 American Society for Microbiology.

Integrated Tools for Future Distributed Engine Control Technologies

NASA Technical Reports Server (NTRS)

Culley, Dennis; Thomas, Randy; Saus, Joseph

2013-01-01

Turbine engines are highly complex mechanical systems that are becoming increasingly dependent on control technologies to achieve system performance and safety metrics. However, the contribution of controls to these measurable system objectives is difficult to quantify due to a lack of tools capable of informing the decision makers. This shortcoming hinders technology insertion in the engine design process. NASA Glenn Research Center is developing a Hardware-inthe- Loop (HIL) platform and analysis tool set that will serve as a focal point for new control technologies, especially those related to the hardware development and integration of distributed engine control. The HIL platform is intended to enable rapid and detailed evaluation of new engine control applications, from conceptual design through hardware development, in order to quantify their impact on engine systems. This paper discusses the complex interactions of the control system, within the context of the larger engine system, and how new control technologies are changing that paradigm. The conceptual design of the new HIL platform is then described as a primary tool to address those interactions and how it will help feed the insertion of new technologies into future engine systems.

Unconsented HIV Testing in Cases of Occupational Exposure: Ethics, Law, and Policy

PubMed Central

Cowan, Ethan; Macklin, Ruth

2012-01-01

Post-exposure prophylaxis (PEP) has substantially reduced the risk of acquiring human immunodeficiency virus (HIV) after an occupational exposure; nevertheless, exposure to HIV remains a concern for emergency department providers. According to published guidelines, PEP should be taken only when source patients are HIV positive or have risk factors for HIV. Initiating PEP when source patients are uninfected puts exposed persons at risk from taking toxic drugs with no compensating benefit. Forgoing PEP if the source is infected results in increased risk of acquiring HIV. What should be done if source patients refuse HIV testing? Is it justifiable to test the blood of these patients over their autonomous objection? The authors review current law and policy and perform an ethical analysis to determine if laws permitting unconsented testing in cases of occupational exposure can be ethically justified. PMID:22994417

Power Extension Package (PEP) system definition extension, orbital service module systems analysis study. Volume 1: Executive summary

NASA Technical Reports Server (NTRS)

1979-01-01

An array deployment assembly, power regulation and control assembly, the necessary interface, and display and control equipment comprise the power extension package (PEP) which is designed to provide increased power and duration, as well as reduce fuel cell cryogen consumption during Spacelab missions. Compatible with all currently defined missions and payloads, PEP imposes minimal weight and volume penalties on sortie missions, and can be installed and removed as needed at the launch site within the normal Orbiter turnaround cycle. The technology on which it is based consists of a modified solar electric propulsion array, standard design regulator and control equipment, and a minimally modified Orbiter design. The requirements from which PEP was derived, and the system and its performance capabilities are described. Features of the recommended project are presented.

Noise exposure in marching bands

NASA Astrophysics Data System (ADS)

Keefe, Joseph

2005-09-01

Previous studies involving orchestras have shown that music ensembles can produce hazardous noise levels. There are no similar data for marching bands and pep bands. In order to evaluate the noise levels produced by marching and pep bands, 1/3-octave-band sound-pressure levels were measured while these groups rehearsed and performed. Data were collected while marching with the bands to ensure a realistic environment. Comparing these data to OSHA and NIOSH criteria, marching and pep band exposures often exceed safe values. For typical exposures, OSHA doses range from 11% to 295%, while NIOSH doses range from 35% to 3055%. Exposures that would be considered hazardous in the workplace are common in marching and pep bands; students and band directors should take steps to recognize the risk posed by various instruments and various locations, and should implement hearing conservation efforts.

Antibody αPEP13h Reacts With Lymphangioleiomyomatosis Cells in Lung Nodules

PubMed Central

Valencia, Julio C.; Steagall, Wendy K.; Zhang, Yi; Fetsch, Patricia; Abati, Andrea; Tsukada, Katsuya; Billings, Eric; Hearing, Vincent J.; Yu, Zu-Xi; Pacheco-Rodriguez, Gustavo

2015-01-01

BACKGROUND: Lymphangioleiomyomatosis (LAM) is characterized by the proliferation in the lung, axial lymphatics (eg, lymphangioleiomyomas), and kidney (eg, angiomyolipomas) of abnormal smooth muscle-like LAM cells, which express melanoma antigens such as Pmel17/gp100 and have dysfunctional tumor suppressor tuberous sclerosis complex (TSC) genes TSC2 or TSC1. Histopathologic diagnosis of LAM in lung specimens is based on identification of the Pmel17 protein with the monoclonal antibody HMB-45. METHODS: We compared the sensitivity of HMB-45 to that of antipeptide antibody αPEP13h, which reacts with a C-terminal peptide of Pmel17. LAM lung nodules were laser-capture microdissected to identify proteins by Western blotting. RESULTS: HMB-45 recognized approximately 25% of LAM cells within the LAM lung nodules, whereas αPEP13h identified > 82% of LAM cells within these structures in approximately 90% of patients. Whereas HMB-45 reacted with epithelioid but not with spindle-shaped LAM cells, αPEP13h identified both spindle-shaped and epithelioid LAM cells, providing greater sensitivity for detection of all types of LAM cells. HMB-45 recognized Pmel17 in premelanosomal organelles; αPEP13h recognized proteins in the cytoplasm as well as in premelanosomal organelles. Both antibodies recognized a Pmel17 variant of approximately 50 kDa. CONCLUSIONS: Based on its sensitivity and specificity, αPEP13h may be useful in the diagnosis of LAM and more sensitive than HMB-45. PMID:25411763

Is ESR Important for Predicting Post-ERCP Pancreatitis?

PubMed Central

Mohammad Alizadeh, Amir Houshang; Afzali, Esmaeil Shamsi; Behzad, Catherine; Mousavi, Mirhadi; Mirsattari, Dariush; Doagoo, Siavash Zafar; Zali, Mohammad Reza

2015-01-01

BACKGROUND Pancreatitis remains the most common complication of endoscopic retrograde cholangiopancreatography (ERCP), resulting in substantial morbidity and occasional mortality. There are notable controversies and conflicting reports about risk factors of post-ERCP pancreatitis (PEP). AIM To evaluate the potential risk factors for PEP at a referral tertiary center, as a sample of the Iranian population. MATERIALS AND METHODS Baseline characteristics and clinical as well as paraclinical information of 780 patients undergoing diagnostic and therapeutic ERCP at Taleghani hospital in Tehran between 2008 and 2012 were reviewed. Data were collected prior to the ERCP, at the time of the procedure, and 24–72 hours after discharge. PEP was diagnosed according to consensus criteria. RESULTS Of the 780 patients who underwent diagnostic ERCP, pancreatitis developed in 26 patients (3.3%). In the multivariable risk model, significant risk factors with adjusted odds ratios (ORs) were age <65 years (OR = 10.647, P = 0.023) and erythrocyte sedimentation rate (ESR) >30 (OR = 6.414, P < 0.001). Female gender, history of recurrent pancreatitis, pre-ERCP hyperamylasemia, and difficult or failed cannulation could not predict PEP. There was no significant difference in the rate of PEP in wire-guided cannulation versus biliary cannulation using a sphincterotome and contrast injection as the conventional method. CONCLUSIONS Performing ERCP may be safer in the elderly. Patients with high ESR may be at greater risk of PEP, which warrants close observation of these patients for signs of pancreatitis after ERCP. PMID:26005364

In Vivo Absorption and Disposition of Cefadroxil after Escalating Oral Doses in Wild-Type and PepT1 Knockout Mice

PubMed Central

Posada, Maria M.; Smith, David E.

2013-01-01

Purpose To determine the effect of PepT1 on the absorption and disposition of cefadroxil, including the potential for saturable intestinal uptake, after escalating oral doses of drug. Methods The absorption and disposition kinetics of [3H]cefadroxil was determined in wild-type and PepT1 knockout mice after 44.5, 89.1, 178, and 356 nmol/g oral doses of drug. The pharmacokinetics of [3H]cefadroxil was also determined in both genotypes after 44.5 nmol/g intravenous bolus doses. Results PepT1 deletion reduced the area under the plasma concentration-time profile (AUC0-120) of cefadroxil by 10-fold, the maximum plasma concentration (Cmax) by 17.5-fold, and increased the time to reach a maximum plasma concentration (Tmax) by 3-fold. There was no evidence of nonlinear intestinal absorption since AUC0-120 and Cmax values changed in a dose-proportional manner. Moreover, the pharmacokinetics of cefadroxil was not different between genotypes after intravenous bolus doses, indicating that PepT1 did not affect drug disposition. Finally, no differences were observed in the peripheral tissue distribution of cefadroxil (i.e., outside gastrointestinal tract) once these tissues were corrected for differences in perfusing blood concentrations. Conclusions The findings demonstrate convincingly the critical role of intestinal PepT1 in both the rate and extent of oral administration for cefadroxil and potentially other aminocephalosporin drugs. PMID:23959853

Highly sensitive ratiometric detection of heparin and its oversulfated chondroitin sulfate contaminant by fluorescent peptidyl probe.

PubMed

Mehta, Pramod Kumar; Lee, Hyeri; Lee, Keun-Hyeung

2017-05-15

The selective and sensitive detection of heparin, an anticoagulant in clinics as well as its contaminant oversulfated chondroitin sulfate (OSCS) is of great importance. We first reported a ratiometric sensing method for heparin as well as OSCS contaminants in heparin using a fluorescent peptidyl probe (Pep1, pyrene-GSRKR) and heparin-digestive enzyme. Pep1 exhibited a highly sensitive ratiometric response to nanomolar concentration of heparin in aqueous solution over a wide pH range (2~11) and showed highly selective ratiometric response to heparin among biological competitors such as hyaluronic acid and chondroitin sulfate. Pep1 showed a linear ratiometric response to nanomolar concentrations of heparin in aqueous solutions and in human serum samples. The detection limit for heparin was calculated to be 2.46nM (R 2 =0.99) in aqueous solutions, 2.98nM (R 2 =0.98) in 1% serum samples, and 3.43nM (R 2 =0.99) in 5% serum samples. Pep1 was applied to detect the contaminated OSCS in heparin with heparinase I, II, and III, respectively. The ratiometric sensing method using Pep1 and heparinase II was highly sensitive, fast, and efficient for the detection of OSCS contaminant in heparin. Pep1 with heparinase II could detect as low as 0.0001% (w/w) of OSCS in heparin by a ratiometric response. Copyright © 2017 Elsevier B.V. All rights reserved.

Post-exposure prophylaxis awareness and use among men who have sex with men in London who use geosocial-networking smartphone applications.

PubMed

Goedel, William C; Hagen, Daniel; Halkitis, Perry N; Greene, Richard E; Griffin-Tomas, Marybec; Brooks, Forrest A; Hickson, DeMarc; Duncan, Dustin T

2017-05-01

The number of new HIV infections continues to be on the rise in many high-income countries, most notably among men who have sex with men (MSM). Despite recent attention to the use of antiretroviral medications as pre-exposure prophylaxis (PrEP) among MSM, considerably less research has been devoted to examining the awareness and use of post-exposure prophylaxis (PEP). Based on a convenience sample of 179 self-reported HIV-uninfected MSM using a geosocial-networking smartphone application, this study is among the first to examine the awareness and use of PEP and their demographic and behavioral correlates among MSM in London. Most respondents (88.3%) had heard of PEP, where 27.4% reported having used it. In multivariable models, the disclosure of one's sexual orientation to their general practitioner (Prevalence ratio [PR]: 3.49; 95% confidence interval (CI): 1.14, 10.70; p = .029) and reporting one's HIV status as negative (rather than unknown) (PR: 11.49; 95% CI: 1.68, 76.92; p = .013) were associated with having heard of PEP; while the recent use of club drugs (PR: 3.02; 95% CI: 1.42, 6.43; p = .004) was associated with having ever used PEP. High awareness and use in this sample suggest that PEP is a valuable risk-reduction strategy that should be capitalized on, be it in addition to or in the absence of PrEP.

Post-exposure prophylaxis awareness and use among men who have sex with men in London who use geosocial-networking smartphone applications

PubMed Central

Goedel, William C.; Hagen, Daniel; Halkitis, Perry N.; Greene, Richard E.; Griffin-Tomas, Marybec; Brooks, Forrest A.; Hickson, DeMarc; Duncan, Dustin T.

2017-01-01

The number of new HIV infections continues to be on the rise in many high-income countries, most notably among men who have sex with men (MSM). Despite recent attention to the use of antiretroviral medications as pre-exposure prophylaxis (PrEP) among MSM, considerably less research has been devoted to examining the awareness and use of post-exposure prophylaxis (PEP). Based on a convenience sample of 179 self-reported HIV-uninfected MSM using a geosocial-networking smartphone application, this study is among the first to examine the awareness and use of PEP and their demographic and behavioral correlates among MSM in London. Most respondents (88.3%) had heard of PEP, where 27.4% reported having used it. In multivariable models, the disclosure of one’s sexual orientation to their general practitioner (Prevalence ratio [PR]: 3.49; 95% confidence interval (CI): 1.14, 10.70; p = .029) and reporting one’s HIV status as negative (rather than unknown) (PR: 11.49; 95% CI: 1.68, 76.92; p = .013) were associated with having heard of PEP; while the recent use of club drugs (PR: 3.02; 95% CI: 1.42, 6.43; p = .004) was associated with having ever used PEP. High awareness and use in this sample suggest that PEP is a valuable risk-reduction strategy that should be capitalized on, be it in addition to or in the absence of PrEP. PMID:27910722

Provision of drugs for post-exposure prophylaxis of HIV for medical students on overseas electives.

PubMed

Franklin, G F; Gray, K; Nathwani, D

2001-10-01

To assess the need for, and the most practical way to provide, HIV post-exposure prophylaxis (PEP) for medical students travelling to areas where this is not readily available. Follow-up questionnaire for all 140 students from Dundee University returning from their medical elective in 2000, 22 of whom took triple therapy for PEP with them on elective. 103/140 students (74%) returned questionnaires. 76/103 (74%) were involved in exposure-prone procedures and 38/103 (37%) reported a significant exposure to potentially infective fluids. Six of this group considered PEP but none reported using it. The greatest perceived risk on elective remained road accidents. 87/103 respondents thought a 24-h helpline for health issues on electives would be useful. A high number of students report significant exposure to potentially infected fluids and this needs to be urgently addressed. There was almost unanimous endorsement of the idea of providing PEP and when it is made easily available prior to travel, students are willing to take it to areas where it is not available. In response to the survey, the investigators are looking at how to increase the current limited supply of PEP (Students may have to pay part of the cost) and the best way to provide a helpline, as it is felt that this could have a broad impact on student safety on electives, not just for issues involving PEP. Copyright 2001 The British Infection Society.

Low-dose rectal diclofenac for prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis: a randomized controlled trial.

PubMed

Otsuka, Taiga; Kawazoe, Seiji; Nakashita, Shunya; Kamachi, Saori; Oeda, Satoshi; Sumida, Chinatsu; Akiyama, Takumi; Ario, Keisuke; Fujimoto, Masaru; Tabuchi, Masanobu; Noda, Takahiro

2012-08-01

Acute pancreatitis is a common complication of endoscopic retrograde cholangiopancreatography (ERCP). Rectal nonsteroidal anti-inflammatory drugs (specifically, 100 mg of diclofenac or indomethacin) have shown promising prophylactic activity in post-ERCP pancreatitis (PEP). However, the 100-mg dose is higher than that ordinarily used in Japan. We performed a prospective randomized controlled study to evaluate the efficacy of low-dose rectal diclofenac for the prevention of PEP. Patients who were scheduled to undergo ERCP were randomized to receive a saline infusion either with 50 mg of rectal diclofenac (diclofenac group) or without (control group) 30 min before ERCP. The dose of diclofenac was reduced to 25 mg in patients weighing <50 kg. The primary outcome measure was the occurrence of PEP. Enrollment was terminated early because the planned interim analysis found a statistically significant intergroup difference in the occurrence of PEP. A total of 104 patients were eligible for this study; 51 patients received rectal diclofenac. Twelve patients (11.5%) developed PEP: 3.9% (2/51) in the diclofenac group and 18.9% (10/53) in the control group (p = 0.017). After ERCP, the incidence of hyperamylasemia was not significantly different between the two groups. Post-ERCP pain was significantly more frequent in the control group than in the diclofenac group (37.7 vs. 7.8%, respectively; p < 0.001). There were no adverse events related to diclofenac. Low-dose rectal diclofenac can prevent PEP.

A review of vacuum insulation research and development in the Building Materials Group of the Oak Ridge National Laboratory

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

Kollie, T.G.; McElroy, D.L.; Fine, H.A.

This report is a summary of the development work on flat-vacuum insulation performed by the Building Materials Group (BMG) in the Metals and Ceramics Division of the Oak Ridge National Laboratory (ORNL) during the last two years. A historical review of the technology of vacuum insulation is presented, and the role that ORNL played in this development is documented. The ORNL work in vacuum insulation has been concentrated in Powder-filled Evacuated Panels (PEPs) that have a thermal resistivity over 2.5 times that of insulating foams and seven times that of many batt-type insulations, such as fiberglass. Experimental results of substitutingmore » PEPs for chlorofluorocarbon (CFC) foal insulation in Igloo Corporation ice coolers are summarized. This work demonstrated that one-dimensional (1D) heat flow models overestimated the increase in thermal insulation of a foam/PEP-composite insulation, but three-dimensional (3D) models provided by a finite-difference, heat-transfer code (HEATING-7) accurately predicted the resistance of the composites. Edges and corners of the ice coolers were shown to cause the errors in the 1D models as well as shunting of the heat through the foam and around the PEPs. The area of coverage of a PEP in a foam/PEP composite is established as an important parameter in maximizing the resistance of such composites. 50 refs., 27 figs,. 22 tabs.« less

Effects of positive expiratory pressure on pulmonary clearance of aerosolized technetium-99m-labeled diethylenetriaminepentaacetic acid in healthy individuals

PubMed Central

de Albuquerque, Isabella Martins; Cardoso, Dannuey Machado; Masiero, Paulo Ricardo; Paiva, Dulciane Nunes; Resqueti, Vanessa Regiane; Fregonezi, Guilherme Augusto de Freitas; Menna-Barreto, Sérgio Saldanha

2016-01-01

ABSTRACT Objective: To evaluate the effects of positive expiratory pressure (PEP) on pulmonary epithelial membrane permeability in healthy subjects. Methods: We evaluated a cohort of 30 healthy subjects (15 males and 15 females) with a mean age of 28.3 ± 5.4 years, a mean FEV1/FVC ratio of 0.89 ± 0.14, and a mean FEV1 of 98.5 ± 13.1% of predicted. Subjects underwent technetium-99m-labeled diethylenetriaminepentaacetic acid (99mTc-DTPA) radioaerosol inhalation lung scintigraphy in two stages: during spontaneous breathing; and while breathing through a PEP mask at one of three PEP levels-10 cmH2O (n = 10), 15 cmH2O (n = 10), and 20 cmH2O (n = 10). The 99mTc-DTPA was nebulized for 3 min, and its clearance was recorded by scintigraphy over a 30-min period during spontaneous breathing and over a 30-min period during breathing through a PEP mask. Results: The pulmonary clearance of 99mTc-DTPA was significantly shorter when PEP was applied-at 10 cmH2O (p = 0.044), 15 cmH2O (p = 0.044), and 20 cmH2O (p = 0.004)-in comparison with that observed during spontaneous breathing. Conclusions: Our findings indicate that PEP, at the levels tested, is able to induce an increase in pulmonary epithelial membrane permeability and lung volume in healthy subjects. PMID:28117469

Changes in small angle X-ray scattering parameters observed upon ligand binding to rabbit muscle pyruvate kinase are not correlated with allosteric transitions†

PubMed Central

Fenton, Aron W.; Williams, Rachel; Trewhella, Jill

2010-01-01

Protein fluorescence and small-angle X-ray scattering (SAXS) have been used to monitor effector affinity and conformational changes previously associated with allosteric regulation in rabbit muscle pyruvate kinase (M1-PYK). In the absence of substrate (phosphoenolpyruvate; PEP), SAXS-monitored conformational changes in M1-PYK elicited by the binding of phenylalanine (an allosteric inhibitor that reduces the affinity of M1-PYK for PEP) are similar to those observed upon binding of alanine or 2-aminobutyric acid. Under the current assay conditions, these small amino acids bind to the protein, but elicit a minimal change in the affinity of the protein for PEP. Therefore, if changes in scattering signatures represent cleft closure via domain rotation as previously interpreted, it can be concluded that these motions are not sufficient to elicit allosteric inhibition. Additionally, although PEP has similar affinities for the free enzyme and the M1-PYK/small-amino-acid complexes (i.e. the small amino acids have minimal allosteric effects), PEP binding elicits different changes in the SAXS signature of the free enzyme vs. the M1-PYK/small-amino-acid complexes. PMID:20712377

Identification of risk factors for post-endoscopic retrograde cholangiopancreatography pancreatitis in a high volume center.

PubMed

Phillip, Veit; Schwab, Miriam; Haf, David; Algül, Hana

2017-01-01

Pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP). Several patients´ or procedure related risk factors for post-ERCP pancreatitis (PEP) have been suggested. The aim of this study was to validate the risk factors for PEP in a high-volume center. All patients undergoing first time ERCP at a tertiary referral center between December 2010 and October 2013 were retrospectively included. PEP was defined according to the Atlanta Classification. 344 patients were included in the final analysis. The risk to develop PEP was increased in patients with chronic pancreatitis (odds ratio 3.7) and after inadvertent cannulation of the pancreatic duct (odds ratio 2.2), which occurred in 26.5% of the patients. Inadvertent cannulation occurred significantly more frequently in patients with difficult cannulation of the papilla duodeni major (odds ratio 12.7; p<0.001). ERCP on call was associated with an increased risk for difficult cannulation (odds ratio 3.0). Inadvertent cannulation of the pancreatic duct is a procedure related risk factor for PEP. Measurements on preventing inadvertent cannulation of the pancreatic duct should be established and studies on prophylactic measurements should focus particularly on patients with inadvertent cannulation of the pancreatic duct.

Understanding dengue virus capsid protein disordered N-Terminus and pep14-23-based inhibition.

PubMed

Faustino, André F; Guerra, Gabriela M; Huber, Roland G; Hollmann, Axel; Domingues, Marco M; Barbosa, Glauce M; Enguita, Francisco J; Bond, Peter J; Castanho, Miguel A R B; Da Poian, Andrea T; Almeida, Fabio C L; Santos, Nuno C; Martins, Ivo C

2015-02-20

Dengue virus (DENV) infection affects millions of people and is becoming a major global disease for which there is no specific available treatment. pep14-23 is a recently designed peptide, based on a conserved segment of DENV capsid (C) protein. It inhibits the interaction of DENV C with host intracellular lipid droplets (LDs), which is crucial for viral replication. Combining bioinformatics and biophysics, here, we analyzed pep14-23 structure and ability to bind different phospholipids, relating that information with the full-length DENV C. We show that pep14-23 acquires α-helical conformation upon binding to negatively charged phospholipid membranes, displaying an asymmetric charge distribution structural arrangement. Structure prediction for the N-terminal segment reveals four viable homodimer orientations that alternatively shield or expose the DENV C hydrophobic pocket. Taken together, these findings suggest a new biological role for the disordered N-terminal region, which may function as an autoinhibitory domain mediating DENV C interaction with its biological targets. The results fit with our current understanding of DENV C and pep14-23 structure and function, paving the way for similar approaches to understanding disordered proteins and improved peptidomimetics drug development strategies against DENV and similar Flavivirus infections.

Fluorescence Quenching of CdSe/ZnS Quantum Dots by Using Black Hole Quencher Molecules Intermediated With Peptide for Biosensing Application.

PubMed

Pillai, Sreenadh Sasidharan; Yukawa, Hiroshi; Onoshima, Daisuke; Biju, Vasudevanpillai; Baba, Yoshinobu

2015-12-17

Quantum dots (QDs) have recently been investigated as fluorescent probes for detecting a very small number of biomolecules and live cells; however, the establishment of molecular imaging technology with on-off control of QD fluorescence remains to be established. Here we have achieved the fluorescence off state of QDs with the conjugation of black hole quencher (BHQ) molecules intermediated with peptide by using streptavidin-QDs585 and biotin-pep-BHQ-1. The fluorescence of streptavidin-QDs585 was decreased by the addition of biotin-pep-BHQ-1 in a dose-dependent manner. It has been suggested that the decrease in QDs585 fluorescence occurred through a Förster resonance energy transfer (FRET) mechanism from the analysis of fluorescence intensity and lifetime of streptavidin-QDs585 and QDs585-pep-BHQ-1. QDs585 fluorescence could be quenched by more than 60% efficiency in this system. The sequence of intermediate peptide (pep) was GPLGVRGK, which can be cleaved by matrix metalloproteinases (MMPs) produced by cancer cells. QDs585-pep-BHQ-1 is thus expected to detect the MMP production by the recovery of QDs585 fluorescence as a new bioanalytical agent for molecular imaging.

Constructing aptamer anchored nanovesicles for enhanced tumor penetration and cellular uptake of water soluble chemotherapeutics.

PubMed

Li, Xin; Zhu, Xiumei; Qiu, Liyan

2016-04-15

Polymersomes represent a promising pharmaceutical vehicle for the delivery of hydrophilic therapeutic agents. However, modification of polymersomes with molecules that confer targeting functions remains challenging because of the strict requirements regarding the weight fractions of the hydrophilic and hydrophobic block polymers. In this study, based on the compatibility between cholesterol and polymeric carriers, polymersomes self-assembled by amphiphilic graft polyphosphazenes were endowed with a targeting function by incorporating the cholesterol-linked aptamer through a simple dialysis method. The aqueous interior of the polymersomes was employed to encapsulate water-soluble doxorubicin hydrochloride. In vivo experiments in tumor-bearing mice showed that the aptamer-anchored vesicle targeted accumulation at the tumor site, favorable penetration through tumor tissue, and incremental endocytosis into tumor cells. Correspondingly, the aptamer-anchored vesicle decreased systemic toxicity and effectively suppressed the growth of subcutaneous MCF-7 xenografts. These findings suggested that vesicles modified with targeted groups via hydrophobic supermolecular interactions could provide a platform for selective delivery of hydrophilic drug. Polymersomes have represented a promising type of pharmaceutical vehicles due to their predominant physical properties. However, it is still a challenge to endow polymersomes with active target function because of strict requirements of the weight fractions of hydrophilic polymer block to hydrophobic one. In this research, by taking advantage of the supermolecular interactions between amphiphilic graft polyphosphazene and cholesterol which was linked to aptamer AS1411, we prepared a targeted functional polymersome (PEP-DOX·HCl-Ap) through a simple method with high loading of water soluble anti-cancer drug doxorubicin hydrochloride. The in vivo experiments in MCF-7 tumor-bearing mice demonstrated several advantages of PEP-DOX·HCl-Ap vesicle such as prolonged circulation time in blood, targeted accumulation at tumor site, permeation through the tumor tissue and incremental endocytosis by tumor cells, which consequently resulted in the significantly improved anti-cancer efficacy. Moreover, this novel polymersome designed in this study has built a research platform to achieve targeted delivery of hydrophilic chemotherapeutics for cancer therapy. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Real-time Simulation of Turboprop Engine Control System

NASA Astrophysics Data System (ADS)

Sheng, Hanlin; Zhang, Tianhong; Zhang, Yi

2017-05-01

On account of the complexity of turboprop engine control system, real-time simulation is the technology, under the prerequisite of maintaining real-time, to effectively reduce development cost, shorten development cycle and avert testing risks. The paper takes RT-LAB as a platform and studies the real-time digital simulation of turboprop engine control system. The architecture, work principles and external interfaces of RT-LAB real-time simulation platform are introduced firstly. Then based on a turboprop engine model, the control laws of propeller control loop and fuel control loop are studied. From that and on the basis of Matlab/Simulink, an integrated controller is designed which can realize the entire process control of the engine from start-up to maximum power till stop. At the end, on the basis of RT-LAB platform, the real-time digital simulation of the designed control system is studied, different regulating plans are tried and more ideal control effects have been obtained.

Booster Engine Service Platforms Delivered to VAB

NASA Image and Video Library

2018-04-17

A new service platform for NASA's Space Launch System booster engines, secured on a flatbed truck, has arrived at the Vehicle Assembly Building (VAB) at the agency's Kennedy Space Center in Florida. It was transported from fabricator Met-Con Inc. in Cocoa, Florida. The platform will be stored in the VAB and used for processing and checkout of the engines for the rocket's twin five-segment solid rocket boosters for Exploration Mission-1 (EM-1). During EM-1, an uncrewed Orion spacecraft will launch on the SLS to a stable orbit beyond the Moon and return to Earth for a splashdown in the Pacific Ocean.

Booster Engine Service Platforms Delivered to VAB

NASA Image and Video Library

2018-04-17

A new service platform for NASA's Space Launch System booster engines has been offloaded from a flatbed truck and is being prepared for the move into the Vehicle Assembly Building (VAB) at the agency's Kennedy Space Center in Florida. The platform was transported from fabricator Met-Con Inc. in Cocoa, Florida. It will be stored in the VAB, and used for processing and checkout of the engines for the rocket's twin five-segment solid rocket boosters for Exploration Mission-1. EM-1 will launch an uncrewed Orion spacecraft to a stable orbit beyond the Moon and bring it back to Earth for a splashdown in the Pacific Ocean.

Booster Engine Service Platforms Delivered to VAB

NASA Image and Video Library

2018-04-17

A new service platform for NASA's Space Launch System booster engines, secured on a flatbed truck, is on its way to the agency's Kennedy Space Center in Florida. It was transported from fabricator Met-Con Inc. in Cocoa, Florida. The platform will be delivered to the Vehicle Assembly Building, where it will be stored and used for processing and checkout of the engines for the rocket's twin five-segment solid rocket boosters for Exploration Mission-1 (EM-1). During EM-1, an uncrewed Orion spacecraft will launch on the SLS to a stable orbit beyond the Moon and return to Earth for a splashdown in the Pacific Ocean.

SLS Booster Engine Service Platforms Delivery

NASA Image and Video Library

2017-07-31

A flatbed truck carrying one of two new service platforms for NASA's Space Launch System booster engines makes its way along the NASA Causeway to the agency's Kennedy Space Center in Florida. The platforms were transported from fabricator Met-Con Inc. in Cocoa, Florida. They will be delivered to the Vehicle Assembly Building, where they will be stored and used for processing and checkout of the engines for the rocket's twin five-segment solid rocket boosters for Exploration Mission-1. EM-1 will launch an uncrewed Orion spacecraft to a stable orbit beyond the Moon and bring it back to Earth for a splashdown in the Pacific Ocean.

CNO and pep solar neutrino measurements and perspectives in Borexino

NASA Astrophysics Data System (ADS)

Davini, S.; Agostini, M.; Appel, S.; Bellini, G.; Benziger, J.; Bick, D.; Bonfini, G.; Bravo, D.; Caccianiga, B.; Calaprice, F.; Caminata, A.; Cavalcante, P.; Chepurnov, A.; D'Angelo, D.; Derbin, A.; Di Noto, L.; Drachnev, I.; Etenko, A.; Fomenko, K.; Franco, D.; Gabriele, F.; Galbiati, C.; Ghiano, C.; Giammarchi, M.; Goeger-Neff, M.; Goretti, A.; Gromov, M.; Hagner, C.; Hungerford, E.; Ianni, Aldo; Ianni, Andrea; Jedrzejczak, K.; Kaiser, M.; Kobychev, V.; Korablev, D.; Korga, G.; Kryn, D.; Laubenstein, M.; Lehnert, B.; Litvinovich, E.; Lombardi, F.; Lombardi, P.; Ludhova, L.; Lukyanchenko, G.; Machulin, I.; Manecki, S.; Maneschg, W.; Marcocci, S.; Meroni, E.; Meyer, M.; Miramonti, L.; Misiaszek, M.; Montuschi, M.; Mosteiro, P.; Muratova, V.; Neumair, B.; Oberauer, L.; Obolensky, M.; Ortica, F.; Pallavicini, M.; Papp, L.; Perasso, L.; Pocar, A.; Ranucci, G.; Razeto, A.; Re, A.; Romani, A.; Roncin, R.; Rossi, N.; Schönert, S.; Semenov, D.; Simgen, H.; Skorokhvatov, M.; Smirnov, O.; Sotnikov, A.; Sukhotin, S.; Suvorov, Y.; Tartaglia, R.; Testera, G.; Thurn, J.; Toropova, M.; Unzhakov, E.; Vishneva, A.; Vogelaar, R. B.; von Feilitzsch, F.; Wang, H.; Weinz, S.; Winter, J.; Wojcik, M.; Wurm, M.; Yokley, Z.; Zaimidoroga, O.; Zavatarelli, S.; Zuber, K.; Zuzel, G.

2016-02-01

The detection of neutrinos emitted in the CNO reactions in the Sun is one of the ambitious goals of Borexino Phase-II. A measurement of CNO neutrinos would be a milestone in astrophysics, and would allow to solve serious issues in current solar models. A precise measurement of the rate of neutrinos from the pep reaction would allow to investigate neutrino oscillations in the MSW transition region. The pep and CNO solar neutrino physics, the measurement in Borexino Phase-I and the perspectives for the new phase are reviewed in this proceeding.

Dancing to a Different Tune: Adaptive Evolution Fine-Tunes Protein Dynamics

DTIC Science & Technology

2015-09-01

homotropic regulator of E. coli PK1. The kcat of the PEP titrations are similar both with (266 ± 3 s-1) and without (243 ± 4 s-1) FBP in solution...affinity; 3 ) P70Q, P70T and A301S (five populations), which have similar PEP affinity to the wild-type, but now have PEP cooperativity in the presence...PROGRAM ELEMENT NUMBER 5b. GRANT NUMBER 5a. CONTRACT NUMBER Form Approved OMB NO. 0704-0188 3 . DATES COVERED (From - To) - UU UU UU UU 19-12-2015

Comprehensive detection of genes causing a phenotype using phenotype sequencing and pathway analysis.

PubMed

Harper, Marc; Gronenberg, Luisa; Liao, James; Lee, Christopher

2014-01-01

Discovering all the genetic causes of a phenotype is an important goal in functional genomics. We combine an experimental design for detecting independent genetic causes of a phenotype with a high-throughput sequencing analysis that maximizes sensitivity for comprehensively identifying them. Testing this approach on a set of 24 mutant strains generated for a metabolic phenotype with many known genetic causes, we show that this pathway-based phenotype sequencing analysis greatly improves sensitivity of detection compared with previous methods, and reveals a wide range of pathways that can cause this phenotype. We demonstrate our approach on a metabolic re-engineering phenotype, the PEP/OAA metabolic node in E. coli, which is crucial to a substantial number of metabolic pathways and under renewed interest for biofuel research. Out of 2157 mutations in these strains, pathway-phenoseq discriminated just five gene groups (12 genes) as statistically significant causes of the phenotype. Experimentally, these five gene groups, and the next two high-scoring pathway-phenoseq groups, either have a clear connection to the PEP metabolite level or offer an alternative path of producing oxaloacetate (OAA), and thus clearly explain the phenotype. These high-scoring gene groups also show strong evidence of positive selection pressure, compared with strictly neutral selection in the rest of the genome.

Inactivation of the PTS as a Strategy to Engineer the Production of Aromatic Metabolites in Escherichia coli.

PubMed

Carmona, Susy Beatriz; Moreno, Fabián; Bolívar, Francisco; Gosset, Guillermo; Escalante, Adelfo

2015-01-01

Laboratory and industrial cultures of Escherichia coli employ media containing glucose which is mainly transported and phosphorylated by the phosphotransferase system (PTS). In these strains, 50% of the phosphoenolpyruvate (PEP), which results from the catabolism of transported glucose, is used as a phosphate donor for its phosphorylation and translocation by the PTS. This characteristic of the PTS limits the production of industrial biocommodities that have PEP as a precursor. Furthermore, when E. coli is exposed to carbohydrate mixtures, the PTS prevents expression of catabolic and non-PTS transport genes by carbon catabolite repression and inducer exclusion. In this contribution, we discuss the main strategies developed to overcome these potentially limiting effects in production strains. These strategies include adaptive laboratory evolution selection of PTS(-) Glc(+) mutants, followed by the generation of strains that recover their ability to grow with glucose as a carbon source while allowing the simultaneous consumption of more than one carbon source. We discuss the benefits of using alternative glucose transport systems and describe the application of these strategies to E. coli strains with specific genetic modifications in target pathways. These efforts have resulted in significant improvements in the production of diverse biocommodities, including aromatic metabolites, biofuels and organic acids. © 2015 S. Karger AG, Basel.

The Use of Surrogate and Patient-Relevant Endpoints in Outcomes-Based Market Access Agreements : Current Debate.

PubMed

Toumi, Mondher; Jarosławski, Szymon; Sawada, Toyohiro; Kornfeld, Åsa

2017-02-01

The high cost of novel treatments is the major driver of negative or restricted reimbursement decisions by healthcare payers in many countries. Costly drugs can be subject to Market Access Agreements (MAAs), which are financial (Commercial Agreements [CAs]) or outcomes-based (Payment for Performance Agreements [P4Ps] or Coverage with Evidence Development agreements [CEDs]). Outcomes in outcomes-based MAAs are assessed through changes in surrogate endpoints (SEPs) or patient-relevant endpoints (PEPs). In May 2015, we reviewed published and grey literature on MAAs between manufacturers and large, institutionalised payers from all geographical areas, and classified the schemes into CAs, P4Ps and CEDs, as well as by therapeutic area and country. Outcomes-based MAAs were further categorized by the endpoint used. Overall, we identified 143 MAAs, 56 (39.2 %) of which were pure CAs, 53 (37.1 %) were CEDs, and 34 (23.8 %) were P4Ps. Among the CEDs, 49 were PEP CEDs and four were SEP CEDs; of the 34 P4Ps, 29 were SEP P4Ps for 30 drugs, and five were PEP P4Ps for at least six drugs; and among 87 outcomes-based MAAs (CEDs + P4Ps), PEP CEDs were the most common (56.3 %), followed by SEP P4Ps (34.1 %). The high proportion of SEPs used in P4Ps contrasts with the high proportion of PEPs used in CEDs. CEDs employ PEPs and it appears that they are used to reduce uncertainty about a drug's clinical outcomes and/or real-life use, and thus allow payers to align a product's value with price. We argue that P4Ps do not reduce uncertainty about real-life effectiveness and can only constitute an outcome guarantee for payers if they are based on PEPs or validated SEPs.

Novel Synthetic, Host-defense Peptide Protects Against Organ Injury/Dysfunction in a Rat Model of Severe Hemorrhagic Shock.

PubMed

Yamada, Noriaki; Martin, Lukas B; Zechendorf, Elisabeth; Purvis, Gareth S D; Chiazza, Fausto; Varrone, Barbara; Collino, Massimo; Shepherd, Joanna; Heinbockel, Lena; Gutsmann, Thomas; Correa, Wilmar; Brandenburg, Klaus; Marx, Gernot; Schuerholz, Tobias; Brohi, Karim; Thiemermann, Christoph

2017-03-10

To evaluate (1) levels of the host-defense/antimicrobial peptide LL-37 in patients with trauma and hemorrhagic shock (HS) and (2) the effects of a synthetic host-defense peptide; Pep19-4LF on multiple organ failure (MOF) associated with HS. HS is a common cause of death in severely injured patients. There is no specific therapy that reduces HS-associated MOF. (1) LL-37 was measured in 47 trauma/HS patients admitted to an urban major trauma center. (2) Male Wistar rats were submitted to HS (90 min, target mean arterial pressure: 27-32 mm Hg) or sham operation. Rats were treated with Pep19-4LF [66 (n = 8) or 333 μg/kg · h (n = 8)] or vehicle (n = 12) for 4 hours following resuscitation. Plasma LL-37 was 12-fold higher in patients with trauma/HS compared to healthy volunteers. HS rats treated with Pep19-4LF (high dose) had a higher mean arterial pressure at the end of the 4-hour resuscitation period (79 ± 4 vs 54 ± 5 mm Hg) and less renal dysfunction, liver injury, and lung inflammation than HS rats treated with vehicle. Pep19-4LF enhanced (kidney/liver) the phosphorylation of (1) protein kinase B and (2) endothelial nitric oxide synthase. Pep19-4LF attenuated the HS-induced (1) translocation of p65 from cytosol to nucleus, (2) phosphorylation of IκB kinase on Ser, and (3) phosphorylation of IκBα on Ser resulting in inhibition of nuclear factor kappa B and formation of proinflammatory cytokines. Pep19-4LF prevented the release of tumor necrosis factor alpha caused by heparan sulfate in human mononuclear cells by binding to this damage-associated molecular pattern. Trauma-associated HS results in release of LL-37. The synthetic host-defense/antimicrobial peptide Pep19-4LF attenuates the organ injury/dysfunction associated with HS.

A police education programme to integrate occupational safety and HIV prevention: protocol for a modified stepped-wedge study design with parallel prospective cohorts to assess behavioural outcomes

PubMed Central

Strathdee, Steffanie A; Arredondo, Jaime; Rocha, Teresita; Abramovitz, Daniela; Rolon, Maria Luisa; Patiño Mandujano, Efrain; Rangel, Maria Gudelia; Olivarria, Horcasitas Omar; Gaines, Tommi; Patterson, Thomas L; Beletsky, Leo

2015-01-01

Introduction Policing practices are key drivers of HIV among people who inject drugs (PWID). This paper describes the protocol for the first study to prospectively examine the impact of a police education programme (PEP) to align law enforcement and HIV prevention. PEPs incorporating HIV prevention (including harm reduction programmes like syringe exchange) have been successfully piloted in several countries but were limited to brief pre–post assessments; the impact of PEPs on policing behaviours and occupational safety is unknown. Objectives Proyecto ESCUDO (SHIELD) aims to evaluate the efficacy of the PEP on uptake of occupational safety procedures, as assessed through the incidence of needle stick injuries (NSIs) (primary outcome) and changes in knowledge of transmission, prevention and treatment of HIV and viral hepatitis; attitudes towards PWID, adverse behaviours that interfere with HIV prevention and protective behaviours (secondary outcomes). Methods/analysis ESCUDO is a hybrid type I design that simultaneously tests an intervention and an implementation strategy. Using a modified stepped-wedge design involving all active duty street-level police officers in Tijuana (N=∼1200), we will administer one 3 h PEP course to groups of 20–50 officers until the entire force is trained. NSI incidence and geocoded arrest data will be assessed from department-wide de-identified data. Of the consenting police officers, a subcohort (N=500) will be randomly sampled from each class to undergo pre-PEP and post-PEP surveys with a semiannual follow-up for 2 years to assess self-reported NSIs, attitudes and behaviour changes. The impact on PWIDs will be externally validated through a parallel cohort of Tijuana PWIDs. Ethics/dissemination Research ethics approval was obtained from the USA and Mexico. Findings will be disseminated through open access to protocol materials through the Law Enforcement and HIV Network. Trial registration number NCT02444403. PMID:26260350

Apoptosis imaging studies in various animal models using radio-iodinated peptide.

PubMed

Kwak, Wonjung; Ha, Yeong Su; Soni, Nisarg; Lee, Woonghee; Park, Se-Il; Ahn, Heesu; An, Gwang Il; Kim, In-San; Lee, Byung-Heon; Yoo, Jeongsoo

2015-01-01

Apoptosis has a role in many medical disorders and treatments; hence, its non-invasive evaluation is one of the most riveting research topics. Currently annexin V is used as gold standard for imaging apoptosis. However, several drawbacks, including high background, slow body clearance, make it a suboptimum marker for apoptosis imaging. In this study, we radiolabeled the recently identified histone H1 targeting peptide (ApoPep-1) and evaluated its potential as a new apoptosis imaging agent in various animal models. ApoPep-1 (CQRPPR) was synthesized, and an extra tyrosine residue was added to its N-terminal end for radiolabeling. This peptide was radiolabeled with (124)I and (131)I and was tested for its serum stability. Surgery- and drug-induced apoptotic rat models were prepared for apoptosis evaluation, and PET imaging was performed. Doxorubicin was used for xenograft tumor treatment in mice, and the induced apoptosis was studied. Tumor metabolism and proliferation were assessed by [(18)F]FDG and [(18)F]FLT PET imaging and compared with ApoPep-1 after doxorubicin treatment. The peptide was radiolabeled at high purity, and it showed reasonably good stability in serum. Cell death was easily imaged by radiolabeled ApoPep-1 in an ischemia surgery model. And, liver apoptosis was more clearly identified by ApoPep-1 rather than [(124)I]annexin V in cycloheximide-treated models. Three doxorubicin doses inhibited tumor growth, which was evaluated by 30-40% decreases of [(18)F]FDG and [(18)F]FLT PET uptake in the tumor area. However, ApoPep-1 demonstrated more than 200% increase in tumor uptake after chemotherapy, while annexin V did not show any meaningful uptake in the tumor compared with the background. Biodistribution data were also in good agreement with the microPET imaging results. All of the experimental data clearly demonstrated high potential of the radiolabeled ApoPep-1 for in vivo apoptosis imaging.

Molecular Steps in the Immune Signaling Pathway Evoked by Plant Elicitor Peptides: Ca2+-Dependent Protein Kinases, Nitric Oxide, and Reactive Oxygen Species Are Downstream from the Early Ca2+ Signal1[OPEN

PubMed Central

Ma, Yi; Zhao, Yichen; Walker, Robin K.; Berkowitz, Gerald A.

2013-01-01

Endogenous plant elicitor peptides (Peps) can act to facilitate immune signaling and pathogen defense responses. Binding of these peptides to the Arabidopsis (Arabidopsis thaliana) plasma membrane-localized Pep receptors (PEPRs) leads to cytosolic Ca2+ elevation, an early event in a signaling cascade that activates immune responses. This immune response includes the amplification of signaling evoked by direct perception of pathogen-associated molecular patterns by plant cells under assault. Work included in this report further characterizes the Pep immune response and identifies new molecular steps in the signal transduction cascade. The PEPR coreceptor BRASSINOSTEROID-INSENSITIVE1 Associated Kinase1 contributes to generation of the Pep-activated Ca2+ signal and leads to increased defense gene expression and resistance to a virulent bacterial pathogen. Ca2+-dependent protein kinases (CPKs) decode the Ca2+ signal, also facilitating defense gene expression and enhanced resistance to the pathogen. Nitric oxide and reduced nicotinamide adenine dinucleotide phosphate oxidase-dependent reactive oxygen species generation (due to the function of Respiratory Burst Oxidase Homolog proteins D and F) are also involved downstream from the Ca2+ signal in the Pep immune defense signal transduction cascade, as is the case with BRASSINOSTEROID-INSENSITIVE1 Associated Kinase1 and CPK5, CPK6, and CPK11. These steps of the pathogen defense response are required for maximal Pep immune activation that limits growth of a virulent bacterial pathogen in the plant. We find a synergism between function of the PEPR and Flagellin Sensing2 receptors in terms of both nitric oxide and reactive oxygen species generation. Presented results are also consistent with the involvement of the secondary messenger cyclic GMP and a cyclic GMP-activated Ca2+-conducting channel in the Pep immune signaling pathway. PMID:24019427

Competition between Förster resonance energy transfer and electron transfer in stoichiometrically assembled semiconductor quantum dot-fullerene conjugates.

PubMed

Stewart, Michael H; Huston, Alan L; Scott, Amy M; Oh, Eunkeu; Algar, W Russ; Deschamps, Jeffrey R; Susumu, Kimihiro; Jain, Vaibhav; Prasuhn, Duane E; Blanco-Canosa, Juan; Dawson, Philip E; Medintz, Igor L

2013-10-22

Understanding how semiconductor quantum dots (QDs) engage in photoinduced energy transfer with carbon allotropes is necessary for enhanced performance in solar cells and other optoelectronic devices along with the potential to create new types of (bio)sensors. Here, we systematically investigate energy transfer interactions between C60 fullerenes and four different QDs, composed of CdSe/ZnS (type I) and CdSe/CdS/ZnS (quasi type II), with emission maxima ranging from 530 to 630 nm. C60-pyrrolidine tris-acid was first coupled to the N-terminus of a hexahistidine-terminated peptide via carbodiimide chemistry to yield a C60-labeled peptide (pepC60). This peptide provided the critical means to achieve ratiometric self-assembly of the QD-(pepC60) nanoheterostructures by exploiting metal affinity coordination to the QD surface. Controlled QD-(pepC60)N bioconjugates were prepared by discretely increasing the ratio (N) of pepC60 assembled per QD in mixtures of dimethyl sulfoxide and buffer; this mixed organic/aqueous approach helped alleviate issues of C60 solubility. An extensive set of control experiments were initially performed to verify the specific and ratiometric nature of QD-(pepC60)N assembly. Photoinitiated energy transfer in these hybrid organic-inorganic systems was then interrogated using steady-state and time-resolved fluorescence along with ultrafast transient absorption spectroscopy. Coordination of pepC60 to the QD results in QD PL quenching that directly tracks with the number of peptides displayed around the QD. A detailed photophysical analysis suggests a competition between electron transfer and Förster resonance energy transfer from the QD to the C60 that is dependent upon a complex interplay of pepC60 ratio per QD, the presence of underlying spectral overlap, and contributions from QD size. These results highlight several important factors that must be considered when designing QD-donor/C60-acceptor systems for potential optoelectronic and biosensing applications.

Evaluation of early immune response-survival relationship in cynomolgus macaques after Anthrax Vaccine Adsorbed vaccination and Bacillus anthracis spore challenge.

PubMed

Sivko, G S; Stark, G V; Tordoff, K P; Taylor, K L; Glaze, E; VanRaden, M; Schiffer, J M; Hewitt, J A; Quinn, C P; Nuzum, E O

2016-12-12

Anthrax Vaccine Adsorbed (AVA, BioThrax) is approved by the US Food and Drug Administration for post-exposure prophylaxis (PEP) of anthrax in adults. The PEP schedule is 3 subcutaneous (SC) doses (0, 14 and 28 days), in conjunction with a 60 day course of antimicrobials. The objectives of this study were to understand the onset of protection from AVA PEP vaccination and to assess the potential for shortening the duration of antimicrobial treatment (http://www.phe.gov/Preparedness/mcm/phemce/Documents/2014-phemce-sip.pdf). We determined the efficacy against inhalation anthrax in nonhuman primates (NHP) of the first two doses of the PEP schedule by infectious challenge at the time scheduled for receipt of the third PEP dose (Day 28). Forty-eight cynomolgus macaques were randomized to five groups and vaccinated with serial dilutions of AVA on Days 0 and 14. NHP were exposed to Bacillus anthracis Ames spores on Day 28 (target dose 200 LD 50 equivalents). Anti-protective antigen (PA) IgG and toxin neutralizing antibody (TNA) responses to vaccination and in post-challenge survivors were determined. Post-challenge blood and selected tissue samples were assessed for B. anthracis at necropsy or end of study (Day 56). Pre-challenge humoral immune responses correlated with survival, which ranged from 24 to 100% survival depending on vaccination group. Surviving, vaccinated animals had elevated anti-PA IgG and TNA levels for the duration of the study, were abacteremic, exhibited no apparent signs of infection, and had no gross or microscopic lesions. However, survivors had residual spores in lung tissues. We conclude that the first two doses of the PEP schedule provide high levels of protection by the scheduled timing of the third dose. These data may also support consideration of a shorter duration PEP antimicrobial regimen. Copyright © 2016 Elsevier Ltd. All rights reserved.

Post-Exposure Prophylaxis (PEP)

MedlinePlus

... Child Transmission of HIV Post-Exposure Prophylaxis (PEP) Pre-Exposure Prophylaxis (PrEP) HIV Treatment HIV Treatment: The Basics Just ... to HIV frequently. Another HIV prevention method, called pre-exposure prophylaxis or PrEP, is when people at high risk ...

Projected Entangled Pair States with non-Abelian gauge symmetries: An SU(2) study

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

Zohar, Erez, E-mail: erez.zohar@mpq.mpg.de; Wahl, Thorsten B.; Burrello, Michele, E-mail: michele.burrello@mpq.mpg.de

Over the last years, Projected Entangled Pair States have demonstrated great power for the study of many body systems, as they naturally describe ground states of gapped many body Hamiltonians, and suggest a constructive way to encode and classify their symmetries. The PEPS study is not only limited to global symmetries, but has also been extended and applied for local symmetries, allowing to use them for the description of states in lattice gauge theories. In this paper we discuss PEPS with a local, SU(2) gauge symmetry, and demonstrate the use of PEPS features and techniques for the study of amore » simple family of many body states with a non-Abelian gauge symmetry. We present, in particular, the construction of fermionic PEPS able to describe both two-color fermionic matter and the degrees of freedom of an SU(2) gauge field with a suitable truncation.« less

Development of a Pediatric Ebola Predictive Score, Sierra Leone1.

PubMed

Fitzgerald, Felicity; Wing, Kevin; Naveed, Asad; Gbessay, Musa; Ross, J C G; Checchi, Francesco; Youkee, Daniel; Jalloh, Mohamed Boie; Baion, David E; Mustapha, Ayeshatu; Jah, Hawanatu; Lako, Sandra; Oza, Shefali; Boufkhed, Sabah; Feury, Reynold; Bielicki, Julia; Williamson, Elizabeth; Gibb, Diana M; Klein, Nigel; Sahr, Foday; Yeung, Shunmay

2018-02-01

We compared children who were positive for Ebola virus disease (EVD) with those who were negative to derive a pediatric EVD predictor (PEP) score. We collected data on all children <13 years of age admitted to 11 Ebola holding units in Sierra Leone during August 2014-March 2015 and performed multivariable logistic regression. Among 1,054 children, 309 (29%) were EVD positive and 697 (66%) EVD negative, with 48 (5%) missing. Contact history, conjunctivitis, and age were the strongest positive predictors for EVD. The PEP score had an area under receiver operating characteristics curve of 0.80. A PEP score of 7/10 was 92% specific and 44% sensitive; 3/10 was 30% specific, 94% sensitive. The PEP score could correctly classify 79%-90% of children and could be used to facilitate triage into risk categories, depending on the sensitivity or specificity required.

Undulator performance on PEP storage ring with different optics

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

Shenoy, G.K.; Viccaro, P.J.; Alp, E.E.

1987-12-01

Our ability to profitably utilize the radiation from undulators proposed for PEP is determined by their performance in the different operating modes and by whether the design tolerance required for acceptable operation of the device can be met with available technology. The purpose of this paper is to provide spectral characteristics for some typical devices calculated using a Monte-Carlo algorithm in which the Lienard-Wiechert potential is integrated over the trajectory of the charged particle along the undulator length. The actual emittance of the particle beam for the various PEP operating modes are included explicitly in the simulations. In addition, wemore » have carried out a single partial analysis of the effects of undulator magnetic field errors on the spectral properties in order to estimate the design tolerance requirements necessary for devices which have been proposed PEP. 6 figs.« less

Structural basis for the substrate specificity of PepA from Streptococcus pneumoniae, a dodecameric tetrahedral protease.

PubMed

Kim, Doyoun; San, Boi Hoa; Moh, Sang Hyun; Park, Hyejin; Kim, Dong Young; Lee, Sangho; Kim, Kyeong Kyu

2010-01-01

Regulated cytosolic proteolysis is one of the key cellular processes ensuring proper functioning of a cell. M42 family proteases show a broad spectrum of substrate specificities, but the structural basis for such diversity of the substrate specificities is lagging behind biochemical data. Here we report the crystal structure of PepA from Streptococcus pneumoniae, a glutamyl aminopeptidase belonging to M42 family (SpPepA). We found that Arg-257 in the substrate binding pocket is strategically positioned so that Arg-257 can make electrostatic interactions with the acidic residue of a substrate at its N-terminus. Structural comparison of the substrate binding pocket of the M42 family proteases, along with the structure-based multiple sequence alignment, argues that the appropriate electrostatic interactions contribute to the selective substrate specificity of SpPepA. Copyright 2009 Elsevier Inc. All rights reserved.

Quantum critical phase with infinite projected entangled paired states

NASA Astrophysics Data System (ADS)

Poilblanc, Didier; Mambrini, Matthieu

2017-07-01

A classification of SU(2)-invariant projected entangled paired states (PEPS) on the square lattice, based on a unique site tensor, has been recently introduced by Mambrini et al. [M. Mambrini, R. Orús, and D. Poilblanc, Phys. Rev. B 94, 205124 (2016), 10.1103/PhysRevB.94.205124]. It is not clear whether such SU(2)-invariant PEPS can either (i) exhibit long-range magnetic order (such as in the Néel phase) or (ii) describe a genuine quantum critical point (QCP) or quantum critical phase (QCPh) separating two ordered phases. Here, we identify a specific family of SU(2)-invariant PEPS of the classification which provides excellent variational energies for the J1-J2 frustrated Heisenberg model, especially at J2=0.5 , corresponding to the approximate location of the QCP or QCPh separating the Néel phase from a dimerized phase. The PEPS are built from virtual states belonging to the 1/2⊗N⊕0 SU(2) representation, i.e., with N "colors" of virtual spin-1/2 . Using a full-update infinite-PEPS approach directly in the thermodynamic limit, based on the corner transfer matrix renormalization algorithm supplemented by a conjugate gradient optimization scheme, we provide evidence of (i) the absence of magnetic order and of (ii) diverging correlation lengths (i.e., showing no sign of saturation with increasing environment dimension) in both the singlet and triplet channels, when the number of colors N ≥3 . We argue that such a PEPS gives a qualitative description of the QCP or QCPh of the J1-J2 model.

In vivo fluorescence imaging of exogenous enzyme activity in the gastrointestinal tract

PubMed Central

Fuhrmann, Gregor; Leroux, Jean-Christophe

2011-01-01

Exogenous enzymes are administered orally to treat several diseases, such as pancreatic insufficiency and lactose intolerance. Due to the proteinaceous nature of enzymes, they are subject to inactivation and/or digestion in the gastrointestinal (GI) tract. Here we describe a convenient fluorescence-based assay to monitor the activity of therapeutic enzymes in real time in vivo in the GI tract. To establish the proof of principle, the assay was applied to proline-specific endopeptidases (PEPs), a group of enzymes recently proposed as adjuvant therapy for celiac disease (a highly prevalent immunogenetic enteropathy). A short PEP-specific peptide sequence which is part of larger immunotoxic sequences of gluten was labeled with a fluorescent dye and a corresponding quencher. Upon enzymatic cleavage, the fluorescence emission was dequenched and detected with an in vivo imaging system. PEPs originating from Flavobacterium meningosepticum (FM) and Myxococcus xanthus (MX) were evaluated after oral administration in rats. While MX PEP could not cleave the peptide in the stomach, FM PEP showed significant gastric activity reaching 40–60% of the maximal in vivo signal intensity. However, both enzymes produced comparable fluorescence signals in the small intestine. Coadministration of an antacid drug significantly enhanced MX PEP’s gastric activity due to increased pH and/or inhibition of stomach proteases. With this simple procedure, differences in the in vivo performance of PEPs, which could not be identified under in vitro conditions, were detected. This imaging assay could be used to study other oral enzymes in vivo and therefore be instrumental in improving their therapeutic efficiency. PMID:21576491

Accelerated healing of cardiovascular textiles promoted by an RGD peptide.

PubMed

Tweden, K S; Harasaki, H; Jones, M; Blevitt, J M; Craig, W S; Pierschbacher, M; Helmus, M N

1995-07-01

Polytetrafluoroethylene (PTFE) and polyethylene terephthalate (Dacron polyester) fabrics are used extensively in cardiovascular devices, e.g. heart valve sewing cuffs and vascular prostheses. While devices containing these fabrics are generally successful, it is recognized that fabrics cause complications prior to tissue ingrowth due to their thrombogenic nature. A surface active synthetic peptide, called PepTite Coating (PepTite), which was modeled after the cell attachment domain of human fibronectin has been marketed as a biocompatible coating. This peptide stimulates cell attachment through the arginine-glycine-aspartic acid (RGD) sequence. Modification of medical implants with PepTite has been shown to promote ingrowth of surrounding cells into the material leading to better tissue integration, reduced inflammation and reduced fibrotic encapsulation. In this study, polyester and PTFE textiles were modified with PepTite. The effectiveness of this coating in enhancing wound healing was investigated in a simple vascular and cardiac valve model. Our results indicate that the RGD-containing peptide, PepTite, promoted the formation of an endothelial-like cell layer on both polyester and PTFE vascular patches in the dog model. PepTite was also found to promote the formation of a significantly thinner neointima (pannus) on polyester as compared to that on its uncoated control. These results were corroborated in the cardiac valve model in which a greater amount of thin pannus and less thrombus were seen on coated polyester sewing cuffs than on control uncoated cuffs. This research shows the promising tissue response to RGD coated textiles and the potential role of this peptide in material passivation via accelerated healing.

Positive expiratory pressure device acceptance by hospitalized children with sickle cell disease is comparable to incentive spirometry.

PubMed

Hsu, Lewis L; Batts, Brenda K; Rau, Joseph L

2005-05-01

The pulmonary complication in sickle cell disease known as acute chest syndrome (ACS) has potential for high morbidity and mortality. A randomized trial demonstrated that incentive spirometry (IS) reduces the rate of ACS, leading to a role for respiratory therapy in hospital management of sickle cell pain. However, use of IS can be limited by chest wall pain, or by difficulty with the coordinated inspiration in a young child. Intermittent positive expiratory pressure (PEP) therapy may be easier for a child's coordination and more comfortable than IS for a child with chest wall pain. To compare PEP therapy with conventional IS for children hospitalized for sickle cell pain with respect to patient satisfaction, length of hospital stay, and progression to ACS. This pilot study enrolled 20 children upon hospitalization for sickle cell pain in the thorax, randomly assigning them to either PEP (n = 11) or IS (n = 9) therapy, administered by a therapist hourly while awake. The randomization assigned an older distribution to PEP than IS (12.3 vs 8.8 y). Patient satisfaction was high for both respiratory care devices, and there was no difference between the PEP and IS groups (4.5 vs 4.4, p = 0.81). Length of hospital stay was similar (5 vs 4.3 d, p = 0.56). No children in either group progressed to ACS. These preliminary results show no difference in the primary outcomes in the 2 groups. Intermittent PEP therapy warrants further study as an alternative to IS for sickle cell patients at high risk for ACS, as effective preventive respiratory therapy.

Heat inactivation of leaf phosphoenolpyruvate carboxylase: Protection by aspartate and malate in C4 plants.

PubMed

Rathnam, C K

1978-01-01

The activity of phosphoenolpyruvate (PEP) carboxylase EC 4.1.1.31 in leaf extracts of Eleusine indica L. Gaertn., a C4 plant, exhibited a temperature optimum of 35-37° C with a complete loss of activity at 50° C. However, the enzyme was protected effectively from heat inactivation up to 55° C by L-aspartate. Activation energies (Ea) for the enzyme in the presence of aspartate were 2.5 times lower than that of the control enzyme. Arrhenius plots of PEP carboxylase activity (±aspartate) showed a break in the slope around 17-20° C with a 3-fold increase in the Ea below the break. The discontinuity in the slopes was abolished by treating the enzyme extracts with Triton X-100, suggesting that PEP carboxylase in C4 plants is associated with lipid and may be a membrane bound enzyme. Depending upon the species, the major C4 acid formed during photosynthesis (malate or aspartate) was found to be more protective than the minor C4 acid against the heat inactivation of their PEP carboxylase. Oxaloacetate, the reaction product, was less effective compared to malate or aspartate. Several allosteric inhibitors of PEP carboxylase were found to be moderately to highly effective in protecting the C4 enzyme while its activators showed no significant effect. PEP carboxylase from C3 species was not protected from thermal inactivation by the C4 acids. The physiological significance of these results is discussed in relation to the high temperature tolerance of C4 plants.

Determination of Free-Form and Peptide Bound Pyrraline in the Commercial Drinks Enriched with Different Protein Hydrolysates

PubMed Central

Liang, Zhili; Li, Lin; Qi, Haiping; Zhang, Xia; Xu, Zhenbo; Li, Bing

2016-01-01

Pyrraline, a causative factor for the recent epidemics of diabetes and cardiovascular disease, is also employed as an indicator to evaluate heat damage and formation of advanced glycation end-products (AGEs) in foods. Peptide-enriched drinks (PEDs) are broadly consumed worldwide due to rapid rate of absorption and perceived health effects. It can be hypothesized that PED is an important source of pyrraline, especially peptide bound pyrraline (Pep-Pyr). In this study we determined free-form pyrraline (Free-Pyr) and Pep-Pyr in drinks enriched with whey protein hydrolysate (WPH), soy protein hydrolysate (SPH) and collagen protein hydrolysate (CPH). A detection method was developed using ultrahigh-performance liquid chromatography with UV-visible detector coupled with tandem mass spectrometry after solid-phase extraction (SPE). The SPE led to excellent recovery rates ranging between 93.2% and 98.5% and a high reproducibility with relative standard deviations (RSD) of <5%. The limits of detection and quantification obtained were 30.4 and 70.3 ng/mL, respectively. Pep-Pyr was identified as the most abundant form (above 96 percent) of total pyrraline, whereas Free-Pyr was present in a small proportion (less than four percent) of total pyrraline. The results indicate that PED is an important extrinsic source of pyrraline, especially Pep-Pyr. As compared with CPH- and SPH-enriched drinks, WPH-enriched drinks contained high content of Pep-Pyr. The Pep-Pyr content is associated with the distribution of peptide lengths and the amino acid compositions of protein in PEDs. PMID:27384561

Light-dependent, plastome-wide association of the plastid-encoded RNA polymerase with chloroplast DNA.

PubMed

Finster, Sabrina; Eggert, Erik; Zoschke, Reimo; Weihe, Andreas; Schmitz-Linneweber, Christian

2013-12-01

Plastid genes are transcribed by two types of RNA polymerases: a plastid-encoded eubacterial-type RNA polymerase (PEP) and nuclear-encoded phage-type RNA polymerases (NEPs). To investigate the spatio-temporal expression of PEP, we tagged its α-subunit with a hemagglutinin epitope (HA). Transplastomic tobacco plants were generated and analyzed for the distribution of the tagged polymerase in plastid sub-fractions, and associated genes were identified under various light conditions. RpoA:HA was detected as early as the 3rd day after imbibition, and was constitutively expressed in green tissue over 60 days of plant development. We found that the tagged polymerase subunit preferentially associated with the plastid membranes, and was less abundant in the soluble stroma fraction. Attachment of RpoA:HA to the membrane fraction during early seedling development was independent of DNA, but at later stages of development, DNA appears to facilitate attachment of the polymerase to membranes. To survey PEP-dependent transcription units, we probed for nucleic acids enriched in RpoA:HA precipitates using a tobacco chloroplast whole-genome tiling array. The most strongly co-enriched DNA fragments represent photosynthesis genes (e.g. psbA, psbC, psbD and rbcL), whose expression is known to be driven by PEP promoters, while NEP-dependent genes were less abundant in RpoA:HA precipitates. Additionally, we demonstrate that the association of PEP with photosynthesis-related genes was reduced during the dark period, indicating that plastome-wide PEP-DNA association is a light-dependent process. © 2013 The Authors The Plant Journal © 2013 John Wiley & Sons Ltd.

Determination of a natural DNMT1 inhibitor, peperomin E, in rat plasma by UFLC-MS/MS and method application in a pharmacokinetic study.

PubMed

Wang, Xin-Zhi; Wen, Hong-Mei; Chai, Chuan; Zhang, Wen-Ying; Gao, Ming; Liu, Rui; Wu, Hao; Liang, Jing-Yu

2017-08-01

Peperomin E (PepE), a naturally occurring secolignan isolated from Peperomia dindygulensis, has drawn much attention recently owing to its anticancer and DNA methyltransferase 1 (DNMT1) inhibitory activity. Here, a simple and sensitive ultra-fast liquid chromatography-tandem mass spectrometry method was developed and validated for the determination of PepE in rat plasma for the first time. Samples were prepared by simple protein precipitation. Separation was performed on an XBridge™ C 18 column using a mobile phase of acetonitrile and 0.1% (v/v) aqueous formic acid. PepE and the internal standard arctigenin were detected in a positive-ion mode using multiple reaction monitoring of the transitions at m/z 413.2 → 261.0 and 373.2 → 137.2, respectively. The calibration curve for PepE was linear over the range of concentrations of 1.46-6000 ng/mL, with a lower limit of quantitation of 1.46 ng/mL. Both intra- and interday precisions were within 11.05%, and the accuracy ranged from -11.5 to 5.51%. The extraction recovery and matrix effect were within acceptable limits. Stability tests showed that PepE remained stable throughout the analytical procedure. The validated method was then used to analyze the pharmacokinetics of PepE administered to rats orally (12.5 and 25 mg/kg) or intravenously (6.25 and 12.5 mg/kg). Copyright © 2017 John Wiley & Sons, Ltd.

Dendritic cells induce specific cytotoxic T lymphocytes against prostate cancer TRAMP-C2 cells loaded with freeze- thaw antigen and PEP-3 peptide.

PubMed

Liu, Xiao-Qi; Jiang, Rong; Li, Si-Qi; Wang, Jing; Yi, Fa-Ping

2015-01-01

Prostate cancer is the most common cancer in men. In this study, we investigated immune responses of cytotoxic T lymphocytes (CTLs) against TRAMP-C2 prostate cancer cells after activation by dendritic cells (DCs) loaded with TRAMP-C2 freeze-thaw antigen and/or PEP-3 peptide in vitro. Bone marrow-derived DC from the bone marrow of the C57BL/6 were induced to mature by using the cytokine of rhGM-CSF and rhIL-4, and loaded with either the freeze-thaw antigen or PEP-3 peptide or both of them. Maturation of DCs was detected by flow cytometry. The killing efficiency of the CTLs on TRAMP-C2 cells were detected by flow cytometry, CCK8, colony formation, transwell migration, and wound-healing assay. The levels of the IFN-γ, TNF-β and IL-12 were measured by enzyme-linked immunosorbent assay (ELISA). Compared with the unloaded DCs, the loaded DCs had significantly increased expression of several phenotypes related to DC maturation. CTLs activated by DCs loaded with freeze-thaw antigen and PEP-3 peptide had more evident cytotoxicity against TRAMP-C2 cells in vitro. The secretion levels of IFN-γ, TNF-β and IL-12, secreted by DCs loaded with antigen and PEP-3 and interaction with T cells, were higher than in the other groups. Our results suggest that the CTLs activated by DCs loaded with TRAMP-C2 freeze-thaw antigen and PEP-3 peptide exert a remarkable killing efficiency against TRAMP-C2 cells in vitro.

The AAVSO Photoelectric Photometry Program in its Scientific and Socio-Historic Context

NASA Astrophysics Data System (ADS)

Percy, John R.

2011-05-01

Photoelectric photometry began in the 1900s through the work of Guthnick, Stebbins, and others who constructed and used photometers based on the recently-discovered photoelectric effect. The mid 20th century saw a confluence of several areas of amateur interest: astronomy, telescope making, radio and electronics, and general interest in space. This is the time when AAVSO photoelectric photometry (PEP) began, with observers using mostly hand-built photometers on hand-built telescopes. The 1980s brought a revolution: affordable off-the-shelf solid-state photometers, and infrastructure such as the International Amateur-Professional Photoelectric Photometry (IAPPP) conferences, books, and journal. The AAVSO developed a formal PEP program in the early 1980s. Its emphasis was on long-term monitoring of pulsating red giants. It was competing, not always successfully, with programs such as active sun-like binaries (RS CVn stars) which offered "instant gratification" in the form of publicity and quick publications. Nevertheless, the AAVSO PEP program has, through careful organization, motivation, and feedback to observers, produced extensive scientific results. In this presentation, I shall describe, as examples, my own work, its scientific significance, its educational benefit to dozens of my students, and its satisfaction to the observers. To some extent, the AAVSO PEP program has been superceded by its CCD program, but there is still a useful place for ongoing PEP observations of thousands of variable stars. Reference: http://www.aavso.org/sites/default/files/newsletter/PEP/lastpepnl.pdf Acknowledgements: I thank NSERC Canada for research support, my students, and AAVSO staff and observers, especially Howard Landis.

Theory of the Protein Equilibrium Population Snapshot by H/D Exchange Electrospray Ionization Mass Spectrometry (PEPS-HDX-ESI-MS) Method used to obtain Protein Folding Energies/Rates and Selected Supporting Experimental Evidence.

PubMed

Liyanage, Rohana; Devarapalli, Nagarjuna; Pyland, Derek B; Puckett, Latisha M; Phan, N H; Starch, Joel A; Okimoto, Mark R; Gidden, Jennifer; Stites, Wesley E; Lay, Jackson O

2012-12-15

Protein equilibrium snapshot by hydrogen/deuterium exchange electrospray ionization mass spectrometry (PEPS-HDX-ESI-MS or PEPS) is a method recently introduced for estimating protein folding energies and rates. Herein we describe the basis for this method using both theory and new experiments. Benchmark experiments were conducted using ubiquitin because of the availability of reference data for folding and unfolding rates from NMR studies. A second set of experiments was also conducted to illustrate the surprising resilience of the PEPS to changes in HDX time, using staphylococcal nuclease and time frames ranging from a few seconds to several minutes. Theory suggests that PEPS experiments should be conducted at relatively high denaturant concentrations, where the protein folding/unfolding rates are slow with respect to HDX and the life times of both the closed and open states are long enough to be sampled experimentally. Upon deliberate denaturation, changes in folding/unfolding are correlated with associated changes in the ESI-MS signal upon fast HDX. When experiments are done quickly, typically within a few seconds, ESI-MS signals, corresponding to the equilibrium population of the native (closed) and denatured (open) states can both be detected. The interior of folded proteins remains largely un-exchanged. Amongst MS methods, the simultaneous detection of both states in the spectrum is unique to PEPS and provides a "snapshot" of these populations. The associated ion intensities are used to estimate the protein folding equilibrium constant (or the free energy change, ΔG). Linear extrapolation method (LEM) plots of derived ΔG values for each denaturant concentration can then be used to calculate ΔG in the absence of denaturant, ΔG(H(2)O). In accordance with the requirement for detection of signals for both the folded and unfolded states, this theoretical framework predicts that PEPS experiments work best at the middle of the denaturation curve where natured and denatured protein molecules are equilibrated at easily detectable ratios, namely 1:1. It also requires that closed and open states have lifetimes measurable in the time frame of the HDX experiment. Because both conditions are met by PEPS, these measurements can provide an accurate assessment of closed/open state populations and thus protein folding energies/rates.

Differences in Awareness of Pre-exposure Prophylaxis and Post-exposure Prophylaxis Among Groups At-Risk for HIV in New York State: New York City and Long Island, NY, 2011-2013.

PubMed

Walters, Suzan M; Rivera, Alexis V; Starbuck, Lila; Reilly, Kathleen H; Boldon, Nyasha; Anderson, Bridget J; Braunstein, Sarah

2017-07-01

Pre-exposure prophylaxis (PrEP) to reduce the risk of HIV was approved in 2012 and post-exposure prophylaxis (PEP) in 2005. We report the differences in awareness of PrEP/PEP and factors associated with awareness by examining 3 risk groups (men who have sex with men (MSM), people who inject drugs, and high-risk heterosexuals). National HIV Behavioral Surveillance system data collected in New York City (NYC) and Long Island, NY in 2011-2013 were used. Logistic regressions by region were developed to estimate adjusted associations [Adjusted Odds Ratios (AOR)] and determine differences in awareness of PrEP/PEP. Awareness of PrEP/PEP was low for all groups. In multivariate analysis controlling for sociodemographic factors, noninjection drug use, HIV status, and exposure to HIV prevention, males who inject drugs in NYC had significantly decreased odds of PrEP/PEP awareness [AOR: 0.45; confidence interval (CI): 0.25 to 0.81] compared with MSM. MSM aged 18-29 years had increased awareness of PrEP (AOR: 2.94; 95% CI 1.11 to 7.80). On Long Island, females who inject drugs (AOR: 0.18; 95% CI: 0.05 to 0.62), males who inject drugs (AOR: 0.14; 95% CI: 0.05 to 0.39), female heterosexuals (AOR: 0.25; 95% CI: 0.11 to 0.59), and male heterosexuals (AOR: 0.32; 95% CI: 0.14 to 0.73) had significantly decreased odds of PrEP/PEP awareness. Black MSM had increased awareness of PrEP (AOR: 4.08 CI:1.21 to 13.73). Large proportions of groups at-risk for HIV were unaware of PrEP/PEP. When comparing risk groups to MSM, we found MSM to have greater awareness in both regions. On Long Island, people who inject drugs and heterosexuals were far less likely to have PrEP/PEP awareness than in NYC. On Long Island, Black MSM had increased PrEP awareness and in NYC MSM aged 18-29 had increased PrEP awareness. These findings suggest that awareness may be spreading through networks and highlight the importance of targeted educational and prevention efforts by group and region.

Improvement of L-phenylalanine production from glycerol by recombinant Escherichia coli strains: The role of extra copies of glpK, glpX, and tktA genes

PubMed Central

2014-01-01

Background For the production of L-phenylalanine (L-Phe), two molecules of phosphoenolpyruvate (PEP) and one molecule erythrose-4-phosphate (E4P) are necessary. PEP stems from glycolysis whereas E4P is formed in the pentose phosphate pathway (PPP). Glucose, commonly used for L-Phe production with recombinant E. coli, is taken up via the PEP-dependent phosphotransferase system which delivers glucose-6-phosphate (G6P). G6P enters either glycolysis or the PPP. In contrast, glycerol is phosphorylated by an ATP-dependent glycerol kinase (GlpK) thus saving one PEP. However, two gluconeogenic reactions (fructose-1,6-bisphosphate aldolase, fructose-1,6-bisphosphatase, FBPase) are necessary for growth and provision of E4P. Glycerol has become an important carbon source for biotechnology and reports on production of L-Phe from glycerol are available. However, the influence of FBPase and transketolase reactions on L-Phe production has not been reported. Results L-Phe productivity of parent strain FUS4/pF81 (plasmid-encoded genes for aroF, aroB, aroL, pheA) was compared on glucose and glycerol as C sources. On glucose, a maximal carbon recovery of 0.19 mM CPhe/CGlucose and a maximal space-time-yield (STY) of 0.13 g l−1 h−1 was found. With glycerol, the maximal carbon recovery was nearly the same (0.18 mM CPhe/CGlycerol), but the maximal STY was higher (0.21 g l−1 h−1). We raised the chromosomal gene copy number of the genes glpK (encoding glycerol kinase), tktA (encoding transketolase), and glpX (encoding fructose-1,6-bisphosphatase) individually. Overexpression of glpK (or its feedback-resistant variant, glpKG232D) had little effect on growth rate; L-Phe production was about 30% lower than in FUS4/pF81. Whereas the overexpression of either glpX or tktA had minor effects on productivity (0.20 mM CPhe/CGlycerol; 0.25 g l−1 h−1 and 0.21 mM CPhe/CGlycerol; 0.23 g l−1 h−1, respectively), the combination of extra genes of glpX and tktA together led to an increase in maximal STY of about 80% (0.37 g l−1 h−1) and a carbon recovery of 0.26 mM CPhe/CGlycerol. Conclusions Enhancing the gene copy numbers for glpX and tktA increased L-Phe productivity from glycerol without affecting growth rate. Engineering of glycerol metabolism towards L-Phe production in E. coli has to balance the pathways of gluconeogenesis, glycolysis, and PPP to improve the supply of the precursors, PEP and E4P. PMID:25012491

Improvement of L-phenylalanine production from glycerol by recombinant Escherichia coli strains: the role of extra copies of glpK, glpX, and tktA genes.

PubMed

Gottlieb, Katrin; Albermann, Christoph; Sprenger, Georg A

2014-07-11

For the production of L-phenylalanine (L-Phe), two molecules of phosphoenolpyruvate (PEP) and one molecule erythrose-4-phosphate (E4P) are necessary. PEP stems from glycolysis whereas E4P is formed in the pentose phosphate pathway (PPP). Glucose, commonly used for L-Phe production with recombinant E. coli, is taken up via the PEP-dependent phosphotransferase system which delivers glucose-6-phosphate (G6P). G6P enters either glycolysis or the PPP. In contrast, glycerol is phosphorylated by an ATP-dependent glycerol kinase (GlpK) thus saving one PEP. However, two gluconeogenic reactions (fructose-1,6-bisphosphate aldolase, fructose-1,6-bisphosphatase, FBPase) are necessary for growth and provision of E4P. Glycerol has become an important carbon source for biotechnology and reports on production of L-Phe from glycerol are available. However, the influence of FBPase and transketolase reactions on L-Phe production has not been reported. L-Phe productivity of parent strain FUS4/pF81 (plasmid-encoded genes for aroF, aroB, aroL, pheA) was compared on glucose and glycerol as C sources. On glucose, a maximal carbon recovery of 0.19 mM C(Phe)/C(Glucose) and a maximal space-time-yield (STY) of 0.13 g l(-1) h(-1) was found. With glycerol, the maximal carbon recovery was nearly the same (0.18 mM C(Phe)/C(Glycerol)), but the maximal STY was higher (0.21 g l(-1) h(-1)). We raised the chromosomal gene copy number of the genes glpK (encoding glycerol kinase), tktA (encoding transketolase), and glpX (encoding fructose-1,6-bisphosphatase) individually. Overexpression of glpK (or its feedback-resistant variant, glpK(G232D)) had little effect on growth rate; L-Phe production was about 30% lower than in FUS4/pF81. Whereas the overexpression of either glpX or tktA had minor effects on productivity (0.20 mM C(Phe)/C(Glycerol); 0.25 g l(-1) h(-1) and 0.21 mM C(Phe)/C(Glycerol); 0.23 g l(-1) h(-1), respectively), the combination of extra genes of glpX and tktA together led to an increase in maximal STY of about 80% (0.37 g l(-1) h(-1)) and a carbon recovery of 0.26 mM C(Phe)/C(Glycerol). Enhancing the gene copy numbers for glpX and tktA increased L-Phe productivity from glycerol without affecting growth rate. Engineering of glycerol metabolism towards L-Phe production in E. coli has to balance the pathways of gluconeogenesis, glycolysis, and PPP to improve the supply of the precursors, PEP and E4P.

Floor Plans Fuel Tank Support, Fuel Platform, and LOX ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Floor Plans - Fuel Tank Support, Fuel Platform, and LOX Platform Plans - Marshall Space Flight Center, F-1 Engine Static Test Stand, On Route 565 between Huntsville and Decatur, Huntsville, Madison County, AL

Booster Engine Service Platforms Delivered to VAB

NASA Image and Video Library

2018-04-17

A new service platform for NASA's Space Launch System booster engines, secured on a flatbed truck, is on its way to the Vehicle Assembly Building (VAB), in view in the distance, at the agency's Kennedy Space Center in Florida. It was transported from fabricator Met-Con Inc. in Cocoa, Florida. The platform will be delivered to the VAB, where it will be stored and used for processing and checkout of the engines for the rocket's twin five-segment solid rocket boosters for Exploration Mission-1 (EM-1). During EM-1, an uncrewed Orion spacecraft will launch on the SLS to a stable orbit beyond the Moon and return to Earth for a splashdown in the Pacific Ocean.

Automatic and integrated micro-enzyme assay (AIμEA) platform for highly sensitive thrombin analysis via an engineered fluorescence protein-functionalized monolithic capillary column.

PubMed

Lin, Lihua; Liu, Shengquan; Nie, Zhou; Chen, Yingzhuang; Lei, Chunyang; Wang, Zhen; Yin, Chao; Hu, Huiping; Huang, Yan; Yao, Shouzhuo

2015-04-21

Nowadays, large-scale screening for enzyme discovery, engineering, and drug discovery processes require simple, fast, and sensitive enzyme activity assay platforms with high integration and potential for high-throughput detection. Herein, a novel automatic and integrated micro-enzyme assay (AIμEA) platform was proposed based on a unique microreaction system fabricated by a engineered green fluorescence protein (GFP)-functionalized monolithic capillary column, with thrombin as an example. The recombinant GFP probe was rationally engineered to possess a His-tag and a substrate sequence of thrombin, which enable it to be immobilized on the monolith via metal affinity binding, and to be released after thrombin digestion. Combined with capillary electrophoresis-laser-induced fluorescence (CE-LIF), all the procedures, including thrombin injection, online enzymatic digestion in the microreaction system, and label-free detection of the released GFP, were integrated in a single electrophoretic process. By taking advantage of the ultrahigh loading capacity of the AIμEA platform and the CE automatic programming setup, one microreaction column was sufficient for many times digestion without replacement. The novel microreaction system showed significantly enhanced catalytic efficiency, about 30 fold higher than that of the equivalent bulk reaction. Accordingly, the AIμEA platform was highly sensitive with a limit of detection down to 1 pM of thrombin. Moreover, the AIμEA platform was robust and reliable to detect thrombin in human serum samples and its inhibition by hirudin. Hence, this AIμEA platform exhibits great potential for high-throughput analysis in future biological application, disease diagnostics, and drug screening.

Cooperative Multi-Agent Mobile Sensor Platforms for Jet Engine Inspection: Concept and Implementation

NASA Technical Reports Server (NTRS)

Litt, Jonathan S.; Wong, Edmond; Krasowski, Michael J.; Greer, Lawrence C.

2003-01-01

Cooperative behavior algorithms utilizing swarm intelligence are being developed for mobile sensor platforms to inspect jet engines on-wing. Experiments are planned in which several relatively simple autonomous platforms will work together in a coordinated fashion to carry out complex maintenance-type tasks within the constrained working environment modeled on the interior of a turbofan engine. The algorithms will emphasize distribution of the tasks among multiple units; they will be scalable and flexible so that units may be added in the future; and will be designed to operate on an individual unit level to produce the desired global effect. This proof of concept demonstration will validate the algorithms and provide justification for further miniaturization and specialization of the hardware toward the true application of on-wing in situ turbine engine maintenance.

Cloud parallel processing of tandem mass spectrometry based proteomics data.

PubMed

Mohammed, Yassene; Mostovenko, Ekaterina; Henneman, Alex A; Marissen, Rob J; Deelder, André M; Palmblad, Magnus

2012-10-05

Data analysis in mass spectrometry based proteomics struggles to keep pace with the advances in instrumentation and the increasing rate of data acquisition. Analyzing this data involves multiple steps requiring diverse software, using different algorithms and data formats. Speed and performance of the mass spectral search engines are continuously improving, although not necessarily as needed to face the challenges of acquired big data. Improving and parallelizing the search algorithms is one possibility; data decomposition presents another, simpler strategy for introducing parallelism. We describe a general method for parallelizing identification of tandem mass spectra using data decomposition that keeps the search engine intact and wraps the parallelization around it. We introduce two algorithms for decomposing mzXML files and recomposing resulting pepXML files. This makes the approach applicable to different search engines, including those relying on sequence databases and those searching spectral libraries. We use cloud computing to deliver the computational power and scientific workflow engines to interface and automate the different processing steps. We show how to leverage these technologies to achieve faster data analysis in proteomics and present three scientific workflows for parallel database as well as spectral library search using our data decomposition programs, X!Tandem and SpectraST.

76 FR 70435 - Combined Notice of Filings #1

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-14

... between National Grid, NYPA, PEP, and MI to be effective 1/1/2012. Filed Date: 11/02/2011. Accession... Agreement No. 1743 between National Grid, NYPA, PEP, and MI to be effective 1/1/2012. Filed Date: 11/02/2011...

Proton-coupled oligopeptide transport by rat renal cortical brush border membrane vesicles: a functional analysis using ACE inhibitors to determine the isoform of the transporter.

PubMed

Temple, C S; Boyd, C A

1998-08-14

We demonstrate that the angiotensin-converting enzyme inhibitors enalapril and captopril inhibit the transport of D-Phe-L-Gln into PepT1-expressing Xenopus oocytes and into rat renal cortical brush border membrane vesicles (BBMV). The kinetics of inhibition are competitive. Enalapril and captopril are not substrates for PepT2 (Boll et al., Proc. Natl. Acad. Sci. 93 (1996) 284-289). Therefore we conclude that in rat renal cortical BBMV this neutral dipeptide is transported via PepT1.

Polydopamine and peptide decorated doxorubicin-loaded mesoporous silica nanoparticles as a targeted drug delivery system for bladder cancer therapy.

PubMed

Wei, Yi; Gao, Li; Wang, Lu; Shi, Lin; Wei, Erdong; Zhou, Baotong; Zhou, Li; Ge, Bo

2017-11-01

We reported a simple polydopamine (PDA)-based surface modification method to prepare novel targeted doxorubicin-loaded mesoporous silica nanoparticles and peptide CSNRDARRC conjugation (DOX-loaded MSNs@PDA-PEP) for enhancing the therapeutic effects on bladder cancer. Drug-loaded NPs were characterized in terms of size, size distribution, zeta potential, transmission electron microscopy (TEM), Brunauer-Emmett-Teller (BET) surface area and drug loading content. In vitro drug release indicated that DOX-loaded MSNs@PDA and MSNs@PDA-PEP had similar release kinetic profiles of DOX. The PDA coating well controlled DOX release and was highly sensitive to pH value. Confocal laser scanning microscopy (CLSM) showed that drug-loaded MSNs could be internalized by human bladder cancer cell line HT-1376, and DOX-loaded MSNs@PDA-PEP had the highest cellular uptake efficiency due to ligand-receptor recognition. The antitumor effects of DOX-loaded nanoparticles were evaluated by the MTT assay in vitro and by a xenograft tumor model in vivo, demonstrating that targeted nanocarriers DOX-loaded MSNs@PDA-PEP were significantly superior to free DOX and DOX-loaded MSNs@PDA. The novel DOX-loaded MSNs@PDA-PEP, which specifically recognized HT-1376 cells, can be used as a potential targeted drug delivery system for bladder cancer therapy.

Transduced PEP-1-Heme Oxygenase-1 Fusion Protein Attenuates Lung Injury in Septic Shock Rats

PubMed Central

Yan, Xue-Tao; Wang, Yan-Lin; Zhang, Zong-Ze; Tang, Jun-Jiao

2018-01-01

Oxidative stress and inflammation have been identified to play a vital role in the pathogenesis of lung injury induced by septic shock. Heme oxygenase-1 (HO-1), an effective antioxidant and anti-inflammatory and antiapoptotic substance, has been used for the treatment of heart, lung, and liver diseases. Thus, we postulated that administration of exogenous HO-1 protein transduced by cell-penetrating peptide PEP-1 has a protective role against septic shock-induced lung injury. Septic shock produced by cecal ligation and puncture caused severe lung damage, manifested in the increase in the lung wet/dry ratio, oxidative stress, inflammation, and apoptosis. However, these changes were reversed by treatment with the PEP-1-HO-1 fusion protein, whereas lung injury in septic shock rats was alleviated. Furthermore, the septic shock upregulated the expression of Toll-like receptor 4 (TLR4) and transcription factor NF-κB, accompanied by the increase of lung injury. Administration of PEP-1-HO-1 fusion protein reversed septic shock-induced lung injury by downregulating the expression of TLR4 and NF-κB. Our study indicates that treatment with HO-1 protein transduced by PEP-1 confers protection against septic shock-induced lung injury by its antioxidant, anti-inflammatory, and antiapoptotic effects. PMID:29682161

The peptide transporter PepT2 mediates the uptake of the glutathione precursor CysGly in astroglia-rich primary cultures.

PubMed

Dringen, R; Hamprecht, B; Bröer, S

1998-07-01

The intracellular content of glutathione in astroglia-rich primary cultures derived from the brains of newborn rats was used as an indicator for the ability of these cultures to utilize cysteinylglycine (CysGly) for glutathione synthesis. After a 24-h starvation period in the absence of glucose and amino acids, CysGly was able to substitute for cysteine plus glycine in the restoration of glutathione. Glutathione restoration from CysGly plus glutamate was only slightly affected by the dipeptides carnosine or serylglycine in a 200-fold excess. Captopril, a substrate of the peptide transporter PepT1, had almost no effect on glutathione restoration. In contrast, with increasing concentrations of alanylalanine or cefadroxil, known substrates of the peptide transporter PepT2, the amount of glutathione restored in the presence of CysGly and glutamate was strongly reduced. Cefadroxil in a 200-fold excess totally prevented the utilization of CysGly for glutathione restoration. The presence of mRNA for PepT2 in astroglia-rich primary cultures was demonstrated by application of RT-PCR. These results demonstrate that PepT2 is expressed in astroglia-rich primary cultures and that this transporter is highly likely to be responsible for the uptake of CysGly in these cultures.

Effects of a school-based sexuality education program on peer educators: the Teen PEP model.

PubMed

Jennings, J M; Howard, S; Perotte, C L

2014-04-01

This study evaluated the impact of the Teen Prevention Education Program (Teen PEP), a peer-led sexuality education program designed to prevent unintended pregnancy and sexually transmitted infections (STIs) including HIV among high school students. The study design was a quasi-experimental, nonrandomized design conducted from May 2007 to May 2008. The sample consisted of 96 intervention (i.e. Teen PEP peer educators) and 61 comparison students from five high schools in New Jersey. Baseline and 12-month follow-up surveys were conducted. Summary statistics were generated and multiple regression analyses were conducted. In the primary intent-to-treat analyses, and secondary non-intent-to-treat analyses, Teen PEP peer educators (versus comparison students) reported significantly greater opportunities to practice sexual risk reduction skills and higher intentions to talk with friends, parents, and sex partners about sex and birth control, set boundaries with sex partners, and ask a partner to be tested for STIs including HIV. In addition in the secondary analysis, Teen PEP peer educators (as compared with the comparison students) had significantly higher scores on knowledge of sexual health issues and ability to refuse risky sexual situations. School-based sexuality education programs offering comprehensive training to peer educators may improve sexual risk behavior knowledge, attitudes and behaviors among high school students.

Triangulation of written assessments from patients, teachers and students: useful for students and teachers?

PubMed

Gran, Sarah Frandsen; Braend, Anja Maria; Lindbaek, Morten

2010-01-01

Many medical students in general practice clerkships experience lack of observation-based feedback. The StudentPEP project combined written feedback from patients, observing teachers and students. This study analyzes the perceived usefulness of triangulated written feedback. A total of 71 general practitioners and 79 medical students at the University of Oslo completed project evaluation forms after a 6-week clerkship. A principal component analysis was performed to find structures within the questionnaire. Regression analysis was performed regarding students' answers to whether StudentPEP was worthwhile. Free-text answers were analyzed qualitatively. Student and teacher responses were mixed within six subscales, with highest agreement on 'Teachers oral and written feedback' and 'Attitude to patient evaluation'. Fifty-four per cent of the students agreed that the triangulation gave concrete feedback on their weaknesses, and 59% valued the teachers' feedback provided. Two statements regarding the teacher's attitudes towards StudentPEP were significantly associated with the student's perception of worthwhileness. Qualitative analysis showed that patient evaluations were encouraging or distrusted. Some students thought that StudentPEP ensured observation and feedback. The patient evaluations increased the students' awareness of the patient perspective. A majority of the students considered the triangulated written feedback beneficial, although time-consuming. The teacher's attitudes strongly influenced how the students perceived the usefulness of StudentPEP.

Cloning and expression of a novel prolyl endopeptidase from Aspergillus oryzae and its application in beer stabilization.

PubMed

Kang, Chao; Yu, Xiao-Wei; Xu, Yan

2015-02-01

A novel prolyl endopeptidase gene from Aspergillus oryzae was cloned and expressed in Pichia pastoris. Amino acid sequence analysis of the prolyl endopeptidase from Aspergillus oryzae (AO-PEP) showed that this enzyme belongs to a class serine peptide S28 family. Expression, purification and characterization of AO-PEP were analyzed. The optimum pH and temperature were pH 5.0 and 40 °C, respectively. The enzyme was activated and stabilized by metal ion Ca(2+) and inhibited by Zn(2+), Mn(2+), Al(3+), and Cu(2+). The K m and k cat values of the purified enzyme for different substrates were evaluated. The results implied that the recombinant AO-PEP possessed higher affinity for the larger substrate. A fed-batch strategy was developed for the high-cell-density fermentation and the enzyme activity reached 1,130 U/l after cultivation in 7 l fermentor. After addition of AO-PEP during the fermentation phase of beer brewing, demonstrated the potential application of AO-PEP in the non-biological stability of beer, which favor further industrial development of this new enzyme in beer stabilization, due to its reducing operational costs, as well as no beer losses unlike regeneration process and beer lost with regenerated polyvinylpolypyrrolidone system.

Effects of a school-based sexuality education program on peer educators: the Teen PEP model

PubMed Central

Jennings, J. M.; Howard, S.; Perotte, C. L.

2014-01-01

This study evaluated the impact of the Teen Prevention Education Program (Teen PEP), a peer-led sexuality education program designed to prevent unintended pregnancy and sexually transmitted infections (STIs) including HIV among high school students. The study design was a quasi-experimental, nonrandomized design conducted from May 2007 to May 2008. The sample consisted of 96 intervention (i.e. Teen PEP peer educators) and 61 comparison students from five high schools in New Jersey. Baseline and 12-month follow-up surveys were conducted. Summary statistics were generated and multiple regression analyses were conducted. In the primary intent-to-treat analyses, and secondary non-intent-to-treat analyses, Teen PEP peer educators (versus comparison students) reported significantly greater opportunities to practice sexual risk reduction skills and higher intentions to talk with friends, parents, and sex partners about sex and birth control, set boundaries with sex partners, and ask a partner to be tested for STIs including HIV. In addition in the secondary analysis, Teen PEP peer educators (as compared with the comparison students) had significantly higher scores on knowledge of sexual health issues and ability to refuse risky sexual situations. School-based sexuality education programs offering comprehensive training to peer educators may improve sexual risk behavior knowledge, attitudes and behaviors among high school students. PMID:24488649

Can PEP-3 Provide a Cognitive Profile in Children with ASD? A Comparison Between the Developmental Ages of PEP-3 and IQ of Leiter-R.

PubMed

De Giacomo, Andrea; Craig, Francesco; Cristella, Arcangelo; Terenzio, Vanessa; Buttiglione, Maura; Margari, Lucia

2016-11-01

The assessment of the intelligence quotient (IQ) in children with autism spectrum disorder (ASD) is important to plan a detailed therapeutic-educative programme. The aim of the study was to evaluate the usefulness of the Psychoeducational Profile-third edition (PEP-3) to estimate the general cognitive development of children with ASD. We recruited 30 children with ASD assessed with the Leiter International Performance Scale-Revised (Leiter-R) and the PEP-3. We compared the IQ of the Leiter-R with the developmental level (DL) of PEP-3. The findings showed a significant positive correlation between IQ with DL of the cognitive verbal/pre-verbal (P = 0.0005), DL of the area of expressive language (P = 0.0004), DL of the area of receptive language (P = 0.0001), DL of fine motor (P = 0.0066), DL of gross motor (P = 0.0217), DL of visuo-motor imitation (P = 0.02), DL of communication (P = 0.0001) and DL of motor (P = 0.0063). These findings show that the DLs could be considered as indicators of cognitive functioning in ASD. © 2015 John Wiley & Sons Ltd.

First Evidence of pep Solar Neutrinos by Direct Detection in Borexino

NASA Astrophysics Data System (ADS)

Bellini, G.; Benziger, J.; Bick, D.; Bonetti, S.; Bonfini, G.; Bravo, D.; Buizza Avanzini, M.; Caccianiga, B.; Cadonati, L.; Calaprice, F.; Carraro, C.; Cavalcante, P.; Chavarria, A.; Chepurnov, A.; D'Angelo, D.; Davini, S.; Derbin, A.; Etenko, A.; Fomenko, K.; Franco, D.; Galbiati, C.; Gazzana, S.; Ghiano, C.; Giammarchi, M.; Goeger-Neff, M.; Goretti, A.; Grandi, L.; Guardincerri, E.; Hardy, S.; Ianni, Aldo; Ianni, Andrea; Korablev, D.; Korga, G.; Koshio, Y.; Kryn, D.; Laubenstein, M.; Lewke, T.; Litvinovich, E.; Loer, B.; Lombardi, F.; Lombardi, P.; Ludhova, L.; Machulin, I.; Manecki, S.; Maneschg, W.; Manuzio, G.; Meindl, Q.; Meroni, E.; Miramonti, L.; Misiaszek, M.; Montanari, D.; Mosteiro, P.; Muratova, V.; Oberauer, L.; Obolensky, M.; Ortica, F.; Otis, K.; Pallavicini, M.; Papp, L.; Perasso, L.; Perasso, S.; Pocar, A.; Quirk, J.; Raghavan, R. S.; Ranucci, G.; Razeto, A.; Re, A.; Romani, A.; Sabelnikov, A.; Saldanha, R.; Salvo, C.; Schönert, S.; Simgen, H.; Skorokhvatov, M.; Smirnov, O.; Sotnikov, A.; Sukhotin, S.; Suvorov, Y.; Tartaglia, R.; Testera, G.; Vignaud, D.; Vogelaar, R. B.; von Feilitzsch, F.; Winter, J.; Wojcik, M.; Wright, A.; Wurm, M.; Xu, J.; Zaimidoroga, O.; Zavatarelli, S.; Zuzel, G.

2012-02-01

We observed, for the first time, solar neutrinos in the 1.0-1.5 MeV energy range. We determined the rate of pep solar neutrino interactions in Borexino to be 3.1±0.6stat±0.3systcounts/(day·100ton). Assuming the pep neutrino flux predicted by the standard solar model, we obtained a constraint on the CNO solar neutrino interaction rate of <7.9counts/(day·100ton) (95% C.L.). The absence of the solar neutrino signal is disfavored at 99.97% C.L., while the absence of the pep signal is disfavored at 98% C.L. The necessary sensitivity was achieved by adopting data analysis techniques for the rejection of cosmogenic C11, the dominant background in the 1-2 MeV region. Assuming the Mikheyev-Smirnov-Wolfenstein large mixing angle solution to solar neutrino oscillations, these values correspond to solar neutrino fluxes of (1.6±0.3)×108cm-2s-1 and <7.7×108cm-2s-1 (95% C.L.), respectively, in agreement with both the high and low metallicity standard solar models. These results represent the first direct evidence of the pep neutrino signal and the strongest constraint of the CNO solar neutrino flux to date.

Design of e-Science platform for biomedical imaging research cross multiple academic institutions and hospitals

NASA Astrophysics Data System (ADS)

Zhang, Jianguo; Zhang, Kai; Yang, Yuanyuan; Ling, Tonghui; Wang, Tusheng; Wang, Mingqing; Hu, Haibo; Xu, Xuemin

2012-02-01

More and more image informatics researchers and engineers are considering to re-construct imaging and informatics infrastructure or to build new framework to enable multiple disciplines of medical researchers, clinical physicians and biomedical engineers working together in a secured, efficient, and transparent cooperative environment. In this presentation, we show an outline and our preliminary design work of building an e-Science platform for biomedical imaging and informatics research and application in Shanghai. We will present our consideration and strategy on designing this platform, and preliminary results. We also will discuss some challenges and solutions in building this platform.

Information Technologies in Higher Education: Lessons Learned in Industrial Engineering

ERIC Educational Resources Information Center

Delgado-Almonte, Milagros; Andreu, Hernando Bustos; Pedraja-Rejas, Liliana

2010-01-01

This article describes a teaching experience in which information and communication technologies were applied in five industrial engineering courses at the Universidad de Tarapaca in Chile. The paper compares the performance and course pass rates of the e-learning platform and portable pocket PC platform with those of the same courses teaching in…

Hardware-in-the-Loop Power Extraction Using Different Real-Time Platforms (PREPRINT)

DTIC Science & Technology

2008-07-01

engine controller ( FADEC ). Incorporating various transient subsystem level models into a complex modeling tool can be a challenging process when each...used can also be modified or replaced as appropriate. In its current configuration, the generic turbine engine model’s FADEC runs primarily on a...simulation in real-time, two platforms were tested: dSPACE and National Instruments’ (NI) LabVIEW Real-Time. For both dSPACE and NI, the engine and FADEC

Paracellular permeation-enhancing effect of AT1002 C-terminal amidation in nasal delivery

PubMed Central

Song, Keon-Hyoung; Kim, Sang-Bum; Shim, Chang-Koo; Chung, Suk-Jae; Kim, Dae-Duk; Rhee, Sang-Ki; Choi, Guang J; Kim, Chul-Hyun; Kim, Kiyoung

2015-01-01

Background The identification of permeation enhancers has gained interest in the development of drug delivery systems. A six-mer peptide, H-FCIGRL-OH (AT1002), is a tight junction modulator with promising permeation-enhancing activity. AT1002 enhances the transport of molecular weight markers or agents with low bioavailability with no cytotoxicity. However, AT1002 is not stable in neutral pH or after incubation under physiological conditions, which is necessary to fully uncover its permeation-enhancing effect. Thus, we increased the stability or mitigated the instability of AT1002 by modifying its terminal amino acids and evaluated its subsequent biological activity. Methods C-terminal-amidated (FCIGRL-NH2, Pep1) and N-terminal-acetylated (Ac-FCIGRL, Pep2) peptides were analyzed by liquid chromatography–mass spectrometry. We further assessed cytotoxicity on cell monolayers, as well as the permeation-enhancing activity following nasal administration of the paracellular marker mannitol. Results Pep1 was nontoxic to cell monolayers and showed a relatively low decrease in peak area compared to AT1002. In addition, administration of mannitol with Pep1 resulted in significant increases in the area under the plasma concentration–time curve and peak plasma concentration at 3.63-fold and 2.68-fold, respectively, compared to mannitol alone. In contrast, no increase in mannitol concentration was shown with mannitol/AT1002 or mannitol/Pep2 compared to the control. Thus, Pep1 increased the stability or possibly reduced the instability of AT1002, which resulted in an increased permeation-enhancing effect of AT1002. Conclusion These results suggest the potential usefulness of C-terminal-amidated AT1002 in enhancing nasal drug delivery, which may lead to the development of a practical drug delivery technology for drugs with low bioavailability. PMID:25848218

Pepino mosaic virus genotype shift in North America and development of a loop-mediated isothermal amplification for rapid genotype identification

PubMed Central

2013-01-01

Background Pepino mosaic, once an emerging disease a decade ago, has become endemic on greenhouse tomatoes worldwide in recent years. Three distinct genotypes of Pepino mosaic virus (PepMV), including EU, US1 and CH2 have been recognized. Our earlier study conducted in 2006–2007 demonstrated a predominant EU genotype in Canada and United States. The objective of the present study was to monitor the dynamic of PepMV genetic composition and its current status in North America. Results Through yearly monitoring efforts in 2009–2012, we detected a dramatic shift in the prevalent genotype of PepMV from the genotype EU to CH2 in North America since early 2010, with another shift from CH2 to US1 occurring in Mexico only two years later. Through genetic diversity analysis using the coat protein gene, such genotype shifting of PepMV in North America was linked to the positive identification of similar sequence variants in two different commercial tomato seed sources used for scion and rootstock, respectively. To allow for a quick identification, a reverse transcription loop-mediated isothermal amplification (RT-LAMP) system was developed and demonstrated to achieve a rapid identification for each of the three genotypes of PepMV, EU, US1 and CH2. Conclusion Through systemic yearly monitoring and genetic diversity analysis, we identified a linkage between the field epidemic isolates and those from commercial tomato seed lots as the likely sources of initial PepMV inoculum that resulted in genetic shifting as observed on greenhouse tomatoes in North America. Application of the genotype-specific RT-LAMP system would allow growers to efficiently determine the genetic diversity on their crops. PMID:23587202

Effects of physical exercise programme on happiness among older people.

PubMed

Khazaee-Pool, M; Sadeghi, R; Majlessi, F; Rahimi Foroushani, A

2015-02-01

This randomized-controlled trial investigated the effect of physical exercise programme (PEP) on happiness among older adults in Nowshahr, Iran. Results of this study on 120 male and female volunteers showed that an 8-week group physical exercise programme was significantly effective in older adults' happiness. Findings showed that physical exercise programme is so beneficial for increasing older adults' happiness. Physical activity is associated with well-being and happiness. The purpose of this study was to determine the effects of an 8-week long physical exercise programme (PEP) on happiness among older adults in Nowshahr, Iran. This was a randomized control trial study. The participants consisted of a group of 120 male and female volunteers (mean ± SD age: 71 ± 5.86 years) in a convenience sampling among older adults in public parks in Nowshahr, Iran. We randomly allocated them into experimental (n = 60) and control (n = 60) groups. A validated instrument was used to measure well-being and happiness [Oxford Happiness Inventory (OHI)]. Respondents were asked to complete the OHI before and 2 months after implementing PEP. The 8-week PEP was implemented with the intervention group. The statistical analysis of the data was conducted using paired t-test, Fisher's exact test and χ(2). Before the intervention, there was no significant difference in the happiness mean score between the case and control groups; however, after implementing PEP, happiness significantly improved among the experimental group (P = 0.001) and did not improve within the control group (P = 0.79). It can be concluded that PEP had positive effects on happiness among older adults. Planning and implementing of physical activity is so important for older happiness. © 2014 John Wiley & Sons Ltd.

Does rectal indomethacin eliminate the need for prophylactic pancreatic stent placement in patients undergoing high-risk ERCP? Post hoc efficacy and cost-benefit analyses using prospective clinical trial data.

PubMed

Elmunzer, B Joseph; Higgins, Peter D R; Saini, Sameer D; Scheiman, James M; Parker, Robert A; Chak, Amitabh; Romagnuolo, Joseph; Mosler, Patrick; Hayward, Rodney A; Elta, Grace H; Korsnes, Sheryl J; Schmidt, Suzette E; Sherman, Stuart; Lehman, Glen A; Fogel, Evan L

2013-03-01

A recent large-scale randomized controlled trial (RCT) demonstrated that rectal indomethacin administration is effective in addition to pancreatic stent placement (PSP) for preventing post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) in high-risk cases. We performed a post hoc analysis of this RCT to explore whether rectal indomethacin can replace PSP in the prevention of PEP and to estimate the potential cost savings of such an approach. We retrospectively classified RCT subjects into four prevention groups: (1) no prophylaxis, (2) PSP alone, (3) rectal indomethacin alone, and (4) the combination of PSP and indomethacin. Multivariable logistic regression was used to adjust for imbalances in the prevalence of risk factors for PEP between the groups. Based on these adjusted PEP rates, we conducted an economic analysis comparing the costs associated with PEP prevention strategies employing rectal indomethacin alone, PSP alone, or the combination of both. After adjusting for risk using two different logistic regression models, rectal indomethacin alone appeared to be more effective for preventing PEP than no prophylaxis, PSP alone, and the combination of indomethacin and PSP. Economic analysis revealed that indomethacin alone was a cost-saving strategy in 96% of Monte Carlo trials. A prevention strategy employing rectal indomethacin alone could save approximately $150 million annually in the United States compared with a strategy of PSP alone, and $85 million compared with a strategy of indomethacin and PSP. This hypothesis-generating study suggests that prophylactic rectal indomethacin could replace PSP in patients undergoing high-risk ERCP, potentially improving clinical outcomes and reducing healthcare costs. A RCT comparing rectal indomethacin alone vs. indomethacin plus PSP is needed.

Increasing the Presence of Underrepresented Minorities in the Geosciences: The Woods Hole Partnership Education Program Model and Outcomes

NASA Astrophysics Data System (ADS)

George, A.; Gutierrez, B.; Jearld, A.; Liles, G.; Scott, O.; Harden, B.

2017-12-01

Launched in 2009, the Partnership Education Program (PEP) is supported by six scientific institutions in Woods Hole, Massachusetts through the Woods Hole Diversity Initiative. PEP, which was shaped by experience with other diversity programs as well as input from scientists in Woods Hole, is designed to promote a diverse scientific community by recruiting talent from minority groups that are under-represented in marine and environmental sciences. Focused on college juniors and seniors with course work in marine and/or environmental sciences, PEP is comprised of a four-week course, "Ocean and Environmental Sciences: Global Climate Change," and a six to eight week individual research project under the guidance of a research mentor. Investigators from the six science institutions serve as course faculty and research mentors. Course credit is through PEP's academic partner, the University of Maryland Eastern Shore. PEP students also participate in seminars, workshops, field trips, at-sea experiences, career development activities, and attend lectures at participating science institutions throughout the summer. Students present their research results at the end of the summer with a 15-minute public presentation. A number of PEP participants then presented their work at professional and scientific meetings, such as AGU, using the program as a gateway to graduate education and career opportunities in the marine and environmental sciences. From 2009 through 2017, 138 students from 86 colleges and universities, including many that previously had sent few or no students or faculty to Woods Hole, have participated in the program. Participating organizations are: Northeast Fisheries Science Center (NOAA Fisheries), Marine Biological Laboratory (MBL), Sea Education Association (SEA), U.S. Geological Survey (USGS), Woods Hole Oceanographic Institution (WHOI), Woods Hole Research Center (WHRC), and University of Maryland Eastern Shore (UMES) - academic partner.

Transmission dynamics and economics of rabies control in dogs and humans in an African city.

PubMed

Zinsstag, J; Dürr, S; Penny, M A; Mindekem, R; Roth, F; Menendez Gonzalez, S; Naissengar, S; Hattendorf, J

2009-09-01

Human rabies in developing countries can be prevented through interventions directed at dogs. Potential cost-savings for the public health sector of interventions aimed at animal-host reservoirs should be assessed. Available deterministic models of rabies transmission between dogs were extended to include dog-to-human rabies transmission. Model parameters were fitted to routine weekly rabid-dog and exposed-human cases reported in N'Djaména, the capital of Chad. The estimated transmission rates between dogs (beta(d)) were 0.0807 km2/(dogs x week) and between dogs and humans (beta(dh)) 0.0002 km2/(dogs x week). The effective reproductive ratio (R(e)) at the onset of our observations was estimated at 1.01, indicating low-level endemic stability of rabies transmission. Human rabies incidence depended critically on dog-related transmission parameters. We simulated the effects of mass dog vaccination and the culling of a percentage of the dog population on human rabies incidence. A single parenteral dog rabies-mass vaccination campaign achieving a coverage of least 70% appears to be sufficient to interrupt transmission of rabies to humans for at least 6 years. The cost-effectiveness of mass dog vaccination was compared to postexposure prophylaxis (PEP), which is the current practice in Chad. PEP does not reduce future human exposure. Its cost-effectiveness is estimated at US $46 per disability adjusted life-years averted. Cost-effectiveness for PEP, together with a dog-vaccination campaign, breaks even with cost-effectiveness of PEP alone after almost 5 years. Beyond a time-frame of 7 years, it appears to be more cost-effective to combine parenteral dog-vaccination campaigns with human PEP compared to human PEP alone.

Transitioning to HIV Pre-Exposure Prophylaxis (PrEP) from Non-Occupational Post-Exposure Prophylaxis (nPEP) in a Comprehensive HIV Prevention Clinic: A Prospective Cohort Study.

PubMed

Siemieniuk, Reed A C; Sivachandran, Nirojini; Murphy, Pauline; Sharp, Andrea; Walach, Christine; Placido, Tania; Bogoch, Isaac I

2015-08-01

The uptake of pre-exposure prophylaxis (PrEP) for HIV prevention remains low. We hypothesized that a high proportion of patients presenting for HIV non-occupational post-exposure prophylaxis (nPEP) would be candidates for PrEP based on current CDC guidelines. Outcomes from a comprehensive HIV Prevention Clinic are described. We evaluated all patients who attended the HIV Prevention Clinic for nPEP between January 1, 2013 and September 30, 2014. Each patient was evaluated for PrEP candidacy based on current CDC-guidelines and subjectively based on physician opinion. Patients were then evaluated for initiation of PrEP if they met guideline suggestions. Demographic, social, and behavioral factors were then analyzed with logistic regression for associations with PrEP candidacy and initiation. 99 individuals who attended the nPEP clinic were evaluated for PrEP. The average age was 32 years (range, 18-62), 83 (84%) were male, of whom 46 (55%) men who had have sex with men (MSM). 31 (31%) met CDC guidelines for PrEP initiation, which had very good agreement with physician recommendation (kappa=0.88, 0.78-0.98). Factors associated with PrEP candidacy included sexual exposure to HIV, prior nPEP use, and lack of drug insurance (p<0.05 for all comparisons). Combining nPEP and PrEP services in a dedicated clinic can lead to identification of PrEP candidates and may facilitate PrEP uptake. Strategies to ensure equitable access of PrEP should be explored such that those without drug coverage may also benefit from this effective HIV prevention modality.

HyPEP FY06 Report: Models and Methods

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

DOE report

2006-09-01

The Department of Energy envisions the next generation very high-temperature gas-cooled reactor (VHTR) as a single-purpose or dual-purpose facility that produces hydrogen and electricity. The Ministry of Science and Technology (MOST) of the Republic of Korea also selected VHTR for the Nuclear Hydrogen Development and Demonstration (NHDD) Project. This research project aims at developing a user-friendly program for evaluating and optimizing cycle efficiencies of producing hydrogen and electricity in a Very-High-Temperature Reactor (VHTR). Systems for producing electricity and hydrogen are complex and the calculations associated with optimizing these systems are intensive, involving a large number of operating parameter variations andmore » many different system configurations. This research project will produce the HyPEP computer model, which is specifically designed to be an easy-to-use and fast running tool for evaluating nuclear hydrogen and electricity production facilities. The model accommodates flexible system layouts and its cost models will enable HyPEP to be well-suited for system optimization. Specific activities of this research are designed to develop the HyPEP model into a working tool, including (a) identifying major systems and components for modeling, (b) establishing system operating parameters and calculation scope, (c) establishing the overall calculation scheme, (d) developing component models, (e) developing cost and optimization models, and (f) verifying and validating the program. Once the HyPEP model is fully developed and validated, it will be used to execute calculations on candidate system configurations. FY-06 report includes a description of reference designs, methods used in this study, models and computational strategies developed for the first year effort. Results from computer codes such as HYSYS and GASS/PASS-H used by Idaho National Laboratory and Argonne National Laboratory, respectively will be benchmarked with HyPEP results in the following years.« less

Factors that influence public awareness of domestic waste characteristics and management in rural areas.

PubMed

Han, Zhiyong; Duan, Qingqing; Fei, Yongqiang; Zeng, Dan; Shi, Guozhong; Li, Haimei; Hu, Meilun

2018-05-01

Public awareness of domestic waste characteristics and management (PADWCM) is a prerequisite for a domestic waste management (DWM) plan. In this study, we considered China as a typical example of developing countries to investigate the public perception of environmental pollution (PEP), its PADWCM, and its socioeconomic factors, using questionnaires and statistical methods. The results indicated that the public PEP was mainly due to obvious environmental contamination in local villages, and the PADWCM is still inadequate in rural areas. However, 83.9% of the respondents agreed that DWM is highly necessary. The PADWCM, including the hazard, recyclability, and characteristic pollution caused by domestic waste, was learned mainly from people's direct PEP, experiences, and repurchasing by recyclers. Education period had highly significant positive correlations and regressions with PEP and PADWCM, respectively. Additionally, education directly affected public awareness in different income and age groups. Demonstration projects had a significant positive effect on the awareness of characteristic pollution caused by domestic waste, which was readily perceived. Propaganda had a significant positive influence on the awareness of treatment necessity. Age and gender had no obvious effects on public PEP and PADWCM. Some aspects of PADWCM requiring a deep understanding became stronger as income increased; however, the PADWCM located close to poor people became weaker. Some aspects of PEP could significantly influence the awareness of characteristic pollution caused by domestic waste and awareness of treatment necessity. Therefore, improving environmental education, performing demonstration projects and effective environmental propaganda, increasing people's income, and attracting young people to participate in DWM will be important for enhancing environmental awareness and DWM in rural areas. Integr Environ Assess Manag 2018;14:395-406. © 2018 SETAC. © 2018 SETAC.

A morpho-functional study using PEP/LVET ratio and global longitudinal strain in patients with dilated cardiomyopathy.

PubMed

Corîci, Oana Maria; Tănasie, Cornelia Andreea; Alexandru, Dragoş Ovidiu; Florescu, Mihaela Corina; Comănescu, Maria Victoria; Kamal, Kamal Constantin; Ţenea-Cojan, Tiberiu Ştefăniţă; Iancău, Maria; Dinescu, Sorin Nicolae

2018-01-01

To assess left ventricular (LV) systolic function and morphology in patients with severe dilated cardiomyopathy (DCM), using both conventional and a complex technique, speckle-tracking echocardiography, and evaluate the correlation between pre-ejection period and left ventricular ejection period (PEP/LVET) ratio, global longitudinal strain (GLS), and severity of the condition. Seventeen patients were enrolled after rigorous criteria. Echocardiography was performed in conventional and speckle-tracking mode, in all patients with DCM, in sinus rhythm. LV dimensions, volumes and ejection fraction (LVEF) were measured. PEP/LVET ratio was obtained from apical 5-chamber axis and was defined as the time between QRS onset and LV ejection reported to LV ejection period. Speckle-tracking imaging was performed in offline mode and GLS was obtained from parasternal 4-, 3-, 2-chamber apical view, by averaging longitudinal peak systolic strain of all 17 LV-segments. New York Heart Association (NYHA) functional class correlated significantly with LVEF (-0.82; p=0.0006), PEP/LVET (0.86; p=0.001) or GLS (0.85; p=0.0002). Considerable correlations were between mitral regurgitation (MR) severity and LVEF (-0.65; p=0.01) or PEP/LVET (0.69; p=0.0059), but higher were between MR severity and GLS (0.76; p=0.0018). Tricuspid regurgitation (TR) grading correlated statistically with LVEF (-0.62; p=0.01), PEP/LVET and GLS (0.6; p=0.018; and 0.62; p=0.014, respectively). As opposed to the parameters in conventional echocardiography, GLS correlated with DCM etiology (p=0.0046) and with the gender (p=0.048). This study demonstrates that, in patients with DCM, assessment of cardiac dyssynchrony can be accurately accomplished by combining parameters in conventional and in speckle-tracking echocardiography.

The community FabLab platform: applications and implications in biomedical engineering.

PubMed

Stephenson, Makeda K; Dow, Douglas E

2014-01-01

Skill development in science, technology, engineering and math (STEM) education present one of the most formidable challenges of modern society. The Community FabLab platform presents a viable solution. Each FabLab contains a suite of modern computer numerical control (CNC) equipment, electronics and computing hardware and design, programming, computer aided design (CAD) and computer aided machining (CAM) software. FabLabs are community and educational resources and open to the public. Development of STEM based workforce skills such as digital fabrication and advanced manufacturing can be enhanced using this platform. Particularly notable is the potential of the FabLab platform in STEM education. The active learning environment engages and supports a diversity of learners, while the iterative learning that is supported by the FabLab rapid prototyping platform facilitates depth of understanding, creativity, innovation and mastery. The product and project based learning that occurs in FabLabs develops in the student a personal sense of accomplishment, self-awareness, command of the material and technology. This helps build the interest and confidence necessary to excel in STEM and throughout life. Finally the introduction and use of relevant technologies at every stage of the education process ensures technical familiarity and a broad knowledge base needed for work in STEM based fields. Biomedical engineering education strives to cultivate broad technical adeptness, creativity, interdisciplinary thought, and an ability to form deep conceptual understanding of complex systems. The FabLab platform is well designed to enhance biomedical engineering education.

Data-acquisition system for environmental monitoring aboard a twin-engined aircraft

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

Tichler, J.; Bernstein, H.; Brown, R.M.

A number of experimental platforms have been used in support of the Multistate Atmospheric Power Production Study (MAP3S) and the Coastal Meteorology programs at Brookhaven National Laboratory. These platforms include a twin-engine Britten Norman Islander aircraft, a motorized van, a variety of boats and temporary enclosures set up in the field. Each platform carried a data logger consisting of a multiplexer, an analog to digital (A/D) converter and a four track endless loop magnetic tape for data storage. In recent years it has become increasingly evident that the data loggers in use were no longer adequate. Since the aircraft providedmore » the most constraints on the data acquisition system as well as being the most important research platform, a data system was designed for that platform with the secondary goal that the system would serve as a prototype for systems to be used on other platforms.« less

Power Extension Package (PEP) system definition extension, orbital service module systems analysis study. Volume 10: PEP project plan

NASA Technical Reports Server (NTRS)

1979-01-01

Contents: project plan summary; project and mission objectives; related studies and technology support activities; technical summary; management; procurement approach; project definition items and schedule; resources; management review; controlled items; and safety, reliability, and quality assurance.

Combining protein-shelled platinum nanoparticles with graphene to build a bionanohybrid capacitor.

PubMed

San, Boi Hoa; Kim, Jang Ah; Kulkarni, Atul; Moh, Sang Hyun; Dugasani, Sreekantha Reddy; Subramani, Vinod Kumar; Thorat, Nanasaheb D; Lee, Hyun Ho; Park, Sung Ha; Kim, Taesung; Kim, Kyeong Kyu

2014-12-23

The electronic properties of biomolecules and their hybrids with inorganic materials can be utilized for the fabrication of nanoelectronic devices. Here, we report the charge transport behavior of protein-shelled inorganic nanoparticles combined with graphene and demonstrate their possible application as a bionanohybrid capacitor. The conductivity of PepA, a bacterial aminopeptidase used as a protein shell (PS), and the platinum nanoparticles (PtNPs) encapsulated by PepA was measured using a field effect transistor (FET) and a graphene-based FET (GFET). Furthermore, we confirmed that the electronic properties of PepA-PtNPs were controlled by varying the size of the PtNPs. The use of two poly(methyl methacrylate) (PMMA)-coated graphene layers separated by PepA-PtNPs enabled us to build a bionanohybrid capacitor with tunable properties. The combination of bioinorganic nanohybrids with graphene is regarded as the cornerstone for developing flexible and biocompatible bionanoelectronic devices that can be integrated into bioelectric circuits for biomedical purposes.

A non-covalent peptide-based carrier for in vivo delivery of DNA mimics.

PubMed

Morris, May C; Gros, Edwige; Aldrian-Herrada, Gudrun; Choob, Michael; Archdeacon, John; Heitz, Frederic; Divita, Gilles

2007-01-01

The dramatic acceleration in identification of new nucleic-acid-based therapeutic molecules has provided new perspectives in pharmaceutical research. However, their development is limited by their poor cellular uptake and inefficient trafficking. Here we describe a short amphipathic peptide, Pep-3, that combines a tryptophan/phenylalanine domain with a lysine/arginine-rich hydrophilic motif. Pep-3 forms stable nano-size complexes with peptide-nucleic acid analogues and promotes their efficient delivery into a wide variety of cell lines, including primary and suspension lines, without any associated cytotoxicity. We demonstrate that Pep-3-mediated delivery of antisense-cyclin B1-charged-PNA blocks tumour growth in vivo upon intratumoral and intravenous injection. Moreover, we show that PEGylation of Pep-3 significantly improves complex stability in vivo and consequently the efficiency of antisense cyclin B1 administered intravenously. Given the biological characteristics of these vectors, we believe that peptide-based delivery technologies hold a true promise for therapeutic applications of DNA mimics.

A non-covalent peptide-based carrier for in vivo delivery of DNA mimics

PubMed Central

Morris, May C.; Gros, Edwige; Aldrian-Herrada, Gudrun; Choob, Michael; Archdeacon, John; Heitz, Frederic; Divita, Gilles

2007-01-01

The dramatic acceleration in identification of new nucleic-acid-based therapeutic molecules has provided new perspectives in pharmaceutical research. However, their development is limited by their poor cellular uptake and inefficient trafficking. Here we describe a short amphipathic peptide, Pep-3, that combines a tryptophan/phenylalanine domain with a lysine/arginine-rich hydrophilic motif. Pep-3 forms stable nano-size complexes with peptide-nucleic acid analogues and promotes their efficient delivery into a wide variety of cell lines, including primary and suspension lines, without any associated cytotoxicity. We demonstrate that Pep-3-mediated delivery of antisense-cyclin B1-charged-PNA blocks tumour growth in vivo upon intratumoral and intravenous injection. Moreover, we show that PEGylation of Pep-3 significantly improves complex stability in vivo and consequently the efficiency of antisense cyclin B1 administered intravenously. Given the biological characteristics of these vectors, we believe that peptide-based delivery technologies hold a true promise for therapeutic applications of DNA mimics. PMID:17341467

Recent developments in the understanding and use of anthrax vaccine adsorbed: achieving more with less.

PubMed

Schiffer, Jarad M; McNeil, Michael M; Quinn, Conrad P

2016-09-01

Anthrax Vaccine Adsorbed (AVA, BioThrax™) is the only Food and Drug Administration (FDA) approved vaccine for the prevention of anthrax in humans. Recent improvements in pre-exposure prophylaxis (PrEP) use of AVA include intramuscular (IM) administration and simplification of the priming series to three doses over 6 months. Administration IM markedly reduced the frequency, severity and duration of injection site reactions. Refinement of animal models for inhalation anthrax, identification of immune correlates of protection and cross-species modeling have created opportunities for reductions in the PrEP booster schedule and were pivotal in FDA approval of a post-exposure prophylaxis (PEP) indication. Clinical and nonclinical studies of accelerated PEP schedules and divided doses may provide prospects for shortening the PEP antimicrobial treatment period. These data may assist in determining feasibility of expanded coverage in a large-scale emergency when vaccine demand may exceed availability. Enhancements to the AVA formulation may broaden the vaccine's PEP application.

Stoichiometry and pH dependence of the rabbit proton-dependent oligopeptide transporter PepT1.

PubMed

Steel, A; Nussberger, S; Romero, M F; Boron, W F; Boyd, C A; Hediger, M A

1997-02-01

1. The intestinal H(+)-coupled peptide transporter PepT1, displays a broad substrate specificity and accepts most charged and neutral di- and tripeptides. To study the proton-to-peptide stoichiometry and the dependence of the kinetic parameters on extracellular pH (pHo), rabbit PepT1 was expressed in Xenopus laevis oocytes and used for uptake studies of radiolabelled neutral and charged dipeptides, voltage-clamp analysis and intracellular pH measurements. 2. PepT1 did not display the substrate-gated anion conductances that have been found to be characteristic of members of the Na(+)- and H(+)-coupled high-affinity glutamate transporter family. In conjunction with previous data on the ion dependence of PepT1, it can therefore be concluded that peptide-evoked charge fluxes of PepT1 are entirely due to H+ movement. 3. Neutral, acidic and basic dipeptides induced intracellular acidification. The rate of acidification, the initial rates of the uptake of radiolabelled peptides and the associated charge fluxes gave proton-substrate coupling ratios of 1:1, 2:1 and 1:1 for neutral, acidic and basic dipeptides, respectively. 4. Maximal transport of the neutral and charged dipeptides Gly-Leu, Gly-Glu, Gly-Lys and Ala-Lys occurred at pHo 5.5, 5.2, 6.2 and 5.8, respectively. The Imax values were relatively pHo independent but the apparent affinity (Km(app) values for these peptides were shown to be highly pHo dependent. 5. Our data show that at physiological pH (pHo 5.5-6.0) PepT1 prefers neutral and acidic peptides. The shift in transport maximum for the acidic peptide Gly-Glu to a lower pH value suggests that acidic dipeptides are transported in the protonated form. The shift in the transport maxima of the basic dipeptides to higher pH values may involve titration of a side-chain on the transporter molecule (e.g. protonation of a histidine group). These considerations have led us to propose a model for coupled transport of neutral, acidic and basic dipeptides.

Pre-exposure and postexposure prophylaxes and the combination HIV prevention methods (The Combine! Study): protocol for a pragmatic clinical trial at public healthcare clinics in Brazil.

PubMed

Grangeiro, Alexandre; Couto, Márcia Thereza; Peres, Maria Fernanda; Luiz, Olinda; Zucchi, Eliana Miura; de Castilho, Euclides Ayres; Estevam, Denize Lotufo; Alencar, Rosa; Wolffenbüttel, Karina; Escuder, Maria Mercedes; Calazans, Gabriela; Ferraz, Dulce; Arruda, Érico; Corrêa, Maria da Gloria; Amaral, Fabiana Rezende; Santos, Juliane Cardoso Villela; Alvarez, Vivian Salles; Kietzmann, Tiago

2015-08-25

Few results from programmes based on combination prevention methods are available. We propose to analyse the degree of protection provided by postexposure prophylaxis (PEP) for consensual sexual activity at healthcare clinics, its compensatory effects on sexual behaviour; and the effectiveness of combination prevention methods and pre-exposure prophylaxis (PrEP), compared with exclusively using traditional methods. A total of 3200 individuals aged 16 years or older presenting for PEP at 5 sexually transmitted disease (STD)/HIV clinics in 3 regions of Brazil will be allocated to one of two groups: the PEP group-individuals who come to the clinic within 72 h after a sexual exposure and start PEP; and the non-PEP group-individuals who come after 72 h but within 30 days of exposure and do not start PEP. Clinical follow-up will be conducted initially for 6 months and comprise educational interventions based on information and counselling for using prevention methods, including PrEP. In the second study phase, individuals who remain HIV negative will be regrouped according to the reported use of prevention methods and observed for 18 months: only traditional methods; combined methods; and PrEP. Effectiveness will be analysed according to the incidence of HIV, syphilis and hepatitis B and C and protected sexual behaviour. A structured questionnaire will be administered to participants at baseline and every 6 months thereafter. Qualitative methods will be employed to provide a comprehensive understanding of PEP-seeking behaviour, preventive choices and exposure to HIV. This study will be conducted in accordance with the resolution of the School of Medicine Research Ethics Commission of Universidade de São Paulo (protocol no. 251/14). The databases will be available for specific studies, after management committee approval. Findings will be presented to researchers, health managers and civil society members by means of newspapers, electronic media and scientific journals and meetings. 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.

Geographical and temporal patterns of rabies post exposure prophylaxis (PEP) incidence in humans in the Mekong River Delta and Southeast Central Coast regions in Vietnam from 2005 to 2015

PubMed Central

Thiem, Vu Dinh; Anh, Dang Duc; Duong, Tran Nhu; Lee, Mihye; Grace, Delia; Nguyen-Viet, Hung

2018-01-01

Background In Vietnam, rabies has been a notifiable disease for more than 40 years. Over the last five years, on average, more than 350,000 people per year have been bitten by dogs and cats while more than 80 human deaths have been reported yearly. No studies have been conducted to evaluate the geographical and temporal patterns of rabies in humans in Vietnam. Therefore, the main objective of this study was to assess the geographical and temporal distributions of rabies post exposure prophylaxis (PEP) incidence in humans in Vietnam from 2005 to 2015. Methods Average incidence rabies (AIR) PEP rates for every 3 or 4 years (2005–2008, 2009–2012 and 2013–2015) were calculated to describe the spatial distribution of rabies PEP. Hotspot analysis was implemented to identify patterns of spatial significance using the Getis-Ord Gi statistic. For temporal pattern analysis, two regions [Mekong River Delta (MRD) and Southeast Central Coast (SCC)], with the highest incidence rates, and the seasonal-decomposition procedure based on loess (STL), were compared to assess their temporal patterns of rabies PEP. Findings We found hotspots in southern Vietnam and coldspots in northern Vietnam during the study period. Rabies cases were limited to specific areas. In addition, the hotspot analysis showed that new risk areas were identified in each period which were not observed in incidence rate maps. The seasonal plots showed seasonal patterns with a strong peak in February/July and a minor peak in October/December in the MRD region. However, in the SCC, a small peak was detected at the early part of each year and a strong peak in the middle of each year. Conclusion Our findings provide insight into understanding the geographical and seasonal patterns of rabies PEP in Vietnam. This study provides evidence to aid policy makers when making decisions and investing resources. Such information may also be utilized to raise public awareness to prevent rabies exposures and reduce unnecessary PEP. PMID:29634746

Device for installing rocket engines

NASA Technical Reports Server (NTRS)

George, T. R., Jr. (Inventor)

1976-01-01

A device for installing rocket engines is reported that is supported at a cant relative to vertical by an axially extensible, tiltable pedestal. A lifting platform supports the rocket engine at its thrust chamber exit, including a mount having a concentric base characterized by a concave bearing surface, a plurality of uniformly spaced legs extended radially from the base, and an annular receiver coaxially aligned with the base and affixed to the distal ends of said legs for receiving the thrust chamber exit. The lifting platform rests on a seat concentrically related to the pedestal and affixed to an extended end portion thereof having a convex bearing surface mated in sliding engagement with the concave bearing surface of the annular base for accommodating a rocking motion of the platform.

An integrated biotechnology platform for developing sustainable chemical processes.

PubMed

Barton, Nelson R; Burgard, Anthony P; Burk, Mark J; Crater, Jason S; Osterhout, Robin E; Pharkya, Priti; Steer, Brian A; Sun, Jun; Trawick, John D; Van Dien, Stephen J; Yang, Tae Hoon; Yim, Harry

2015-03-01

Genomatica has established an integrated computational/experimental metabolic engineering platform to design, create, and optimize novel high performance organisms and bioprocesses. Here we present our platform and its use to develop E. coli strains for production of the industrial chemical 1,4-butanediol (BDO) from sugars. A series of examples are given to demonstrate how a rational approach to strain engineering, including carefully designed diagnostic experiments, provided critical insights about pathway bottlenecks, byproducts, expression balancing, and commercial robustness, leading to a superior BDO production strain and process.

Psycho-education with problem solving (PEPS) therapy for adults with personality disorder: a pragmatic multi-site community-based randomised clinical trial.

PubMed

McMurran, Mary; Crawford, Mike J; Reilly, Joseph G; McCrone, Paul; Moran, Paul; Williams, Hywel; Adams, Clive E; Duggan, Conor; Delport, Juan; Whitham, Diane; Day, Florence

2011-08-24

Impairment in social functioning is a key component of personality disorder. Therefore psycho-education and problem solving (PEPS) therapy may benefit people with this disorder. Psycho-education aims to educate, build rapport, and motivate people for problem solving therapy. Problem solving therapy aims to help clients solve interpersonal problems positively and rationally, thereby improving social functioning and reducing distress. PEPS therapy has been evaluated with community adults with personality disorder in an exploratory trial. At the end of treatment, compared to a wait-list control group, those treated with PEPS therapy showed better social functioning, as measured by the Social Functioning Questionnaire (SFQ). A definitive evaluation is now being conducted to determine whether PEPS therapy is a clinically and cost-effective treatment for people with personality disorder This is a pragmatic, two-arm, multi-centre, parallel, randomised controlled clinical trial. The target population is community-dwelling adults with one or more personality disorder, as identified by the International Personality Disorder Examination (IPDE). Inclusion criteria are: Living in the community (including residential or supported care settings); presence of one or more personality disorder; aged 18 or over; proficiency in spoken English; capacity to provide informed consent. Exclusion criteria are: Primary diagnosis of a functional psychosis; insufficient degree of literacy, comprehension or attention to be able to engage in trial therapy and assessments; currently engaged in a specific programme of psychological treatment for personality disorder or likely to start such treatment during the trial period; currently enrolled in any other trial. Suitable participants are randomly allocated to PEPS therapy plus treatment as usual (TAU) or TAU only. We aim to recruit 340 men and women. The primary outcome is social functioning as measured by the SFQ. A reduction (i.e., an improvement) of 2 points or more on the SFQ at follow-up 72 weeks post-randomisation is our pre-specified index of clinically significant change. Secondary outcomes include a reduction of unscheduled service usage and an increase in scheduled service usage; improved quality of life; and a reduction in mental distress. PEPS therapy has potential as an economical, accessible, and acceptable intervention for people with personality disorder. The results from this randomised controlled trial will tell us if PEPS therapy is effective and cost-effective. If so, then it will be a useful treatment for inclusion in a broader menu of treatment options for this group of service users. International Standard Randomised Controlled Trial Number - ISRCTN70660936.

Psycho-education with problem solving (PEPS) therapy for adults with personality disorder: A pragmatic multi-site community-based randomised clinical trial

PubMed Central

2011-01-01

Background Impairment in social functioning is a key component of personality disorder. Therefore psycho-education and problem solving (PEPS) therapy may benefit people with this disorder. Psycho-education aims to educate, build rapport, and motivate people for problem solving therapy. Problem solving therapy aims to help clients solve interpersonal problems positively and rationally, thereby improving social functioning and reducing distress. PEPS therapy has been evaluated with community adults with personality disorder in an exploratory trial. At the end of treatment, compared to a wait-list control group, those treated with PEPS therapy showed better social functioning, as measured by the Social Functioning Questionnaire (SFQ). A definitive evaluation is now being conducted to determine whether PEPS therapy is a clinically and cost-effective treatment for people with personality disorder Methods This is a pragmatic, two-arm, multi-centre, parallel, randomised controlled clinical trial. The target population is community-dwelling adults with one or more personality disorder, as identified by the International Personality Disorder Examination (IPDE). Inclusion criteria are: Living in the community (including residential or supported care settings); presence of one or more personality disorder; aged 18 or over; proficiency in spoken English; capacity to provide informed consent. Exclusion criteria are: Primary diagnosis of a functional psychosis; insufficient degree of literacy, comprehension or attention to be able to engage in trial therapy and assessments; currently engaged in a specific programme of psychological treatment for personality disorder or likely to start such treatment during the trial period; currently enrolled in any other trial. Suitable participants are randomly allocated to PEPS therapy plus treatment as usual (TAU) or TAU only. We aim to recruit 340 men and women. The primary outcome is social functioning as measured by the SFQ. A reduction (i.e., an improvement) of 2 points or more on the SFQ at follow-up 72 weeks post-randomisation is our pre-specified index of clinically significant change. Secondary outcomes include a reduction of unscheduled service usage and an increase in scheduled service usage; improved quality of life; and a reduction in mental distress. Discussion PEPS therapy has potential as an economical, accessible, and acceptable intervention for people with personality disorder. The results from this randomised controlled trial will tell us if PEPS therapy is effective and cost-effective. If so, then it will be a useful treatment for inclusion in a broader menu of treatment options for this group of service users. Trial Registration International Standard Randomised Controlled Trial Number - ISRCTN70660936 PMID:21864370

PEP3 overexpression shortens lag phase but does not alter growth rate in Saccharomyces cerevisiae exposed to acetic acid stress

PubMed Central

Ding, Jun; Holzwarth, Garrett; Bradford, C. Samuel; Cooley, Ben; Yoshinaga, Allen S.; Patton-Vogt, Jana; Abeliovich, Hagai; Penner, Michael H.; Bakalinsky, Alan T.

2017-01-01

In fungi, two recognized mechanisms contribute to pH homeostasis: the plasma membrane proton-pumping ATPase that exports excess protons and the vacuolar proton-pumping ATPase (V-ATPase) that mediates vacuolar proton uptake. Here, we report that overexpression of PEP3 which encodes a component of the HOPS and CORVET complexes involved in vacuolar biogenesis, shortened lag phase in Saccharomyces cerevisiae exposed to acetic acid stress. By confocal microscopy, PEP3-overexpressing cells stained with the vacuolar membrane-specific dye, FM4-64 had more fragmented vacuoles than the wild-type control. The stained overexpression mutant was also found to exhibit about 3.6-fold more FM4-64 fluorescence than the wild-type control as determined by flow cytometry. While the vacuolar pH of the wild-type strain grown in the presence of 80 mM acetic acid was significantly higher than in the absence of added acid, no significant difference was observed in vacuolar pH of the overexpression strain grown either in the presence or absence of 80 mM acetic acid. Based on an indirect growth assay, the PEP3-overexpression strain exhibited higher V-ATPase activity. We hypothesize that PEP3 overexpression provides protection from acid stress by increasing vacuolar surface area and V-ATPase activity and, hence, proton-sequestering capacity. PMID:26051671

Direct observation of binding stress-induced crystalline orientation change in piezoelectric plate sensors

NASA Astrophysics Data System (ADS)

Wu, Wei; Shih, Wei-Heng; Shih, Wan Y.

2016-03-01

We have examined the mechanism of the detection resonance frequency shift, Δf/f, of a 1370 μm long and 537 μm wide [Pb(Mg1/3Nb2/3)O3]0.65[PbTiO3]0.35 (PMN-PT) piezoelectric plate sensor (PEPS) made of a 8-μm thick PMN-PT freestanding film. The Δf/f of the PEPS was monitored in a three-step binding model detections of (1) binding of maleimide-activated biotin to the sulfhydryl on the PEPS surface followed by (2) binding of streptavidin to the bound biotin and (3) subsequent binding of biotinylated probe deoxyribonucleic acid to the bound streptavidin. We used a PMN-PT surrogate made of the same 8-μm thick PMN-PT freestanding film that the PEPS was made of but was about 1 cm in length and width to carry out crystalline orientation study using X-ray diffraction (XRD) scan around the (002)/(200) peaks after each of the binding steps. The result of the XRD studies indicated that each binding step caused the crystalline orientation of the PMN-PT thin layer to switch from the vertical (002) orientation to the horizontal (200) orientation, and most of the PEPS detection Δf/f was due to the change in the lateral Young's modulus of the PMN-PT thin layer as a result of the crystalline orientation change.

In roots of Arabidopsis thaliana, the damage-associated molecular pattern AtPep1 is a stronger elicitor of immune signalling than flg22 or the chitin heptamer.

PubMed

Poncini, Lorenzo; Wyrsch, Ines; Dénervaud Tendon, Valérie; Vorley, Thomas; Boller, Thomas; Geldner, Niko; Métraux, Jean-Pierre; Lehmann, Silke

2017-01-01

Plants interpret their immediate environment through perception of small molecules. Microbe-associated molecular patterns (MAMPs) such as flagellin and chitin are likely to be more abundant in the rhizosphere than plant-derived damage-associated molecular patterns (DAMPs). We investigated how the Arabidopsis thaliana root interprets MAMPs and DAMPs as danger signals. We monitored root development during exposure to increasing concentrations of the MAMPs flg22 and the chitin heptamer as well as of the DAMP AtPep1. The tissue-specific expression of defence-related genes in roots was analysed using a toolkit of promoter::YFPN lines reporting jasmonic acid (JA)-, salicylic acid (SA)-, ethylene (ET)- and reactive oxygen species (ROS)- dependent signalling. Finally, marker responses were analysed during invasion by the root pathogen Fusarium oxysporum. The DAMP AtPep1 triggered a stronger activation of the defence markers compared to flg22 and the chitin heptamer. In contrast to the tested MAMPs, AtPep1 induced SA- and JA-signalling markers in the root and caused a severe inhibition of root growth. Fungal attack resulted in a strong activation of defence genes in tissues close to the invading fungal hyphae. The results collectively suggest that AtPep1 presents a stronger danger signal to the Arabidopsis root than the MAMPs flg22 and chitin heptamer.

Preejection period can be calculated using R peak instead of Q.

PubMed

Seery, Mark D; Kondrak, Cheryl L; Streamer, Lindsey; Saltsman, Thomas; Lamarche, Veronica M

2016-08-01

Preejection period (PEP) is a common measure of sympathetic nervous system activation in psychophysiological research, which makes it important to measure reliably for as many participants as possible. PEP is typically calculated as the interval between the onset or peak of the electrocardiogram Q wave and the impedance cardiography B point, but the Q wave can lack clear definition and even its peak is not visible for all participants. We thus investigated the feasibility of using the electrocardiogram R wave peak (Rpeak ) instead of Q because it can be consistently identified with ease and precision. Across four samples (total N = 408), young adult participants completed a variety of minimally metabolically demanding laboratory tasks after a resting baseline. Results consistently supported a close relationship between absolute levels of the Rpeak -B interval and PEP (accounting for approximately 90% of the variance at baseline and 89% during task performance, on average), but for reactivity values, Rpeak -B was practically indistinguishable from PEP (accounting for over 98% of the variance, on average). Given that using Rpeak rather than the onset or peak of Q saves time, eliminates potential subjectivity, and can be applied to more participants (i.e., those without a visible Q wave), findings suggest that Rpeak -B likely provides an adequate estimate of PEP when absolute levels are of interest and clearly does so for within-person changes. © 2016 Society for Psychophysiological Research.

The Burden of Rabies in Tanzania and Its Impact on Local Communities

PubMed Central

Sambo, Maganga; Cleaveland, Sarah; Ferguson, Heather; Lembo, Tiziana; Simon, Cleophas; Urassa, Honorati; Hampson, Katie

2013-01-01

Background Rabies remains a major public health threat in many parts of the world and is responsible for an estimated 55,000 human deaths annually. The burden of rabies is estimated to be around US$20 million in Africa, with the highest financial expenditure being the cost of post-exposure prophylaxis (PEP). However, these calculations may be substantial underestimates because the costs to households of coping with endemic rabies have not been investigated. We therefore aimed to estimate the household costs, health-seeking behaviour, coping strategies, and outcomes of exposure to rabies in rural and urban communities in Tanzania. Methods and Findings Extensive investigative interviews were used to estimate the incidence of human deaths and bite exposures. Questionnaires with bite victims and their families were used to investigate health-seeking behaviour and costs (medical and non-medical costs) associated with exposure to rabies. We calculated that an average patient in rural Tanzania, where most people live on less than US$1 per day, would need to spend over US$100 to complete WHO recommended PEP schedules. High costs and frequent shortages of PEP led to poor compliance with PEP regimens, delays in presentation to health facilities, and increased risk of death. Conclusion The true costs of obtaining PEP were twice as high as those previously reported from Africa and should be considered in re-evaluations of the burden of rabies. PMID:24244767

Phosphoenolpyruvate Transporter Enables Targeted Perturbation During Metabolic Analysis of L-Phenylalanine Production With Escherichia coli.

PubMed

Tröndle, Julia; Albermann, Christoph; Weiner, Michael; Sprenger, Georg A; Weuster-Botz, Dirk

2018-05-01

Usually perturbation of the metabolism of cells by addition of substrates is applied for metabolic analysis of production organisms, but perturbation studies are restricted to the endogenous substrates of the cells under study. The goal of this study is to overcome this limitation by making phosphoenolpyruvate (PEP) available for perturbation studies with Escherichia coli producing L-phenylalanine. A production strain overexpressing a PEP-transporter variant (UhpT-D388C) is applied in a standardized fed-batch production-process on a 42 L-scale. Four parallel short-term perturbation experiments of 20 min are performed with glucose and glycerol as fed-batch carbon sources after rapid media transition of cells from the production-process. PEP is added after 9 min and is immediately consumed by the cells with up to 1.5 mmol g CDW -1  h -1 . L-phenylalanine production rates increased by up to 200% after addition of PEP. This clearly indicates an intracellular PEP-limitation in the L-phenylalanine production strain under study. Thus, it is shown that overexpressing specific transporters for analytical reasons makes exogenous substrates available as perturbation substrates for metabolic analyses of cells sampled from production-processes and thereby allows a very targeted perturbation of whole-cell metabolism. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

First evidence of pep solar neutrinos by direct detection in Borexino.

PubMed

Bellini, G; Benziger, J; Bick, D; Bonetti, S; Bonfini, G; Bravo, D; Buizza Avanzini, M; Caccianiga, B; Cadonati, L; Calaprice, F; Carraro, C; Cavalcante, P; Chavarria, A; Chepurnov, A; D'Angelo, D; Davini, S; Derbin, A; Etenko, A; Fomenko, K; Franco, D; Galbiati, C; Gazzana, S; Ghiano, C; Giammarchi, M; Goeger-Neff, M; Goretti, A; Grandi, L; Guardincerri, E; Hardy, S; Ianni, Aldo; Ianni, Andrea; Korablev, D; Korga, G; Koshio, Y; Kryn, D; Laubenstein, M; Lewke, T; Litvinovich, E; Loer, B; Lombardi, F; Lombardi, P; Ludhova, L; Machulin, I; Manecki, S; Maneschg, W; Manuzio, G; Meindl, Q; Meroni, E; Miramonti, L; Misiaszek, M; Montanari, D; Mosteiro, P; Muratova, V; Oberauer, L; Obolensky, M; Ortica, F; Otis, K; Pallavicini, M; Papp, L; Perasso, L; Perasso, S; Pocar, A; Quirk, J; Raghavan, R S; Ranucci, G; Razeto, A; Re, A; Romani, A; Sabelnikov, A; Saldanha, R; Salvo, C; Schönert, S; Simgen, H; Skorokhvatov, M; Smirnov, O; Sotnikov, A; Sukhotin, S; Suvorov, Y; Tartaglia, R; Testera, G; Vignaud, D; Vogelaar, R B; von Feilitzsch, F; Winter, J; Wojcik, M; Wright, A; Wurm, M; Xu, J; Zaimidoroga, O; Zavatarelli, S; Zuzel, G

2012-02-03

We observed, for the first time, solar neutrinos in the 1.0-1.5 MeV energy range. We determined the rate of pep solar neutrino interactions in Borexino to be 3.1±0.6{stat}±0.3{syst}  counts/(day·100  ton). Assuming the pep neutrino flux predicted by the standard solar model, we obtained a constraint on the CNO solar neutrino interaction rate of <7.9  counts/(day·100  ton) (95% C.L.). The absence of the solar neutrino signal is disfavored at 99.97% C.L., while the absence of the pep signal is disfavored at 98% C.L. The necessary sensitivity was achieved by adopting data analysis techniques for the rejection of cosmogenic {11}C, the dominant background in the 1-2 MeV region. Assuming the Mikheyev-Smirnov-Wolfenstein large mixing angle solution to solar neutrino oscillations, these values correspond to solar neutrino fluxes of (1.6±0.3)×10{8}  cm{-2} s^{-1} and <7.7×10{8}  cm{-2} s{-1} (95% C.L.), respectively, in agreement with both the high and low metallicity standard solar models. These results represent the first direct evidence of the pep neutrino signal and the strongest constraint of the CNO solar neutrino flux to date.

Enrofloxacin and Probiotic Lactobacilli Influence PepT1 and LEAP-2 mRNA Expression in Poultry.

PubMed

Pavlova, Ivelina; Milanova, Aneliya; Danova, Svetla; Fink-Gremmels, Johanna

2016-12-01

Expression of peptide transporter 1 (PepT1) and liver-expressed antimicrobial peptide 2 (LEAP-2) in chickens can be influenced by food deprivation, pathological conditions and drug administration. Effect of three putative probiotic Lactobacillus strains and enrofloxacin on the expression of PepT1 and LEAP-2 mRNA was investigated in Ross 308 chickens. One-day-old chicks (n = 24) were allocated to following groups: control (without treatment); group treated with probiotics via feed; group treated with a combination of probiotics and enrofloxacin; and a group given enrofloxacin only. The drug was administered at a dose of 10 mg kg -1 , via drinking water for 5 days. Samples from liver, duodenum and jejunum were collected 126 h after the start of the treatment. Expression levels of PepT1 and LEAP-2 were determined by real-time polymerase chain reaction and were statistically evaluated by Mann-Whitney test. Enrofloxacin administered alone or in combination with probiotics provoked a statistically significant up-regulation of PepT1 mRNA levels in the measured organ sites. These changes can be attributed to a tendency of improvement in utilization of dietary peptide and in body weight gain. LEAP-2 mRNA expression levels did not change significantly in enrofloxacin-treated chickens in comparison with control group.

The GridEcon Platform: A Business Scenario Testbed for Commercial Cloud Services

NASA Astrophysics Data System (ADS)

Risch, Marcel; Altmann, Jörn; Guo, Li; Fleming, Alan; Courcoubetis, Costas

Within this paper, we present the GridEcon Platform, a testbed for designing and evaluating economics-aware services in a commercial Cloud computing setting. The Platform is based on the idea that the exact working of such services is difficult to predict in the context of a market and, therefore, an environment for evaluating its behavior in an emulated market is needed. To identify the components of the GridEcon Platform, a number of economics-aware services and their interactions have been envisioned. The two most important components of the platform are the Marketplace and the Workflow Engine. The Workflow Engine allows the simple composition of a market environment by describing the service interactions between economics-aware services. The Marketplace allows trading goods using different market mechanisms. The capabilities of these components of the GridEcon Platform in conjunction with the economics-aware services are described in this paper in detail. The validation of an implemented market mechanism and a capacity planning service using the GridEcon Platform also demonstrated the usefulness of the GridEcon Platform.

Control of cell growth on 3D-printed cell culture platforms for tissue engineering.

PubMed

Tan, Zhikai; Liu, Tong; Zhong, Juchang; Yang, Yikun; Tan, Weihong

2017-12-01

Biocompatible tissue growth has excellent prospects for tissue engineering. These tissues are built over scaffolds, which can influence aspects such as cell adhesion, proliferation rate, morphology, and differentiation. However, the ideal 3D biological structure has not been developed yet. Here, we applied the electro-hydrodynamic jet (E-jet) 3D printing technology using poly-(lactic-co-glycolic acid, PLGA) solution to print varied culture platforms for engineered tissue structures. The effects of different parameters (electrical voltage, plotting speed, and needle sizes) on the outcome were investigated. We compared the biological compatibility of the 3D printed culture platforms with that of random fibers. Finally, we used the 3D-printed PLGA platforms to culture fibroblasts, the main cellular components of loose connective tissue. The results show that the E-jet printed platforms could guide and improve cell growth. These highly aligned fibers were able to support cellular alignment and proliferation. Cell angle was consistent with the direction of the fibers, and cells cultured on these fibers showed a much faster migration, potentially enhancing wound healing performance. Thus, the potential of this technology for 3D biological printing is large. This process can be used to grow biological scaffolds for the engineering of tissues. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3281-3292, 2017. © 2017 Wiley Periodicals, Inc.

Isolation, characterization, and expression analyses of plant elicitor peptides (Pep) genes in maize

USDA-ARS?s Scientific Manuscript database

Insect-induced defenses occur in nearly all plants and are regulated by conserved signaling pathways. In plant families, peptides with analogous activity have remained elusive. Peps are conserved signals across diverse plant families regulating antiherbivore defenses and are likely to be the missing...

Texting Parents: Evaluation Report and Executive Summary

ERIC Educational Resources Information Center

Miller, Sarah; Davison, Jenny; Yohanis, Jamie; Sloan, Seaneen; Gildea, Aideen; Thurston, Allen

2017-01-01

This report presents the findings from an efficacy trial and process evaluation of the Parent Engagement Programme (PEP). The PEP was a school-level intervention designed to improve pupil outcomes by engaging parents in their children's learning. The programme was developed collaboratively by research teams from the University of Bristol and…

Sesame Street PEP Handbook. Second Edition.

ERIC Educational Resources Information Center

Children's Television Workshop, New York, NY.

This handbook for early childhood educators describes the Sesame Street PEP, an educational enrichment program for 3- to 5-year-olds that makes learning a fun and challenging adventure by using the educational goals of the Sesame Street show, children's books, and developmentally appropriate activities. This program seeks to: (1) stimulate…

42 CFR 484.205 - Basis of payment.

Code of Federal Regulations, 2010 CFR

2010-10-01

... episode payment (PEP) adjustment due to an intervening event defined as a beneficiary elected transfer or... new physician certification of the new plan of care. The PEP adjustment is determined in accordance with § 484.235. (3) An outlier payment is determined in accordance with § 484.240. (b) Episode payment...

75 FR 75462 - Notice of Proposed Information Collection Requests

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-03

... used in a timely manner; (3) is the estimate of burden accurate; (4) how might the Department enhance... collected from administrators at Carol M. White Physical Education Program (PEP) projects and analyses of... the PEP, and will inform future improvements to the program. Requests for copies of the proposed...

42 CFR 484.205 - Basis of payment.

Code of Federal Regulations, 2014 CFR

2014-10-01

... episode payment (PEP) adjustment due to an intervening event defined as a beneficiary elected transfer or... new physician certification of the new plan of care. The PEP adjustment is determined in accordance with § 484.235. (3) An outlier payment is determined in accordance with § 484.240. (b) Episode payment...

42 CFR 484.205 - Basis of payment.

Code of Federal Regulations, 2013 CFR

2013-10-01

... episode payment (PEP) adjustment due to an intervening event defined as a beneficiary elected transfer or... new physician certification of the new plan of care. The PEP adjustment is determined in accordance with § 484.235. (3) An outlier payment is determined in accordance with § 484.240. (b) Episode payment...

42 CFR 484.205 - Basis of payment.

Code of Federal Regulations, 2012 CFR

2012-10-01

... episode payment (PEP) adjustment due to an intervening event defined as a beneficiary elected transfer or... new physician certification of the new plan of care. The PEP adjustment is determined in accordance with § 484.235. (3) An outlier payment is determined in accordance with § 484.240. (b) Episode payment...

42 CFR 484.205 - Basis of payment.

Code of Federal Regulations, 2011 CFR

2011-10-01

... episode payment (PEP) adjustment due to an intervening event defined as a beneficiary elected transfer or... new physician certification of the new plan of care. The PEP adjustment is determined in accordance with § 484.235. (3) An outlier payment is determined in accordance with § 484.240. (b) Episode payment...

Cells for tissue engineering of cardiac valves.

PubMed

Jana, Soumen; Tranquillo, Robert T; Lerman, Amir

2016-10-01

Heart valve tissue engineering is a promising alternative to prostheses for the replacement of diseased or damaged heart valves, because tissue-engineered valves have the ability to remodel, regenerate and grow. To engineer heart valves, cells are harvested, seeded onto or into a three-dimensional (3D) matrix platform to generate a tissue-engineered construct in vitro, and then implanted into a patient's body. Successful engineering of heart valves requires a thorough understanding of the different types of cells that can be used to obtain the essential phenotypes that are expressed in native heart valves. This article reviews different cell types that have been used in heart valve engineering, cell sources for harvesting, phenotypic expression in constructs and suitability in heart valve tissue engineering. Natural and synthetic biomaterials that have been applied as scaffold systems or cell-delivery platforms are discussed with each cell type. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

An engineered microbial platform for direct biofuel production from brown macroalgae.

PubMed

Wargacki, Adam J; Leonard, Effendi; Win, Maung Nyan; Regitsky, Drew D; Santos, Christine Nicole S; Kim, Peter B; Cooper, Susan R; Raisner, Ryan M; Herman, Asael; Sivitz, Alicia B; Lakshmanaswamy, Arun; Kashiyama, Yuki; Baker, David; Yoshikuni, Yasuo

2012-01-20

Prospecting macroalgae (seaweeds) as feedstocks for bioconversion into biofuels and commodity chemical compounds is limited primarily by the availability of tractable microorganisms that can metabolize alginate polysaccharides. Here, we present the discovery of a 36-kilo-base pair DNA fragment from Vibrio splendidus encoding enzymes for alginate transport and metabolism. The genomic integration of this ensemble, together with an engineered system for extracellular alginate depolymerization, generated a microbial platform that can simultaneously degrade, uptake, and metabolize alginate. When further engineered for ethanol synthesis, this platform enables bioethanol production directly from macroalgae via a consolidated process, achieving a titer of 4.7% volume/volume and a yield of 0.281 weight ethanol/weight dry macroalgae (equivalent to ~80% of the maximum theoretical yield from the sugar composition in macroalgae).

Network Upgrade for the SLC: PEP II Network

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

Crane, M.; Call, M.; Clark, S.

2011-09-09

The PEP-II control system required a new network to support the system functions. This network, called CTLnet, is an FDDI/Ethernet based network using only TCP/IP protocols. An upgrade of the SLC Control System micro communications to use TCP/IP and SLCNET would allow all PEP-II control system nodes to use TCP/IP. CTLnet is private and separate from the SLAC public network. Access to nodes and control system functions is provided by multi-homed application servers with connections to both the private CTLnet and the SLAC public network. Monitoring and diagnostics are provided using a dedicated system. Future plans and current status informationmore » is included.« less

Radiosynthesis of a new PSMA targeting ligand ([18F]FPy-DUPA-Pep).

PubMed

Malik, Noeen; Machulla, Hans-Jürgen; Solbach, Christoph; Winter, Gordon; Reske, Sven N; Zlatopolskiy, Boris

2011-07-01

Due to the specificity of expression of PSMA (prostate specific membrane antigen) particularly in prostate cancer cells (e.g. LNCaP), numerous PSMA ligands have been synthesized until now. In the current study, we synthesized DUPA-Pep having 2-[3-(1,3-dicarboxypropyl)ureido]pentanedioic acid (DUPA) linked via 8-aminooctanoic acid to two phenylalanine residues and chose 6-[(18)F]fluoronicotinic acid 2,3,5,6-tetrafluorophenyl ester [(18)F]FPy-TFP as a prosthetic group for coupling. [(18)F]FPy-DUPA-Pep was obtained in a radiochemical yield of 48±0.9% (decay uncorrected) within 50 min with a chemical purity of >98%. Copyright © 2011 Elsevier Ltd. All rights reserved.

Microfabrication of a platform to measure and manipulate the mechanics of engineered microtissues.

PubMed

Ramade, Alexandre; Legant, Wesley R; Picart, Catherine; Chen, Christopher S; Boudou, Thomas

2014-01-01

Engineered tissues can be used to understand fundamental features of biology, develop organotypic in vitro model systems, and as engineered tissue constructs for replacing damaged tissue in vivo. However, a key limitation is an inability to test the wide range of parameters that might impact the engineered tissue in a high-throughput manner and in an environment that mimics the three-dimensional (3D) native architecture. We developed a microfabricated platform to generate arrays of microtissues embedded within 3D micropatterned matrices. Microcantilevers simultaneously constrain microtissue formation and report forces generated by the microtissues in real time, opening the possibility to use high-throughput, low-volume screening for studies on engineered tissues. Thanks to the micrometer scale of the microtissues, this platform is also suitable for high-throughput monitoring of drug-induced effect on architecture and contractility in engineered tissues. Moreover, independent variations of the mechanical stiffness of the cantilevers and collagen matrix allow the measurement and manipulation of the mechanics of the microtissues. Thus, our approach will likely provide valuable opportunities to elucidate how biomechanical, electrical, biochemical, and genetic/epigenetic cues modulate the formation and maturation of 3D engineered tissues. In this chapter, we describe the microfabrication, preparation, and experimental use of such microfabricated tissue gauges. Copyright © 2014 Elsevier Inc. All rights reserved.

Millstone: software for multiplex microbial genome analysis and engineering

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

Goodman, Daniel B.; Kuznetsov, Gleb; Lajoie, Marc J.

Inexpensive DNA sequencing and advances in genome editing have made computational analysis a major rate-limiting step in adaptive laboratory evolution and microbial genome engineering. Here, we describe Millstone, a web-based platform that automates genotype comparison and visualization for projects with up to hundreds of genomic samples. To enable iterative genome engineering, Millstone allows users to design oligonucleotide libraries and create successive versions of reference genomes. Millstone is open source and easily deployable to a cloud platform, local cluster, or desktop, making it a scalable solution for any lab.

Millstone: software for multiplex microbial genome analysis and engineering.

PubMed

Goodman, Daniel B; Kuznetsov, Gleb; Lajoie, Marc J; Ahern, Brian W; Napolitano, Michael G; Chen, Kevin Y; Chen, Changping; Church, George M

2017-05-25

Inexpensive DNA sequencing and advances in genome editing have made computational analysis a major rate-limiting step in adaptive laboratory evolution and microbial genome engineering. We describe Millstone, a web-based platform that automates genotype comparison and visualization for projects with up to hundreds of genomic samples. To enable iterative genome engineering, Millstone allows users to design oligonucleotide libraries and create successive versions of reference genomes. Millstone is open source and easily deployable to a cloud platform, local cluster, or desktop, making it a scalable solution for any lab.

Millstone: software for multiplex microbial genome analysis and engineering

DOE PAGES

Goodman, Daniel B.; Kuznetsov, Gleb; Lajoie, Marc J.; ...

2017-05-25

Inexpensive DNA sequencing and advances in genome editing have made computational analysis a major rate-limiting step in adaptive laboratory evolution and microbial genome engineering. Here, we describe Millstone, a web-based platform that automates genotype comparison and visualization for projects with up to hundreds of genomic samples. To enable iterative genome engineering, Millstone allows users to design oligonucleotide libraries and create successive versions of reference genomes. Millstone is open source and easily deployable to a cloud platform, local cluster, or desktop, making it a scalable solution for any lab.

Information Technology Curriculum Development for Participation and Equity Programs.

ERIC Educational Resources Information Center

Post, Maarten; And Others

A study explored ways in which training in information technology could be included in Participation and Equity Programs (PEP) in the areas of hospitality/tourism, retailing, and business and finance. The research team conducted a literature search, obtained completed questionnaires from 10 colleges offering a total of 22 PEPs, visited an…

Does the "Pupil Enterprise Programme" Influence Grades among Pupils with Special Needs?

ERIC Educational Resources Information Center

Johansen, Vegard; Somby, Hege M.

2016-01-01

This paper asks whether the Pupil Enterprise Programme (PEP) is a suitable working method for improving academic performance among pupils with special needs. Overall, 20% of pupils participate in PEP at some point during lower secondary school. Results from multilevel regression modelling indicate that pupils with special needs who have…

Comprehensive Physical Education Program Model

ERIC Educational Resources Information Center

Kamiya, Artie

2005-01-01

In 2004, the Wake County Public School System (North Carolina) received $1.3 million as one of 237 national winners of the $70 million federal Carol M. White Physical Education Program (PEP) Grant competition. The PEP Grant program is funded by the U.S. Department of Education and provides monies to school districts able to demonstrate the…

Student Achievement in New York State, 1985-86.

ERIC Educational Resources Information Center

New York State Education Dept., Albany. Div. of Educational Testing.

This report summarizes the 1985-86 results for three New York state examination programs--the elementary school Pupil Evaluation Program (PEP) and the high school Regents and Regents Competency Tests. Results on the PEP showed passing rates improved steadily over the last four years. About one-half of New York State's graduating seniors are…

75 FR 19673 - Petition for Exemption From the Vehicle Theft Prevention Standard; Saab

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-15

... module (BCM), passive entry passive start module (PEPS), intrusion/inclination sensor, an immobilizer... must be performed by communication between the PEPS and the BCM jointly with the UID (key fob... Saab 9-3, has been designed to enhance the functionality and theft protection provided by Saab's first...

Power Extension Package (PEP) system definition extension, orbital service module systems analysis study. Volume 11: PEP, cost, schedules, and work breakdown structure dictionary

NASA Technical Reports Server (NTRS)

1979-01-01

Cost scheduling and funding data are presented for the reference design of the power extension package. Major schedule milestones are correlated with current Spacelab flight dates. Funding distributions provide for minimum expenditure during the first year of the project.

Post-event processing in social anxiety disorder after real-life social situations - An ambulatory assessment study.

PubMed

Helbig-Lang, Sylvia; von Auer, Maxie; Neubauer, Karolin; Murray, Eileen; Gerlach, Alexander L

2016-09-01

Excessive post-mortem processing after social situations, a core symptom of social anxiety disorder (SAD), is thought to contribute to the perpetuation of social anxiety by consolidating negative self-schemata. Empirical findings on actual mechanisms underlying this so-called Post-Event Processing (PEP) are still scarce. The present study sought to identify variables associated with the experience of PEP after real-life social situations in a sample of 49 individuals diagnosed with SAD. Using an ambulatory assessment approach, individuals were asked to report on each distressing social event experienced during one week. A total of 192 events were captured. Hierarchical linear modeling indicated that next to trait social anxiety, the type of social situation (performance vs. interaction situations), self-focused attention, safety behavior use, and negative affect predicted levels of PEP after social situations. These findings add to the growing literature that emphasizes the importance of situational factors for the experience of PEP, and highlight potential venues to prevent it. Copyright © 2016 Elsevier Ltd. All rights reserved.

A new method for detection and discrimination of Pepino mosaic virus isolates using high resolution melting analysis of the triple gene block 3.

PubMed

Hasiów-Jaroszewska, Beata; Komorowska, Beata

2013-10-01

Diagnostic methods distinguished different Pepino mosaic virus (PepMV) genotypes but the methods do not detect sequence variation in particular gene segments. The necrotic and non-necrotic isolates (pathotypes) of PepMV share a 99% sequence similarity. These isolates differ from each other at one nucleotide site in the triple gene block 3. In this study, a combination of real-time reverse transcription polymerase chain reaction and high resolution melting curve analysis of triple gene block 3 was developed for simultaneous detection and differentiation of PepMV pathotypes. The triple gene block 3 region carrying a transition A → G was amplified using two primer pairs from twelve virus isolates, and was subjected to high resolution melting curve analysis. The results showed two distinct melting curve profiles related to each pathotype. The results also indicated that the high resolution melting method could readily differentiate between necrotic and non-necrotic PepMV pathotypes. Copyright © 2013 Elsevier B.V. All rights reserved.

Trypsin inhibitors from Capsicum baccatum var. pendulum leaves involved in Pepper yellow mosaic virus resistance.

PubMed

Moulin, M M; Rodrigues, R; Ribeiro, S F F; Gonçalves, L S A; Bento, C S; Sudré, C P; Vasconcelos, I M; Gomes, V M

2014-11-07

Several plant organs contain proteinase inhibitors, which are produced during normal plant development or are induced upon pathogen attack to suppress the enzymatic activity of phytopathogenic microorganisms. In this study, we examined the presence of proteinase inhibitors, specifically trypsin inhibitors, in the leaf extract of Capsicum baccatum var. pendulum inoculated with PepYMV (Pepper yellow mosaic virus). Leaf extract from plants with the accession number UENF 1624, which is resistant to PepYMV, was collected at 7 different times (0, 24, 48, 72, 96, 120, and 144 h). Seedlings inoculated with PepYMV and control seedlings were grown in a growth chamber. Protein extract from leaf samples was partially purified by reversed-phase chromatography using a C2/C18 column. Residual trypsin activity was assayed to detect inhibitors followed by Tricine-SDS-PAGE analysis to determine the N-terminal peptide sequence. Based on trypsin inhibitor assays, trypsin inhibitors are likely constitutively synthesized in C. baccatum var. pendulum leaf tissue. These inhibitors are likely a defense mechanism for the C. baccatum var. pendulum- PepYMV pathosystem.

Detection of Instrumental Drifts in the PEP II LER BPM System

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

Wittmer, W.; Fisher, A.S.; Martin, D.J.

2007-11-07

During the last PEP-II run a major goal was to bring the Low-Energy Ring optics as close as possible to the design. A large number of BPMs exhibited sudden artificial jumps that interfered with this effort. The source of the majority of these jumps had been traced to the filter-isolator boxes (FIBs) near the BPM buttons. A systematic approach to find and repair the failing units had been developed and implemented. Despite this effort, the instrumental orbit jumps never completely disappeared. To trace the source of this behavior a test setup, using a spare Bergoz MX-BPM processor (kindly provided bymore » SPEAR III at SSRL), was connected in parallel to various PEP-II BPM processors. In the course of these measurements a slow instrumental orbit drift was found which was clearly not induced by a moving positron beam. Based on the size of the system and the limited time before PEP-II closes in Oct.2008, an accelerator improvement project was initiated to install BERGOZ BPM-MX processors close to all sextupoles.« less

SwePep, a database designed for endogenous peptides and mass spectrometry.

PubMed

Fälth, Maria; Sköld, Karl; Norrman, Mathias; Svensson, Marcus; Fenyö, David; Andren, Per E

2006-06-01

A new database, SwePep, specifically designed for endogenous peptides, has been constructed to significantly speed up the identification process from complex tissue samples utilizing mass spectrometry. In the identification process the experimental peptide masses are compared with the peptide masses stored in the database both with and without possible post-translational modifications. This intermediate identification step is fast and singles out peptides that are potential endogenous peptides and can later be confirmed with tandem mass spectrometry data. Successful applications of this methodology are presented. The SwePep database is a relational database developed using MySql and Java. The database contains 4180 annotated endogenous peptides from different tissues originating from 394 different species as well as 50 novel peptides from brain tissue identified in our laboratory. Information about the peptides, including mass, isoelectric point, sequence, and precursor protein, is also stored in the database. This new approach holds great potential for removing the bottleneck that occurs during the identification process in the field of peptidomics. The SwePep database is available to the public.

Effects of fasting and refeeding on the digestive tract of zebrafish (Danio rerio) fed with Spirulina (Arthrospira platensis), a high protein feed source.

PubMed

Lo Cascio, Patrizia; Calabrò, Concetta; Bertuccio, Clara; Paterniti, Irene; Palombieri, Deborah; Calò, Margherita; Albergamo, Ambrogina; Salvo, Andrea; Gabriella Denaro, Maria

2017-07-01

In the present work, morphological and molecular effects of short-term feed deprivation and refeeding with Spirulina (Arthrospira platensis) on zebrafish digestive tract were determined. Once elucidated the proximate composition of Spirulina feed, immunohistochemical and western blot analyses of peptide transporter (PepT1) and cholecystokinin (CCK8) were carried out in the gastrointestinal tract of zebrafish, previously morphologically investigated. Two and five fasting days caused not only morphostructural alterations, but also the downregulation of PepT1 and CCK8 proteins. Conversely, the recovery of normal morphological conditions, along with an increased PepT1 and CCK8 expression, were observed after refeeding with Spirulina. The increase of PepT1 expression in zebrafish may be responsible for the enhanced CCK8 secretion, so that both proteins may contribute to an improved digestion process during refeeding. These observations could be supported not only by compensatory mechanisms induced by fasting and refeeding but also by an higher protein quality of Spirulina-based diet.

Integrating Antiretroviral Strategies for Human Immunodeficiency Virus Prevention: Post- and Pre-Exposure Prophylaxis and Early Treatment.

PubMed

Grant, Robert M; Smith, Dawn K

2015-12-01

Best practices for integrating human immunodeficiency virus (HIV) testing and antiretroviral interventions for prevention and treatment are suggested based on research evidence and existing normative guidance. The goal is to provide high-impact prevention services during periods of substantial risk. Antiretroviral medications are recommended for postexposure prophylaxis (PEP), pre-exposure prophylaxis (PrEP), and treatment of HIV infection. We reviewed research evidence and current normative guidelines to identify best practices for integrating these high-impact prevention strategies. More sensitive HIV tests used for screening enable earlier diagnosis and treatment of HIV infection, more appropriate counseling, and help limit drug resistance. A fully suppressive PEP regimen should be initiated based on exposure history or physical findings when sensitive diagnostic testing is delayed or not available and antibody tests are negative. Transitions from PEP to PrEP are often warranted because HIV exposure events may continue to occur. This algorithmic approach to integrating PEP, PrEP, and early treatment decisions may increase the uptake of these interventions by a greater number and diversity of knowledgeable healthcare providers.

Integrating Antiretroviral Strategies for Human Immunodeficiency Virus Prevention: Post- and Pre-Exposure Prophylaxis and Early Treatment

PubMed Central

Grant, Robert M.; Smith, Dawn K.

2015-01-01

Best practices for integrating human immunodeficiency virus (HIV) testing and antiretroviral interventions for prevention and treatment are suggested based on research evidence and existing normative guidance. The goal is to provide high-impact prevention services during periods of substantial risk. Antiretroviral medications are recommended for postexposure prophylaxis (PEP), pre-exposure prophylaxis (PrEP), and treatment of HIV infection. We reviewed research evidence and current normative guidelines to identify best practices for integrating these high-impact prevention strategies. More sensitive HIV tests used for screening enable earlier diagnosis and treatment of HIV infection, more appropriate counseling, and help limit drug resistance. A fully suppressive PEP regimen should be initiated based on exposure history or physical findings when sensitive diagnostic testing is delayed or not available and antibody tests are negative. Transitions from PEP to PrEP are often warranted because HIV exposure events may continue to occur. This algorithmic approach to integrating PEP, PrEP, and early treatment decisions may increase the uptake of these interventions by a greater number and diversity of knowledgeable healthcare providers. PMID:26512356

Social anxiety and vulnerability for problematic drinking in college students: the moderating role of post-event processing.

PubMed

Potter, Carrie M; Galbraith, Todd; Jensen, Dane; Morrison, Amanda S; Heimberg, Richard G

2016-09-01

Socially anxious college students are at increased risk for engaging in problematic drinking (i.e. heavy or risky drinking) behaviors that are associated with the development of an alcohol use disorder. The present study examined whether post-event processing (PEP), repeatedly thinking about and evaluating one's performance in a past social situation, strengthens the association between social anxiety and vulnerability to problematic drinking among college students. Eighty-three college drinkers with high or low social anxiety participated in a social interaction task and were exposed to a manipulation that either promoted or inhibited PEP about the social interaction. Among participants randomized to the PEP promotion condition, those with high social anxiety exhibited a greater urge to use alcohol after the social interaction and greater motivation to drink to cope with depressive symptoms over the week following the manipulation than did those with low social anxiety. These findings suggest that targeting PEP in college drinking intervention programs may improve the efficacy of such programs for socially anxious students.

Specific Immunoassays for Placental Alkaline Phosphatase As a Tumor Marker

PubMed Central

Stinghen, Sérvio T.; Moura, Juliana F.; Zancanella, Patrícia; Rodrigues, Giovanna A.; Pianovski, Mara A.; Lalli, Enzo; Arnold, Dodie L.; Minozzo, João C.; Callefe, Luis G.; Ribeiro, Raul C.; Figueiredo, Bonald C.

2006-01-01

Human placental (hPLAP) and germ cell (PLAP-like) alkaline phosphatases are polymorphic and heat-stable enzymes. This study was designed to develop specific immunoassays for quantifying hPLAP and PLAP-like enzyme activity (EA) in sera of cancer patients, pregnant women, or smokers. Polyclonal sheep anti-hPLAP antibodies were purified by affinity chromatography with whole hPLAP protein (ICA-PLAP assay) or a synthetic peptide (aa 57–71) of hPLAP (ICA-PEP assay); the working range was 0.1–11 U/L and cutoff value was 0.2 U/L EA for nonsmokers. The intra- and interassay coefficients of variation were 3.7%–6.5% (ICA-PLAP assay) and 9.0%–9.9% (ICA-PEP assay). An insignificant cross-reactivity was noted for high levels of unheated intestinal alkaline phosphatase in ICA-PEP assay. A positive correlation between the regression of tumor size and EA was noted in a child with embryonal carcinoma. It can be concluded that ICA-PEP assay is more specific than ICA-PLAP, which is still useful to detect other PLAP/PLAP-like phenotypes. PMID:17489017

The Study on Collaborative Manufacturing Platform Based on Agent

NASA Astrophysics Data System (ADS)

Zhang, Xiao-yan; Qu, Zheng-geng

To fulfill the trends of knowledge-intensive in collaborative manufacturing development, we have described multi agent architecture supporting knowledge-based platform of collaborative manufacturing development platform. In virtue of wrapper service and communication capacity agents provided, the proposed architecture facilitates organization and collaboration of multi-disciplinary individuals and tools. By effectively supporting the formal representation, capture, retrieval and reuse of manufacturing knowledge, the generalized knowledge repository based on ontology library enable engineers to meaningfully exchange information and pass knowledge across boundaries. Intelligent agent technology increases traditional KBE systems efficiency and interoperability and provides comprehensive design environments for engineers.

Curating the Web: Building a Google Custom Search Engine for the Arts

ERIC Educational Resources Information Center

Hennesy, Cody; Bowman, John

2008-01-01

Google's first foray onto the web made search simple and results relevant. With its Co-op platform, Google has taken another step toward dramatically increasing the relevancy of search results, further adapting the World Wide Web to local needs. Google Custom Search Engine, a tool on the Co-op platform, puts one in control of his or her own search…

Short-Term and Long-Term Effects of an Exercise-Based Patient Education Programme in People with Multiple Sclerosis: A Pilot Study

PubMed Central

Haas, Christian T.

2017-01-01

Background. Although people with Multiple Sclerosis (pwMS) benefit from physical exercise, they still show reduced physical activity and exercise behaviour. This study aimed to investigate short- and long-term effects of an exercise-based patient education programme (ePEP) that focuses on empowering pwMS to a sustainable and self-regulated exercise training management. Methods. Fourteen pwMS were randomly assigned to immediate experimental group (EG-I: n = 8) and waitlist-control group (EG-W: n = 6) and attended biweekly in a six-week ePEP. All participants were measured for walking ability, quality of life, fatigue, and self-efficacy towards physical exercise before and after the ePEP, after 12 weeks, and one year after baseline. Short-term effects were analysed in a randomised control trial and long-term effects of all ePEP participants (EG-I + EG-W = EG-all) in a quasi-experimental design. Results. Only functional gait significantly improved in EG-I compared to EG-W (p = 0.008, r = −0.67). Moderate to large effects were found in EG-all for walking ability. Not significant, however, relevant changes were detected for quality of life and fatigue. Self-efficacy showed no changes. Conclusion. The ePEP seems to be a feasible option to empower pwMS to a self-regulated and sustainable exercise training management shown in long-term walking improvements. PMID:28900546

Proteome analysis of Lactobacillus helveticus H9 during growth in skim milk.

PubMed

Chen, Y F; Zhao, W J; Wu, R N; Sun, Z H; Zhang, W Y; Wang, J C; Bilige, M; Zhang, H P

2014-12-01

Lactobacillus helveticus H9 was isolated from traditionally fermented yak milk in Tibet (China) with the ability to produce the antihypertensive peptides Val-Pro-Pro (VPP) and Ile-Pro-Pro (IPP) during milk fermentation. To understand the changes in the protein expression of L. helveticus H9, proteome analysis was performed at 3 different growth stages, lag phase (pH 6.1), log phase (pH 5.1), and stationary phase (pH 4.5) using 2-dimensional electrophoresis (2-DE). Further analysis showed that 257 differential protein spots were found and 214 protein spots were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS). The cellular functions of the differentially expressed proteins were complex. Interestingly, the proteolytic system-related proteins aminopeptidase N (PepN), aminopeptidase E (PepE), endopeptidase O2 (PepO2), and oligopeptide transport system permease protein (OppC) were observed only on the maps of pH 5.1 and pH 4.5, which was consistent with the presence of angiotensin I-converting enzyme (ACE)-inhibitory peptides VPP and IPP during these 2 growth stages (log phase and stationary phase). These results, combined with a previous study of gene expression of the proteolytic system, led us to conclude that the Opp transport system, pepE, and pepO2 are likely related to the production of ACE-inhibitory peptides. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.