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.

Optimization of Dynamic Aperture of PEP-X Baseline Design

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

Wang, Min-Huey; /SLAC; Cai, Yunhai

2010-08-23

SLAC is developing a long-range plan to transfer the evolving scientific programs at SSRL from the SPEAR3 light source to a much higher performing photon source. Storage ring design is one of the possibilities that would be housed in the 2.2-km PEP-II tunnel. The design goal of PEPX storage ring is to approach an optimal light source design with horizontal emittance less than 100 pm and vertical emittance of 8 pm to reach the diffraction limit of 1-{angstrom} x-ray. The low emittance design requires a lattice with strong focusing leading to high natural chromaticity and therefore to strong sextupoles. Themore » latter caused reduction of dynamic aperture. The dynamic aperture requirement for horizontal injection at injection point is about 10 mm. In order to achieve the desired dynamic aperture the transverse non-linearity of PEP-X is studied. The program LEGO is used to simulate the particle motion. The technique of frequency map is used to analyze the nonlinear behavior. The effect of the non-linearity is tried to minimize at the given constrains of limited space. The details and results of dynamic aperture optimization are discussed in this paper.« less

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.

Student Voices: Perspectives on Peer-to-Peer Sexual Health Education.

PubMed

Layzer, Carolyn; Rosapep, Lauren; Barr, Sherry

2017-07-01

This process study is a companion to a randomized evaluation of a school-based, peer-led comprehensive sexual health education program, Teen Prevention Education Program (Teen PEP), in which 11th- and 12th-grade students are trained by school health educators to conduct informative workshops with ninth-grade peers in schools in North Carolina. The process study was designed to understand youth participants' perspectives on the program in order to gain insight into program effectiveness. This is a mixed-methods study in 7 schools, with online surveys (N = 88) and 8 focus groups with peer educators (N = 116), end-of-program surveys (N = 1122), 8 focus groups with ninth-grade workshop participants (N = 89), and observations of the Teen PEP class and workshops during the semester of implementation in each school, 2012-2014. Both peer educators and ninth graders perceived benefits of participating in Teen PEP across a range of domains, including intentions, skills, and knowledge and that the peer education modality was important in their valuation of the experience. Our findings suggest that the peer-led comprehensive sexual health education approach embodied in Teen PEP can be an important educational mechanism for teaching students information and skills to promote sexual health. © 2017, American School Health Association.

Further empirical data on the psychoeducational profile-revised (PEP-R): reliability and validation with the Vineland adaptive behavior scales.

PubMed

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

2010-03-01

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 Autistic Disorder symptoms under the age of 12 years, including low-functioning individuals, was examined. Results yielded data of interest especially in terms of: Cronbach's alpha, interrater reliability, and validation with the Vineland Adaptive Behavior Scales. These findings help complete the instrument's statistical description and augment its usefulness, not only in designing treatment programs for these individuals, but also as an instrument for verifying the efficacy of intervention.

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,…

Pep Rally at the O. K. Corral.

ERIC Educational Resources Information Center

Leff, Laurel

1979-01-01

The program at Deep Springs College combines cattle ranching with traditional college courses. The two-year program is designed to develop a student's focus on loftier ideals and a critical perspective of society, stressing community responsibility and self-reliance. (JMF)

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.

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.

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

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...

APRN Usability Testing of a Tailored Computer-Mediated Health Communication Program

PubMed Central

Lin, Carolyn A.; Neafsey, Patricia J.; Anderson, Elizabeth

2010-01-01

This study tested the usability of a touch-screen enabled “Personal Education Program” (PEP) with Advanced Practice Registered Nurses (APRN). The PEP is designed to enhance medication adherence and reduce adverse self-medication behaviors in older adults with hypertension. An iterative research process was employed, which involved the use of: (1) pre-trial focus groups to guide the design of system information architecture, (2) two different cycles of think-aloud trials to test the software interface, and (3) post-trial focus groups to gather feedback on the think-aloud studies. Results from this iterative usability testing process were utilized to systematically modify and improve the three PEP prototype versions—the pilot, Prototype-1 and Prototype-2. Findings contrasting the two separate think-aloud trials showed that APRN users rated the PEP system usability, system information and system-use satisfaction at a moderately high level between trials. In addition, errors using the interface were reduced by 76 percent and the interface time was reduced by 18.5 percent between the two trials. The usability testing processes employed in this study ensured an interface design adapted to APRNs' needs and preferences to allow them to effectively utilize the computer-mediated health-communication technology in a clinical setting. PMID:19940619

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…

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.

Bioinspired Design of Polycaprolactone Composite Nanofibers as Artificial Bone Extracellular Matrix for Bone Regeneration Application.

PubMed

Gao, Xiang; Song, Jinlin; Zhang, Yancong; Xu, Xiao; Zhang, Siqi; Ji, Ping; Wei, Shicheng

2016-10-07

The design and development of functional biomimetic systems for programmed stem cell response is a field of topical interest. To mimic bone extracellular matrix, we present an innovative strategy for constructing drug-loaded composite nanofibrous scaffolds in this study, which could integrate multiple cues from calcium phosphate mineral, bioactive molecule, and highly ordered fiber topography for the control of stem cell fate. Briefly, inspired by mussel adhesion mechanism, a polydopamine (pDA)-templated nanohydroxyapatite (tHA) was synthesized and then surface-functionalized with bone morphogenetic protein-7-derived peptides via catechol chemistry. Afterward, the resulting peptide-loaded tHA (tHA/pep) particles were blended with polycaprolactone (PCL) solution to fabricate electrospun hybrid nanofibers with random and aligned orientation. Our research demonstrated that the bioactivity of grafted peptides was retained in composite nanofibers. Compared to controls, PCL-tHA/pep composite nanofibers showed improved cytocompatibility. Moreover, the incorporated tHA/pep particles in nanofibers could further facilitate osteogenic differentiation potential of human mesenchymal stem cells (hMSCs). More importantly, the aligned PCL-tHA/pep composite nanofibers showed more osteogenic activity than did randomly oriented counterparts, even under nonosteoinductive conditions, indicating excellent performance of biomimetic design in cell fate decision. After in vivo implantation, the PCL-tHA/pep composite nanofibers with highly ordered structure could significantly promote the regeneration of lamellar-like bones in a rat calvarial critical-sized defect. Accordingly, the presented strategy in our work could be applied for a wide range of potential applications in not only bone regeneration application but also pharmaceutical science.

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

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

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...

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...

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.

Ectopic expression of protein kinase C-β sensitizes head and neck squamous cell carcinoma to diterpene esters.

PubMed

Adams, Ryan A; D'Souza, Marjorie M A; Pierce, Carly J; Korica, Natasa; Wallwork, Ben; Parsons, Peter G; Panizza, Benedict; Boyle, Glen M

2015-03-01

The objective of this study was to examine the effect of specific Protein kinase C (PKC) isoform re-expression in solid malignancies, particularly head and neck squamous cell carcinoma cell lines, and the impact this may have on treatment with known activators of PKC. The constitutive expression of PKC isoforms were determined in six head and neck squamous cell carcinoma (SCC) cell lines. Cytotoxicity of the prototypic phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA) and the novel diterpene ester PEP005 was established. Viral transduction to re-express PKCβ isoforms in two of these cell lines was performed, and its effect on the sensitivity to the compounds was quantified. Tongue and hypopharyngeal SCC cell lines were resistant to both TPA and PEP005, with the concentration required to inhibit growth by 50% (IC50) being >1,000 ng/ml. CAL-27 (tongue SCC) and FaDu (hypopharyngeal SCC) cell lines re-expressing PKCβI and -βII isoforms demonstrated IC50 of 1-5 ng/ml with TPA or PEP005. Re-expression of PKCβ in head and neck SCC cell lines leads to cells one thousand-times more sensitive to the cytotoxic effects of phorbol or diterpene esters in culture. This highlights the importance of the isoform in tumor progression and presents the potential benefit of these compounds in malignancies expressing the protein, and in combination therapy. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

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

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.

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.

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.

The enhancement of adaptation and psychological well-being among victims of flooding and landslide in Thailand.

PubMed

Oba, Nongnut; Suntayakorn, Chanjar; Sangkaewsri, Roongsri; Longchupol, Chaowanee; Lohitpintu, Itsareat; Kumsri, Tongbai

2010-03-01

To explore the needs of potential enhancement for adaptation and to examine the effectiveness of the potential enhancement program for adaptation and psychological well-being among victims of flooding and landslide in Lublae district Uttaradit Province, Thailand. 3 step of research and development; the needs of potential enhancement for adaptation among victims of flooding and landslide were analyzed by focus group discussion, the potential enhancement program (PEP) was designed by brainstorming of three groups of stakeholder; victims, health volunteers and health personnel and the effectiveness of PEP was tested by the difference of adaptation and psychological well-being perception among victims of flooding and landslide between before and after intervention. Thumbun Maepou, Lublae district, Uttaradit Province, Thailand. The needs of potential enhancement among victims of flooding and landslide were set up warning network along the risk canal and mountain, first aid training for health volunteer, and program of psychological health promotion. The PEP composed of community flooding and landslide rehearsal training, health education and dissemination and knowledge management. Total adaptation and psychological wellbeing of samples after intervention were significantly higher than that of before intervention at 0.05 and 0.001, respectively. The restoration of adaptation and psychological well-being among victims of flooding and landslide were essential to maintained holistic health.

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.

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…

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).

76 FR 8722 - Notice of Submission for OMB Review

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-15

... student outcomes, the American Institutes for Research proposes a two-phase research design, drawing on survey data to be collected from administrators at Carol M. White Physical Education Program (PEP... collection (raw data and survey). Affected Public: Not-for-profit institutions; State, Local, or Tribal...

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.

A Nationwide Learning-Style Assessment of Undergraduate Athletic Training Students in CAAHEP-Accredited Athletic Training Programs

PubMed Central

Stradley, Stephanie L.; Buckley, Bernadette D.; Kaminski, Thomas W.; Horodyski, MaryBeth; Fleming, David; Janelle, Christopher M.

2002-01-01

Objective: To identify the learning styles and preferred environmental characteristics of undergraduate athletic training students in Commission on Accreditation of Allied Health Education Programs (CAAHEP)-accredited athletic training education programs and to determine if learning-style differences existed among geographic regions of the country. Design and Setting: Fifty CAAHEP-accredited athletic training programs were randomly selected in proportion to the number of programs in each geographic region. Ten students from each school were selected to complete the Kolb Learning Style Inventory (LSI) and the Productivity Environmental Preference Survey (PEPS). Subjects: A total of 193 undergraduate athletic training students (84 men, 109 women) with a mean age of 22.3 ± 2.8 years completed the PEPS, while 188 students completed the LSI. Measurements: We used chi-square analyses to determine if differences existed in learning-style type and if these differences were based on geographic location. We calculated analysis of variance to determine if there were any geographic differences in the mean overall combination scores of the LSI. Descriptive statistics were used to evaluate the PEPS. Results: The overall return rate was 38%. The chi-square analyses revealed no significant difference in learning-style type for athletic training students, regardless of the geographic region. The LSI yielded a relatively even distribution of learning styles: 29.3% of the students were accommodators, 19.7% were divergers, 21.8% were convergers, and 29.3% were assimilators. The overall mean combination scores were 4.9 (abstract-concrete) and 4.9 (active-reflective), and analysis of variance indicated no significant difference in the mean combination scores among the geographic regions. The PEPS revealed that undergraduate athletic training students demonstrated a strong preference for learning in the afternoon. Conclusions: Undergraduate athletic training students demonstrated great diversity in learning style. Educators must strongly consider this diversity and incorporate teaching methods that will benefit all types of learners. PMID:12937535

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…

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...

The Philippine Experience in Curriculum Development for Population Education: The State of the Art. Population Education Research Utilization. Monograph Series 1, Part 1.

ERIC Educational Resources Information Center

Arellano-Reyes, Ma. Felicitas; Villanueva, Carmelita L.

This booklet reviews the development and implementation of population education programs in the Philippines. Section one describes the Population Education Program (PEP), a national program sponsored by the Philippine Department of Education and UNESCO. PEP's goals are to develop curriculum, train teachers, and encourage research for population…

PEP-II Hardware Reliability

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

Allen, C. W.

2005-04-28

Hardware reliability takes on special importance in large accelerator facilities intended to work as factories; i.e., when they are expected to deliver design performance for extended periods of time. The PEP-II B-Factory at SLAC is such a facility. In this paper, we summarize PEP-II reliability statistics from the first four years of production running. The four running periods extended from January 12 through October 31, 2000, from February 4, 2001 through June 30, 2002, from November 15, 2002 through June 30, 2003, and from September 9, 2003 through July 31, 2004. These four periods are designated Runs 1, 2, 3,more » and 4 in the discussion and tables presented in the paper. The first four runs encompassed 30,359 hours. During this time, PEP-II was delivering luminosity to the BaBar detector 57.9 percent of the time. In addition, 5.3 percent of the time was used for scheduled dedicated machine development work, and 4.5 percent was scheduled off for maintenance, installations, or safety checks. Injection and tuning accounted for 19.9 percent. The remaining 12.4 percent was lost due to malfunctions. During this time period, a total of 9701 malfunctions were reported, but most did not interrupt the running program. The unscheduled down time, a total of 3883 hours, was attributed to 1724 of these malfunctions. Mean Time to Fail (MTTF) and Mean Time to Repair (MTTR) are presented for each of the major subsystems, and long-term availability trends are discussed.« less

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…

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…

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…

The effectiveness of physical exercise training in pain, mobility, and psychological well-being of older persons living in nursing homes.

PubMed

Tse, Mimi M Y; Tang, Shuk Kwan; Wan, Vanessa T C; Vong, Sinfia K S

2014-12-01

Pain is common in the aging population, particularly among older residents of nursing homes. It has been found that 50% of older people living in the community have been experiencing chronic pain, and the number increased to 80% for older residents of nursing homes. Exercise is an effective non-pharmacological intervention that can reduce pain and improve physical and psychological functions. A quasi-experimental study with a pretest-posttest control group designed was conducted to evaluate the effects of a physical exercise program (PEP) on older residents of nursing homes who have chronic pain. Three-hundred-ninety-six older residents with chronic pain were recruited from 10 nursing homes run by non-governmental organizations in Hong Kong. The average age of the older residents was 85.44 ± 6.29. Five nursing homes were randomized to the experimental group with PEP (n = 225, age = 85.45 ± 6.25); the other five nursing homes were randomized to the control group without the PEP (n = 171, age = 85.44 ± 6.35). PEP was an eight-week training program given by a physiotherapist and nurses once a week. It consisted of warm-up exercises, muscle strengthening, stretching, balancing, and self-administered massage to acupressure points. At the end of each PEP session, pamphlets with pictures illustrating the "exercise of the day" were given to the older residents of nursing homes as a tool to enhance their self-management skills. The control group received no training during the eight weeks. Upon completion of the PEP, the experimental group experienced a significantly greater reduction in pain intensity from 4.19 ± 2.25 (on an 11 point scale) to 2.67 ± 2.08, as compared to the control group (p < .05). In addition, the psychological well-being (happiness, loneliness, life satisfaction, and depression) of the experimental group was significantly improved (p < .05). Copyright © 2014 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

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.

Piquing Student Interest with Pharmacology: An Interdisciplinary Program Helps High School Students Learn Biology and Chemistry Principles

ERIC Educational Resources Information Center

Halpin, Myra J.; Hoeffler, Leanne; Schwartz-Bloom, Rochelle D.

2005-01-01

To help students learn science concepts, Pharmacology Education Partnership (PEP)--a science education program that incorporates relevant topics related to drugs and drug abuse into standard biology and chemistry curricula was developed. The interdisciplinary PEP curriculum provides six modules to teach biology and chemistry principles within the…

PEP Run Report for Integrated Test A, Caustic Leaching in UFP-VSL-T01A, Oxidative Leaching in UFP-VSL-T02A

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

Guzman-Leong, Consuelo E.; Bredt, Ofelia P.; Burns, Carolyn A.

2009-12-04

Pacific Northwest National Laboratory (PNNL) was tasked by Bechtel National Inc. (BNI) on the River Protection Project-Hanford Tank Waste Treatment and Immobilization Plant (RPP-WTP) project to perform research and development activities to resolve technical issues identified for the Pretreatment Facility (PTF). The Pretreatment Engineering Platform (PEP) was designed and constructed and operated as part of a plan to respond to issue M12, “Undemonstrated Leaching Processes.”(a) The PEP, located in the Process Engineering Laboratory-West (PDLW) located in Richland, Washington, is a 1/4.5-scale test platform designed to simulate the WTP pretreatment caustic leaching, oxidative leaching, ultrafiltration solids concentration, and slurry washing processes.more » The PEP replicates the WTP leaching processes using prototypic equipment and control strategies. The PEP also includes non-prototypic ancillary equipment to support the core processing.« less

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.

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

A community and culture-centered approach to developing effective cardiovascular health messages.

PubMed

Kandula, Namratha R; Khurana, Neerja R; Makoul, Gregory; Glass, Sara; Baker, David W

2012-10-01

Little is known about how best to target cardiovascular health promotion messages to minorities. This study describes key lessons that emerged from a community and culture-centered approach to developing a multimedia, coronary heart disease (CHD) patient education program (PEP) for medically underserved South Asian immigrants. The prototype PEP integrated the surface structures (e.g. language) and deeper structures (e.g. explanatory models (EMs), values) of South Asians' socio-cultural context. Seven focus groups and 13 individual interviews were used to investigate South Asians' reactions and obtain qualitative feedback after viewing the culturally targeted PEP. Qualitative data were organized into emergent thematic constructs. Participants (n=56) mean age was 51 years and 48 % were Hindi speakers. Community members had a strong, negative reaction to some of the targeted messages, "This statement is a bold attack. You are pin-pointing one community." Other important themes emerged from focus groups and interviews about the PEP: 1) it did not capture the community's heterogeneity; 2) did not sufficiently incorporate South Asians' EMs of CHD; and 3) did not address economic barriers to CHD prevention. Feedback was used to revise the PEP. A community and culture-centered approach to developing cardiovascular health promotion messages revealed tensions between the researcher's vantage point of "cultural targeting" and the community's perceptions and reactions to these messages. Engaging communities in every phase of message design, incorporating their EMs, recognizing community heterogeneity, and addressing economic and structural barriers, are critical steps to ensuring that health promotion messages reach their intended audience and achieve true cultural appropriateness.

Introducing leprosy post-exposure prophylaxis into the health systems of India, Nepal and Indonesia: a case study.

PubMed

Tiwari, A; Mieras, L; Dhakal, K; Arif, M; Dandel, S; Richardus, J H

2017-09-29

Leprosy has a wide range of clinical and socio-economic consequences. India, Indonesia and Nepal contribute significantly to the global leprosy burden. After integration, the health systems are pivotal in leprosy service delivery. The Leprosy Post Exposure Prophylaxis (LPEP) program is ongoing to investigate the feasibility of providing single dose rifampicin (SDR) as post-exposure prophylaxis (PEP) to the contacts of leprosy cases in various health systems. We aim to compare national leprosy control programs, and adapted LPEP strategies in India, Nepal and Indonesia. The purpose is to establish a baseline of the health system's situation and document the subsequent adjustment of LPEP, which will provide the context for interpreting the LPEP results in future. The study followed the multiple-case study design with single units of analysis. The data collection methods were direct observation, in-depth interviews and desk review. The study was divided into two phases, i.e. review of national leprosy programs and description of the LPEP program. The comparative analysis was performed using the WHO health system frameworks (2007). In all countries leprosy services including contact tracing is integrated into the health systems. The LPEP program is fully integrated into the established national leprosy programs, with SDR and increased documentation, which need major additions to standard procedures. PEP administration was widely perceived as well manageable, but the additional LPEP data collection was reported to increase workload in the first year. The findings of our study led to the recommendation that field-based leprosy research programs should keep health systems in focus. The national leprosy programs are diverse in terms of organizational hierarchy, human resource quantity and capacity. We conclude that PEP can be integrated into different health systems without major structural and personal changes, but provisions are necessary for the additional monitoring requirements.

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.

PepComposer: computational design of peptides binding to a given protein surface

PubMed Central

Obarska-Kosinska, Agnieszka; Iacoangeli, Alfredo; Lepore, Rosalba; Tramontano, Anna

2016-01-01

There is a wide interest in designing peptides able to bind to a specific region of a protein with the aim of interfering with a known interaction or as starting point for the design of inhibitors. Here we describe PepComposer, a new pipeline for the computational design of peptides binding to a given protein surface. PepComposer only requires the target protein structure and an approximate definition of the binding site as input. We first retrieve a set of peptide backbone scaffolds from monomeric proteins that harbor the same backbone arrangement as the binding site of the protein of interest. Next, we design optimal sequences for the identified peptide scaffolds. The method is fully automatic and available as a web server at http://biocomputing.it/pepcomposer/webserver. PMID:27131789

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.

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.

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

Technical Basis of Scaling Relationships for the Pretreatment Engineering Platform

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

Kuhn, William L.; Arm, Stuart T.; Huckaby, James L.

Pacific Northwest National Laboratory has been tasked by Bechtel National Inc. (BNI) on the River Protection Project-Waste Treatment Plant (RPP-WTP) project to perform research and development activities. The Pretreatment Engineering Platform (PEP) is being designed and constructed as part of a plan to respond to an issue raised by the WTP External Flowsheet Review Team (EFRT) entitled “Undemonstrated Leaching Processes” and numbered M12. The PEP replicates the WTP leaching process using prototypic equipment and control strategies. The approach for scaling PEP performance data to predict WTP performance is critical to the successful resolution of the EFRT issue. This report describesmore » the recommended PEP scaling approach, PEP data interpretation and provides recommendations on test conduct and data requirements.« less

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

Edco-tourism; A Coastal Management Program to Improve Social Economics

NASA Astrophysics Data System (ADS)

Rakhmanissazly, Arsi; Intan Permatasari, Anggun; Peranginangin, Ely Chandra

2018-02-01

Coastal erosion is a natural process even in pristine environments. Mangrove is tropical coastal vegetation that may prevent and controls the soil erosion. As the longest coastline country in the world, Indonesia has great ecological potential of mangrove. Sadly, according to Food and Agriculture Organization (FAO) since 2007 Indonesia has lost 40% of mangrove forest because of deforestation for the last three decades. Langkat regency placed as the most destructive mangrove forests in North Sumatera about 25% of total area hectares due to severe damage. Green Belt Lubuk Kertang is a Corporate Social Responsibility (CSR) program held by PT PERTAMINA EP Asset 1 Pangkalan Susu Field (PEP) aims to overcome deforestation problem by implementing the concept of edco-tourism mangrove. Edco-tourism is a concept that combines educational and environmental as the basis of local tourism management. By implementing this concept PEP may create multiplier effect not only by saving environmental issues but also socio - economical for local communities. This study shows the impacts of the program for some aspects. By using Shannon - Wienner indicator shows the biodiversity index has increased since the program began three years ago. Not only biodiversity number but also group’s income of local community increase obtained from the retributions. Furthermore, this program is social investment for PEP to engage company - community relations during operational by gaining license to operate. PEP attempt to implement integrated coastal zone management to balance environmental, technical, socio - economic and recreational objectives, into an eco - coastal sustainable system.

Effectiveness of adding voluntary pelvic floor muscle contraction to a Pilates exercise program: an assessor-masked randomized controlled trial.

PubMed

Torelli, Luiza; de Jarmy Di Bella, Zsuzsanna Ilona Katalin; Rodrigues, Claudinei Alves; Stüpp, Liliana; Girão, Manoel João Batista Castello; Sartori, Marair Gracio Ferreira

2016-11-01

The purpose of this study was to evaluate the effectiveness of adding voluntary pelvic floor muscle contraction (PFMC) to a Pilates exercise program in sedentary nulliparous women. Fifty-seven healthy nulliparous and physically inactive women were randomized to a Pilates exercise program (PEP) with or without PFMC. Forty-eight women concluded this study (24 participants for each group). Each woman was evaluated before and after the PEP, by a physiotherapist and an urogynecologist (UG). Neither of the professionals was revealed to them. This physiotherapist measured their pelvic floor muscle strength by using both a perineometer (Peritron) and vaginal palpation (Oxford Scale). The UG, who performed 3D perineal ultrasound examinations, collected their data and evaluated the results for pubovisceral muscle thickness and the levator hiatus area (LA). Both professionals were blinded to the group allocation. The protocol for both groups consisted of 24 bi-weekly 1-h individual sessions of Pilates exercises, developed by another physiotherapist who specializes in PFM rehabilitation and the Pilates technique. The PEP+ PFMC group showed significantly greater strength improvements than the PEP group when comparing the Oxford scale, vaginal pressure and pubovisceral muscle thickness during contraction measurements at baseline and post-treatment. Our findings suggest that adding a voluntary PFMC to a Pilates exercise program is more effective than Pilates alone in improving PFM strength in sedentary nulliparous women.

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

Effects of a Physical Exercise Program (PEP-Aut) on Autistic Children's Stereotyped Behavior, Metabolic and Physical Activity Profiles, Physical Fitness, and Health-Related Quality of Life: A Study Protocol.

PubMed

Ferreira, José Pedro; Andrade Toscano, Chrystiane Vasconcelos; Rodrigues, Aristides Machado; Furtado, Guilherme Eustaquio; Barros, Mauro Gomes; Wanderley, Rildo Souza; Carvalho, Humberto Moreira

2018-01-01

Physical exercise has shown positive effects on symptomatology and on the reduction of comorbidities in population with autism spectrum disorder (ASD). However, there is still no consensus about the most appropriate exercise intervention model for children with ASD. The physical exercise program for children with autism (PEP-Aut) protocol designed allow us to (i) examine the multivariate associations between ASD symptoms, metabolic profile, physical activity level, physical fitness, and health-related quality of life of children with ASD; (ii) assess the effects of a 40-week exercise program on all these aspects of children with ASD. The impact of the exercise program will be assessed based on the sequence of the two phases. Phase 1 is a 12-week cross-sectional study assessing the symptomatology, metabolic profile, physical fitness and physical activity levels, socioeconomic status profile, and health-related quality of life of participants. This phase is the baseline of the following phase. Phase 2 is a 48-week intervention study with a 40-week intervention with exercise that will take place in a specialized center for children with ASD in the city of Maceió-Alagoas, Brazil. The primary outcomes will be change in the symptomatic profile and the level of physical activity of children. Secondary outcomes will be anthropometric and metabolic profiles, aerobic function, grip strength, socioeconomic status, and health-related quality of life. The study will provide critical information on the efficacy of exercise for children with ASD and help guide design and delivery of future programs.

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.

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.

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.

Laboratory Tests on Post-Filtration Precipitation in the WTP Pretreatment Process

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

Russell, Renee L.; Peterson, Reid A.; Rinehart, Donald E.

Pacific Northwest National Laboratory (PNNL) has been tasked by Bechtel National Inc. (BNI) on the River Protection Project-Hanford Tank Waste Treatment and Immobilization Plant (RPP-WTP) project to perform research and development activities to resolve technical issues identified for the Pretreatment Facility (PTF). The Pretreatment Engineering Platform (PEP) was designed, constructed, and operated as part of a plan to respond to issue M12, "Undemonstrated Leaching Processes," of the External Flowsheet Review Team (EFRT) issue response plan (Barnes et al. 2006). The PEP is a 1/4.5-scale test platform designed to simulate the WTP pretreatment caustic leaching, oxidative leaching, ultrafiltration solids concentration, andmore » slurry washing processes. The PEP replicates the WTP leaching processes using prototypic equipment and control strategies. A simplified flow diagram of the PEP system is shown in Figure 1.1. Two operating scenarios are currently being evaluated for the ultrafiltration process (UFP) and leaching operations. The first scenario has caustic leaching performed in the UFP-2 ultrafiltration feed vessels (i.e., vessel UFP-VSL-T02A in the PEP; and vessels UFP-VSL-00002A and B in the WTP PTF). The second scenario has caustic leaching conducted in the UFP-1 ultrafiltration feed preparation vessels (i.e., vessels UFP-VSL-T01A and B in the PEP; vessels UFP-VSL-00001A and B in the WTP PTF).« less

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.

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

Blended Infant Massage-Parenting Enhancement Program on Recovering Substance-Abusing Mothers' Parenting Stress, Self-Esteem, Depression, Maternal Attachment, and Mother-Infant Interaction.

PubMed

Porter, Luz S; Porter, Brian O; McCoy, Virginia; Bango-Sanchez, Vivian; Kissel, Bonnie; Williams, Marjorie; Nunnewar, Sachin

2015-12-01

This study aimed to determine whether a blended Infant Massage-Parenting Enhancement Program (IMPEP) improved maternal psychosocial health outcomes (parenting stress, depressive symptoms, self-esteem, maternal attachment) and maternal-infant interaction among substance-addicted mothers (SAMs) actively engaged in outpatient rehabilitation. Designed as a randomized, three-group controlled trial testing two levels of psychoeducational intervention (IMPEP vs. PEP) and a control group (standard care parenting resources), the study was conducted in two substance abuse centers in southeast Florida on a convenience sample of 138 recovering SAM-infant pairs. IMPEP or PEP classes were held weekly on Weeks 2-5, with data collected at baseline (Week 1), Week 6, and Week 12 via structured interviews, observation (Observation Checklist on Maternal-Infant Interaction), and self-administered questionnaires (Abidin Parenting Stress Index, Beck Depression Inventory, Rosenberg Self-Esteem Scale, Muller's Maternal Attachment Inventory), analyzed descriptively and inferentially using Kruskall-Wallis analysis of variance and post hoc Wilcoxon rank sum and Mann-Whitney U tests. Both IMPEP and PEP groups had significantly increased Parenting Stress Index scores (decreased parenting stress) and decreased Beck Depression Inventory scores (decreased depressive symptoms) compared to controls at Week 12, whereas there were no clinically meaningful differences among study groups in Rosenberg Self-Esteem Scale, Muller's Maternal Attachment Inventory, or Observation Checklist on Maternal-Infant Interaction scores. Only the IMPEP group showed significant improvements in both psychological and physical (waist-hip ratio) measures of parenting stress over time. The findings suggest that infant massage blended into a structured parenting program has value-added effects in decreasing parenting stress and maternal depressive symptoms, but not on SAM's self-esteem, attachment, or maternal-infant interaction. Copyright © 2015. Published by Elsevier B.V.

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.

Sustainable Eco Coastal Development Through Corporate Social Responsibility (CSR) Program

NASA Astrophysics Data System (ADS)

Rakhmanissazly, Arsi; Mursito Ardy, Yong; Abdullah

2017-02-01

Besides technical problems the company’s operational constraints that may effect high deficiency for the company is the company - community conflicts. Company - community conflict can also arise depends on the geographic conditions and characteristics of the community itself. Some studies has show that coastal community have higher level of social risk when compared to non-coastal community. Also, the coastal community ussually only rely on what sea provides as their main livelihood. Because of the level of education still contemtible the community couldn’t optimized the potential of their own area. Corporate Social Responsibility (CSR) har emerged as an important approach for addressing the social and environmental impact of company activities. Through CSR program, PT Pertamina EP Asset 3 Tambun Field (PEP) try to form value integration by utilizing resources from the community and the company by making sustainable eco - coastal living in Desa Tambaksari, Karawang, one of PEP working area. Using sustainable livelihood approach begin with compiling data by doing social mapping PEP has initiate the area to becoming Fish Processing Industry Centre. By implementing PDCA in every steps of the program, PEP has multiplied some other programs such as Organic Fish Feed Processing, Seaweed Farming and Waste Bank for Green Coastal Village. These program is PEP’s effort to create a sustainability environment by enhancing the community’s potentials as well as resolving social problems around Tambaksari. The most important result besides getting our license to operate from the community, is the community itself can grow into an eco coastal sustainable system.

STEM Pathways: Examining Persistence in Rigorous Math and Science Course Taking

ERIC Educational Resources Information Center

Ashford, Shetay N.; Lanehart, Rheta E.; Kersaint, Gladis K.; Lee, Reginald S.; Kromrey, Jeffrey D.

2016-01-01

From 2006 to 2012, Florida Statute §1003.4156 required middle school students to complete electronic personal education planners (ePEPs) before promotion to ninth grade. The ePEP helped them identify programs of study and required high school coursework to accomplish their postsecondary education and career goals. During the same period Florida…

Defining and Measuring Parenting for Educational Success: A Critical Discourse Analysis of the Parent Education Profile

ERIC Educational Resources Information Center

Prins, Esther; Toso, Blaire Willson

2008-01-01

The Parent Education Profile (PEP) is an instrument used by family literacy programs to rate parents' support for children's literacy development. This article uses Critical Discourse Analysis to examine how the PEP constructs the ideal parent, the text's underlying assumptions about parenting and education, and its ideological effects. The…

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

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 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.

Effects of a Physical Exercise Program (PEP-Aut) on Autistic Children’s Stereotyped Behavior, Metabolic and Physical Activity Profiles, Physical Fitness, and Health-Related Quality of Life: A Study Protocol

PubMed Central

Ferreira, José Pedro; Andrade Toscano, Chrystiane Vasconcelos; Rodrigues, Aristides Machado; Furtado, Guilherme Eustaquio; Barros, Mauro Gomes; Wanderley, Rildo Souza; Carvalho, Humberto Moreira

2018-01-01

Physical exercise has shown positive effects on symptomatology and on the reduction of comorbidities in population with autism spectrum disorder (ASD). However, there is still no consensus about the most appropriate exercise intervention model for children with ASD. The physical exercise program for children with autism (PEP-Aut) protocol designed allow us to (i) examine the multivariate associations between ASD symptoms, metabolic profile, physical activity level, physical fitness, and health-related quality of life of children with ASD; (ii) assess the effects of a 40-week exercise program on all these aspects of children with ASD. The impact of the exercise program will be assessed based on the sequence of the two phases. Phase 1 is a 12-week cross-sectional study assessing the symptomatology, metabolic profile, physical fitness and physical activity levels, socioeconomic status profile, and health-related quality of life of participants. This phase is the baseline of the following phase. Phase 2 is a 48-week intervention study with a 40-week intervention with exercise that will take place in a specialized center for children with ASD in the city of Maceió-Alagoas, Brazil. The primary outcomes will be change in the symptomatic profile and the level of physical activity of children. Secondary outcomes will be anthropometric and metabolic profiles, aerobic function, grip strength, socioeconomic status, and health-related quality of life. The study will provide critical information on the efficacy of exercise for children with ASD and help guide design and delivery of future programs. PMID:29552551

Next Generation * Natural Gas (NG)2 Information Requirements--Executive Summary

EIA Publications

2000-01-01

The Energy Information Administration (EIA) has initiated the Next Generation * Natural Gas (NG)2 project to design and implement a new and comprehensive information program for natural gas to meet customer requirements in the post-2000 time frame.

The Application of Behavior Change Theory to Family-Based Services: Improving Parent Empowerment in Children's Mental Health

ERIC Educational Resources Information Center

Olin, S. Serene; Hoagwood, Kimberly E.; Rodriguez, James; Ramos, Belinda; Burton, Geraldine; Penn, Marlene; Crowe, Maura; Radigan, Marleen; Jensen, Peter S.

2010-01-01

We describe the development of a parent empowerment program (PEP) using a community-based participatory research approach. In collaboration with a group of dedicated family advocates working with the Mental Health Association of New York City and state policy makers, academic researchers took an iterative approach to crafting and refining PEP to…

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…

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

Program BB for calculation of PEP corrector strengths for beam-bump excitation

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

Kheifets, S.

Excitation of a beam-bump (BB) can be effectively used for a number of goals. Since BB is sensitive only to perturbations of elements which are located inside it, errors and their consequencies spaced separately can be singled out and studied one by one. This technique in principle can be used to study the uniformity of the quadrupole distribution around the ring, the beam stays clear size of the machine at different locations, the polarity and probably even the strength of sextupole magnets, alignments of different monitors, etc. It can be used also to increase the beam cross section if thatmore » appears to be desirable. Design of PEP correctors does not allow to use them for excitation of a halfwave BB. The minimum number of correctors which can be used in this situation is three. The situation for horizontal plane is aggravated still more since most of horizontal correctors are hooked in pairs. The presence of sextupole magnets interlacing the correctors makes it necessary to use iterative procedure to find the corrector strengths for BB, since a perturbed orbit is influenced by a field of a sextupole magnet which in turn depends on the perturbed orbit value in the sextupole. Since the strength of sextupoles are rather small as the first guess of corrector strengths for iterative procedure can be taken the linear solution neglecting sextupoles. This paper describes the program BB itself, and some results of calculations with BB for PEP. 3 refs., 4 figs., 6 tabs.« less

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.

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.

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.

75 FR 34891 - Carol M. White Physical Education Program; Catalog of Federal Domestic Assistance (CFDA) Number...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-18

...The Assistant Deputy Secretary for Safe and Drug-Free Schools announces priorities, requirements, and definitions for the Carol M. White Physical Education Program (PEP). The Assistant Deputy Secretary may use one or more of these priorities, requirements, and definitions for competitions in fiscal year (FY) 2010 and later years. We take this action to align PEP projects more closely with best practices and research related to improving children's health and fitness, to improve students' physical activity, and to improve students' ability to meet their State physical education standards.

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

Economic evaluation of an oral rabies vaccination program for control of a domestic dog-coyote rabies epizootic: 1995-2006.

PubMed

Shwiff, Stephanie A; Kirkpatrick, Katy N; Sterner, Ray T

2008-12-01

To conduct a benefit-cost analysis of the results of the domestic dog and coyote (DDC) oral rabies vaccine (ORV) program in Texas from 1995 through 2006 by use of fiscal records and relevant public health data. Retrospective benefit-cost analysis. Procedures-Pertinent economic data were collected in 20 counties of south Texas affected by a DDC-variant rabies epizootic. The costs and benefits afforded by a DDC ORV program were then calculated. Costs were the total expenditures of the ORV program. Benefits were the savings associated with the number of potentially prevented human postexposure prophylaxis (PEP) treatments and animal rabies tests for the DDC-variant rabies virus in the epizootic area and an area of potential disease expansion. Total estimated benefits of the program approximately ranged from $89 million to $346 million, with total program costs of $26,358,221 for the study period. The estimated savings (ie, damages avoided) from extrapolated numbers of PEP treatments and animal rabies tests yielded benefit-cost ratios that ranged from 3.38 to 13.12 for various frequen-cies of PEP and animal testing. In Texas, the use of ORV stopped the northward spread and led to the progressive elimination of the DDC variant of rabies in coyotes (Canis latrans). The decision to implement an ORV program was cost-efficient, although many unknowns were involved in the original decision, and key economic variables were identified for consideration in future planning of ORV programs.

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.

A Comparison of Factors that Influence the Quality of PEPs in Title I Schools

ERIC Educational Resources Information Center

Williams, Connie Jean

2009-01-01

The purpose of this study was to investigate the relationship between school-based organizational structures that support teachers' development of Personalized Education Plans (PEPs) and their quality as written for third through fifth grade students in each of two Title I schools. A causal comparative design was implemented. Teachers' responses…

Word Frequency Analysis MOS: 95C. Skill Levels 1 & 2.

DTIC Science & Technology

1981-05-01

EMTAEEN I Bt.ANKST 2 BLANK-. S 1 SLIND I BREA~ CNCD I EGICK I Of I flf.NG 2 BR~OKE N 1 BULBS t BLNK 2 aUtK. 2 BUT 14 By 3 C 9 C ,;LL I CALLS 4 CAN 1 C’O0... POLICIES 4 PCPULATION I PCta 7 PEP7.3m 3 PCSIT ION I POSSIBLE I FC!TS I I’!’!P .q I P.,FPsCRIBED 2 PkEt NCE I PRESENT 1 ppVi l I PR Iok 54 PR I SCNER

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).

Power Extension Package (PEP) system definition extension, orbital service module systems analysis study. Volume 4: PEP functional specification

NASA Technical Reports Server (NTRS)

1979-01-01

The functional, performance, design, and test requirements for the Orbiter power extension package and its associated ground support equipment are defined. Both government and nongovernment standards and specifications are cited for the following subsystems: electrical power, structural/mechanical, avionics, and thermal control. Quality control assurance provisions and preparation for delivery are also discussed.

Power Extension Package (PEP) system definition extension, orbital service module systems analysis study. Volume 7: PEP logistics and training plan requirements

NASA Technical Reports Server (NTRS)

1979-01-01

Recommendations for logistics activities and logistics planning are presented based on the assumption that a system prime contractor will perform logistics functions to support all program hardware and will implement a logistics system to include the planning and provision of products and services to assure cost effective coverage of the following: maintainability; maintenance; spares and supply support; fuels; pressurants and fluids; operations and maintenance documentation training; preservation, packaging and packing; transportation and handling; storage; and logistics management information reporting. The training courses, manpower, materials, and training aids required will be identified and implemented in a training program.

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

Effects of a short-term parental education program on childhood atopic dermatitis: a randomized controlled trial.

PubMed

Futamura, Masaki; Masuko, Ikuyo; Hayashi, Keiichi; Ohya, Yukihiro; Ito, Komei

2013-01-01

Parental education is important in managing childhood atopic dermatitis (AD). We evaluated the long-term effects of a 2-day parental education program (PEP) on childhood AD. In an investigator-blinded, randomized controlled trial, 59 children age 6 months to 6 years with moderate to severe AD and their mothers were recruited in Japan. Participants were given a booklet about AD and received conventional treatment alone or in combination with a 2-day PEP comprising three lectures, three practical sessions, and a group discussion. The primary outcome was evaluation of eczema severity using SCORing Atopic Dermatitis (SCORAD) at 6 months. Secondary outcomes included changes in symptom scores, amount of corticosteroid used, parental quality of life as determined according to the Dermatitis Family Impact questionnaire, and change in parental anxiety regarding the use of corticosteroids in their children. Participants in the PEP group had a significantly lower SCORAD score than those in the control group at 6 months (mean difference 10.0, 95% confidence interval [CI] = 2.3-17.7, p = 0.01) and objective SCORAD score (mean difference 7.1, 95% CI = 0.8-13.5, p = 0.03). The sleeplessness symptom score (mean difference 1.6, 95% CI = 0.0-3.1, p = 0.048) and corticosteroid anxiety score (p = 0.02) in the PEP group were significantly better than in the control group at 6 months. There was no significant difference between groups in the amount of corticosteroid used or quality of life. The PEP had positive long-term effects on eczema severity and parental anxiety about corticosteroid usage. © 2013 Wiley Periodicals, Inc.

Computational tools and lattice design for the PEP-II B-Factory

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

Cai, Y.; Irwin, J.; Nosochkov, Y.

1997-02-01

Several accelerator codes were used to design the PEP-II lattices, ranging from matrix-based codes, such as MAD and DIMAD, to symplectic-integrator codes, such as TRACY and DESPOT. In addition to element-by-element tracking, we constructed maps to determine aberration strengths. Furthermore, we have developed a fast and reliable method (nPB tracking) to track particles with a one-turn map. This new technique allows us to evaluate performance of the lattices on the entire tune-plane. Recently, we designed and implemented an object-oriented code in C++ called LEGO which integrates and expands upon TRACY and DESPOT. {copyright} {ital 1997 American Institute of Physics.}

Computational tools and lattice design for the PEP-II B-Factory

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

Cai Yunhai; Irwin, John; Nosochkov, Yuri

1997-02-01

Several accelerator codes were used to design the PEP-II lattices, ranging from matrix-based codes, such as MAD and DIMAD, to symplectic-integrator codes, such as TRACY and DESPOT. In addition to element-by-element tracking, we constructed maps to determine aberration strengths. Furthermore, we have developed a fast and reliable method (nPB tracking) to track particles with a one-turn map. This new technique allows us to evaluate performance of the lattices on the entire tune-plane. Recently, we designed and implemented an object-oriented code in C++ called LEGO which integrates and expands upon TRACY and DESPOT.

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

PEP Support Laboratory Leaching and Permeate Stability Tests

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

Russell, Renee L.; Peterson, Reid A.; Rinehart, Donald E.

2009-09-25

Pacific Northwest National Laboratory (PNNL) has been tasked by Bechtel National Inc. (BNI) on the River Protection Project-Hanford Tank Waste Treatment and Immobilization Plant (RPP-WTP) project to perform research and development activities to resolve technical issues identified for the Pretreatment Facility (PTF). The Pretreatment Engineering Platform (PEP) was designed, constructed, and operated as part of a plan to respond to issue M12, "Undemonstrated Leaching Processes," of the External Flowsheet Review Team (EFRT) issue response plan.( ) The PEP is a 1/4.5-scale test platform designed to simulate the WTP pretreatment caustic leaching, oxidative leaching, ultrafiltration solids concentration, and slurry washing processes.more » The PEP replicates the WTP leaching processes using prototypic equipment and control strategies. A simplified flow diagram of the PEP system is shown in Figure 1.1. Two operating scenarios are currently being evaluated for the ultrafiltration process (UFP) and leaching operations. The first scenario has caustic leaching performed in the UFP-2 ultrafiltration feed vessels (i.e., vessel UFP-VSL-T02A in the PEP and vessels UFP-VSL-00002A and B in the WTP PTF). The second scenario has caustic leaching conducted in the UFP-1 ultrafiltration feed preparation vessels (i.e., vessels UFP-VSL-T01A and B in the PEP and vessels UFP-VSL-00001A and B in the WTP PTF). In both scenarios, 19-M sodium hydroxide solution (NaOH, caustic) is added to the waste slurry in the vessels to leach solid aluminum compounds (e.g., gibbsite, boehmite). Caustic addition is followed by a heating step that uses direct injection of steam to accelerate the leach process. Following the caustic leach, the vessel contents are cooled using vessel cooling jackets and/or external heat exchangers. The main difference between the two scenarios is that for leaching in UFP-VSL-T01A and B, the 19-M NaOH is added to un-concentrated waste slurry (3 to 8 wt% solids), while for leaching in UFP-VSL-T02A, the slurry is concentrated to nominally 20 wt% solids using cross-flow ultrafiltration before adding caustic.« less

Solid-phase extraction in combination with dispersive liquid-liquid microextraction and ultra-high performance liquid chromatography-tandem mass spectrometry analysis: the ultra-trace determination of 10 antibiotics in water samples.

PubMed

Liang, Ning; Huang, Peiting; Hou, Xiaohong; Li, Zhen; Tao, Lei; Zhao, Longshan

2016-02-01

A novel method, solid-phase extraction combined with dispersive liquid-liquid microextraction (SPE-DLLME), was developed for ultra-preconcentration of 10 antibiotics in different environmental water samples prior to ultra-high performance liquid chromatography-tandem mass spectrometry detection. The optimized results were obtained as follows: after being adjusted to pH 4.0, the water sample was firstly passed through PEP-2 column at 10 mL min(-1), and then methanol was used to elute the target analytes for the following steps. Dichloromethane was selected as extraction solvent, and methanol/acetonitrile (1:1, v/v) as dispersive solvent. Under optimal conditions, the calibration curves were linear in the range of 1-1000 ng mL(-1) (sulfamethoxazole, cefuroxime axetil), 5-1000 ng mL(-1) (tinidazole), 10-1000 ng mL(-1) (chloramphenicol), 2-1000 ng mL(-1) (levofloxacin oxytetracycline, doxycycline, tetracycline, and ciprofloxacin) and 1-400 ng mL(-1) (sulfadiazine) with a good precision. The LOD and LOQ of the method were at very low levels, below 1.67 and 5.57 ng mL(-1), respectively. The relative recoveries of the target analytes were in the range from 64.16% to 99.80% with relative standard deviations between 0.7 and 8.4%. The matrix effect of this method showed a great decrease compared with solid-phase extraction and a significant value of enrichment factor (EF) compared with dispersive liquid-liquid microextraction. The developed method was successfully applied to the extraction and analysis of antibiotics in different water samples with satisfactory results.

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

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.

The Physics Entrepreneurship Program - 11 Years of Teaching and Practicing Innovation and Entrepreneurship to Graduate Students and Beyond

NASA Astrophysics Data System (ADS)

Caner, Edward

2012-02-01

The Physics Entrepreneurship Program (PEP) at Case Western Reserve University is a MS in Physics, Entrepreneurship Track that teaches physics, business, and innovation. PEP admitted its first class in 2000 with the original goal of empowering physicists to be successful entrepreneurs. Since Y2K, much has happened in the world's economies and markets, and we have shifted our goals to include a strong innovation component. For instance, our metrics have changed from ``companies created'' to ``capital raised by our students'' (i.e., grants and investment in innovation), which allows our students to participate in an apprentice-type relationship with a more experienced entrepreneur before venturing out on their own (which could take many years before they are ready). We will describe the program, how we teach innovation, student and alumni activities and how difficult it is to operate a sustainable graduate program in this arena.

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

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.

IMMEDIATE AND FOLLOW-UP EFFECTS OF A POSTURE EDUCATION PROGRAM FOR ELEMENTARY SCHOOL STUDENTS

PubMed Central

dos Santos, Natália Brites; Sedrez, Juliana Adami; Candotti, Cláudia Tarragô; Vieira, Adriane

2017-01-01

ABSTRACT Objective: To assess the short- and medium-term effects of the posture education program (PEP) for students of elementary school regarding theoretical knowledge and posture during activities of daily living (ADLs). Methods: The sample consisted of 38 students (aged 8-12 years) in the third grade of elementary school in Porto Alegre, Rio Grande do Sul (Southern Brazil). The children were evaluated in three moments: prior to attending the PEP (pretest); after attending the PEP (post-test); and five months after the conclusion of the PEP, immediately after a learning review of four lessons (five months follow-up). The posture during ADLs and the theoretical knowledge about spine and body posture were assessed, based on specific instruments (layout for assessing the dynamic posture - LADy; and questionnaire). The Friedman test, post hoc Wilcoxon test, and Bonferroni correction were applied to identify the differences among the evaluative moments, as they are statistically significant at α<0.05. Results: No statistically significant difference was found between the post-test and follow-up concerning the theoretical knowledge. In addition, no statistically significant difference was found between post-test and follow-up in relation to ADLs; however, the performance of students was higher in the post-test and follow-up, when compared with the pretest. Conclusions: Immediately after the PEP’s conclusion, the students improved their posture in ADLs. These positive effects and the theoretical knowledge were retained in the follow-up (after the review lessons). PMID:28977326

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.

School-based prevention of depressive symptoms: A randomized controlled study of the effectiveness and specificity of the Penn Resiliency Program.

PubMed

Gillham, Jane E; Reivich, Karen J; Freres, Derek R; Chaplin, Tara M; Shatté, Andrew J; Samuels, Barbra; Elkon, Andrea G L; Litzinger, Samantha; Lascher, Marisa; Gallop, Robert; Seligman, Martin E P

2007-02-01

The authors investigated the effectiveness and specificity of the Penn Resiliency Program (PRP; J. E. Gillham, L. H. Jaycox, K. J. Reivich, M. E. P. Seligman, & T. Silver, 1990), a cognitive-behavioral depression prevention program. Children (N = 697) from 3 middle schools were randomly assigned to PRP, Control (CON), or the Penn Enhancement Program (PEP; K. J. Reivich, 1996; A. J. Shatté, 1997), an alternate intervention that controls for nonspecific intervention ingredients. Children's depressive symptoms were assessed through 3 years of follow-up. There was no intervention effect on average levels of depressive symptoms in the full sample. Findings varied by school. In 2 schools, PRP significantly reduced depressive symptoms across the follow-up relative to both CON and PEP. In the 3rd school, PRP did not prevent depressive symptoms. The authors discuss the findings in relation to previous research on PRP and the dissemination of prevention programs. Copyright 2007 APA, all rights reserved.

School-Based Prevention of Depressive Symptoms: A Randomized Controlled Study of the Effectiveness and Specificity of the Penn Resiliency Program

PubMed Central

Gillham, Jane E.; Reivich, Karen J.; Freres, Derek R.; Chaplin, Tara M.; Shatté, Andrew J.; Samuels, Barbra; Elkon, Andrea G. L.; Litzinger, Samantha; Lascher, Marisa; Gallop, Robert; Seligman, Martin E. P.

2015-01-01

The authors investigated the effectiveness and specificity of the Penn Resiliency Program (PRP; J. E. Gillham, L. H. Jaycox, K. J. Reivich, M. E. P. Seligman, & T. Silver, 1990), a cognitive–behavioral depression prevention program. Children (N = 697) from 3 middle schools were randomly assigned to PRP, Control (CON), or the Penn Enhancement Program (PEP; K. J. Reivich, 1996; A. J. Shatté, 1997), an alternate intervention that controls for nonspecific intervention ingredients. Children’s depressive symptoms were assessed through 3 years of follow-up. There was no intervention effect on average levels of depressive symptoms in the full sample. Findings varied by school. In 2 schools, PRP significantly reduced depressive symptoms across the follow-up relative to both CON and PEP. In the 3rd school, PRP did not prevent depressive symptoms. The authors discuss the findings in relation to previous research on PRP and the dissemination of prevention programs. PMID:17295559

BPM Breakdown Potential in the PEP-II B-factory Storage Ring Collider

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

Weathersby, Stephen; Novokhatski, Alexander; /SLAC

2010-02-10

High current B-Factory BPM designs incorporate a button type electrode which introduces a small gap between the button and the beam chamber. For achievable currents and bunch lengths, simulations indicate that electric potentials can be induced in this gap which are comparable to the breakdown voltage. This study characterizes beam induced voltages in the existing PEP-II storage ring collider BPM as a function of bunch length and beam current.

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.

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

State Education Department: Security over Pupil Evaluation Program and Program Evaluation Test Materials Needs Improvement. Report 91-S-2.

ERIC Educational Resources Information Center

New York State Office of the Comptroller, Albany.

Findings of an audit of the New York State Education Department's procedures to maintain security over Pupil Evaluation Program (PEP) and Program Evaluation Test (PET) examination materials are presented in this report. The audit sought to determine whether the department's security procedures adequately prevented unauthorized access to exam…

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.

Lessons Learned in Student Venture Creation

NASA Astrophysics Data System (ADS)

Caner, Edward

The Physics Entrepreneurship Master's Program (PEP) at Case Western Reserve University is now in its 15th year of operation. PEP is a 27 credit-hour Master of Science in Physics, Entrepreneurship Track. The curriculum can be tailored to the needs of each student. Coursework consists of graduate-level classes in science, business, intellectual property law, and innovation. A master's thesis is required that is based on a real-world project in innovation or entrepreneurship within an existing company or startup (possibly the student's). PEP faculty help students connect with mentors, advisors, partners, funding sources and job opportunities. In this talk I will chronicle several pitfalls that we have encountered with our ''real world'' student projects and start-up businesses, several of which met their complete demise despite showing great promise for success. I will discuss how we have learned to avoid most of these pitfalls by taking surprisingly simple actions.

Preventing Adolescents' Externalizing and Internalizing Symptoms: Effects of the Penn Resiliency Program

ERIC Educational Resources Information Center

Cutuli, J. J.; Gillham, Jane E.; Chaplin, Tara M.; Reivich, Karen J.; Seligman, Martin E. P.; Gallop, Robert J.; Abenavoli, Rachel M.; Freres, Derek R.

2013-01-01

This study reports secondary outcome analyses from a past study of the Penn Resiliency Program (PRP), a cognitive-behavioral depression prevention program for middle-school aged children. Middle school students (N = 697) were randomly assigned to PRP, PEP (an alternate intervention), or control conditions. Gillham et al., (2007) reported analyses…

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.

Human rabies surveillance and control in China, 2005-2012.

PubMed

Song, Miao; Tang, Qing; Rayner, Simon; Tao, Xiao-Yan; Li, Hao; Guo, Zhen-Yang; Shen, Xin-Xin; Jiao, Wen-Tao; Fang, Wei; Wang, Jun; Liang, Guo-Dong

2014-04-18

Rabies reemerged in China during the 1990s with a gradual increase in the number and geographical dispersion of cases. As a consequence, a national surveillance program was introduced in 2005 to investigate the outbreak in terms of vaccination coverage, PEP treatment, and geographical and social composition. The surveillance program was coordinated at the national level by the Chinese Center for Disease Control (CCDC) with data collected by regional health centres and provincial CCDCs, and from other official sources. Various statistical and multivariate analysis techniques were then used to evaluate the role and significance of implemented policies and strategies related to rabies prevention and control over this period. From 2005-2012, 19,221 cases were reported across 30 provinces, but these primarily occurred in rural areas of southern and eastern China, and were predominantly associated with farmers, students and preschool children. In particular, detailed analysis of fatalities reported from 2010 to 2011 shows they were associated with very low rates of post exposure treatment compared to the cases with standard PEP. Nevertheless, regulation of post-exposure prophylaxis quality, together with improved management and vaccination of domesticated animals, has improved prevention and control of rabies. The various control policies implemented by the government has played a key role in reducing rabies incidences in China. However, level of PEP treatment varies according to sex, age, degree and site of exposure, as well as the source of infection. Regulation of PEP quality together with improved management and vaccination of domesticated animals have also helped to improve prevention and control of rabies.

Human rabies surveillance and control in China, 2005–2012

PubMed Central

2014-01-01

Background Rabies reemerged in China during the 1990s with a gradual increase in the number and geographical dispersion of cases. As a consequence, a national surveillance program was introduced in 2005 to investigate the outbreak in terms of vaccination coverage, PEP treatment, and geographical and social composition. Methods The surveillance program was coordinated at the national level by the Chinese Center for Disease Control (CCDC) with data collected by regional health centres and provincial CCDCs, and from other official sources. Various statistical and multivariate analysis techniques were then used to evaluate the role and significance of implemented policies and strategies related to rabies prevention and control over this period. Results From 2005–2012, 19,221 cases were reported across 30 provinces, but these primarily occurred in rural areas of southern and eastern China, and were predominantly associated with farmers, students and preschool children. In particular, detailed analysis of fatalities reported from 2010 to 2011 shows they were associated with very low rates of post exposure treatment compared to the cases with standard PEP. Nevertheless, regulation of post-exposure prophylaxis quality, together with improved management and vaccination of domesticated animals, has improved prevention and control of rabies. Conclusions The various control policies implemented by the government has played a key role in reducing rabies incidences in China. However, level of PEP treatment varies according to sex, age, degree and site of exposure, as well as the source of infection. Regulation of PEP quality together with improved management and vaccination of domesticated animals have also helped to improve prevention and control of rabies. PMID:24742224

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

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

LEGO - A Class Library for Accelerator Design and Simulation

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

Cai, Yunhai

1998-11-19

An object-oriented class library of accelerator design and simulation is designed and implemented in a simple and modular fashion. All physics of single-particle dynamics is implemented based on the Hamiltonian in the local frame of the component. Symplectic integrators are used to approximate the integration of the Hamiltonian. A differential algebra class is introduced to extract a Taylor map up to arbitrary order. Analysis of optics is done in the same way both for the linear and non-linear cases. Recently, Monte Carlo simulation of synchrotron radiation has been added into the library. The code is used to design and simulatemore » the lattices of the PEP-II and SPEAR3. And it is also used for the commissioning of the PEP-II. Some examples of how to use the library will be given.« less

Effectiveness of hepatitis A vaccination as post-exposure prophylaxis

PubMed Central

Parrón, Ignasi; Planas, Caritat; Manzanares-Laya, Sandra; Martínez, Ana; Sala, Maria Rosa; Minguell, Sofia; Jané, Mireia

2017-01-01

ABSTRACT Hepatitis A (HA) has been a vaccine-preventable disease since 1995. In Catalonia, a universal combined hepatitis A+B vaccination program of preadolescents was initiated at the end of 1998. However, outbreaks are reported each year and post-exposure prophylaxis (PEP) with hepatitis A virus (HAV) vaccine or immunoglobulin (IG) is recommended to avoid cases. The aim of this study was to assess the effectiveness of HAV vaccine and IG in preventing hepatitis A cases in susceptible exposed people. A retrospective cohort study of contacts of HA cases involved in outbreaks reported in Catalonia between January 2006 and December 2012 was made. The rate ratios and 95% confidence intervals (CI) of HA in susceptible contacts receiving HAV or IG versus those without PEP were calculated. There were 3550 exposed persons in the outbreaks studied: 2381 received one dose of HAV vaccine (Hepatitis A or hepatitis A+B), 190 received IG, and 611 received no PEP. 368 exposed subjects received one dose of HAV vaccine and IG simultaneously and were excluded from the study. The effectiveness of PEP was 97.6% (95% CI 96.2–98.6) for HAV vaccine and 98.3% (95% CI 91.3–99.9) for IG; the differences were not statistically significant (p = 0.36). The elevated effectiveness of HAV vaccination for PEP in HA outbreaks, similar to that of IG, and the long-term protection of active immunization, supports the preferential use of vaccination to avoid secondary cases. PMID:27925847

Effectiveness of hepatitis A vaccination as post-exposure prophylaxis.

PubMed

Parrón, Ignasi; Planas, Caritat; Godoy, Pere; Manzanares-Laya, Sandra; Martínez, Ana; Sala, Maria Rosa; Minguell, Sofia; Torner, Nuria; Jané, Mireia; Domínguez, Angela

2017-02-01

Hepatitis A (HA) has been a vaccine-preventable disease since 1995. In Catalonia, a universal combined hepatitis A+B vaccination program of preadolescents was initiated at the end of 1998. However, outbreaks are reported each year and post-exposure prophylaxis (PEP) with hepatitis A virus (HAV) vaccine or immunoglobulin (IG) is recommended to avoid cases. The aim of this study was to assess the effectiveness of HAV vaccine and IG in preventing hepatitis A cases in susceptible exposed people. A retrospective cohort study of contacts of HA cases involved in outbreaks reported in Catalonia between January 2006 and December 2012 was made. The rate ratios and 95% confidence intervals (CI) of HA in susceptible contacts receiving HAV or IG versus those without PEP were calculated. There were 3550 exposed persons in the outbreaks studied: 2381 received one dose of HAV vaccine (Hepatitis A or hepatitis A+B), 190 received IG, and 611 received no PEP. 368 exposed subjects received one dose of HAV vaccine and IG simultaneously and were excluded from the study. The effectiveness of PEP was 97.6% (95% CI 96.2-98.6) for HAV vaccine and 98.3% (95% CI 91.3-99.9) for IG; the differences were not statistically significant (p = 0.36). The elevated effectiveness of HAV vaccination for PEP in HA outbreaks, similar to that of IG, and the long-term protection of active immunization, supports the preferential use of vaccination to avoid secondary cases.

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.

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.

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.

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.

Final report on the oxidation of energetic materials in supercritical water. Final Air Force report

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

Buelow, S.J.; Allen, D.; Anderson, G.K.

1995-04-03

The objective of this project was to determine the suitability of oxidation in supercritical fluids (SCO), particularly water (SCWO), for disposal of propellants, explosives, and pyrotechnics (PEPs). The SCO studies of PEPs addressed the following issues: The efficiency of destruction of the substrate. The products of destruction contained in the effluents. Whether the process can be conducted safely on a large scale. Whether energy recovery from the process is economically practicable. The information essential for process development and equipment design was also investigated, including issues such as practical throughput of explosives through a SCWO reactor, reactor materials and corrosion, andmore » models for process design and optimization.« less

Robust Grasp Design Using Grasp Force Focus Positioning

DTIC Science & Technology

1991-12-12

the time for reviewing instructons. search-ng e isting date sources. gathering and maintainng the data needed, and completing and review ng the...of a larger scale task currently being studied at AFIT; a task which demonstrates intelligent part mating skills. The specific task involves the use of...program to generate the appropriate data for graphical analysis. The robotic hand model used in this study is based on the Utah/MIT Dexterous

77 FR 39490 - Notice of Proposed Information Collection Requests; Office of Planning, Evaluation and Policy...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-03

... DEPARTMENT OF EDUCATION Notice of Proposed Information Collection Requests; Office of Planning, Evaluation and Policy Development; Evaluation of the Carol M. White Physical Education Program SUMMARY: The Carol M. White Physical Education Program (PEP) supports a variety of projects that encourage fitness...

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.

JLEIC SRF cavity RF Design

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

Wang, Shaoheng; Guo, Jiquan; Wang, Haipeng

2016-05-01

The initial design of a low higher order modes (HOM) impedance superconducting RF (SRF) cavity is presented in this paper. The design of this SRF cavity is for the proposed Jefferson Lab Electron Ion Collider (JLEIC). The electron ring of JLEIC will operate with electrons of 3 to 10 GeV energy. The ion ring of JLEIC will operate with protons of up to 100 GeV energy. The bunch lengths in both rings are ~12 mm (RMS). In order to maintain the short bunch length in the ion ring, SRF cavities are adopted to provide large enough gradient. In the firstmore » phase of JLEIC, the PEP II RF cavities will be reused in the electron ring to lower the initial cost. The frequency of the SRF cavities is chosen to be the second harmonic of PEP II cavities, 952.6 MHz. In the second phase of JLEIC, the same frequency SRF cavities may replace the normal conducting PEP II cavities to achieve higher luminosity at high energy. At low energies, the synchro-tron radiation damping effect is quite weak, to avoid the coupled bunch instability caused by the intense closely-spaced electron bunches, low HOM impedance of the SRF cavities combined with longitudinal feedback sys-tem will be necessary.« less

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.

A database system for characterization of munitions items in conventional ammunition demilitarization stockpiles

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

Chun, K.C.; Chiu, S.Y.; Ditmars, J.D.

1994-05-01

The MIDAS (Munition Items Disposition Action System) database system is an electronic data management system capable of storage and retrieval of information on the detailed structures and material compositions of munitions items designated for demilitarization. The types of such munitions range from bulk propellants and small arms to projectiles and cluster bombs. The database system is also capable of processing data on the quantities of inert, PEP (propellant, explosives and pyrotechnics) and packaging materials associated with munitions, components, or parts, and the quantities of chemical compounds associated with parts made of PEP materials. Development of the MIDAS database system hasmore » been undertaken by the US Army to support disposition of unwanted ammunition stockpiles. The inventory of such stockpiles currently includes several thousand items, which total tens of thousands of tons, and is still growing. Providing systematic procedures for disposing of all unwanted conventional munitions is the mission of the MIDAS Demilitarization Program. To carry out this mission, all munitions listed in the Single Manager for Conventional Ammunition inventory must be characterized, and alternatives for resource recovery and recycling and/or disposal of munitions in the demilitarization inventory must be identified.« less

Outcomes of a Postexposure Prophylaxis Program at the Korle-Bu Teaching Hospital in Ghana: A Retrospective Cohort Study.

PubMed

Tetteh, Raymond A; Nartey, Edmund T; Lartey, Margaret; Mantel-Teeuwisse, Aukje K; Leufkens, Hubert G M; Nortey, Priscilla A; Dodoo, Alexander N O

2015-01-01

The risk for occupational exposure to HIV is a serious public health problem that is well characterized in the developed world, but less so in the developing countries such as Ghana. This study was undertaken to examine the characteristics of occupational exposure to HIV and the utilization of a risk assessment system (RAS)-based postexposure prophylaxis (PEP) among health care workers (HCWs) and health care students (HCSs) in the Korle-Bu Teaching Hospital (KBTH). During the study period (January 2005-December 2010), a total of 260 and 35 exposures were reported by HCWs and HCSs, respectively. Ward attendants reported the highest incidence rate of 6.46 of 100 person-years (P-Y). The incidence of high-risk exposures was 0.33 of 100 P-Y (n = 65); 60.0% occurred during a procedure of disposing of a needle and 24.6% during a cannula insertion. A total of 289 of the 295 individuals were administered PEP, of which 181 (62.6%) completed the 6-month follow-up testing schedule and none sero-converted. This shows that with a good RAS in place, it is possible to deploy an effective PEP program in a typical African teaching hospital like the KBTH in Accra, Ghana. © The Author(s) 2013.

The efficacy of chimeric vaccines constructed with PEP-1 and Ii-Key linking to a hybrid epitope from heterologous viruses.

PubMed

Liu, Xue-lan; Shan, Wen-jie; Xu, Shan-shan; Zhang, Jin-jing; Xu, Fa-zhi; Xia, Sheng-lin; Dai, Yin

2015-09-01

The heterologous epitope-peptide from different viruses may represent an attractive candidate vaccine. In order to evaluate the role of cell-permeable peptide (PEP-1) and Ii-Key moiety from the invariant chain (Ii) of MHC on the heterologous peptide chimeras, we linked the two vehicles to hybrid epitopes on the VP2 protein (aa197-209) of the infectious bursal disease virus and HN protein (aa345-353) of the Newcastle disease virus. The chimeric vaccines were prepared and injected into mice. The immune effects were measured by indirect ELISA. The results showed that the vehicle(s) could significantly boost immune effects against the heterologous epitope peptide. The Ii-Key-only carrier induced more effective immunological responses, compared with the PEP-1 and Ii-Key hybrid vehicle. The carrier-peptide hybrids all showed strong colocalization with major histocompatibility complex (MHC) class II molecules compared with the epitope-peptide (weakly-binding) after co-transfection into 293T cells. Together, our results lay the groundwork for designing new hybrid vaccines based on Ii-Key and/or PEP-1 peptides. Copyright © 2015 The International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

What Community-Based HIV Prevention Organizations Say About Their Role in Biomedical HIV Prevention.

PubMed

Smith, Dawn K; Maier, Emily; Betts, Joshua; Gray, Simone; Kolodziejski, Brian; Hoover, Karen W

2016-10-01

Community-based organizations (CBOs) are critical to delivery of effective HIV prevention because of their reach to key populations. This online survey of a national sample of CBOs assessed their awareness of, interest in, and resources needed to provide nonoccupational postexposure prophylaxis (nPEP), preexposure prophylaxis (PrEP), and HIV treatment as prevention (TasP). One hundred seventy-five CBOs participated: 87 clinical and 88 nonclinical CBOs. For nPEP, PrEP, and TasP, program managers reported that awareness was high (94%, 90%, 85%), meeting current client need was low (20%, 13%, 18%), and the likelihood of increasing their current provision with additional resources was somewhat high (62%, 64%, 62%). Clinical CBOs were more prepared to support expansion of these biomedical interventions than nonclinical CBOs. Meeting the information, training, and resource needs of CBOs is critical for effective collaboration to reduce the number of new HIV infections through expanded delivery of PrEP, nPEP, and TasP.

Use of HIV postexposure prophylaxis by dental health care personnel: an overview and updated recommendations.

PubMed

Cleveland, Jennifer L; Barker, Laurie; Gooch, Barbara F; Beltrami, Elise M; Cardo, Denise

2002-12-01

The authors conducted a study on the use of postexposure prophylaxis, or PEP, for exposure to human immunodeficiency virus, or HIV, among dental health care personnel, or DHCP, enrolled in a surveillance system established by the Centers for Disease Control and Prevention, or CDC. They also discuss updated U.S. Public Health Service, or USPHS, recommendations for managing occupational exposures to HIV, as well as considerations for dentistry. The authors analyzed occupational exposures reported by DHCP to the CDC to describe characteristics of the exposure (for example, type and severity), the source patient's HIV status and use of PEP. From June 1995 through August 2001, DHCP reported 208 exposures--199 percutaneous injuries, six mucous membrane exposures and three skin exposures--to the CDC. One-third of these percutaneous injuries were caused by small-bore hollow syringe needles, and most (66 percent) were moderate in depth. Nearly half the devices involved (46 percent) were visibly bloody at the time of injury. Per the criteria described in USPHS guidelines, one-half of the injuries were categorized as "less severe." Twenty-four (13 percent) known source patients were HIV-positive; 14 had symptomatic HIV infection or a high viral load. In this study, three in four DHCP exposed to an HIV-positive source warranted a three-drug PEP regimen. Twenty-nine (24 percent) DHCP exposed to a source patient who subsequently was found to be HIV-negative took PEP; six took PEP for five to 29 days. No exposures resulted in HIV infection. Findings of this study are consistent with earlier reports indicating that the risk of HIV transmission in dental settings is low. Strategies such as rapid HIV testing of source patients and follow-up counseling may reduce unnecessary use of PEP. Dental practices should develop comprehensive, written programs for preventing and managing occupational exposures to blood.

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

Foreign Personnel Exchange Programs: A Supporting Effort in Building Partnership Capacity

DTIC Science & Technology

2008-01-01

New Zealand Defence Force Relating to the Conduct ofExercise Long Look, (obtained from Daryl J. Cambell , 16 January, 2008). 45. U.S. Department...Daryl J. Cambell , 16 January, 2008). Commandant of the Marine Corps. 1STHALF CY 2008 A VIATION PERSONNEL EXCHANGE PROGRAM (PEP) AND lINTER-SERVICE

Effects of a dolphin interaction program on children with autism spectrum disorders – an exploratory research

PubMed Central

2012-01-01

Background Interaction programs involving dolphins and patients with various pathologies or developmental disorders (e.g., cerebral palsy, intellectual impairment, autism, atopic dermatitis, post-traumatic stress disorder, depression) have stimulated interest in their beneficial effects and therapeutic potential. However, the true effects observed in different clinical and psycho-educational setups are still controversial. Results An evaluation protocol consisting of the Childhood Autism Rating Scale (CARS), Psychoeducational Profile-Revised (PEP-R), Autism Treatment Evaluation Checklist (ATEC), Theory of Mind Tasks (ToM Tasks) and a custom-made Interaction Evaluation Grid (IEG) to evaluate behavioural complexity during in-pool interactions was applied to 10 children diagnosed with Autism Spectrum Disorders. The ATEC, ToM Tasks and CARS results show no benefits of the dolphin interaction program. Interestingly, the PEP-R suggests some statistically significant effects on ‘Overall development score’, as well as on their ‘Fine motor development’, ‘Cognitive performance’ and ‘Cognitive verbal development’. Also, a significant evolution in behavioural complexity was shown by the IEG. Conclusions This study does not support significant developmental progress resulting from the dolphin interaction program. PMID:22537536

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

BaBar superconducting coil: design, construction and test

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

Bell, R A; Berndt, M; Burgess, W

2001-01-26

The BABAR Detector, located in the PEP-II B-Factory at the Stanford Linear Accelerator Center, includes a large 1.5 Tesla superconducting solenoid, 2.8 m bore and length 3.7 m. The two layer solenoid is wound with an aluminum stabilized conductor which is graded axially to produce a {+-} 3% field uniformity in the tracking region. This paper summarizes the 3 year design, fabrication and testing program of the superconducting solenoid. The work was carried out by an international collaboration between INFN, LLNL and SLAC. The coil was constructed by Ansaldo Energia. Critical current measurements of the superconducting strand, cable and conductor,more » cool-down, operation with the thermo-siphon cooling, fast and slow discharges, and magnetic forces are discussed in detail.« less

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.

Sensitizing basal-like breast cancer to chemotherapy using nanoparticles conjugated with interference peptide

NASA Astrophysics Data System (ADS)

Sorolla, A.; Ho, D.; Wang, E.; Evans, C. W.; Ormonde, C. F. G.; Rashwan, R.; Singh, R.; Iyer, K. Swaminathan; Blancafort, P.

2016-04-01

Basal-like breast cancers are highly aggressive malignancies associated with very poor prognosis. Although these cancers may initially respond to first-line treatment, they become highly resistant to standard chemotherapy in the metastatic setting. Chemotherapy resistance in basal-like breast cancers is associated with highly selective overexpression of the homeobox transcription factor Engrailed 1 (EN1). Herein, we propose a novel therapeutic strategy using poly(glycidyl methacrylate) nanoparticles decorated with poly(acrylic acid) that enable dual delivery of docetaxel and interference peptides designed to block or inhibit EN1 (EN1-iPep). We demonstrate that EN1-iPep is highly selective in inducing apoptotic cell death in basal-like cancer cells with negligible effects in a non-neoplastic human mammary epithelial cell line. Furthermore, we show that treatment with EN1-iPep results in a highly synergistic pharmacological interaction with docetaxel in inhibiting cancer cell growth. The incorporation of these two agents in a single nanoformulation results in greater anticancer efficacy than current nanoparticle-based treatments used in the clinical setting.Basal-like breast cancers are highly aggressive malignancies associated with very poor prognosis. Although these cancers may initially respond to first-line treatment, they become highly resistant to standard chemotherapy in the metastatic setting. Chemotherapy resistance in basal-like breast cancers is associated with highly selective overexpression of the homeobox transcription factor Engrailed 1 (EN1). Herein, we propose a novel therapeutic strategy using poly(glycidyl methacrylate) nanoparticles decorated with poly(acrylic acid) that enable dual delivery of docetaxel and interference peptides designed to block or inhibit EN1 (EN1-iPep). We demonstrate that EN1-iPep is highly selective in inducing apoptotic cell death in basal-like cancer cells with negligible effects in a non-neoplastic human mammary epithelial cell line. Furthermore, we show that treatment with EN1-iPep results in a highly synergistic pharmacological interaction with docetaxel in inhibiting cancer cell growth. The incorporation of these two agents in a single nanoformulation results in greater anticancer efficacy than current nanoparticle-based treatments used in the clinical setting. Electronic supplementary information (ESI) available. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c6ob00583g

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.

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

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.

EFRT M12 Issue Resolution: Comparison of PEP and Bench-Scale Oxidative Leaching Results

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

Rapko, Brian M.; Brown, Christopher F.; Eslinger, Paul W.

2009-08-14

Pacific Northwest National Laboratory (PNNL) has been tasked by Bechtel National Inc. (BNI) on the River Protection Project-Hanford Tank Waste Treatment and Immobilization Plant (RPP-WTP) project to perform research and development activities to resolve technical issues identified for the Pretreatment Facility (PTF). The Pretreatment Engineering Platform (PEP) was designed and constructed and is to be operated as part of a plan to respond to issue M12, “Undemonstrated Leaching Processes.” The PEP is a 1/4.5-scale test platform designed to simulate the WTP pretreatment caustic leaching, oxidative leaching, ultrafiltration solids concentration, and slurry washing processes. The PEP replicates the WTP leaching processesmore » using prototypic equipment and control strategies. The PEP also includes non-prototypic ancillary equipment to support the core processing. Two operating scenarios are currently being evaluated for the ultrafiltration process (UFP) and leaching operations. The first scenario has caustic leaching performed in the UFP-2 ultrafiltration feed vessels (i.e., vessel UFP-VSL-T02A in the PEP; and vessels UFP-VSL-00002A and B in the WTP PTF). The second scenario has caustic leaching conducted in the UFP-1 ultrafiltration feed preparation vessels (i.e., vessels UFP-VSL-T01A and B in the PEP; vessels UFP-VSL-00001A and B in the WTP PTF). In both scenarios, 19-M sodium hydroxide solution (NaOH, caustic) is added to the waste slurry in the vessels to dissolve solid aluminum compounds (e.g., gibbsite, boehmite). Caustic addition is followed by a heating step that uses direct steam injection to accelerate the leaching process. Following the caustic leach, the vessel contents are cooled using vessel cooling jackets and/or external heat exchangers. The main difference between the two scenarios is that for leaching in UFP1, the 19-M NaOH is added to un-concentrated waste slurry (3 to 8 wt% solids), while for leaching in UFP2, the slurry is concentrated to nominally 20 wt% solids using cross-flow ultrafiltration before the addition of caustic. For wastes that have significantly high chromium content, the caustic leaching and slurry dewatering is followed by adding sodium permanganate to UFP-VSL-T02A, and the slurry is subjected to oxidative leaching at nominally ambient temperature. The purpose of the oxidative leaching is to selectively oxidize the poorly alkaline-soluble Cr(III) believed to be the insoluble form in Hanford tank sludge to the much more alkaline-soluble Cr(VI), e.g., chromate. The work described in this report provides the test results that are related to the efficiency of the oxidative leaching process to support process modeling based on tests performed with a Hanford waste simulant. The tests were completed both at the lab-bench scale and in the PEP. The purpose of this report is to summarize the results from both scales that are related to oxidative leaching chemistry to support a scale factor for the submodels to be used in the G2 model, which predicts WTP operating performance. Owing to schedule constraints, the PEP test data to be included in this report are limited to those from Integrated Tests A (T01 A/B caustic leaching) and B (T02A caustic leaching).« less

Meeting the Learning Needs of Students: A Rural High-Need School District's Systemic Leadership Development Initiative

ERIC Educational Resources Information Center

Browne-Ferrigno, Tricia; Maynard, Brenda

2005-01-01

The Principals Excellence Program (PEP), a cohort-based professional development project for administrator-certified practitioners, is one of 24 projects across the United States supported by federal funds from the No Child Left Behind legislation. The three-year program is conducted through a partnership between Pike County School District, a…

Student Voices: Perspectives on Peer-to-Peer Sexual Health Education

ERIC Educational Resources Information Center

Layzer, Carolyn; Rosapep, Lauren; Barr, Sherry

2017-01-01

Background: This process study is a companion to a randomized evaluation of a school-based, peer-led comprehensive sexual health education program, Teen Prevention Education Program (Teen PEP), in which 11th- and 12th-grade students are trained by school health educators to conduct informative workshops with ninth-grade peers in schools in North…

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

PEP Integrated Test D Run Report Caustic and Oxidative Leaching in UFP-VSL-T02A

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

Sevigny, Gary J.; Bredt, Ofelia P.; Burns, Carolyn A.

2009-12-11

Pacific Northwest National Laboratory (PNNL) has been tasked by Bechtel National Inc. (BNI) on the River Protection Project-Hanford Tank Waste Treatment and Immobilization Plant (RPP-WTP) project to perform research and development activities to resolve technical issues identified for the Pretreatment Facility (PTF). The Pretreatment Engineering Platform (PEP) was designed, constructed and operated as part of a plan to respond to issue M12, "Undemonstrated Leaching Processes" of the External Flowsheet Review Team (EFRT) issue response plan. The PEP is a 1/4.5-scale test platform designed to simulate the WTP pretreatment caustic leaching, oxidative leaching, ultrafiltration solids concentration, and slurry washing processes. Themore » PEP replicates the WTP leaching processes using prototypic equipment and control strategies. The PEP also includes non-prototypic ancillary equipment to support the core processing. Two operating scenarios are currently being evaluated for the ultrafiltration process (UFP) and leaching operations. The first scenario (Test B and D) has caustic leaching performed in the UFP-2 ultrafiltration feed vessels (i.e., vessel UFP-VSL-T02A in the PEP and vessels UFP-VSL-00002A and B in the WTP PTF). The second scenario (Test A) has caustic leaching conducted in the UFP-1 ultrafiltration feed preparation vessels (i.e., vessels UFP-VSL-T01A and B in the PEP and vessels UFP VSL-00001A and B in the WTP PTF). In Test D, 19M sodium hydroxide (NaOH, caustic) was added to the waste slurry in the UFP VSL T02 vessel after the solids were concentrated to ~20% undissolved solids. The NaOH was added to leach solid aluminum compounds (e.g., gibbsite, boehmite). Caustic addition is followed by heating to 85°C using direct injection of steam to accelerate the leach process. The main difference of Test D compared to Test B is that the leach temperature is 85°C for 24 hrs as compared to 100°C for 12 hours. The other difference is the Test D simulant had Cr in the simulant from the start of processing and Test B had Cr added to adjust the simulant composition after aluminum leaching. Following the caustic leach, the UFP-VSL-T02A vessel contents are cooled using the vessel cooling jacket. The slurry was then concentrated to 17 wt% undissolved solids and washed with inhibited water to remove NaOH and other soluble salts. Next, the slurry was oxidatively leached using sodium permanganate to solubilize chrome. The slurry was then washed to remove the dissolved chrome and concentrated.« less

The Ilocos Norte Communities against Rabies Exposure Elimination Project in the Philippines: Epidemiological and Economic Aspects.

PubMed

Valenzuela, Loida M; Jayme, Sarah I; Amparo, Anna Charinna B; Taylor, Louise H; Dela Cruz, Maria Pinky Z; Licuan, Dianne A; Gamal-Bitao, Rosebelle; Nel, Louis H

2017-01-01

As canine rabies control in Africa and Asia transitions from research-led proof-of-concept studies to government-led programs for elimination, experience and evidence of their impact and costs must be shared for the benefit of future programs. The Ilocos Norte Communities against Rabies Exposure project was implemented in April 2012 by the provincial veterinary and health offices and supported by many other partners. It delivered a comprehensive dog vaccination program and increased awareness of the need for postexposure prophylaxis (PEP), aiming to eliminate human and animal rabies cases from Ilocos Norte by 2015. Prior to the intervention, confirmed rabies cases in dogs were between 19 and 50 per year (2008-2011). The primary outcome of the project was a reduction in rabies cases in both dogs and humans to 0 in 2014 and 2015, which has subsequently been maintained. Animal bite consultations increased significantly during the project. Economic data for the dog vaccination and PEP components of the project were collated for two sites: Laoag City (an urban setting) and Dingras Municipality (a rural setting) between 2012 and 2014. The average programmatic cost of vaccinating each dog was $4.54 in Laoag City and $8.65 in Dingras, and costs fell as the project reached more dogs. The average costs of providing PEP were $69.72 per patient and $49.02 per patient for the two sites, respectively, again falling as the project reached more people. External donor contributions contributed less than 20% of dog vaccination costs and less than 1% of PEP costs. The project demonstrated that rabies elimination can be achieved in a short period of time, with concerted effort across multiple sectors. A lack of clear dog population estimates hampered interpretation of some aspects of the programme. From 2016, the provincial government has assumed complete responsibility for the programme and must now continue the vaccination and surveillance efforts. Although safeguards are in place, reintroduction from surrounding areas remains a threat, and vigilance must be maintained.

Future Synchrotron Light Sources Based on Ultimate Storage Rings

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

Cai, Yunhai; /SLAC

2012-04-09

The main purpose of this talk is to describe how far one might push the state of the art in storage ring design. The talk will start with an overview of the latest developments and advances in the design of synchrotron light sources based on the concept of an 'ultimate' storage ring. The review will establish how bright a ring based light source might be, where the frontier of technological challenges are, and what the limits of accelerator physics are. Emphasis will be given to possible improvements in accelerator design and developments in technology toward the goal of achieving anmore » ultimate storage ring. An ultimate storage ring (USR), defined as an electron ring-based light source having an emittance in both transverse planes at the diffraction limit for the range of X-ray wavelengths of interest for a scientific community, would provide very high brightness photons having high transverse coherence that would extend the capabilities of X-ray imaging and probe techniques beyond today's performance. It would be a cost-effective, high-coherence 4th generation light source, competitive with one based on energy recovery linac (ERL) technology, serving a large number of users studying material, chemical, and biological sciences. Furthermore, because of the experience accumulated over many decades of ring operation, it would have the great advantage of stability and reliability. In this paper we consider the design of an USR having 10-pm-rad emittance. It is a tremendous challenge to design a storage ring having such an extremely low emittance, a factor of 100 smaller than those in existing light sources, especially such that it has adequate dynamic aperture and beam lifetime. In many ultra-low emittance designs, the injection acceptances are not large enough for accumulation of the electron beam, necessitating on-axis injection where stored electron bunches are completely replaced with newly injected ones. Recently, starting with the MAX-IV 7-bend achromatic cell, we have made significant progress with the design of PEP-X, a USR that would inhabit the decommissioned PEP-II tunnel at SLAC. The enlargement of the dynamic aperture is largely a result of the cancellations of the 4th-order resonances in the 3rd-order achromats and the effective use of lattice optimization programs. In this paper, we will show those cancellations of the 4th-order resonances using an analytical approach based on the exponential Lie operators and the Poisson brackets. Wherever possible, our analytical results will be compared with their numerical counterparts. Using the derived formulae, we will construct 4th-order geometric achromats and use them as modules for the lattice of the PEP-X USR, noting that only geometric terms are canceled to the 4th order.« less

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

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.

A Randomized Controlled Trial of Individual Family Psychoeducational Psychotherapy and Omega-3 Fatty Acids in Youth with Subsyndromal Bipolar Disorder

PubMed Central

Young, Andrea S.; Vesco, Anthony T.; Nader, Elias S.; Healy, K. Zachary; Gardner, William; Wolfson, Hannah L.; Arnold, L. Eugene

2015-01-01

Abstract Objective: This pilot study evaluates efficacy of omega-3 fatty acid supplementation (Ω3), individual family psychoeducational psychotherapy (IF-PEP), and their combination in youth with subsyndromal bipolar disorders (bipolar disorder not otherwise specified [BP-NOS], cyclothymic disorder [CYC]). Methods: This study was a 12 week, randomized trial of Ω3 versus placebo and IF-PEP versus active monitoring (AM) using a 2 × 2 design (Ω3 + PEP: n = 5; Ω3 + AM: n = 5; placebo + PEP: n = 7; placebo + AM: n = 6). Twenty-three youth ages 7–14 with BP-NOS or CYC were recruited via community advertisements and clinician referrals. Participants could be taking stable medication for attention-deficit/hyperactivity disorder and sleep aids, but no other psychotropics. Independent evaluators assessed participants at screen, baseline, and 2, 4, 6, 9, and 12 weeks. Primary outcome measures were the Kiddie Schedule for Affective Disorders (K-SADS) Depression (KDRS) and Mania (KMRS) Rating Scales, Children's Depression Rating Scale-Revised (CDRS-R), and Young Mania Rating Scale (YMRS). Ω3/placebo conditions were double-blind; independent evaluators were blind to psychotherapy condition. Results: Most participants (83%) completed the 12 week trial. Side effects were uncommon and mild. Intent-to-treat analyses indicated significant improvement in depressive symptoms (KDRS) for combined treatment relative to placebo and AM (p = 0.01, d = 1.70). Across groups, manic symptoms improved over time without significant treatment effects. Effect of IF-PEP on child depression compared with AM was medium (d = 0.63, CDRS-R) to large (d = 1.24, KDRS). Effect of Ω3 on depression was medium (d = 0.48, KDRS). Conclusion: IF-PEP and Ω3 are well tolerated and associated with improved mood symptoms among youth with BP-NOS and CYC. Clinicaltrials.gov Identifier: NCT01507753 PMID:26682997

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.

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.

Drug Violations and Aviation Accidents: Findings from the U.S. Mandatory Drug Testing Programs

PubMed Central

Li, Guohua; Baker, Susan P.; Zhao, Qi; Brady, Joanne E.; Lang, Barbara H.; Rebok, George W.; DiMaggio, Charles

2012-01-01

Aims To assess the role of drug violations in aviation accidents. Design Case-control analysis. Setting Commercial aviation in the United States. Participants Aviation employees who were tested for drugs during 1995 through 2005 under the post-accident testing program (cases, n=4,977) or under the random testing program (controls, n=1,129,922). Measurements Point prevalence of drug violations, odds ratio of accident involvement, and attributable risk in the population. A drug violation was defined as a confirmed positive test for marijuana (≥ 50 ng/ml), cocaine (≥ 300 ng/ml), amphetamines (≥1000 ng/ml), opiates (≥ 2000 ng/ml), or phencyclidine (≥ 25 ng/ml). Findings The prevalence of drug violations was 0.64% [95% confidence interval (CI), 0.62–0.65%] in random drug tests and 1.82% (95% CI, 1.47–2.24%) in post-accident tests. The odds of accident involvement for employees who tested positive for drugs was almost three times the odds for those who tested negative (odds ratio 2.90, 95% CI, 2.35–3.57), with an estimated attributable risk of 1.2%. Marijuana accounted for 67.3% of the illicit drugs detected. The proportion of illicit drugs represented by amphetamines increased progressively during the study period, from 3.4% in 1995 to 10.3% in 2005 (p<0.0001). Conclusions Use of illicit drugs by aviation employees is associated with a significantly increased risk of accident involvement. Due to the very low prevalence, drug violations contribute to only a small fraction of aviation accidents. PMID:21306594

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.

76 FR 22684 - Draft Environmental Impact Statement (DEIS) for the Real Property Master Plan at the Presidio of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-22

... Department of Defense foreign language Proficiency Enhancement Program (PEP) changes the student-to... as part of the POM- centric alternative. (3) The POM and OMC alternative proposes new construction at...

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...

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...

Optimizing COD removal from greywater by photoelectro-persulfate process using Box-Behnken design: assessment of effluent quality and electrical energy consumption.

PubMed

Ahmadi, Mehdi; Ghanbari, Farshid

2016-10-01

Greywater (GW) is a potential source for water reuse in various applications. However, GW treatment is still a vital issue in water reuse in cases of environmental standards and risk to public health. This study investigates optimization and modeling of a hybrid process for COD removal from GW. Persulfate (PS) was simultaneously activated by electrogenerated ferrous ion (EC) and UV to generate sulfate radical. Photoelectro-persulfate (PEPS) was optimized by Box-Behnken design and the effects of four variables (pH, PS dosage, current density, and electrolysis time) were evaluated on COD removal. The results and several coefficients showed that the obtained model was acceptable for predicting the COD removal. Moreover, under optimum conditions (pH = 6.9, PS = 8.8 mM, current density = 2.0 mA/cm(2), and 49.3 min electrolysis time), BOD5, turbidity, TSS, phosphate, and UV254 were effectively removed and COD and BOD5 values reached to discharge standards. Different configurations of the processes were assessed for COD removal. The order of COD removal efficiency followed: PS < Fe(II) < UV/PS ≤ Fe(II)/PS < Fe(II)/PS/UV < electrocoagulation ≤ electrocoagulation/UV < electro-PS < PEPS. The monitoring PS concentration during 60 min reaction time in the aforesaid processes indicated that PEPS could remarkably activate PS. The solution pH was also monitored and related results revealed that the presence of PS during the 10 min first time decreased pH value while production of hydroxide ion at cathode increased pH significantly. Finally, the contribution of electrochemical process in the electrical energy consumption was far less than that of photolysis process in hybrid PEPS process.

Preparation, Characterization and Activity of a Peptide-Cellulosic Aerogel Protease Sensor from Cotton.

PubMed

Edwards, J Vincent; Fontenot, Krystal R; Prevost, Nicolette T; Pircher, Nicole; Liebner, Falk; Condon, Brian D

2016-10-26

Nanocellulosic aerogels (NA) provide a lightweight biocompatible material with structural properties, like interconnected high porosity and specific surface area, suitable for biosensor design. We report here the preparation, characterization and activity of peptide-nanocellulose aerogels (PepNA) made from unprocessed cotton and designed with protease detection activity. Low-density cellulosic aerogels were prepared from greige cotton by employing calcium thiocyanate octahydrate/lithium chloride as a direct cellulose dissolving medium. Subsequent casting, coagulation, solvent exchange and supercritical carbon dioxide drying afforded homogeneous cellulose II aerogels of fibrous morphology. The cotton-based aerogel had a porosity of 99% largely dominated by mesopores (2-50 nm) and an internal surface of 163 m²·g -1 . A fluorescent tripeptide-substrate (succinyl-alanine-proline-alanine-4-amino-7-methyl-coumarin) was tethered to NA by (1) esterification of cellulose C6 surface hydroxyl groups with glycidyl-fluorenylmethyloxycarbonyl (FMOC), (2) deprotection and (3) coupling of the immobilized glycine with the tripeptide. Characterization of the NA and PepNA included techniques, such as elemental analysis, mass spectral analysis, attenuated total reflectance infrared imaging, nitrogen adsorption, scanning electron microscopy and bioactivity studies. The degree of substitution of the peptide analog attached to the anhydroglucose units of PepNA was 0.015. The findings from mass spectral analysis and attenuated total reflectance infrared imaging indicated that the peptide substrate was immobilized on to the surface of the NA. Nitrogen adsorption revealed a high specific surface area and a highly porous system, which supports the open porous structure observed from scanning electron microscopy images. Bioactivity studies of PepNA revealed a detection sensitivity of 0.13 units/milliliter for human neutrophil elastase, a diagnostic biomarker for inflammatory diseases. The physical properties of the aerogel are suitable for interfacing with an intelligent protease sequestrant wound dressing.

A new star (sensor) is born

NASA Astrophysics Data System (ADS)

Leijtens, Johan; Vliegenthart, Willem; Lampridis, Dimitris; Vacanti, Giuseppe; Monna, Bert; Bechthum, Elbert; Hagenaars, Koen; van der Heide, Erik; Kruijff, Michiel; van Breukelen, Eddie; LeMair, Anita

2017-11-01

In the frame of the Dutch Prequalification for ESA Programs(PEP), as part of the efforts to design an integrated optical attitude control subsytem (IOPACS), a consortium of TNO and several SME's in the Netherlands have been working on a novel type of startracker called MABS (Multiple Aperture Baffled Startracker). The system comprises a single cast metal housing with four reflective optical telescopes which use only structural internal baffling. Inherent to the design are a very high stability and excellent co-alignment between the apertures, a significant decrease in system size and low recurring production cost. The concept is a radical change from more common multiple startracker setups. The presentation will concentrate on the validity of the concept, the predicted performance and benefits for space applications, the produced breadboard and measured performances as well as the costing aspects.

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

Compensatory Prekindergarteners' I.Q. Gain Correlated with Third Grade Reading Achievement.

ERIC Educational Resources Information Center

Archer, Philip D.; Sewall, Michael B.

The purpose of this study was to investigate the correlation between gain on the Stanford-Binet Intelligence Test (S-B) in compensatory prekindergarten programs, and scores on the New York State Pupil Evaluation Program (PEP), Reading Section, over three years later. Four hundred and five subjects showed a correlation of 0.42 for the pre-post S-B…

Improved Evolutionary Programming with Various Crossover Techniques for Optimal Power Flow Problem

NASA Astrophysics Data System (ADS)

Tangpatiphan, Kritsana; Yokoyama, Akihiko

This paper presents an Improved Evolutionary Programming (IEP) for solving the Optimal Power Flow (OPF) problem, which is considered as a non-linear, non-smooth, and multimodal optimization problem in power system operation. The total generator fuel cost is regarded as an objective function to be minimized. The proposed method is an Evolutionary Programming (EP)-based algorithm with making use of various crossover techniques, normally applied in Real Coded Genetic Algorithm (RCGA). The effectiveness of the proposed approach is investigated on the IEEE 30-bus system with three different types of fuel cost functions; namely the quadratic cost curve, the piecewise quadratic cost curve, and the quadratic cost curve superimposed by sine component. These three cost curves represent the generator fuel cost functions with a simplified model and more accurate models of a combined-cycle generating unit and a thermal unit with value-point loading effect respectively. The OPF solutions by the proposed method and Pure Evolutionary Programming (PEP) are observed and compared. The simulation results indicate that IEP requires less computing time than PEP with better solutions in some cases. Moreover, the influences of important IEP parameters on the OPF solution are described in details.

Academician Basov, high-power lasers, and the antimissile defense problem

NASA Astrophysics Data System (ADS)

Zarubin, Peter Vasilievich

2013-02-01

A review of the extensive program of the pioneering research and development of high-power lasers and laser radar undertaken in the USSR during the years 1964 to 1978 under the scientific supervision of N.G. Basov is presented. In the course of this program, many high-energy lasers with unique properties were created, new big research and design teams were formed, and the laser production and testing facilities were extended and developed. The program was fulfilled at many leading research institutions and design bureaus of the USSR Academy of Sciences and defense industry.

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.

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

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…

Effects of two educational programmes aimed at improving the utilization of non-opioid analgesics in family medicine clinics in Mexico.

PubMed

Doubova, Svetlana Vladislavovna; Mino-León, Dolores; Reyes-Morales, Hortensia; Flores-Hernandez, Sergio; Torres-Arreola, Laura del Pilar; Pérez-Cuevas, Ricardo

2010-08-01

To develop and test two educational programmes (interactive and passive) aimed at improving family doctors' (FD) prescribing practices and patient's knowledge and use of non-opioid analgesics (NOA). The educational programmes were conducted in two family medicine clinics by using a three-stage approach: baseline evaluation, design, and implementation of educational activities, and post-programme evaluation. An interactive educational programme (IEP) was compared with a passive educational programme (PEP); both were participated by FDs and patients. The IEP for FDs comprised of workshops, discussion groups, in-service training and guidelines, while for patients the IEP consisted of an interactive session with a video, leaflets and a discussion. The PEP consisted in delivering the guidelines to the FDs and the leaflets to patients. The effect of the programmes on the FDs was measured through the appropriateness of prescriptions and analysed using the differences-in-differences estimator (D-in-D), and on patients through changes in self-medication and in their knowledge about the proper use and adverse events by analysing the inter- and intra-group differences before and after the programmes. The IEP obtained better results to improve appropriate FDs prescription of NOA than PEP (D-in-D = 15%). Regarding the patients, the PEP group reached higher reduction of self-medication than the IEP group (13.4% vs. 9.1%); the knowledge of proper NOA use increased by 8.5% in both groups, whereas knowledge of NOA-related adverse events was better in the IEP (39.6%) than in the PEP group (9.2%). The IEP was better to improve the doctors' abilities to prescribe NOAs, and both programmes improved patients' knowledge.

Recognition mechanism of p63 by the E3 ligase Itch

PubMed Central

Bellomaria, Alessia; Barbato, Gaetano; Melino, Gerry; Paci, Maurizio; Melino, Sonia

2012-01-01

The HECT-containing E3 ubiquitin ligase Itch mediates the degradation of several proteins, including p63 and p73, involved in cell specification and fate. Itch contains four WW domains, which are essential for recognition on the target substrate, which contains a short proline-rich sequence. Several signaling complexes containing these domains have been associated with human diseases such as muscular dystrophy, Alzheimer’s or Huntington’s diseases. To gain further insight into the structural determinants of the Itch-WW2 domain, we investigated its interaction with p63. We assigned, by 3D heteronuclear NMR experiments, the backbone and side chains of the uniformly ¹³C-¹⁵N-labeled Itch-WW2. In vitro interaction of Itch-WW2 domain with p63 was studied using its interactive p63 peptide, pep63. Pep63 is an 18-mer peptide corresponding to the region from 534–551 residue of p63, encompassing the PPxY motif that interacts with the Itch-WW domains, and we identified the residues involved in this molecular recognition. Moreover, here, a strategy of stabilization of the conformation of the PPxY peptide has been adopted, increasing the WW-ligand binding. We demonstrated that cyclization of pep63 leads to an increase of both the biological stability of the peptide and of the WW-ligand complex. Stable metal-binding complexes of the pep63 have been also obtained, and localized oxidative damage on Itch-WW2 domain has been induced, demonstrating the possibility of use of metal-pep63 complexes as models for the design of metal drugs to inhibit the Itch-WW-p63 recognition in vivo. Thus, our data suggest a novel strategy to study and inhibit the recognition mechanism of Itch E3-ligase. PMID:22935697

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

Buchanan, Charles D.; Cline, David B.; Byers, N.

Progress in the various components of the UCLA High-Energy Physics Research program is summarized, including some representative figures and lists of resulting presentations and published papers. Principal efforts were directed at the following: (I) UCLA hadronization model, PEP4/9 e{sup +}e{sup {minus}} analysis, {bar P} decay; (II) ICARUS and astroparticle physics (physics goals, technical progress on electronics, data acquisition, and detector performance, long baseline neutrino beam from CERN to the Gran Sasso and ICARUS, future ICARUS program, and WIMP experiment with xenon), B physics with hadron beams and colliders, high-energy collider physics, and the {phi} factory project; (III) theoretical high-energy physics;more » (IV) H dibaryon search, search for K{sub L}{sup 0} {yields} {pi}{sup 0}{gamma}{gamma} and {pi}{sup 0}{nu}{bar {nu}}, and detector design and construction for the FNAL-KTeV project; (V) UCLA participation in the experiment CDF at Fermilab; and (VI) VLPC/scintillating fiber R D.« less

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

Not Available

Progress in the various components of the UCLA High-Energy Physics Research program is summarized, including some representative figures and lists of resulting presentations and published papers. Principal efforts were directed at the following: (I) UCLA hadronization model, PEP4/9 e{sup +}e{sup {minus}} analysis, {bar P} decay; (II) ICARUS and astroparticle physics (physics goals, technical progress on electronics, data acquisition, and detector performance, long baseline neutrino beam from CERN to the Gran Sasso and ICARUS, future ICARUS program, and WIMP experiment with xenon), B physics with hadron beams and colliders, high-energy collider physics, and the {phi} factory project; (III) theoretical high-energy physics;more » (IV) H dibaryon search, search for K{sub L}{sup 0} {yields} {pi}{sup 0}{gamma}{gamma} and {pi}{sup 0}{nu}{bar {nu}}, and detector design and construction for the FNAL-KTeV project; (V) UCLA participation in the experiment CDF at Fermilab; and (VI) VLPC/scintillating fiber R & D.« less

Supplier's Status for Critical Solid Propellants, Explosive, and Pyrotechnic Ingredients

NASA Technical Reports Server (NTRS)

Sims, B. L.; Painter, C. R.; Nauflett, G. W.; Cramer, R. J.; Mulder, E. J.

2000-01-01

In the early 1970's a program was initiated at the Naval Surface Warfare Center/Indian Head Division (NSWC/IHDIV) to address the well-known problems associated with availability and suppliers of critical ingredients. These critical ingredients are necessary for preparation of solid propellants and explosives manufactured by the Navy. The objective of the program was to identify primary and secondary (or back-up) vendor information for these critical ingredients, and to develop suitable alternative materials if an ingredient is unavailable. In 1992 NSWC/IHDIV funded Chemical Propulsion Information Agency (CPIA) under a Technical Area Task (TAT) to expedite the task of creating a database listing critical ingredients used to manufacture Navy propellant and explosives based on known formulation quantities. Under this task CPIA provided employees that were 100 percent dedicated to the task of obtaining critical ingredient suppliers information, selecting the software and designing the interface between the computer program and the database users. TAT objectives included creating the Explosive Ingredients Source Database (EISD) for Propellant, Explosive and Pyrotechnic (PEP) critical elements. The goal was to create a readily accessible database, to provide users a quick-view summary of critical ingredient supplier's information and create a centralized archive that CPIA would update and distribute. EISD funding ended in 1996. At that time, the database entries included 53 formulations and 108 critical used to manufacture Navy propellant and explosives. CPIA turned the database tasking back over to NSWC/IHDIV to maintain and distribute at their discretion. Due to significant interest in propellant/explosives critical ingredients suppliers' status, the Propellant Development and Characterization Subcommittee (PDCS) approached the JANNAF Executive committee (EC) for authorization to continue the critical ingredient database work. In 1999, JANNAF EC approved the PDCS panel task. This paper is designed to emphasize the necessity of maintaining a JANNAF community supported database, which monitors PEP critical ingredient suppliers' status. The final product of this task is a user friendly, searchable database that provides a quick-view summary of critical ingredient supplier's information. This database must be designed to serve the needs of JANNAF and the propellant and energetic commercial manufacturing community as well. This paper provides a summary of the type of information to archive each critical ingredient.

Ethylene glycol-linked amino acid diester prodrugs of oleanolic acid for PepT1-mediated transport: synthesis, intestinal permeability and pharmacokinetics.

PubMed

Cao, Feng; Jia, Jinghao; Yin, Zhi; Gao, Yahan; Sha, Lei; Lai, Yisheng; Ping, Qineng; Zhang, Yihua

2012-08-06

The purposes of this study were to expand the structure of parent drugs selected for peptide transporter 1 (PepT1)-targeted ester prodrug design and to improve oral bioavailability of oleanolic acid (OA), a Biopharmaceutics Classification System (BCS) class IV drug. Through an ethoxy linker the carboxylic acid group of OA was conjugated with the carboxylic acid group of different amino acid promoieties to form six diester prodrugs. The effective permeability (P(eff)) of prodrugs was screened by in situ rat single-pass intestinal perfusion (SPIP) model in two buffers with different pH (6.0 and 7.4) as PepT1 employs a proton-gradient as the driving force. Compared to OA, 2.5-fold, 2.3-fold, 2.2-fold, 2.1-fold, and 1.9-fold enhancement of P(eff) in buffer with pH 6.0 was observed for L-Phe ester (5c), L-Val ester (5a), L-Lys ester (5e), D-Phe ester (5d), and D-Val ester (5b), respectively. Furthermore, P(eff) of 5a, 5c, 5d and 5e in pH 6.0 was significantly higher than that in pH 7.4 (p < 0.01), respectively. These results showed that the H(+) concentration of perfusion solution had great effect on the transport of the prodrugs across intestinal membrane. For the further evaluation of affinity to PepT1, inhibition studies were performed by coperfusing 0.1 mM prodrug with 50 mM glycyl-sarcosine (Gly-Sar, a typical substrate of PepT1). It turned out that the P(eff) of 5a, 5b, 5c and L-Tyr ester (6f) significantly reduced in the presence of Gly-Sar (1.7-fold, 2.2-fold, 1.9-fold, and 1.4-fold, respectively). We supposed that it may be attributed to PepT1 mediated transport of these prodrugs. 5a and 6f were selected as the optimal target prodrugs for oral absorption in vivo. Following intragastric administration of 300 mg/kg (calculated as OA) 5a, 6f and OA in three groups of rats, compared with group OA, Cmax for the group of 5a and 6f was enhanced by 1.56-fold and 1.54-fold, respectively. Fapp of group 5a and 6f was 2.21- and 2.04-fold increased, respectively, indicating that 5a and 6f had better oral absorption than OA. The combined results also suggest that diester prodrugs which conjugated two carboxylic acid groups of proper amino acid promoieties and parent drug through a linker can be used for PepT1-targeted prodrug design. With this strategy, oral bioavailability of OA in rats could be improved significantly.

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

Introducing Human Sexuality into the Population Education Curriculum. The State-of-the-Art. Population Education Research Utilization Monograph Series 1 Part 3.

ERIC Educational Resources Information Center

Villanueva, Carmelita L.; Arellano-Reyes, Ma. Felicitas

This paper explores one problem area that hampers the introduction and acceptance of sex education in schools. Specifically, the paper reviews problems related to the human sexuality component of population education programs in the Philippines. Research on the experiences of the Population Education Program (PEP) is discussed, as well as research…

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.

Pan European Phenological database (PEP725): a single point of access for European data

NASA Astrophysics Data System (ADS)

Templ, Barbara; Koch, Elisabeth; Bolmgren, Kjell; Ungersböck, Markus; Paul, Anita; Scheifinger, Helfried; Rutishauser, This; Busto, Montserrat; Chmielewski, Frank-M.; Hájková, Lenka; Hodzić, Sabina; Kaspar, Frank; Pietragalla, Barbara; Romero-Fresneda, Ramiro; Tolvanen, Anne; Vučetič, Višnja; Zimmermann, Kirsten; Zust, Ana

2018-06-01

The Pan European Phenology (PEP) project is a European infrastructure to promote and facilitate phenological research, education, and environmental monitoring. The main objective is to maintain and develop a Pan European Phenological database (PEP725) with an open, unrestricted data access for science and education. PEP725 is the successor of the database developed through the COST action 725 "Establishing a European phenological data platform for climatological applications" working as a single access point for European-wide plant phenological data. So far, 32 European meteorological services and project partners from across Europe have joined and supplied data collected by volunteers from 1868 to the present for the PEP725 database. Most of the partners actively provide data on a regular basis. The database presently holds almost 12 million records, about 46 growing stages and 265 plant species (including cultivars), and can be accessed via http://www.pep725.eu/ . Users of the PEP725 database have studied a diversity of topics ranging from climate change impact, plant physiological question, phenological modeling, and remote sensing of vegetation to ecosystem productivity.

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.

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.

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.

75 FR 30103 - Petition for Exemption From the Vehicle Theft Prevention Standard; Ford Motor Company

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-28

... (BCM), the PEP/RFA module and the PCM. Ford pointed out that in addition to the programmed key, the... concludes that the device will provide four of the five types of performance listed in Sec. 543.6(a)(3...

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.

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.

Multiple genetic resistances in Capsicum spp.

PubMed

Bento, C S; de Souza, A G; Sudré, C P; Pimenta, S; Rodrigues, R

2017-09-27

This study aimed to identify Capsicum genotypes with resistance to bacterial spot (BS), anthracnose and Pepper yellow mosaic virus (PepYMV). Fifty-four genotypes of Capsicum spp were evaluated. Resistance reaction against BS was evaluated using three replicates, testing hypersensitivity and quantitative resistance in leaves. After evaluation, inoculated leaves were detached from the plants, being then cultivated until reproductive stage for evaluations anthracnose resistance in immature and mature fruit, totalizing 18 fruits per genotype. For PepYMV resistance was performed with five replications. Each genotype reaction was evaluated by a scoring scale, using the area under the disease progress curve for each pathosystem, and incubation period for the three systems. The latent period was evaluated only for the pathosystem Capsicum-Colletotrichum gloeosporioides. Means were grouped by the Scott-Knott test. Measures of dissimilarity matrix among the genotypes were obtained by Gower's algorithm and the grouping was obtained by the UPGMA clustering method. The accessions belonging to the Capsicum frutescens were the most susceptible to the three diseases. At least one genotype of Capsicum baccatum var. pendulum, Capsicum annuum, and Capsicum chinense showed resistance potential to BS and PepYMV, for use in breeding programs. The accession UENF 1381 (C. annuum) was resistant to the three pathogens.

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

Structural Analysis of Pyrolytic Graphite Optics for the HiPEP Ion Thruster

NASA Technical Reports Server (NTRS)

Meckel, Nicole; Polaha, Jonathan; Juhlin, Nils

2006-01-01

The long lifetime requirements of interplanetary exploration missions is driving the need to develop long-life components for the electric propulsion thrusters that are being targeted for these missions. One of the primary life-limiting components of ion thrusters are the optics, which are continuously eroded during the operation of the thruster. Pyrolytic graphite optics are being considered for the High Power Electric Propulsion (HiPEP) ion thruster because of their very high resistance to erosion. This paper describes the structural analysis of the HiPEP pyrolytic graphite. A description of the development of the grid model, as well as the development of the effective properties and stress concentrations in the apertured area of the grids is included. An evaluation of the use of curved grids shows that the increased stiffness (compared to flat grids) prevents intergrid impact during launch, however, the residual stresses introduced by curving the grids pushes the resulting peak stresses beyond the critical stress. As a result, flat grids are recommended as the design solution. Thermally induced grid displacements during normal thruster operation are also presented.

Preclinical Investigations Reveal the Broad-Spectrum Neutralizing Activity of Peptide Pep19-2.5 on Bacterial Pathogenicity Factors

PubMed Central

Sánchez-Gómez, Susana; Martinez de Tejada, Guillermo; Dömming, Sabine; Brandenburg, Julius; Kaconis, Yani; Hornef, Mathias; Dupont, Aline; Marwitz, Sebastian; Goldmann, Torsten; Ernst, Martin; Gutsmann, Thomas; Schürholz, Tobias

2013-01-01

Bacterial infections are known to cause severe health-threatening conditions, including sepsis. All attempts to get this disease under control failed in the past, and especially in times of increasing antibiotic resistance, this leads to one of the most urgent medical challenges of our times. We designed a peptide to bind with high affinity to endotoxins, one of the most potent pathogenicity factors involved in triggering sepsis. The peptide Pep19-2.5 reveals high endotoxin neutralization efficiency in vitro, and here, we demonstrate its antiseptic/anti-inflammatory effects in vivo in the mouse models of endotoxemia, bacteremia, and cecal ligation and puncture, as well as in an ex vivo model of human tissue. Furthermore, we show that Pep19-2.5 can bind and neutralize not only endotoxins but also other bacterial pathogenicity factors, such as those from the Gram-positive bacterium Staphylococcus aureus. This broad neutralization efficiency and the additive action of the peptide with common antibiotics makes it an exceptionally appropriate drug candidate against bacterial sepsis and also offers multiple other medication opportunities. PMID:23318793

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.

Pan European Phenological database (PEP725): a single point of access for European data.

PubMed

Templ, Barbara; Koch, Elisabeth; Bolmgren, Kjell; Ungersböck, Markus; Paul, Anita; Scheifinger, Helfried; Rutishauser, This; Busto, Montserrat; Chmielewski, Frank-M; Hájková, Lenka; Hodzić, Sabina; Kaspar, Frank; Pietragalla, Barbara; Romero-Fresneda, Ramiro; Tolvanen, Anne; Vučetič, Višnja; Zimmermann, Kirsten; Zust, Ana

2018-06-01

The Pan European Phenology (PEP) project is a European infrastructure to promote and facilitate phenological research, education, and environmental monitoring. The main objective is to maintain and develop a Pan European Phenological database (PEP725) with an open, unrestricted data access for science and education. PEP725 is the successor of the database developed through the COST action 725 "Establishing a European phenological data platform for climatological applications" working as a single access point for European-wide plant phenological data. So far, 32 European meteorological services and project partners from across Europe have joined and supplied data collected by volunteers from 1868 to the present for the PEP725 database. Most of the partners actively provide data on a regular basis. The database presently holds almost 12 million records, about 46 growing stages and 265 plant species (including cultivars), and can be accessed via http://www.pep725.eu/ . Users of the PEP725 database have studied a diversity of topics ranging from climate change impact, plant physiological question, phenological modeling, and remote sensing of vegetation to ecosystem productivity.

Pan European Phenological database (PEP725): a single point of access for European data

NASA Astrophysics Data System (ADS)

Templ, Barbara; Koch, Elisabeth; Bolmgren, Kjell; Ungersböck, Markus; Paul, Anita; Scheifinger, Helfried; Rutishauser, This; Busto, Montserrat; Chmielewski, Frank-M.; Hájková, Lenka; Hodzić, Sabina; Kaspar, Frank; Pietragalla, Barbara; Romero-Fresneda, Ramiro; Tolvanen, Anne; Vučetič, Višnja; Zimmermann, Kirsten; Zust, Ana

2018-02-01

The Pan European Phenology (PEP) project is a European infrastructure to promote and facilitate phenological research, education, and environmental monitoring. The main objective is to maintain and develop a Pan European Phenological database (PEP725) with an open, unrestricted data access for science and education. PEP725 is the successor of the database developed through the COST action 725 "Establishing a European phenological data platform for climatological applications" working as a single access point for European-wide plant phenological data. So far, 32 European meteorological services and project partners from across Europe have joined and supplied data collected by volunteers from 1868 to the present for the PEP725 database. Most of the partners actively provide data on a regular basis. The database presently holds almost 12 million records, about 46 growing stages and 265 plant species (including cultivars), and can be accessed via http://www.pep725.eu/. Users of the PEP725 database have studied a diversity of topics ranging from climate change impact, plant physiological question, phenological modeling, and remote sensing of vegetation to ecosystem productivity.

Generation of food-grade recombinant Lactobacillus casei delivering Myxococcus xanthus prolyl endopeptidase

PubMed Central

Alvarez-Sieiro, Patricia; Martin, Maria Cruz; Redruello, Begoña; del Rio, Beatriz; Ladero, Victor; Palanski, Brad A.; Khosla, Chaitan; Fernandez, Maria; Alvarez, Miguel A.

2015-01-01

Prolyl endopeptidases (PEP), a family of serine proteases with the ability to hydrolyze the peptide bond on the carboxyl side of an internal proline residue, are able to degrade immunotoxic peptides responsible for celiac disease (CD), such as a 33-residue gluten peptide (33-mer). Oral administration of PEP has been suggested as a potential therapeutic approach for CD, although delivery of the enzyme to the small intestine requires intrinsic gastric stability or advanced formulation technologies. We have engineered two food-grade Lactobacillus casei strains to deliver PEP in an in vitro model of small intestine environment. One strain secretes PEP into the extracellular medium, whereas the other retains PEP in the intracellular environment. The strain that secretes PEP into the extracellular medium is the most effective to degrade the 33-mer and is resistant to simulated gastrointestinal stress. Our results suggest that in a future, after more studies and clinical trials, an engineered food-grade Lactobacillus strain may be useful as a vector for in situ production of PEP in the upper small intestine of CD patients. PMID:24752841

Physical Education, Politics, and SPEAK Out! Day

ERIC Educational Resources Information Center

Claxton, David; Kopp, Rachael; Skidmore, Lauren; Williams, Kimberly

2013-01-01

This article discusses the importance of politics in the lives of physical educators. Politics affects many decisions that are made about physical education programs (PEPs). In public schools, politics can affect the number of certified physical education teachers, available facilities, class sizes, and number of days per week that students go to…

PECONIC ESTUARY: AN INVENTORY OF SUBMERGED AQUATIC VEGETATION AND HARDENED SHORELINES FOR THE PECONIC ESTUARY, NEW YORK

EPA Science Inventory

Executive Summary The Peconic Estuary Program (PEP) is interested in the extent of eelgrass and other submerged aquatic vegetation and in documenting changes in the shorelines of the Peconic Estuary. The Suffolk County Department of Health Services' Office of Ecology provided fun...

STEM Pathways: Examining Persistence in Rigorous Math and Science Course Taking

NASA Astrophysics Data System (ADS)

Ashford, Shetay N.; Lanehart, Rheta E.; Kersaint, Gladis K.; Lee, Reginald S.; Kromrey, Jeffrey D.

2016-12-01

From 2006 to 2012, Florida Statute §1003.4156 required middle school students to complete electronic personal education planners (ePEPs) before promotion to ninth grade. The ePEP helped them identify programs of study and required high school coursework to accomplish their postsecondary education and career goals. During the same period Florida required completion of the ePEP, Florida's Career and Professional Education Act stimulated a rapid increase in the number of statewide high school career academies. Students with interests in STEM careers created STEM-focused ePEPs and may have enrolled in STEM career academies, which offered a unique opportunity to improve their preparedness for the STEM workforce through the integration of rigorous academic and career and technical education courses. This study examined persistence of STEM-interested (i.e., those with expressed interest in STEM careers) and STEM-capable (i.e., those who completed at least Algebra 1 in eighth grade) students ( n = 11,248), including those enrolled in STEM career academies, in rigorous mathematics and science course taking in Florida public high schools in comparison with the national cohort of STEM-interested students to measure the influence of K-12 STEM education efforts in Florida. With the exception of multi-race students, we found that Florida's STEM-capable students had lower persistence in rigorous mathematics and science course taking than students in the national cohort from ninth to eleventh grade. We also found that participation in STEM career academies did not support persistence in rigorous mathematics and science courses, a prerequisite for success in postsecondary STEM education and careers.

Simulation of PEP-II Accelerator Backgrounds Using TURTLE

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

Barlow, R.J.; Fieguth, T.; /SLAC

2006-02-15

We present studies of accelerator-induced backgrounds in the BaBar detector at the SLAC B-Factory, carried out using LPTURTLE, a modified version of the DECAY TURTLE simulation package. Lost-particle backgrounds in PEP-II are dominated by a combination of beam-gas bremstrahlung, beam-gas Coulomb scattering, radiative-Bhabha events and beam-beam blow-up. The radiation damage and detector occupancy caused by the associated electromagnetic shower debris can limit the usable luminosity. In order to understand and mitigate such backgrounds, we have performed a full program of beam-gas and luminosity-background simulations, that include the effects of the detector solenoidal field, detailed modeling of limiting apertures in bothmore » collider rings, and optimization of the betatron collimation scheme in the presence of large transverse tails.« less

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

Josephson, Gary B.; Geeting, John GH; Bredt, Ofelia P.

Pacific Northwest National Laboratory (PNNL) has been tasked by Bechtel National Inc. (BNI) on the River Protection Project-Waste Treatment Plant (RPP-WTP) project to perform research and development activities to resolve technical issues identified for the Pretreatment Facility (PTF). The Pretreatment Engineering Platform (PEP) was designed, constructed, and operated as part of a plan to respond to issue M12, "Undemonstrated Leaching Processes." The PEP is a 1/4.5-scale test platform designed to simulate the WTP pretreatment caustic leaching, oxidative leaching, ultrafiltration solids concentration, and slurry washing processes. The PEP replicates the WTP leaching processes using prototypic equipment and control strategies. The PEPmore » also includes non-prototypic ancillary equipment to support the core processing. Two operating scenarios are currently being evaluated for the ultrafiltration process (UFP) and leaching operations. The first scenario has caustic leaching performed in the UFP-2 ultrafiltration feed vessels (i.e., vessel UFP-VSL-T02A in the PEP; and vessels UFP-VSL-00002A and B in the WTP PTF). The second scenario has caustic leaching conducted in the UFP-1 ultrafiltration feed preparation vessels (i.e., vessels UFP-VSL-T01A and B in the PEP; vessels UFP-VSL-00001A and B in the WTP PTF). In both scenarios, 19-M sodium hydroxide solution (NaOH, caustic) is added to the waste slurry in the vessels to leach solid aluminum compounds (e.g., gibbsite, boehmite). Caustic addition is followed by a heating step that uses direct injection of steam to accelerate the leach process. Following the caustic leach, the vessel contents are cooled using vessel cooling jackets and/or external heat exchangers. The main difference between the two scenarios is that for leaching in UFP-1, the 19-M NaOH is added to un-concentrated waste slurry (3-8 wt% solids), while for leaching in UFP-2, the slurry is concentrated to nominally 20 wt% solids using cross-flow ultrafiltration before the addition of caustic. In both scenarios, following the caustic leach, the slurry was then concentrated to 17 wt% and washed with inhibited water to remove NaOH and other soluble salts. Next, the slurry was oxidatively leached using sodium permanganate to solubilize chrome. The slurry was then washed to remove the dissolved chrome and concentrated.« less

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.

Functionalized PLA-PEG nanoparticles targeting intestinal transporter PepT1 for oral delivery of acyclovir.

PubMed

Gourdon, Betty; Chemin, Caroline; Moreau, Amélie; Arnauld, Thomas; Baumy, Philippe; Cisternino, Salvatore; Péan, Jean-Manuel; Declèves, Xavier

2017-08-30

Targeting intestinal di- and tri-peptide transporter PepT1 with prodrugs is a successful strategy to improve oral drug bioavailability, as demonstrated with valacyclovir, a prodrug of acyclovir. The aim of this new drug delivery strategy is to over-concentrate a poorly absorbed drug on the intestinal membrane surface by targeting PepT1 with functionalized polymer nanoparticles. In the present study, poly(lactic acid)-poly(ethylene glycol)-ligand (PLA-PEG-ligand) nanoparticles were obtained by nanoprecipitation. A factorial experimental design allowed us to identify size-influent parameters and to obtain optimized ≈30nm nanoparticles. Valine, Glycylsarcosine, Valine-Glycine, and Tyrosine-Valine were chemically linked to PLA-PEG. In Caco-2 cell monolayer model, competition between functionalized nanoparticles and [ 3 H]Glycylsarcosine, a strong substrate of PepT1, reduced [ 3 H]Glycylsarcosine transport from 22 to 46%. Acyclovir was encapsulated with a drug load of ≈10% in valine-functionalized nanoparticles, resulting in a 2.7-fold increase in permeability as compared to the free drug. An in vivo pharmacokinetic study in mice compared oral absorption of acyclovir after administration of 25mg/kg of valacyclovir, free or encapsulated acyclovir in functionalized nanoparticles. Acyclovir encapsulation did not statistically modify AUC or C max , but increased t 1/2 and MRT 1.3-fold as compared to free acyclovir. This new strategy is promising for poorly absorbed drugs by oral administration. Copyright © 2017 Elsevier B.V. All rights reserved.

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 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

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.

Preparation, Characterization and Activity of a Peptide-Cellulosic Aerogel Protease Sensor from Cotton

PubMed Central

Edwards, J. Vincent; Fontenot, Krystal R.; Prevost, Nicolette T.; Pircher, Nicole; Liebner, Falk; Condon, Brian D.

2016-01-01

Nanocellulosic aerogels (NA) provide a lightweight biocompatible material with structural properties, like interconnected high porosity and specific surface area, suitable for biosensor design. We report here the preparation, characterization and activity of peptide-nanocellulose aerogels (PepNA) made from unprocessed cotton and designed with protease detection activity. Low-density cellulosic aerogels were prepared from greige cotton by employing calcium thiocyanate octahydrate/lithium chloride as a direct cellulose dissolving medium. Subsequent casting, coagulation, solvent exchange and supercritical carbon dioxide drying afforded homogeneous cellulose II aerogels of fibrous morphology. The cotton-based aerogel had a porosity of 99% largely dominated by mesopores (2–50 nm) and an internal surface of 163 m2·g−1. A fluorescent tripeptide-substrate (succinyl-alanine-proline-alanine-4-amino-7-methyl-coumarin) was tethered to NA by (1) esterification of cellulose C6 surface hydroxyl groups with glycidyl-fluorenylmethyloxycarbonyl (FMOC), (2) deprotection and (3) coupling of the immobilized glycine with the tripeptide. Characterization of the NA and PepNA included techniques, such as elemental analysis, mass spectral analysis, attenuated total reflectance infrared imaging, nitrogen adsorption, scanning electron microscopy and bioactivity studies. The degree of substitution of the peptide analog attached to the anhydroglucose units of PepNA was 0.015. The findings from mass spectral analysis and attenuated total reflectance infrared imaging indicated that the peptide substrate was immobilized on to the surface of the NA. Nitrogen adsorption revealed a high specific surface area and a highly porous system, which supports the open porous structure observed from scanning electron microscopy images. Bioactivity studies of PepNA revealed a detection sensitivity of 0.13 units/milliliter for human neutrophil elastase, a diagnostic biomarker for inflammatory diseases. The physical properties of the aerogel are suitable for interfacing with an intelligent protease sequestrant wound dressing. PMID:27792201

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.

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.

Recognition mechanism of p63 by the E3 ligase Itch: novel strategy in the study and inhibition of this interaction.

PubMed

Bellomaria, Alessia; Barbato, Gaetano; Melino, Gerry; Paci, Maurizio; Melino, Sonia

2012-10-01

The HECT-containing E3 ubiquitin ligase Itch mediates the degradation of several proteins, including p63 and p73, involved in cell specification and fate. Itch contains four WW domains, which are essential for recognition on the target substrate, which contains a short proline-rich sequence. Several signaling complexes containing these domains have been associated with human diseases such as muscular dystrophy, Alzheimer's or Huntington's diseases. To gain further insight into the structural determinants of the Itch-WW2 domain, we investigated its interaction with p63. We assigned, by 3D heteronuclear NMR experiments, the backbone and side chains of the uniformly (13)C-(15)N-labeled Itch-WW2. In vitro interaction of Itch-WW2 domain with p63 was studied using its interactive p63 peptide, pep63. Pep63 is an 18-mer peptide corresponding to the region from 534-551 residue of p63, encompassing the PPxY motif that interacts with the Itch-WW domains, and we identified the residues involved in this molecular recognition. Moreover, here, a strategy of stabilization of the conformation of the PPxY peptide has been adopted, increasing the WW-ligand binding. We demonstrated that cyclization of pep63 leads to an increase of both the biological stability of the peptide and of the WW-ligand complex. Stable metal-binding complexes of the pep63 have been also obtained, and localized oxidative damage on Itch-WW2 domain has been induced, demonstrating the possibility of use of metal-pep63 complexes as models for the design of metal drugs to inhibit the Itch-WW-p63 recognition in vivo. Thus, our data suggest a novel strategy to study and inhibit the recognition mechanism of Itch E3-ligase.

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.

Training model to institutionalize population education in the in-service education programme for elementary school teachers.

PubMed

Dugenia, M E

1982-12-01

The goal of the Philippine Population Education Program (PEP) since its inception in 1972 is to institutionalize population education in the formal educational system. The PEP Training Section views institutionalization of population education in the inservice education program for elementary school teachers as part of the process of making it an integral part of that program. In practice elementary school teachers periodically attend training programs organized by division or district supervisors and school principals. This is the usual modality through which teachers are updated on or informed about new thrusts and recent developments in teaching content, strategies, and methodologies. In this context, the PEP Training Section convened a seminar workshop in December 1981 for 10 subject area supervisors from the 3 large geographic island groups of Luzon, Visayas, and Mindanao. They represented 10 school divisions and subject areas where population education is integrated. The specific objectives of the 5 day activity were to: discuss existing inservice training programs in the school divisions; prepare a training model incorporating population education in the overall division inservice training program; and develop a content chart or a listing of topical areas on population education for the training model. 1 of the outputs of the seminar workshop was a training model incorporating population education in the regular inservice training programs using 3 delivery schemes, i.e., seminar workship on the teaching of specific subject areas; district staff meeting and/or echo seminars organized by district supervisors following division seminars; and regular teachers' meeting at the school level organized by school principals. Another output was a content chart listing suggested topics in population education classified according to subject areas into which they will be incorporated. The semninar workshop concluded with a plan to try out the model using the identified modalities in respective school divisions during the year 1982 and an agreement to reconvene for a feedback conference after the tryout. During the feedback conference held in August 1982, certain factors that are critical for the institutionalization of population education in the inservice training programs for teachers were identified: need for support of the top officials of the school division; need for diffusion of the training to other subject areas; and need for involvement of the supervisory hierarchy. The pilot experience showed that involvement of the supervisory hierarchy in charge of training of teachers in planning and organization of inservice training programs facilitates training and articulates and corrdinates training management.

Affective Management Strategies for Behavior Disordered Students--Elementary and Secondary Levels.

ERIC Educational Resources Information Center

Burkholder, Lynn D.; And Others

The Positive Education Program (PEP) in Cuyahoga, Ohio, incorporates a token economy and group process approach into the daily school routine for emotionally disturbed and behaviorally handicapped students. At elementary and secondary levels, minimum rules and expectations as well as privileges awarded for behaviors are clearly set forth. The…

75 FR 25025 - Bureau of Educational and Cultural Affairs (ECA) Request for Grant Proposals: U.S. Professional...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-06

... Section 26 USC 501(c)(3) may submit proposals to cooperate with the Bureau in the administration of this... Leadership (PAL) and the Professional Advising Leadership Expansion (PEP) programs. Funding not to exceed.... 3. Logistics The recipient will be responsible for international and domestic travel arrangements...

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.

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.

Enthalpy of sublimation as measured using a silicon oscillator

NASA Astrophysics Data System (ADS)

Shakeel, Hamza; Pomeroy, J. M.

In this study, we report the enthalpy of sublimation of common gases (nitrogen, oxygen, argon, carbon dioxide, neon, krypton, xenon, and water vapor) using a large area silicon oscillator with a sub-ng (~0.027 ng/cm2) mass sensitivity. The double paddle oscillator design enables high frequency stability (17 ppb) at cryogenic temperatures and provides a consistent technique for enthalpy measurements. The enthalpies of sublimation are derived from the rate of mass loss during programmed thermal desorption and are detected as a change in the resonance frequency of the self-tracking oscillator. These measured enthalpy values show excellent agreement with the accepted literature values.

Strategic Investment Plan Fiscal Year 1993.

DTIC Science & Technology

1993-09-01

Groundwater ........................ 283 Heavy Metals in Soils, Sludges, Sediments and Water .................... 321 Energetics in Soils and Groundwater...technologies and tools to achieve a design for reconfiguring existing PEP production facilities into agile factories which will reduce total life cycle wastes...facilities. When use of existing facilities is not practical, a special demonstration testbed may be built. The factory design will then be developed

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.

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.

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.

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.

Prenatal stress and balance of the child's cardiac autonomic nervous system at age 5-6 years.

PubMed

van Dijk, Aimée E; van Eijsden, Manon; Stronks, Karien; Gemke, Reinoud J B J; Vrijkotte, Tanja G M

2012-01-01

Autonomic nervous system (ANS) misbalance is a potential causal factor in the development of cardiovascular disease. The ANS may be programmed during pregnancy due to various maternal factors. Our aim is to study maternal prenatal psychosocial stress as a potential disruptor of cardiac ANS balance in the child. Mothers from a prospective birth cohort (ABCD study) filled out a questionnaire at gestational week 16 [IQR 12-20], that included validated instruments for state anxiety, depressive symptoms, pregnancy-related anxiety, parenting daily hassles and job strain. A cumulative stress score was also calculated (based on 80(th) percentiles). Indicators of cardiac ANS in the offspring at age 5-6 years are: pre-ejection period (PEP), heart rate (HR), respiratory sinus arrhythmia (RSA) and cardiac autonomic balance (CAB), measured with electrocardiography and impedance cardiography in resting supine and sitting positions. 2,624 mother-child pairs, only single births, were available for analysis. The stress scales were not significantly associated with HR, PEP, RSA and CAB (p≥0.17). Accumulation of maternal stress was also not associated with HR, PEP, RSA and CAB (p≥0.07). Results did not support the hypothesis that prenatal maternal psychosocial stress deregulates cardiac ANS balance in the offspring, at least in rest, and at the age of five-six years.

Processing digital images and calculation of beam emittance (pepper-pot method for the Krion source)

NASA Astrophysics Data System (ADS)

Alexandrov, V. S.; Donets, E. E.; Nyukhalova, E. V.; Kaminsky, A. K.; Sedykh, S. N.; Tuzikov, A. V.; Philippov, A. V.

2016-12-01

Programs for the pre-processing of photographs of beam images on the mask based on Wolfram Mathematica and Origin software are described. Angles of rotation around the axis and in the vertical plane are taken into account in the generation of the file with image coordinates. Results of the emittance calculation by the Pep_emit program written in Visual Basic using the generated file in the test mode are presented.

The Woods Hole Partnership Education Program: Increasing Diversity in the Ocean and Environmental Sciences in One Influential Science Community

NASA Astrophysics Data System (ADS)

Jearld, A.

2011-12-01

To increase diversity in one influential science community, a consortium of public and private institutions created the Woods Hole Partnership Education Program, or PEP, in 2008. Participating institutions are the Marine Biological Laboratory, Northeast Fisheries Science Center of NOAA's Fisheries Service, Sea Education Association, U.S. Geological Survey, Woods Hole Oceanographic Institution, the Woods Hole Research Center, and University of Maryland Eastern Shore. Aimed at college juniors and seniors with some course work in marine and/or environmental sciences, PEP is a four-week course and a six-to-eight-week individual research project under the guidance of a research mentor. Forty-six students have participated to date. Investigators from the science institutions serve as course faculty and research mentors. We listened to experts regarding critical mass, mentoring, adequate support, network recruitment, and then built a program based on those features. Three years in we have a program that works and that has its own model for choosing applicants and for matching with mentors. We continue fine-tuning our match process, enhancing mentoring skills, preparing our students for a variety of lab cultures, and setting expectations high while remaining supportive. Our challenges now are to keep at it, using leverage instead of capacity to make a difference. Collaboration, not competition, is key since a rising tide floats all boats.

Induced-fit Mechanism for Prolyl Endopeptidase

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

Li, Min; Chen, Changqing; Davies, David R.

2010-11-15

Prolyl peptidases cleave proteins at proline residues and are of importance for cancer, neurological function, and type II diabetes. Prolyl endopeptidase (PEP) cleaves neuropeptides and is a drug target for neuropsychiatric diseases such as post-traumatic stress disorder, depression, and schizophrenia. Previous structural analyses showing little differences between native and substrate-bound structures have suggested a lock-and-key catalytic mechanism. We now directly demonstrate from seven structures of Aeromonus punctata PEP that the mechanism is instead induced fit: the native enzyme exists in a conformationally flexible opened state with a large interdomain opening between the {beta}-propeller and {alpha}/{beta}-hydrolase domains; addition of substrate tomore » preformed native crystals induces a large scale conformational change into a closed state with induced-fit adjustments of the active site, and inhibition of this conformational change prevents substrate binding. Absolute sequence conservation among 28 orthologs of residues at the active site and critical residues at the interdomain interface indicates that this mechanism is conserved in all PEPs. This finding has immediate implications for the use of conformationally targeted drug design to improve specificity of inhibition against this family of proline-specific serine proteases.« 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

First-episode psychosis and migration in Italy (PEP-Ita migration): a study in the Italian mental health services

PubMed Central

2014-01-01

Background It has been frequently reported a higher incidence of psychotic disorders in immigrants than in native populations. There is, however, a lack of knowledge about risk factors which may explain this phenomenon. A better understanding of the causes of psychosis among first-generation migrants is highly needed, particularly in Italy, a country with a recent massive migration. Methods/Design The “Italian study on first-episode psychosis and migration (PEP-Ita)” is a prospective observational study over a two-year period (1 January 2012–31 December 2013) which will be carried out in 11 Italian mental health centres. All participating centres will collect data about all new cases of migrants with first-episode psychosis. The general purpose (“core”) of the PEP-Ita study is to explore the socio-demographic and clinical characteristics, and the pathways to care of a population of first-episode psychosis migrants in Italy. Secondary aims of the study will be: 1) to understand risk and protective factors for the development of psychotic disorders in migrants; 2) to evaluate the correlations between psychopathology of psychotic disorders in migrants and socio-demographic characteristics, migration history, life experiences; 3) to evaluate the clinical and social outcomes of first-episode psychoses in migrants. Discussion The results of the PEP-Ita study will allow a better understanding of risk factors for psychosis in first-generation migrants in Italy. Moreover, our results will contribute to the development of prevention programmes for psychosis and to the improvement of early intervention treatments for the migrant population in Italy. PMID:24957972

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.

GO, an exec for running the programs: CELL, COLLIDER, MAGIC, PATRICIA, PETROS, TRANSPORT, and TURTLE

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

Shoaee, H.

1982-05-01

An exec has been written and placed on the PEP group's public disk to facilitate the use of several PEP related computer programs available on VM. The exec's program list currently includes: CELL, COLLIDER, MAGIC, PATRICIA, PETROS, TRANSPORT, and TURTLE. In addition, provisions have been made to allow addition of new programs to this list as they become available. The GO exec is directly callable from inside the Wylbur editor (in fact, currently this is the only way to use the GO exec.). It provides the option of running any of the above programs in either interactive or batch mode.more » In the batch mode, the GO exec sends the data in the Wylbur active file along with the information required to run the job to the batch monitor (BMON, a virtual machine that schedules and controls execution of batch jobs). This enables the user to proceed with other VM activities at his/her terminal while the job executes, thus making it of particular interest to the users with jobs requiring much CPU time to execute and/or those wishing to run multiple jobs independently. In the interactive mode, useful for small jobs requiring less CPU time, the job is executed by the user's own Virtual Machine using the data in the active file as input. At the termination of an interactive job, the GO exec facilitates examination of the output by placing it in the Wylbur active file.« less

GO, an exec for running the programs: CELL, COLLIDER, MAGIC, PATRICIA, PETROS, TRANSPORT and TURTLE

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

Shoaee, H.

1982-05-01

An exec has been written and placed on the PEP group's public disk (PUBRL 192) to facilitate the use of several PEP related computer programs available on VM. The exec's program list currently includes: CELL, COLLIDER, MAGIC, PATRICIA, PETROS, TRANSPORT, and TURTLE. In addition, provisions have been made to allow addition of new programs to this list as they become available. The GO exec is directly callable from inside the Wylbur editor (in fact, currently this is the only way to use the GO exec.) It provides the option of running any of the above programs in either interactive ormore » batch mode. In the batch mode, the GO exec sends the data in the Wylbur active file along with the information required to run the job to the batch monitor (BMON, a virtual machine that schedules and controls execution of batch jobs). This enables the user to proceed with other VM activities at his/her terminal while the job executes, thus making it of particular interest to the users with jobs requiring much CPU time to execute and/or those wishing to run multiple jobs independently. In the interactive mode, useful for small jobs requiring less CPU time, the job is executed by the user's own Virtual Machine using the data in the active file as input. At the termination of an interactive job, the GO exec facilitates examination of the output by placing it in the Wylbur active file.« less

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…

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.

PEP Support: Laboratory Scale Leaching and Permeate Stability Tests

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

Russell, Renee L.; Peterson, Reid A.; Rinehart, Donald E.

2010-05-21

This report documents results from a variety of activities requested by the Hanford Tank Waste Treatment and Immobilization Plant (WTP). The activities related to caustic leaching, oxidative leaching, permeate precipitation behavior of waste as well as chromium (Cr) leaching are: • Model Input Boehmite Leaching Tests • Pretreatment Engineering Platform (PEP) Support Leaching Tests • PEP Parallel Leaching Tests • Precipitation Study Results • Cr Caustic and Oxidative Leaching Tests. Leaching test activities using the PEP simulant provided input to a boehmite dissolution model and determined the effect of temperature on mass loss during caustic leaching, the reaction rate constantmore » for the boehmite dissolution, and the effect of aeration in enhancing the chromium dissolution during caustic leaching. Other tests were performed in parallel with the PEP tests to support the development of scaling factors for caustic and oxidative leaching. Another study determined if precipitate formed in the wash solution after the caustic leach in the PEP. Finally, the leaching characteristics of different chromium compounds under different conditions were examined to determine the best one to use in further testing.« less

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.

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.

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.

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

What Causes Reliance on English? Challenges and Instructional Suggestions in a Drive for Using a Target Language Only

ERIC Educational Resources Information Center

Bae, Gyseon; Kim, Eunju

2008-01-01

Given the raised graduation requirement of the proficiency Enhancement Program (PEP) to attain proficiency levels of "2+," "2+," and "2," the importance of target language use has been highly emphasized across language schools at Defense Language Institute Foreign Language Center (DLIFLC). This article discusses some of the challenges associated…

Alternatives to Traditional Cardio-Labs: The Interactive Fitness Experience

ERIC Educational Resources Information Center

Barney, David; Mauch, Lois

2007-01-01

In the last four years Carol M. White Physical Education Program (PEP) grants have been made available to physical educators with the purpose of combating the obesity crisis that plagues the country. Through an application process, and based on the needs of the school district, funds are awarded to help and assist physical education programs…

75 FR 34910 - Office of Safe and Drug-Free Schools; Overview Information; Carol M. White Physical Education...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-18

... M. White Physical Education Program (PEP) provides grants to local educational agencies (LEAs) and... this competition, this priority is an absolute priority. Under 34 CFR 75.105(c)(3), we consider only...(c)(2)(i), we will award an additional 3 points to an application that meets this priority. This...

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

Code of Federal Regulations, 2014 CFR

2014-07-01

... monitor. 3.3.4.4Pb Performance Evaluation Program (PEP) Procedures. Each year, one performance evaluation... Information 2. Quality System Requirements 3. Measurement Quality Check Requirements 4. Calculations for Data... 10 of this appendix) and at a national level in references 1, 2, and 3 of this appendix. 1...

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

Code of Federal Regulations, 2013 CFR

2013-07-01

... monitor. 3.3.4.4Pb Performance Evaluation Program (PEP) Procedures. Each year, one performance evaluation... Information 2. Quality System Requirements 3. Measurement Quality Check Requirements 4. Calculations for Data... 10 of this appendix) and at a national level in references 1, 2, and 3 of this appendix. 1...

Development of a Web-Based Intervention for Addressing Distress in Caregivers of Patients Receiving Stem Cell Transplants: Formative Evaluation With Qualitative Interviews and Focus Groups

PubMed

Pensak, Nicole Amoyal; Joshi, Tanisha; Simoneau, Teresa; Kilbourn, Kristin; Carr, Alaina; Kutner, Jean; Laudenslager, Mark L

2017-06-22

Caregivers of cancer patients experience significant burden and distress including depression and anxiety. We previously demonstrated the efficacy of an eight session, in-person, one-on-one stress management intervention to reduce distress in caregivers of patients receiving allogeneic hematopoietic stem cell transplants (allo-HSCT). The objective of this study was to adapt and enhance the in-person caregiver stress management intervention to a mobilized website (eg, tablet, smartphone, or computer-based) for self-delivery in order to enhance dissemination to caregiver populations most in need. We used an established approach for development of a mhealth intervention, completing the first two research and evaluation steps: Step One: Formative Research (eg, expert and stakeholder review from patients, caregivers, and palliative care experts) and Step Two: Pretesting (eg, Focus Groups and Individual Interviews with caregivers of patients with autologous HSCT (auto-HSCT). Step one included feedback elicited for a mock-up version of Pep-Pal session one from caregiver, patients and clinician stakeholders from a multidisciplinary palliative care team (N=9 caregivers and patient stakeholders and N=20 palliative care experts). Step two included two focus groups (N=6 caregivers) and individual interviews (N=9 caregivers) regarding Pep-Pal's look and feel, content, acceptability, and potential usability/feasibility. Focus groups and individual interviews were audio-recorded. In addition, individual interviews were transcribed, and applied thematic analysis was conducted in order to gain an in-depth understanding to inform the development and refinement of the mobilized caregiver stress management intervention, Pep-Pal (PsychoEducation and skills for Patient caregivers). Overall, results were favorable. Pep-Pal was deemed acceptable for caregivers of patients receiving an auto-HSCT. The refined Pep-Pal program consisted of 9 sessions (Introduction to Stress, Stress and the Mind Body Connection, How Thoughts Can Lead to Stress, Coping with Stress, Strategies for Maintaining Energy and Stamina, Coping with Uncertainty, Managing Changing Relationships and Communicating Needs, Getting the Support You Need, and Improving Intimacy) delivered via video instruction through a mobilized website. Feedback from stakeholder groups, focus groups, and individual interviews provided valuable feedback in key areas that was integrated into the development of Pep-Pal with the goal of enhancing dissemination, engagement, acceptability, and usability. ©Nicole Amoyal Pensak, Tanisha Joshi, Teresa Simoneau, Kristin Kilbourn, Alaina Carr, Jean Kutner, Mark L. Laudenslager. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 22.06.2017.

Effects of Supervised Structured Aerobic Exercise Training Program on Interleukin-6, Nitric Oxide Synthase-1, and Cyclooxygenase-2 in Type 2 Diabetes Mellitus.

PubMed

Karimi, Hossein; Rehman, Syed Shakil Ur; Gillani, Syed Amir

2017-06-01

To determine the effects of supervised structured aerobic exercise training (SSAET) program on interleukin-6 (IL-6), nitric oxide synthase 1 (NOS-1), and cyclooxygenase-2 (COX-2) in type 2 diabetes mellitus (T2DM). Randomized controlled trial. Riphah Rehabilitation and Research Centre, Railways General Hospital, Rawalpindi, from January 2015 to June 2016. Patients of either gender of minimum one year history of T2DM ranging from 40-70 years of age were included. Those with chronic systemic diseases, history of regular exercise, smoking, and those on dietary plan were excluded. Atotal of 195 patients were screened; 120 were selected and 102 agreed to participate in the study. They were randomly placed into experimental and control groups. SSAETprogram, routine medication, and dietary plan were applied in experimental group; whereas, control group was managed with routine medication and dietary plan for 25 weeks. IL-6, NOS-1, and COX-2 were assessed at baseline and 25 weeks. SSAET program, routine medication and dietary plan showed significantly improved IL-6 (pre-mean=0.25 ±0.11ng/ml, post-mean=0.19 ±0.04 ng/ml), NOS-1 (pre-median=4.65 ng/ml, IQ range=1.04 ng/ml), (post-median=2.72 ng/ml, IQ range=1.60 ng/ml), and COX-2 (pre-mean=18.72 ±4.42 ng/ml, post-mean=15.18 ±2.63 ng/ml) in experimental group, as compared with control group managed by routine medication and dietary plan, where deterioration was noted in IL-6 (pre-mean=0.23 ±0.08 ng/ml, post-mean=0.27 ±0.08 ng/ml) and COX-2 (pre-mean=18.49 ±4.56 ng/ml, postmean=19.10 ±4.76 ng/ml), while NOS-1 slight improvement (pre-mean=4.99 ng/ml, IQ range=2.67 ng/ml), (postmean=4.56 ng/ml, IQ range=3.85 ng/ml). Statistically at the baseline the p-values were not significant (p>0.05) in both experimental and control groups for IL-6, COX-2 and NOS-1; while after 25 weeks of intervention, the experimental group showed significant improvement (p<0.05) in comparison with the control group. SSAET program, routine medication, and dietary plan had positive effect on IL-6, NOS-1, and COX-2 in T2DM patients.

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.

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 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.

Particle Engulfment and Pushing By Solidifying Interfaces - Recent Theoretical and Experimental Developments

NASA Technical Reports Server (NTRS)

Stefanescu, D. M.; Catalina, A. V.; Juretzko, Frank R.; Sen, Subhayu; Curreri, P. A.

2003-01-01

The objective of the work on Particle Engulfment and Pushing by Solidifying Interfaces (PEP) include: 1) to obtain fundamental understanding of the physics of particle pushing and engulfment, 2) to develop mathematical models to describe the phenomenon, and 3) to perform critical experiments in the microgravity environment of space to provide benchmark data for model validation. Successful completion of this project will yield vital information relevant to a diverse area of terrestrial applications. With PEP being a long term research effort, this report will focus on advances in the theoretical treatment of the solid/liquid interface interaction with an approaching particle, experimental validation of some aspects of the developed models, and the experimental design aspects of future experiments to be performed on board the International Space Station.

Numerical assessment of residual formability in sheet metal products: towards design for sustainability

NASA Astrophysics Data System (ADS)

Falsafi, Javad; Demirci, Emrah; Silberschmidt, Vadim. V.

2016-08-01

A new computational scheme is presented to addresses cold recyclability of sheet- metal products. Cold recycling or re-manufacturing is an emerging area studied mostly empirically; in its current form, it lacks theoretical foundation especially in the area of sheet metals. In this study, a re-formability index was introduced based on post-manufacture residual formability in sheet metal products. This index accounts for possible levels of deformation along different strain paths based on Polar Effective Plastic Strain (PEPS) technique. PEPS is strain-path independent, hence provides a foundation for residual formability analysis. A user- friendly code was developed to implement this assessment in conjunction with advanced finite- element (FE) analysis. The significance of this approach is the advancement towards recycling of sheet metal products without melting them.

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...

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.

Upper Atmospheric Effects of the HF Active Auroral Research Program Ionospheric Research Instrument (HAARP IRI)

DTIC Science & Technology

1993-05-01

RESEARCH INSTRUMENT ( HAARP IRI) V. Eccles R. Armstrong Mission Research Corporation One Tara Blvd Nashua, NH 03062-2801 May 1993 Scientific Report No...INSTRUMENT ( HAARP IRI) PR 2310 STA G3 WU BM6. AUTHOR(S) V. Eccles and R. Armstrong 7. PERFOR•IlNG ORGANIZATION NAME(S) AND AOORESS(ES) 8. PERFORMING...Because the HAARP (HF Active Auroral Research Program) facility is designed to mimic and investigate certain natural processes, a study of possible

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.

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.

Options for Organizing the Tanker Airlift Control Center Flight Dispatch Function: An Exploratory Concept Study

DTIC Science & Technology

2000-06-01

it poised to fall? Am I prepared to pay the applicable capital gains tax ? Each of these questions could represent a decision frame. The...Center (FEDSIM). AMC Corporate Systems Analysis, Design , and Implementation PEP 18 TACC Project. Falls Chruch , VA: Federal Systems Integration and

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.

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.

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.

[Behavioral intervention for preschool children with autism – outcome of parent-based Intervention].

PubMed

Molnár, Claire; Eldevik, Sigmund

2017-01-01

Early intensive behavioral intervention (EIBI) has proved to be an effective intervention for children with autism spectrum disorder (ASD). In this exploratory study, we evaluated the effects of a community-based service model with parents as active therapists. 13 children with ASD between 2 and 5 years of age at intake participated in the study. A waiting-list control design was employed. The children received 1 year of home-based EIBI for approximately 20 hours a week, their parents functioning as primary therapists. The waiting-list control group consisted of seven children who were tested 6 months before the intervention commenced. The intervention was based on the University of California at Los Angeles Young Autism Project model (UCLA YAP; Lovaas, 1981, 1987, 2003). The Psychoeducational Profile (3rd ed., PEP-3), the Parenting Stress Index (PSI), and the Childhood Autism Rating Scale (2nd ed., CARS 2) were used to measure outcome. In addition, a mental developmental index (MDI) was calculated on the basis of the Cognitive Verbal/Preverbal subscale of the PEP-3. After 1 year of EIBI, we found a significant increase in the PEP-3 scores and MDI scores as well as a significant reduction in the CARS 2 scores. No significant changes were seen when participants were on the waiting list. The stress level of the parents did not change significantly and in fact showed overall a slight decrease. This model of providing EIBI appears to hold some promise. Comprehensive parental involvement did not affect their stress level. The study need to be replicated with a larger sample and an improved design.

Design and mechanistic study of a novel gold nanocluster-based drug delivery system.

PubMed

Li, Qinzhen; Pan, Yiting; Chen, Tiankai; Du, Yuanxin; Ge, Honghua; Zhang, Buchang; Xie, Jianping; Yu, Haizhu; Zhu, Manzhou

2018-05-22

Chemically-triggered drug delivery systems (DDSs) have been extensively studied as they do not require specialized equipment to deliver the drug and can deeply penetrate human tissue. However, their syntheses are complicated and they tend to be cytotoxic, which restricts their clinical utility. In this work, the self-regulated drug loading and release capabilities of peptide-protected gold nanoclusters (Pep-Au NCs) are investigated using vancomycin (Van) as the model drug. Gold nanoclusters (Au NCs) coated with a custom-designed pentapeptide are synthesized as drug delivery nanocarriers and loaded with Van - a spontaneous process reliant on the specific binding between Van and the custom-designed peptide. The Van-loaded Au NCs show comparable antimicrobial activity with Van on its own, and the number of Van released by the Pep-Au NCs is found to be proportional to the amount of bacteria present. The controlled nature of the Van release is very encouraging, and predominantly due to the stronger binding affinity of Van with bacteria than that with Au NCs. In addition, these fluorescent Au NCs could also be used to construct temperature sensors, which enable the in vitro and in vivo bioimaging.

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.

An Examination of Physical Education Data Sources and Collection Procedures during a Federally Funded Grant

ERIC Educational Resources Information Center

Dauenhauer, Brian D.; Keating, Xiaofen D.; Lambdin, Dolly

2018-01-01

Purpose: This study aimed to conduct an in-depth investigation into physical education data sources and collection procedures in a district that was awarded a Physical Education Program (PEP) grant. Method: A qualitative, multi-site case study was conducted in which a single school district was the overarching case and eight schools served as…

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…

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...

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...

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...

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.

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.

A unique power supply for the PEP II klystron at SLAC

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

Cassel, R.; Nguyen, M.N.

1997-07-01

Each of the eight 1.2 MW RF klystrons for the PEP-II storage rings require a 2.5 MVA DC power supply of 83 Kv at 23 amps. The design for the supply was base on three factors, low cost, small size to fit existing substation pads, and good protection against damage to the klystron including klystron gun arcs. The supply uses a 12 pulse 12.5 KV primary thyristor star point controller with primary filter inductor to provide rapid voltage control, good voltage regulation, and fast turn off during klystron tube faults. The supply also uses a unique secondary rectifier, filter capacitormore » configuration to minimize the energy available under a klystron fault. The voltage control is from 0--90 KV with a regulation of < 0.1% and voltage ripple of < 1% P-P, (< 0.2% RMS) above 60 KV. The supply utilizes a thyristor crowbar, which under a klystron tube arc limits the energy in the klystron arc to < 5 joules. If the thyristor crowbar is disabled the energy supplied is < 40 joules into the arc. The size of the supply was reduced small enough to fit the existing PEP transformer yard pads. The cost of the power supply was < $140 per KVA.« less

Novel cyclo-peptides inhibit Ebola pseudotyped virus entry by targeting primed GP protein.

PubMed

Li, Quanjie; Ma, Ling; Yi, Dongrong; Wang, Han; Wang, Jing; Zhang, Yongxin; Guo, Ying; Li, Xiaoyu; Zhou, Jinming; Shi, Yi; Gao, George F; Cen, Shan

2018-07-01

Ebola virus (EBOV) causes fatal hemorrhagic fever with high death rates in human. Currently, there are no available clinically-approved prophylactic or therapeutic treatments. The recently solved crystal structure of cleavage-primed EBOV glycoprotein (GPcl) in complex with the C domain of endosomal protein Niemann-Pick C1 (NPC1) provides a new target for the development of EBOV entry inhibitors. In this work, a computational approach using docking and molecular dynamic simulations is carried out for the rational design of peptide inhibitors. A novel cyclo-peptide (Pep-3.3) was identified to target at the late stage of EBOV entry and exhibit specific inhibitory activity against EBOV-GP pseudotyped viruses, with 50% inhibitory concentration (IC50) of 5.1 μM. In vitro binding assay and molecular simulations revealed that Pep-3.3 binds to GPcl with a KD value of 69.7 μM, through interacting with predicted residues in the hydrophobic binding pocket of GPcl. Mutation of predicted residues T83 caused resistance to Pep-3.3 inhibition in viral infectivity, providing preliminary support for the model of the peptide binding to GPcl. This study demonstrates the feasibility of inhibiting EBOV entry by targeting GPcl with peptides. Copyright © 2018 Elsevier B.V. All rights reserved.

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.

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.

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.

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.

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.

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.

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.

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.

PVT-NG sensor final report.

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

Mitchell, Dean James; Brusseau, Charles A.

2012-01-01

This document is a final report for the polyvinyl toluene (PVT) neutron-gamma (PVT-NG) project, which was sponsored by the Domestic Nuclear Detection Office (DNDO). The PVT-NG sensor uses PVT detectors for both gamma and neutron detection. The sensor exhibits excellent spectral resolution and gain stabilization, which are features that are beneficial for detection of both gamma-ray and neutron sources. In fact, the ability to perform isotope identification based on spectra that were measured by the PVT-NG sensor was demonstrated. As described in a previous report, the neutron sensitivity of the first version of the prototype was about 25% less thanmore » the DNDO requirement of 2.5 cps/ng for bare Cf-252. This document describes design modifications that were expected to improve the neutron sensitivity by about 50% relative to the PVT-NG prototype. However, the project was terminated before execution of the design modifications after portal vendors demonstrated other technologies that enable neutron detection without the use of He-3. Nevertheless, the PVT-NG sensor development demonstrated several performance goals that may be useful in future portal designs.« less

SH2 Ligand Prediction-Guidance for In-Silico Screening.

PubMed

Li, Shawn S C; Li, Lei

2017-01-01

Systematic identification of binding partners for SH2 domains is important for understanding the biological function of the corresponding SH2 domain-containing proteins. Here, we describe two different web-accessible computer programs, SMALI and DomPep, for predicting binding ligands for SH2 domains. The former was developed using a Scoring Matrix method and the latter based on the Support Vector Machine model.

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.

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.

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.

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

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.

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.

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.

Salivary Pepsin Lacks Sensitivity as a Diagnostic Tool to Evaluate Extraesophageal Reflux Disease.

PubMed

Dy, Fei; Amirault, Janine; Mitchell, Paul D; Rosen, Rachel

2016-10-01

To determine the sensitivity of salivary pepsin compared with multichannel intraluminal impedance with pH testing (pH-MII), endoscopy, and gastroesophageal reflux disease (GERD) questionnaires. We prospectively recruited 50 children from Boston Children's Hospital who were undergoing pH-MII to evaluate for GERD. The patients completed 24-hour pH-MII testing, completed symptom and quality of life questionnaires, and provided a saliva specimen that was analyzed using the PepTest lateral flow test. A subset of patients also underwent bronchoscopy and esophagogastroduodenoscopy. Receiver operating characteristic curve analyses were performed to determine the sensitivity of salivary pepsin compared with each reference standard. Twenty-one of the 50 patients (42%) were salivary pepsin-positive, with a median salivary pepsin concentration of 10 ng/mL (IQR, 10-55 ng/mL). There was no significant difference in the distributions of acid, nonacid, total reflux episodes, full column reflux, or any other reflux variable in patients who were pepsin-positive compared with those who were pepsin-negative (P > .50). There was no significant correlation between the number of reflux episodes and pepsin concentration (P > .10). There was no positive relationship between salivary pepsin positivity, any extraesophageal symptoms or quality of life scores, or inflammation on bronchoscopy or esophagogastroduodenoscopy (P > .30). Salivary pepsin measurement has a low sensitivity for predicting pathological gastroesophageal reflux in children. 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.

Effectiveness of Metacognitive Therapy in Patients with Social Anxiety Disorder: A Pilot Investigation.

PubMed

Lakshmi, Jayasree; Sudhir, Paulomi Matam; Sharma, Mahendra Prakash; Math, Suresh Bada

2016-01-01

Metacognitive therapy (MCT) is a recent psychological intervention for emotional disorders. Its efficacy in social anxiety disorder (SAD) is yet to be established. We examined the effectiveness of an MCT in patients with SAD. A two group case-control design with baseline, post, and 3 months follow-up was adopted. The control group received training in applied relaxation (AR). Four patients with Diagnostic and Statistical Manual-IV diagnosis of social anxiety were sequentially allotted to receive either MCT or AR. Patients were assessed on postevent processing (PEP), social anxiety, depression, and fear on negative evaluation. Clinical significance was calculated. MCT was more effective than AR in reducing social avoidance, PEP, and self-consciousness. While overall both interventions were effective in reducing social anxiety, MCT was marginally more effective. MCT may be a promising therapeutic approach in the management of SAD.

Lattice Commissioning Stretgy Simulation for the B Factory

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

Lee, M.; Whittum, D.; Yan, Y.

2011-08-26

To prepare for the PEP-II turn on, we have studied one commissioning strategy with simulated lattice errors. Features such as difference and absolute orbit analysis and correction are discussed. To prepare for the commissioning of the PEP-II injection line and high energy ring (HER), we have developed a system for on-line orbit analysis by merging two existing codes: LEGO and RESOLVE. With the LEGO-RESOLVE system, we can study the problem of finding quadrupole alignment and beam position (BPM) offset errors with simulated data. We have increased the speed and versatility of the orbit analysis process by using a command filemore » written in a script language designed specifically for RESOLVE. In addition, we have interfaced the LEGO-RESOLVE system to the control system of the B-Factory. In this paper, we describe online analysis features of the LEGO-RESOLVE system and present examples of practical applications.« less

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.

Children with Autism Show Altered Autonomic Adaptation to Novel and Familiar Social Partners.

PubMed

Neuhaus, Emily; Bernier, Raphael A; Beauchaine, Theodore P

2016-05-01

Social deficits are fundamental to autism spectrum disorder (ASD), and a growing body of research implicates altered functioning of the autonomic nervous system (ANS), including both sympathetic and parasympathetic branches. However, few studies have explored both branches concurrently in ASD, particularly within the context of social interaction. The current study investigates patterns of change in indices of sympathetic (pre-ejection period; PEP) and parasympathetic (respiratory sinus arrhythmia; RSA) cardiac influence as boys (ages 8-11 years) with (N = 18) and without (N = 18) ASD engage in dyadic social interaction with novel and familiar social partners. Groups showed similar patterns of autonomic change during interaction with the novel partner, but differed in heart rate, PEP, and RSA reactivity while interacting with a familiar partner. Boys without ASD evinced decreasing sympathetic and increasing parasympathetic influence, whereas boys with ASD increased in sympathetic influence. Boys without ASD also demonstrated more consistent ANS responses across partners than those with ASD, with parasympathetic responding differentiating familiar and novel interaction partners. Finally, PEP slopes with a familiar partner correlated with boys' social skills. Implications include the importance of considering autonomic state during clinical assessment and treatment, and the potential value of regulation strategies as a complement to intervention programs aiming to support social cognition and behavior. Autism Res 2016, 9: 579-591. © 2015 International Society for Autism Research, Wiley Periodicals, Inc. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.

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

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

The impact of ions on allosteric functions in human liver pyruvate kinase

PubMed Central

Alontaga, Aileen Y.

2010-01-01

Experimental designs used to monitor the magnitude of an allosteric response can greatly influence observed values. We report here the impact of buffer, monovalent cation, divalent cation and anion on the magnitude of the allosteric regulation of the affinity of human liver pyruvate kinase (hL-PYK) for substrate, phosphoenolpyruvate (PEP). The magnitudes of the allosteric activation by fructose-1,6-bisphosphate (Fru-1,6-BP) and the allosteric inhibition by alanine are independent of most, but not all buffers tested. However, these magnitudes are dependent on whether Mg2+ or Mn2+ is included as the divalent cation. In the presence of Mn2+, any change in Kapp-PEP caused by Fru-1,6-BP is minimal. hL-PYK activity does not appear to require monovalent cation. Monovalent cation binding in the active site impacts PEP affinity with minimum influence on the magnitude of allosteric coupling. However, Na+ and Li+ reduce the magnitude of the allosteric response to Fru-1,6-BP, likely due to mechanisms outside of the active site. Which anion is used to maintain a constant monovalent cation concentration also influences the magnitude of the allosteric response. The value of determining the impact of ions on allosteric function can be appreciated by considering that representative structures used in comparative studies have often been determined using protein crystals grown in diverse buffer and salt conditions. PMID:21609859

A Radar-like Iron based Nanohybrid as an Efficient and Stable Electrocatalyst for Oxygen Reduction

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

Zhong, X. Y.; Liu, Lin; Wang, Xinde

2014-05-21

The present study shows a design concept for fabricating Fe-PyNG hybrid via strong coupling between FePc and pyridine-N. The prominent features of the Fe-PyNG hybrid include high electrocatalytic activity, superior durability, and better performance than Pt/C toward ORR in alkaline media. These features potentially make Fe-PyNG an outstanding nonprecious metal cathode catalyst for fuel cells. The incorporation of Fe ion and pyridine-N afforded effective bonding and synergetic coupling effects, which lead to significant electrocatalytic performance. DFT calculations indicate that N-modified Fe is a superior site for OOH adsorption and ORR reaction. Meanwhile, the strong chemical bonding between FePc and pyridynemore » in PyNG leads to its superior stability. We believe that our present synthetic strategy can be further extended to develop other metal complexes/N-doped carbon materials for broad applications in the field of catalysts, batteries, and supercapacitors. This work was supported by National Basic Research Program of China (973 Program) (2013CB733501), the National Natural Science Foundation of China (NSFC-21306169, 21176221, 21136001 and 21101137), Zhejiang Provincial Natural Science Foundation of China (ZJNSF-R4110345) and the New Century Excellent Talents in University Program (NCET-10-0979). We thank Prof. Youqun Zhu for Instruments support. D. Mei is supported by the US Department of Energy, Office of Basic Energy Sciences, Division of Chemical Sciences, Geosciences & Biosciences. Pacific Northwest National Laboratory (PNNL) is a multiprogram national laboratory operated for DOE by Battelle. Computing time was granted by the grand challenge of computational catalysis of the William R. Wiley Environmental Molecular Sciences Laboratory (EMSL). EMSL is a national scientific user facility located at Pacific Northwest National Laboratory (PNNL) and sponsored by DOE’s Office of Biological and Environmental Research.« less

Productivity Enhancement Program (PEP) for the Power Plant Division, Naval Air Rework Facility, North Island, San Diego. Preliminary Data Required.

DTIC Science & Technology

1984-02-01

97322 C9 571H0 NOTE 1--Ht» 360214-77 M.ORKID MDRA i D - \\—r— .ofjTxx .05r51-8* 62 ZBJA 0 ZANA D YBFA 0 : : 1.S508-P81 2F-SEE...Navy Recruiting Command (Code 20) Commanding Officer, Naval Aerospace Medical Institute (Library Code 12) (2) Commanding Officer Naval Technical

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.

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

Effects of endurance and high intensity training on ICAM-1 and VCAM-1 levels and arterial pressure in obese and normal weight adolescents.

PubMed

Kargarfard, Mehdi; Lam, Eddie T C; Shariat, Ardalan; Asle Mohammadi, Mahmoud; Afrasiabi, Saleh; Shaw, Ina; Shaw, Brandon S

2016-09-01

Obesity prevalence has increased in Iranian adolescents in recent years. However, few studies have examined the impact of intervention programs on this health issue. The main objective of this study was to evaluate the effects of 8-week endurance training (ET) and high intensity interval training (HIIT) on intercellular adhesion molecule-1(ICAM-1) and vascular adhesion molecule-1(VCAM-1) levels among obese and normal-weight male adolescents. Thirty obese and 30 normal-weight subjects were assigned to the ET, HIIT, or control group for eight weeks. Before and after the intervention, ICAM-1, VCAM-1, body weight, BMI, VO2max, and blood pressures were measured. SPSS (Version 21) was used for data analysis, and the significance level was set at p < 0.05. Mixed design ANOVAs indicated that the obese participants had significantly (p < 0.05) lower ICAM-1 levels in the ET (from 509 ± 61 ng/ml to 387 ± 43 ng/ml) and HIIT (from 517 ± 72 ng/ml to 374 ± 50 ng/ml), but their VCAM-1 level was significantly (p < 0.05) reduced only after the HIIT (from 1689 ± 119 ng/ml to 1282 ± 63 ng/ml). Similarly, normal weight participants significantly (p < 0.05) lowered their ICAM-1 levels in the ET (from 296 ± 18 ng/ml to 216 ± 14 ng/ml) and HIIT (from 289 ± 22 ng/ml to 202 ± 12 ng/ml), but their VCAM-1 level was significantly (p < 0.05) reduced only after the HIIT (from 895 ± 50 ng/ml to 673 ± 142 ng/ml). Systolic blood pressure and diastolic blood pressures of all the participants were significantly (p < 0.01) decreased at the conclusion of the ET and HIIT. While both the ET and HIIT were useful in lowering the SBP and DBP of the participants, HIIT was more effective than ET in reducing ICAM-1 and VCAM-1 content in normal and obese adolescents.

Controlling and fine tuning the physical properties of two identical metal coordination sites in de novo designed three stranded coiled coil peptides.

PubMed

Iranzo, Olga; Chakraborty, Saumen; Hemmingsen, Lars; Pecoraro, Vincent L

2011-01-19

Herein we report how de novo designed peptides can be used to investigate whether the position of a metal site along a linear sequence that folds into a three-stranded α-helical coiled coil defines the physical properties of Cd(II) ions in either CdS(3) or CdS(3)O (O-being an exogenous water molecule) coordination environments. Peptides are presented that bind Cd(II) into two identical coordination sites that are located at different topological positions at the interior of these constructs. The peptide GRANDL16PenL19IL23PenL26I binds two Cd(II) as trigonal planar 3-coordinate CdS(3) structures whereas GRANDL12AL16CL26AL30C sequesters two Cd(II) as pseudotetrahedral 4-coordinate CdS(3)O structures. We demonstrate how for the first peptide, having a more rigid structure, the location of the identical binding sites along the linear sequence does not affect the physical properties of the two bound Cd(II). However, the sites are not completely independent as Cd(II) bound to one of the sites ((113)Cd NMR chemical shift of 681 ppm) is perturbed by the metalation state (apo or [Cd(pep)(Hpep)(2)](+) or [Cd(pep)(3)](-)) of the second center ((113)Cd NMR chemical shift of 686 ppm). GRANDL12AL16CL26AL30C shows a completely different behavior. The physical properties of the two bound Cd(II) ions indeed depend on the position of the metal center, having pK(a2) values for the equilibrium [Cd(pep)(Hpep)(2)](+) → [Cd(pep)(3)](-) + 2H(+) (corresponding to deprotonation and coordination of cysteine thiols) that range from 9.9 to 13.9. In addition, the L26AL30C site shows dynamic behavior, which is not observed for the L12AL16C site. These results indicate that for these systems one cannot simply assign a "4-coordinate structure" and assume certain physical properties for that site since important factors such as packing of the adjacent Leu, size of the intended cavity (endo vs exo) and location of the metal site play crucial roles in determining the final properties of the bound Cd(II).

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.

Cost-Effectiveness Evaluation of a Novel Integrated Bite Case Management Program for the Control of Human Rabies, Haiti 2014–2015

PubMed Central

Undurraga, Eduardo A.; Meltzer, Martin I.; Tran, Cuc H.; Atkins, Charisma Y.; Etheart, Melissa D.; Millien, Max F.; Adrien, Paul; Wallace, Ryan M.

2017-01-01

Haiti has the highest burden of rabies in the Western hemisphere, with 130 estimated annual deaths. We present the cost-effectiveness evaluation of an integrated bite case management program combining community bite investigations and passive animal rabies surveillance, using a governmental perspective. The Haiti Animal Rabies Surveillance Program (HARSP) was first implemented in three communes of the West Department, Haiti. Our evaluation encompassed all individuals exposed to rabies in the study area (N = 2,289) in 2014–2015. Costs (2014 U.S. dollars) included diagnostic laboratory development, training of surveillance officers, operational costs, and postexposure prophylaxis (PEP). We used estimated deaths averted and years of life gained (YLG) from prevented rabies as health outcomes. HARSP had higher overall costs (range: $39,568–$80,290) than the no-bite-case-management (NBCM) scenario ($15,988–$26,976), partly from an increased number of bite victims receiving PEP. But HARSP had better health outcomes than NBCM, with estimated 11 additional annual averted deaths in 2014 and nine in 2015, and 654 additional YLG in 2014 and 535 in 2015. Overall, HARSP was more cost-effective (US$ per death averted) than NBCM (2014, HARSP: $2,891–$4,735, NBCM: $5,980–$8,453; 2015, HARSP: $3,534–$7,171, NBCM: $7,298–$12,284). HARSP offers an effective human rabies prevention solution for countries transitioning from reactive to preventive strategies, such as comprehensive dog vaccination. PMID:28719253

Cost-Effectiveness Evaluation of a Novel Integrated Bite Case Management Program for the Control of Human Rabies, Haiti 2014-2015.

PubMed

Undurraga, Eduardo A; Meltzer, Martin I; Tran, Cuc H; Atkins, Charisma Y; Etheart, Melissa D; Millien, Max F; Adrien, Paul; Wallace, Ryan M

2017-06-01

AbstractHaiti has the highest burden of rabies in the Western hemisphere, with 130 estimated annual deaths. We present the cost-effectiveness evaluation of an integrated bite case management program combining community bite investigations and passive animal rabies surveillance, using a governmental perspective. The Haiti Animal Rabies Surveillance Program (HARSP) was first implemented in three communes of the West Department, Haiti. Our evaluation encompassed all individuals exposed to rabies in the study area ( N = 2,289) in 2014-2015. Costs (2014 U.S. dollars) included diagnostic laboratory development, training of surveillance officers, operational costs, and postexposure prophylaxis (PEP). We used estimated deaths averted and years of life gained (YLG) from prevented rabies as health outcomes. HARSP had higher overall costs (range: $39,568-$80,290) than the no-bite-case-management (NBCM) scenario ($15,988-$26,976), partly from an increased number of bite victims receiving PEP. But HARSP had better health outcomes than NBCM, with estimated 11 additional annual averted deaths in 2014 and nine in 2015, and 654 additional YLG in 2014 and 535 in 2015. Overall, HARSP was more cost-effective (US$ per death averted) than NBCM (2014, HARSP: $2,891-$4,735, NBCM: $5,980-$8,453; 2015, HARSP: $3,534-$7,171, NBCM: $7,298-$12,284). HARSP offers an effective human rabies prevention solution for countries transitioning from reactive to preventive strategies, such as comprehensive dog vaccination.

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

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

Ball Powder Production Wastewater Biodegradation Support Studies - With Nitroglycerine

DTIC Science & Technology

1989-02-01

in the wastewater. Characterization of the ball powder wastewater stream showed an actual average NG inlet concentration of 192 mg/L. Pilot test...the first phase of pilot testing, the recommendation was made to conduct an additional pilot test phase to determine the effect of nitroglycerin (NG...NG by aerobic bacteria, a pilot program was undertaken with the following objectives: 1) to determine the concentration of NG in the ball powder

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.

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.

Leprosy Post-Exposure Prophylaxis (LPEP) programme: study protocol for evaluating the feasibility and impact on case detection rates of contact tracing and single dose rifampicin

PubMed Central

Barth-Jaeggi, Tanja; Steinmann, Peter; Mieras, Liesbeth; van Brakel, Wim; Richardus, Jan Hendrik; Tiwari, Anuj; Bratschi, Martin; Cavaliero, Arielle; Vander Plaetse, Bart; Mirza, Fareed; Aerts, Ann

2016-01-01

Introduction The reported number of new leprosy patients has barely changed in recent years. Thus, additional approaches or modifications to the current standard of passive case detection are needed to interrupt leprosy transmission. Large-scale clinical trials with single dose rifampicin (SDR) given as post-exposure prophylaxis (PEP) to contacts of newly diagnosed patients with leprosy have shown a 50–60% reduction of the risk of developing leprosy over the following 2 years. To accelerate the uptake of this evidence and introduction of PEP into national leprosy programmes, data on the effectiveness, impact and feasibility of contact tracing and PEP for leprosy are required. The leprosy post-exposure prophylaxis (LPEP) programme was designed to obtain those data. Methods and analysis The LPEP programme evaluates feasibility, effectiveness and impact of PEP with SDR in pilot areas situated in several leprosy endemic countries: India, Indonesia, Myanmar, Nepal, Sri Lanka and Tanzania. Complementary sites are located in Brazil and Cambodia. From 2015 to 2018, contact persons of patients with leprosy are traced, screened for symptoms and assessed for eligibility to receive SDR. The intervention is implemented by the national leprosy programmes, tailored to local conditions and capacities, and relying on available human and material resources. It is coordinated on the ground with the help of the in-country partners of the International Federation of Anti-Leprosy Associations (ILEP). A robust data collection and reporting system is established in the pilot areas with regular monitoring and quality control, contributing to the strengthening of the national surveillance systems to become more action-oriented. Ethics and dissemination Ethical approval has been obtained from the relevant ethics committees in the countries. Results and lessons learnt from the LPEP programme will be published in peer-reviewed journals and should provide important evidence and guidance for national and global policymakers to strengthen current leprosy elimination strategies. PMID:27856484

ANALYSIS OF PROTEIN DIGESTS BY nano- SCX/RP/MSMS WITH pH SALT GRADIENT SCX ELUTION

EPA Science Inventory

The objective of this study was to optimize chromatographic parameters for complex peptide mixture analyses using two dimensional nano-LC/MSMS system. It used a strong cation exchange (SCX) and reversed phase chromatography (RP). The SCX solvent system was designed to promote pep...

47 CFR 1.1307 - Actions that may have a significant environmental effect, for which Environmental Assessments...

Code of Federal Regulations, 2010 CFR

2010-10-01

... preserve. (3) Facilities that: (i) May affect listed threatened or endangered species or designated... peak envelope power (PEP), as defined in § 2.1 of this chapter. For the case of the Cellular... section. (3) In general, when the guidelines specified in § 1.1310 are exceeded in an accessible area due...

47 CFR 1.1307 - Actions that may have a significant environmental effect, for which Environmental Assessments...

Code of Federal Regulations, 2014 CFR

2014-10-01

... designated wildlife preserve. (3) Facilities that: (i) May affect listed threatened or endangered species or... isotropically radiated power (EIRP), or peak envelope power (PEP), as defined in § 2.1 of this chapter. For the... (d) of this section. (3) In general, when the guidelines specified in § 1.1310 are exceeded in an...

47 CFR 1.1307 - Actions that may have a significant environmental effect, for which Environmental Assessments...

Code of Federal Regulations, 2013 CFR

2013-10-01

... designated wildlife preserve. (3) Facilities that: (i) May affect listed threatened or endangered species or... isotropically radiated power (EIRP), or peak envelope power (PEP), as defined in § 2.1 of this chapter. For the... (d) of this section. (3) In general, when the guidelines specified in § 1.1310 are exceeded in an...

47 CFR 1.1307 - Actions that may have a significant environmental effect, for which Environmental Assessments...

Code of Federal Regulations, 2011 CFR

2011-10-01

... preserve. (3) Facilities that: (i) May affect listed threatened or endangered species or designated... peak envelope power (PEP), as defined in § 2.1 of this chapter. For the case of the Cellular... section. (3) In general, when the guidelines specified in § 1.1310 are exceeded in an accessible area due...

47 CFR 1.1307 - Actions that may have a significant environmental effect, for which Environmental Assessments...

Code of Federal Regulations, 2012 CFR

2012-10-01

... designated wildlife preserve. (3) Facilities that: (i) May affect listed threatened or endangered species or... isotropically radiated power (EIRP), or peak envelope power (PEP), as defined in § 2.1 of this chapter. For the... paragraphs (c) and (d) of this section. (3) In general, when the guidelines specified in § 1.1310 are...

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

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.

Comparison of yoga and walking-exercise on cardiac time intervals as a measure of cardiac function in elderly with increased pulse pressure.

PubMed

Patil, Satish Gurunathrao; Patil, Shankargouda S; Aithala, Manjunatha R; Das, Kusal Kanti

Arterial aging along with increased blood pressure(BP) has become the major cardiovascular(CV) risk in elderly. The aim of the study was to compare the effects of yoga program and walking-exercise on cardiac function in elderly with increased pulse pressure (PP). An open label, parallel-group randomized controlled study design was adopted. Elderly individuals aged ≥60 years with PP≥60mmHg were recruited for the study. Yoga (study) group (n=30) was assigned for yoga training and walking (exercise) group (n=30) for walking with loosening practices for one hour in the morning for 6days in a week for 3 months. The outcome measures were cardiac time intervals derived from pulse wave analysis and ECG: resting heart rate (RHR), diastolic time(DT), ventricular ejection time(LVET), upstroke time(UT), ejection duration index (ED%), pre-ejection period (PEP), rate pressure product (RPP) and percentage of mean arterial pressure (%MAP). The mean within-yoga group change in RHR(bpm) was 4.41 (p=0.031), PD(ms): -50.29 (p=0.042), DT(ms): -49.04 (p=0.017), ED%: 2.107 (p=0.001), ES(mmHg/ms): 14.62 (p=0.118), ET(ms): -0.66 (p=0.903), UT(ms): -2.54 (p=0.676), PEP(ms): -1.25 (p=0.11) and %MAP: 2.08 (p=0.04). The mean within-control group change in HR (bpm) was 0.35 (p=0.887), PD (ms): 11.15(p=0.717), DT (ms): 11.3 (p=0.706), ED%: -0.101 (p=0.936), ES (mmHg/ms): 0.75 (p=0.926), ET(ms): 2.2 (p=0.721), UT(ms):4.7(p=455), PEP (ms): 2.1(p=0.11), %MAP: 0.65 (p=0.451). A significant difference between-group was found in RHR (p=0.036), PD (p=0.02), ED% (p=0.049), LVET (p=0.048), DT (p=0.02) and RPP (p=0.001). Yoga practice for 3 months showed a significant improvement in diastolic function with a minimal change in systolic function. Yoga is more effective than walking in improving cardiac function in elderly with high PP. Copyright © 2017 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

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.

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

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 ...

BioPepDB: an integrated data platform for food-derived bioactive peptides.

PubMed

Li, Qilin; Zhang, Chao; Chen, Hongjun; Xue, Jitong; Guo, Xiaolei; Liang, Ming; Chen, Ming

2018-03-12

Food-derived bioactive peptides play critical roles in regulating most biological processes and have considerable biological, medical and industrial importance. However, a large number of active peptides data, including sequence, function, source, commercial product information, references and other information are poorly integrated. BioPepDB is a searchable database of food-derived bioactive peptides and their related articles, including more than four thousand bioactive peptide entries. Moreover, BioPepDB provides modules of prediction and hydrolysis-simulation for discovering novel peptides. It can serve as a reference database to investigate the function of different bioactive peptides. BioPepDB is available at http://bis.zju.edu.cn/biopepdbr/ . The web page utilises Apache, PHP5 and MySQL to provide the user interface for accessing the database and predict novel peptides. The database itself is operated on a specialised server.

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.

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.

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.

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.

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.

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.

Identification of Unique Metabolites of the Designer Opioid Furanyl Fentanyl.

PubMed

Goggin, Melissa M; Nguyen, An; Janis, Gregory C

2017-06-01

The illicit drug market has seen an increase in designer opioids, including fentanyl and methadone analogs, and other structurally unrelated opioid agonists. The designer opioid, furanyl fentanyl, is one of many fentanyl analogs clandestinely synthesized for recreational use and contributing to the fentanyl and opioid crisis. A method has been developed and validated for the analysis of furanyl fentanyl and furanyl norfentanyl in urine specimens from pain management programs. Approximately 10% of samples from a set of 500 presumptive heroin-positive urine specimens were found to contain furanyl fentanyl, with an average concentration of 33.8 ng/mL, and ranging from 0.26 to 390 ng/mL. Little to no furanyl norfentanyl was observed; therefore, the furanyl fentanyl specimens were further analyzed by untargeted high-resolution mass spectrometry to identify other metabolites. Multiple metabolites, including a dihydrodiol metabolite, 4-anilino-N-phenethyl-piperidine (4-ANPP) and a sulfate metabolite were identified. The aim of the presented study was to identify the major metabolite(s) of furanyl fentanyl and estimate their concentrations for the purpose of toxicological monitoring. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Dysregulation of the adipoinsular axis -- a mechanism for the pathogenesis of hyperleptinemia and adipogenic diabetes induced by fetal programming.

PubMed

Vickers, M H; Reddy, S; Ikenasio, B A; Breier, B H

2001-08-01

Obesity and its related disorders are the most prevalent health problems in the Western world. Using the paradigm of fetal programming we developed a rodent model which displays the phenotype of obesity and metabolic disorders commonly observed in human populations. We apply maternal undernutrition throughout gestation, generating a nutrient-deprived intrauterine environment to induce fetal programming. Maternal undernutrition results in fetal growth retardation and in significantly decreased body weight at birth. Programmed offspring develop hyperphagia, obesity, hypertension, hyperleptinemia and hyperinsulinism during adult life and postnatal hypercaloric nutrition amplifies the metabolic abnormalities induced by fetal programming. The adipoinsular axis has been proposed as a primary candidate for linking the status of body fat mass to the function of the pancreatic beta-cells. We therefore investigated the relationship between circulating plasma concentrations of leptin and insulin and immunoreactivity in the endocrine pancreas for leptin and leptin receptor (OB-R) in genetically normal rats that were programmed to become obese during adult life. Virgin Wistar rats were time mated and randomly assigned to receive food either available ad libitum (AD group) or at 30% of the ad libitum available intake (UN group). Offspring from UN mothers were significantly smaller at birth than AD offspring (AD 6.13+/-0.04 g, UN 4.02+/-0.03 g, P<0.001). At weaning, offspring were assigned to one of two diets (a standard control diet or a hypercaloric diet consisting of 30% fat) for the remainder of the study. At the time of death (125 days of age), UN offspring had elevated (P<0.005) fasting plasma insulin (AD control 1.417+/-0.15 ng/ml, UN control 2.493+/-0.33 ng/ml, AD hypercaloric 1.70+/-0.17 ng/ml, UN hypercaloric 2.608+/-0.41 ng/ml) and leptin (AD control 8.8+/-1.6 ng/ml, UN control 14.32+/-1.9 ng/ml, AD hypercaloric 15.11+/-1.8 ng/ml, UN hypercaloric 30.18+/-5.3 ng/ml) concentrations, which were further increased (P<0.05) by postnatal hypercaloric nutrition. The elevated plasma insulin and leptin concentrations were paralleled by increased immunolabeling for leptin in the peripheral cells of the pancreatic islets. Dual immunofluorescence histochemistry for somatostatin and leptin revealed that leptin was co-localized in the pancreatic delta-cells. OB-R immunoreactivity was evenly distributed throughout the pancreatic islets and was not changed by programming nor hypercaloric nutrition. Our data suggest that reduced substrate supply during fetal development can trigger permanent dysregulation of the adipoinsular feedback system leading to hyperleptinemia, hyperinsulinism and compensatory leptin production by pancreatic delta-cells in a further attempt to reduce insulin hypersecretion in the progression to adipogenic diabetes.

KSC-2012-1329

NASA Image and Video Library

2012-02-14

COCOA BEACH, Fla. -- Ed Mango, program manager for NASA's Commercial Crew Program CCP, talks to industry partners and stakeholders during a preproposal conference at the Courtyard Marriott in Cocoa Beach, Fla. At left, are Cheryl McPhillips, the NASA Participant Evaluation Panel PEP chair for the Commercial Crew Program CCP, and Lee Pagel, the NASA PEP deputy. The meeting focused on information related to NASA's release of the Commercial Crew Integrated Capability CCiCap Announcement for Proposals on Feb. 7. More than 50 people from 25 aerospace companies attended the conference to find out what the space agency would be looking for in terms of milestones, funding, schedules, strategies, safety cultures, business modules and eventual flight certification standards of integrated crew space transportation systems. The goal of the CCiCap is to develop an indigenous U.S. transportation system that can safely, affordably and routinely fly to low Earth orbit destinations, including the International Space Station. Proposals are due March 23 and NASA plans to award multiple Space Act Agreements, valued from $300 million to $500 million each, toward the development of fully integrated commercial crew transportation systems in the summer of 2012. For more information, visit www.nasa.gov/commercialcrew Photo credit: Kim Shiflett The Ground Systems Development and Operations Program is developing the necessary ground systems, infrastructure and operational approaches required to safely process, assemble, transport and launch the next generation of rockets and spacecraft in support of NASA’s exploration objectives. Future work also will replace the antiquated communications, power and vehicle access resources with modern efficient systems. Some of the utilities and systems slated for replacement have been used since the VAB opened in 1965. For more information, visit http://www.nasa.gov/exploration/systems/ground/index.html Photo credit: NASA/Kim Shiflett

Continuation of support for the Intercampus Institute for Research at Particle Accelerators. Final technical report

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

Caldwell, D.; Eisner, A.

1997-10-01

During the budget period beginning May 16, 1995, the UCSD group of the U.C. Intercampus Institute for Research at Particle Accelerators devoted approximately 75% of its effort to the PEP-II B Factory and the associated BABAR detector at SLAC, and 25% of its effort to the LSND collaboration at LAMPF. Michael Sullivan spent all of his time on PEP-II, while Alan Eisner split his time between BABAR and LSND. Sullivan remained a critical member of the group designing the PEP-II interaction region and the machine-detector interface; and, in fact, toward the end of the period he left IIRPA to becomemore » a SLAC employee, in order to ensure his continued participation in those efforts. That work has focused on developing an interaction region in which the accelerator can achieve the required high specific luminosity while, at the same time, maintaining low enough beam background to allow a detector to operate. Both requirements are essential to achieving the primary physics goal of not only detecting but doing detailed measurements of CP violation. Eisner`s work on the BABAR detector concentrated on the electromagnetic (CsI crystal) calorimeter. With the calorimeter geometry largely established, he turned his attention more fully to the areas of calorimeter data acquisition and calibration. The data acquisition focus, was on understaning the performance of the proposed system via calculations and simulations, a joint project with Yao-xin Wang of the UCSB IIRPA group.« less

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.

PepsNMR for 1H NMR metabolomic data pre-processing.

PubMed

Martin, Manon; Legat, Benoît; Leenders, Justine; Vanwinsberghe, Julien; Rousseau, Réjane; Boulanger, Bruno; Eilers, Paul H C; De Tullio, Pascal; Govaerts, Bernadette

2018-08-17

In the analysis of biological samples, control over experimental design and data acquisition procedures alone cannot ensure well-conditioned 1 H NMR spectra with maximal information recovery for data analysis. A third major element affects the accuracy and robustness of results: the data pre-processing/pre-treatment for which not enough attention is usually devoted, in particular in metabolomic studies. The usual approach is to use proprietary software provided by the analytical instruments' manufacturers to conduct the entire pre-processing strategy. This widespread practice has a number of advantages such as a user-friendly interface with graphical facilities, but it involves non-negligible drawbacks: a lack of methodological information and automation, a dependency of subjective human choices, only standard processing possibilities and an absence of objective quality criteria to evaluate pre-processing quality. This paper introduces PepsNMR to meet these needs, an R package dedicated to the whole processing chain prior to multivariate data analysis, including, among other tools, solvent signal suppression, internal calibration, phase, baseline and misalignment corrections, bucketing and normalisation. Methodological aspects are discussed and the package is compared to the gold standard procedure with two metabolomic case studies. The use of PepsNMR on these data shows better information recovery and predictive power based on objective and quantitative quality criteria. Other key assets of the package are workflow processing speed, reproducibility, reporting and flexibility, graphical outputs and documented routines. Copyright © 2018 Elsevier B.V. All rights reserved.