PEP talk

International Nuclear Information System (INIS)

Anon.

1980-01-01

The newly operating PEP electron-positron storage ring, built by the Berkeley and Stanford Laboratories, was dedicated on 5 September. PEP comes on with some unusual handicaps. It is of course competing with PETRA at DESY. It is late and it will take all the ingenuity and imagination that this great Lab, with its great traditions, can muster to catch up and show the world that US physics is strong and that the large funds vested here are well spent

PEP-II: An asymmetric B factory

International Nuclear Information System (INIS)

1993-06-01

In this report, the authors have described an updated conceptual design for the high-luminosity Asymmetric B Factory (PEP-II) to be built in the PEP tunnel culmination of more than four years of effort aimed at the design and construction of an asymmetric e + e - collider capable of achieving a luminosity of L = 3 x 10 33 cm -2 s -1 . All aspects of the conceptual design were scrutinized in March 1991 by a DOE technical review committee chaired by Dr. L. Edward Temple. The design was deemed feasible and capable of achieving its physics goals. Furthermore, the cost estimate, schedule, and management plan for the project were fully endorsed by the committee. This updated conceptual design report captures the technical progress since the March 1991 review and reflects the lower cost estimate corresponding to the improved design. Although the PEP-II design has continued to evolve, no technical scope changes have been made that invalidate the conclusion of the DOE review. The configuration adopted utilizes two storage rings, an electron ring operating at 9 GeV and a positron ring at 3.1 GeV, each with a circumference of 2200 m. The high-energy ring is an upgrade of the PEP storage ring at SLAC; all PEP magnets and most power supplies will be reused. The upgrade consists primarily of replacing the PEP vacuum chamber and RF system with newly designed versions optimized for the high-current environment of PEP-II. The low-energy ring will be newly constructed and will be situated atop the high-energy ring in the PEP tunnel. Utilities already installed in the PEP tunnel are largely sufficient to operate the two PEP-II storage rings

The Prevention Program for Externalizing Problem Behavior (PEP) Improves Child Behavior by Reducing Negative Parenting: Analysis of Mediating Processes in a Randomized Controlled Trial

Science.gov (United States)

Hanisch, Charlotte; Hautmann, Christopher; Plück, Julia; Eichelberger, Ilka; Döpfner, Manfred

2014-01-01

Background: Our indicated Prevention program for preschool children with Externalizing Problem behavior (PEP) demonstrated improved parenting and child problem behavior in a randomized controlled efficacy trial and in a study with an effectiveness design. The aim of the present analysis of data from the randomized controlled trial was to identify…

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.

Science.gov (United States)

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.

Detecting effects of the indicated prevention Programme for Externalizing Problem behaviour (PEP) on child symptoms, parenting, and parental quality of life in a randomized controlled trial.

Science.gov (United States)

Hanisch, Charlotte; Freund-Braier, Inez; Hautmann, Christopher; Jänen, Nicola; Plück, Julia; Brix, Gabriele; Eichelberger, Ilka; Döpfner, Manfred

2010-01-01

Behavioural parent training is effective in improving child disruptive behavioural problems in preschool children by increasing parenting competence. The indicated Prevention Programme for Externalizing Problem behaviour (PEP) is a group training programme for parents and kindergarten teachers of children aged 3-6 years with externalizing behavioural problems. To evaluate the effects of PEP on child problem behaviour, parenting practices, parent-child interactions, and parental quality of life. Parents and kindergarten teachers of 155 children were randomly assigned to an intervention group (n = 91) and a nontreated control group (n = 64). They rated children's problem behaviour before and after PEP training; parents also reported on their parenting practices and quality of life. Standardized play situations were video-taped and rated for parent-child interactions, e.g. parental warmth. In the intention to treat analysis, mothers of the intervention group described less disruptive child behaviour and better parenting strategies, and showed more parental warmth during a standardized parent-child interaction. Dosage analyses confirmed these results for parents who attended at least five training sessions. Children were also rated to show less behaviour problems by their kindergarten teachers. Training effects were especially positive for parents who attended at least half of the training sessions. CBCL: Child Behaviour Checklist; CII: Coder Impressions Inventory; DASS: Depression anxiety Stress Scale; HSQ: Home-situation Questionnaire; LSS: Life Satisfaction Scale; OBDT: observed behaviour during the test; PCL: Problem Checklist; PEP: prevention programme for externalizing problem behaviour; PPC: Parent Problem Checklist; PPS: Parent Practices Scale; PS: Parenting Scale; PSBC: Problem Setting and Behaviour checklist; QJPS: Questionnaire on Judging Parental Strains; SEFS: Self-Efficacy Scale; SSC: Social Support Scale; TRF: Caregiver-Teacher Report Form.

Status Report on PEP-II Performance

International Nuclear Information System (INIS)

Matter, Regina S.

2002-01-01

PEP-II [1-9] is an e+e- collider with asymmetric energies (3.1 and 9 GeV, respectively) in a 2200 m tunnel at the Stanford Linear Accelerator Center. The collider produces B mesons to study a particle physics effect called CP violation as well as other physics topics. PEP-II was completed in 1998 with the first luminosity generated in July of that year. The installation of the BaBar Detector was finished in May 1999. The overall layout of PEP-II is shown in Figure 1 and the interaction region of PEP-II in Figure 2. The accelerator parameters and achievements of the High Energy Ring (HER) are listed in Table 1 and those for the Low Energy Ring (LER) in Table 2. The two beams collide at a single point in the IR2 hall where the BaBar detector is located. Beam parameters at the best luminosity are shown in Table 3 and PEP-II milestones in Table 4. In August 1999 PEP-II passed the world's record for luminosity which was 8.1x10 32 /cm 2 /s. The present luminosity in PEP-II is 2.15x10 33 /cm 2 /s which is 72% of the design. In June 2000 PEP-II delivered an integrated luminosity of 150 pb -1 in one day, which is above the design integrated luminosity per day of 135 pb -1 . Over the past year PEP-II has delivered over 12 fb -1 to BaBar. BaBar has logged over 11 pb -1 . The present plan is collide until the end of October 2000 followed by a three month installation period

Therapeutical Administration of Peptide Pep19-2.5 and Ibuprofen Reduces Inflammation and Prevents Lethal Sepsis

Science.gov (United States)

Barcena Varela, Sergio; Ferrer-Espada, Raquel; Reiling, Norbert; Goldmann, Torsten; Gutsmann, Thomas; Mier, Walter; Schürholz, Tobias; Drömann, Daniel; Brandenburg, Klaus; Martinez de Tejada, Guillermo

2015-01-01

Sepsis is still a major cause of death and many efforts have been made to improve the physical condition of sepsis patients and to reduce the high mortality rate associated with this disease. While achievements were implemented in the intensive care treatment, all attempts within the field of novel therapeutics have failed. As a consequence new medications and improved patient stratification as well as a thoughtful management of the support therapies are urgently needed. In this study, we investigated the simultaneous administration of ibuprofen as a commonly used nonsteroidal anti-inflammatory drug (NSAID) and Pep19-2.5 (Aspidasept), a newly developed antimicrobial peptide. Here, we show a synergistic therapeutic effect of combined Pep19-2.5-ibuprofen treatment in an endotoxemia mouse model of sepsis. In vivo protection correlates with a reduction in plasma levels of both tumor necrosis factor α and prostaglandin E, as a likely consequence of Pep19-2.5 and ibuprofen-dependent blockade of TLR4 and COX pro-inflammatory cascades, respectively. This finding is further characterised and confirmed in a transcriptome analysis of LPS-stimulated human monocytes. The transcriptome analyses showed that Pep19-2.5 and ibuprofen exerted a synergistic global effect both on the number of regulated genes as well as on associated gene ontology and pathway expression. Overall, ibuprofen potentiated the anti-inflammatory activity of Pep19-2.5 both in vivo and in vitro, suggesting that NSAIDs could be useful to supplement future anti-sepsis therapies. PMID:26197109

PEP liquid level system

International Nuclear Information System (INIS)

Lauritzen, T.; Sah, R.C.

1981-03-01

A liquid level system has been installed in the accelerator housing of the PEP storage ring. This instrument spans the entire 2.2 km circumference of the PEP project, and over one hundred readouts provide reference elevations which are used for the accurate alignment of accelerator components. The liquid level has proven to be extremely precise (+-0.10 mm) and quick to use, and it has contributed to the accurate alignment of PEP before beam turn-on. Since the liquid level readouts are rigidly attached to the accelerator housing, the liquid level has been a convenient means to monitor the settling of the accelerator housing

Luminosity monitor at PEP

International Nuclear Information System (INIS)

Fox, J.D.; Franklin, M.E.B.

1981-02-01

The luminosity monitor system utilized by the MKII Detector and by the PEP operators is described. This system processes information from 56 photomultipliers and calculates independent luminosities for each of the 3 colliding bunches in PEP. Design considerations, measurement techniques, and sources of error in the luminosity measurement are discussed

PEP storage ring: current status

International Nuclear Information System (INIS)

Rees, J.R.

1981-02-01

This report comments on the performance of the subsystems of PEP, discusses the beam dynamical behavior of the machine and compares it with our expectations and, finally, describes plans for improving PEP

High-resolution spectrometer at PEP

International Nuclear Information System (INIS)

Weiss, J.M.; HRS Collaboration.

1982-01-01

A description is presented of the High Resolution Spectrometer experiment (PEP-12) now running at PEP. The advanced capabilities of the detector are demonstrated with first physics results expected in the coming months

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

Science.gov (United States)

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.

PEP Run Report for Simulant Shakedown/Functional Testing

Energy Technology Data Exchange (ETDEWEB)

Josephson, Gary B.; Geeting, John GH; Bredt, Ofelia P.; Burns, Carolyn A.; Golovich, Elizabeth C.; Guzman-Leong, Consuelo E.; Kurath, Dean E.; Sevigny, Gary J.

2009-12-29

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 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 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

InverPep: A database of invertebrate antimicrobial peptides.

Science.gov (United States)

Gómez, Esteban A; Giraldo, Paula; Orduz, Sergio

2017-03-01

The aim of this work was to construct InverPep, a database specialised in experimentally validated antimicrobial peptides (AMPs) from invertebrates. AMP data contained in InverPep were manually curated from other databases and the scientific literature. MySQL was integrated with the development platform Laravel; this framework allows to integrate programming in PHP with HTML and was used to design the InverPep web page's interface. InverPep contains 18 separated fields, including InverPep code, phylum and species source, peptide name, sequence, peptide length, secondary structure, molar mass, charge, isoelectric point, hydrophobicity, Boman index, aliphatic index and percentage of hydrophobic amino acids. CALCAMPI, an algorithm to calculate the physicochemical properties of multiple peptides simultaneously, was programmed in PERL language. To date, InverPep contains 702 experimentally validated AMPs from invertebrate species. All of the peptides contain information associated with their source, physicochemical properties, secondary structure, biological activity and links to external literature. Most AMPs in InverPep have a length between 10 and 50 amino acids, a positive charge, a Boman index between 0 and 2 kcal/mol, and 30-50% hydrophobic amino acids. InverPep includes 33 AMPs not reported in other databases. Besides, CALCAMPI and statistical analysis of InverPep data is presented. The InverPep database is available in English and Spanish. InverPep is a useful database to study invertebrate AMPs and its information could be used for the design of new peptides. The user-friendly interface of InverPep and its information can be freely accessed via a web-based browser at http://ciencias.medellin.unal.edu.co/gruposdeinvestigacion/prospeccionydisenobiomoleculas/InverPep/public/home_en. Copyright © 2016 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.

Skew quad compensation at PEP

International Nuclear Information System (INIS)

Murray, J.J.

1977-10-01

Rotational and focal effects of solenoids used in PEP detectors will cause severe perturbations of machine beam optics and must be corrected. Ordinarily this would be accomplished by the addition of compensating solenoids and adjustment of insertion quadrupole strengths. It has been found that an arbitrary cross plane coupling representing the effects of solenoids and/or skew quads in any combination can be synthesized (or compensated) exactly using a quartet of skew quads combined with other erect transport elements in a wide variety of configurations. Specific skew quad compensating systems for PEP have been designed and are under study by PEP staff. So far no fundamental flaws have been discovered. In view of that, PEP management has tentatively authorized the use of such a system in the PEP-4, PEP-9 experiments and proposes to leave the question open ''without prejudice'' for other experiments. Use of skew quad compensation involves an imponderable risk, of course, simply because the method is new and untested. But in addition to providing the only known method for dealing with skew quad perturbations, skew quad compensation, as an alternate to compensating solenoids, promises to be much cheaper, to require much less power and to occupy much less space in the IR's. The purpose of this note is to inform potential users of the foregoing situation and to explain skew quad compensation more fully. 2 refs., 1 fig., 1 tab

The Danish PEP registry: experience with the use of postexposure prophylaxis (PEP) following sexual exposure to HIV from 1998 to 2006

DEFF Research Database (Denmark)

Lunding, Suzanne; Katzenstein, Terese L; Kronborg, Gitte

2010-01-01

BACKGROUND: Studies indicate that antiretroviral postexposure prophylaxis (PEP) after sexual exposure to HIV reduce the risk of infection considerably. Since 1998 PEP after sexual HIV exposure within the preceding 24 hours, has been available in Denmark. PEP can only be prescribed at clinical...... centers with specialists experienced in HIV treatment. The objective of this study is to describe the use of PEP after sexual exposure from 1998 to 2006. METHODS: The Danish PEP registry collects data from all cases of PEP use in Denmark after exposure to HIV through a structured questionnaire. RESULTS......: There were 374 cases of PEP use after sexual exposure. The incidence increased from 5 cases in 1997 to 87 in 2006. PEP was used by heterosexuals (40%) as well as men who have sex with men (57%). The HIV-status of the source was unknown in 41% of the cases of which 90% involved a source belonging to a high...

Pep3p/Pep5p complex: a putative docking factor at multiple steps of vesicular transport to the vacuole of Saccharomyces cerevisiae.

OpenAIRE

Srivastava, A; Woolford, C A; Jones, E W

2000-01-01

Pep3p and Pep5p are known to be necessary for trafficking of hydrolase precursors to the vacuole and for vacuolar biogenesis. These proteins are present in a hetero-oligomeric complex that mediates transport at the vacuolar membrane. PEP5 interacts genetically with VPS8, implicating Pep5p in the earlier Golgi to endosome step and/or in recycling from the endosome to the Golgi. To understand further the cellular roles of Pep3p and Pep5p, we isolated and characterized a set of pep3 conditional ...

Muon shielding for PEP

International Nuclear Information System (INIS)

Jenkins, T.M.; Thomas, R.H.

1974-01-01

The first stage of construction of PEP will consist of electron and positron storage rings. At a later date a 200 GeV proton storage ring may be added. It is judicious therefore, to ensure that the first and second phases of construction are compatible with each other. One of several factors determining the elevation at which the storage rings will be constructed is the necessity to provide adequate radiation shielding. The overhead shielding of PEP is determined by the reproduction of neutrons in the hadron cascade generated by primary protons lost from the storage ring. The minimum overburden planned for PEP is 5.5 meters of earth (1100 gm cm/sup /minus/2/). To obtain a rough estimate of the magnitude of the muon radiation problem this note presents some preliminary calculations. Their purpose is intended merely to show that the presently proposed design for PEP will present no major shielding problems should the protons storage ring be installed. More detailed calculations will be made using muon yield computer codes developed at CERN and NAL and muon transport codes developed at SLAC, when details of the proton storage ring become settled. 9 refs., 4 figs

Collimation issues for the PEP-II B-factory

International Nuclear Information System (INIS)

Sullivan, M.

1997-12-01

This note describes how beam collimation affects detector backgrounds at the collision point for the PEP-II B-factory, a joint effort of three laboratories: LBNL, LLNL, and SLAC. Beam collimation controls the transverse size as well as the maximum allowed energy spread of the beam. The location of synchrotron radiation masks is determined by the transverse size of the beam in that the masks must prevent radiation generated by beam particles located at large transverse beam positions from directly striking the detector beam pipe. Collimation of the energy spread of the beam is important in the control of backgrounds produced by beam particles that strike a gas molecule (lost beam particles). The author describes some preliminary information from background studies during the first months of commissioning the high energy ring of the PEP-II B-factory and present some model predictions for synchrotron radiation backgrounds when collimators are not present

The Danish PEP registry: experience with the use of postexposure prophylaxis (PEP) following sexual exposure to HIV from 1998 to 2006

DEFF Research Database (Denmark)

Lunding, Suzanne; Katzenstein, Terese L; Kronborg, Gitte

2010-01-01

centers with specialists experienced in HIV treatment. The objective of this study is to describe the use of PEP after sexual exposure from 1998 to 2006. METHODS: The Danish PEP registry collects data from all cases of PEP use in Denmark after exposure to HIV through a structured questionnaire. RESULTS......: There were 374 cases of PEP use after sexual exposure. The incidence increased from 5 cases in 1997 to 87 in 2006. PEP was used by heterosexuals (40%) as well as men who have sex with men (57%). The HIV-status of the source was unknown in 41% of the cases of which 90% involved a source belonging to a high...... risk group, and 63% involved exposure by receptive anal intercourse. PEP was administered within 24 hours in 95% of the cases and the median time to initiation (N = 225) was 11.0 hours (range 0.5-60.0). PEP was completed by 65%. CONCLUSIONS: This nationwide study showed a steady but moderate increase...

Epidermal growth factor inhibits glycylsarcosine transport and hPepT1 expression in a human intestinal cell line

DEFF Research Database (Denmark)

Nielsen, C U; Amstrup, J; Steffansen, B

2001-01-01

(max) decreased from 2.61 +/- 0.4 to 1.06 +/- 0.1 nmol x cm(-2) x min(-1) (n = 3, P PepT1 mRNA (using glucose-6-phosphate dehydrogenase mRNA as control......) in cells treated with EGF. Western blotting indicated a decrease in hPepT1 protein in cell lysates. We conclude that EGF treatment decreases Gly-Sar transport in Caco-2 cells by decreasing the number of peptide transporter molecules in the apical membrane....

An asymmetric B factory based on PEP

International Nuclear Information System (INIS)

1991-02-01

In this report we describe a design for a high-luminosity Asymmetric B Factory to be built in the PEP tunnel on the SLAC site. This proposal, a collaborative effort SLAC, LBL, and LLNL, is the culmination of more than two years of effort aimed at the design and construction of an asymmetric e + e - collider capable of achieving a luminosity of L = 3 x 10 33 cm -2 s -1 . The configuration adopted utilizes two storage rings, and electron ring operating at 9 GeV and a positron ring at 3.1 GeV, each with a circumference of 2200 m. The high-energy ring is an upgrade of the PEP storage ring at SLAC; all PEP magnets and most power supplies will be reused. The upgrade consists primarily of replacing the PEP vacuum chamber and RF system with newly designed versions optimized for the high-current environment of the B Factory. The low-energy ring will be newly constructed and will be situated atop the high-energy ring in the PEP tunnel. Utilities already installed in the PEP tunnel are largely sufficient to operate the two B Factory storage rings

PEP-II injection timing and controls

International Nuclear Information System (INIS)

Bharadwaj, V.; Browne, M.; Crane, M.; Gromme, T.; Himel, T.; Ross, M.; Stanek, M.; Ronan, M.

1997-07-01

Hardware has been built and software written and incorporated in the existing SLC accelerator control system to control injection of beam pulses from the accelerator into the PEP-II storage rings currently under construction. Hardware includes a CAMAC module to delay the machine timing fiducial in order that a beam pulse extracted from a damping ring will be injected into a selected group of four 476 MHz buckets in a PEP-II ring. Further timing control is accomplished by shifting the phase of the bunches stored in the damping rings before extraction while leaving the phase of the PEP-II stored beam unchanged. The software which drives timing devices on a pulse-to-pulse basis relies on a dedicated communication link on which one scheduling microprocessor broadcasts a 128-bit message to all distributed control microprocessors at 360 Hz. PEP-II injection will be driven by the scheduling microprocessor according to lists specifying bucket numbers in arbitrary order, and according to scheduling constraints maximizing the useful beam delivered to the SLC collider currently in operation. These lists will be generated by a microprocessor monitoring the current stored per bucket in each of the PEP-II rings

Background sources at PEP

International Nuclear Information System (INIS)

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

1988-01-01

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, γ-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

Inhibition of E. coli P-enolpyruvate carboxylase by P-enol-3-bromopyruvate

International Nuclear Information System (INIS)

Asem, K.; Smith, T.E.

1986-01-01

The generality of the mechanism based inhibition of P-enolpyruvate carboxylases (PEPCase) by P-enol-3-bromopyruvate (BrPEP) was tested by measuring its effects on the allosterically regulated enzyme from E. coli. In the presence of 1mM Mn 2+ , BrPEP appears to be a competitive inhibitor (K/sub i/ = 0.0087mM) of PEPCase. Incubation of 0.005mM PEPCase with 0.5mM (or 1.0mM)BrPEP along with H 14 CO 3 - and Mn 2+ , yielded, upon reduction with NaBH 4 , a protein containing radioactivity in an amount approximately proportional to that expected from the loss of catalytic activity. At both a 25- and a 50-fold excess (0.5mM and 1.0mM, respectively) of BrPEP to PEPCase subunits, first order loss of activity occurred with k values of 5.24 x 10 -3 min -1 and 1.03 x 10 -2 min -1 , respectively. At the lower concentration of BrPEP the inactivation process appeared to be reversible after 40 min with no further inhibition occurring even up to two hours of incubation. At the higher concentration of BrPEP, the rate of inhibition slowed dramatically after 50 min and appeared insignificant over the next hour. These data suggest that BrPEP irreversibly inactivates the E. coli PEP carboxylase, but that there may be considerable dissociation of the product, Br-oxaloacetate, before irreversible binding occurs, and that the reduced rate of inactivation may be due to depletion of BrPEP

An asymmetric B factory based on PEP

Energy Technology Data Exchange (ETDEWEB)

1991-02-01

In this report we describe a design for a high-luminosity Asymmetric B Factory to be built in the PEP tunnel on the SLAC site. This proposal, a collaborative effort SLAC, LBL, and LLNL, is the culmination of more than two years of effort aimed at the design and construction of an asymmetric e{sup +}e{sup {minus}} collider capable of achieving a luminosity of L = 3 {times} 10{sup 33} cm{sup {minus}2} s{sup {minus}1}. The configuration adopted utilizes two storage rings, and electron ring operating at 9 GeV and a positron ring at 3.1 GeV, each with a circumference of 2200 m. The high-energy ring is an upgrade of the PEP storage ring at SLAC; all PEP magnets and most power supplies will be reused. The upgrade consists primarily of replacing the PEP vacuum chamber and RF system with newly designed versions optimized for the high-current environment of the B Factory. The low-energy ring will be newly constructed and will be situated atop the high-energy ring in the PEP tunnel. Utilities already installed in the PEP tunnel are largely sufficient to operate the two B Factory storage rings.

Anti-inflammatory effect of transduced PEP-1-heme oxygenase-1 in Raw 264.7 cells and a mouse edema model

International Nuclear Information System (INIS)

Kwon, Soon Won; Sohn, Eun Jeong; Kim, Dae Won; Jeong, Hoon Jae; Kim, Mi Jin; Ahn, Eun Hee; Kim, Young Nam; Dutta, Suman; Kim, Duk-Soo; Park, Jinseu; Eum, Won Sik; Hwang, Hyun Sook; Choi, Soo Young

2011-01-01

Highlights: → Recombinant PEP-1 heme oxygenase-1 expression vector was constructed and overexpressed. → We investigated transduction efficiency of PEP-1-HO-1 protein in Raw 264.7 cells. → PEP-1-HO-1 was efficiently transduced into Raw 264.7 cells in a dose and time dependent manner. → PEP-1-HO-1 exerted anti-inflammatory activity in Raw 264.7 cells and in a mice edema model. → 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 2+ ), is up-regulated by several cellular stress and cell injuries, including inflammation, 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.

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

Science.gov (United States)

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.

Effects of a School-Based Sexuality Education Program on Peer Educators: The Teen PEP Model

Science.gov (United States)

Jennings, J. M.; Howard, S.; Perotte, C. L.

2014-01-01

This study evaluated the impact of the Teen Prevention Education Program (Teen PEP), a peer-led sexuality education program designed to prevent unintended pregnancy and sexually transmitted infections (STIs) including HIV among high school students. The study design was a quasi-experimental, nonrandomized design conducted from May 2007 to May…

New particle searches at PEP

International Nuclear Information System (INIS)

Berley, D.; Bulos, F.; Cheng, D.

1988-01-01

The new particles that could be produced at PEP are discussed in terms of their specific signatures and production rates. We find that a small number of general signatures characterize these particles. Backgrounds associated with the general signatures are considered and necessary rejection rates are calculated. We describe several typical detectors and tabulate the requirements they place on the PEP machine and the experimental areas. 10 figs., 2 tabs

Luminosity upgrade possibilities for the PEP-II B-Factory

CERN Document Server

Sullivan, M

2003-01-01

PEP-II is an asymmetric e sup + e sup - collider being constructed in the SLAC PEP tunnel by SLAC, LBNL, and LLNL. The two beams have energies of 3.1 GeV and 9.0 GeV and are made to collide at a single interaction point. PEP-II has a 2200 m circumference. The nominal parameters for PEP-II are listed in Table 1. The High Energy Ring (HER) of PEP-II started commissioning in 1997. The Low Energy Ring (LER) will be commissioned in the summer of 1998. The BaBar detector is to be installed starting January 1999. Studies for increasing the luminosity in PEP-II beyond the design are underway. A brief summary of the possibilities are presented here. Improvements to the integrated luminosity will be implemented gradually. Major luminosity improvements will likely come in two phased upgrades. Several of these possibilities are summarized in Table 1.

LUMINOSITY UPGRADE POSSIBILITIES FOR THE PEP-II B-FACTORY

International Nuclear Information System (INIS)

Sullivan, Michael K

2003-01-01

PEP-II is an asymmetric e + e - collider being constructed in the SLAC PEP tunnel by SLAC, LBNL, and LLNL. The two beams have energies of 3.1 GeV and 9.0 GeV and are made to collide at a single interaction point. PEP-II has a 2200 m circumference. The nominal parameters for PEP-II are listed in Table 1. The High Energy Ring (HER) of PEP-II started commissioning in 1997. The Low Energy Ring (LER) will be commissioned in the summer of 1998. The BaBar detector is to be installed starting January 1999. Studies for increasing the luminosity in PEP-II beyond the design are underway. A brief summary of the possibilities are presented here. Improvements to the integrated luminosity will be implemented gradually. Major luminosity improvements will likely come in two phased upgrades. Several of these possibilities are summarized in Table 1

PEP-II: An asymmetric B factory. Conceptual design report

Energy Technology Data Exchange (ETDEWEB)

1993-06-01

In this report, the authors have described an updated conceptual design for the high-luminosity Asymmetric B Factory (PEP-II) to be built in the PEP tunnel culmination of more than four years of effort aimed at the design and construction of an asymmetric e{sub +}e{sub {minus}} collider capable of achieving a luminosity of L = 3 {times} 10{sup 33} cm{sup {minus}2} s{sup {minus}1}. All aspects of the conceptual design were scrutinized in March 1991 by a DOE technical review committee chaired by Dr. L. Edward Temple. The design was deemed feasible and capable of achieving its physics goals. Furthermore, the cost estimate, schedule, and management plan for the project were fully endorsed by the committee. This updated conceptual design report captures the technical progress since the March 1991 review and reflects the lower cost estimate corresponding to the improved design. Although the PEP-II design has continued to evolve, no technical scope changes have been made that invalidate the conclusion of the DOE review. The configuration adopted utilizes two storage rings, an electron ring operating at 9 GeV and a positron ring at 3.1 GeV, each with a circumference of 2200 m. The high-energy ring is an upgrade of the PEP storage ring at SLAC; all PEP magnets and most power supplies will be reused. The upgrade consists primarily of replacing the PEP vacuum chamber and RF system with newly designed versions optimized for the high-current environment of PEP-II. The low-energy ring will be newly constructed and will be situated atop the high-energy ring in the PEP tunnel. Utilities already installed in the PEP tunnel are largely sufficient to operate the two PEP-II storage rings.

Luminosity with more bunches in PEP

International Nuclear Information System (INIS)

Corbett, W.J.

1990-12-01

The near term accelerator physics program for PEP includes experiments in a collider mode with up to 9 bunches in each beam. In this memo, luminosity data from the 3 x 3 configuration is first used to calculate vertical beam size, emittance and tune shift as a function of current. The data is then used to extrapolate to the case with either 6 x 6 or 9 x 9 bunches colliding in PEP. Vertical emittance growth from the separated bunch optics and dispersion at the IP are included in the calculations. The conclusion is that given a 90 mA current drive limitation in PEP, operating with 6 x 6 bunches yields the maximum luminosity. 9 refs., 6 figs

Butyrate transcriptionally enhances peptide transporter PepT1 expression and activity.

Directory of Open Access Journals (Sweden)

Guillaume Dalmasso

Full Text Available BACKGROUND: PepT1, an intestinal epithelial apical di/tripeptide transporter, is normally expressed in the small intestine and induced in colon during chronic inflammation. This study aimed at investigating PepT1 regulation by butyrate, a short-chain fatty acid produced by commensal bacteria and accumulated inside inflamed colonocyte. RESULTS: We found that butyrate treatment of human intestinal epithelial Caco2-BBE cells increased human PepT1 (hPepT1 promoter activity in a dose- and time-dependent manner, with maximal activity observed in cells treated with 5 mM butyrate for 24 h. Under this condition, hPepT1 promoter activity, mRNA and protein expression levels were increased as assessed by luciferase assay, real-time RT-PCR and Western blot, respectively. hPepT1 transport activity was accordingly increased by approximately 2.5-fold. Butyrate did not alter hPepT1 mRNA half-life indicating that butyrate acts at the transcriptional level. Molecular analyses revealed that Cdx2 is the most important transcription factor for butyrate-induced increase of hPepT1 expression and activity in Caco2-BBE cells. Butyrate-activated Cdx2 binding to hPepT1 promoter was confirmed by gel shift and chromatin immunoprecipitation. Moreover, Caco2-BBE cells overexpressing Cdx2 exhibited greater hPepT1 expression level than wild-type cells. Finally, treatment of mice with 5 mM butyrate added to drinking water for 24 h increased colonic PepT1 mRNA and protein expression levels, as well as enhanced PepT1 transport activity in colonic apical membranes vesicles. CONCLUSIONS: Collectively, our results demonstrate that butyrate increases PepT1 expression and activity in colonic epithelial cells, which provides a new understanding of PepT1 regulation during chronic inflammation.

The Woods Hole Partnership Education Program (PEP) (Invited)

Science.gov (United States)

Jearld, A.; Liles, G.; Gutierrez, B.

2013-12-01

In March 2009, the Woods Hole Diversity Initiative (WHDI) launched the Partnership Education Program (PEP), a multi-institutional effort to increase diversity in the student population (and ultimately the work force) in the Woods Hole science community. PEP, a summer research internship program, is open to students of all backgrounds but is designed especially to provide opportunities for individuals from populations under-represented in science, technology, engineering, and mathematics (STEM) and who otherwise would not have had the opportunity to come to Woods Hole to study or do research. A month-long course, 'Ocean and Environmental Sciences: Global Climate Change,' sets the stage for their summer research projects. The PEP model is emerging as an effective and sustainable approach to bringing students into the STEM research community. PEP is carefully structured to provide critical support for students as they complete their undergraduate experience and prepare for careers and/or graduate school. In its first five years, PEP has brought to the Woods Hole science community more than 75 students from over 50 colleges and universities, including many that do not typically send talent into marine and/or ecological research. PEP is unusual (perhaps even unique) in that it is a collaborative initiative involving seven partner institutions. Working together, the PEP collaborative has established a critical mass of under-represented students who are now in graduate school and/or working in STEM areas.

P.E.P

International Nuclear Information System (INIS)

Paterson, J.M.

1980-07-01

The design and construction of the PEP project is briefly reviewed. The initial testing of the storage ring system and its present performance is described. The short-range plans for continuing development are discussed

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

Science.gov (United States)

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 .

Getting PrEPared for HIV Prevention Navigation: Young Black Gay Men Talk About HIV Prevention in the Biomedical Era.

Science.gov (United States)

Mutchler, Matt G; McDavitt, Bryce; Ghani, Mansur A; Nogg, Kelsey; Winder, Terrell J A; Soto, Juliana K

2015-09-01

Biomedical HIV prevention strategies, such as pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP), represent new opportunities to reduce critically high HIV infection rates among young black men who have sex with men (YBMSM). We report results of 24 dyadic qualitative interviews (N=48), conducted in Los Angeles, CA, exploring how YBMSM and their friends view PrEP and PEP. Interviews were analyzed using a grounded theory approach. Participants had widely divergent levels of knowledge about these prevention methods. Misconceptions and mistrust regarding PrEP were common, and concerns were expressed about PrEP-related stigma and the potential for gossip among peers who might assume a person on PrEP was HIV-positive. Yet participants also framed PrEP and PEP as valuable new options within an expanded "tool kit" of HIV prevention strategies that created possibilities for preventing new HIV infections, dating men with a different HIV status, and decreased anxiety about exposure to HIV. We organized themes around four main areas: (1) information and misinformation about biomedical HIV prevention; (2) expectations about PrEP, sexual behavior, and stigma; (3) gossip, disclosure, and "spreading the word" about PrEP and PEP; and (4) the roles of PrEP and PEP in an expanded HIV prevention tool kit. The findings suggest a need for guidance in navigating the increasingly complex array of HIV-prevention options available to YBMSM. Such "prevention navigation" could counter misconceptions and address barriers, such as stigma and mistrust, while helping YBMSM make informed selections from among expanded HIV prevention options.

Estimate of coherent tune shifts for PEP

International Nuclear Information System (INIS)

Yao, C.Y.; Chao, A.W.

1981-02-01

Transverse and longitudinal instabilities for a bunched PEP beam with a Gaussian distribution are treated using the standard technique in which instability problems are solved by looking for eigenvalues of the linearized Vlasov equation. The eigen solutions are conveniently expanded in terms of the Laquerre polynomials, and the eigenvalues are given by a symmetric matrix whose elements can be expressed in infinite series. The well-known formalism is used to obtain the matrix formula, and then applied numerically to the PEP ring to estimate the transverse coherent tune shifts. The impedance used is that estimated for the PEP RF cavities. The agreement with experimental data seems reasonable

Storage rings, internal targets and PEP

International Nuclear Information System (INIS)

Spencer, J.E.

1986-11-01

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

Ca 2+ signaling by plant Arabidopsis thaliana Pep peptides depends on AtPepR1, a receptor with guanylyl cyclase activity, and cGMP-activated Ca 2+ channels

KAUST Repository

Qia, Zhi

2010-11-18

A family of peptide signaling molecules (AtPeps) and their plasma membrane receptor AtPepR1 are known to act in pathogendefense signaling cascades in plants. Little is currently known about the molecular mechanisms that link these signaling peptides and their receptor, a leucine-rich repeat receptor-like kinase, to downstream pathogen-defense responses. We identify some cellular activities of these molecules that provide the context for a model for their action in signaling cascades. AtPeps activate plasma membrane inwardly conducting Ca 2+ permeable channels in mesophyll cells, resulting in cytosolic Ca 2+ elevation. This activity is dependent on their receptor as well as a cyclic nucleotide-gated channel (CNGC2). We also show that the leucine-rich repeat receptor- like kinase receptor AtPepR1 has guanylyl cyclase activity, generating cGMP from GTP, and that cGMP can activate CNGC2- dependent cytosolic Ca 2+ elevation. AtPep-dependent expression of pathogen-defense genes (PDF1.2, MPK3, and WRKY33) is mediated by the Ca 2+ signaling pathway associated with AtPep peptides and their receptor. The work presented here indicates that extracellular AtPeps, which can act as danger-associated molecular patterns, signal by interaction with their receptor, AtPepR1, a plasma membrane protein that can generate cGMP. Downstream from AtPep and AtPepR1 in a signaling cascade, the cGMP-activated channel CNGC2 is involved in AtPep- and AtPepR1-dependent inward Ca 2+ conductance and resulting cytosolic Ca 2+ elevation. The signaling cascade initiated by AtPeps leads to expression of pathogen- defense genes in a Ca 2+-dependent manner.

BERKELEY: Collaboration on PEP-II

International Nuclear Information System (INIS)

Anon.

1995-01-01

Since the announcement by President Clinton in October 1993 that the US Department of Energy would going ahead the PEPII Asymmetric B Factory project (a joint proposal of the Stanford Linear Accelerator Center - SLAC, the Lawrence Berkeley National Laboratory - LBNL, and the Lawrence Livermore National Laboratory - LLNL), LBNL has continued its strong support of the project (for a review, see October, page 9). LBNL accelerator physicists have been active in the design of PEP-II since 1988 - shortly after the original concept was suggested by LBNL Deputy Director Pier Oddone. Indeed, the original feasibility study for such a machine was a joint LBNLSLAC- Caltech effort led by Swapan Chattopadhyay, now head of LBNL's Center for Beam Physics (CBP) in the Accelerator & Fusion Research Division (AFRD). The effort grew to include about seven full-time LBNL accelerator physicists (along with about 15 SLAC and LLNL physicists) during the formal design phase, which began in late 1989. This effort encompassed three editions of the Conceptual Design Report, along with innumerable reviews, as is typical of today's accelerator projects. Taking advantage of an experienced engineering staff, fresh from the successful completion of the Advanced Light Source (ALS), LBNL has been assigned lead responsibility for the challenging Low Energy Ring (LER) of the PEP-II project, an entirely new storage ring to be added to the PEP tunnel. The LBNL design team is headed by CBP accelerator physicist Michael Zisman and senior engineers Ron Yourd (who served as the Project Manager for the ALS) and Hank Hsieh (a recent addition to the LBNL staff who was Project Engineer for the NSLS storage rings at BNL and most recently served as Project Engineer for the DAFNE project at Frascati). LBNL is also represented in the overall management of the PEP-II project by Tom Elioff, who serves as Deputy to the Project Director Jonathan Dorfan at SLAC. (Elioff served in the same role for the original

Single wavelength standard wiggler for PEP

International Nuclear Information System (INIS)

Brunk, W.; Fischer, G.; Spencer, J.

1979-03-01

A 1lambda planar wiggler has been designed that will be used for the initial operation of the 4 to 18 GeV storage ring PEP. Three of these wigglers will be installed symmetrically around the ring at 120 0 intervals in three of six available 5 m straight sections with the purpose of providing: (1) beam size control to obtain better luminosities below 15 GeV, and (2) decreased damping times to obtain better injection rates at lower energies. Design goals are discussed and a description of the final system including cost estimates is given. Expected results and usage in PEP are discussed. Some possibilities for production of synchrotron radiation and beam monitoring with shorter wavelength, multiple-period wigglers at PEP energies are also discussed. Comparison to a wiggler now operating in SPEAR is given

Status of PEP and TPC/2γ

International Nuclear Information System (INIS)

Zapalac, G.

1989-06-01

The TPC/2γ program at PEP has been upgraded by increasing the PEP luminosity and by the adding of a vertex chamber to the TPC detector. These improvements will allow a strong program in B and τ physics, and will contribute to ongoing studies in two-photon physics and hadronization. 10 refs., 3 figs

PEP-II prototype klystron

International Nuclear Information System (INIS)

Fowkes, W.R.; Caryotakis, G.; Lee, T.G.; Pearson, C.; Wright, E.L.

1993-04-01

A 540-kW continuous-wave (cw) klystron operating at 476 MHz was developed for use as a power source for testing PEP-II rf accelerating cavities and rf windows. It also serves as a prototype for a 1.2 MW cw klystron presently being developed as a potential rf source for asymmetric colliding ring use. The design incorporates the concepts and many of the parts used in the original 353 MHz PEP klystron developed sixteen years ago. The superior computer simulation codes available today result in improved performance with the cavity frequencies, drift lengths, and output circuit optimized for the higher frequency.The design and operating results of this tube are described with particular emphasis on the factors which affect efficiency and stability

Development of HyPEP, A Hydrogen Production Plant Efficiency Calculation Program

International Nuclear Information System (INIS)

Lee, Young Jin; Park, Ji Won; Lee, Won Jae; Shin, Young Joon; Kim, Jong Ho; Hong, Sung Deok; Lee, Seung Wook; Hwang, Moon Kyu

2007-12-01

Development of HyPEP program for assessing the steady-state hydrogen production efficiency of the nuclear hydrogen production facilities was carried out. The main developmental aims of the HyPEP program are the extensive application of the GUI for enhanced user friendliness and the fast numerical solution scheme. These features are suitable for such calculations as the optimisation calculations. HyPEP was developed with the object-oriented programming techniques. The components of the facility was modelled as objects in a hierarchical structure where the inheritance property of the object oriented program were extensively applied. The Delphi program language which is based on the Object Pascal was used for the HyPEP development. The conservation equations for the thermal hydraulic flow network were setup and the numerical solution scheme was developed and implemented into HyPEP beta version. HyPEP beta version has been developed with working GUI and the numerical solution scheme implementation. Due to the premature end of this project the fully working version of HyPEP was not produced

Prevention of 5-fluorouracil-caused growth inhibition in Sordaria fimicola.

Science.gov (United States)

Schoen, H F; Berech, J

1977-02-01

Growth (dry weight accumulation) of Sordaria fimicola in standing liquid culture (sucrose-nitrate-salts-vitamins) is inhibited by the presence of 5 muM 5-fluorouracil in the medium. This inhibition is completely prevented by uracil, deoxyuridine, and 5-bromouracil, partly prevented (40 to 90% of growth observed without 5-fluorouracil) by uridine, thymidine, and 5-bromodeoxyuridine, and slightly prevented by trifluorothymine, cytosine, cytidine, deoxycytidine, and 5-methylcytosine (all at 0.5 to 1 mM). Thymidine and thymine riboside were without any apparent effect. Growth is also inhibited by 0.2 mM 6-azauracil, and this inhibition was completely prevented by uracil and uridine, partly prevented by deoxyuridine, 5-bromouracil, cytidine, and 5-methylcytosine, and slightly prevented by thymine, thymidine, 5-bromodeoxyuridine, cytosine, and deoxycytidine. The data suggest that the observed inhibition of growth by 5-fluorouracil is due to inhibition of both ribonucleic acid and deoxyribonucleic acid synthesis. The data also allow inferences concerning pyrimidine interconversions in S. fimicola; i.e., thymine can be anabolized to thymidylic acid without first being demethylated, although demethylation appears to occur also.

Configuring the SLC linac for injection into PEP

International Nuclear Information System (INIS)

Bane, K.L.F.

1989-01-01

From time to time the normal SLC physics program is to be interrupted so that beam can be delivered to PEP. In order that the switch to PEP injection (and the switch back again) can be accomplished quickly and easily, the gun, the damping rings, the linac phase ramp, the energy profile of the linac klystrons for the scavenger bunch, and the entire positron production system are to be kept the same as in the SLC configuration. What mainly remains to be changed is the linac klystron profile for the leading two bunches - those going to PEP. The new klystron profile must be such that it leaves these two beams (1) with final energies that match that of the storage ring and (2) with final energy spectra that fit within the energy aperture of the PEP transfer line. The conditions that need to be met in order to achieve these two goals are discussed in this note. 1 ref., 2 figs

Seepage into PEP tunnel

International Nuclear Information System (INIS)

Weidner, H.

1990-01-01

The current rate of seepage into the PEP tunnel in the vicinity of IR-10 is very low compared to previous years. Adequate means of handling this low flow are in place. It is not clear whether the reduction in the flow is temporary, perhaps due to three consecutive dry years, or permanent due to drainage of a perched water table. During PEP construction a large amount of effort was expended in attempts to seal the tunnel, with no immediate effect. The efforts to ''manage'' the water flow are deemed to be successful. By covering equipment to protect it from dripping water and channeling seepage into the drainage gutters, the seepage has been reduced to a tolerable nuisance. There is no sure, safe procedure for sealing a leaky shotcreted tunnel

Progress of the PEP-II B-factory

International Nuclear Information System (INIS)

Seeman, J.; Browne, M.; Cai, Y.; Colocho, W.; Decker, F.-J.; Donald, M.; Ecklund, S.; Erickson, R.; Fisher, A.; Fox, J.; Heifets, S.; Iverson, R.; Kozanecki, W.; Krejcik, P.; Kulikov, A.; Novokhatski, A.; Schuh, P.; Schwarz, H.; Stanek, M.; Sullivan, M.; Teytelman, D.; Turner, J.; Wienands, U.; Yan, Y.; Yocky, J.; Biagini, M.; Zisman, M.

2003-01-01

PEP-II is an e + e - B-Factory Collider located at SLAC operating at the Upsilon 4S resonance. PEP-II has delivered, over the past five years, an integrated luminosity to the BaBar detector of over 139 fb -1 and has reached a luminosity of 6.58 x 10 36 /cm 2 /s. Steady progress is being made in reaching higher luminosity. The goal over the next several years is to reach a luminosity of at least 2 x 10 34 /cm 2 /s. The accelerator physics issues being addressed in PEP-II to reach this goal include the electron cloud instability, beam-beam effects, parasitic beam-beam effects, high RF beam loading, shorter bunches, lower beta y*, interaction region operation, and coupling control. A view of the PEP-II tunnel is shown in Figure 1. The present parameters of the PEP-II B-Factory are shown in Table 1 compared to the design. The present peak luminosity is 219% of design and the best integrated luminosity per month is 7.4 fb -1 that is 225% of design. The best luminosity per month is shown in Figure 2. The integrated luminosity over a month is shown in Figure 3 and the total integrated luminosity in shown in Figure 4. The progress in luminosity has come from correcting the orbits, adding specific orbit bumps to correct coupling and dispersion issues, lowering the beta y* in the LER, and moving the fractional horizontal tunes in both rings to just above the half integer (<0.52)

PEP-II RF System Operation and Performance

International Nuclear Information System (INIS)

McIntosh, P.

2005-01-01

The Low Energy Ring (LER) and High Energy Ring (HER) RF systems have operated now on PEP-II since July 1998 and have assisted in breaking all design luminosity records back in June 2001. Luminosity on PEP-II has steadily increased since then as a consequence of larger e+ and e- beam currents being accumulated. This has meant that the RF systems have inevitably been driven harder, not only to achieve these higher stored beam currents, but also to reliably keep the beams circulating whilst at the same time minimizing the number of aborts due to RF system faults. This paper details the current PEP-II RF system configurations for both rings, as well as future upgrade plans spanning the next 3-5 years. Limitations of the current RF system configurations are presented, highlighting improvement projects which will target specific areas within the RF systems to ensure that adequate operating overheads are maintained and reliable operation is assured. The Low Energy Ring (LER) and High Energy Ring (HER) RF systems have operated now on PEP-II since July 1998 and have assisted in breaking all design luminosity records back in June 2001. Luminosity on PEP-II has steadily increased since then as a consequence of larger e+ and e- beam currents being accumulated. This has meant that the RF systems have inevitably been driven harder, not only to achieve these higher stored beam currents, but also to reliably keep the beams circulating whilst at the same time minimizing the number of aborts due to RF system faults. This paper details the current PEP-II RF system configurations for both rings, as well as future upgrade plans spanning the next 3-5 years. Limitations of the current RF system configurations are presented, highlighting improvement projects which will target specific areas within the RF systems to ensure that adequate operating overheads are maintained and reliable operation is assured

StraPep: a structure database of bioactive peptides

Science.gov (United States)

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

Performance of the PEP-II B-Factory Collider at SLAC

International Nuclear Information System (INIS)

Seeman, J.; Browne, M.; Cai, Y.; Colocho, W.; Decker, F.J.; Donald, M.H.; Ecklund, S.; Erickson, R.A.; Fisher, A.S.; Fox, J.D.; Heifets, S.A.; Iverson, R.H.; Kulikov, A.; Li, N.; Novokhatski, A.; Ross, M.C.; Schuh, P.; Smith, T.J.; Sonnad, K.G.; Stanek, M.; Sullivan, M.K.

2006-01-01

PEP-II is an e + e - asymmetric B-Factory Collider located at SLAC operating at the Upsilon 4S resonance (3.1 GeV x 9 GeV). It has reached a luminosity of 9.21 x 10 33 /cm 2 /s and has delivered an integrated luminosity of 710 pb -1 in one day. PEP-II has delivered, over the past six years, an integrated luminosity to the BaBar detector of over 262 fb -1 . PEP-II operates in continuous injection mode for both beams boosting the integrated luminosity. The peak positron current has reached 2.45 A in 1588 bunches. Steady progress is being made in reaching higher luminosity. The goal over the next several years is to reach a luminosity of 2.1 x 10 34 /cm 2 /s. The accelerator physics issues being addressed in PEP-II to reach this goal include the electron cloud instability, beam-beam effects, parasitic beam-beam effects, high RF beam loading, shorter bunches, lower β* y interaction region operation, and coupling control. Figure 1 shows the PEP-II tunnel

Vacuum system for the Stanford-LBL storage ring (PEP)

International Nuclear Information System (INIS)

Bostic, D.; Cummings, U.; Dean, N.; Jeong, B.; Jurow, J.

1975-03-01

The vacuum system for PEP will be similar in design, construction and operation to the system currently in operation at SPEAR. There will, of course, be quantitative differences since the closed path of PEP will be 10 times longer than the SPEAR path. Some qualitative differences will also arise since the radiated synchrotron power for PEP will be about 13 times greater than for SPEAR giving rise to an increased linear power density incident on the chamber wall. Other differences arise from the higher energy spectrum of the synchrotron radiation. The SPEAR vacuum system has been in operation since April 1972 and has proven satisfactory in design, construction and operation. The chamber has been subject to synchrotron radiation for approximately 300 ampere-hours and beam lifetimes are now more than several hours. The details of the PEP design and the SPEAR operating experience will be further discussed in this paper. 1 ref., 4 figs

PEP instrumentation and control system

Energy Technology Data Exchange (ETDEWEB)

Melen, R.

1980-06-01

This paper describes the operating characteristics of the primary components that form the PEP Instrumentation and Control System. Descriptions are provided for the computer control system, beam monitors, and other support systems.

PEP instrumentation and control system

International Nuclear Information System (INIS)

Melen, R.

1980-06-01

This paper describes the operating characteristics of the primary components that form the PEP Instrumentation and Control System. Descriptions are provided for the computer control system, beam monitors, and other support systems

Operation of PEP longitudinal feedback system

International Nuclear Information System (INIS)

Allen, M.A.; Karvonen, L.G.; McConnell, R.A.; Schwarz, H.

1981-03-01

In order to suppress longitudinal coupled-bunch oscillations which might limit the capabilities of PEP, the 18 GeV e + e - storage ring at SLAC, a longitudinal feedback system is utilized. A frequency domain feedback system was chosen with the frequency spectrum of the stored beam being sampled close to a symmetry point in the ring where the feedback cavity itself is also located. The symmetry point chosen is symmetry point 5 which lies half-way between interaction regions 4 and 6. The system has been installed in PEP and is now operational. However, at stored currents up to the maximum stored in PEP to date at 14.5 GeV (approximately 40 mA in 6 bunches), the ring has been stable to all modes of longitudinal coupled-bunch oscillations both barycentric and the other fundamental modes. By deliberately detuning the main accelerating cavities, small multibunch oscillations can be introduced which, in turn, can be damped by the feedback system. Under optimized beam conditions the feedback system could be adjusted to positive feedback and excite oscillations with relatively small power to the feedback cavity. This will be described along with other details of the system

Knowledge, Attitude and Practice of Post-Exposure Prophylaxis (PEP)

African Journals Online (AJOL)

user

Their levels of knowledge and indications for. PEP as well as ... uninfected patient and even re-infection of an already infected .... Surgical cuts/wounds. 7 ... Table 4: Knowledge of time of administration of PEP. Time .... respondents to be uncertain about the existence of such ... Surely, before the advent of this long awaited.

A missing-bending-magnet scheme for PEP

International Nuclear Information System (INIS)

Liu, R.Z.; Winick, H.

1988-01-01

This article presents a missing-bending-magnet scheme for PEP as a modification that could be considered if PEP were available as a fully dedicated synchrotron radiation source. The scheme can be applied to one or more PEP sextants without changing the rest. By removing some bending magnets, rearranging the remaining magnets, and adding two quadrupoles, ten additional straight sections per sextant can be created, each 5 m or more in length, for insertion devices. Beam lines therefrom, plus possible beam lines from bending magnets would enter a continuous experimental hall instead of individual tunnels and halls for each beam line. This should result in construction cost savings and increased operations efficiency. The ideal beam orbit is unchanged at the two ends and the middle of the sextant. At the end of the curved part of the sextant the lattice functions match those of the long interaction region straight section in the low emittance configuration of PEP. The electron beam characteristics in the newly created straight sections are described, including the enlargement of the horizontal beam size due to the nonzero dispersion. Some disadvantages of the scheme are increased operations complexity due to the need for nine new quadrupole families, increased beam emittance (by 14.5% is one sextant is modified), and reduced dynamic aperture. However, the dynamic aperture is still about as large as the physical aperture and should be adequate for good beam lifetime and injection. (orig.)

Positron--Electron Project (PEP)

International Nuclear Information System (INIS)

Rees, J.R.

1977-01-01

PEP, an 18-GeV electron-positron colliding-beam storage ring facility at SLAC, is being built by a team from LBL and SLAC. Construction is under way and completion is scheduled for Fall of 1979. A summary is given of the design of the facility, and the status of the project is reported

Precision surveying system for PEP

International Nuclear Information System (INIS)

Gunn, J.; Lauritzen, T.; Sah, R.; Pellisier, P.F.

1977-01-01

A semi-automatic precision surveying system is being developed for PEP. Reference elevations for vertical alignment will be provided by a liquid level. The short range surveying will be accomplished using a Laser Surveying System featuring automatic data acquisition and analysis

Transverse instability excited by rf deflecting modes for PEP

International Nuclear Information System (INIS)

Chao, A.W.; Yao, C.Y.

1979-11-01

We have looked at the possible transverse instability effects which are caused by the deflecting modes of the rf cavities in PEP. The results are obtained by applying the expression of the instability damping rate. We have assumed that there equal bunches equally spaced in PEP. We have worked out the equivalent for a single bunch beam. The effect of chromaticity ξ is included as a frequency shift in the bunch mode spectra. We rewrite this result in terms of the transverse wake field instead of the impedance. We include an application of the Sacherer formalism to the case of resistive wall. The resulting expression of the damping rate contains two terms. The first term corresponds to the effect of the short wake fields; it agrees with the result of the head-tail instability as derived by Sands. A numerical estimate of this resistive-wall head tail case for PEP is given. It re-confirms that the resistive wall instability is not a serious problem for PEP. The second term gives the effect of long wake fields and it agrees with the result of Courant and Sessler. 10 refs., 2 figs

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

Science.gov (United States)

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

2015-12-01

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

PEP radiation shielding tests in SLAC A Beam

International Nuclear Information System (INIS)

Ash, W.; DeStaebler, H.; Harris, J.; Jenkins, T.; Murray, J.

1977-09-01

Radiation shielding tests designed to simulate possible conditions in and around the PEP experimental halls were conducted. The SLAC A Beam was targeted in the block tunnel at a point about midway between End Station A and Beam Dump East. At that site it was relatively easy to rearrange the concrete block structure to simulate the various shielding configurations under consideration for PEP. Extensive surveys of neutron and ionizing radiation were made. Complete results of the shielding tests are given

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

Science.gov (United States)

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…

KEKB and PEP-II B Factories

International Nuclear Information System (INIS)

Seeman, J.T.

1997-01-01

Two asymmetric B-Factories KEKB at KEK and PEP-II at SLAC are under construction, designed to study CP violation in the b-quark sector with a center of mass energy of 10.58 GeV. These two new accelerators are high luminosity two-ring two-energy e + e - colliders with one interaction point. There are many challenging accelerator physics and engineering issues associated with the high beam currents and high luminosities of these rings. The chosen solutions to these issues and the general parameters of the two rings are described in detail side-by-side. KEKB and PEP-II are well into the installation phase and are both scheduled to be completed in 1998. The particle physics programs are scheduled to start in 1999

Factors Associated With Forensic Nurses Offering HIV nPEP Status Post Sexual Assault.

Science.gov (United States)

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

2015-09-01

Nonoccupational, postexposure 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 (adjusted odds ratio [AOR] 64.15, 95% confidence interval [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. © The Author(s) 2014.

miR-378 Activates the Pyruvate-PEP Futile Cycle and Enhances Lipolysis to Ameliorate Obesity in Mice

Directory of Open Access Journals (Sweden)

Yong Zhang

2016-03-01

Full Text Available Obesity has been linked to many health problems, such as diabetes. However, there is no drug that effectively treats obesity. Here, we reveal that miR-378 transgenic mice display reduced fat mass, enhanced lipolysis, and increased energy expenditure. Notably, administering AgomiR-378 prevents and ameliorates obesity in mice. We also found that the energy deficiency seen in miR-378 transgenic mice was due to impaired glucose metabolism. This impairment was caused by an activated pyruvate-PEP futile cycle via the miR-378-Akt1-FoxO1-PEPCK pathway in skeletal muscle and enhanced lipolysis in adipose tissues mediated by miR-378-SCD1. Our findings demonstrate that activating the pyruvate-PEP futile cycle in skeletal muscle is the primary cause of elevated lipolysis in adipose tissues of miR-378 transgenic mice, and it helps orchestrate the crosstalk between muscle and fat to control energy homeostasis in mice. Thus, miR-378 may serve as a promising agent for preventing and treating obesity in humans.

Isolation and characterization of PEP3, a gene required for vacuolar biogenesis in Saccharomyces cerevisiae.

OpenAIRE

Preston, R A; Manolson, M F; Becherer, K; Weidenhammer, E; Kirkpatrick, D; Wright, R; Jones, E W

1991-01-01

The Saccharomyces cerevisiae PEP3 gene was cloned from a wild-type genomic library by complementation of the carboxypeptidase Y deficiency in a pep3-12 strain. Subclone complementation results localized the PEP3 gene to a 3.8-kb DNA fragment. The DNA sequence of the fragment was determined; a 2,754-bp open reading frame predicts that the PEP3 gene product is a hydrophilic, 107-kDa protein that has no significant similarity to any known protein. The PEP3 predicted protein has a zinc finger (CX...

An asymmetric Β-factory based on PEP

International Nuclear Information System (INIS)

Oddone, P.

1989-01-01

This paper reviews the motivation for building asymmetric B-factories based on storage rings and describes the current LBL/SLAC study to develop such a factory by modifying the PEP storage ring and adding a new low energy (2.5-3 GeV) storage ring. Collisions between the beam of the modified high energy PEP ring and the low energy ring lead to a luminosity of 2 x 10 33 cm- 2 sec - 1 at E cm = Y(4s) with currents of 0.8A in each beam. Further increases in current can lead to luminosities close to 10 34 cm - 2 sec - 1

New results on flavor production at PEP

International Nuclear Information System (INIS)

Barbaro-Galtieri, A.

1984-05-01

This report includes results from five PEP detectors: DELCO, HRS, MAC, MARK II and TPC. All, except the TPC, are presently taking data at PEP. The TPC is being upgraded: a new superconducting coil is being installed and other improvements are being implemented. The results discussed here are either new or improved since the Cornell Conference. New results on Particle Searches and a limit on neutrino generations are discussed. New data are included on weak couplings of c and b quarks. Various new results on hadron production are reported. All data were obtained in e +- collisions with total energy √s=29 GeV. 54 references

Optical beam diagnostics on PEP

International Nuclear Information System (INIS)

Sabersky, A.P.

1981-02-01

In designing the PEP optical diagnostics we have been able to build on the experience gained with SPEAR. Most of the problems at SPEAR could be traced to the optical diagnostic system being inside the tunnel. A machine shutdown is required for any maintenance or modification. This implies that in order to make such an instrument successful, a large engineering effort must be mounted to ensure 100% operation at startup. The functions that do not work at startup may never be made to work; this has happened at several machines. Experimental setups are likewise risky and time consuming. A point which has been borne out in both SPEAR and PEP is that the mechanical part of the instrument, the special vacuum chamber, the optical mounts, the alignment and adjustments, require approximately 60% of the effort and cost of the optical diagnostics. It is far better to economize on detectors and electronics than on mechanical and optical essentials

DomPep--a general method for predicting modular domain-mediated protein-protein interactions.

Directory of Open Access Journals (Sweden)

Lei Li

Full Text Available Protein-protein interactions (PPIs are frequently mediated by the binding of a modular domain in one protein to a short, linear peptide motif in its partner. The advent of proteomic methods such as peptide and protein arrays has led to the accumulation of a wealth of interaction data for modular interaction domains. Although several computational programs have been developed to predict modular domain-mediated PPI events, they are often restricted to a given domain type. We describe DomPep, a method that can potentially be used to predict PPIs mediated by any modular domains. DomPep combines proteomic data with sequence information to achieve high accuracy and high coverage in PPI prediction. Proteomic binding data were employed to determine a simple yet novel parameter Ligand-Binding Similarity which, in turn, is used to calibrate Domain Sequence Identity and Position-Weighted-Matrix distance, two parameters that are used in constructing prediction models. Moreover, DomPep can be used to predict PPIs for both domains with experimental binding data and those without. Using the PDZ and SH2 domain families as test cases, we show that DomPep can predict PPIs with accuracies superior to existing methods. To evaluate DomPep as a discovery tool, we deployed DomPep to identify interactions mediated by three human PDZ domains. Subsequent in-solution binding assays validated the high accuracy of DomPep in predicting authentic PPIs at the proteome scale. Because DomPep makes use of only interaction data and the primary sequence of a domain, it can be readily expanded to include other types of modular domains.

The PEP-II project-wide database

International Nuclear Information System (INIS)

Chan, A.; Calish, S.; Crane, G.; MacGregor, I.; Meyer, S.; Wong, J.

1995-05-01

The PEP-II Project Database is a tool for monitoring the technical and documentation aspects of this accelerator construction. It holds the PEP-II design specifications, fabrication and installation data in one integrated system. Key pieces of the database include the machine parameter list, magnet and vacuum fabrication data. CAD drawings, publications and documentation, survey and alignment data and property control. The database can be extended to contain information required for the operations phase of the accelerator and detector. Features such as viewing CAD drawing graphics from the database will be implemented in the future. This central Oracle database on a UNIX server is built using ORACLE Case tools. Users at the three collaborating laboratories (SLAC, LBL, LLNL) can access the data remotely, using various desktop computer platforms and graphical interfaces

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

Science.gov (United States)

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.

Prevention of atrial fibrillation by Renin-Angiotensin system inhibition a meta-analysis

DEFF Research Database (Denmark)

Schneider, Markus; Hua, Tsushung A; Böhm, Michael

2010-01-01

The authors reviewed published clinical trial data on the effects of renin-angiotensin system (RAS) inhibition for the prevention of atrial fibrillation (AF), aiming to define when RAS inhibition is most effective.......The authors reviewed published clinical trial data on the effects of renin-angiotensin system (RAS) inhibition for the prevention of atrial fibrillation (AF), aiming to define when RAS inhibition is most effective....

Prevention effect of allopurinol on post-endoscopic retrograde cholangiopancreatography pancreatitis: a meta-analysis of prospective randomized controlled trials.

Directory of Open Access Journals (Sweden)

Wei-Li Cao

Full Text Available BACKGROUND: Pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP which can be severe and cause death in approximately 10% of cases. Up to now, six randomized controlled trials (RCTs have been found relevant to the effect of allopurinol on prevention of Post-ERCP pancreatitis (PEP. However, these results remained controversial. OBJECTIVE: To conduct a meta-analysis with RCTs published in full text to determine the effectiveness of prophylactic allopurinol of different dosages and administration time in the incidence and severity of PEP. METHODS: Literature search was performed in PubMed, Embase, Web of Science and Cochrane Library from databases inception to May 2014. RCTs comparing the effect of allopurinol with placebo on prevention of PEP were included. Statistical heterogeneity was quantitatively evaluated byχ2 test with the significance set P50%. RESULTS: Six RCTs consisting of 1974 participants were eventually included. The incidences of PEP in allopurinol group and placebo group were 8.4%(83/986 and 9.9%(98/988 respectively. Meta-analysis showed no evident prevention effect of allopurinol on the incidence of PEP (RR 0.75, 95%CI 0.39-1.42 with significant heterogeneity (I2 = 70.4%, P = 0.005. When studies were stratified according to the dosages and administration time of allopurinol they applied, there was still no evident prevention effect of allopurinol on mild, moderate or severe PEP. However, statistically substantial heterogeneity was presented in the subgroup of moderate PEP when the effect of high dose of allopurinol was analyzed (Imoderate2 = 82.3%, Pmoderate = 0.018. Statistically significant heterogeneity was also observed in subgroup of mild PEP, when the effect of long adminstration time of allopurinol was investigated (Imild2 = 62.8%, Pmild = 0.068. CONCLUSION: The prophylactic use of allopurinol in different dosages and administration time had no effect

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

Science.gov (United States)

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.

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

Science.gov (United States)

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.

PEP magnet power supply systems

International Nuclear Information System (INIS)

Jackson, L.T.

1977-01-01

The dc electrical requirements of the PEP magnets fall mainly into two categories: (1) high power and current of single polarity and (2) low-power bi-polar. The first category will be thyristor-chopper controlled off common 600 V dc busses. The second group will utilize continuously controlled push-pull transistor actuators

Diagnosing the PEP-II Injection System

Energy Technology Data Exchange (ETDEWEB)

Decker, F.-J.; Donald, M.H.; Iverson, R.H.; Kulikov, A.; Pappas, G.C.; Weaver, M.; /SLAC

2005-05-09

The injection of beam into the PEP-II B-Factory, especially into the High Energy Ring (HER) has some challenges. A high background level in the BaBar detector has for a while inhibited us from trickling charge into the HER similar to the Low Energy Ring (LER). Analyzing the injection system has revealed many issues which could be improved. The injection bump between two kickers was not closed, mainly because the phase advance wasn't exactly 180{sup o} and the two kicker strengths were not balanced. Additionally we found reflections which kick the stored beam after the main kick and cause the average luminosity to drop about 3% for a 10 Hz injection rate. The strength of the overall kick is nearly twice as high as the design, indicating a much bigger effective septum thickness. Compared with single beam the background is worse when the HER beam is colliding with the LER beam. This hints that the beam-beam force and the observed vertical blow-up in the HER pushes the beam and especially the injected beam further out to the edge of the dynamic aperture or beyond.

Diagnosing the PEP-II Injection System

International Nuclear Information System (INIS)

Decker, F.-J.; Donald, M.H.; Iverson, R.H.; Kulikov, A.; Pappas, G.C.; Weaver, M.; SLAC

2005-01-01

The injection of beam into the PEP-II B-Factory, especially into the High Energy Ring (HER) has some challenges. A high background level in the BaBar detector has for a while inhibited us from trickling charge into the HER similar to the Low Energy Ring (LER). Analyzing the injection system has revealed many issues which could be improved. The injection bump between two kickers was not closed, mainly because the phase advance wasn't exactly 180 o and the two kicker strengths were not balanced. Additionally we found reflections which kick the stored beam after the main kick and cause the average luminosity to drop about 3% for a 10 Hz injection rate. The strength of the overall kick is nearly twice as high as the design, indicating a much bigger effective septum thickness. Compared with single beam the background is worse when the HER beam is colliding with the LER beam. This hints that the beam-beam force and the observed vertical blow-up in the HER pushes the beam and especially the injected beam further out to the edge of the dynamic aperture or beyond

PEP-II design update and R ampersand D results

International Nuclear Information System (INIS)

Zisman, M.S.

1993-01-01

We describe the present status of the PEP-II asymmetric β factory design undertaken by SLAC, LBL, and LLNL. Design optimization during the past year and changes from the original CDR design are described. R ampersand D activities have focused primarily on the key technology areas of vacuum, RF, and feedback system design. Recent progress in these areas is described. The R ampersand D results have verified our design assumptions and provide further confidence in the design of PEP-II

Recent improvements in luminosity at PEP

International Nuclear Information System (INIS)

Helm, R.; Allen, M.; Chao, A.

1983-03-01

We will describe improvements which have led to new records for peak and average luminosity at PEP. Comparison of recent results with several earlier lattice and optical modifications shows rather good correlation with the predictions of a beam-beam simulation program

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

Energy Technology Data Exchange (ETDEWEB)

Sevigny, Gary J.; Bredt, Ofelia P.; Burns, Carolyn A.; Kurath, Dean E.; Geeting, John GH; Golovich, Elizabeth C.; Guzman-Leong, Consuelo E.; Josephson, Gary B.

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. 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. 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

Ca 2+ signaling by plant Arabidopsis thaliana Pep peptides depends on AtPepR1, a receptor with guanylyl cyclase activity, and cGMP-activated Ca 2+ channels

KAUST Repository

Qia, Zhi; Verma, Rajeev K.; Gehring, Christoph A; Yamaguchi, Yube; Zhao, Yichen; Ryan, Clarence A.; Berkowitz, Gerald A.

2010-01-01

receptor- like kinase receptor AtPepR1 has guanylyl cyclase activity, generating cGMP from GTP, and that cGMP can activate CNGC2- dependent cytosolic Ca 2+ elevation. AtPep-dependent expression of pathogen-defense genes (PDF1.2, MPK3, and WRKY33

PEP cooling water systems and underground piped utilities design criteria report

International Nuclear Information System (INIS)

Hall, F.; Robbins, D.

1975-10-01

This paper discusses the cooling systems required by the PEP Storage Ring. Particular topics discussed are: Cooling tower systems, RF cavity and vacuum chamber LCW cooling systems, klystron and ring magnet LLW cooling systems, Injection magnet LCW Cooling Systems; PEP interaction area detector LCW Cooling Systems; and underground piped utilities. 1 ref., 20 figs

An Over-damped Cavity Longitudinal Kicker for the PEP-II LER

CERN Document Server

McIntosh, P

2003-01-01

Both rings of PEP-II use drift tube kickers in the longitudinal bunch-by-bunch feedback system. Efforts are now underway to increase the stored beam currents and luminosity of PEP-II, and beam-induced heating of these structures, particularly in the Low Energy Ring (LER) is of concern. An alternative kicker design based on the over-damped cavity kicker, first developed by INFN-Frascati is being built for PEP-II. This low loaded Q (or wide bandwidth) structure is fed by a network of ridged waveguides coupled to a simple pill-box cavity. Beam induced RF power is also coupled out of the cavity to external loads, so that the higher order modes (HOMs) excited in the structure are well-damped. This paper details the kicker design for PEP-II and discusses some of the design trade-offs between shunt impedance and bandwidth, as well as the influence of the feedthroughs on the kicker parameters. Estimates of the expected power deposition in the cavity are also provided.

Glyceryl trinitrate for prevention of post-ERCP pancreatitis and improve the rate of cannulation: a meta-analysis of prospective, randomized, controlled trials.

Directory of Open Access Journals (Sweden)

Jiexia Ding

Full Text Available BACKGROUND: Acute pancreatitis is the most common complication of diagnostic and therapeutic endoscopic retrograde cholangiopancreatography (ERCP. Several clinical trials used glyceryl trinitrate (GTN to prevent the incidence of post-ERCP pancreatitis (PEP. However, the results were still controversial. OBJECTIVE: To conduct a meta-analysis of published, full-length, randomized controlled trials evaluating the effect of prophylactic GTN on the prevention of PEP, improve the rate of cannulation and the prevention of hyperamylasemia. METHODS: Literature searches were conducted using PubMed, EMBASE, The Cochrane Library and Web of Knowledge databases, using keywords "post-ERCP" and "pancreatitis" and limited in randomized controlled trials. RESULTS: Twelve RCTs involving 2649 patients were included. Eleven RCTs compared GTN with placebo for PEP prevention. Meta-analysis showed the overall incidence of PEP was significantly reduced by GTN treatment (RR 0.67; 95% CI, 0.52-0.87. Nevertheless, GTN administration did not decrease the incidence of moderate to severe PEP (RR 0.70; 95% CI, 0.42-1.15. Subgroup analyses revealed that GTN administered by sublingual was more effective than transdermal and topical in reducing the incidence of PEP. Besides, the prophylactic effect of GTN was far more obvious in the group of high PEP incidence than in the group of low PEP incidence. Additionally, the incidence of hyperamylasemia was significantly reduced by GTN treatment (RR 0.69; 95% CI, 0.54-0.90. No differences of the successful cannulation rate of bile ducts (RR 1.03; 95% CI, 0.99-1.06 attributable to GTN were observed. CONCLUSION: Prophylactic use of GTN reduced the overall incidence of PEP and hyperamylasemia. However, GTN was not helpful for the severity of PEP and the rate of cannulation.

Nuclear physics at PEP: First test and future plans

International Nuclear Information System (INIS)

Van Bibber, K.; Dietrich, F.S.; Melnikoff, S.O.

1986-09-01

A test run of internal target nuclear physics at the PEP storage ring is described. The Time Projection Chamber (TPC-2γ detector) was used to detect the inelastically scattered electron and complete hadronic final state in the interaction of 14.5 GeV electrons with D 2 , Ar and Xe gas targets. The data comprise mostly low-x low-Q 2 events, but some deep inelastic scattering as well. The future possibilities of a dedicated nuclear physics program at PEP are outlined. 15 refs., 25 figs

Event rates to be expected at PEP

International Nuclear Information System (INIS)

Richter, B.

1988-01-01

As a guide for planning experiments at PEP, some estimates are given of average luminosity, charged and neutral particle yields vs. momentum, QED test capabilities, and weak interaction effects. 2 figs

Plans for PEP survey and alignment: Status report

International Nuclear Information System (INIS)

Gunn, J.; Sah, R.

1975-01-01

This note discusses the current state of survey and alignment plans for PEP Stage I. Several surveying techniques are described; one is described in considerable detail. The survey and alignment task for PEP consists of positioning approximately 700 ring magnets, 100 injection line magnets, and 100 miscellaneous components. The alignment tolerances are tight and they are set by the requirement that closed orbit distortions must be small for proper storage ring operation. The alignment problem is aggravated by the circumstance that the storage ring components are placed in tunnels which span a large area (over 700 meters across) and which do not permit long lines of sight. 6 ref., 1 fig

Problems in obtaining polarized e+ and e- beams and perspectives for PEP

International Nuclear Information System (INIS)

Chao, A.W.

1980-09-01

A matrix formalism for polarization calculation, as well as its comparison with other methods, is briefly discussed. The prediction for SPEAR is compared with experimental measurements. An estimate is offered for the transverse polarization for PEP. Various schemes for obtaining the longitudinal polarization in PEP are studied

Pep-3D-Search: a method for B-cell epitope prediction based on mimotope analysis.

Science.gov (United States)

Huang, Yan Xin; Bao, Yong Li; Guo, Shu Yan; Wang, Yan; Zhou, Chun Guang; Li, Yu Xin

2008-12-16

The prediction of conformational B-cell epitopes is one of the most important goals in immunoinformatics. The solution to this problem, even if approximate, would help in designing experiments to precisely map the residues of interaction between an antigen and an antibody. Consequently, this area of research has received considerable attention from immunologists, structural biologists and computational biologists. Phage-displayed random peptide libraries are powerful tools used to obtain mimotopes that are selected by binding to a given monoclonal antibody (mAb) in a similar way to the native epitope. These mimotopes can be considered as functional epitope mimics. Mimotope analysis based methods can predict not only linear but also conformational epitopes and this has been the focus of much research in recent years. Though some algorithms based on mimotope analysis have been proposed, the precise localization of the interaction site mimicked by the mimotopes is still a challenging task. In this study, we propose a method for B-cell epitope prediction based on mimotope analysis called Pep-3D-Search. Given the 3D structure of an antigen and a set of mimotopes (or a motif sequence derived from the set of mimotopes), Pep-3D-Search can be used in two modes: mimotope or motif. To evaluate the performance of Pep-3D-Search to predict epitopes from a set of mimotopes, 10 epitopes defined by crystallography were compared with the predicted results from a Pep-3D-Search: the average Matthews correlation coefficient (MCC), sensitivity and precision were 0.1758, 0.3642 and 0.6948. Compared with other available prediction algorithms, Pep-3D-Search showed comparable MCC, specificity and precision, and could provide novel, rational results. To verify the capability of Pep-3D-Search to align a motif sequence to a 3D structure for predicting epitopes, 6 test cases were used. The predictive performance of Pep-3D-Search was demonstrated to be superior to that of other similar programs

The key determinants of perceived external prestige (PEP – Qualitative research approach

Directory of Open Access Journals (Sweden)

Tamara Sušanj Šulentić

2017-01-01

Full Text Available Perceived external prestige (PEP is a well-known concept oriented towards describing the way members of a certain organization interpret and assess their organisational reputation. Such perception can significantly affect employees’ identification and loyalty to the organisation as well as their job satisfaction and work performance. According to the social identification theory, people define themselves and others with respect to their belonging to a particular group or organization, and their basic motive is a personal need for self-respect and a sense of pride. Employees’ perception of being members of an important, reputable and significant organisation contributes to the feeling of self-respect, which increases their individual social value and status. According to literature, there are only few objections to the concept of PEP, mainly those related to the determination of its structure and, with it, to its management. Although there is a growing literature on PEP, it is still not clear whether PEP is a one-dimensional or a multidimensional construct. If PEP is a multidimensional concept, it is important to specify its key components, in order to enhance the management of favourable organizational prestige in a real work environment. The purpose of this paper was to determine the structure of PEP and important sources of information, based on which, employees value the prestige of their organisation. Qualitative research was conducted, comprising nine semi-structured interviews with communication experts working for a multinational organisation operating in several European countries. The results of this paper indicate that PEP is a multidimensional construct, with several components, important for its creation and management. Those components can be grouped into three main categories: track record of success and the position of the organisation on the market, social impact of the organisation on the immediate environment and the

EFRT M-12 Issue Resolution: Caustic-Leach Rate Constants from PEP and Laboratory-Scale Tests

Energy Technology Data Exchange (ETDEWEB)

Mahoney, Lenna A.; Rassat, Scot D.; Eslinger, Paul W.; Aaberg, Rosanne L.; Aker, Pamela M.; Golovich, Elizabeth C.; Hanson, Brady D.; Hausmann, Tom S.; Huckaby, James L.; Kurath, Dean E.; Minette, Michael J.; Sundaram, S. K.; Yokuda, Satoru T.

2010-01-01

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. 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. The work described in this report addresses caustic leaching under WTP conditions, based on tests performed with a Hanford waste simulant. Because gibbsite leaching kinetics are rapid (gibbsite is expected to be dissolved by the time the final leach temperature is reached), boehmite leach kinetics are the main focus of the caustic-leach tests. The tests were completed at the laboratory-scale and in the PEP, which is a 1/4.5-scale mock-up of key PTF process equipment. Two laboratory-scale caustic-leach tests were performed for each of the PEP runs. For each PEP run, unleached slurry was taken from the PEP caustic-leach vessel for one batch and used as feed for both of the corresponding laboratory-scale tests.

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

Science.gov (United States)

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.

Beam Aborts in PEP-II Rings and Lingering Drift Chamber Currents

International Nuclear Information System (INIS)

Meshkat, N.

2004-01-01

The BABAR detector at SLAC was designed to study CP-violation in B-meson decays from electron-positron collisions in the PEP-II electron-positron storage rings. Background radiation in the High Energy Ring (HER) and Low Energy Ring (LER) of PEP-II has the potential to damage the sensitive equipment in the BABAR detector. As a result, the beams in the HER and LER can be aborted to prevent such damage. In the span of a few microseconds, the HER and LER currents drop from, for example, 1450 micro Amps and 2300 micro Amps, respectively, to zero. At this time the voltage in the Drift Chamber is rapidly ramped down from a potential of 1930 V to a safe potential of 800 V, thus we would expect the currents in the Drift Chamber to quickly go to zero once the beams are aborted. However, we observe an average 15 second delay in the measured time it takes for all current in the Drift Chamber to fall below 1 micro Amp. This delay has been hypothesized as an instrumentation issue and not as a physical phenomenon. The specific sources of this error are still not completely known, but analysis suggests that it results from the interplay of the CAEN High Voltage supplies and the EPICS system and/or limitations within those systems

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

Science.gov (United States)

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.

The First Year of the BABAR Experiment at PEP-II

Energy Technology Data Exchange (ETDEWEB)

Barrera, Barbara

2000-12-18

The BABAR detector, situated at the SLAC PEP-II asymmetric e{sup +}e{sup -} collider, has been recording data at energies on and around the {Upsilon}(4S) resonance since May 1999. In this paper, we briefly describe the PEP-II B Factory and the BABAR detector. The performance presently achieved by the experiment in the areas of tracking, vertexing, calorimetry and particle identification is reviewed. Analysis concepts that are used in the various papers submitted to this conference are also discussed.

Modes of Antiviral Action of Chemical Portions and Constituents from Woad Root Extract against Influenza Virus A FM1

Directory of Open Access Journals (Sweden)

Jia-Hang Su

2016-01-01

Full Text Available Woad root has been used for the prevention of influenza for hundreds of years in many Asian countries. In this study, the antiviral modes of clemastanin B (CB, epigoitrin, phenylpropanoid portion (PEP, and the mixture of phenylpropanoids, alkaloids, and organic acid portions (PEP + ALK + OA from wood root extract against influenza virus A FM1 were investigated. The results revealed that CB, epigoitrin, PEP, and PEP + ALK + OA exert their anti-influenza activity via inhibiting the virus multiplication, prophylaxis, and blocking the virus attachment. The primary mode of action of PEP and PEP + ALK + OA is the inhibition of virus replication. The inhibitory effect on virus attachment and multiplication is the main modes for epigoitrin. All the compounds or chemical portions from woad root extract tested in this study do not have direct virucidal activity. Our results provided the comprehensive analysis of the antiviral mechanism of wood root extract.

EFRT M-12 Issue Resolution: Comparison of Filter Performance at PEP and CUF Scale

Energy Technology Data Exchange (ETDEWEB)

Daniel, Richard C.; Billing, Justin M.; Bontha, Jagannadha R.; Brown, Christopher F.; Eslinger, Paul W.; Hanson, Brady D.; Huckaby, James L.; Karri, Naveen K.; Kimura, Marcia L.; Kurath, Dean E.; Minette, Michael J.

2010-01-22

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.(a) 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 PEP also includes non-prototypic ancillary equipment to support the core processing.

EFRT M-12 Issue Resolution: Comparison of PEP and Bench-Scale Oxidative Leaching Results

Energy Technology Data Exchange (ETDEWEB)

Rapko, Brian M.; Schonewill, Philip P.; Brown, Christopher F.; Eslinger, Paul W.; Fountain, Matthew S.; Hausmann, Tom S.; Huckaby, James L.; Hanson, Brady D.; Kurath, Dean E.; Minette, Michael J.

2010-01-01

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. 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.

EFRT M-12 Issue Resolution: Comparison of PEP and Bench-Scale Oxidative Leaching Results

International Nuclear Information System (INIS)

Rapko, Brian M.; Schonewill, Philip P.; Brown, Christopher F.; Eslinger, Paul W.; Fountain, Matthew S.; Hausmann, Tom S.; Huckaby, James L.; Hanson, Brady D.; Kurath, Dean E.; Minette, Michael J.

2010-01-01

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. 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.

EFRT M-12 Issue Resolution: Comparison of Filter Performance at PEP and CUF Scale

International Nuclear Information System (INIS)

Daniel, Richard C.; Billing, Justin M.; Bontha, Jagannadha R.; Brown, Christopher F.; Eslinger, Paul W.; Hanson, Brady D.; Huckaby, James L.; Karri, Naveen K.; Kimura, Marcia L.; Kurath, Dean E.; Minette, Michael J.

2010-01-01

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.(a) 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 PEP also includes non-prototypic ancillary equipment to support the core processing.

Evolutionary divergence of the plant elicitor peptides (Peps) and their receptors: interfamily incompatibility of perception but compatibility of downstream signalling

KAUST Repository

Lori, M.

2015-05-22

Plant elicitor peptides (Peps) are potent inducers of pattern-triggered immunity and amplify the immune response against diverse pathogens. Peps have been discovered and studied extensively in Arabidopsis and only recently orthologs in maize were also identified and characterized in more detail. Here, the presence of PROPEPs, the Pep precursors, and PEPRs, the Pep receptors, was investigated within the plant kingdom. PROPEPs and PEPRs were identified in most sequenced species of the angiosperms. The conservation and compatibility of the Pep-PEPR-system was analysed by using plants of two distantly related dicot families, Brassicaceae and Solanaceae, and a representative family of monocot plants, the Poaceae. All three plant families contain important crop plants, including maize, rice, tomato, potato, and canola. Peps were not recognized by species outside of their plant family of origin, apparently because of a divergence of the Pep sequences. Three family-specific Pep motifs were defined and the integration of such a motif into the Pep sequence of an unrelated Pep enabled its perception. Transient transformation of Nicotiana benthamiana with the coding sequences of the AtPEPR1 and ZmPEPR1a led to the recognition of Pep peptides of Brassicaceae or Poaceae origin, respectively, and to the proper activation of downstream signalling. It was concluded that signalling machinery downstream of the PEPRs is highly conserved whereas the leucine-rich repeat domains of the PEPRs co-evolved with the Peps, leading to distinct motifs and, with it, interfamily incompatibility.

Hazard Analysis for the Pretreatment Engineering Platform (PEP)

Energy Technology Data Exchange (ETDEWEB)

Sullivan, Robin S.; Geeting, John GH; Lawrence, Wesley E.; Young, Jonathan

2008-07-10

The Pretreatment Engineering Platform (PEP) is designed to perform a demonstration on an engineering scale to confirm the Hanford Waste Treatment Plant Pretreatment Facility (PTF) leaching and filtration process equipment design and sludge treatment process. The system will use scaled prototypic equipment to demonstrate sludge water wash, caustic leaching, oxidative leaching, and filtration. Unit operations to be tested include pumping, solids washing, chemical reagent addition and blending, heating, cooling, leaching, filtration, and filter cleaning. In addition, the PEP will evaluate potential design changes to the ultrafiltration process system equipment to potentially enhance leaching and filtration performance as well as overall pretreatment throughput. The skid-mounted system will be installed and operated in the Processing Development Laboratory-West at Pacific Northwest National Laboratory (PNNL) in Richland, Washington.

Evaluation of the BEAM--BEAM effect in PEP using Myer's simulation program

International Nuclear Information System (INIS)

Hutton, A.

1982-09-01

The program BEAM BEAM written by Steve Myers for the LEP machine at CERN has given encouraging results in the simulation of the beam-beam effect in electron-positron storage rings. It therefore seemed worthwhile to apply the program to PEP with two main intentions. Firstly, to confirm the validity of the program by comparison with experimental data from previous PEP runs and secondly, to search for an improvement in the operating conditions of PEP. Clearly a successful prediction would also enhance the credibility of the program. The program itself has been extensively described in the literature and will not be repeated here, except for some comments of direct relevance to the present simulation. 14 refs., 15 figs., 4 tabs

Integrating Antiretroviral Strategies for Human Immunodeficiency Virus Prevention: Post- and Pre-Exposure Prophylaxis and Early Treatment.

Science.gov (United States)

Grant, Robert M; Smith, Dawn K

2015-12-01

Best practices for integrating human immunodeficiency virus (HIV) testing and antiretroviral interventions for prevention and treatment are suggested based on research evidence and existing normative guidance. The goal is to provide high-impact prevention services during periods of substantial risk. Antiretroviral medications are recommended for postexposure prophylaxis (PEP), pre-exposure prophylaxis (PrEP), and treatment of HIV infection. We reviewed research evidence and current normative guidelines to identify best practices for integrating these high-impact prevention strategies. More sensitive HIV tests used for screening enable earlier diagnosis and treatment of HIV infection, more appropriate counseling, and help limit drug resistance. A fully suppressive PEP regimen should be initiated based on exposure history or physical findings when sensitive diagnostic testing is delayed or not available and antibody tests are negative. Transitions from PEP to PrEP are often warranted because HIV exposure events may continue to occur. This algorithmic approach to integrating PEP, PrEP, and early treatment decisions may increase the uptake of these interventions by a greater number and diversity of knowledgeable healthcare providers.

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

Science.gov (United States)

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 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.

A new lattice for PEP

International Nuclear Information System (INIS)

Rees, J.; Wiedemann, H.

1976-01-01

A new low-beta configuration has been proposed for PEP which has a reduced β/sub y/* and is capable of delivering design luminosity with lower circulating beam currents that those required in the standard configuration described in the Conceptual Design Report of February, 1976. A feasibility study has been carried out and it is reported in PTM-65, September 8, 1976, by Lee, Morton and Wiedemann. The beam-stay-clear region is specified in PTM-66, September 3, 1976 by H. Wiedemann. The principal advantages of the new lattice are that the lower beam currents lead to lower higher-order-mode power and permit reduction of the total rf power required which in turn reduces both capital cost and operating cost. Its disadvantages stem primarily from the relatively high maximum beta values which occur in the interaction-region quadrupoles. These produce high chromaticities which require a generally stronger sextupole system for their compensation. The advantages outweigh the disadvantages and the new 11-cm-beta configuration has been adopted as the design configuration for energies of 15-GeV and lower. In the remainder of this report we shall discuss the implications of this new configuration for the various systems of PEP. 1 fig., 3 tabs

PEP-II status report

International Nuclear Information System (INIS)

Dorfan, J.M.

1998-06-01

The main design features of the PEP-II asymmetric two-ring electron-positron B Factory collider, built at the Stanford Linear Accelerator Center, are described. This facility will complete construction in June 1998. The high energy ring, completed in May 1997, has had 3 months of commissioning and successfully stored 0.75 A of electrons. The success of the high energy ring testing validates not only its ring components, but also the injection system, the RF system and the control system all of which are common to the two rings

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

Science.gov (United States)

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-pep

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

Directory of Open Access Journals (Sweden)

Wenhan Chen

Full Text Available 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/

First Evidence of pep Solar Neutrinos by Direct Detection in Borexino

Science.gov (United States)

Bellini, G.; Benziger, J.; Bick, D.; Bonetti, S.; Bonfini, G.; Bravo, D.; Buizza Avanzini, M.; Caccianiga, B.; Cadonati, L.; Calaprice, F.; Carraro, C.; Cavalcante, P.; Chavarria, A.; Chepurnov, A.; D'Angelo, D.; Davini, S.; Derbin, A.; Etenko, A.; Fomenko, K.; Franco, D.; Galbiati, C.; Gazzana, S.; Ghiano, C.; Giammarchi, M.; Goeger-Neff, M.; Goretti, A.; Grandi, L.; Guardincerri, E.; Hardy, S.; Ianni, Aldo; Ianni, Andrea; Korablev, D.; Korga, G.; Koshio, Y.; Kryn, D.; Laubenstein, M.; Lewke, T.; Litvinovich, E.; Loer, B.; Lombardi, F.; Lombardi, P.; Ludhova, L.; Machulin, I.; Manecki, S.; Maneschg, W.; Manuzio, G.; Meindl, Q.; Meroni, E.; Miramonti, L.; Misiaszek, M.; Montanari, D.; Mosteiro, P.; Muratova, V.; Oberauer, L.; Obolensky, M.; Ortica, F.; Otis, K.; Pallavicini, M.; Papp, L.; Perasso, L.; Perasso, S.; Pocar, A.; Quirk, J.; Raghavan, R. S.; Ranucci, G.; Razeto, A.; Re, A.; Romani, A.; Sabelnikov, A.; Saldanha, R.; Salvo, C.; Schönert, S.; Simgen, H.; Skorokhvatov, M.; Smirnov, O.; Sotnikov, A.; Sukhotin, S.; Suvorov, Y.; Tartaglia, R.; Testera, G.; Vignaud, D.; Vogelaar, R. B.; von Feilitzsch, F.; Winter, J.; Wojcik, M.; Wright, A.; Wurm, M.; Xu, J.; Zaimidoroga, O.; Zavatarelli, S.; Zuzel, G.

2012-02-01

We observed, for the first time, solar neutrinos in the 1.0-1.5 MeV energy range. We determined the rate of pep solar neutrino interactions in Borexino to be 3.1±0.6stat±0.3systcounts/(day·100ton). Assuming the pep neutrino flux predicted by the standard solar model, we obtained a constraint on the CNO solar neutrino interaction rate of Mikheyev-Smirnov-Wolfenstein large mixing angle solution to solar neutrino oscillations, these values correspond to solar neutrino fluxes of (1.6±0.3)×108cm-2s-1 and <7.7×108cm-2s-1 (95% C.L.), respectively, in agreement with both the high and low metallicity standard solar models. These results represent the first direct evidence of the pep neutrino signal and the strongest constraint of the CNO solar neutrino flux to date.

Optimizing the injection straight of PEP II asymmetric B Factory at SLAC

International Nuclear Information System (INIS)

Bulos, F.; Bloom, E.; Davies-White, W.; Donald, M.; Fairfield, K.; Fieguth, T.; Godfrey, G.; Holtzapple, R.; Hutton, A.; Loew, G.; Miller, R.; Sukiennicki, B.; Wen, H.; Ronan, M.

1992-04-01

The asymmetric energy PEP II B Factory proposed as an upgrade of PEP at the Stanford Linear Accelerator Center requires both a powerful low emittance source of e - e + and a very reliable and efficient injection system. The SLC linac fulfills the source requirement very well. We describe here the optimization of the optics of the injection straight to insure reliable and efficient injection

Optimizing the injection straight of PEP II asymmetric B factory at SLAC

International Nuclear Information System (INIS)

Bulos, F.; Bloom, E.; Davies-White, W.; Donald, M.; Fairfield, K.; Fieguth, T.; Godfrey, G.; Holtzapple, R.; Hutton, A.; Loew, G.; Miller, R.; Sukiennicki, B.; Wen, H.

1992-01-01

The asymmetric energy PEP II B Factory proposed as an upgrade of PEP at the Stanford Linear Accelerator Center requires both a powerful low emittance source of e - e + and a very reliable and efficient injection system. The SLC linac fulfills the source requirement very well. We describe here the optimization of the optics of the injection straight to insure reliable and efficient injection

Inhibition of Mutation: A Novel Approach to Preventing and Treating Cancer

National Research Council Canada - National Science Library

Romesberg, Floyd E

2007-01-01

.... Specific biochemical pathways are responsible for introducing mutation to the genome. Using drug(s) to inhibit one or more of these proteins and thereby prevent cancer is a novel and unique cancer prevention approach...

In roots of Arabidopsis thaliana, the damage-associated molecular pattern AtPep1 is a stronger elicitor of immune signalling than flg22 or the chitin heptamer.

Directory of Open Access Journals (Sweden)

Lorenzo Poncini

Full Text Available Plants interpret their immediate environment through perception of small molecules. Microbe-associated molecular patterns (MAMPs such as flagellin and chitin are likely to be more abundant in the rhizosphere than plant-derived damage-associated molecular patterns (DAMPs. We investigated how the Arabidopsis thaliana root interprets MAMPs and DAMPs as danger signals. We monitored root development during exposure to increasing concentrations of the MAMPs flg22 and the chitin heptamer as well as of the DAMP AtPep1. The tissue-specific expression of defence-related genes in roots was analysed using a toolkit of promoter::YFPN lines reporting jasmonic acid (JA-, salicylic acid (SA-, ethylene (ET- and reactive oxygen species (ROS- dependent signalling. Finally, marker responses were analysed during invasion by the root pathogen Fusarium oxysporum. The DAMP AtPep1 triggered a stronger activation of the defence markers compared to flg22 and the chitin heptamer. In contrast to the tested MAMPs, AtPep1 induced SA- and JA-signalling markers in the root and caused a severe inhibition of root growth. Fungal attack resulted in a strong activation of defence genes in tissues close to the invading fungal hyphae. The results collectively suggest that AtPep1 presents a stronger danger signal to the Arabidopsis root than the MAMPs flg22 and chitin heptamer.

Proline iminopeptidase PepI overexpressing Lactobacillus casei as an adjunct starter in Edam cheese

Science.gov (United States)

Navidghasemizad, Sahar; Takala, Timo M; Alatossava, Tapani; Saris, Per EJ

2013-01-01

In this study the growth of genetically modified Lactobacillus casei LAB6, overexpressing proline iminopeptidase PepI and its capacity to increase free proline was investigated during ripening of Edam cheese. The strain successfully survived 12 weeks of ripening period in cheese. The food-grade plasmid pLEB604, carrying the pepI gene, was stable, and PepI enzyme was active in LAB6 cells isolated at different stages of the ripening process. However, HPLC analyses indicated that Lb. casei LAB6 could not increase the amount of free proline in ripened cheese. PMID:23851577

Human immunodeficiency virus and hepatitis B virus infection prevention following occupational exposure among staff at a regional referral hospital in Western Kenya

Directory of Open Access Journals (Sweden)

Barbara Kabai Burmen

2018-01-01

Full Text Available Background: Postexposure prophylaxis (PEP with antiretroviral therapy (ART and vaccination against hepatitis B virus (HBV aides in preventing human immunodeficiency virus (HIV infection and HBV, respectively, from accidental or occupational exposure. We assessed compliance to guidelines for HIV and HBV prevention after occupational exposure among hospital staff at a referral Kenyan hospital. Methods: We reviewed PEP registers for hospital staff reporting an occupational injury at a referral hospital in Western Kenya between January 2011 and December 2012. Proportions were used to summarize number of participants receiving the recommended services, Kaplan–Meier curves were used to describe time to ART initiation, and Chi-square statistics was used to describe the association between participant characteristics and PEP completion rates. P < 0.05 was considered statistically significant. Results: Majority of documented hospital staff (n = 52 were health workers (63% and students (27% and had high HIV risk exposures (97%. All had timely PEP initiation with 50% completing PEP. Completion rates did not vary by gender (P = 0.78, exposure type (P = 1.0, or department of exposure (P = 0.75. Retesting for HIV and negativity rates at months 1.5, 3, and 6 were 96%, 25%, and 17% and 100%, 100%, and 100%, respectively. At the time of exposure, 17% (9 of staff were HBV vaccinated and HBV status of sources was unknown; no intervention was provided for HBV prevention. Conclusions: Low rates of completion and follow-up negate intended benefits of PEP. Efforts should be directed to enforce universal precaution practices and completion of PEP. Low rates of HBV testing and vaccination illustrate the need for support for the implementation of HBV prevention guidelines.

Design and mechanism of action of a novel bacteria-selective antimicrobial peptide from the cell-penetrating peptide Pep-1

International Nuclear Information System (INIS)

Zhu, W.L.; Lan Hongliang; Park, Il-Seon; Kim, Jae Il; Jin, H.Z.; Hahm, Kyung-Soo; Shin, S.Y.

2006-01-01

Here, we report the successful design of a novel bacteria-selective antimicrobial peptide, Pep-1-K (KKTWWKTWWTKWSQPKKKRKV). Pep-1-K was designed by replacing Glu-2, Glu-6, and Glu-11 in the cell-penetrating peptide Pep-1 with Lys. Pep-1-K showed strong antibacterial activity against reference strains (MIC = 1-2 μM) of Gram-positive and Gram-negative bacteria as well as against clinical isolates (MIC = 1-8 μM) of methicillin-resistant Staphylococcus aureus and multidrug-resistant Pseudomonas aeruginosa. In contrast, Pep-1-K did not cause hemolysis of human erythrocytes even at 200 μM. These results indicate that Pep-1-K may be a good candidate for antimicrobial drug development, especially as a topical agent against antibiotic-resistant microorganisms. Tryptophan fluorescence studies indicated that the lack of hemolytic activity of Pep-1-K correlated with its weak ability to penetrate zwitterionic phosphatidylcholine/cholesterol (10:1, w/w) vesicles, which mimic eukaryotic membranes. Furthermore, Pep-1-K caused little or no dye leakage from negatively charged phosphatidylethanolamine/phosphatidylglycerol (7:3, w/w) vesicles, which mimic bacterial membranes but had a potent ability to cause depolarization of the cytoplasmic membrane potential of intact S. aureus cells. These results suggested that Pep-1-K kills microorganisms by not the membrane-disrupting mode but the formation of small channels that permit transit of ions or protons but not molecules as large as calcein

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

Science.gov (United States)

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.

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

Science.gov (United States)

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.

Status report of PEP-4

International Nuclear Information System (INIS)

Kamae, Tuneyoshi

1982-01-01

The present status of PEP-4 is reported. The cosmic ray test of a TPC without magnetic field was done in July, 1981, and tracks were observed on the first day of the test. The entire PEP-4 detector was tested with 3.9 kG magnetic field in November, 1981, and various trigger configurations were tested. The TPC performed well during the test, and a preliminary analysis gave an encouraging position resolution which is expected to be improved with the correction for various non-uniformity and by refining the fitting procedure. Furthermore, the detection efficiency of the muon chamber was about 99 %. In November and December, 1981, the cosmic ray test of the hexagonal calorimeter was carried out. The performance was just as expected. Noise did not pose any problem, and the peak of the Fourier coefficient gave a nice overall calibration of the calorimeter. There are some problems to be solved in future. With the TPC, the impurities in the gas, the electronic noise, the hooks and the magnetic coil should be improved. In addition, there are some problems with the inner drift chamber, the hexagonal calorimeter and the relativistic rise measured by the TPC. The very recent results with the first e + e - beam obtained in February, 1982, are briefly reported, although the events have not been fully analyzed. (Ito, K.)

Topology in quantum states. PEPS formalism and beyond

Energy Technology Data Exchange (ETDEWEB)

Aguado, M [Max-Planck-Institut fuer Quantenoptik. Hans-Kopfermann-Str. 1. D-85748 Garching (Germany); Cirac, J I [Max-Planck-Institut fuer Quantenoptik. Hans-Kopfermann-Str. 1. D-85748 Garching (Germany); Vidal, G [School of Physical Sciences. University of Queensland, Brisbane, QLD, 4072 (Australia)

2007-11-15

Topology has been proposed as a tool to protect quantum information encoding and processes. Work concerning the meaning of topology in quantum states as well as its characterisation in the projected entangled pair state (PEPS) formalism and related schemes is reviewed.

Pharmacologic inhibition of lactate production prevents myofibroblast differentiation.

Science.gov (United States)

Kottmann, Robert Matthew; Trawick, Emma; Judge, Jennifer L; Wahl, Lindsay A; Epa, Amali P; Owens, Kristina M; Thatcher, Thomas H; Phipps, Richard P; Sime, Patricia J

2015-12-01

Myofibroblasts are one of the primary cell types responsible for the accumulation of extracellular matrix in fibrosing diseases, and targeting myofibroblast differentiation is an important therapeutic strategy for the treatment of pulmonary fibrosis. Transforming growth factor-β (TGF-β) has been shown to be an important inducer of myofibroblast differentiation. We previously demonstrated that lactate dehydrogenase and its metabolic product lactic acid are important mediators of myofibroblast differentiation, via acid-induced activation of latent TGF-β. Here we explore whether pharmacologic inhibition of LDH activity can prevent TGF-β-induced myofibroblast differentiation. Primary human lung fibroblasts from healthy patients and those with pulmonary fibrosis were treated with TGF-β and or gossypol, an LDH inhibitor. Protein and RNA were analyzed for markers of myofibroblast differentiation and extracellular matrix generation. Gossypol inhibited TGF-β-induced expression of the myofibroblast marker α-smooth muscle actin (α-SMA) in a dose-dependent manner in both healthy and fibrotic human lung fibroblasts. Gossypol also inhibited expression of collagen 1, collagen 3, and fibronectin. Gossypol inhibited LDH activity, the generation of extracellular lactic acid, and the rate of extracellular acidification in a dose-dependent manner. Furthermore, gossypol inhibited TGF-β bioactivity in a dose-dependent manner. Concurrent treatment with an LDH siRNA increased the ability of gossypol to inhibit TGF-β-induced myofibroblast differentiation. Gossypol inhibits TGF-β-induced myofibroblast differentiation through inhibition of LDH, inhibition of extracellular accumulation of lactic acid, and inhibition of TGF-β bioactivity. These data support the hypothesis that pharmacologic inhibition of LDH may play an important role in the treatment of pulmonary fibrosis. Copyright © 2015 the American Physiological Society.

Research advances in the prevention and treatment of pancreatitis after endoscopic retrograde cholangiopancreatography

Directory of Open Access Journals (Sweden)

ZHANG Weifeng

2018-03-01

Full Text Available Endoscopic retrograde cholangiopancreatography (ERCP is an important technique for the diagnosis and treatment of biliary and pancreatic diseases and post-ERCP pancreatitis (PEP is the most common complication of ERCP. Since the birth of ERCP, the prevention and treatment of PEP has become the focus of international research. In recent years, much progress has been made in the aspects of risk factors, pharmacological prevention, and prophylactic stent implantation in the pancreatic duct. Since these research findings are not consistent, further clinical studies are needed to demonstrate such findings.

Detecting β-thalassaemia mutations from a single cell by PEP and RDB

Institute of Scientific and Technical Information of China (English)

YI Ping; LI Li; YAO Hong; ZHOU Yuan-guo; DENG Bing; CHEN Zhu-qin

2006-01-01

Objective:To evaluate the possibility of the technology involving PEP and RDB for detecting β-thalassaemia multipoint mutations from a single cell simultaneously. Methods: A set of allele specific oligonucleotide (ASO) probes used for detecting 8 familiar β-thalassaemia mutations (CD41-42, IVS- Ⅱ -654, CD17, TATA box nt-28, CD71-72, TATA box nt-29, CD26, IVS- Ⅰ -5) were immobilized on a strip of nylon membrane. The genome of a individual cell was amplified by primer extension preamplification (PEP) with the mixture of15-base random oligonucleotides. The aliquots from PEP were used to amplify the objective gene fractions of β-thalassaemia gene by nested or semi-nested PCR. The membrane was hybridized with the final amplified products and then treated with Streptavidin-HRP and color development.Results :Totally 30 lymphocytes were picked up from blood samples of 1 healthy female and 4 patients with known β-thalassaemia mutations respectively. Each single lymphocyte was lysed in the proteinase K buffer. The amplification efficacy was 94.0% and alle drop-out(ADO) rate was 8.0%. Revert dot blot (RDB) was applied to the final amplified products from the 5 participants. The results of diagnosis were the same to the expected, and their genotypes were N/N, CD17 (A→T)/N, IVS- Ⅱ -654(C→T)/CD17(A → T), CD41-42 (-CTTT)/N and TATA box nt-28 (A→G)/N, respectively. Conclusion: The technology involving PEP and RDB could detectmultiple β-thalassaemia mutations from a single cell simultaneously,and the research provides experimental evidences for the feasibility of applying PEP and DNA array technology to screening multiple genetic mutations from a single cell, and will be applied to preimplantation genetic diagnosis and non-invasive prenatal diagnosis for β-thalassaemia.

Review of e+e- physics at PEP - 1982

International Nuclear Information System (INIS)

Hollebeek, R.

1982-10-01

Results obtained at PEP by the MARK II, MAC and DELCO collaborations in the past year are reviewed. They include QED tests, measurements of tau lepton properties, charm and bottom fragmentation functions, scaling violations, energy correlations and the total hadronic cross section

Some schemes for on-line correction of the closed orbit, dispersion and beta functions in PEP

International Nuclear Information System (INIS)

Donald, M.H.R.; Blocker, C.; Chao, A.W.; Hollebeek, R.J.; Lee, M.J.; Linstadt, J.E.; Siegrist, J.L.; Spencer, N.

1981-02-01

PEP has been operated successfully under computer control. It is necessary for colliding beam operation that the errors in closed orbits, dispersion and beta functions be corrected. The schemes in the PEP control program for on-line correction of these errors are described in this paper. The orbit control tasks in the PEP control system perform the functions of data gathering, data presentation (color display, printing), calculation and setting of corrector magnets. The tasks are generally small and modular, taking information from the database, processing it, then returning the results to the database. The PEP operator communicates with the tasks through touch panels monitored by the Director program. The display task, which displays orbit and corrector information on a TV color display, provides the main information required by the operator

Design and performance of PEP dc-power systems

International Nuclear Information System (INIS)

Jackson, T.

1981-03-01

The PEP Magnet Power Supply System represents a significant departure from previous technology with the goal of improved performance at lower cost. In nineteen of the magnet families around the ring, Chopper power supplies are used. The many choppers are powered from two 2 MW dc supplies, and control the average power to the various magnet loads by pulse-width modulation at a 2 kilohertz repetition rate. Each chopper utilizes SCR's for switching, and stores sufficient capacitive energy for turn-off on command. Most of the energy is recirculated, resulting in high-efficiency. The two kilohertz chopping rate allows a one kilohertz unity-gain bandwidth in the current-regulator loop, and this wide bandwidth, coupled with low drift components in the error-detection system, provides a high-performance system. The PEP system has also shown that the chopper system is economical compared to standard multi-pulse controlled-rectifier

SwePep, a database designed for endogenous peptides and mass spectrometry.

Science.gov (United States)

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.

Robust Control of PEP Formation Rate in the Carbon Fixation Pathway of C4 Plants by a Bi-functional Enzyme

Directory of Open Access Journals (Sweden)

Hart Yuval

2011-10-01

Full Text Available Abstract Background C4 plants such as corn and sugarcane assimilate atmospheric CO2 into biomass by means of the C4 carbon fixation pathway. We asked how PEP formation rate, a key step in the carbon fixation pathway, might work at a precise rate, regulated by light, despite fluctuations in substrate and enzyme levels constituting and regulating this process. Results We present a putative mechanism for robustness in C4 carbon fixation, involving a key enzyme in the pathway, pyruvate orthophosphate dikinase (PPDK, which is regulated by a bifunctional enzyme, Regulatory Protein (RP. The robust mechanism is based on avidity of the bifunctional enzyme RP to its multimeric substrate PPDK, and on a product-inhibition feedback loop that couples the system output to the activity of the bifunctional regulator. The model provides an explanation for several unusual biochemical characteristics of the system and predicts that the system's output, phosphoenolpyruvate (PEP formation rate, is insensitive to fluctuations in enzyme levels (PPDK and RP, substrate levels (ATP and pyruvate and the catalytic rate of PPDK, while remaining sensitive to the system's input (light levels. Conclusions The presented PPDK mechanism is a new way to achieve robustness using product inhibition as a feedback loop on a bifunctional regulatory enzyme. This mechanism exhibits robustness to protein and metabolite levels as well as to catalytic rate changes. At the same time, the output of the system remains tuned to input levels.

Vacuum system design for the PEP-II B Factory High-Energy Ring

International Nuclear Information System (INIS)

Perkins, C.; Bostic, D.; Daly, E.

1994-06-01

The design of the vacuum system for the PEP-II B Factory High-Energy Ring is reviewed. The thermal design and vacuum requirements are particularly challenging in PEP-II due to high stored beam currents up to 3.0 amps in 1658 bunches. The vacuum chambers for the HER arcs are fabricated by electron beam welding extruded copper sections up to 6 m long. Design of these chambers and the vacuum PumPing configuration is described with results from vacuum and thermal analyses

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.

Science.gov (United States)

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

Upgrades to PEP-II Tune Measurements

Energy Technology Data Exchange (ETDEWEB)

Fisher, Alan S.

2002-07-30

The tune monitors for the two-ring PEP-II collider convert signals from one set of four BPM-type pickup buttons per ring into horizontal and vertical differences, which are then downconverted from 952 MHz (twice the RF) to baseband. Two-channel 10-MHz FFT spectrum analyzers show spectra in X-window displays in the Control Room, to assist PEP operators. When operating with the original system near the beam-beam limit, collisions broadened and flattened the tune peaks, often bringing them near the noise floor. We recently installed new downconverters that increase the signal-to-noise ratio by about 5 dB. In addition, we went from one to two sets of pickups per ring, near focusing and defocusing quadrupoles, so that signals for both planes originate at locations with large amplitudes. We also have just installed a tune tracker, based on a digital lock-in amplifier (one per tune plane) that is controlled by an EPICS software feedback loop. The tracker monitors the phase of the beam's response to a sinusoidal excitation, and adjusts the drive frequency to track the middle of the 1 go-degree phase transition across the tune resonance. We plan next to test an outer loop controlling the tune quadrupoles based on this tune measurement.

Upgrades to PEP-II Tune Measurements

Energy Technology Data Exchange (ETDEWEB)

Fisher, Alan S.

2002-07-30

The tune monitors for the two-ring PEP-II collider convert signals from one set of four BPM-type pickup buttons per ring into horizontal and vertical differences, which are then downconverted from 952 MHz (twice the RF) to baseband. Two-channel l0-MHz FFT spectrum analyzers show spectra in X-window displays in the Control Room, to assist PEP operators. When operating with the original system near the beam-beam limit, collisions broadened and flattened the tune peaks, often bringing them near the noise floor. We recently installed new downconverters that increase the signal-to-noise ratio by about 5 dB. In addition, we went from one to two sets of pickups per ring, near focusing and defocusing quadrupoles, so that signals for both planes originate at locations with large amplitudes. We also have just installed a tune tracker, based on a digital lock-in amplifier (one per tune plane) that is controlled by an EPICS software feedback loop. The tracker monitors the phase of the beam's response to a sinusoidal excitation, and adjusts the drive frequency to track the middle of the 180-degree phase transition across the tune resonance. We plan next to test an outer loop controlling the tune quadrupoles based on this tune measurement.

Upgrades to PEP-II tune measurements

International Nuclear Information System (INIS)

Fisher, Alan S.; Petree, Mark; Wienands, Uli; Allison, Stephanie; Laznovsky, Michael; Seeman, Michael; Robin, Jolene

2002-01-01

The tune monitors for the two-ring PEP-II collider convert signals from one set of four BPM-type pickup buttons per ring into horizontal and vertical differences, which are then downconverted from 952 MHz (twice the RF) to baseband. Two-channel 10-MHz FFT spectrum analyzers show spectra in X-window displays in the Control Room, to assist PEP operators. When operating with the original system near the beam-beam limit, collisions broadened and flattened the tune peaks, often bringing them near the noise floor. We recently installed new downconverters that increase the signal-to-noise ratio by about 5 dB. In addition, we went from one to two sets of pickups per ring, near focusing and defocusing quadrupoles, so that signals for both planes originate at locations with large amplitudes. We also have just installed a tune tracker, based on a digital lock-in amplifier (one per tune plane) that is controlled by an EPICS software feedback loop. The tracker monitors the phase of the beam's response to a sinusoidal excitation, and adjusts the drive frequency to track the middle of the 180-degree phase transition across the tune resonance. We plan next to test an outer loop controlling the tune quadrupoles based on this tune measurement

Geotechnical investigations of the PEP site

International Nuclear Information System (INIS)

Gould, R.S.

1976-02-01

The purpose of this paper is to summarize the general nature of the geology and rock and soil formations of the PEP site as they relate to the design and construction of the project; to describe site investigation programs and to catalog the geotechnical information presently available about the site. The recently-completed investigation of subterranean conditions around the PEP ring when coupled with previous surveys gives us a good understanding of what to expect with regard to tunneling, undertaking larger underground excavations and constructing research halls are the interaction areas. It bears out the predictions made in Jacobs and Associates' report of 1973; i.e., that the ring housing construction is classified as soft-ground tunneling and that large underground openings, such as region 10 and the injection junction structures, will require great attention to support. A shield or shields will probably be required. On the positive side, the site affords very good conditions for soft-ground tunneling. Water will be a problem in some areas, but not an unsolvable one. The possibility of encountering lethal or explosive gases, almost always the case in tunneling in California's coastal formations, exists but has not been ascertained. Finally, no reasons to change current cost estimates or schedules have merged from the investigation. 13 refs., 1 fig

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

Science.gov (United States)

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.

Use of NSAIDs via the Rectal Route for the Prevention of Pancreatitis after ERCP in All-Risk Patients: An Updated Meta-Analysis

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Lei-Min Yu

2018-01-01

Full Text Available The aim of this study was to assess the efficacy of the rectal administration of nonsteroidal anti-inflammatory drugs (NSAIDs in preventing post-ERCP pancreatitis (PEP. We searched database for randomized controlled trials (RCTs comparing periprocedural rectal administration of NSAIDs with placebo for the prevention of PEP. The rectal administration of NSAIDs significantly decreased the incidence of PEP in the whole patient population (odds ratio (OR: 0.44, 95% confidence interval (CI: 0.30–0.64, P<0.0001, high-risk patients (OR: 0.34, 95% CI: 0.19–0.58, P=0.0001, and all-risk patients (OR: 0.51, 95% CI: 0.31–0.84, P=0.008. The incidence of PEP was reduced by indomethacin (OR: 0.54, 95% CI: 0.36–0.82, P=0.004 and diclofenac (OR: 0.27, 95% CI: 0.15–0.46, P<0.00001. The administration of NSAIDs before (OR: 0.42, 95% CI: 0.25–0.73, P=0.002 or after (OR: 0.39, 95% CI: 0.27–0.56, P<0.00001 ERCP reduced PEP. The NSAIDs were associated with a reduction in mild PEP (OR: 0.55, 95% CI: 0.36–0.83, P=0.004 and moderate-to-severe PEP (OR: 0.47, 95% CI: 0.28–0.79, P=0.004. The rectal administration of NSAIDs reduced the incidence of PEP in high-risk and all-risk patients.

Beam-beam depolarization in SPEAR and PEP

International Nuclear Information System (INIS)

Montague, B.W.

1977-01-01

In this note some approximate estimates are made of depolarization due to beam-beam forces in SPEAR and PEP, using the results of a calculation by Kondratenko. The model assumes head-on collisions between bunches of Gaussian distribution in the transverse directions; the force on the weak-beam particle is taken to be a δ-function at the interaction point. 1 ref

Crystal Ball at PEP

International Nuclear Information System (INIS)

Bartel, W.; Bulos, F.; Luke, D.; Peck, C.; Strauch, K.

1975-01-01

The modifications to the SPEAR version of the Crystal Ball required by the higher energies at PEP are discussed. Since the hadron multiplicity is expected to rise as log s, their average energy must rise. On the other hand, if the hadrons are produced in jets, the low energy part of their spectrum is not heavily depleted. This implies that modifications for high energy particles should not deteriorate low energy performance. An external iron calorimeter for measuring the high energy hadrons, charged and neutral, is considered. To improve the angular resolution on γ's, an active internal converter has been studied, estimates have been made of its expected performance, and difficulties requiring further study have been outlined

τ physics using the TPC/2γ facility at HiLum PEP

International Nuclear Information System (INIS)

Bloom, E.D.

1991-01-01

Plans for a TPC/2γ facility program using HiLum PEP for τ physics are presented. The detector and its performance are described in some detail. The possibilities for a τ physics program with an integrated luminosity of 1 fb -1 are discussed. The physics issues are reviewed, particularly the τ'1-prong' problem, and preliminary results on τ → ν τ K +- X + X - + ≥ 0 Neutrals are shown. The performance of HiLum PEP is also presented, and expectations for the future are discussed. (R.P.) 15 refs., 14 figs., 3 tabs

Enrofloxacin and Probiotic Lactobacilli Influence PepT1 and LEAP-2 mRNA Expression in Poultry

NARCIS (Netherlands)

Pavlova, Ivelina; Milanova, Aneliya; Danova, Svetla; Fink-Gremmels, Johanna

2016-01-01

Expression of peptide transporter 1 (PepT1) and liver-expressed antimicrobial peptide 2 (LEAP-2) in chickens can be influenced by food deprivation, pathological conditions and drug administration. Effect of three putative probiotic Lactobacillus strains and enrofloxacin on the expression of PepT1

PEP activity and expression of photosynthesis genes required for embryo and seed development in Arabidopsis

Directory of Open Access Journals (Sweden)

Dmitry eKremnev

2014-08-01

Full Text Available Chloroplast biogenesis and function is essential for proper plant embryo and seed development but the molecular mechanisms underlying the role of plastids during embryogenesis are poorly understood. Expression of plastid encoded genes is dependent on two different transcription machineries; a plastid-encoded bacterial-type RNA polymerase (PEP and a nuclear-encoded phage-type RNA polymerase (NEP, which recognize distinct types of promoters. However, the division of labor between PEP and NEP during plastid development and in mature chloroplasts is unclear. We show here that PRIN2 and CSP41b, two proteins identified in plastid nucleoid preparations, are essential for proper plant embryo development. Using Co-IP assays and native PAGE we have shown a direct physical interaction between PRIN2 and CSP41b. Moreover, PRIN2 and CSP41b form a distinct protein complex in vitro that binds DNA. The prin2.2 and csp41b-2 single mutants displayed pale phenotypes, abnormal chloroplasts with reduced transcript levels of photosynthesis genes and defects in embryo development. The respective csp41b-2prin2.2 homo/heterozygote double mutants produced abnormal white colored ovules and shrunken seeds. Thus, the csp41b-2prin2.2 double mutant is embryo lethal. In silico analysis of available array data showed that a large number of genes traditionally classified as PEP dependent genes are transcribed during early embryo development from the pre-globular stage to the mature-green-stage. Taken together, our results suggest that PEP activity and consequently the switch from NEP to PEP activity, is essential during embryo development and that the PRIN2-CSP41b DNA binding protein complex possibly is important for full PEP activity during this process.

Biochemical and biological properties of the binding of human fibrinogen to M protein in group A streptococci

International Nuclear Information System (INIS)

Whitnack, E.; Beachey, E.H.

1985-01-01

Fibrinogen is known to bind to group A streptococci and precipitate with extracts containing streptococcal M protein. The authors have previously shown that the binding of fibrinogen to M-positive streptococci prevents opsonization by complement and protects that organism from phagocytosis in nonimmune blood. In the present study, they used 3 H-labeled fibrinogen, a highly purified peptide fragment of type 24 M protein (pep M24), and anti-pep M sera to show that fibrinogen binds to M-positive streptococci with high affinity; occupation of the high-affinity binding sites suffices to protect the organism from phagocytosis; proteolytic treatments that remove M protein from streptococcal cells abolish binding; binding is competitively inhibited by anti-pep M sera; pep M24 precipitates fibrinogen; and binding to type 24 cells is inhibited by pep M24. They conclude that M protein is the cell surface structure principally responsible for binding fibrinogen on the surface of M-positive streptococci and that this binding contributes to the known antiopsonic property of M proteins

Does glyceryl nitrate prevent post-ERCP pancreatitis? A prospective, randomized, double-blind, placebo-controlled multicenter trial

DEFF Research Database (Denmark)

Nøjgaard, Camilla; Hornum, Mads; Elkjaer, Margarita

2009-01-01

OBJECTIVE: Acute pancreatitis is the most dreaded complication of ERCP. Two studies have shown a significant effect of glyceryl nitrate (GN) in preventing post-ERCP pancreatitis (PEP). We wanted to evaluate this promising effect in a larger study with a realistically precalculated incidence of PEP...... (PL) was an identical-looking patch applied before ERCP. A total of 401 patients received GN; 405 received PL. RESULTS: Forty-seven patients had PEP (5.8%), 18 (4.5%) in the GN group and 29 (7.1%) in the PL group. The relative risk reduction of PEP in the GN group of 36% (95% CI, 11%-65%) compared...... (P = .006) were more common in the GN group. Significant variables predictive of PEP were not having biliary stones extracted; hypotension after ERCP; morphine, propofol, glucagon, and general anesthesia during the procedure; or no sufentanil during the procedure. CONCLUSIONS: The trial showed...

Pep1, a secreted effector protein of Ustilago maydis, is required for successful invasion of plant cells.

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Gunther Doehlemann

2009-02-01

Full Text Available The basidiomycete Ustilago maydis causes smut disease in maize. Colonization of the host plant is initiated by direct penetration of cuticle and cell wall of maize epidermis cells. The invading hyphae are surrounded by the plant plasma membrane and proliferate within the plant tissue. We identified a novel secreted protein, termed Pep1, that is essential for penetration. Disruption mutants of pep1 are not affected in saprophytic growth and develop normal infection structures. However, Deltapep1 mutants arrest during penetration of the epidermal cell and elicit a strong plant defense response. Using Affymetrix maize arrays, we identified 116 plant genes which are differentially regulated in Deltapep1 compared to wild type infections. Most of these genes are related to plant defense. By in vivo immunolocalization, live-cell imaging and plasmolysis approaches, we detected Pep1 in the apoplastic space as well as its accumulation at sites of cell-to-cell passages. Site-directed mutagenesis identified two of the four cysteine residues in Pep1 as essential for function, suggesting that the formation of disulfide bridges is crucial for proper protein folding. The barley covered smut fungus Ustilago hordei contains an ortholog of pep1 which is needed for penetration of barley and which is able to complement the U. maydis Deltapep1 mutant. Based on these results, we conclude that Pep1 has a conserved function essential for establishing compatibility that is not restricted to the U. maydis / maize interaction.

Development of a high-power RF cavity for the PEP-II B factory

International Nuclear Information System (INIS)

Rimmer, R.A.; Allen, M.A.; Saba, J.; Schwarz, H.

1995-03-01

The authors describe the development and fabrication of the first high-power RF cavity for PEP-II. Design choices and fabrication technologies for the first cavity and subsequent production cavities are described. Conditioning and high-power testing of the first and subsequent cavities are discussed, as well as integration of the cavity into modular RF systems for both high-energy and low-energy rings. Plans for installation of the cavity raft assemblies in the RF sections of the PEP tunnel are also considered

On setting magnets in the PEP beam-transport line

International Nuclear Information System (INIS)

Peterson, J.M.

1979-01-01

This paper discusses magnets in the PEP beam-transport line. Topics discussed are: conditioning, direction of excitation, rate of excitation; determination of the excitation current for the principal bend magnets; steering mechanisms; bump magnets; and determination of excitation currents of the quadrupole magnets

The Optical Design of the PEP-II Injection Beamlines

CERN Document Server

Fieguth, T

1996-01-01

The optical design of the PEP-II electron and positron Injection Beamlines is described. Use of the existing high power, low emittance beams available from the SLC damping rings require that pulsed extraction of 9.0 GeV electrons and 3.1 GeV positrons for injection into the PEP-II rings occur in the early sectors of the accelerator. More than 5 kilometers of new beam transport lines have been designed and are being constructed to bring these beams to their respective rings. The optical design maximizes the tolerance to errors especially to those contributing to beam size and position jitter. Secondly, the design minimizes costs by utilizing existing components or component designs and minimizing the number required. Here we discuss important attributes including choice of lattice, specification of error tolerances, including errors in construction, alignment, field errors, power supply stability, and orbit correction.

Transverse feedback systems for the PEP-II B-factory

International Nuclear Information System (INIS)

Corlett, J.N.; Barry, W.; Byrd, J.M.; Lambertson, G.; Johnson, J.; Fahmie, M.

1995-10-01

Growth rates of coherent beam oscillations are faster than the natural damping mechanisms for the parameters of the PEP-II B-factory storage rings at nominal currents, even with damping of cavity higher order modes (HOM's). With 165 8 bunches separated by 4.2 ns, and a large current of up to 3A (2.14 A nominal in the low energy ring), many coupled-bunch modes are excited by the resistive wall impedance and cavity higher order mode impedance. Fastest growth times of transverse rigid-bunch modes of approximately 300 ps are expected, two orders of magnitude faster than the radiation damping time. We will provide broadband, bunch-by-bunch feedback to suppress this coherent motion of the beam. Experience gained with a prototype system, installed and successfully operating at the LBNL Advanced Light Source (ALS), has been used extensively in developing the design of the PEP-II systems

The Optical Design of the PEP-II Injection Beamlines

Energy Technology Data Exchange (ETDEWEB)

Fieguth, Ted

2003-05-23

The optical design of the PEP-II electron and positron Injection Beamlines is described. Use of the existing high power, low emittance beams available from the SLC damping rings require that pulsed extraction of 9.0 GeV electrons and 3.1 GeV positrons for injection into the PEP-II rings occur in the early sectors of the accelerator. More than 5 kilometers of new beam transport lines have been designed and are being constructed to bring these beams to their respective rings. The optical design maximizes the tolerance to errors especially to those contributing to beam size and position jitter. Secondly, the design minimizes costs by utilizing existing components or component designs and minimizing the number required. Here we discuss important attributes including choice of lattice, specification of error tolerances, including errors in construction, alignment, field errors, power supply stability, and orbit correction.

Pre-exposure and postexposure prophylaxes and the combination HIV prevention methods (The Combine! Study): protocol for a pragmatic clinical trial at public healthcare clinics in Brazil.

Science.gov (United States)

Grangeiro, Alexandre; Couto, Márcia Thereza; Peres, Maria Fernanda; Luiz, Olinda; Zucchi, Eliana Miura; de Castilho, Euclides Ayres; Estevam, Denize Lotufo; Alencar, Rosa; Wolffenbüttel, Karina; Escuder, Maria Mercedes; Calazans, Gabriela; Ferraz, Dulce; Arruda, Érico; Corrêa, Maria da Gloria; Amaral, Fabiana Rezende; Santos, Juliane Cardoso Villela; Alvarez, Vivian Salles; Kietzmann, Tiago

2015-08-25

Few results from programmes based on combination prevention methods are available. We propose to analyse the degree of protection provided by postexposure prophylaxis (PEP) for consensual sexual activity at healthcare clinics, its compensatory effects on sexual behaviour; and the effectiveness of combination prevention methods and pre-exposure prophylaxis (PrEP), compared with exclusively using traditional methods. A total of 3200 individuals aged 16 years or older presenting for PEP at 5 sexually transmitted disease (STD)/HIV clinics in 3 regions of Brazil will be allocated to one of two groups: the PEP group-individuals who come to the clinic within 72 h after a sexual exposure and start PEP; and the non-PEP group-individuals who come after 72 h but within 30 days of exposure and do not start PEP. Clinical follow-up will be conducted initially for 6 months and comprise educational interventions based on information and counselling for using prevention methods, including PrEP. In the second study phase, individuals who remain HIV negative will be regrouped according to the reported use of prevention methods and observed for 18 months: only traditional methods; combined methods; and PrEP. Effectiveness will be analysed according to the incidence of HIV, syphilis and hepatitis B and C and protected sexual behaviour. A structured questionnaire will be administered to participants at baseline and every 6 months thereafter. Qualitative methods will be employed to provide a comprehensive understanding of PEP-seeking behaviour, preventive choices and exposure to HIV. This study will be conducted in accordance with the resolution of the School of Medicine Research Ethics Commission of Universidade de São Paulo (protocol no. 251/14). The databases will be available for specific studies, after management committee approval. Findings will be presented to researchers, health managers and civil society members by means of newspapers, electronic media and scientific journals

Inhibition of aldose reductase prevents experimental allergic airway inflammation in mice.

Directory of Open Access Journals (Sweden)

Umesh C S Yadav

2009-08-01

Full Text Available The bronchial asthma, a clinical complication of persistent inflammation of the airway and subsequent airway hyper-responsiveness, is a leading cause of morbidity and mortality in critically ill patients. Several studies have shown that oxidative stress plays a key role in initiation as well as amplification of inflammation in airways. However, still there are no good anti-oxidant strategies available for therapeutic intervention in asthma pathogenesis. Most recent studies suggest that polyol pathway enzyme, aldose reductase (AR, contributes to the pathogenesis of oxidative stress-induced inflammation by affecting the NF-kappaB-dependent expression of cytokines and chemokines and therefore inhibitors of AR could be anti-inflammatory. Since inhibitors of AR have already gone through phase-III clinical studies for diabetic complications and found to be safe, our hypothesis is that AR inhibitors could be novel therapeutic drugs for the prevention and treatment of asthma. Hence, we investigated the efficacy of AR inhibition in the prevention of allergic responses to a common natural airborne allergen, ragweed pollen that leads to airway inflammation and hyper-responsiveness in a murine model of asthma.Primary Human Small Airway Epithelial Cells (SAEC were used to investigate the in vitro effects of AR inhibition on ragweed pollen extract (RWE-induced cytotoxic and inflammatory signals. Our results indicate that inhibition of AR prevents RWE -induced apoptotic cell death as measured by annexin-v staining, increase in the activation of NF-kappaB and expression of inflammatory markers such as inducible nitric oxide synthase (iNOS, cycloxygenase (COX-2, Prostaglandin (PG E(2, IL-6 and IL-8. Further, BALB/c mice were sensitized with endotoxin-free RWE in the absence and presence of AR inhibitor and followed by evaluation of perivascular and peribronchial inflammation, mucin production, eosinophils infiltration and airway hyperresponsiveness. Our results

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

Science.gov (United States)

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

The PEP-II Project: Low-Energy Ring Design and Project Status

International Nuclear Information System (INIS)

Zisman, Michael S.

2006-01-01

We describe the present status of the PEP-II project. The project comprises four major systems: Injector, High-Energy Ring (HER), Low-Energy Ring (LER), and Interaction Region (IR). We focus in detail on the design of the LER, as its parameters and requirements are most closely related to those required for the Beijing Tau-Charm Factory rings. The PEP-II LER is a high-current, 3.1-GeV positron ring mounted above the 9-GeV HER. The LER uses a wiggler located in one of its six straight sections to provide emittance control and additional damping. We describe the rather complicated IR, which must transport the LER beam into the plane of the HER, focus it to a common beam size, and separate the beams after the head-on collisions. Both permanent magnet and conventional electromagnets are used in this area. The LER lattice has now adopted a simplified non-interleaved sextupole correction scheme that has reduced the required number of sextupoles substantially. We describe the LER vacuum system, one of the most challenging subsystems in PEP-II. It employs several technologies. In the arcs, aluminum extrusions and titanium sublimation pumps are employed; the straight sections use stainless steel chambers with lumped ion pumps. In the wiggler area, an extended copper photon dump with nonevaporable getter (NEG) pumps is employed to handle the very large synchrotron radiation power. The design of the room-temperature RF system, the bunch-by-bunch longitudinal and transverse feedback systems, and some of the special diagnostics will be described briefly. The PEP-II project remains on schedule to begin commissioning of the HER in April 1997, followed by the LER a year later

Progress on PEP-II magnet power conversion system

International Nuclear Information System (INIS)

Bellomo, P.; Genova, L.; Jackson, T.; Shimer, D.

1996-01-01

The various power systems for supplying the PEP-II DC magnets rely exclusively on switchmode conversion, utilizing a variety of means depending on the requirements. All of the larger power supplies, ranging from 10 to 200 kW, are powered from DC sources utilizing rectified 480 V AC. Choppers can be used for the series connected strings, but for smaller groups and individual magnets, inverters driving high-frequency transformers with rectifiers comprise the best approach. All of the various systems use a ''building block'' approach of multiple standard-size units connected in series or parallel to most cost-effectively deal with a great range of voltage and current requirements. Utilization of existing infrastructure from PEP-I has been a cost-effective determinant. Equipment is being purchased either off-the-shelf, through performance specification, or by hardware purchase based on design-through-prototype. The corrector magnet power system, utilizing inexpensive, off-the-shelf, four-quadrant switching motor-controllers, has already proven very reliable: 120 of the total of 900 units have been running on the injection system for four months with no failures

Progress on PEP-II magnet power conversion system

Energy Technology Data Exchange (ETDEWEB)

Bellomo, P.; Genova, L. [Stanford Linear Accelerator Center, Menlo Park, CA (United States); Jackson, T. [Lawrence Berkeley National Lab., CA (United States); Shimer, D. [Lawrence Livermore National Lab., CA (United States)

1996-06-04

The various power systems for supplying the PEP-II DC magnets rely exclusively on switchmode conversion, utilizing a variety of means depending on the requirements. All of the larger power supplies, ranging from 10 to 200 kW, are powered from DC sources utilizing rectified 480 V AC. Choppers can be used for the series connected strings, but for smaller groups and individual magnets, inverters driving high-frequency transformers with rectifiers comprise the best approach. All of the various systems use a ``building block`` approach of multiple standard-size units connected in series or parallel to most cost-effectively deal with a great range of voltage and current requirements. Utilization of existing infrastructure from PEP-I has been a cost-effective determinant. Equipment is being purchased either off-the-shelf, through performance specification, or by hardware purchase based on design-through-prototype. The corrector magnet power system, utilizing inexpensive, off-the-shelf, four-quadrant switching motor-controllers, has already proven very reliable: 120 of the total of 900 units have been running on the injection system for four months with no failures.

Antioxidant drugs to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis: What does evidence suggest?

Science.gov (United States)

Fuentes-Orozco, Clotilde; Dávalos-Cobián, Carlos; García-Correa, Jesús; Ambriz-González, Gabriela; Macías-Amezcua, Michel Dassaejv; García-Rentería, Jesús; Rendón-Félix, Jorge; Chávez-Tostado, Mariana; Cuesta-Márquez, Lizbeth Araceli; Alvarez-Villaseñor, Andrea Socorro; Cortés-Flores, Ana Olivia; González-Ojeda, Alejandro

2015-06-07

To determine whether or not the use of antioxidant supplementation aids in the prevention of post- endoscopic retrograde cholangiopancreatography pancreatitis. A systematic review of randomized controlled trials (RCTs) was made to evaluate the preventive effect of prophylactic antioxidant supplementation in post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP). The inclusion criteria included: acute post-endoscopic retrograde cholangiopancreatography pancreatitis in adults; randomized clinical trials with the use of any antioxidant as an intervention compared with placebo, to reduce PEP. The outcome measure was the incidence and severity of PEP. Twelve RCTs involving 3110 patients since 1999 were included. The antioxidants used were selenite, β-carotene, and pentoxifylline (each one in one trial), N-acetylcysteine (NAC) in three trials, and allopurinol in six trials. The group of patients treated with NAC received different doses; either oral or intravenous, and allopurinol-treated patients received five different oral doses in two different administration periods. The results are expressed with raw numbers, proportions, as well as mean and standard deviations. The incidence of pancreatitis between groups was analyzed with Pearson's χ(2) test or Fisher's exact test (F). The main outcome is expressed as relative risks and 95%CI. The incidence of pancreatitis in all antioxidant treatment groups was 8.6%, whereas it was 9.7% in the control group. The antioxidants used were selenite, β-carotene, and pentoxifylline (each one in one trial), NAC in three trials, and allopurinol in six trials. In allopurinol trials, three different dosifications were used; two trials reported a low dosage (of less than 400 mg), two trials reported a moderate dose (600 mg) and the remaining two employed higher doses (more than 900 mg). Supplementation was not associated with a significant reduction in the incidence of PEP [relative risk (RR) = 0.93; 95%CI: 0.82-1.06; P

The HtrA-like serine protease PepD interacts with and modulates the Mycobacterium tuberculosis 35-kDa antigen outer envelope protein.

Directory of Open Access Journals (Sweden)

Mark J White

2011-03-01

Full Text Available Mycobacterium tuberculosis remains a significant global health concern largely due to its ability to persist for extended periods within the granuloma of the host. While residing within the granuloma, the tubercle bacilli are likely to be exposed to stress that can result in formation of aberrant proteins with altered structures. Bacteria encode stress responsive determinants such as proteases and chaperones to deal with misfolded or unfolded proteins. pepD encodes an HtrA-like serine protease and is thought to process proteins altered following exposure of M. tuberculosis to extra-cytoplasmic stress. PepD functions both as a protease and chaperone in vitro, and is required for aspects of M. tuberculosis virulence in vivo. pepD is directly regulated by the stress-responsive two-component signal transduction system MprAB and indirectly by extracytoplasmic function (ECF sigma factor SigE. Loss of PepD also impacts expression of other stress-responsive determinants in M. tuberculosis. To further understand the role of PepD in stress adaptation by M. tuberculosis, a proteomics approach was taken to identify binding proteins and possible substrates of this protein. Using subcellular fractionation, the cellular localization of wild-type and PepD variants was determined. Purified fractions as well as whole cell lysates from Mycobacterium smegmatis or M. tuberculosis strains expressing a catalytically compromised PepD variant were immunoprecipitated for PepD and subjected to LC-MS/MS analyses. Using this strategy, the 35-kDa antigen encoding a homolog of the PspA phage shock protein was identified as a predominant binding partner and substrate of PepD. We postulate that proteolytic cleavage of the 35-kDa antigen by PepD helps maintain cell wall homeostasis in Mycobacterium and regulates specific stress response pathways during periods of extracytoplasmic stress.

Recent high precision surveys at PEP

International Nuclear Information System (INIS)

Sah, R.C.

1980-12-01

The task of surveying and aligning the components of PEP has provided an opportunity to develop new instruments and techniques for the purpose of high precision surveys. The new instruments are quick and easy to use, and they automatically encode survey data and read them into the memory of an on-line computer. When measurements of several beam elements have been taken, the on-line computer analyzes the measured data, compares them with desired parameters, and calculates the required adjustments to beam element support stands

Structure of PEP-PEO block copolymer micelles: Exploiting the complementarity of small-angle X-ray scattering and static light scattering

DEFF Research Database (Denmark)

Jensen, Grethe Vestergaard; Shi, Qing; Hernansanz, María J.

2011-01-01

)-b-poly(ethylene oxide) (PEP-PEO) in a 70% ethanol solution are investigated. The polymers have identical PEP blocks of 5.0 kDa and varying PEO blocks of 2.8-49 kDa. The SLS contrasts of PEP and PEO are similar, providing a homogeneous contrast, making SLS ideal for determining the overall micelle morphology. The SAXS...... contrasts of the two components are very different, allowing for resolution of the internal micelle structure. A core-shell model with a PEP core and PEO corona is fitted simultaneously to the SAXS and SLS data using the different contrasts of the two blocks for each technique. With increasing PEO molecular...

Locality at the boundary implies gap in the bulk for 2D PEPS

DEFF Research Database (Denmark)

Kastoryano, Michael J.; Lucia, Angelo; Perez-Garcia, David

2018-01-01

Proving that the parent Hamiltonian of a Projected Entangled Pair State (PEPS) is gapped remains an important open problem. We take a step forward in solving this problem by showing that if the boundary state of any rectangular subregion is a quasi-local Gibbs state of the virtual indices, then t...... boundary theories and dynamical properties in an interacting many body system. We show that the proof can be extended to MPO-injective PEPS, and speculate that the assumption on the locality of the boundary Hamiltonian follows from exponential decay of correlations in the bulk....

Design features and operational characteristics of the PEP beam-transport and injection system

International Nuclear Information System (INIS)

Peterson, J.M.; Brown, K.L.; Truher, J.B.

1981-03-01

The PEP beam-transport system was designed to transmit 4-to-15 GeV electron and positron beams from the SLAC linac within a +- 0.8% momentum band, to have flexible tuning of the betatron and off-momentum functions for matching into the PEP storage ring, and to have convenient operating characteristics. The transport lines were brought into operation quickly and have operated well. Electron injection has been consistent and efficient and relatively easy to accomplish. Positron injection also has been satisfactory but is variable and more sensitive to ring conditions

PEP-II IR-2 Alignment

International Nuclear Information System (INIS)

Seryi, A

2004-01-01

This paper describes the first results and preliminary analysis obtained with several alignment monitoring systems recently installed in the PEP-II interaction region. The hydrostatic level system, stretched wire system, and laser tracker have been installed in addition to the existing tiltmeters and LVDT sensors. These systems detected motion of the left raft, which correlated primarily with the low energy ring (LER) current. The motion is of the order of 120 micrometers. The cause was identified as synchrotron radiation heating the beampipe, causing its expansion which then results in its deformation and offset of the IR quadrupoles. We also discuss further plans on measurements, analysis and means to counteract this motion

rf reference line for PEP

International Nuclear Information System (INIS)

Schwarz, H.D.; Weaver, J.N.

1979-03-01

A rf phase reference line in 6 segments around the 2200 meter circumference PEP storage ring is described. Each segment of the reference line is phase stabilized by its own independent feedback system, which uses an amplitude modulated reflection from the end of each line. The modulation is kept small and decoupled from the next segment to avoid crosstalk and significant modulation of the rf drive signal. An error evaluation of the system is made. The technical implementation and prototype performance are described. Prototype tests indicate that the phase error around the ring can be held below 1 degree with this relatively simple system

rf reference line for PEP

Energy Technology Data Exchange (ETDEWEB)

Schwarz, H.D.; Weaver, J.N.

1979-03-01

A rf phase reference line in 6 segments around the 2200 meter circumference PEP storage ring is described. Each segment of the reference line is phase stabilized by its own independent feedback system, which uses an amplitude modulated reflection from the end of each line. The modulation is kept small and decoupled from the next segment to avoid crosstalk and significant modulation of the rf drive signal. An error evaluation of the system is made. The technical implementation and prototype performance are described. Prototype tests indicate that the phase error around the ring can be held below 1 degree with this relatively simple system.

An asymmetric B-meson factory at PEP

International Nuclear Information System (INIS)

Garren, A.; Chattopadhyay, S.; Chin, Y.; Oddone, P.; Zisman, M.S.; Donald, M.; Feldman, G.; Paterson, J.M.; Rees, J.

1989-03-01

A preliminary design for a B-factory has been made using asymmetric collisions between positrons in the PEP storage ring and electrons in a new, log-energy ring. The design utilizes small-aperture, permanent-magnet quadrupoles close to the interaction point (IP). Optimization of optical and beam parameters at the IP will be discussed, as well as the lattice design of the interaction region and of the rings. 7 refs., 3 figs., 2 tabs

RF feedback simulation results for PEP-II

International Nuclear Information System (INIS)

Tighe, R.; Corredoura, P.

1995-06-01

A model of the RF feedback system for PEP-II has been developed to provide time-domain simulation and frequency-domain analysis of the complete system. The model includes the longitudinal beam dynamics, cavity fundamental resonance, feedback loops, and the nonlinear klystron operating near saturation. Transients from an ion clearing gap and a reference phase modulation from the longitudinal feedback system are also studied. Growth rates are predicted and overall system stability examined

APS [Advanced Photon Source] interests in PEP

International Nuclear Information System (INIS)

Moncton, D.E.; Shenoy, G.K.; Mills, D.M.

1987-11-01

As one of the very few high-energy electron storage rings in the world, potentially available for synchrotron radiation studies, PEP represents an opportunity to accomplish certain preconstruction R and D tasks relevant to the successful construction and operation of dedicated user facilities such as the Advanced Photon Source (APS) at Argonne. Three topical areas are discussed: Accelerator R and D, Insertion Devices (ID) R and D, and Beam Line Instrumentation R and D

Bunch-by-bunch feedback for PEP II

International Nuclear Information System (INIS)

Oxoby, G.; Claus, R.; Eisen, N.; Fox, J.; Hindi, H.; Hoeflich, J.; Olsen, J.; Sapozhnikov, L.; Linscott, I.

1993-01-01

The proposed PEP II B factory at SLAC requires a feedback to damp out longitudinal synchrotron oscillations. A time domain, downsampled, bunch-by-bunch feedback system in which each bunch is treated as an oscillator being driven by disturbances from other bunches is presented as we review the evolution of the system design. Results from a synchrotron oscillation damping experiment conducted at the SLAC/SSRL/SPEAR ring are also presented in this paper

e sup + e sup - Factories: PEP-II, KEKB, DAPHINE

CERN Document Server

Guiducci, S

2001-01-01

In 1999 two B-factories, PEP-II and KEK, and a PHI-factory, DAPHINE, started their physics experiments. A status report of the three factories is presented. A description of the interaction regions, strongly influenced by the detector requirements, and of the machine background in the detectors is presented.

Swamp plots for dynamic aperture studies of PEP-II lattices

International Nuclear Information System (INIS)

Yan, Y.T.; Irwin, J.; Cai, Y.; Chen, T.; Ritson, D.

1995-01-01

With a newly developed algorithm using resonance basis Lie generators and their evaluation with action-angle Poisson bracket maps (nPB tracking) the authors have been able to perform fast tracking for dynamic aperture studies of PEP-II lattices as well as incorporate lattice nonlinearities in beam-beam studies. They have been able to better understand the relationship between dynamic apertures and the tune shift and resonance coefficients in the generators of the one-turn maps. To obtain swamp plots (dynamic aperture vs. working point) of the PEP-II lattices, they first compute a one-turn resonance basis map for a nominal working point and then perform nPB tracking by switching the working point while holding fixed all other terms in the map. Results have been spot-checked by comparing with element-by-element tracking

Micellization of symmetric PEP-PEO block copolymers in water molecular weight dependence

CERN Document Server

Kaya, H; Allgaier, J; Stellbrink, J; Richter, D

2002-01-01

The micellar behaviour of the amphiphilic block copolymer poly-(ethylene-propylene)-poly-(ethylene oxide) (PEP-PEO) in aqueous solution has been studied with small-angle neutron scattering. The polymer was studied over a wide range of molecular weights, always keeping the volume of the blocks equal. The scattering behaviour of the solutions showed that a morphological transition takes place upon lowering the molecular weight. The high molecular weight block copolymers all build spherical, monodisperse micelles with large aggregation numbers. At low molecular weights, however, cylindrical micelles are formed. An interesting intermediate case is represented by the PEP2-PEO2 system, in which a morphological transition occurs upon dilution. (orig.)

Radiosynthesis of a new PSMA targeting ligand ([18F]FPy-DUPA-Pep)

International Nuclear Information System (INIS)

Malik, Noeen; Machulla, Hans-Juergen; Solbach, Christoph; Winter, Gordon; Reske, Sven N.; Zlatopolskiy, Boris

2011-01-01

Due to the specificity of expression of PSMA (prostate specific membrane antigen) particularly in prostate cancer cells (e.g. LNCaP), numerous PSMA ligands have been synthesized until now. In the current study, we synthesized DUPA-Pep having 2-[3-(1,3-dicarboxypropyl)ureido]pentanedioic acid (DUPA) linked via 8-aminooctanoic acid to two phenylalanine residues and chose 6-[ 18 F]fluoronicotinic acid 2,3,5,6-tetrafluorophenyl ester [ 18 F]FPy-TFP as a prosthetic group for coupling. [ 18 F]FPy-DUPA-Pep was obtained in a radiochemical yield of 48±0.9% (decay uncorrected) within 50 min with a chemical purity of >98%.

Vesicles mimicking normal and cancer cell membranes exhibit differential responses to the cell-penetrating peptide Pep-1.

Science.gov (United States)

Almarwani, Bashiyar; Phambu, Esther Nzuzi; Alexander, Christopher; Nguyen, Ha Aimee T; Phambu, Nsoki; Sunda-Meya, Anderson

2018-06-01

The cell-penetrating peptide (CPP) Pep-1 presents a great potential in drug delivery due to its intrinsic property to cross plasma membrane. However, its mechanism of entry into the cell remains unresolved. In this study, we compare the selectivity of Pep-1 towards vesicles mimicking normal and cancer cell membranes. The interaction was performed in a wide range of peptide-to-lipid molar ratios using infrared (IR), fluorescence, scanning electron microscopy (SEM), thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) techniques. At low peptide concentration, fluorescence experiments show that lipid-phosphatidylserine (PS) seems to enable Pep-1 translocation into cancer cell membrane as evidenced by the blue shift of its maximal emission wavelength. DSC data show that Pep-1 induces segregation of lipids. At high peptide concentration, IR data indicate that the interaction of Pep-1 is relatively stronger with normal cell membrane than with cancer cell membrane through the phosphate groups, while the interaction is weaker with normal cell membrane than with cancer cell membrane through the carbonyl groups. TGA and DSC data reveal that vesicles of normal cell membrane are thermally more stable than vesicles of cancer cell membrane. This suggests that the additional lipid PS included in cancer cell membrane has a destabilizing effect on the membrane structure. SEM images reveal that Pep-1 form superstructures including spherical particles and fibrils in the presence of both model membranes. PS seems to enhance peptide transport across cellular membranes. The biophysical techniques in this study provide valuable insights into the properties of CPPs in drug delivery systems. Copyright © 2018 Elsevier B.V. All rights reserved.

Searches for new particles at PEP

International Nuclear Information System (INIS)

Jonker, M.J.

1986-05-01

The status of searches for new particles at the PEP storage ring is reviewed. The result of the excited electron search by MARKII is presented and a limit on the coupling strength of the e*eγ vertex is given. The search for single photons in the ASP and MAC detectors is reported and the results are used to set limits on the number of light neutrino species and, in the context of supersymmetry (SUSY) theories, are interpreted as setting simultaneous limits on the masses of the selectron and photino

Operator interface for the PEP-II low level RF control system

International Nuclear Information System (INIS)

Allison, S.; Claus, R.

1997-05-01

This paper focuses on the operational aspects of the low level RF control system being built for the PEP-II storage rings at SLAC. Subsystems requiring major operational considerations include displays for monitor and control from UNIX workstations, slow feedback loops and control sequences residing on microprocessors, and various client applications in the existing SLAC Linear Collider (SLC) control system. Since commissioning of PEP-II RF is currently in-progress, only those parts of the control system used during this phase are discussed in detail. Based on past experience with the SLC control system, it is expected that effort expended during commissioning on a solid user interface will result in smoother transition to full reliable 24-hour-a-day operation

Inhibition of Chondrocyte Hypertrophy of Osteoarthritis by Disruptor Peptide

Science.gov (United States)

2017-07-01

with PTHR and inhibits the pathogenic beta-catenin- mediated PTHR signaling switch. In Aim 2, we will define the role of disruptor peptide in...confirmed that disruptor peptide conjugated to penetratin can enter cells. Importantly, disruptor peptide can reverse the beta-catenin- mediated PTH... mediated PTHR signaling switch in chondrocytes. Mouse primary chondrocytes express both β-catenin and PTHR. Our data showed that Pen-dis- pep

What is the benefit of the biomedical and behavioral interventions in preventing HIV transmission?

Directory of Open Access Journals (Sweden)

Ricardo Kuchenbecker

2015-09-01

Full Text Available ABSTRACTIntroduction:Scientific evidence supports the sinergy between biomedical and behavioral interventions aimed at preventing the transmission of HIV as a strategy to eradicate AIDS.Objective:To characterize comparatively the benefits from biomedical and behavioral interventions to prevent HIV transmission.Methods:Narrative review. We performed a comparative analysis of the benefits of studied interventions by means of estimating the number needed to treat (NNT. Evaluated interventions: counseling activities for behavior change to prevent exposure to HIV; antiretroviral pre-exposure prophylaxis (PrEP and antiretroviral post-exposure prophylasis (PEP for HIV and treatment of serodiscordant couples as a strategy for prevention of HIV transmission (TasP.Results:counseling interventions and TasP have smaller NNTs, equal to, respectively, 11 (95%CI 9 - 18 at 12 months and 34 (95%CI 23 - 54 in 42 months comparatively to PrEP interventions, that resulted in 41 (95%CI 28 - 67 individuals receiving antiretrovirals in order to prevent one case of HIV infection at 36 months for men and serodiscordant couples. PEP interventions are associated with protective effects estimated at 81%. Lack of trials evaluating PEP prevents estimate of NNT.Conclusion:The estimate of the NNT can be a helpful parameter in the comparison between the effectiveness of different behavioral and biomedical HIV prevention strategies. Studies evaluating the benefit and safety of combined behavioral and biomedical interventions are needed, especially considering the attributable fraction of each component. Integration of behavioral and biomedical interventions is required to achieve complete suppression of the virus, and thus reducing viral replication, infectivity and the number of cases.

PepArML: A Meta-Search Peptide Identification Platform for Tandem Mass Spectra.

Science.gov (United States)

Edwards, Nathan J

2013-12-01

The PepArML meta-search peptide identification platform for tandem mass spectra provides a unified search interface to seven search engines; a robust cluster, grid, and cloud computing scheduler for large-scale searches; and an unsupervised, model-free, machine-learning-based result combiner, which selects the best peptide identification for each spectrum, estimates false-discovery rates, and outputs pepXML format identifications. The meta-search platform supports Mascot; Tandem with native, k-score and s-score scoring; OMSSA; MyriMatch; and InsPecT with MS-GF spectral probability scores—reformatting spectral data and constructing search configurations for each search engine on the fly. The combiner selects the best peptide identification for each spectrum based on search engine results and features that model enzymatic digestion, retention time, precursor isotope clusters, mass accuracy, and proteotypic peptide properties, requiring no prior knowledge of feature utility or weighting. The PepArML meta-search peptide identification platform often identifies two to three times more spectra than individual search engines at 10% FDR.

Pretreatment Engineering Platform (PEP) Integrated Test B Run Report--Caustic and Oxidative Leaching in UFP-VSL-T02A

Energy Technology Data Exchange (ETDEWEB)

Geeting, John GH; Bredt, Ofelia P.; Burns, Carolyn A.; Golovich, Elizabeth C.; Guzman-Leong, Consuelo E.; Josephson, Gary B.; Kurath, Dean E.; Sevigny, Gary J.; Aaberg, Rosanne L.

2009-12-10

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. 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.

EFRT M-12 Issue Resolution: Comparison of Filter Performance at PEP and CUF Scale

Energy Technology Data Exchange (ETDEWEB)

Daniel, Richard C.; Billing, Justin M.; Bontha, Jagannadha R.; Brown, Christopher F.; Eslinger, Paul W.; Hanson, Brady D.; Huckaby, James L.; Karri, Naveen K.; Kimura, Marcia L.; Kurath, Dean E.; Minette, Michael J.

2009-08-13

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 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 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 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

EFRT M-12 Issue Resolution: Comparison of Filter Performance at PEP and CUF Scale

International Nuclear Information System (INIS)

Daniel, Richard C.; Billing, Justin M.; Bontha, Jagannadha R.; Brown, Christopher F.; Eslinger, Paul W.; Hanson, Brady D.; Huckaby, James L.; Karri, Naveen K.; Kimura, Marcia L.; Kurath, Dean E.; Minette, Michael J.

2009-01-01

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 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 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 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

PepJ is a new extracellular proteinase of Aspergillus nidulans.

Science.gov (United States)

Emri, T; Szilágyi, M; László, K; M-Hamvas, M; Pócsi, I

2009-01-01

Under carbon starvation, Aspergillus nidulans released a metallo-proteinase with activities comparable to those of PrtA, the major extracellular serine proteinase of the fungus. The relative molar mass of the enzyme was 19 kDa as determined with both denaturing and renaturing SDS PAGE, while its isoelectric point and pH and temperature optima were 8.6, 5.5 and 65 degrees C, respectively. The enzyme was stable at pH 3.5-10.5 and was still active at 95 degrees C in the presence of azocasein substrate. MALDI-TOF MS analysis demonstrated that the proteinase was encoded by the pepJ gene (locus ID AN7962.3), and showed high similarity to deuterolysin from Aspergillus oryzae. The size of the mature enzyme, its EDTA sensitivity and heat stability also supported the view that A. nidulans PepJ is a deuterolysin-type metallo-proteinase.

Radiosynthesis of a new PSMA targeting ligand ([18F]FPy-DUPA-Pep).

Science.gov (United States)

Malik, Noeen; Machulla, Hans-Jürgen; Solbach, Christoph; Winter, Gordon; Reske, Sven N; Zlatopolskiy, Boris

2011-07-01

Due to the specificity of expression of PSMA (prostate specific membrane antigen) particularly in prostate cancer cells (e.g. LNCaP), numerous PSMA ligands have been synthesized until now. In the current study, we synthesized DUPA-Pep having 2-[3-(1,3-dicarboxypropyl)ureido]pentanedioic acid (DUPA) linked via 8-aminooctanoic acid to two phenylalanine residues and chose 6-[(18)F]fluoronicotinic acid 2,3,5,6-tetrafluorophenyl ester [(18)F]FPy-TFP as a prosthetic group for coupling. [(18)F]FPy-DUPA-Pep was obtained in a radiochemical yield of 48±0.9% (decay uncorrected) within 50 min with a chemical purity of >98%. Copyright © 2011 Elsevier Ltd. All rights reserved.

Letter of intent for the study of CP violation and heavy flavor physics at PEP-II

Energy Technology Data Exchange (ETDEWEB)

BaBar Collaboration

1994-06-18

This report discusses the following topics on CP violation and heavy flavor physics experiments: Physics at PEP-II; detector overview; PEP-II and the interaction region; vertex detector; main tracking chamber; particle identification; electromagnetic calorimeter; muon and neutral hadron detector; magnet coil and flux return; electronics, trigger, and data acquisition; computing; CP asymmetry simulations; collaboration issues; project organization and management; and budget and schedule.

Letter of intent for the study of CP violation and heavy flavor physics at PEP-II

International Nuclear Information System (INIS)

1994-01-01

This report discusses the following topics on CP violation and heavy flavor physics experiments: Physics at PEP-II; detector overview; PEP-II and the interaction region; vertex detector; main tracking chamber; particle identification; electromagnetic calorimeter; muon and neutral hadron detector; magnet coil and flux return; electronics, trigger, and data acquisition; computing; CP asymmetry simulations; collaboration issues; project organization and management; and budget and schedule

PEP-II Beta Beat Fixes with MIA

International Nuclear Information System (INIS)

Yan, Y

2004-01-01

We first find a virtual accelerator for the HER or the LER through determination of all quadrupole strengths and sextupole feed-downs as well as all BPM gains and BPM cross-plane couplings by an SVD-enhanced Least-squares fitting of the quantities derivable from a complete set of orbits. These quantities are the phase advances, the Green's functions, and the tilt angles and axis ratios of the coupling eigen ellipses. They are obtained by analyzing turn-by-turn Beam Position Monitor (BPM) data with a high-resolution model-independent analysis (MIA). Once the virtual accelerator is found, we select a limited number of key quadrupoles, for example, the linear trombone quadrupoles and the global skews, for Least-square fitting of their strengths to minimize the beta beat while keeping other optics characters unchanged if not improved. We then dial in these limited number of quadrupole strength changes to the real accelerator (HER or LER) to achieve a better-performance PEP-II. Noticeable achievement by this MIA technique has been that MIA has helped PEP-II achieve its breaking record peak luminosity of 6.5 x 10 33 cm -2 s -1 in 2003 by bringing the LER working tune to near half integer and simultaneously fixing the beta beat, which would, otherwise, be difficult without MIA because of the strong LER coupling effect

PEP Laser Surveying System

International Nuclear Information System (INIS)

Lauritzen, T.; Sah, R.C.

1979-03-01

A Laser Surveying System has been developed to survey the beam elements of the PEP storage ring. This system provides automatic data acquisition and analysis in order to increase survey speed and to minimize operator error. Two special instruments, the Automatic Readout Micrometer and the Small Automatic Micrometer, have been built for measuring the locations of fiducial points on beam elements with respect to the light beam from a laser. These instruments automatically encode offset distances and read them into the memory of an on-line computer. Distances along the beam line are automatically encoded with a third instrument, the Automatic Readout Tape Unit. When measurements of several beam elements have been taken, the on-line computer analyzes the measured data, compared them with desired parameters, and calculates the required adjustments to beam element support stands

Terapêutica da sarcoidose: importância da avaliação da PEP

Directory of Open Access Journals (Sweden)

Ema Sacadura Leite

1998-01-01

Full Text Available RESUMO: A clearance do DTPA marcado com 99mTc pode ser um método não invasivo para determinar a Permeabilidade Epitelial Pulmonar (PEP. Os objectivos do nosso estudo consistiram em avaliar a PEP de doentes com sarcoidose por aquele método e: 1 Correlacionar o seu valor com os testes funcionais respiratórios – capacidade vital (CV, volume expiratório máximo no primeiro segundo (VEMS, compliance pulmonar estática (St Cpl, difusão de monóxido de carbono (DLCO e pressão arterial de oxigénio (PaO2 com a TAC, com a fixação pulmonar de Gallium 67 e com o valor de enzima conversora de angiotensina (ECA; 2 Avaliar sea PEP poderá preverá evolução da doença pulmonar, podendo ser, nessa perspectiva, um indicador útil a ter em conta na decisão de tratar a sarcoidose pulmonar.Estudámos 34 doentes com sarcoidose confirmada por biópsia (idade média 43.3±10.9, 27/34 do sexo feminino, 20% estadio 0, 23% estadio 1, 26% estadio n e 31% estadio III ou IV, tempo de evolução da doença 3. 7±5.4 anos. Os doentes foram divididos em dois grupos: a com PEP normal – grupo 0 (n=14, b com PEP aumentada – grupo 1 (n=20. O teste Anova e o teste de Fisher foram utilizados para testar 1. A analise da covariância e teste de Mc Nemar foram utilizados para testar 2.Encontrámos uma correlação estatisticamente significativa entre os valores da PEP e a CV (G0=102.6±18.3vsG1=86.4±19.7, p=0.01, FEV1, (G0=105.4±20.5 vs G1=85.8±21.5, p=0.0 19, DLCO (G0=100.4 19.4 vs G1=83.2±22.2, p=0.02 e cintigrafia pulmonar com Gallium 67 positiva (p=0.05. Os nossos resultados sugeriram ainda que a PEP poderá prever a evolução da compliance pulmonar estática (p=0.069.Parece assim que a determinação da PEP através da clearance de99mTc – DTPA possivelmente será útil na decisão clínica de iniciar (ou reiniciar tratamento, em doentes com

Development and characterization of an exposure platform suitable for physico-chemical, morphological and toxicological characterization of printer-emitted particles (PEPs).

Science.gov (United States)

Pirela, Sandra V; Pyrgiotakis, Georgios; Bello, Dhimiter; Thomas, Treye; Castranova, Vincent; Demokritou, Philip

2014-06-01

An association between laser printer use and emissions of particulate matter (PM), ozone and volatile organic compounds has been reported in recent studies. However, the detailed physico-chemical, morphological and toxicological characterization of these printer-emitted particles (PEPs) and possible incorporation of engineered nanomaterials into toner formulations remain largely unknown. In this study, a printer exposure generation system suitable for the physico-chemical, morphological, and toxicological characterization of PEPs was developed and used to assess the properties of PEPs from the use of commercially available laser printers. The system consists of a glovebox type environmental chamber for uninterrupted printer operation, real-time and time-integrated particle sampling instrumentation for the size fractionation and sampling of PEPs and an exposure chamber for inhalation toxicological studies. Eleven commonly used laser printers were evaluated and ranked based on their PM emission profiles. Results show PM peak emissions are brand independent and varied between 3000 to 1 300 000 particles/cm³, with modal diameters ranging from 49 to 208 nm, with the majority of PEPs in the nanoscale (printer toner) raises questions about health implications to users. The presented PEGS platform will help in assessing the toxicological profile of PEPs and the link to the physico-chemical and morphological properties of emitted PM and toner formulations.

PEP-II RF feedback system simulation

Energy Technology Data Exchange (ETDEWEB)

Tighe, R [Stanford Linear Accelerator Center, Menlo Park, CA (United States)

1996-08-01

A model containing the fundamental impedance of the PEP-II cavity along with the longitudinal beam dynamics and RF feedback system components is in use. It is prepared in a format allowing time-domain as well as frequency-domain analysis and full graphics capability. Matlab and Simulink are control system design and analysis programs (widely available) with many built-in tools. The model allows the use of compiled C-code modules for compute intensive portions. We desire to represent as nearly as possible the components of the feedback system including all delays, sample rates and applicable nonlinearities. (author)

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

Energy Technology Data Exchange (ETDEWEB)

Rapko, Brian M.; Brown, Christopher F.; Eslinger, Paul W.; Fountain, Matthew S.; Hausmann, Tom S.; Huckaby, James L.; Hanson, Brady D.; Kurath, Dean E.; Minette, Michael J.

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 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 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

Evolutionary divergence of the plant elicitor peptides (Peps) and their receptors: interfamily incompatibility of perception but compatibility of downstream signalling

KAUST Repository

Lori, M.; van Verk, M. C.; Hander, T.; Schatowitz, H.; Klauser, D.; Flury, P.; Gehring, Christoph A; Boller, T.; Bartels, S.

2015-01-01

Plant elicitor peptides (Peps) are potent inducers of pattern-triggered immunity and amplify the immune response against diverse pathogens. Peps have been discovered and studied extensively in Arabidopsis and only recently orthologs in maize were

Radiosynthesis of a new PSMA targeting ligand ([{sup 18}F]FPy-DUPA-Pep)

Energy Technology Data Exchange (ETDEWEB)

Malik, Noeen, E-mail: noeen.malik@uniklinik-ulm.d [Clinic for Nuclear Medicine, University Hospital, Ulm (Germany); Machulla, Hans-Juergen; Solbach, Christoph; Winter, Gordon; Reske, Sven N.; Zlatopolskiy, Boris [Clinic for Nuclear Medicine, University Hospital, Ulm (Germany)

2011-07-15

Due to the specificity of expression of PSMA (prostate specific membrane antigen) particularly in prostate cancer cells (e.g. LNCaP), numerous PSMA ligands have been synthesized until now. In the current study, we synthesized DUPA-Pep having 2-[3-(1,3-dicarboxypropyl)ureido]pentanedioic acid (DUPA) linked via 8-aminooctanoic acid to two phenylalanine residues and chose 6-[{sup 18}F]fluoronicotinic acid 2,3,5,6-tetrafluorophenyl ester [{sup 18}F]FPy-TFP as a prosthetic group for coupling. [{sup 18}F]FPy-DUPA-Pep was obtained in a radiochemical yield of 48{+-}0.9% (decay uncorrected) within 50 min with a chemical purity of >98%.

Transduced PEP-1-PON1 proteins regulate microglial activation and dopaminergic neuronal death in a Parkinson's disease model.

Science.gov (United States)

Kim, Mi Jin; Park, Meeyoung; Kim, Dae Won; Shin, Min Jea; Son, Ora; Jo, Hyo Sang; Yeo, Hyeon Ji; Cho, Su Bin; Park, Jung Hwan; Lee, Chi Hern; Kim, Duk-Soo; Kwon, Oh-Shin; Kim, Joon; Han, Kyu Hyung; Park, Jinseu; Eum, Won Sik; Choi, Soo Young

2015-09-01

Parkinson's disease (PD) is an oxidative stress-mediated neurodegenerative disorder caused by selective dopaminergic neuronal death in the midbrain substantia nigra. Paraoxonase 1 (PON1) is a potent inhibitor of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) against oxidation by destroying biologically active phospholipids with potential protective effects against oxidative stress-induced inflammatory disorders. In a previous study, we constructed protein transduction domain (PTD) fusion PEP-1-PON1 protein to transduce PON1 into cells and tissue. In this study, we examined the role of transduced PEP-1-PON1 protein in repressing oxidative stress-mediated inflammatory response in microglial BV2 cells after exposure to lipopolysaccharide (LPS). Moreover, we identified the functions of transduced PEP-1-PON1 proteins which include, mitigating mitochondrial damage, decreasing reactive oxidative species (ROS) production, matrix metalloproteinase-9 (MMP-9) expression and protecting against 1-methyl-4-phenylpyridinium (MPP(+))-induced neurotoxicity in SH-SY5Y cells. Furthermore, transduced PEP-1-PON1 protein reduced MMP-9 expression and protected against dopaminergic neuronal cell death in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice model. Taken together, these results suggest a promising therapeutic application of PEP-1-PON1 proteins against PD and other inflammation and oxidative stress-related neuronal diseases. Copyright © 2015 Elsevier Ltd. All rights reserved.

Measurement of the leptonic structure functions of the photon at PEP [Positron Electron Project

International Nuclear Information System (INIS)

Cain, M.P.

1987-01-01

At beam energies available at the PEP e + e - storage ring at the Stanford Linear Accelerator Center the cross-section for two-photon particle production is sufficiently large to warrant an investigation of this O(α 4 ) process. Of particular interest is the two-photon process ee → eeμμ at non-zero Q 2 . This channel is not only relatively easy to observe experimentally but also serves as a model for the process ee → eeq bar q. For the case of inelastic eγ scattering the cross-section could be parameterized in terms of the photon structure functions F 1 (x,Q 2 ) and F 2 (x,Q 2 ). In this thesis I will present data on the process ee → eeμμ collected by the Two-Photon collaboration (PEP-9) at PEP. For the subset of data which proceeds by inelastic eγ scattering I will present a procedure for extracting the QED photon structure functions and apply this method to the data. 42 refs., 44 figs

Effect of the Electron Cloud and CSR on the Upgrade of the PEP-II

International Nuclear Information System (INIS)

Heifets, Samuel A

2001-01-01

Effects of the electron cloud and of the coherent synchrotron radiation (CSR) on the possible upgrade of the PEP-II B-factory are studied. PEP-II B factory operates with parameters shown in Table 1 and already exceeds the design luminosity. Nevertheless, a possibility of upgrading the machine to even higher luminosities is under consideration [1]. Several scenarios are summarized in Table 2. This paper describes effects of the electron cloud and of the coherent synchrotron radiation (CSR) on the proposed upgrades of the PEP-II B-factory. The first effect was observed [3] and caused [4] the degradation of the emittance at KEK B-factory. The analytic expression for the e-wake [2] is used in calculations of the head-tail instability. Other obvious effects of higher beam currents such as additional heat load are not considered. The short wave length CSR has been recently observed at Brookhaven [6]. Consideration of the effect of such CSR on the beam dynamics is based on our previous paper [7

Performance evaluation of PEP

International Nuclear Information System (INIS)

Zisman, M.S.

1987-10-01

An investigation of collective effects has been undertaken to assess the possibilities for using the low emittance operating mode of the PEP storage ring as a dedicated source of synchrotron radiation. Beam current limitations associated with longitudinal and transverse instabilities, and the expected emittance growth due to intrabeam scattering have been studied as a function of beam energy. Calculations of the beam lifetime due to Touschek and gas scattering are presented, and the growth times of coupled-bunch instabilities are estimated. In general, the results are encouraging, and no fundamental problems have been uncovered. It appears that beam currents up to about 10 mA per bunch should be achievable, and that the emittance growth is not a severe problem at an energy of about 8 GeV. A feedback system to deal with coupled-bunch instabilities is likely to be required. 7 refs., 13 figs

Complement inhibition by hydroxychloroquine prevents placental and fetal brain abnormalities in antiphospholipid syndrome.

Science.gov (United States)

Bertolaccini, Maria Laura; Contento, Gregorio; Lennen, Ross; Sanna, Giovanni; Blower, Philip J; Ma, Michelle T; Sunassee, Kavitha; Girardi, Guillermina

2016-12-01

Placental ischemic disease and adverse pregnancy outcomes are frequently observed in patients with antiphospholipid syndrome (APS). Despite the administration of conventional antithrombotic treatment a significant number of women continue to experience adverse pregnancy outcomes, with uncertain prevention and management. Efforts to develop effective pharmacological strategies for refractory obstetric APS cases will be of significant clinical benefit for both mothers and fetuses. Although the antimalarial drug, hydroxychloroquine (HCQ) is increasingly used to treat pregnant women with APS, little is known about its efficacy and mechanism of action of HCQ. Because complement activation plays a crucial and causative role in placental ischemia and abnormal fetal brain development in APS we hypothesised that HCQ prevents these pregnancy complications through inhibition of complement activation. Using a mouse model of obstetric APS that closely resembles the clinical condition, we found that HCQ prevented fetal death and the placental metabolic changes -measured by proton magnetic resonance spectroscopy in APS-mice. Using 111 In labelled antiphospholipid antibodies (aPL) we identified the placenta and the fetal brain as the main organ targets in APS-mice. Using this same method, we found that HCQ does not inhibit aPL binding to tissues as was previously suggested from in vitro studies. While HCQ did not affect aPL binding to fetal brain it prevented fetal brain abnormal cortical development. HCQ prevented complement activation in vivo and in vitro. Complement C5a levels in serum samples from APS patients and APS-mice were lower after treatment with HCQ while the antibodies titres remained unchanged. HCQ prevented not only placental insufficiency but also abnormal fetal brain development in APS. By inhibiting complement activation, HCQ might also be an effective antithrombotic therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

EFRT M-12 Issue Resolution: Caustic Leach Rate Constants from PEP and Laboratory-Scale Tests

Energy Technology Data Exchange (ETDEWEB)

Mahoney, Lenna A.; Rassat, Scot D.; Eslinger, Paul W.; Aaberg, Rosanne L.; Aker, Pamela M.; Golovich, Elizabeth C.; Hanson, Brady D.; Hausmann, Tom S.; Huckaby, James L.; Kurath, Dean E.; Minette, Michael J.; Sundaram, S. K.; Yokuda, Satoru T.

2009-08-14

Testing Summary 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 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 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 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 UFP-1, the 19-M NaOH is added to un-concentrated waste slurry (3 to 8 wt% solids), while for leaching in UFP-2, the slurry is

EFRT M-12 Issue Resolution: Caustic Leach Rate Constants from PEP and Laboratory-Scale Tests

International Nuclear Information System (INIS)

Mahoney, Lenna A.; Rassat, Scot D.; Eslinger, Paul W.; Aaberg, Rosanne L.; Aker, Pamela M.; Golovich, Elizabeth C.; Hanson, Brady D.; Hausmann, Tom S.; Huckaby, James L.; Kurath, Dean E.; Minette, Michael J.; Sundaram, S. K.; Yokuda, Satoru T.

2009-01-01

Testing Summary 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 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 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 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 UFP-1, the 19-M NaOH is added to un-concentrated waste slurry (3 to 8 wt% solids), while for leaching in UFP-2, the slurry is concentrated

Status of the PEP-II asymmetric B-Factory

International Nuclear Information System (INIS)

Mattison, T.S.

1994-11-01

The PEP-II project is an e + e - storage ring complex with unequal energy beams to study CP violation in the B meson system. High luminosity requires a large number of bunches and a low value of beta at the collision point. The high beam current requires advances in vacuum chambers, damped RF cavities, and feedback systems. Machine elements inside the detector are required to achieve low beta values and magnetic separation

Measuring, calculating and estimating PEP's parasitic mode loss parameters

International Nuclear Information System (INIS)

Weaver, J.N.

1981-01-01

This note discusses various ways the parasitic mode losses from a bunched beam to a vacuum chamber can be measured, calculated or estimated. A listing of the parameter, k, for the various PEP ring components is included. A number of formulas for calculating multiple and single pass losses are discussed and evaluated for several cases. 25 refs., 1 fig., 1 tab

Preliminary design considerations for the stage 1 PEP lattice

International Nuclear Information System (INIS)

Helm, R.H.; Lee, M.J.

1974-07-01

A general description of the proposed PEP e + e - storage ring is discussed in the paper. We discuss the lattice and its operating characteristics in more detail, show how the design luminosity operative regions may be met and outline the limits of the operative regions of the beam parameters in several modes of operation. 18 refs., 16 figs., 1 tab

PEP-II vacuum system pressure profile modeling using EXCEL

International Nuclear Information System (INIS)

Nordby, M.; Perkins, C.

1994-06-01

A generic, adaptable Microsoft EXCEL program to simulate molecular flow in beam line vacuum systems is introduced. Modeling using finite-element approximation of the governing differential equation is discussed, as well as error estimation and program capabilities. The ease of use and flexibility of the spreadsheet-based program is demonstrated. PEP-II vacuum system models are reviewed and compared with analytical models

Gain control through divisive inhibition prevents abrupt transition to chaos in a neural mass model.

Science.gov (United States)

Papasavvas, Christoforos A; Wang, Yujiang; Trevelyan, Andrew J; Kaiser, Marcus

2015-09-01

Experimental results suggest that there are two distinct mechanisms of inhibition in cortical neuronal networks: subtractive and divisive inhibition. They modulate the input-output function of their target neurons either by increasing the input that is needed to reach maximum output or by reducing the gain and the value of maximum output itself, respectively. However, the role of these mechanisms on the dynamics of the network is poorly understood. We introduce a novel population model and numerically investigate the influence of divisive inhibition on network dynamics. Specifically, we focus on the transitions from a state of regular oscillations to a state of chaotic dynamics via period-doubling bifurcations. The model with divisive inhibition exhibits a universal transition rate to chaos (Feigenbaum behavior). In contrast, in an equivalent model without divisive inhibition, transition rates to chaos are not bounded by the universal constant (non-Feigenbaum behavior). This non-Feigenbaum behavior, when only subtractive inhibition is present, is linked to the interaction of bifurcation curves in the parameter space. Indeed, searching the parameter space showed that such interactions are impossible when divisive inhibition is included. Therefore, divisive inhibition prevents non-Feigenbaum behavior and, consequently, any abrupt transition to chaos. The results suggest that the divisive inhibition in neuronal networks could play a crucial role in keeping the states of order and chaos well separated and in preventing the onset of pathological neural dynamics.

Pep2Path: automated mass spectrometry-guided genome mining of peptidic natural products.

Directory of Open Access Journals (Sweden)

Marnix H Medema

2014-09-01

Full Text Available Nonribosomally and ribosomally synthesized bioactive peptides constitute a source of molecules of great biomedical importance, including antibiotics such as penicillin, immunosuppressants such as cyclosporine, and cytostatics such as bleomycin. Recently, an innovative mass-spectrometry-based strategy, peptidogenomics, has been pioneered to effectively mine microbial strains for novel peptidic metabolites. Even though mass-spectrometric peptide detection can be performed quite fast, true high-throughput natural product discovery approaches have still been limited by the inability to rapidly match the identified tandem mass spectra to the gene clusters responsible for the biosynthesis of the corresponding compounds. With Pep2Path, we introduce a software package to fully automate the peptidogenomics approach through the rapid Bayesian probabilistic matching of mass spectra to their corresponding biosynthetic gene clusters. Detailed benchmarking of the method shows that the approach is powerful enough to correctly identify gene clusters even in data sets that consist of hundreds of genomes, which also makes it possible to match compounds from unsequenced organisms to closely related biosynthetic gene clusters in other genomes. Applying Pep2Path to a data set of compounds without known biosynthesis routes, we were able to identify candidate gene clusters for the biosynthesis of five important compounds. Notably, one of these clusters was detected in a genome from a different subphylum of Proteobacteria than that in which the molecule had first been identified. All in all, our approach paves the way towards high-throughput discovery of novel peptidic natural products. Pep2Path is freely available from http://pep2path.sourceforge.net/, implemented in Python, licensed under the GNU General Public License v3 and supported on MS Windows, Linux and Mac OS X.

Mesomorphic phase behaviour of low molar mass PEP-PDMS diblock copolymers synthesized by anionic polymerization

International Nuclear Information System (INIS)

Vigild, M.E.

1997-10-01

The phase behaviour of low molar mass poly(ethylene-alt-propylene) -poly(dimethylsiloxane) (PEP-PDMS) is investigated in this thesis by the combination of dynamical mechanical spectroscopy (rheology) to measure phase transition temperatures, and small-angle x-ray scattering to identify the morphology of encountered phases. Samples of PEP-PDMS in the range of 0.2-0.7 in volume fraction of PEP are studied. This diblock copolymer system exhibits the three classical phases of lamellar sandwich structure (LAM), hexagonally packed cylinders (HEX), and spheres arranged on a body centered cubic lattice (BCC). Furthermore the gyroid phase (Ia3d symmetry) of two interpenetrating networks was also identified as a stable phase of the PEP-PDMS system. Time resolved measurements of small-angle neutron scattering in tandem with simultaneous in-situ rheological measurements are performed on samples showing transitions between different ordered phases. The identification of especially the BCC and gyroid phases from scattering experiments is treated. By performing mesoscopic crystallographic measurements using a custom built goniometer it was unambiguously shown that the application of shear to an unoriented powder-like sample introduces uniaxial orientation of the gyroid phase. The orientation of the ordered phase is otherwise random, causing a two-dimensional powder. Finally this dissertation presents a discussion of relevant parameters for the description of diblock copolymer phase behaviour together with descriptions of anionic polymerization for the synthesis of copolymers, and various experimental techniques for the characterization of diblocks. (au)

Mesomorphic phase behaviour of low molar mass PEP-PDMS diblock copolymers synthesized by anionic polymerization

Energy Technology Data Exchange (ETDEWEB)

Vigild, M.E.

1997-10-01

The phase behaviour of low molar mass poly(ethylene-alt-propylene) -poly(dimethylsiloxane) (PEP-PDMS) is investigated in this thesis by the combination of dynamical mechanical spectroscopy (rheology) to measure phase transition temperatures, and small-angle x-ray scattering to identify the morphology of encountered phases. Samples of PEP-PDMS in the range of 0.2-0.7 in volume fraction of PEP are studied. This diblock copolymer system exhibits the three classical phases of lamellar sandwich structure (LAM), hexagonally packed cylinders (HEX), and spheres arranged on a body centered cubic lattice (BCC). Furthermore the gyroid phase (Ia3d symmetry) of two interpenetrating networks was also identified as a stable phase of the PEP-PDMS system. Time resolved measurements of small-angle neutron scattering in tandem with simultaneous in-situ rheological measurements are performed on samples showing transitions between different ordered phases. The identification of especially the BCC and gyroid phases from scattering experiments is treated. By performing mesoscopic crystallographic measurements using a custom built goniometer it was unambiguously shown that the application of shear to an unoriented powder-like sample introduces uniaxial orientation of the gyroid phase. The orientation of the ordered phase is otherwise random, causing a two-dimensional powder. Finally this dissertation presents a discussion of relevant parameters for the description of diblock copolymer phase behaviour together with descriptions of anionic polymerization for the synthesis of copolymers, and various experimental techniques for the characterization of diblocks. (au). 9 tabs., 40 ills., 81 refs.

Impedance of the PEP-II DIP screen

Energy Technology Data Exchange (ETDEWEB)

Ng, C -K [Stanford Linear Accelerator Center, Menlo Park, CA (United States); Weiland, T

1996-08-01

The vacuum chamber of a storage ring normally consists of periodically spaced pumping slots. The longitudinal impedance of slots are analyzed in this paper. It is found that although the broad-band impedance is tolerable, the narrow-band impedance, as a consequence of the periodicity of the slots, may exceed the stability limit given by natural damping with no feedback system on. Based on this analysis, the PEP-II distributed-ion-pump (DIP) screen uses long grooves with hidden holes cut halfway to reduce both the broad-band and narrow-band impedances. (author)

Search for heavy neutrino production at PEP

International Nuclear Information System (INIS)

Feldman, G.J.

1985-10-01

We report a search for long-lived heavy neutrinos produced by the neutral weak current in e + e - annihilation at 29 GeV at PEP. Data from the Mark II detector are examined for evidence of events with one or two separated vertices in the radial range of 2 mm to 10 cm. No events were found that were consistent with the hypothesis of heavy neutrino production, eliminating the possibility of heavy neutrinos with decay lengths of 1 to 20 cm in mass range 1 to 13 GeV/c 2

Impedance of the PEP-II DIP screen

International Nuclear Information System (INIS)

Ng, C.K.; Weiland, T.

1995-09-01

The vacuum chamber of a storage ring normally consists of periodically spaced pumping slots. The longitudinal impedance of slots are analyzed in this paper. It is found that although the broad-band impedance is tolerable, the narrow-band impedance, as a consequence of the periodicity of the slots, may exceed the stability limit given by natural damping with no feedback system on. Based on this analysis, the PEP-II distributed-ion-pump (DIP) screen uses long grooves with hidden holes cut halfway to reduce both the broad-band and narrow-band impedances

Tests of μ-e universality for weak neutral currents at PEP

International Nuclear Information System (INIS)

Cline, D.B.; Resvanis, L.K.

1988-01-01

Two techniques are proposed to test the universality of the μ/minus/e weak neutral current interaction of large Q 2 . Both techniques require large statistics and some degree of longitudinal e + ,e/sup minus/ polarization but are otherwise feasible at PEP

Evolutionary divergence of the plant elicitor peptides (Peps) and their receptors : interfamily incompatibility of perception but compatibility of downstream signalling

NARCIS (Netherlands)

Lori, Martina; van Verk, Marcel C; Hander, Tim; Schatowitz, Hendrik; Klauser, Dominik; Flury, Pascale; Gehring, Christoph A; Boller, Thomas; Bartels, Sebastian

2015-01-01

Plant elicitor peptides (Peps) are potent inducers of pattern-triggered immunity and amplify the immune response against diverse pathogens. Peps have been discovered and studied extensively in Arabidopsis and only recently orthologs in maize were also identified and characterized in more detail.

Optimization of Dynamic Aperture of PEP-X Baseline Design

Energy Technology Data Exchange (ETDEWEB)

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

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. The 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.

Optimization of Dynamic Aperture of PEP-X Baseline Design

International Nuclear Information System (INIS)

Wang, Min-Huey

2010-01-01

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. The 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.

Epigenetic Histone Deacetylation Inhibition Prevents the Development and Persistence of Temporal Lobe Epilepsy.

Science.gov (United States)

Reddy, Sandesh D; Clossen, Bryan L; Reddy, Doodipala Samba

2018-01-01

Epilepsy is a chronic brain disease characterized by repeated unprovoked seizures. Currently, no drug therapy exists for curing epilepsy or disease modification in people at risk. Despite several emerging mechanisms, there have been few studies of epigenetic signaling in epileptogenesis, the process whereby a normal brain becomes progressively epileptic because of precipitating factors. Here, we report a novel role of histone deacetylation as a critical epigenetic mechanism in epileptogenesis. Experiments were conducted using the histone deacetylase (HDAC) inhibitor sodium butyrate in the hippocampus kindling model of temporal lobe epilepsy (TLE), a classic model heavily used to approve drugs for treatment of epilepsy. Daily treatment with butyrate significantly inhibited HDAC activity and retarded the development of limbic epileptogenesis without affecting after-discharge signal. HDAC inhibition markedly impaired the persistence of seizure expression many weeks after epilepsy development. Moreover, subchronic HDAC inhibition for 2 weeks resulted in a striking retardation of epileptogenesis. HDAC inhibition, unexpectedly, also showed erasure of the epileptogenic state in epileptic animals. Finally, butyrate-treated animals exhibited a powerful reduction in mossy fiber sprouting, a morphologic index of epileptogenesis. Together these results underscore that HDAC inhibition prevents the development of TLE, indicating HDAC's critical signaling role in epileptogenesis. These findings, therefore, envisage a unique novel therapy for preventing or curing epilepsy by targeting the epigenetic HDAC pathway. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

ARA-PEPs: a repository of putative sORF-encoded peptides in Arabidopsis thaliana.

Science.gov (United States)

Hazarika, Rashmi R; De Coninck, Barbara; Yamamoto, Lidia R; Martin, Laura R; Cammue, Bruno P A; van Noort, Vera

2017-01-17

Many eukaryotic RNAs have been considered non-coding as they only contain short open reading frames (sORFs). However, there is increasing evidence for the translation of these sORFs into bioactive peptides with potent signaling, antimicrobial, developmental, antioxidant roles etc. Yet only a few peptides encoded by sORFs are annotated in the model organism Arabidopsis thaliana. To aid the functional annotation of these peptides, we have developed ARA-PEPs (available at http://www.biw.kuleuven.be/CSB/ARA-PEPs ), a repository of putative peptides encoded by sORFs in the A. thaliana genome starting from in-house Tiling arrays, RNA-seq data and other publicly available datasets. ARA-PEPs currently lists 13,748 sORF-encoded peptides with transcriptional evidence. In addition to existing data, we have identified 100 novel transcriptionally active regions (TARs) that might encode 341 novel stress-induced peptides (SIPs). To aid in identification of bioactivity, we add functional annotation and sequence conservation to predicted peptides. To our knowledge, this is the largest repository of plant peptides encoded by sORFs with transcript evidence, publicly available and this resource will help scientists to effortlessly navigate the list of experimentally studied peptides, the experimental and computational evidence supporting the activity of these peptides and gain new perspectives for peptide discovery.

Enrofloxacin and Probiotic Lactobacilli Influence PepT1 and LEAP-2 mRNA Expression in Poultry.

Science.gov (United States)

Pavlova, Ivelina; Milanova, Aneliya; Danova, Svetla; Fink-Gremmels, Johanna

2016-12-01

Expression of peptide transporter 1 (PepT1) and liver-expressed antimicrobial peptide 2 (LEAP-2) in chickens can be influenced by food deprivation, pathological conditions and drug administration. Effect of three putative probiotic Lactobacillus strains and enrofloxacin on the expression of PepT1 and LEAP-2 mRNA was investigated in Ross 308 chickens. One-day-old chicks (n = 24) were allocated to following groups: control (without treatment); group treated with probiotics via feed; group treated with a combination of probiotics and enrofloxacin; and a group given enrofloxacin only. The drug was administered at a dose of 10 mg kg -1 , via drinking water for 5 days. Samples from liver, duodenum and jejunum were collected 126 h after the start of the treatment. Expression levels of PepT1 and LEAP-2 were determined by real-time polymerase chain reaction and were statistically evaluated by Mann-Whitney test. Enrofloxacin administered alone or in combination with probiotics provoked a statistically significant up-regulation of PepT1 mRNA levels in the measured organ sites. These changes can be attributed to a tendency of improvement in utilization of dietary peptide and in body weight gain. LEAP-2 mRNA expression levels did not change significantly in enrofloxacin-treated chickens in comparison with control group.

The PEP injection system

International Nuclear Information System (INIS)

Brown, K.L.; Avery, R.T.; Peterson, J.M.

1988-01-01

A system to transport 10-to-15-GeV electron and positron beams from the Stanford Linear Accelerator and to inject them into the PEP storage ring under a wide variety of lattice configurations has been designed. Optically, the transport line consists of three 360/degree/ phase-shift sections of FODO lattice, with bending magnets interspersed in such a way as to provide achromaticity, convenience in energy and emittance definition, and independent tuning of the various optical parameters for matching into the ring. The last 360/degree/ of phase shift has 88 milliradians of bend in a vertical plane and deposits the beam at the injection septum via a Lambertson magnet. Injection is accomplished by launching the beam with several centimeters of radial betatron amplitude in a fast bump provided by a triad of pulsed kicker magnets. Radiation damping reduces the collective amplitude quickly enough to allow injection at a high repetition rate

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

Science.gov (United States)

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.…

PEP surveying procedures and equipment

International Nuclear Information System (INIS)

Linker, F.

1982-06-01

The PEP Survey and Alignment System, which employs both laser-based and optical survey methods, is described. The laser is operated in conjunction with the Tektronix 4051 computer and surveying instruments such as ARM and SAM, system which is designed to automate data input, reduction, and production of alignment instructions. The laser system is used when surveying ring quadrupoles, main bend magnets, sextupoles, and is optional when surveying RF cavities and insertion quadrupoles. Optical methods usually require that data be manually entered into the computer for alignment, but in some cases, an element can be aligned using nominal values of fiducial locations without use of the computer. Optical surveying is used in the alignment of NIT and SIT, low field bend magnets, wigglers, RF cavities, and insertion quadrupoles

PEP-II RF cavity revisited

International Nuclear Information System (INIS)

Rimmer, R.A.; Koehler, G.; Li, D.; Hartman, N.; Folwell, N.; Hodgson, J.; Ko, K.; McCandless, B.

1999-01-01

This report describes the results of numerical simulations of the PEP-II RF cavity performed after the completion of the construction phase of the project and comparisons are made to previous calculations and measured results. These analyses were performed to evaluate new calculation techniques for the HOM distribution and RF surface heating that were not available at the time of the original design. These include the use of a high frequency electromagnetic element in ANSYS and the new Omega 3P code to study wall losses, and the development of broadband time domain simulation methods in MAFIA for the HOM loading. The computed HOM spectrum is compared with cavity measurements and observed beam-induced signals. The cavity fabrication method is reviewed, with the benefit of hindsight, and simplifications are discussed

Gain control through divisive inhibition prevents abrupt transition to chaos in a neural mass model

Science.gov (United States)

Papasavvas, Christoforos A.; Wang, Yujiang; Trevelyan, Andrew J.; Kaiser, Marcus

2016-01-01

Experimental results suggest that there are two distinct mechanisms of inhibition in cortical neuronal networks: subtractive and divisive inhibition. They modulate the input-output function of their target neurons either by increasing the input that is needed to reach maximum output or by reducing the gain and the value of maximum output itself, respectively. However, the role of these mechanisms on the dynamics of the network is poorly understood. We introduce a novel population model and numerically investigate the influence of divisive inhibition on network dynamics. Specifically, we focus on the transitions from a state of regular oscillations to a state of chaotic dynamics via period-doubling bifurcations. The model with divisive inhibition exhibits a universal transition rate to chaos (Feigenbaum behavior). In contrast, in an equivalent model without divisive inhibition, transition rates to chaos are not bounded by the universal constant (non-Feigenbaum behavior). This non-Feigenbaum behavior, when only subtractive inhibition is present, is linked to the interaction of bifurcation curves in the parameter space. Indeed, searching the parameter space showed that such interactions are impossible when divisive inhibition is included. Therefore, divisive inhibition prevents non-Feigenbaum behavior and, consequently, any abrupt transition to chaos. The results suggest that the divisive inhibition in neuronal networks could play a crucial role in keeping the states of order and chaos well separated and in preventing the onset of pathological neural dynamics. PMID:26465514

Background sources and masks for Mark II detector at PEP

International Nuclear Information System (INIS)

Kadyk, J.

1981-06-01

The shielding masks currently at use in several of the current experiments at PEP are the result of an early organized effort to understand the sources of particle background expected at PEP, followed by the evolution of the conceptual designs into actual hardware. The degree and kind of background particle loading which could be tolerated was expected to differ significantly among the different experiments, and several designs emerged from the common study. Qualitatively, the types of radiations studied were, Synchrotron Radiation (SR), Beam Gas Bremsstrahlung (BGB), and, to a limited extent others, e.g., Electroproduction (EP). Calculations will be given of predicted occupancies in the pipe counter and other sensitive elements at small radius, since these will be most susceptible to the SR and BGB backgrounds. The calculations presented in this note are specific to the Mark II detector. Some general statements will be made first about the character of each of the various types of backgrounds considered, then some detailed calculations made for application to the Mark II detector

Investigation of the substrate specificity of the proton coupled peptide transporter PepT_So from Shewanella oneidensis

DEFF Research Database (Denmark)

Prabhala, Bala Krishna; Aduri, Nanda Gowtham; Hald, Helle

2015-01-01

a strikingly high sequence identity, can be used to rationalize its mechanism and substrate preference. However, very little is known about the substrate specificity of PepTSo. To elaborate on this, the natural peptide specificity of PepTSo was investigated. Di and tri-peptides were found to be substrates...... for PepTSo in contrast to mono- and tetrapeptides as was indicated by previous competition studies. Interestingly, a negatively charged side chain was better accommodated on the dipeptide N- than the C-terminus position. Inversely, a positive charged side chain appeared to be tolerated better...

Community Screening for Preschool Child Inhibition to Offer the "Cool Little Kids" Anxiety Prevention Programme

Science.gov (United States)

Beatson, Ruth M.; Bayer, Jordana K.; Perry, Alexandra; Mathers, Megan; Hiscock, Harriet; Wake, Melissa; Beesley, Kate; Rapee, Ronald M.

2014-01-01

Temperamental inhibition has been identified as a key risk factor for childhood anxiety and internalizing problems. An efficacious early prevention programme for shy/inhibited children has been developed; however, accurate, efficient and acceptable screening is needed to support wider implementation. We explore community screening options in the…

A zero-length bellows for the PEP-II High-Energy Ring

International Nuclear Information System (INIS)

Nordby, M.; Daly, E.F.; Kurita, N.; Langton, J.

1995-08-01

Due to the beamline space constrictions and the modular design of the vacuum system, a conventional bellows can not be used everywhere in the PEP-II High-Energy Ring (HER) arcs. A zero-length ''Flex Flange'' was developed which actually performs better than a more standard bellows. The Flex Flange fits the space available while still preserving the modularity of the system. Furthermore, the design provides for an accurate match-up between adjoining octagonal copper chambers despite the large fabrication and assembly tolerances and high operational loads. Beam chamber continuity is ensured by an integral RF seal ring which is easy to install and fault-tolerant. Heating from synchrotron radiation and higher-order mode trapping is managed to ensure a robust connection despite the 3,000 mA beam current of the PEP-II HER. The Flex Flange concept is versatile and adaptable to many applications, yet economical both in space needed and cost

Particle searches in e+e- experiments at PEP and PETRA

International Nuclear Information System (INIS)

Lau, K.H.

1982-10-01

This talk reviews recent results in new particle searches performed by experiments at the high energy e + e - storage rings PEP and PETRA. It concentrates on recent searches for: hadrons with a new quark flavor, spin-1/2 charged heavy leptons, spin-0 charged leptons, spin-0 point-like scalars or pseudoscalars, and neutral heavy leptons

The PEP [positron-electron-proton] electron-positron ring: PEP Stage I

International Nuclear Information System (INIS)

Rees, J.R.

1974-01-01

The first stage of the positron-electron-proton (PEP) colliding-beam system which has been under joint study by a Lawrence Berkeley Laboratory-Stanford Linear Accelerator Center team for the past two years, will be the electron-positron storage ring. The physics justification for the e/sup /plus//e/sup /minus// ring is summarized briefly and the proposed facility is described. The ring will have six arcs having gross radii of about 220 m and six interaction regions located at the centers of straight sections about 130 m long. The longitudinal distance left free for experimental apparatus around the interaction regions will be 20 m. The range of operating beam energies will be from 5 GeV to 15 GeV. The design luminosity at 15 GeV will be 10 32 cm/sup /minus/2/s/sup/minus/1/, and the luminosity will vary approximately as the square of the beam energy. Alternative methods under consideration for adjusting the beam cross-section are discussed. The designs of the storage ring subsystems and of the conventional facilities including the experimental halls at the interaction regions are described. 7 refs., 8 figs., 3 tabs

Genetic inhibition of PKA phosphorylation of RyR2 prevents dystrophic cardiomyopathy

NARCIS (Netherlands)

Sarma, Satyam; Li, Na; van Oort, Ralph J.; Reynolds, Corey; Skapura, Darlene G.; Wehrens, Xander H. T.

2010-01-01

Aberrant intracellular Ca(2+) regulation is believed to contribute to the development of cardiomyopathy in Duchenne muscular dystrophy. Here, we tested whether inhibition of protein kinase A (PKA) phosphorylation of ryanodine receptor type 2 (RyR2) prevents dystrophic cardiomyopathy by reducing SR

RF system design for the PEP-II B Factory

International Nuclear Information System (INIS)

Schwarz, H.; Rimmer, R.

1994-06-01

The paper presents an overview of the design of the RF system for the PEP-II B Factory. An RF station consists of either two or four single-cell cavities driven by a 1.2 MW klystron through a waveguide distribution network. A variety of feedback loops stabilize the RF and its interaction with the beam. System parameters and all the relevant parameters of klystron and cavities are given

Reliable 6 PEP LTPS device for AMOLED's

Science.gov (United States)

Chou, Cheng-Wei; Wang, Pei-Yun; Hu, Chin-Wei; Chang, York; Chuang, Ching-Sang; Lin, Yusin

2013-09-01

This study presents a TFT structure which has less photo process and higher cost competitiveness in AMOLED display markets. A novel LTPS based 6 masks TFT structure for bottom emission AMOLED display is demonstrated in this paper. High field effect mobility (PMOS < 80 cm2/Vs ) and high reliability (PBTS △Vth< 0.02V @ 50oC VG=15V 10ks) was accomplished without the high temperature and rapid thermal annealing (RTA) activation process. Furthermore, a 14-inch AMOLED TV was achieved on the proposed 6-pep TFT backplane using the Gen. 3.5 mass production factory.

Radiation and electrical safety systems for PEP

International Nuclear Information System (INIS)

Smith, H.; Constant, T.; Crook, K.; Fitch, J.; Taylor, T.

1981-02-01

At SLAC, the Personnel Protection System (PPS) protects people from radiation hazards. For PEP, the system has been expanded to include protection against electrical and RF hazards. This paper describes the overall system design, giving particular attention to the novel features not found in similar systems in other areas of SLAC. These include the Restricted Access Mode to allow limited occupancy in the ring while high voltage or RF may be present, the automatic badge reader system for improving the efficiency of entry logging and control, and the solid state lighting control system for switching large lighting loads with minimum electro-magetic interference

BABAR - the detector for the PEP II B Factory at SLAC

International Nuclear Information System (INIS)

Lueth, V.

1994-09-01

BABAR refers to the detector that is being designed for the PEP II B-Factory at SLAC to perform a comprehensive study of CP violation in B meson decays. The design requirements and the principal detector components are briefly described. A summary of the expected physics performance is presented

Pep-up: A review of the Umgeni Valley Project evaulation process ...

African Journals Online (AJOL)

Pep-up: A review of the Umgeni Valley Project evaulation process. Tim Wright. Abstract. No Abstract. Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT · Creative Commons License This work is licensed under a Creative Commons Attribution 3.0 License.

Cloning and nucleotide sequence analysis of pepV, a carnosinase gene from Lactobacillus delbrueckii subsp. lactis DSM 7290, and partial characterization of the enzyme.

Science.gov (United States)

Vongerichten, K F; Klein, J R; Matern, H; Plapp, R

1994-10-01

Cell extracts of Lactobacillus delbrueckii subsp. lactis DSM 7290 were found to exhibit unique peptolytic ability against unusual beta-alanyl-dipeptides. In order to clone the gene encoding this activity, designated pepV, a gene library of strain DSM 7290 genomic DNA, prepared in the low-copy-number plasmid pLG339, was screened for heterologous expression in Escherichia coli. Recombinant clones harbouring pepV were identified by their ability to allow the utilization of carnosine (beta-alanyl-histidine) as a source of histidine by the E. coli mutant strain UK197 (pepD, hisG). Complementation was observed in a colony harbouring a recombinant plasmid (pKV101), carrying pepV. A 2.4 kb fragment containing pepV was subcloned and its nucleotide sequence revealed an open reading frame (ORF) of 1413 nucleotides, corresponding to a protein with predicted molecular mass of 51998 Da. A single transcription initiation site 71 bp upstream of the ATG translational start codon was identified by primer extension. No significant homology was detected between pepV or its deduced amino acid sequence with any entry in the databases. The only similarity was found in a region conserved in the ArgE/DapE/CPG2/YscS family of proteins. This observation, and protease inhibitor studies, indicated that pepV is of the metalloprotease type. A second ORF present in the sequenced fragment showed extensive homology to a variety of amino acid permeases from E. coli and Saccharomyces cerevisiae.

A Parallel Controls Software Approach for PEP II: AIDA and Matlab Middle Layer

International Nuclear Information System (INIS)

Wittmer, W.; Colocho, W.; White, G.

2007-01-01

The controls software in use at PEP II (Stanford Control Program - SCP) had originally been developed in the eighties. It is very successful in routine operation but due to its internal structure it is difficult and time consuming to extend its functionality. This is problematic during machine development and when solving operational issues. Routinely, data has to be exported from the system, analyzed offline, and calculated settings have to be reimported. Since this is a manual process, it is time consuming and error-prone. Setting up automated processes, as is done for MIA (Model Independent Analysis), is also time consuming and specific to each application. Recently, there has been a trend at light sources to use MATLAB as the platform to control accelerators using a 'MATLAB Middle Layer' (MML), and so called channel access (CA) programs to communicate with the low level control system (LLCS). This has proven very successful, especially during machine development time and trouble shooting. A special CA code, named AIDA (Accelerator Independent Data Access), was developed to handle the communication between MATLAB, modern software frameworks, and the SCP. The MML had to be adapted for implementation at PEP II. Colliders differ significantly in their designs compared to light sources, which poses a challenge. PEP II is the first collider at which this implementation is being done. We will report on this effort, which is still ongoing

Study of Beam-Beam Effects at PEP-II

International Nuclear Information System (INIS)

Narsky, I

2004-01-01

Using a self-consistent three-dimensional simulation running on parallel supercomputers, we have modeled the beam-beam interaction at the PEP-II asymmetric e + e - collider. To provide guidance for luminosity improvement, we scanned the tunes and currents in both rings and computed their impact on the luminosity and transverse beam sizes. We also studied the effects of colliding the beams with a small crossing angle. Where possible, the code was benchmarked against experimental measurements of luminosity and beam sizes, yielding an acceptable agreement

Arginase inhibition prevents the development of hypertension and improves insulin resistance in obese rats.

Science.gov (United States)

Peyton, Kelly J; Liu, Xiao-Ming; Shebib, Ahmad R; Johnson, Fruzsina K; Johnson, Robert A; Durante, William

2018-04-27

This study investigated the temporal activation of arginase in obese Zucker rats (ZR) and determined if arginase inhibition prevents the development of hypertension and improves insulin resistance in these animals. Arginase activity, plasma arginine and nitric oxide (NO) concentration, blood pressure, and insulin resistance were measured in lean and obese animals. There was a chronological increase in vascular and plasma arginase activity in obese ZR beginning at 8 weeks of age. The increase in arginase activity in obese animals was associated with a decrease in insulin sensitivity and circulating levels of arginine and NO. The rise in arginase activity also preceded the increase in blood pressure in obese ZR detected at 12 weeks of age. Chronic treatment of 8-week-old obese animals with an arginase inhibitor or L-arginine for 4 weeks prevented the development of hypertension and improved plasma concentrations of arginine and NO. Arginase inhibition also improved insulin sensitivity in obese ZR while L-arginine supplementation had no effect. In conclusion, arginase inhibition prevents the development of hypertension and improves insulin sensitivity while L-arginine administration only mitigates hypertension in obese animals. Arginase represents a promising therapeutic target in ameliorating obesity-associated vascular and metabolic dysfunction.

Responses of mRNA expression of PepT1 in small intestine to ...

African Journals Online (AJOL)

STORAGESEVER

2009-05-04

May 4, 2009 ... 2National Key Laboratory of Animal Nutrition, Beijing, 100193, China. 3College ... porters are present in tissues of sheep, cows, pigs and .... PepT1; Peptide transporter, GAPDH; Glyceraldehyde-3-phosphate dehydrogenase.

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

International Nuclear Information System (INIS)

Guzman-Leong, Consuelo E.; Bredt, Ofelia P.; Burns, Carolyn A.; Daniel, Richard C.; Su, Yin-Fong; Geeting, John G.H.; Golovich, Elizabeth C.; Josephson, Gary B.; Kurath, Dean E.; Sevigny, Gary J.; Smith, Dennese M.; Valdez, Patrick L.J.; Yokuda, Satoru T.; Young, Joan K.

2009-01-01

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. 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.

PEP computer control system

International Nuclear Information System (INIS)

1979-03-01

This paper describes the design and performance of the computer system that will be used to control and monitor the PEP storage ring. Since the design is essentially complete and much of the system is operational, the system is described as it is expected to 1979. Section 1 of the paper describes the system hardware which includes the computer network, the CAMAC data I/O system, and the operator control consoles. Section 2 describes a collection of routines that provide general services to applications programs. These services include a graphics package, data base and data I/O programs, and a director programm for use in operator communication. Section 3 describes a collection of automatic and semi-automatic control programs, known as SCORE, that contain mathematical models of the ring lattice and are used to determine in real-time stable paths for changing beam configuration and energy and for orbit correction. Section 4 describes a collection of programs, known as CALI, that are used for calibration of ring elements

Background estimates for PEP

International Nuclear Information System (INIS)

Martin, F.

1975-04-01

The beam gas bremsstrahlung radiation for PEP has been studied in detail using the ray trace program TURTLE. With this program, an electron (positron) trajectory starting at an interaction region is traced through the storage ring until it radiates, then the radiated electron is traced until it stops in the beam pipe. The relative number of electrons stopping between the strong focusing quadrupoles is used to determine a rate at which electromagnetic showers will occur in the region of the experimental apparatus. It was found that 2.46% of the radiated electrons will stop in the interaction region. Assuming a uniform pressure of 2 x 10/sup /minus/9/ Torr in the vacuum pipe for a residual gas (X/sub o/ = 34.7 gm/cm 2 ), 2.5 x 10 5 electrons (positrons) will stop in the interaction region per beam (4 x 10 12 electrons at 15 GeV) per second. If the luminosity is 10 32 , this rate is equivalent to a cross section of 2.5 x 10/sup /minus/27/ cm 2 . 4 figs., 3 tabs

An Orbit And Dispersion Correction Scheme for the PEP II

International Nuclear Information System (INIS)

Cai, Y.; Donald, M.; Shoaee, H.; White, G.; Yasukawa, L.A.

2011-01-01

To achieve optimum luminosity in a storage ring it is vital to control the residual vertical dispersion. In the original PEP storage ring, a scheme to control the residual dispersion function was implemented using the ring orbit as the controlling element. The 'best' orbit not necessarily giving the lowest vertical dispersion. A similar scheme has been implemented in both the on-line control code and in the simulation code LEGO. The method involves finding the response matrices (sensitivity of orbit/dispersion at each Beam-Position-Monitor (BPM) to each orbit corrector) and solving in a least squares sense for minimum orbit, dispersion function or both. The optimum solution is usually a subset of the full least squares solution. A scheme of simultaneously correcting the orbits and dispersion has been implemented in the simulation code and on-line control system for PEP-II. The scheme is based on the eigenvector decomposition method. An important ingredient of the scheme is to choose the optimum eigenvectors that minimize the orbit, dispersion and corrector strength. Simulations indicate this to be a very effective way to control the vertical residual dispersion.

The PEP-II/BaBar Project-Wide Database using World Wide Web and Oracle*Case

International Nuclear Information System (INIS)

Chan, A.; Crane, G.; MacGregor, I.; Meyer, S.

1995-12-01

The PEP-II/BaBar Project Database is a tool for monitoring the technical and documentation aspects of the accelerator and detector construction. It holds the PEP-II/BaBar design specifications, fabrication and installation data in one integrated system. Key pieces of the database include the machine parameter list, components fabrication and calibration data, survey and alignment data, property control, CAD drawings, publications and documentation. This central Oracle database on a UNIX server is built using Oracle*Case tools. Users at the collaborating laboratories mainly access the data using World Wide Web (WWW). The Project Database is being extended to link to legacy databases required for the operations phase

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

Science.gov (United States)

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.

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

Directory of Open Access Journals (Sweden)

Timo Stressler

Full Text Available 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.

Fabrication process for the PEP II RF cavities

Energy Technology Data Exchange (ETDEWEB)

Franks, R.M.; Rimmer, R.A. [Lawrence Berkeley National Lab., CA (United States); Schwarz, H. [Stanford Linear Accelerator Center, Menlo Park, CA (United States)

1997-06-05

This paper presents the major steps used in the fabrication of the 26 RF Cavities required for the PEP-II B-factory. Several unique applications of conventional processes have been developed and successfully implemented: electron beam welding (EBW), with minimal porosity, of .75 inch (19 mm) copper cross-sections; extensive 5-axis milling of water channels; electroplating of .37 inch (10 mm) thick OFE copper; tuning of the cavity by profiling beam noses prior to final joining with the cavity body; and machining of the cavity interior, are described here.

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.

Science.gov (United States)

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.

Control electronics of the PEP RF system

International Nuclear Information System (INIS)

Pellegrin, J.L.; Schwarz, H.

1981-01-01

The operation of the major components used for controlling the phase and field level of the PEP RF cavities is described. The control electronics of one RF station is composed of several control loops: each cavity has a tuners' servo loop which maintains the frequency constant and also keeps the fields of each cavity balanced; the total gap voltage developed by a pair of cavities is regulated by a gap voltage controller; finally, the phase variation along the amplification chain, the klystron and the cavities are compensated by a phase lock loop. The design criteria of each loop are set forth and the circuit implementation and test results are presented

A first look at a polarimeter for EPIC or PEP

International Nuclear Information System (INIS)

Toner, W.T.

1988-01-01

A derivation of the resolution function is given in terms of machine parameters and detector resolution. A preliminary design is outlined for a pair spectrometer to detect high energy backscattered laser photons. A more careful examination is needed of the asymmetry as a function of resolution, of laser geometry and rates, and of problems associated with installing and using the system at PEP. 2 figs., 1 tab

RF feedback simulation for the PEP-II B Factory

International Nuclear Information System (INIS)

Tighe, R.

1994-06-01

A model, of the beam and RF system for PEP-11 has been developed to allow both time-domain simulation and frequency-domain analysis of the complete system. The model includes the full set of feedback loops and nonlinear elements such as the beam and klystron. The model may be used to predict beam and feedback stability in the presence of nonlinearities through time-domain simulation as well as system frequency response about a given operating point

Calibration of the beam-position monitor system for the SLAC PEP-II B factory

International Nuclear Information System (INIS)

Johnson, R.; Smith, S.; Kurita, N.

1997-06-01

The Beam-Position Monitors (BPM) for the PEP-II B Factory consist of four 1.5-cm diameter button style pickups mounted on the diagonals of the quadrupole vacuum chambers. Before installation of the vacuum chambers in the quadrupole assemblies, the electrical center of the BPMs is measured with respect to the mechanical center in a calibration test stand. In this paper the calibration test stand is described and the precision and accuracy of the calibrations are presented. After installation of the quadrupole assemblies in the PEP-II tunnel, the passive attenuation for each channel of the system is measured to preserve the accuracy of the calibration. Finally, the active electronics includes an onboard calibrator. Results for these portions of the calibration are presented

Development of the Positive Emotions Program for Schizophrenia (PEPS: an intervention to improve pleasure and motivation in schizophrenia

Directory of Open Access Journals (Sweden)

Alexandra eNguyen

2016-02-01

Full Text Available Objectives: The efficacy of drug-based treatments and psychological interventions on the primary negative symptoms of schizophrenia remains limited. Recent literature has distinguished negative symptoms associated with a diminished capacity to experience, from those associated with a limited capacity for expression. The Positive Emotions Program for Schizophrenia (PEPS is a new method that specifically aims to reduce the syndrome of a diminished capacity to experience. Methods: The intervention’s vital ingredients were identified through a literature review of emotion in schizophrenia and positive psychology. The program has been beta-tested on various groups of healthcare professionals. Results: A detailed description of the final version of PEPS is presented here. The French version of the program is freely downloadable. Conclusions: PEPS is a specific, short, easy to use, group-based intervention to improve pleasure and motivation in schizophrenia. It was built considering a recovery-oriented approach to schizophrenia.

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

Energy Technology Data Exchange (ETDEWEB)

Guzman-Leong, Consuelo E.; Bredt, Ofelia P.; Burns, Carolyn A.; Daniel, Richard C.; Su, Yin-Fong; Geeting, John GH; Golovich, Elizabeth C.; Josephson, Gary B.; Kurath, Dean E.; Sevigny, Gary J.; Smith, Dennese M.; Valdez, Patrick LJ; Yokuda, Satoru T.; Young, Joan K.

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. 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.

The PEP-II Asymmetric B Factory: Design details and R ampersand D results

International Nuclear Information System (INIS)

Bloom, E.; DeStaebler, H.; Dorfan, J.

1994-06-01

PEP-II, a 9 GeV x 3.1 GeV electron-positron collider with a design luminosity of 3 x 10 33 cm -2 s -1 has now been approved for construction by SLAC, LBL and LLNL for the purpose of studying CP violation in the B bar B system. This upgrade project involves replacing the vacuum and RF systeum of PEP, which will serve as the high-energy ring (HER), along with the addition of a new low-energy ring (LER) mounted atop the HER. Designs for both rings are described, and the anticipated project construction schedule is indicated. Collider operation will begin at the end of 1998. An aggressive R ampersand D program has been carried out to validate our design choices; key results in the areas of lattice design, vacuum, RF, and multibunch feedback are summarized

PEP-II asymmetric B Factory: Design update and R ampersand D results

International Nuclear Information System (INIS)

Zisman, M.S.; Bell, R.A.; Dorfan, J.; Schwarz, H.; Barletta, W.A.; Calderon, M.

1992-07-01

PEP-II, a 9 GeV x 3.1 GeV e + e - collider with a design luminosity of 3 x 10 33 cm -2 s -1 , was proposed jointly by SLAC, LBL, and LLNL. Recent efforts have continued towards an optimized design. In addition, an aggressive R ampersand D program is under way to validate our design choices. Fabrication of a low-power prototype RF cavity is complete, and impedance measurements are beginning. A 500-kW, 476-MHz klystron has been completed; it will be used for testing both high-power RF windows and a prototype high-power cavity (now under design in collaboration with Chalk River Laboratory). Vacuum studies have demonstrated that chambers with suitable photodesorption properties can be fabricated. A mockup of the two-ring arc area has been completed and used to investigate alignment and stability issues. The PEP-II project is ready to begin construction as soon as funds become available

Trigger drift chamber for the upgraded mark II detector at PEP

Science.gov (United States)

Ford, W. T.; Smith, J. G.; Wagner, S. R.; Weber, P.; White, S. L.; Alvarez, M.; Calviño, F.; Fernandez, E.

1987-04-01

A small cylindrical track detector was built as an array of single-wire drift cells with aluminized mylar cathode tubes. Point measurement resolution of ˜ 90 μm was achieved with a drift gas of 50% argon-50% ethane at atmospheric pressure. The chamber construction, electronics, and calibration are discussed. Performance results from PEP colliding-beam data are presented.

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

Science.gov (United States)

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.

PEP725 Pan European Phenological Database

Science.gov (United States)

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

2010-09-01

Europe is in the fortunate situation that it has a long tradition in phenological networking: the history of collecting phenological data and using them in climatology has its starting point in 1751 when Carl von Linné outlined in his work Philosophia Botanica methods for compiling annual plant calendars of leaf opening, flowering, fruiting and leaf fall together with climatological observations "so as to show how areas differ". Recently in most European countries, phenological observations have been carried out routinely for more than 50 years by different governmental and non governmental organisations and following different observation guidelines, the data stored at different places in different formats. This has been really hampering pan European studies as one has to address many network operators to get access to the data before one can start to bring them in a uniform style. From 2004 to 2009 the COST-action 725 established a European wide data set of phenological observations. But the deliverables of this COST action was not only the common phenological database and common observation guidelines - COST725 helped to trigger a revival of some old networks and to establish new ones as for instance in Sweden. At the end of 2009 the COST action the database comprised about 8 million data in total from 15 European countries plus the data from the International Phenological Gardens IPG. In January 2010 PEP725 began its work as follow up project with funding from EUMETNET the network of European meteorological services and of ZAMG the Austrian national meteorological service. PEP725 not only will take over the part of maintaining, updating the COST725 database, but also to bring in phenological data from the time before 1951, developing better quality checking procedures and ensuring an open access to the database. An attractive webpage will make phenology and climate impacts on vegetation more visible in the public enabling a monitoring of vegetation development.

Status of the Object Oriented Program based Graphic User Interface Development for HyPEP

International Nuclear Information System (INIS)

Lee, Young Jin; Park, Ji Won; Hwang, Moon Kyu

2007-01-01

Hydrogen is being promoted as the energy-carrier for the future under the proposed hydrogen economy. As large reservoirs of hydrogen molecules do not exist in nature, the hydrogen needs to be produced using other energies such as nuclear, coal, natural gas, etc. The nuclear hydrogen production facility, where nuclear power is used to split water to produce hydrogen molecules, is presented as one of the optimal solutions for the large scale hydrogen production. Compared to other large scale hydrogen production methods, the nuclear hydrogen production can have better overall economics and less damaging environmental impacts such as global warming and pollution. In order to assess the overall economics of the hydrogen production, it is important to assess the hydrogen production efficiencies. In the conceptual design stage of the plant, various different plant layouts need to be studied to optimize the production efficiency. The main development aim of the HyPEP (Hydrogen Production Efficiency calculator Program) is the rapid assessment of the overall hydrogen production efficiency of a nuclear hydrogen production facility. The program is being developed with extensive GUI features to enhance the user-friendliness and the rapid model build-ups. This paper presents the current status of the development of HyPEP especially the GUI. HyPEP is being developed under an International Nuclear Engineering Research Initiative (I-NERI) Project

A randomized trial of rectal indomethacin and sublingual nitrates to prevent post-ERCP pancreatitis.

Science.gov (United States)

Sotoudehmanesh, Rasoul; Eloubeidi, Mohamad Ali; Asgari, Ali Ali; Farsinejad, Maryam; Khatibian, Morteza

2014-06-01

Acute pancreatitis is the most common adverse event of endoscopic retrograde cholangiopancreatography (ERCP). Recent data suggest that indomethacin can reduce the risk of post-ERCP pancreatitis (PEP) in high-risk individuals. However, whether the combination of indomethacin and sublingual nitrates is superior to indomethacin alone is unknown. Therefore, we aimed to evaluate the efficacy of rectally administered indomethacin plus sublingual nitrate compared with indomethacin alone to prevent PEP. During a 17-month period, all eligible patients who underwent ERCP were enrolled in this study. We excluded patients who had undergone a prior endoscopic sphincterotomy. In a double-blind controlled randomized trial, patients received a suppository containing 100 mg of indomethacin, plus 5 mg of sublingual nitrate (group A), or a suppository containing 100 mg of indomethacin, plus sublingual placebo (group B), before ERCP. Serum amylase levels and clinically pertinent evaluations were measured in all patients after ERCP. Of the 300 enrolled patients, 150 received indomethacin plus nitrate. Thirty-three patients developed pancreatitis: 10 (6.7%) in group A and 23 (15.3%) in group B (P=0.016, risk ratio=0.39, 95% confidence intervals (CI): 0.18-0.86). More than 80% of the patients were at high risk of developing pancreatitis after ERCP. Absolute risk reduction, relative risk reduction, and number needed to treat for the prevention of PEP were 8.6% (95% CI: 4.7-14.5), 56.2% (95% CI: 50.6-60.8), and 12 (95% CI: 7-22), respectively. Combination of rectal indomethacin and sublingual nitrate given before ERCP was significantly more likely to reduce the incidence of PEP than indomethacin suppository alone. Multicenter trials to confirm these promising findings are needed.

Exopolysaccharide-associated protein sorting in environmental organisms: the PEP-CTERM/EpsH system. Application of a novel phylogenetic profiling heuristic

Directory of Open Access Journals (Sweden)

Ward Naomi

2006-08-01

Full Text Available Abstract Background Protein translocation to the proper cellular destination may be guided by various classes of sorting signals recognizable in the primary sequence. Detection in some genomes, but not others, may reveal sorting system components by comparison of the phylogenetic profile of the class of sorting signal to that of various protein families. Results We describe a short C-terminal homology domain, sporadically distributed in bacteria, with several key characteristics of protein sorting signals. The domain includes a near-invariant motif Pro-Glu-Pro (PEP. This possible recognition or processing site is followed by a predicted transmembrane helix and a cluster rich in basic amino acids. We designate this domain PEP-CTERM. It tends to occur multiple times in a genome if it occurs at all, with a median count of eight instances; Verrucomicrobium spinosum has sixty-five. PEP-CTERM-containing proteins generally contain an N-terminal signal peptide and exhibit high diversity and little homology to known proteins. All bacteria with PEP-CTERM have both an outer membrane and exopolysaccharide (EPS production genes. By a simple heuristic for screening phylogenetic profiles in the absence of pre-formed protein families, we discovered that a homolog of the membrane protein EpsH (exopolysaccharide locus protein H occurs in a species when PEP-CTERM domains are found. The EpsH family contains invariant residues consistent with a transpeptidase function. Most PEP-CTERM proteins are encoded by single-gene operons preceded by large intergenic regions. In the Proteobacteria, most of these upstream regions share a DNA sequence, a probable cis-regulatory site that contains a sigma-54 binding motif. The phylogenetic profile for this DNA sequence exactly matches that of three proteins: a sigma-54-interacting response regulator (PrsR, a transmembrane histidine kinase (PrsK, and a TPR protein (PrsT. Conclusion These findings are consistent with the hypothesis

Supramolecular structure of enterobacterial wild-type lipopolysaccharides (LPS), fractions thereof, and their neutralization by Pep19-2.5.

Science.gov (United States)

Brandenburg, Klaus; Heinbockel, Lena; Correa, Wilmar; Fukuoka, Satoshi; Gutsmann, Thomas; Zähringer, Ulrich; Koch, Michel H J

2016-04-01

Lipopolysaccharides (LPS) belong to the strongest immune-modulating compounds known in nature, and are often described as pathogen-associated molecular patterns (PAMPs). In particular, at higher concentrations they are responsible for sepsis and the septic shock syndrome associated with high lethality. Since most data are indicative that LPS aggregates are the bioactive units, their supramolecular structures are considered to be of outmost relevance for deciphering the molecular mechanisms of its bioactivity. So far, however, most of the data available addressing this issue, were published only for the lipid part (lipid A) and the core-oligosaccharide containing rough LPS, representing the bioactive unit. By contrast, it is well known that most of the LPS specimen identified in natural habitats contain the smooth-form (S-form) LPS, which carry additionally a high-molecular polysaccharide (O-chain). To fill this lacuna and going into a more natural system, here various wild-type (smooth form) LPS including also some LPS fractions were investigated by small-angle X-ray scattering with synchrotron radiation to analyze their aggregate structure. Furthermore, the influence of a recently designed synthetic anti-LPS peptide (SALP) Pep19-2.5 on the aggregate structure, on the binding thermodynamics, and on the cytokine-inducing activity of LPS were characterized, showing defined aggregate changes, high affinity binding and inhibition of cytokine secretion. The data obtained are suitable to refine our view on the preferences of LPS for non-lamellar structures, representing the highest bioactive forms which can be significantly influenced by the binding with neutralizing peptides such as Pep19-2.5. Copyright © 2016 Elsevier Inc. All rights reserved.

Operation and performance of the PEP-II prototype longitudinal damping system at ALS

International Nuclear Information System (INIS)

Teytelman, D.; Claus, R.; Fox, J.

1995-05-01

A modular programmable longitudinal feedback system has been developed as a component of the PEP-II R+D program. This system is based on a family of VME and VXI packaged signal processing functions which implement a general purpose digital feedback controller for accelerators with bunch spacings of 2 ns. A complete PEP-II prototype system has been configured and installed for use at the LBL Advanced Light Source. The system configuration used for tests at the ALS is described and results are presented showing the action of the feedback system. Open and closed loop results showing the detection and calculation of feedback signals from bunch motion are presented and the system is shown to damp coupled-bunch instabilities in the ALS. Use of the system for accelerator diagnostics is illustrated via measurement of grow-damp transients which quantify growth rates without feedback, damping rates with feedback, and identify unstable modes

Trigger drift chamber for the upgraded Mark II detector at PEP

International Nuclear Information System (INIS)

Ford, W.T.; Smith, J.G.; Wagner, S.R.; Weber, P.; White, S.L.; Alvarez, M.; Calvino, F.; Fernandez, E.; Universidad Autonoma de Barcelona

1987-01-01

A small cylindrical track detector was built as an array of single-wire drift cells with aluminized mylar cathode tubes. Point measurement resolution of ∝90 μm was achieved with a drift gas of 50% argon-50% ethane at atmospheric pressure. The chamber construction, electronics, and calibration are discussed. Performance results from PEP colliding-beam data are presented. (orig.)

Donepezil prevents RANK-induced bone loss via inhibition of osteoclast differentiation by downregulating acetylcholinesterase

Directory of Open Access Journals (Sweden)

Tsuyoshi Sato

2015-09-01

Conclusions: AChE promotes osteoclast differentiation in vitro. Donepezil inhibits osteoclast function in vitro and prevents bone loss by suppressing bone resorption in vivo, suggesting the possibility that donepezil reduces fracture risk in patients with Alzheimer's disease.

PEP-II Transverse Feedback Electronics Upgrade

International Nuclear Information System (INIS)

Weber, J.; Chin, M.; Doolittle, L.; Akre, R.

2005-01-01

The PEP-II B Factory at the Stanford Linear Accelerator Center (SLAC) requires an upgrade of the transverse feedback system electronics. The new electronics require 12-bit resolution and a minimum sampling rate of 238 Msps. A Field Programmable Gate Array (FPGA) is used to implement the feedback algorithm. The FPGA also contains an embedded PowerPC 405 (PPC-405) processor to run control system interface software for data retrieval, diagnostics, and system monitoring. The design of this system is based on the Xilinx(R) ML300 Development Platform, a circuit board set containing an FPGA with an embedded processor, a large memory bank, and other peripherals. This paper discusses the design of a digital feedback system based on an FPGA with an embedded processor. Discussion will include specifications, component selection, and integration with the ML300 design

PEP-II Transverse Feedback Electronics Upgrade

International Nuclear Information System (INIS)

Weber, J.M.; Chin, M.J.; Doolittle, L.R.; Akre, R.

2006-01-01

The PEP-II B Factory at the Stanford Linear Accelerator Center (SLAC) requires an upgrade of the transverse feedback system electronics. The new electronics require 12-bit resolution and a minimum sampling rate of 238 Msps. A Field Programmable Gate Array (FPGA) is used to implement the feedback algorithm. The FPGA also contains an embedded PowerPC 405 (PPC-405) processor to run control system interface software for data retrieval, diagnostics, and system monitoring. The design of this system is based on the Xilinx(reg s ign) ML300 Development Platform, a circuit board set containing an FPGA with an embedded processor, a large memory bank, and other peripherals. This paper discusses the design of a digital feedback system based on an FPGA with an embedded processor. Discussion will include specifications, component selection, and integration with the ML300 design

PEP-II Transverse Feedback Electronics Upgrade

CERN Document Server

Weber, Jonah; Chin, Michael; Doolittle, Lawrence

2005-01-01

The PEP-II B Factory at the Stanford Linear Accelerator Center (SLAC) requires an upgrade of the transverse feedback system electronics. The new electronics require 12-bit resolution and a minimum sampling rate of 238 Msps. A Field Programmable Gate Array (FPGA) is used to implement the feedback algorithm. The FPGA also contains an embedded PowerPC 405 (PPC-405) processor to run control system interface software for data retrieval, diagnostics, and system monitoring. The design of this system is based on the Xilinx® ML300 Development Platform, a circuit board set containing an FPGA with an embedded processor, a large memory bank, and other peripherals. This paper discusses the design of a digital feedback system based on an FPGA with an embedded processor. Discussion will include specifications, component selection, and integration with the ML300 design.

Search for Ne in e−μ+ events at petra and pep energies

Directory of Open Access Journals (Sweden)

K. Yamanashi

1978-03-01

Full Text Available We propose a way to check the possible existence of an electron-type neutral heavy lepton Ne which decays into e−μ+νμ. In the region of cosθcoll < 0 eμ signals due to Ne are expected to exceed those due to τ± at PETRA and PEP energies.

PEP-X: An Ultimate Storage Ring Based on Fourth-Order Geometric Achromats

Energy Technology Data Exchange (ETDEWEB)

Cai, Yunhai; Bane, Karl; Hettel, Robert; Nosochkov, Yuri; Wang, Min-Huey; /SLAC

2012-04-06

We have designed an 'ultimate' storage ring for the PEP-X light source that achieves the diffraction limited emittances (at 1.5 {angstrom}) of 12 pm-rad in both horizontal and vertical planes with a 4.5-GeV beam. These emittances include the contribution of intrabeam scattering at a nominal current of 200 mA in 3300 bunches. This quality beam in conjunction with a conventional 4-m undulator in a straight section can generate synchrotron radiation having a spectral brightness above 10{sup 22} [photons/s/mm{sup 2}/mrad{sup 2}/0.1% BW] at a 10 keV photon energy. The high coherence at the diffraction limit makes PEP-X competitive with 4th generation light sources based on an energy recovery linac. In addition, the beam lifetime is several hours and the dynamic aperture is large enough to allow off-axis injection. The alignment and stability tolerances, though challenging, are achievable. A ring with all these properties is only possible because of several major advances in mitigating the effects of nonlinear resonances.

RF Feedback Analysis for 4 cavities per klystron in PEP-II

International Nuclear Information System (INIS)

Corredoura, P.; Tighe, R.

1994-06-01

Lattice changes in the PEP-II high energy ring have made the concept of driving four cavities with a single klystron an attractive option. This paper examines the topology from a RF feedback point of view. Sources of error are identified and their magnitudes are estimated. The effect on the performance of the longitudinal impedance reducing feedback loops is calculated using control theory and Mathematica

In Depth Diagnostics for RF System Operation in the PEP-II B Factory

International Nuclear Information System (INIS)

Van Winkle, Daniel; Fox, John; Teytelman, Dmitry; SLAC

2005-01-01

The PEP-II RF systems incorporate numerous feedback loops in the low-level processing for impedance control and operating point regulation. The interaction of the multiple loops with the beam is complicated, and the systems incorporate online diagnostic tools to configure the feedback loops as well as to record fault files in the case of an RF abort. Rapid and consistent analysis of the RF-related beam aborts and other failures is critical to the reliable operation of the B-Factory, especially at the recently achieved high beam currents. Procedures and algorithms used to extract diagnostic information from time domain fault files are presented and illustrated via example interpretations of PEP-II fault file data. Example faults presented will highlight the subtle interpretation required to determine the root cause. Some such examples are: abort kicker firing asynchronously, klystron and cavity arcs, beam loss leading to longitudinal instability, tuner read back jumps and poorly configured low-level RF feedback loop

TRACKING SIMULATIONS NEAR HALF-INTEGER RESONANCE AT PEP-II

International Nuclear Information System (INIS)

Nosochkov, Yuri

2003-01-01

Beam-beam simulations predict that PEP-II luminosity can be increased by operating the horizontal betatron tune near and above a half-integer resonance. However, effects of the resonance and its synchrotron sidebands significantly enhance betatron and chromatic perturbations which tend to reduce dynamic aperture. In the study, chromatic variation of horizontal tune near the resonance was minimized by optimizing local sextupoles in the Interaction Region. Dynamic aperture was calculated using tracking simulations in LEGO code. Dependence of dynamic aperture on the residual orbit, dispersion and β distortion after correction was investigated

Analysis of the wake field effects in the PEP-II storage rings with extremely high currents

Energy Technology Data Exchange (ETDEWEB)

Novokhatski, A., E-mail: novo@slac.stanford.edu; Seeman, J.; Sullivan, M.

2014-01-21

We present the history and analysis of different wake field effects throughout the operational life of the PEP-II SLAC B-factory. Although the impedance of the high and low energy rings is small, the intense high-current beams generated a lot of power. The effects from these wake fields are: heating and damage of vacuum beam chamber elements like RF seals, vacuum valves, shielded bellows, BPM buttons and ceramic tiles; vacuum spikes, vacuum instabilities and high detector background; and beam longitudinal and transverse instabilities. We also discuss the methods used to eliminate these effects. Results of this analysis and the PEP-II experience may be very useful in the design of new storage rings and light sources.

Modeling Lost-Particle Accelerator Backgrounds in PEP-II Using LPTURTLE

CERN Document Server

Fieguth, Theodore; Kozanecki, Witold

2005-01-01

Background studies during the design, construction, commissioning, operation and improvement of BaBar and PEP-II have been greatly influenced by results from a program referred to as LPTURTLE (Lost Particle TURTLE a modified version of Decay TURTLE) which was originally conceived for the purpose of studying gas background for SLC. This venerable program is still in use today. We describe its use, capabilities and improvements and refer to current results now being applied to BaBar.

Impedance analysis of the PEP-II vacuum chamber

International Nuclear Information System (INIS)

Ng, C.K.; Weiland, T.

1995-05-01

The PEP-II high energy ring (HER) vacuum chamber consists of a copper tube with periodically spaced pumping slots. The impedance of the vacuum chamber due to the slots is analyzed. Both narrow-band and broadband impedances are considered as well as longitudinal and transverse components thereof. It is found that although the broad-band impedance is tolerable, the narrow-band impedance may exceed the instability limit given by the natural damping with no feedback system on. Traveling wave modes in the chamber are the major source of this high value narrow-band impedance. We also study the dependences of the impedance on the slot length and the geometrical cross section

5-Hydroxytryptamine 1A/7 and 4alpha receptors differentially prevent opioid-induced inhibition of brain stem cardiorespiratory function.

Science.gov (United States)

Wang, Xin; Dergacheva, Olga; Kamendi, Harriet; Gorini, Christopher; Mendelowitz, David

2007-08-01

Opioids evoke respiratory depression, bradycardia, and reduced respiratory sinus arrhythmia, whereas serotonin (5-HT) agonists stimulate respiration and cardiorespiratory interactions. This study tested whether serotonin agonists can prevent the inhibitory effects of opioids on cardiorespiratory function. Spontaneous and rhythmic inspiratory-related activity and gamma-aminobutyric acid (GABA) neurotransmission to premotor parasympathetic cardioinhibitory neurons in the nucleus ambiguus were recorded simultaneously in an in vitro thick slice preparation. The mu-opioid agonist fentanyl inhibited respiratory frequency. The 5-hydroxytryptamine 1A/7 receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin increased respiratory frequency by itself and also prevented the fentanyl-induced respiratory depression. The 5-hydroxytryptamine 4alpha agonist BIMU-8 did not by itself change inspiratory activity but prevented the mu-opioid-mediated respiratory depression. Both spontaneous and inspiratory-evoked GABAergic neurotransmission to cardiac vagal neurons were inhibited by fentanyl. 8-Hydroxy-2-(di-n-propylamino)tetralin inhibited spontaneous but not inspiratory-evoked GABAergic activity to parasympathetic cardiac neurons. However, 8-hydroxy-2-(di-n-propylamino)tetralin differentially altered the opioid-mediated depression of inspiratory-evoked GABAergic activity but did not change the opioid-induced reduction in spontaneous GABAergic neurotransmission. In contrast, BIMU-8 did not alter GABAergic neurotransmission to cardiac vagal neurons by itself but prevented the fentanyl depression of both spontaneous and inspiratory-elicited GABAergic neurotransmission to cardiac vagal neurons. In the presence of tetrodotoxin, the inhibition of GABAergic inhibitory postsynaptic currents with fentanyl is prevented by coapplication of BIMU-8, indicating that BIMU-8 acts at presynaptic GABAergic terminals to prevent fentanyl-induced depression. These results suggest that activation of 5

Responses of mRNA expression of PepT1 in small intestine to ...

African Journals Online (AJOL)

To study the effect of circulation small peptides concentration on mRNA expression in small intestine, graded amount of soybean small peptides (SSP) were infused into lactating goats through duodenal fistulas. Peptide-bound amino acid (PBAA) concentration in arterial plasma and the mRNA expression of PepT1 was ...

PEP3 overexpression shortens lag phase but does not alter growth rate in Saccharomyces cerevisiae exposed to acetic acid stress

Science.gov (United States)

Ding, Jun; Holzwarth, Garrett; Bradford, C. Samuel; Cooley, Ben; Yoshinaga, Allen S.; Patton-Vogt, Jana; Abeliovich, Hagai; Penner, Michael H.; Bakalinsky, Alan T.

2017-01-01

In fungi, two recognized mechanisms contribute to pH homeostasis: the plasma membrane proton-pumping ATPase that exports excess protons and the vacuolar proton-pumping ATPase (V-ATPase) that mediates vacuolar proton uptake. Here, we report that overexpression of PEP3 which encodes a component of the HOPS and CORVET complexes involved in vacuolar biogenesis, shortened lag phase in Saccharomyces cerevisiae exposed to acetic acid stress. By confocal microscopy, PEP3-overexpressing cells stained with the vacuolar membrane-specific dye, FM4-64 had more fragmented vacuoles than the wild-type control. The stained overexpression mutant was also found to exhibit about 3.6-fold more FM4-64 fluorescence than the wild-type control as determined by flow cytometry. While the vacuolar pH of the wild-type strain grown in the presence of 80 mM acetic acid was significantly higher than in the absence of added acid, no significant difference was observed in vacuolar pH of the overexpression strain grown either in the presence or absence of 80 mM acetic acid. Based on an indirect growth assay, the PEP3-overexpression strain exhibited higher V-ATPase activity. We hypothesize that PEP3 overexpression provides protection from acid stress by increasing vacuolar surface area and V-ATPase activity and, hence, proton-sequestering capacity. PMID:26051671

Indomethacin and diclofenac in the prevention of post-ERCP pancreatitis: a systematic review and meta-analysis of prospective controlled trials.

Science.gov (United States)

Patai, Árpád; Solymosi, Norbert; Mohácsi, László; Patai, Árpád V

2017-06-01

Diclofenac and indomethacin are the most studied drugs for preventing post-ERCP pancreatitis (PEP). However, there are no prospective, randomized multicenter trials with a sufficient number of patients for correct evaluation of their efficacy. Our aim was to evaluate all prospective trials published in full text that studied the efficacy of diclofenac or indomethacin and were controlled with placebo or non-treatment for the prevention of PEP in adult patients undergoing ERCP. Systematic search of databases (PubMed, Scopus, Web of Science, Cochrane) for relevant studies published from inception to 30 June 2016. Our meta-analysis of 4741 patients from 17 trials showed that diclofenac or indomethacin significantly decreased the risk ratio (RR) of PEP to 0.60 (95% confidence interval [CI], 0.46-0.78; P = .0001), number needed to treat (NNT) was 20, and the reduction of RR of moderate to severe PEP was 0.64 (95% CI, 0.43-0.97; P = .0339). The efficacy of indomethacin compared with diclofenac was similar (P = .98). The efficacy of indomethacin or diclofenac did not differ according to timing (P = .99) or between patients with average-risk and high-risk for PEP (P = .6923). The effect of non-rectal administration of indomethacin or diclofenac was not significant (P = .1507), but the rectal route was very effective (P = .0005) with an NNT of 19. The administration of indomethacin or diclofenac was avoided in patients with renal failure. Substantial adverse events were not detected. The use of rectally administered diclofenac or indomethacin before or closely after ERCP is inexpensive and safe and is recommended in every patient (without renal failure) undergoing ERCP. (Registration number: CRD42016042726, http://www.crd.york.ac.uk/prospero/.). Copyright © 2017 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

A unique power supply for the PEP II klystron at SLAC

International Nuclear Information System (INIS)

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 capacitor 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

PEP-II RF Cavity Revisited (LCC-0032)

Energy Technology Data Exchange (ETDEWEB)

Rimmer, R.

2004-03-23

This report describes the results of numerical simulations of the PEP-II RF cavity performed after the completion of the construction phase of the project and comparisons are made to previous calculations and measured results. These analyses were performed to evaluate new calculation techniques for the HOM distribution and RF surface heating that were not available at the time of the original design. These include the use of a high frequency electromagnetic element in ANSYS and the new Omega 3P code to study wall losses, and the development of broadband time domain simulation methods in MAFIA for the HOM loading. The computed HOM spectrum is compared with cavity measurements and observed beam-induced signals. The cavity fabrication method is reviewed, with the benefit of hindsight, and simplifications are discussed.

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

Science.gov (United States)

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.

RF feedback development for the PEP-II B Factory

Energy Technology Data Exchange (ETDEWEB)

Corredoura, P.; Sapozhnikov, L.; Tighe, R.

1994-06-01

In PEP-II heavy beam loading along with a relatively long revolution period combine to strongly drive lower coupled-bunch modes through interaction with the fundamental cavity mode. Feedback techniques can be applied to reduce the cavity impedance seen by the beam. Several RF feedback loops are planned to reduce the growth rates down to a level which can be damped by the relatively low power bunch-by-bunch longitudinal feedback system. This paper describes the RF feedback loops as well as hardware tests using a 500 kW klystron, analog and digital feedback loops, and a low power test cavity.

RF feedback development for the PEP-II B Factory

International Nuclear Information System (INIS)

Corredoura, P.; Sapozhnikov, L.; Tighe, R.

1994-06-01

In PEP-II heavy beam loading along with a relatively long revolution period combine to strongly drive lower coupled-bunch modes through interaction with the fundamental cavity mode. Feedback techniques can be applied to reduce the cavity impedance seen by the beam. Several RF feedback loops are planned to reduce the growth rates down to a level which can be damped by the relatively low power bunch-by-bunch longitudinal feedback system. This paper describes the RF feedback loops as well as hardware tests using a 500 kW klystron, analog and digital feedback loops, and a low power test cavity

Study of heavy quark production with the Mark II at PEP

International Nuclear Information System (INIS)

Abrams, G.; Amidei, D.; Baden, A.

1983-10-01

The methods adopted by the Mark II collaboration to study heavy quark production at PEP are described. Two complementary techniques are used: D* tagging using the decay chain D* + . D 0 π + , D 0 → K - π + , and inclusive lepton tagging using the characteristic p/sub T/ distributions to distinguish contributions from b and c quarks. These techniques are used to derive information about heavy quark fragmentation and about the weak coupling of heavy quarks

Psycho-education with problem solving (PEPS therapy for adults with personality disorder: A pragmatic multi-site community-based randomised clinical trial

Directory of Open Access Journals (Sweden)

Duggan Conor

2011-08-01

Full Text Available Abstract Background Impairment in social functioning is a key component of personality disorder. Therefore psycho-education and problem solving (PEPS therapy may benefit people with this disorder. Psycho-education aims to educate, build rapport, and motivate people for problem solving therapy. Problem solving therapy aims to help clients solve interpersonal problems positively and rationally, thereby improving social functioning and reducing distress. PEPS therapy has been evaluated with community adults with personality disorder in an exploratory trial. At the end of treatment, compared to a wait-list control group, those treated with PEPS therapy showed better social functioning, as measured by the Social Functioning Questionnaire (SFQ. A definitive evaluation is now being conducted to determine whether PEPS therapy is a clinically and cost-effective treatment for people with personality disorder Methods This is a pragmatic, two-arm, multi-centre, parallel, randomised controlled clinical trial. The target population is community-dwelling adults with one or more personality disorder, as identified by the International Personality Disorder Examination (IPDE. Inclusion criteria are: Living in the community (including residential or supported care settings; presence of one or more personality disorder; aged 18 or over; proficiency in spoken English; capacity to provide informed consent. Exclusion criteria are: Primary diagnosis of a functional psychosis; insufficient degree of literacy, comprehension or attention to be able to engage in trial therapy and assessments; currently engaged in a specific programme of psychological treatment for personality disorder or likely to start such treatment during the trial period; currently enrolled in any other trial. Suitable participants are randomly allocated to PEPS therapy plus treatment as usual (TAU or TAU only. We aim to recruit 340 men and women. The primary outcome is social functioning as measured

Study of an instability of the PEP-II positron beam (Ohmi effect and Multipactoring)

Energy Technology Data Exchange (ETDEWEB)

Heifets, S A [Stanford Linear Accelerator Center, Menlo Park, CA (United States)

1996-08-01

The processes defining the density distribution of the photoelectrons are quite complicated. In this study, a simplified model of the instability was used to get a quick estimate of the growth rate of the instability and the relative importance of the parameters, as has been done in Ohmi`s paper. The production rate and dynamics of the photoelectrons are studied for the PEP-II parameters. The growth rate of the transverse instability driven by the primary photoelectrons is of the order of 0.7 msec for the PEP-II parameters. The multipactoring at resonance currents cannot produce large electron density due to the final energy spread caused by the finite bunch length and the intrinsic energy spread of the secondary electrons. Production of the secondary electrons may lead to large average densities. The ion can be produced in electron collisions with the residual gas with density of the order of the electron density. (G.K.)

Search for scalar electrons at PEP

International Nuclear Information System (INIS)

Wilson, R.J.

1983-08-01

Experimental results from e + e - reactions at the Positron Electron Project (PEP) using the High Resolution Spectrometer (HRS) are presented. Events with two electrons, and no other charged particles, in the final state are studied. Limits are given for the production of scalar-electrons predicted by models based on supersymmetry. In particular the pair production of such particles through s-channel single photon annihilation and t-channel inelastic scattering is considered. The data are well described by quantum electrodynamics (QED) but we observe one event which is also consistent with a supersymmetric model. Using this single event we find that the mass, M/sub se/, of these scalar-electrons es excluded, to 95% CL, in the range 1.8 less than or equal to M/sub se/ less than or equal to 14.2 GeV/c 2 . A description of the HRS detector is given with particular emphasis on the electronic trigger system

Rottlerin Inhibits ROS Formation and Prevents NFκB Activation in MCF-7 and HT-29 Cells

Directory of Open Access Journals (Sweden)

Emanuela Maioli

2009-01-01

Full Text Available Rottlerin, a polyphenol isolated from Mallotus Philippinensis, has been recently used as a selective inhibitor of PKC δ, although it can inhibit many kinases and has several biological effects. Among them, we recently found that Rottlerin inhibits the Nuclear Factor κB (NFκB, activated by either phorbol esters or H2O2. Because of the redox sensitivity of NFκB and on the basis of Rottlerin antioxidant property, we hypothesized that Rottlerin could prevent NFκB activation acting as a free radicals scavenger, as other natural polyphenols. The current study confirms the antioxidant property of Rottlerin against the 2,2-diphenyl-1-picrylhydrazyl radical (DPPH in vitro and against oxidative stress induced by H2O2 and by menadione in culture cells. We also demonstrate that Rottlerin prevents TNFα-dependent NFκB activation in MCF-7 cells and in HT-29 cells transfected with the NFκB-driven plasmid pBIIX-LUC, suggesting that Rottlerin can inhibit NFκB via several pathways and in several cell types.

Dendritic cells induce specific cytotoxic T lymphocytes against prostate cancer TRAMP-C2 cells loaded with freeze- thaw antigen and PEP-3 peptide.

Science.gov (United States)

Liu, Xiao-Qi; Jiang, Rong; Li, Si-Qi; Wang, Jing; Yi, Fa-Ping

2015-01-01

Prostate cancer is the most common cancer in men. In this study, we investigated immune responses of cytotoxic T lymphocytes (CTLs) against TRAMP-C2 prostate cancer cells after activation by dendritic cells (DCs) loaded with TRAMP-C2 freeze-thaw antigen and/or PEP-3 peptide in vitro. Bone marrow-derived DC from the bone marrow of the C57BL/6 were induced to mature by using the cytokine of rhGM-CSF and rhIL-4, and loaded with either the freeze-thaw antigen or PEP-3 peptide or both of them. Maturation of DCs was detected by flow cytometry. The killing efficiency of the CTLs on TRAMP-C2 cells were detected by flow cytometry, CCK8, colony formation, transwell migration, and wound-healing assay. The levels of the IFN-γ, TNF-β and IL-12 were measured by enzyme-linked immunosorbent assay (ELISA). Compared with the unloaded DCs, the loaded DCs had significantly increased expression of several phenotypes related to DC maturation. CTLs activated by DCs loaded with freeze-thaw antigen and PEP-3 peptide had more evident cytotoxicity against TRAMP-C2 cells in vitro. The secretion levels of IFN-γ, TNF-β and IL-12, secreted by DCs loaded with antigen and PEP-3 and interaction with T cells, were higher than in the other groups. Our results suggest that the CTLs activated by DCs loaded with TRAMP-C2 freeze-thaw antigen and PEP-3 peptide exert a remarkable killing efficiency against TRAMP-C2 cells in vitro.

The PEP electron-positron ring

International Nuclear Information System (INIS)

Rees, J.R.

1988-01-01

The first stage of the positron-electron-proton (PEP) colliding-beam system which has been under joint study by a Lawrence Berkeley Laboratory-Stanford Linear Accelerator Center team for the past two years, will be the electron-positron storage ring. The physics justification for the e + e/sup minus/ ring is summarized briefly and the proposed facility is described. The ring will have six arcs having gross radii of about 220 m and six interaction regions located at the centers of straight sections about 130 m long. The longitudinal distance left free for experimental apparatus at the intersection regions will be 20 m. The range of operating beam energies will be from 5 GeV to 15 GeV. The design luminosity at 15 GeV will be 10 32 cm/sup minus 2/s/sup minus 1/, and the luminosity will vary approximately as the square of the beam energy. Alternative methods under consideration for adjusting the beam cross-section are discussed. The designs of the storage ring subsystems and of the conventional facilities including the experimental halls at the interaction regions are described

Scaling of gain with energy spread and energy in the PEP FEL

International Nuclear Information System (INIS)

Fisher, A.S.

1992-01-01

The Sag Harbor paper on the PEP FEL discusses the scaling of various FEL parameters with energy spread σ var-epsilon . I will repeat some of this material here and then examine the benefit of increasing the energy spread. How much energy spread can be achieved with damping wigglers is the next topic. Finally, I consider the dependence of gain and saturation length on beam energy and undulator field

The key determinants of perceived external prestige (PEP) – Qualitative research approach

OpenAIRE

Tamara Sušanj Šulentić; Krešimir Žnidar; Jurica Pavičić

2017-01-01

Perceived external prestige (PEP) is a well-known concept oriented towards describing the way members of a certain organization interpret and assess their organisational reputation. Such perception can significantly affect employees’ identification and loyalty to the organisation as well as their job satisfaction and work performance. According to the social identification theory, people define themselves and others with respect to their belonging to a particular group or organization, and th...

Bunch-by-bunch longitudinal feedback system for PEP-II

International Nuclear Information System (INIS)

Oxoby, G.; Claus, R.; Fox, J.

1994-06-01

This paper describes the implementation of the bunch-by-bunch longitudinal feedback system for the PEP-II B Factory. Bunch spacing down to 2 ns is achieved using 500 Megasamples per second A/D and D/A converters, and AT ampersand T 1610 Digital Signal Processors are integrated to run a downsampled feedback algorithm for each bunch in parallel. This general purpose programmable system, packaged in VXI and VME, is modular and scalable to offer portability to other accelerator rings. The control and monitoring hardware and software architecture have been developed to provide ease of operation as well as diagnostic tools for machine physics

Numerical simulation of the PEP-II beam position monitor

Energy Technology Data Exchange (ETDEWEB)

Kurita, N; Martin, D; Ng, C -K; Smith, S [Stanford Linear Accelerator Center, Menlo Park, CA (United States); Weiland, T

1996-08-01

We use MAFIA to analyze the PEP-II button-type beam position monitor (BPM). Employing proper termination of the BPM into a coaxial cable, the output signal at the BPM is determined. Thus the issues of signal sensitivity and power output can be addressed quantitatively, including all transient effects and wakefields. Besides this first quantitative analysis of a true BPM 3D structure, we find that internal resonant modes are a major source of high value narrow-band impedances. The effects of these resonances on coupled-bunch instabilities are discussed. An estimate of the power dissipation in the ceramic vacuum seal under high current operation is given. (author)

Beam-beam effects for the PEP-II B Factory

International Nuclear Information System (INIS)

Furman, M.A.; Eden, J.R.

1993-05-01

We present a summary of a fairly extensive study of beam-beam issues that arise in the design of PEP-II. Most of these studies are carried out with ''strong-strong'' multiparticle tracking simulations. We focus on: choice of nominal beam-beam parameter, strength of the parasitic collisions, injection issues, performance and tradeoffs with unequal beam-beam parameters. We comment only briefly on beam lifetime. We conclude that: the beams are sufficiently well separated so that the parasitic collisions are effectively weak; that small inequalities in the beam-beam parameters may imply more comfortable performance margins; and that vertical injection with vertical beam separation is more comfortable than horizontal

Numerical simulation of the PEP-II beam position monitor

International Nuclear Information System (INIS)

Kurita, N.; Martin, D.; Ng, C.K.; Smith, S.; Weiland, T.

1995-09-01

The authors use MAFIA to analyze the PEP-II button-type beam position monitor (BPM). Employing proper termination of the BPM into a coaxial cable, the output signal at the BPM is determined. Thus the issues of signal sensitivity and power output can be addressed quantitatively, including all transient effects and wakefields. Besides this first quantitative analysis of a true BPM 3D structure, they find that internal resonant modes are a major-source of high value narrow-band impedances. The effects of these resonances on coupled-bunch instabilities are discussed. An estimate of the power dissipation in the ceramic vacuum seal under high current operation is given

Regulatory T-Cell Augmentation or Interleukin-17 Inhibition Prevents Calcineurin Inhibitor-Induced Hypertension in Mice.

Science.gov (United States)

Chiasson, Valorie L; Pakanati, Abhinandan R; Hernandez, Marcos; Young, Kristina J; Bounds, Kelsey R; Mitchell, Brett M

2017-07-01

The immunosuppressive calcineurin inhibitors cyclosporine A and tacrolimus alter T-cell subsets and can cause hypertension, vascular dysfunction, and renal toxicity. We and others have reported that cyclosporine A and tacrolimus decrease anti-inflammatory regulatory T cells and increase proinflammatory interleukin-17-producing T cells; therefore, we hypothesized that inhibition of these effects using noncellular therapies would prevent the hypertension, endothelial dysfunction, and renal glomerular injury induced by calcineurin inhibitor therapy. Daily treatment of mice with cyclosporine A or tacrolimus for 1 week significantly decreased CD4 + /FoxP3 + regulatory T cells in the spleen and lymph nodes, as well as induced hypertension, vascular injury and dysfunction, and glomerular mesangial expansion in mice. Daily cotreatment with all-trans retinoic acid reported to increase regulatory T cells and decrease interleukin-17-producing T cells, prevented all of the detrimental effects of cyclosporine A and tacrolimus. All-trans retinoic acid also increased regulatory T cells and prevented the hypertension, endothelial dysfunction, and glomerular injury in genetically modified mice that phenocopy calcineurin inhibitor-treated mice (FKBP12-Tie2 knockout). Treatment with an interleukin-17-neutralizing antibody also increased regulatory T-cell levels and prevented the hypertension, endothelial dysfunction, and glomerular injury in cyclosporine A-treated and tacrolimus-treated mice and FKBP12-Tie2 knockout mice, whereas an isotype control had no effect. Augmenting regulatory T cells and inhibiting interleukin-17 signaling using noncellular therapies prevents the cardiovascular and renal toxicity of calcineurin inhibitors in mice. © 2017 American Heart Association, Inc.

Simulation of PEP-II Accelerator Backgrounds Using TURTLE

CERN Document Server

Barlow, Roger J; Kozanecki, Witold; Majewski, Stephanie; Roudeau, Patrick; Stocchi, Achille

2005-01-01

We present studies of accelerator-induced backgrounds in the BaBar detector at the SLAC B-Factory, carried out using a modified version ofthe 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 programme of beam-gas and luminosity-background simulations, that include the effects of the detector solenoidal field, detailed modelling of limiting apertures in both collider rings, and optimization of the betatron collimation scheme in the presence of large transverse tails.

Dual Power Supplies for PEP-II Injection Kickers

CERN Document Server

Olszewski, Joseph; Iverson, Richard; Kulikov, Artem; Pappas, Chris

2005-01-01

Originally the PEP-II injection kickers where powered by one power supply. Since the kicker magnets where not perfectly matched, the stored beam got excited by about 7% of the maximum kicker amplitude. This led to luminosity losses which were especially obvious for trickle injection when the detector is on for data taking. Therefore two independant power supplies with thyratrons in the tunnel next to the kicker magnet were installed. This also reduces the necessary power by about a factor of five since there are no long cables that have to be charged. The kickers are now independantly adjustable to eliminate any non-closure of the kicker system and therefore excitation of the stored beam. Setup, commissioning and fine tuning of this system are discussed.

Dual Power Supplies for PEP-II Injection Kickers

Energy Technology Data Exchange (ETDEWEB)

Olszewski, J; Decker, F.-J.; Iverson, R.H.; Kulikov, A.; Pappas, C.; /SLAC

2005-05-25

Originally the PEP-II injection kickers were powered by one power supply. Since the kicker magnets where not perfectly matched, the stored beam got excited by about 7% of the maximum kicker amplitude. This led to luminosity losses which were especially obvious for trickle injection when the detector is on for data taking. Therefore two independent power supplies with thyratrons in the tunnel next to the kicker magnet were installed. This also reduces the necessary power by about a factor of four since there are no long cables that have to be charged. The kickers are now independently adjustable to eliminate any non-closure of the kicker system and therefore excitation of the stored beam. Setup, commissioning and fine tuning of this system are discussed.

Dual Power Supplies for PEP-II Injection Kickers

International Nuclear Information System (INIS)

Olszewski, J; Decker, F.-J.; Iverson, R.H.; Kulikov, A.; Pappas, C.; SLAC

2005-01-01

Originally the PEP-II injection kickers were powered by one power supply. Since the kicker magnets where not perfectly matched, the stored beam got excited by about 7% of the maximum kicker amplitude. This led to luminosity losses which were especially obvious for trickle injection when the detector is on for data taking. Therefore two independent power supplies with thyratrons in the tunnel next to the kicker magnet were installed. This also reduces the necessary power by about a factor of four since there are no long cables that have to be charged. The kickers are now independently adjustable to eliminate any non-closure of the kicker system and therefore excitation of the stored beam. Setup, commissioning and fine tuning of this system are discussed

Induced-fit Mechanism for Prolyl Endopeptidase

Energy Technology Data Exchange (ETDEWEB)

Li, Min; Chen, Changqing; Davies, David R.; Chiu, Thang K. (NIH); (LSU); (Chinese Aca. Sci.)

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 to 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.

PEGASYS---A proposed internal target facility for the PEP storage ring

International Nuclear Information System (INIS)

Van Biber, K.

1988-07-01

A proposal for an integral gas-jet target and forward spectrometer for the PEP storage ring is described. The beam structure, allowable, luminosity (L = 10 33 cm/sup /minus/2/s/sup /minus/1/ for H 2 , D 2 ) and energy (E/sub e/ ≤ 15 GeV) make the ring ideal for multiparticle coincidence studies in the scaling regime, and where perturbative QCD may be an apt description of some exclusive and semi-inclusive reactions. 14 refs., 7 figs

Effect of CO2 enrichment and high photosynthetic photon flux densities (PPFD) on rubisco and PEP-case activities of in vitro cultured strawberry plants

International Nuclear Information System (INIS)

Desjardins, Y.; Beeson, R.; Gosselin, A.

1989-01-01

Standard growing conditions in vitro (low light and CO 2 ) are not conducive to autotrophy. An experiment was conducted to improve photosynthesis in vitro in the hope of increasing survival in acclimatization. A factorial experiment was elaborated where CO 2 and PPFD were supplied to in vitro cultured strawberry plants in the rooting stage. Activities of carboxylating enzymes were determined after 4 weeks of culture. The activities of non-activated and activated rubisco and PEP-Case were measured after extraction of the enzymes and a reaction with NaH 14 CO 3 followed by scintillation counting spectroscopy. High CO 2 concentration significantly increased net assimilation rates (NAR) by 165% over the control for both 1650 and 3000 ppm CO 2 . High PPFD only increased NAR by 12 and 35% for 150 and 250 μmol·m -2 ·s -1 respectively over the control. Plants grown at 3000 ppm CO 2 had the highest level of chlorophyll/g FW with 97% more than the control. The activity of PEP-Case was the highest at high light levels and high CO 2 with rates of 1.65 for 1650 ppm versus 1.22 mmol CO 2 mg -1 chl. h -1 at 250 μmol·m -2 ·s -1 . There was no difference in PEP activity at low light levels. The rubisco activity was lower at 1650 and 3000 ppm CO 2 . Increases in NAR correlate more closely to the PEP-Case than to Rubisco activity. Physiological significance of high activity of PEP-Case over rubisco will be discussed

Inhibition of the Unfolded Protein Response Mechanism Prevents Cardiac Fibrosis.

Directory of Open Access Journals (Sweden)

Jody Groenendyk

Full Text Available Cardiac fibrosis attributed to excessive deposition of extracellular matrix proteins is a major cause of heart failure and death. Cardiac fibrosis is extremely difficult and challenging to treat in a clinical setting due to lack of understanding of molecular mechanisms leading to cardiac fibrosis and effective anti-fibrotic therapies. The objective in this study was to examine whether unfolded protein response (UPR pathway mediates cardiac fibrosis and whether a pharmacological intervention to modulate UPR can prevent cardiac fibrosis and preserve heart function.We demonstrate here that the mechanism leading to development of fibrosis in a mouse with increased expression of calreticulin, a model of heart failure, stems from impairment of endoplasmic reticulum (ER homeostasis, transient activation of the unfolded protein response (UPR pathway and stimulation of the TGFβ1/Smad2/3 signaling pathway. Remarkably, sustained pharmacologic inhibition of the UPR pathway by tauroursodeoxycholic acid (TUDCA is sufficient to prevent cardiac fibrosis, and improved exercise tolerance.We show that the mechanism leading to development of fibrosis in a mouse model of heart failure stems from transient activation of UPR pathway leading to persistent remodelling of cardiac tissue. Blocking the activation of the transiently activated UPR pathway by TUDCA prevented cardiac fibrosis, and improved prognosis. These findings offer a window for additional interventions that can preserve heart function.

Inhibition of fatty acid synthase prevents preadipocyte differentiation

International Nuclear Information System (INIS)

Schmid, Bernhard; Rippmann, Joerg F.; Tadayyon, Moh; Hamilton, Bradford S.

2005-01-01

Inhibition of fatty acid synthase (FAS) reduces food intake in rodents. As adipose tissue expresses FAS, we sought to investigate the effect of reduced FAS activity on adipocyte differentiation. FAS activity was suppressed either pharmacologically or by siRNA during differentiation of 3T3-L1 cells. Cerulenin (10 μM), triclosan (50 μM), and C75 (50 μM) reduced dramatically visible lipid droplet accumulation, while incorporation of [1- 14 C]acetate into lipids was reduced by 75%, 70%, and 90%, respectively. Additionally, the substances reduced FAS, CEBPα, and PPARγ mRNA by up to 85% compared to that of control differentiated cells. Transient transfection with FAS siRNA suppressed FAS mRNA and FAS activity, and this was accompanied by reduction of CEBPα and PPARγ mRNA levels, and complete prevention of lipid accumulation. CD36, a late marker of differentiation, was also reduced. Together, these results suggest that FAS generated signals may be essential to support preadipocyte differentiation

Operation of the PEP transverse beam feedback

International Nuclear Information System (INIS)

Olson, C.W.; Paterson, J.M.; Pellegrin, J.L.; Rees, J.R.

1981-02-01

The PEP Storage Ring has been equipped with a wide band beam feedback system capable of damping the vertical and horizontal motion of six bunches. The oscillation detection is done at a symmetry point on the Storage Ring and feedback is applied at the same location one orbital period later. The signal is synchronously gated and the system appears as twelve independent feedback loops, operating on the two coordinates of each of the six bunches. Two beam deflection electrodes are driven each by a low-Q push-pull amplifier which is tuned at the 72nd harmonic of the revolution frequency and suppressed-carrier modulation is generated by a sequence of the detected bunch oscillations. The design parameters are reviewed as well as the salient features of the hardware, and the impact of this system on the machine operation is evaluated in the light of experimental results

The PEP-II abort kicker system

International Nuclear Information System (INIS)

Lamare, J de; Donaldson, A.; Kulikov, A. Lipari, J.

1997-07-01

The PEP-II project has two storage rings. The HER (High Energy Ring) has up to 1.48 A of electron beam at 9 GeV, and the LER (Low Energy Ring) has up to 2.14 A of positron beam at 3.1 GeV. To protect the HER and LER beam lines in the event of a ring component failure, each ring has an abort kicker system which directs the beam into a dump when a failure is detected. Due to the high current of the beams, the beam kick is tapered from 100% to 80% in 7.33 uS (the beam transit time around the time). This taper distributes the energy evenly across the window which separates the ring from the beam dump such that the window is not damaged. The abort kicker trigger is synchronized with the ion clearing gap of the beam allowing for the kicker field to rise from 0-80% in 370 nS. This report discusses the design of the system controls, interlocks, power supplies, and modulator

Ba anti Bar status report on the design of a detector for the study of CP violation at PEP-II at SLAC

International Nuclear Information System (INIS)

1993-06-01

Experiments designed to measure CP-violating asymmetries in the B meson system must emphasize exclusive state reconstruction with the highest possible resolution and efficiency. In the case of B 0 mesons produced in pairs at the Υ(4S) resonance at an asymmetric e + e - storage ring, this capability must be accompanied by precise vertex reconstruction in the direction of the e + e - beams (henceforth the z direction). These are difficult requirements, beyond the scope of any existing storage ring detector. The challenge of designing an asymmetric storage ring capable of producing the large number of neutral B meson pairs required to measure CP-violating asymmetries in decays to CP eigenstates has been handsomely met in the PEP-II design. As the first asymmetric e + e - storage ring, PEP-II presents a novel set of experimental challenges to a 4π detector. This Status Report describes the design of a new detector fully capable of exploiting the physics opportunities provided by PEP-II

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.

Science.gov (United States)

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.

The PEP-II Lower Pressure HER Vacuum Chamber

International Nuclear Information System (INIS)

DeBarger, S.; Metcalfe, S.; Seeman, J.; Sullivan, M.; Wienands, U.; Wright, D.

2006-01-01

This new vacuum chamber has been installed from 12 to 21 meters upstream of the BaBar detector in the PEP-II High Energy Ring (HER) to reduce lost particle backgrounds. The backgrounds from HER now dominate the backgrounds in the BaBar detector and the present vacuum pressure is 1 x 10 -9 Torr. The new chamber will increase the pumping significantly by adding 18 x 2000 l/s titanium sublimation pumps to the existing 5 x 440 l/s ion pumps, and is expected to reduce the pressure by about a factor of five. Features of the chamber include improved water cooling, improved vacuum conductance through copper RF screens featuring over 15,000 small square holes and the ability to sublimate titanium while the beam is still on

The electron-cloud instability in PEP-II: An update

International Nuclear Information System (INIS)

Furman, M.A.; Lambertson, G.R.

1997-05-01

The authors present an update on the estimate of the growth time of the multi-bunch transverse instability in the PEP-II collider arising from the interaction of the positron beam with the accumulated electron cloud. They estimate the contributions to the growth rate arising from the dipole magnets and from the pumping straight sections. They emphasize those quantities upon which the instability is most sensitive. The simulation includes measured data on the secondary emission yield for TiN-coated samples of the actual vacuum chamber. Although the analysis is still in progress, they conclude that the instability risetime is of order 1 ms, which is well within the range controllable by the feedback system

Coherent x-rays from PEP

International Nuclear Information System (INIS)

Baird, S.; Nuhn, H.-D.; Tatchyn, R.; Winick, H.; Fisher, A.S.; Gallardo, J.C.; Pellegrini, C.

1991-01-01

This paper explores the use of a large-circumference, high-energy, electron-positron collider such as PEP to drive a free-electron laser (FEL), producing high levels of coherent power at short wavelengths. The author consider Self-Amplified Spontaneous Emission (SASE), in which electron bunches with low emittance, high peak current and small energy spread radiate coherently in a single passthrough a long undulator. As the electron beam passes down the undulator, its interaction with the increasingly intense spontaneous radiation causes a bunch density modulation at the optical wavelength, resulting in stimulated emissional growth of coherent power in a single pass. The need for optical-cavity mirrors, which place a lower limit on the wavelength of a conventional FEL oscillator, is avoided. The authors explore various combinations of electron-beam and undulator parameters, as well as special undulator designs and optical klystrons (OK), to reach high average or peak coherent power at wavelengths around 40 angstrom by achieving significant exponential gain or full saturation. Examples are presented for devices that achieve high peak coherent power (up to about 400 MW) with lower average coherent power (about 20 mW) and other devices which produce a few watts of average coherent power

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

Science.gov (United States)

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.

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

Science.gov (United States)

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.

Injection system for the PEP II asymmetric B Factory at SLAC

International Nuclear Information System (INIS)

Fieguth, T.; Bloom, E.; Bulos, F.; Davies-White, W.; Donald, M.; Fairfield, K.; Godfrey, G.; Holtzapple, R.; Ronan, M.; Zisman, M.

1992-01-01

The asymmetric energy B Factory proposed as an upgrade of PEP at Stanford Linear Accelerator Center will require a highly reliable and efficient injection system. The conceptual design has shown the feasibility of extracting 9 GeV electrons and 3.1 GeV positrons from the existing linac and injecting equal charges into 1658 buckets in each of the two rings of the collider. An injection study group has continued the development and study of this proposal and has generated workable designs for many related systems and subsystems. (author) 3 refs.; 4 figs.; 2 tabs

Dietary Intervention with β-Lactoglobulin-Derived Peptides and a Specific Mixture of Fructo-Oligosaccharides and Bifidobacterium breve M-16V Facilitates the Prevention of Whey-Induced Allergy in Mice by Supporting a Tolerance-Prone Immune Environment

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Atanaska I. Kostadinova

2017-10-01

Full Text Available Cow’s milk allergy (CMA prevails in infants and brings increased risk of developing other allergic diseases. Oral administration of specific β-lactoglobulin (BLG-derived peptides (PepMix and a specific blend of short- and long-chain fructo-oligosaccharides and Bifidobacterium breve M-16V (FF/Bb was found to partially prevent CMA development in mice. In this study, we aimed to expand the knowledge on the preventive potential and the underlying mechanisms of this approach. Three-week-old female C3H/HeOuJ mice were orally exposed to PepMix±FF/Bb prior to a 5-week oral sensitization with whole whey and cholera toxin as an adjuvant. The acute allergic skin response was determined after an intradermal challenge with whole whey protein. Following an oral challenge with whey, regulatory T cells (Tregs in the small intestine lamina propria (SI-LP and mRNA expression of immune markers in the Peyer’s patches (PP were investigated. The early impact of PepMix and FF/Bb interventions on the immune system during the oral tolerance (OT induction phase was investigated after the last OT administration. Pre-exposing mice to PepMix+FF/Bb partially prevented the acute allergic skin response compared to PBS and increased Tregs and activated T cells in the SI-LP compared to sham-sensitized mice. It also increased the mRNA expression of Tbet over GATA3 in the PP of whey-sensitized mice. Directly upon the 6-day OT phase, FF/Bb intervention enhanced cecal content levels of propionic and butyric acid in PepMix-fed mice and the former was positively correlated with Foxp3+ cell numbers in the colon. In the PP of PepMix+FF/Bb-exposed mice, IL-22 mRNA expression increased and IL-10 followed the same tendency, while the Foxp3 expression was increased over GATA3 and RorγT. In the colon, the Tbet mRNA expression increased over GATA3, while IL-22 decreased. In addition, the Foxp3+/GATA3+ and regulatory/effector T cell ratios in the mesenteric lymph nodes and the CD11b

Atorvastatin prevents Aβ oligomer-induced neurotoxicity in cultured rat hippocampal neurons by inhibiting Tau cleavage

Science.gov (United States)

Sui, Hai-juan; Zhang, Ling-ling; Liu, Zhou; Jin, Ying

2015-01-01

Aim: The proteolytic cleavage of Tau is involved in Aβ-induced neuronal dysfunction and cell death. In this study, we investigated whether atorvastatin could prevent Tau cleavage and hence prevent Aβ1–42 oligomer (AβO)-induced neurotoxicity in cultured cortical neurons. Methods: Cultured rat hippocampal neurons were incubated in the presence of AβOs (1.25 μmol/L) with or without atorvastatin pretreatment. ATP content and LDH in the culture medium were measured to assess the neuronal viability. Caspase-3/7 and calpain protease activities were detected. The levels of phospho-Akt, phospho-Erk1/2, phospho-GSK3β, p35 and Tau proteins were measured using Western blotting. Results: Treatment of the neurons with AβO significantly decreased the neuronal viability, induced rapid activation of calpain and caspase-3/7 proteases, accompanied by Tau degradation and relatively stable fragments generated in the neurons. AβO also suppressed Akt and Erk1/2 kinase activity, while increased GSK3β and Cdk5 activity in the neurons. Pretreatment with atorvastatin (0.5, 1, 2.5 μmol/L) dose-dependently inhibited AβO-induced activation of calpain and caspase-3/7 proteases, and effectively diminished the generation of Tau fragments, attenuated synaptic damage and increased neuronal survival. Atorvastatin pretreatment also prevented AβO-induced decreases in Akt and Erk1/2 kinase activity and the increases in GSK3β and Cdk5 kinase activity. Conclusion: Atorvastatin prevents AβO-induced neurotoxicity in cultured rat hippocampal neurons by inhibiting calpain- and caspase-mediated Tau cleavage. PMID:25891085

Secondary Electron Yield Measurements and Groove Chambers Tests in the PEP-II Beam Line Straights Sections

International Nuclear Information System (INIS)

Pivi, M

2008-01-01

Beam instability caused by the electron cloud has been observed in positron and proton storage rings and it is expected to be a limiting factor in the performance of the positron Damping Ring (DR) of future Linear Colliders such as ILC and CLIC [1, 2]. In the Positron Low Energy Ring (LER) of the PEP-II accelerator, we have installed vacuum chambers with rectangular grooves in a straight magnetic-free section to test this promising possible electron cloud mitigation technique. We have also installed a special chamber to monitor the secondary electron yield of TiN and TiZrV (NEG) coating, Copper, Stainless Steel and Aluminum under the effect of electron and photon conditioning in situ in the beam line. In this paper, we describe the ongoing R and D effort to mitigate the electron cloud effect for the ILC damping ring, the latest results on in situ secondary electron yield conditioning and recent update on the groove tests in PEP-II

A proposed orbit and vertical dispersion correction system for PEP

International Nuclear Information System (INIS)

Close, E.; Cornacchia, M.; King, A.S.; Lee, M.J.

1978-07-01

The proposed arrangement of position monitors and dipole magnets for the closed orbit correction system in PEP is described. The computer code ALIGN, which simulates and corrects closed orbit displacements, has been used to study the most effective layout of monitors and correctors. The vertical dispersion function has been computed before and after closed orbit correction. The results indicate that the residual vertical dispersion after the orbit is corrected could exceed the tolerable values. A correction procedure for the vertical dispersion has been studied with the compute code CO-OP and this scheme of correction has been verified experimentally in SPEAR. 9 refs., 8 figs., 2 tabs

Commissioning experience from PEP-II HER longitudinal feedback

International Nuclear Information System (INIS)

Prabhakar, S.; Teytelman, D.; Fox, J.; Young, A.; Corredoura, P.; Tighe, R.

1998-06-01

The DSP-based bunch-by-bunch feedback system installed in the PEP-II HER has been used to damp HOM-induced instabilities at beam currents up to 6-5 mA during commissioning. Beam pseudospectra calcualted from feedback system data indicate the presence of coupled bunch modes that oincide with the 0-M-2 cavity HOM. Bunch current and synchronous phase measurements are also extracted from the data. These measurements reveal the impedance seen by the beam at revolution harmonics. The impedance peak at 3*frev indicates incorrect parking of the idle cavities, and explains the observed instability of mode 3. Bunch synchrotron tunes are calculated from lorentzian fits to the data. Bunch-to-bunch time variation due to the cavity transient is shown to be large enough to result in Landau damping of coupled bunch modes

Knowledge and acceptability of alternative HIV prevention bio-medical products among MSM who bareback.

Science.gov (United States)

Nodin, N; Carballo-Diéguez, A; Ventuneac, A M; Balan, I C; Remien, R

2008-01-01

Condom use is the best available strategy to prevent HIV infection during sexual intercourse. However, since many people choose not to use condoms in circumstances in which HIV risk exists, alternatives to condom use for HIV prevention are needed. Currently there are several alternative bio-medical HIV-prevention products in different stages of development: microbicides, vaccines, post-exposure prophylaxis (PEP) and pre-exposure prophylaxis (PrEP). Seventy-two men who have sex with men (MSM) who took part in a study on Internet use and intentional condomless anal intercourse were asked about these four products during a semi-structured interview. The questions explored knowledge and acceptability of all the products and willingness to participate in microbicide and vaccine trials. Qualitative analysis of the data suggests that these men had virtually no knowledge of PrEP, very limited knowledge of microbicides, some information about PEP and considerably more knowledge about vaccines. Reactions towards the products were generally positive except for PrEP, for which reactions were polarized as either enthusiastic or negative. With the exception of PrEP, many men expressed willingness to use the products in the future. Most men would be willing to participate in trials for microbicides and vaccines if given basic reassurances. Concerns over negative side effects and preoccupation with possible infection were some of the motives given for non-willingness to participate in a vaccine trial. These results should inform the development of future trials of biomedical prevention products.

ACL Injury Prevention Training Results in Modification of Hip and Knee Mechanics During a Drop-Landing Task.

Science.gov (United States)

Pollard, Christine D; Sigward, Susan M; Powers, Christopher M

2017-09-01

Injury prevention training has been shown to be effective in reducing the incidence of noncontact anterior cruciate ligament (ACL) injury; however, the underlying reason for the success of these training programs is unclear. To investigate whether an ACL injury prevention program that has been shown to reduce the incidence of ACL injury alters sagittal plane hip and knee biomechanics during a drop-landing task. Descriptive laboratory study. Thirty female club soccer players (age range, 11-17 years) with no history of knee injury participated in this study. Kinematics and ground-reaction forces were collected while each participant performed a drop-landing task prior to and immediately after participation in a 12-week ACL injury prevention training program. After ACL injury prevention training, participants demonstrated decreased knee extensor moments ( P = .03), increased energy absorption at the hip ( P = .04), decreased knee-to-hip extensor moment ratios ( P = .05), and decreased knee-to-hip energy absorption ratios ( P = .03). Participation in an ACL injury prevention training program decreased reliance on the knee extensor muscles and improved use of the hip extensor muscles, which may explain the protective effect of this type of training program on ACL injury. Based on these findings, clinicians can better understand how ACL injury prevention training, such as the Prevent Injury and Enhance Performance (PEP) Program, may change movement behavior at both the hip and knee. Furthermore, the study findings may support the implementation of the PEP Program, or a similar program, for clinicians aiming to improve use of the hip in an effort to reduce knee loading and consequent injuries.

Local chromatic correction scheme for LER of PEP-II

International Nuclear Information System (INIS)

Forest, E.; Robin, D.; Zholents, A.; Donald, M.; Helm, R.; Irwin, J.; Sullivan, M.K.

1993-01-01

The correction of the chromaticity of low-beta insertions in storage rings is usually made with sextupole lenses in the ring arcs. When decreasing the beta functions at the interaction point (IP), this technique becomes fairly ineffective, since it fails to properly correct the higher-order chromatic aberrations. Here we consider the approach for ampersand PEP-II B Factory low energy ring (LER) where the chromatic effects of the quadrupole lenses generating low beta functions at the IP are corrected locally with two families of sextupoles, one family for each plane. For the IP straight section the lattice is designed in such a way that the chromatic aberrations are made small and sextupole-like aberrations are eliminated. The results of dimensional tracking simulations are presented

Metalloproteinase inhibition prevents acute respiratory distress syndrome.

Science.gov (United States)

Carney, D E; McCann, U G; Schiller, H J; Gatto, L A; Steinberg, J; Picone, A L; Nieman, G F

2001-08-01

-3 prevented lung injury in our model of endotoxin-induced ARDS. The proposed mechanism of COL-3 is a synergistic inhibition of the terminal neutrophil effectors MMPs and NE. Similar to the universal practice of prophylaxis against gastric stress ulceration and deep venous thromboses in trauma patients, chemically modified tetracyclines may likewise be administered to prevent acute lung injury in critically injured patients at risk of developing ARDS. Copyright 2001 Academic Press.

High-power RF window and coupler development for the PEP-II B Factory

International Nuclear Information System (INIS)

Neubauer, M.; Fant, K.; Hodgson, J.; Judkins, J.; Schwarz, H.; Rimmer, R.A.

1995-05-01

We describe the fabrication and testing of the RF windows designed to transmit power to the PEP-II 476 MHz cavities. Design choices to maximize the reliability of the window are discussed. Fabrication technologies for the window are described and finite-element analysis of the assembly process is presented. Conditioning and high-power testing of the window are discussed. Design of the coupler assembly including the integration of the window and other components is reported

Interleukin-1β inhibits insulin signaling and prevents insulin-stimulated system A amino acid transport in primary human trophoblasts.

Science.gov (United States)

Aye, Irving L M H; Jansson, Thomas; Powell, Theresa L

2013-12-05

Interleukin-1β (IL-1β) promotes insulin resistance in tissues such as liver and skeletal muscle; however the influence of IL-1β on placental insulin signaling is unknown. We recently reported increased IL-1β protein expression in placentas of obese mothers, which could contribute to insulin resistance. In this study, we tested the hypothesis that IL-1β inhibits insulin signaling and prevents insulin-stimulated amino acid transport in cultured primary human trophoblast (PHT) cells. Cultured trophoblasts isolated from term placentas were treated with physiological concentrations of IL-1β (10pg/ml) for 24h. IL-1β increased the phosphorylation of insulin receptor substrate-1 (IRS-1) at Ser307 (inhibitory) and decreased total IRS-1 protein abundance but did not affect insulin receptor β expression. Furthermore, IL-1β inhibited insulin-stimulated phosphorylation of IRS-1 (Tyr612, activation site) and Akt (Thr308) and prevented insulin-stimulated increase in PI3K/p85 and Grb2 protein expression. IL-1β alone stimulated cRaf (Ser338), MEK (Ser221) and Erk1/2 (Thr202/Tyr204) phosphorylation. The inflammatory pathways nuclear factor kappa B and c-Jun N-terminal kinase, which are involved in insulin resistance, were also activated by IL-1β treatment. Moreover, IL-1β inhibited insulin-stimulated System A, but not System L amino acid uptake, indicating functional impairment of insulin signaling. In conclusion, IL-1β inhibited the insulin signaling pathway by inhibiting IRS-1 signaling and prevented insulin-stimulated System A transport, thereby promoting insulin resistance in cultured PHT cells. These findings indicate that conditions which lead to increased systemic maternal or placental IL-1β levels may attenuate the effects of maternal insulin on placental function and consequently fetal growth. Published by Elsevier Ireland Ltd.

Implications of shorter cells in PEP

International Nuclear Information System (INIS)

Wiedemann, H.

1975-01-01

Further studies on the beam-stay-clear requirements in PEP led to the conclusion that the vertical aperture needed to be enlarged. There are two main reasons for that: Observations at SPEAR indicate that the aperture should be large enough for a fully coupled beam. Full coupling of the horizontal and vertical betatron oscillations occurs not only occasionally when the energy, tune or betatron function at the interaction point is changed but also due to the beam/endash/beam effect of two strong colliding beams. The second reason for an increased aperture requirement is the nonlinear perturbation of the particle trajectories by the sextupoles. This perturbation increases a fully coupled beam by another 50% to 80%. Both effects together with a +-5 mm allowance for closed orbit perturbation result in a vertical beam-stay-clear in the bending magnets of +-4.8 to +-5.6 cm, compared to the present +-2.0 cm. This beam-stay-clear, together with additional space for vacuum chamber, etc., leads to very costly bending magnets. In this note, a shorter cell length is proposed which would reduce considerably the vertical beam-stay-clear requirements in the bending magnets. 7 figs

Chloride channel inhibition by a red wine extract and a synthetic small molecule prevents rotaviral secretory diarrhoea in neonatal mice

Science.gov (United States)

Ko, Eun-A; Jin, Byung-Ju; Namkung, Wan; Ma, Tonghui; Thiagarajah, Jay R.; Verkman, A. S.

2014-01-01

Background Rotavirus is the most common cause of severe secretory diarrhoea in infants and young children globally. The rotaviral enterotoxin, NSP4, has been proposed to stimulate calcium-activated chloride channels (CaCC) on the apical plasma membrane of intestinal epithelial cells. We previously identified red wine and small molecule CaCC inhibitors. Objective To investigate the efficacy of a red wine extract and a synthetic small molecule, CaCCinh-A01, in inhibiting intestinal CaCCs and rotaviral diarrhoea. Design Inhibition of CaCC-dependent current was measured in T84 cells and mouse ileum. The effectiveness of an orally administered wine extract and CaCCinh-A01 in inhibiting diarrhoea in vivo was determined in a neonatal mouse model of rotaviral infection. Results Screening of ~150 red wines revealed a Cabernet Sauvignon that inhibited CaCC current in T84 cells with IC50 at a ~1:200 dilution, and higher concentrations producing 100% inhibition. A >1 kdalton wine extract prepared by dialysis, which retained full inhibition activity, blocked CaCC current in T84 cells and mouse intestine. In rotavirus-inoculated mice, oral administration of the wine extract prevented diarrhoea by inhibition of intestinal fluid secretion without affecting rotaviral infection. The wine extract did not inhibit the cystic fibrosis chloride channel (CFTR) in cell cultures, nor did it prevent watery stools in neonatal mice administered cholera toxin, which activates CFTR-dependent fluid secretion. CaCCinh-A01 also inhibited rotaviral diarrhoea. Conclusions Our results support a pathogenic role for enterocyte CaCCs in rotaviral diarrhoea and demonstrate the antidiarrhoeal action of CaCC inhibition by an alcohol-free, red wine extract and by a synthetic small molecule. PMID:24052273

δ-Tocotrienol, a natural form of vitamin E, inhibits pancreatic cancer stem-like cells and prevents pancreatic cancer metastasis.

Science.gov (United States)

Husain, Kazim; Centeno, Barbara A; Coppola, Domenico; Trevino, Jose; Sebti, Said M; Malafa, Mokenge P

2017-05-09

The growth, metastasis, and chemotherapy resistance of pancreatic ductal adenocarcinoma (PDAC) is characterized by the activation and growth of tumor-initiating cells in distant organs that have stem-like properties. Thus, inhibiting growth of these cells may prevent PDAC growth and metastases. We have demonstrated that δ-tocotrienol, a natural form of vitamin E (VEDT), is bioactive against cancer, delays progression, and prevents metastases in transgenic mouse models of PDAC. In this report, we provide the first evidence that VEDT selectively inhibits PDAC stem-like cells. VEDT inhibited the viability, survival, self-renewal, and expression of Oct4 and Sox2 transcription factors in 3 models of PDAC stem-like cells. In addition, VEDT inhibited the migration, invasion, and several biomarkers of epithelial-to-mesenchymal transition and angiogenesis in PDAC cells and tumors. These processes are critical for tumor metastases. Furthermore, in the L3.6pl orthotopic model of PDAC metastases, VEDT significantly inhibited growth and metastases of these cells. Finally, in an orthotopic xenograft model of human PDAC stem-like cells, we showed that VEDT significantly retarded the growth and metastases of gemcitabine-resistant PDAC human stem-like cells. Because VEDT has been shown to be safe and to reach bioactive levels in humans, this work supports investigating VEDT for chemoprevention of PDAC metastases.

Cepharanthine Prevents Estrogen Deficiency-Induced Bone Loss by Inhibiting Bone Resorption

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Chen-he Zhou

2018-03-01

Full Text Available Osteoporosis is a common health problem worldwide caused by an imbalance of bone formation vs. bone resorption. However, current therapeutic approaches aimed at enhancing bone formation or suppressing bone resorption still have some limitations. In this study, we demonstrated for the first time that cepharanthine (CEP, derived from Stephania cepharantha Hayata exerted a protective effect on estrogen deficiency-induced bone loss. This protective effect was confirmed to be achieved through inhibition of bone resorption in vivo, rather than through enhancement of bone formation in vivo. Furthermore, the in vitro study revealed that CEP attenuated receptor activator of nuclear factor κB ligand (RANKL-induced osteoclast formation, and suppressed bone resorption by impairing the c-Jun N-terminal kinase (JNK and phosphatidylinositol 3-kinase (PI3K-AKT signaling pathways. The inhibitory effect of CEP could be partly reversed by treatment with anisomycin (a JNK and p38 agonist and/or SC79 (an AKT agonist in vitro. Our results thus indicated that CEP could prevent estrogen deficiency-induced bone loss by inhibiting osteoclastogenesis. Hence, CEP might be a novel therapeutic agent for anti-osteoporosis therapy.

cGMP-Phosphodiesterase Inhibition Prevents Hypoxia-Induced Cell Death Activation in Porcine Retinal Explants.

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Lorena Olivares-González

Full Text Available Retinal hypoxia and oxidative stress are involved in several retinal degenerations including diabetic retinopathy, glaucoma, central retinal artery occlusion, or retinopathy of prematurity. The second messenger cyclic guanosine monophosphate (cGMP has been reported to be protective for neuronal cells under several pathological conditions including ischemia/hypoxia. The purpose of this study was to evaluate whether the accumulation of cGMP through the pharmacological inhibition of phosphodiesterase (PDE with Zaprinast prevented retinal degeneration induced by mild hypoxia in cultures of porcine retina. Exposure to mild hypoxia (5% O2 for 24h reduced cGMP content and induced retinal degeneration by caspase dependent and independent (PARP activation mechanisms. Hypoxia also produced a redox imbalance reducing antioxidant response (superoxide dismutase and catalase activities and increasing superoxide free radical release. Zaprinast reduced mild hypoxia-induced cell death through inhibition of caspase-3 or PARP activation depending on the cell layer. PDE inhibition also ameliorated the effects of mild hypoxia on antioxidant response and the release of superoxide radical in the photoreceptor layer. The use of a PKG inhibitor, KT5823, suggested that cGMP-PKG pathway is involved in cell survival and antioxidant response. The inhibition of PDE, therefore, could be useful for reducing retinal degeneration under hypoxic/ischemic conditions.

PEP quark search proportional chambers

Energy Technology Data Exchange (ETDEWEB)

Parker, S I; Harris, F; Karliner, I; Yount, D [Hawaii Univ., Honolulu (USA); Ely, R; Hamilton, R; Pun, T [California Univ., Berkeley (USA). Lawrence Berkeley Lab.; Guryn, W; Miller, D; Fries, R [Northwestern Univ., Evanston, IL (USA)

1981-04-01

Proportional chambers are used in the PEP Free Quark Search to identify and remove possible background sources such as particles traversing the edges of counters, to permit geometric corrections to the dE/dx and TOF information from the scintillator and Cerenkov counters, and to look for possible high cross section quarks. The present beam pipe has a thickness of 0.007 interaction lengths (lambdasub(i)) and is followed in both arms each with 45/sup 0/ <= theta <= 135/sup 0/, ..delta..phi=90/sup 0/ by 5 proportional chambers, each 0.0008 lambdasub(i) thick with 32 channels of pulse height readout, and by 3 thin scintillator planes, each 0.003 lambdasub(i) thick. Following this thin front end, each arm of the detector has 8 layers of scintillator (one with scintillating light pipes) interspersed with 4 proportional chambers and a layer of lucite Cerenkov counters. Both the calculated ion statistics and measurements using He-CH/sub 4/ gas in a test chamber indicate that the chamber efficiencies should be >98% for q=1/3. The Landau spread measured in the test was equal to that observed for normal q=1 traversals. One scintillator plane and thin chamber in each arm will have an extra set of ADC's with a wide gate bracketing the normal one so timing errors and tails of earlier pulses should not produce fake quarks.

Acacetin inhibits glutamate release and prevents kainic acid-induced neurotoxicity in rats.

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Tzu-Yu Lin

Full Text Available An excessive release of glutamate is considered to be a molecular mechanism associated with several neurological diseases that causes neuronal damage. Therefore, searching for compounds that reduce glutamate neurotoxicity is necessary. In this study, the possibility that the natural flavone acacetin derived from the traditional Chinese medicine Clerodendrum inerme (L. Gaertn is a neuroprotective agent was investigated. The effect of acacetin on endogenous glutamate release in rat hippocampal nerve terminals (synaptosomes was also investigated. The results indicated that acacetin inhibited depolarization-evoked glutamate release and cytosolic free Ca(2+ concentration ([Ca(2+]C in the hippocampal nerve terminals. However, acacetin did not alter synaptosomal membrane potential. Furthermore, the inhibitory effect of acacetin on evoked glutamate release was prevented by the Cav2.2 (N-type and Cav2.1 (P/Q-type channel blocker known as ω-conotoxin MVIIC. In a kainic acid (KA rat model, an animal model used for excitotoxic neurodegeneration experiments, acacetin (10 or 50 mg/kg was administrated intraperitoneally to the rats 30 min before the KA (15 mg/kg intraperitoneal injection, and subsequently induced the attenuation of KA-induced neuronal cell death and microglia activation in the CA3 region of the hippocampus. The present study demonstrates that the natural compound, acacetin, inhibits glutamate release from hippocampal synaptosomes by attenuating voltage-dependent Ca(2+ entry and effectively prevents KA-induced in vivo excitotoxicity. Collectively, these data suggest that acacetin has the therapeutic potential for treating neurological diseases associated with excitotoxicity.

Theophylline prevents NAD+ depletion via PARP-1 inhibition in human pulmonary epithelial cells

International Nuclear Information System (INIS)

Moonen, Harald J.J.; Geraets, Liesbeth; Vaarhorst, Anika; Bast, Aalt; Wouters, Emiel F.M.; Hageman, Geja J.

2005-01-01

Oxidative DNA damage, as occurs during exacerbations in chronic obstructive pulmonary disease (COPD), highly activates the nuclear enzyme poly(ADP-ribose)polymerase-1 (PARP-1). This can lead to cellular depletion of its substrate NAD + , resulting in an energy crisis and ultimately in cell death. Inhibition of PARP-1 results in preservation of the intracellular NAD + pool, and of NAD + -dependent cellular processes. In this study, PARP-1 activation by hydrogen peroxide decreased intracellular NAD + levels in human pulmonary epithelial cells, which was found to be prevented in a dose-dependent manner by theophylline, a widely used compound in the treatment of COPD. This enzyme inhibition by theophylline was confirmed in an ELISA using purified human PARP-1 and was found to be competitive by nature. These findings provide new mechanistic insights into the therapeutic effect of theophylline in oxidative stress-induced lung pathologies

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

International Nuclear Information System (INIS)

Cai Yunhai; Irwin, John; Nosochkov, Yuri; Yan, Yiton

1997-01-01

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

PEP II: RF and feedback R ampersand D

International Nuclear Information System (INIS)

Hindi, H.: Fox, J.; Eisen, N.; Linscott, I.; Oxoby, G.; Pendleton, R.; Sapozhnikov, L.; Schwarz, H.D.; Rimmer, R.; Lambertson, A.; Voelker, F.; Serio, M.

1992-11-01

The key elements of the PEP 11 approach to dealing with the problem of coupled-bunch instabilities are presented. The approach involves using warm copper RF cavities with damping waveguides (above the cutoff of the fundamental) attached to the cavity walls. These couple out the troublesome higher-order modes (HOMs) into absorbing loads, while the fundamental mode remains in the cavity. The Q of the worst HOM is reduced to below 70. Instabilities due to residual coupling are damped using a bunch-by-bunch feedback system, which is implemented using digital signal processors. A prototype cavity has been built and the concept of HOM damping has been verified. A prototype feedback system has been built and tested at SPEAR. Results to date indicate that the combination of damped cavities and bunch-by-bunch feedback provide a very effective means of dealing with the problem

Inhibition of Cyclooxygenase-2 Prevents Chronic and Recurrent Cystitis

Directory of Open Access Journals (Sweden)

Thomas J. Hannan

2014-11-01

Full Text Available The spread of multidrug-resistant microorganisms globally has created an urgent need for novel therapeutic strategies to combat urinary tract infections (UTIs. Immunomodulatory therapy may provide benefit, as treatment of mice with dexamethasone during acute UTI improved outcome by reducing the development of chronic cystitis, which predisposes to recurrent infection. Here we discovered soluble biomarkers engaged in myeloid cell development and chemotaxis that were predictive of future UTI recurrence when elevated in the sera of young women with UTI. Translation of these findings revealed that temperance of the neutrophil response early during UTI, and specifically disruption of bladder epithelial transmigration of neutrophils by inhibition of cyclooxygenase-2, protected mice against chronic and recurrent cystitis. Further, proteomics identified bladder epithelial remodeling consequent to chronic infection that enhances sensitivity to neutrophil damage. Thus, cyclooxygenase-2 expression during acute UTI is a critical molecular trigger determining disease outcome and drugs targeting cyclooxygenase-2 could prevent recurrent UTI.

Status of the PEP-II B-factory high energy ring

International Nuclear Information System (INIS)

Wienands, U.; Reuter, E.; Bellomo, P.; Daly, E.; Fisher, A.; Gracia, J.; Kulikov, A.; Kurita, N.; Pietryka, M.; Seeman, J.T.; Taylor; Belser, C.; Bertolini, L.; Mugge, M.; Swan, J.

1996-01-01

The 9 GeV High Energy Ring (HER) of the PEP-II B Factory is an electron storage ring under construction at SLAC. Significant progress has been made in the last year on all systems. As of mid 1996, all 192 dipoles have been installed, with installation of the quadrupoles underway. The vacuum system, for design currents up to 3 A average, is in production using a recently commissioned e-beam welder. Beam instrumentation systems are being fabricated. The interaction region will bring the HER beam into collision with the 3 GeV beam of the Low Energy Ring; design of this section of the HER is in an advanced stage. 8 refs., 3 figs., 1 tab

A Novel Function for the Streptococcus pneumoniae Aminopeptidase N: Inhibition of T Cell Effector Function through Regulation of TCR Signaling

Directory of Open Access Journals (Sweden)

Lance K. Blevins

2017-11-01

Full Text Available Streptococcus pneumoniae (Spn causes a variety of disease states including fatal bacterial pneumonia. Our previous finding that introduction of Spn into an animal with ongoing influenza virus infection resulted in a CD8+ T cell population with reduced effector function gave rise to the possibility of direct regulation by pneumococcal components. Here, we show that treatment of effector T cells with lysate derived from Spn resulted in inhibition of IFNγ and tumor necrosis factor α production as well as of cytolytic granule release. Spn aminopeptidase N (PepN was identified as the inhibitory bacterial component and surprisingly, this property was independent of the peptidase activity found in this family of proteins. Inhibitory activity was associated with reduced activation of ZAP-70, ERK1/2, c-Jun N-terminal kinase, and p38, demonstrating the ability of PepN to negatively regulate TCR signaling at multiple points in the cascade. These results reveal a novel immune regulatory function for a bacterial aminopeptidase.

Beam Commissioning of the PEP-II High Energy Ring

International Nuclear Information System (INIS)

Wienands, U.; Anderson, S.; Assmann, R.; Bharadwaj, V.; Cai, Y.; Clendenin, J.; Corredoura, P.; Decker, F.J.; Donald, M.; Ecklund, S.; Emma, P.; Erickson, R.; Fox, J.; Fieguth, T.; Fisher, A.; Heifets, S.; Hill, A.; Himel, T.; Iverson, R.; Johnson, R.; Judkins, J.; Krejcik, P.; Kulikov, A.; Lee, M.; Mattison, T.; Minty, M.; Nosochkov, Y.; Phinney, N.; Placidi, M.; Prabhakar, S.; Ross, M.; Smith, S.; Schwarz, H.; Stanek, M.; Teytelman, D.; Traller, R.; Turner, J.; Zimmermann, F.; Barry, W.; Chattopadhyay, S.; Corlett, J.; Decking, W.; Furman, M.; Nishimura, H.; Portmann, G.; Rimmer, R.; Zholents, A.; Zisman, M.; Kozanecki, W.; Hofmann, A.; Zotter, B.; Steier, C.; Bialowons, W.; Lomperski, M.; Lumpkin, A.; Reichel, I.; Safranek, J.; Smith, V.; Tighe, R.; Sullivan, M.; Byrd, J.; Li, D.

1998-01-01

The PEP-II High Energy Ring (HER), a 9 GeV electron storage ring, has been in commissioning since spring 1997. Initial beam commissioning activities focused on systems checkout and commissioning and on determining the behavior of the machine systems at high beam currents. This phase culminated with the accumulation of 0.75 A of stored beam-sufficient to achieve design luminosity--in January 1998 after 3.5 months of beam time. Collisions with the 3 GeV positron beam of the Low Energy Ring (LER) were achieved in Summer of 1998. At high beam currents, collective instabilities have been seen. Since then, commissioning activities for the HER have shifted in focus towards characterization of the machine and a rigorous program to understand the machine and the beam dynamics is presently underway

Detector solenoid compensation in the PEP-II B-Factory

International Nuclear Information System (INIS)

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

1995-01-01

The PEP-II experimental detector includes a strong 1.5 T solenoid field in the interaction region (IR). With the fringe fields, the solenoid extends over a range of 6 m. Additional complications are that (1) it is displaced longitudinally from the interaction point (IP) by about 40 cm, (2) neither beam is parallel to the solenoid axis, and (3) the solenoid overlaps a dipole and a quadrupole on either side of the IP. In each half IR the correction system includes a set of skew quadrupoles, dipole correctors and normal quadrupoles to independently compensate the coupling, orbit perturbation, dispersion and focusing effect produced by the solenoid. The correction schemes for the Low Energy Ring (LER) and for the High Energy Ring (HER) are described, and the impact on the dynamic aperture is evaluated

Ba{anti B}ar status report on the design of a detector for the study of CP violation at PEP-II at SLAC

Energy Technology Data Exchange (ETDEWEB)

1993-06-01

Experiments designed to measure CP-violating asymmetries in the B meson system must emphasize exclusive state reconstruction with the highest possible resolution and efficiency. In the case of B{sup 0} mesons produced in pairs at the {Upsilon}(4S) resonance at an asymmetric e{sup +}e{sup {minus}} storage ring, this capability must be accompanied by precise vertex reconstruction in the direction of the e{sup +}e{sup {minus}} beams (henceforth the z direction). These are difficult requirements, beyond the scope of any existing storage ring detector. The challenge of designing an asymmetric storage ring capable of producing the large number of neutral B meson pairs required to measure CP-violating asymmetries in decays to CP eigenstates has been handsomely met in the PEP-II design. As the first asymmetric e{sup +}e{sup {minus}} storage ring, PEP-II presents a novel set of experimental challenges to a 4{pi} detector. This Status Report describes the design of a new detector fully capable of exploiting the physics opportunities provided by PEP-II.

Dynamic Aperture Improvement of PEP-II Lattices Using Resonance Basis Lie Generators

Energy Technology Data Exchange (ETDEWEB)

Yan, Yiton T

2003-08-11

To simplify the engineering efforts of implementing the PEP-II lattices, many modifications have been made to these lattices since the conceptual design report. During the development and evolution of the lattices, changes in a lattice would often result in a significant reduction in the dynamic aperture. At such times, we often relied on a non-linear analysis using the one-turn resonance basis Lie generator to identify the cause of the degradation. In this paper, we will present such examples to facilitate the usage of map for diagnosing the problems in lattice design.

Study of coupled-bunch collective effects in the PEP-II B-Factory

International Nuclear Information System (INIS)

Byrd, J.

1993-05-01

We present an overview of the calculated longitudinal and transverse coupled-bunch (CB) growth using the measured RF cavity higher order mode impedance and estimated resistive wall (RW) impedance for the proposed PEP-II B-Factory, a dual-ring electron-positron collider. We also describe a visual method of representing the effective beam impedance and corresponding growth rates which is especially useful for understanding the dependence of growth rate on higher order mode frequency and Q, spread of HOM frequencies between cells, and for determining the requirements of the CB feedback systems

Clinical effect of endoscopic nasobiliary drainage in prevention of post-ERCP pancreatitis in patients with choledocholithiasis

Directory of Open Access Journals (Sweden)

ZHAO Xiaowen

2014-08-01

Full Text Available ObjectiveTo investigate the clinical effect of endoscopic nasobiliary drainage (ENBD in the prevention of post-endoscopic retrograde cholangiopancreatography (ERCP pancreatitis (PEP and hyperamylasemia in patients with choledocholithiasis. MethodsA total of 560 patients with choledocholithiasis who underwent ERCP from October 2010 to December 2013 were included in the study. ENBD was performed in 371 patients (test group, and the other 189 patients were designated as control group. Serum amylase level was measured at 3 and 24 h after ERCP, and the incidence of PEP and hyperamylasemia was determined. Comparison of continuous data between the two groups was made by t test, while comparison of rates was made by chi-square test. ResultsThe incidence rates of PEP and hyperamylasemia in the test group were 8.1% (30/371 and 13.7% (51/371, respectively, significantly lower than those in the control group (13.8%, 26/189; 21.2%, 40/189, (χ2 = 4.47, P=0.034; χ2=5.06, P=0.024. The serum amylase levels at 3 and 24 h after ERCP in the test group were 215.34±304.00 U/L and 199.38±273.32 U/L, respectively, significantly lower those in the control group (283.28±261.76 U/L and 257.05±199.25 U/L (t=2.61, P=0.01; t=2.57, P=0.01. ConclusionENBD can effectively reduce the incidence of PEP and hyperamylasemia in patients with choledocholithiasis.

Hydrogen sulphide-releasing diclofenac derivatives inhibit breast cancer-induced osteoclastogenesis in vitro and prevent osteolysis ex vivo.

Science.gov (United States)

Frantzias, J; Logan, J G; Mollat, P; Sparatore, A; Del Soldato, P; Ralston, S H; Idris, A I

2012-03-01

Hydrogen sulphide (H(2)S) and prostaglandins are both involved in inflammation, cancer and bone turnover, and non-steroidal anti-inflammatory drugs (NSAIDs) and H(2)S donors exhibit anti-inflammatory and anti-tumour properties. H(2)S-releasing diclofenac (S-DCF) derivatives are a novel class of NSAIDs combining the properties of a H(2)S donor with those of a conventional NSAID. We studied the effects of the S-DCF derivatives ACS15 and ACS32 on osteoclast and osteoblast differentiation and activity in vitro, human and mouse breast cancer cells support for osteoclast formation and signalling in vitro, and osteolysis ex vivo. The S-diclofenac derivatives ACS15 and ACS32 inhibited the increase in osteoclast formation induced by human MDA-MB-231 and MCF-7 and mouse 4T1 breast cancer cells without affecting breast cancer cell viability. Conditioned media from human MDA-MB-231 cells enhanced IκB phosphorylation and osteoclast formation and these effects were significantly inhibited following treatment by ACS15 and ACS32, whereas the parent compound diclofenac had no effects. ACS15 and ACS32 inhibited receptor activator of NFκB ligand-induced osteoclast formation and resorption, and caused caspase-3 activation and apoptosis in mature osteoclasts via a mechanism dependent on IKK/NFκB inhibition. In calvaria organ culture, human MDA-MB-231 cells caused osteolysis, and this effect was completely prevented following treatment with ACS15 and ACS32. S-diclofenac derivatives inhibit osteoclast formation and activity, suppress breast cancer cell support for osteoclastogenesis and prevent osteolysis. This suggests that H(2)S-releasing diclofenac derivatives exhibit anti-resorptive properties, which might be of clinical value in the treatment of osteolytic bone disease. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

Prodrugs of purine and pyrimidine analogues for the intestinal di/tri-peptide transporter PepT1

DEFF Research Database (Denmark)

Thomsen, Anne Engelbrecht; Friedrichsen, Gerda Marie; Sørensen, Arne Hagsten

2003-01-01

, novel L-Glu-Sar and D-Glu-Ala ester prodrugs of acyclovir and 1-(2-hydroxyethyl)-linked thymine were synthesized and their affinities for hPepT1 in Caco-2 cells were determined. Furthermore, the degradation of the prodrugs was investigated in various aqueous and biological media and compared...... to the corresponding hydrolysis of the prodrug valaciclovir. Affinity studies showed that the L-Glu-Sar prodrugs had high affinity for hPepT1 (K(i) approximately 0.2-0.3 mM), whereas the D-Glu-Ala prodrugs had poor affinity (K(i) approximately 50 mM). The pH-rate profiles of the prodrugs D-Glu[1-(2-hydroxyethyl......)thymine]-Ala and L-Glu[acyclovir]-Sar showed specific base catalyzed degradation at pH above 4.5 and 5.5, respectively. This implicates that the degradation rates at pH approximately 7.4 (t(1/2) approximately 3.5 and 5.5 h) are approximately 25 times faster than at upper small intestinal pH approximately 6.0. In 10...

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

Science.gov (United States)

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

Sirtuin 6 prevents matrix degradation through inhibition of the NF-κB pathway in intervertebral disc degeneration

Energy Technology Data Exchange (ETDEWEB)

Kang, Liang [Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China); Hu, Jia [Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China); Weng, Yuxiong [Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China); Jia, Jie [Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China); Zhang, Yukun, E-mail: zhangyukuncom@126.com [Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China)

2017-03-15

Intervertebral disc degeneration (IDD) is marked by imbalanced metabolism of the extracellular matrix (ECM) in the nucleus pulposus (NP) of intervertebral discs. This study aimed to determine whether sirtuin 6 (SIRT6), a member of the sirtuin family of nicotinamide adenine dinucleotide-dependent deacetylases, protects the NP from ECM degradation in IDD. Our study showed that expression of SIRT6 markedly decreased during IDD progression. Overexpression of wild-type SIRT6, but not a catalytically inactive mutant, prevented IL-1β-induced NP ECM degradation. SIRT6 depletion by RNA interference in NP cells caused ECM degradation. Moreover, SIRT6 physically interacted with nuclear factor-κB (NF-κB) catalytic subunit p65, transcriptional activity of which was significantly suppressed by SIRT6 overexpression. These results suggest that SIRT6 prevented NP ECM degradation in vitro via inhibiting NF-κB-dependent transcriptional activity and that this effect depended on its deacetylase activity. - Highlights: • SIRT6 expression is decreased in degenerative nucleus pulposus (NP) tissues. • SIRT6 overexpression lowers IL-1β-induced matrix degradation of NP. • SIRT6 inhibition induces matrix degradation of NP. • SIRT6 prevents matrix degradation of NP via the NF-κB signaling pathway.

Sirtuin 6 prevents matrix degradation through inhibition of the NF-κB pathway in intervertebral disc degeneration

International Nuclear Information System (INIS)

Kang, Liang; Hu, Jia; Weng, Yuxiong; Jia, Jie; Zhang, Yukun

2017-01-01

Intervertebral disc degeneration (IDD) is marked by imbalanced metabolism of the extracellular matrix (ECM) in the nucleus pulposus (NP) of intervertebral discs. This study aimed to determine whether sirtuin 6 (SIRT6), a member of the sirtuin family of nicotinamide adenine dinucleotide-dependent deacetylases, protects the NP from ECM degradation in IDD. Our study showed that expression of SIRT6 markedly decreased during IDD progression. Overexpression of wild-type SIRT6, but not a catalytically inactive mutant, prevented IL-1β-induced NP ECM degradation. SIRT6 depletion by RNA interference in NP cells caused ECM degradation. Moreover, SIRT6 physically interacted with nuclear factor-κB (NF-κB) catalytic subunit p65, transcriptional activity of which was significantly suppressed by SIRT6 overexpression. These results suggest that SIRT6 prevented NP ECM degradation in vitro via inhibiting NF-κB-dependent transcriptional activity and that this effect depended on its deacetylase activity. - Highlights: • SIRT6 expression is decreased in degenerative nucleus pulposus (NP) tissues. • SIRT6 overexpression lowers IL-1β-induced matrix degradation of NP. • SIRT6 inhibition induces matrix degradation of NP. • SIRT6 prevents matrix degradation of NP via the NF-κB signaling pathway.

A test of planar spark counters at the PEP storage ring

International Nuclear Information System (INIS)

Atwood, W.B.; Bowden, G.B.; Bonneaud, G.R.; Klem, D.E.; Ogawa, A.; Pestov, Yu.N.; Pitthan, R.; Sugahara, R.

1983-01-01

A test of planar spar counters (PSCs) at the PEP electron-positron storage ring showed the following. PSCs can be used under harsh experimental conditions without long term degradation of resolution. On-line time-of-flight resolutions were below 200 ps, coordinate resolutions better than 4 mm, both limited to these values by the resistivity of the semiconducting glass and the electronics used. The best single counter time resolution under realistic conditions at the storage ring was 76 ps. Pulse height was a good indicator of the number of particles striking a counter. Subsequent measurements using cosmis rays gave a single counter time resolution of 50 ps. (orig.)

High-power RF window design for the PEP-II B Factory

International Nuclear Information System (INIS)

Neubauer, M.; Hodgson, J.; Ng, C.; Schwarz, H.; Skarpaas, K.; Kroll, N.; Rimmer, R.

1994-06-01

We describe the design of RF windows to transmit up to 500 kW CW to the PEP-II 476 MHz cavities. RF analysis of the windows using high-frequency simulation codes are described. These provide information about the power loss distribution in the ceramic and tim matching properties of the structure. Finite-element analyses of the resulting temperature distribution and thermal stresses are presented. Fabrication methods including a proposed scheme to compensate for thermal expansion s are discussed and hardware tests to validate this approach are described. The effects of surface coatings (intentional and otherwise) and the application of air cooling are considered

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

International Nuclear Information System (INIS)

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

1997-01-01

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 1997 American Institute of Physics

Mind magic: a pilot study of preventive mind-body-based stress reduction in behaviorally inhibited and activated children

NARCIS (Netherlands)

Jellesma, F.C.; Cornelis, J.

2012-01-01

Purpose of study: The aim of this pilot study was to examine a mind-body-based preventive intervention program and to determine relationships between children's behavioral inhibition system (BIS) and behavioral activation system, stress, and stress reduction after the program. Design of study:

[Lactobacillus rhamnosus GG conditioned medium prevents E. coli meningitis by inhibiting nuclear factor-κB pathway].

Science.gov (United States)

Zeng, Qing; He, Xiao-Long; Xiao, Han-Sheng; DU, Lei; Li, Yu-Jing; Chen, Le-Cheng; Tian, Hui-Wen; Huang, Sheng-He; Cao, Hong

2017-01-20

To investigate whether Lactobacillus rhamnosus GG conditioned medium(LGG-CM)has preventive effect against E. coli K1-induced neuropathogenicity in vitro by inhibiting nuclear factor-κB (NF-κB) signaling pathway. An in vitro blood-brain barrier (BBB) model was constructed using human brain microvascular endothelial cells (HBMECs). The effect of LGG-CM on E. coli-actived NF-κB signaling pathway was assayed using Western blotting. Invasion assay and polymorphonuclear leukocyte (PMN) transmigration assay were performed to explore whether LGG-CM could inhibit E. coli invasion and PMN transmigration across the BBB in vitro. The expressions of ZO-1 and CD44 were detected using Western blotting and immunofluorescence. The changes of trans-epithelial electric resistance (TEER) and bacterial translocation were determined to evaluate the BBB permeability. Pre-treament with LGG-CM inhibited E. coli-activated NF-κB signaling pathway in HBMECs and decreased the invasion of E. coli K1 and transmigration of PMN. Western blotting showed that LGG-CM could alleviate E. coli-induced up-regulation of CD44 and down-regulation of ZO-1 expressions in HBMECs. In addition, pre-treatment with LGG-CM alleviated E. coli K1-induced reduction of TEER and suppressed bacterial translocation across the BBB in vitro. LGG-CM can block E. coli-induced activation of NF-κB signaling pathway and thereby prevents E. coli K1-induced neuropathogenicity by decreasing E. coli K1 invasion rates and PMN transmigration.

The Cellular Prion Protein Prevents Copper-Induced Inhibition of P2X4 Receptors

Directory of Open Access Journals (Sweden)

Ramón A. Lorca

2011-01-01

Full Text Available Although the physiological function of the cellular prion protein (PrPC remains unknown, several evidences support the notion of its role in copper homeostasis. PrPC binds Cu2+ through a domain composed by four to five repeats of eight amino acids. Previously, we have shown that the perfusion of this domain prevents and reverses the inhibition by Cu2+ of the adenosine triphosphate (ATP-evoked currents in the P2X4 receptor subtype, highlighting a modulatory role for PrPC in synaptic transmission through regulation of Cu2+ levels. Here, we study the effect of full-length PrPC in Cu2+ inhibition of P2X4 receptor when both are coexpressed. PrPC expression does not significantly change the ATP concentration-response curve in oocytes expressing P2X4 receptors. However, the presence of PrPC reduces the inhibition by Cu2+ of the ATP-elicited currents in these oocytes, confirming our previous observations with the Cu2+ binding domain. Thus, our observations suggest a role for PrPC in modulating synaptic activity through binding of extracellular Cu2+.

Pizza Parties, Pep Rallies, and Practice Tests: Strategies Used by High School Principals to Raise Percent Proficient

Science.gov (United States)

Hollingworth, Liz; Dude, David J.; Shepherd, Julie K.

2010-01-01

This study explores ways high school principals are responding to the demands of education reform to raise student test scores on achievement tests used for accountability purposes. Anecdotal evidence suggests administrators have instituted pizza parties and pep rallies to motivate students to do their best and practice tests to prepare students…

Reação de híbridos, linhagens e progênies de pimentão à requeima causada por Phytophthora capsici e ao mosaico amarelo causado por Pepper yellow mosaic vírus (PepYMV Reaction of hybrids, lines and progenies of sweet pepper the blight caused by Phytophthora capsici and to Pepper yellow mosaic virus (PepYMV

Directory of Open Access Journals (Sweden)

Ildon Rodrigues do Nascimento

2007-02-01

Full Text Available A requeima do pimentão (Capsicum annuum L. causada por Phytophthora capsici e o mosaico amarelo causado por PepYMV são prioridades nos programas de melhoramento de pimentão em andamento no Brasil. Foram avaliados três híbridos comerciais (Magali R, Atenas F1 e Fortuna Super F1, cinco linhagens, 20 híbridos experimentais e duas progênies F2:4 do programa de melhoramento da Universidade Federal de Lavras/HortiAgro Sementes quanto à reação a P. capsici e a PepYMV. Os experimentos foram montados independentemente em blocos casualizados, com quatro e duas repetições, respectivamente. Cada parcela foi constituída de oito plantas instaladas em bandejas de 128 células, que foram mantidas em estufa com cobertura plástica e laterais teladas. As avaliações foram feitas do 4º ao 14º e do 15º ao 40º dias após a inoculação (DAI para P. capsici e PepYMV, respectivamente. A inoculação com P. capsici foi feita pormeio da distribuição de 5 mL de suspensão com 10(4 zoósporos/mL no solo ao redor do colo de cada planta. A inoculação mecânica de PepYMV foi feita a partir de macerados de folhas de Nicotiana tabacum cv. TNN, previamente infectadas. Os híbridos Magali R e Fortuna Super, foram suscetíveis a P. capsici, enquanto que o acesso Criollo de Morellos 334, a linhagem PIM-013 e as progênies PIX-03 pl#03-2 e PIX-030 pl#06-3 (ambas originadas do cruzamento com Criollo de Morellos, foram resistentes. Reação de resistência a P. capsici foi também observada para os híbridos experimentais que tiveram PIM-013 como uma das linhagens parentais. Criollo de Morellos 334, as progênies PIX-03 pl#03-2 e PIX-030 pl#06-3, o híbrido comercial Magali R e outros 6 híbridos experimentais que tinham como um dos genitores a linhagem MYR-29 forma ressitentes ao PepYMV. As progênies PIX-03 pl#03-2 e PIX-030 pl#06-3 são fontes promissoras de resistência a ambos os patógenos para serem desenvolvidas e exploradas em programas de melhoramento

Studies on combination effects of peplomycin and x-ray irradiation

International Nuclear Information System (INIS)

Munenaga, Yasuichi

1984-01-01

In order to study effects and methods of combination of peplomycin (PEP) and x-ray irradiation, inhibitory effects on DNA synthesis were investigated with synchronized cells from the parotid gland of mice treated with isoproterenol (IPR) and inhibitory effects on cell proliferation were investigated with Ehrlich solid tumor cells. PEP had dose-dependent effects on the inhibition of DNA synthesis and on the prolongation of cell cycles in the IPR-treated mouse cells. When 3.0 and 5.0 mg/kg of PEP were combined with 200 rad of x-ray irradiation at the early phase of G 1 , synergistic effects on the inhibition of DNA synthesis were seen. This was most noted in the group with PEP 30 minutes before irradiation. PEP had also dose-dependent inhibitory effects on the proliferation of Ehrlich solid tumor cells. This was increased when x-ray irradiation was combined with PEP. Inhibitory effects on the proliferation of tumor cells were greater when PEP was given before x-ray irradiation than after x-ray irradiation, regardless of the amount. The greatest effect was seen in the group with PEP 30 minutes before irradiation, as well as in the experiment with IPR-treated mouse cells. (Namekawa, K.)

PEP conceptual design report

International Nuclear Information System (INIS)

1976-02-01

The accelerator system design, the physical plant, the experimental areas, cost estimates, and schedules for PEP are discussed. The main component of the proposed facility is a storage ring in which beams of positrons and electrons circulate in opposite directions in a vacuum chamber embedded in a magnetic guide field having six bending arcs and six long straight sections. The electrons and positrons to be stored in it are produced in the SLAC linac and are introduced into the storage ring via two beam transport paths emanating from the end of the two-mile accelerator. Beams of energies up to 18 GeV can be stored, and, at a future date, components could be added to permit energies as high as 22 GeV. Provisions are also made in the design of the ring housing so that a synchrotron-radiation research facility could be added in the future. The energy lost from the beams by synchrotron radiation is restored by a high-power radio frequency accelerating system which employs klystrons to drive the accelerating structures at a frequency of 353 MHz. The system is capable of delivering five megawatts of power to the beams. Low pressures will be sustained by means of long, narrow sputter-ion pumps located in the vacuum chamber in the bending magnets directly alongside the beams. The proposed storage ring is designed to generate a luminosity (reaction rate per unit reaction cross section) of more than 10 31 cm -2 sec -1 per interaction region at beam energies between 5 GeV and 18 GeV and a maximum luminosity of 10 32 cm -2 sec -1 per interaction region at a beam energy of 15 GeV

Self-diffusion investigations on a series of PEP-PDMS diblock copolymers with different morphologies by pulsed field gradient NMR

DEFF Research Database (Denmark)

Rittig, F.; Karger, J.; Papadakis, C.M.

1999-01-01

We report on temperature-dependent self-diffusion measurements of compositionally different and non-entangled poly(ethylene-co-propylene)-b-poly(dimethylsiloxane) PEP-PDMS diblock copolymers in the melt above and below the order-to-disorder transition temperature. Depending on the dimensionality...

Cigarette Smoke-Induced Emphysema and Pulmonary Hypertension Can Be Prevented by Phosphodiesterase 4 and 5 Inhibition in Mice

Science.gov (United States)

Pichl, Alexandra; Bednorz, Mariola; Ghofrani, Hossein Ardeschir; Schermuly, Ralph Theo; Seeger, Werner; Grimminger, Friedrich; Weissmann, Norbert

2015-01-01

Rationale Chronic obstructive pulmonary disease (COPD) is a widespread disease, with no curative therapies available. Recent findings suggest a key role of NO and sGC-cGMP signaling for the pathogenesis of the disease. Previous data suggest a downregulation/inactivation of the cGMP producing soluble guanylate cyclase, and sGC stimulation prevented cigarette smoke-induced emphysema and pulmonary hypertension (PH) in mice. We thus aimed to investigate if the inhibition of the cGMP degrading phosphodiesterase (PDE)5 has similar effects. Results were compared to the effects of a PDE 4 inhibitor (cAMP elevating) and a combination of both. Methods C57BL6/J mice were chronically exposed to cigarette smoke and in parallel either treated with Tadalafil (PDE5 inhibitor), Piclamilast (PDE4 inhibitor) or both. Functional measurements (lung compliance, hemodynamics) and structural investigations (alveolar and vascular morphometry) as well as the heart ratio were determined after 6 months of tobacco smoke exposure. In addition, the number of alveolar macrophages in the respective lungs was counted. Results Preventive treatment with Tadalafil, Piclamilast or a combination of both almost completely prevented the development of emphysema, the increase in lung compliance, tidal volume, structural remodeling of the lung vasculature, right ventricular systolic pressure, and right ventricular hypertrophy induced by cigarette smoke exposure. Single, but not combination treatment prevented or reduced smoke-induced increase in alveolar macrophages. Conclusion Cigarette smoke-induced emphysema and PH could be prevented by inhibition of the phosphodiesterases 4 and 5 in mice. PMID:26058042

Inhibition of fatty acid biosynthesis prevents adipocyte lipotoxicity on human osteoblasts in vitro

Science.gov (United States)

Elbaz, Alexandre; Wu, Xiying; Rivas, Daniel; Gimble, Jeffrey M; Duque, Gustavo

2010-01-01

Abstract Although increased bone marrow fat in age-related bone loss has been associated with lower trabecular mass, the underlying mechanism responsible remains unknown. We hypothesized that marrow adipocytes exert a lipotoxic effect on osteoblast function and survival through the reversible biosynthesis of fatty acids (FA) into the bone marrow microenvironment. We have used a two-chamber system to co-culture normal human osteoblasts (NHOst) with differentiating pre-adipocytes in the absence or presence of an inhibitor of FA synthase (cerulenin) and separated by an insert that allowed unidirectional trafficking of soluble factors only and prevented direct cell–cell contact. Supernatants were assayed for the presence of FA using mass spectophotometry. After 3 weeks in co-culture, NHOst showed significantly lower levels of differentiation and function based on lower mineralization and expression of alkaline phosphatase, osterix, osteocalcin and Runx2. In addition, NHOst survival was affected by the presence of adipocytes as determined by MTS-formazan and TUNEL assays as well as higher activation of caspases 3/7. These toxic effects were inhibited by addition of cerulenin. Furthermore, culture of NHOst with either adipocyte-conditioned media alone in the absence of adipocytes themselves or with the addition of the most predominant FA (stearate or palmitate) produced similar toxic results. Finally, Runx2 nuclear binding was affected by addition of either adipocyte conditioned media or FA into the osteogenic media. We conclude that the presence of FA within the marrow milieu can contribute to the age-related changes in bone mass and can be prevented by the inhibition of FA synthase. PMID:19382912

The vacuum system for the PEP II high energy ring straight sections

International Nuclear Information System (INIS)

Wienands, U.; Daly, E.; Heifets, S.A.; Kulikov, A.; Kurita, N.; Nordby, M.; Perkins, C.; Reuter, E.; Seeman, J.T.; Belser, F.C.; Berg, J.; Holdener, F.R.; Kerns, J.A.; McDaniel, M.R.; Stoeffl, W.

1995-01-01

The six straight sections of the PEP II High Energy Ring (HER) serve various functions: lattice tuning, beam injection and abort, providing space for rf cavities, longitudinal and transverse feedback, beam diagnostics and the interaction point. A stainless steel vacuum system has been designed; prototypes are currently being built. Cooling is required due to radiation coming from the last arc dipole and resistive losses in the vacuum chamber. Although the nominal beam current of the HER is 1 A the vacuum system is designed for 3 A to provide margin and an upgrade path. 5 refs., 7 figs

Effects of parasitic beam-beam interaction during the injection process at the PEP-II B Factory

International Nuclear Information System (INIS)

Chin, Y.H.

1992-06-01

This paper is concerned with beam-beam effects during the injection process at the proposed asymmetric SLAC/LBL/LLNL B-Factory, PEP-II. It is shown that the parasitic beam-beam interaction can lead to a significant blowup in the vertical size of the injected beam. Simulation results for the horizontal and the vertical injection schemes are presented, and their performances are studied

Harmonic strengths of PEP dipoles and some related effects and lessons

International Nuclear Information System (INIS)

Spencer, J.E.

1981-09-01

The harmonic content of magnets such as the standard PEP bend is (among other things) a function of excitation current, the way the current is set and even the magnetization history. For instance, harmonic strengths generally vary not only with the magnitude of the current but the direction and rate at which the current is approached and set. The field distribution resulting from different procedures can vary markedly depending on both the mechanical and magnetic design and the degree to which eddy current effects are emphasized. Variations among magnets of the same design result from variations in the iron as well as overall magnet fabrication procedures. Because the field distribution may also depend in the previous history of a magnet, all PEP dipoles were subjected to what are called ''magnetization'' and ''standardization'' cycles before measurement---the latter depending on the former and intended to set the initial conditions of the magnet to a reproducible standard. The primary goal of the magnetic measurements was then to determine the dipole strength as a function of current for each magnet based on a practical setting algorithm. The main constraints on the algorithm were reproducibility of the integrated field, speed, power and reduction of higher harmonics. Quadrupole and sextupole strengths were also measured on about one-half of the magnets at one current. This note presents the data and discusses it from the the viewpoint of subsequent measurements with stored beams. The most important conclusion is that inability to fully distribute laminations according to heat number and/or strike number results in ''magnetic personalities'' among the magnets which are quite difficult to deal with afterwards although one can distribute ''non-standard'' magnets to minimize orbit distributions. 26 refs., 8 figs., 3 tabs

Design of a high-power test model of the PEP-II rf cavity

International Nuclear Information System (INIS)

Schwarz, H.D.; Bell, R.A.; Hodgson, J.A.

1993-05-01

The design of a normal-conducting high-power test cavity (HPTC) for PEP-II is described. The cavity includes HOM loading waveguides and provisions for testing two alternate input coupling schemes. 3-D electromagnetic field simulations provided input information for the surface power deposition. Finite element codes were utilized for thermal and stress analyses of the cavity to arrive at a suitable mechanical design capable of handling the high power dissipation. The mechanical design approach with emphasis on the cooling channel layout and mechanical stress reduction is described

Inhibition of macrophage oxidative stress prevents the reduction of ABCA-1 transporter induced by advanced glycated albumin.

Science.gov (United States)

de Souza Pinto, Raphael; Castilho, Gabriela; Paim, Bruno Alves; Machado-Lima, Adriana; Inada, Natalia M; Nakandakare, Edna Regina; Vercesi, Aníbal Eugênio; Passarelli, Marisa

2012-05-01

We investigated the role of aminoguanidine and benfotiamine on the inhibition of reactive oxygen species (ROS) generation in macrophages induced by advanced glycated albumin (AGE-albumin) and its relationship with cell cholesterol homeostasis, emphasizing the expression of the ATP binding cassette transporter A-1 (ABCA-1). AGE-albumin was made by incubating fatty acid-free albumin with 10 mM glycolaldehyde. ROS production and ABCA-1 protein level were determined by flow cytometry in J774 macrophages treated along time with control (C) or AGE-albumin alone or in the presence of aminoguanidine or benfotiamine. Mitochondrial function was evaluated by oxygraphy. Compared to C-albumin, AGE-albumin increased ROS production in macrophages, which was ascribed to the activities of NADPH oxidase and of the mitochondrial system. Mitochondrial respiratory chain activity was reduced in cells incubated with AGE-albumin. ROS generation along time was associated with the reduction in macrophage ABCA-1 protein level. Aminoguanidine prevented ROS elevation and restored the ABCA-1 content in macrophages; on the other hand, benfotiamine that promoted a lesser reduction in ROS generation was not able to restore ABCA-1 levels. Inhibition of oxidative stress induced by AGE-albumin prevents disturbances in reverse cholesterol transport by curbing the reduction of ABCA-1 elicited by advanced glycation in macrophages and therefore may contribute to the prevention of atherosclerosis in diabetes mellitus.

Dipeptide model prodrugs for the intestinal oligopeptide transporter. Affinity for and transport via hPepT1 in the human intestinal Caco-2 cell line

DEFF Research Database (Denmark)

Nielsen, C U; Andersen, R; Brodin, Birger

2001-01-01

-moieties for benzyl alcohol have been shown to maintain affinity for hPepT1. The primary aim of the present study was to investigate if modifications of the benzyl alcohol model drug influence the corresponding D-Glu-Ala and D-Asp-Ala model prodrugs' affinity for hPepT1 in Caco-2 cells. A second aim...... was to investigate the transepithelial transport and hydrolysis parameters for D-Asp(BnO)-Ala and D-Glu(BnO)-Ala across Caco-2 cell monolayers. In the present study, all investigated D-Asp-Ala and D-Glu-Ala model prodrugs retained various degrees of affinity for hPepT1 in Caco-2 cells. These affinities are used....... Transepithelial transport studies performed using Caco-2 cells of D-Asp(BnO)-Ala and D-Glu(BnO)-Ala showed that the K(m) for transepithelial transport was not significantly different for the two compounds. The maximal transport rate of the carrier-mediated flux component does not differ between the two model...

Streak-Camera Measurements with High Currents in PEP-II and Variable Optics in SPEAR3

Energy Technology Data Exchange (ETDEWEB)

Cheng, Weixeng; Fisher, Alan, a Corbett, Jeff; /SLAC

2008-06-05

A dual-axis, synchroscan streak camera was used to measure longitudinal bunch profiles in three storage rings at SLAC: the PEP-II low- and high-energy rings, and SPEAR3. At high currents, both PEP rings exhibit a transient synchronous-phase shift along the bunch train due to RF-cavity beam loading. Bunch length and profile asymmetry were measured along the train for a range of beam currents. To avoid the noise inherent in a dual-axis sweep, we accumulated single-axis synchroscan images while applying a 50-ns gate to the microchannel plate. To improve the extinction ratio, an upstream mirror pivoting at 1 kHz was synchronized with the 2kHz MCP gate to deflect light from other bunches off the photocathode. Bunch length was also measured on the HER as a function of beam energy. For SPEAR3 we measured bunch length as a function of single-bunch current for several lattices: achromatic, low-emittance and low momentum compaction. In the first two cases, resistive and reactive impedance components can be extracted from the longitudinal bunch profiles. In the low-alpha configurations, we observed natural bunch lengths approaching the camera resolution, requiring special care to remove instrumental effects, and saw evidence of periodic bursting.

Identifying Lattice, Orbit, And BPM Errors in PEP-II

International Nuclear Information System (INIS)

Decker, F.-J.; SLAC

2005-01-01

The PEP-II B-Factory is delivering peak luminosities of up to 9.2 · 10 33 1/cm 2 · l/s. This is very impressive especially considering our poor understanding of the lattice, absolute orbit and beam position monitor system (BPM). A few simple MATLAB programs were written to get lattice information, like betatron functions in a coupled machine (four all together) and the two dispersions, from the current machine and compare it the design. Big orbit deviations in the Low Energy Ring (LER) could be explained not by bad BPMs (only 3), but by many strong correctors (one corrector to fix four BPMs on average). Additionally these programs helped to uncover a sign error in the third order correction of the BPM system. Further analysis of the current information of the BPMs (sum of all buttons) indicates that there might be still more problematic BPMs

HOM power propagation and attenuation in PEP-II B-factory

International Nuclear Information System (INIS)

Lin, X.E.; Ng, C.K.; Ko, K.

1997-09-01

Most of the higher-order-mode (HOM) power that propagates in the PEP-II rings is generated i the RF cavities but its content in terms of TE and TM components has not been accurately determined. For purpose of shielding beamline components such as bellows and BPMs from TE power penetration and determining the heating on the cavity HOM absorber, this HOM power content and its distribution profile around the rings are needed. This paper calculates the TE and TM contributions of the RF cavities to the circulating HOM power and their transmission properties at another cavity downstream. By considering both the generation in, and scattering by the cavities, as well as the attenuation along the vacuum chamber, a complete distribution profile for the TE and TM HOM power can be obtained

A Chimeric Peptide Composed of a Dermaseptin Derivative and an RNA III-Inhibiting Peptide Prevents Graft-Associated Infections by Antibiotic-Resistant Staphylococci

Science.gov (United States)

Balaban, Naomi; Gov, Yael; Giacometti, Andrea; Cirioni, Oscar; Ghiselli, Roberto; Mocchegiani, Federico; Orlando, Fiorenza; D'Amato, Giuseppina; Saba, Vittorio; Scalise, Giorgio; Bernes, Sabina; Mor, Amram

2004-01-01

Staphylococcal bacteria are a prevalent cause of infections associated with foreign bodies and indwelling medical devices. Bacteria are capable of escaping antibiotic treatment through encapsulation into biofilms. RNA III-inhibiting peptide (RIP) is a heptapeptide that inhibits staphylococcal biofilm formation by obstructing quorum-sensing mechanisms. K4-S4(1-13)a is a 13-residue dermaseptin derivative (DD13) believed to kill bacteria via membrane disruption. We tested each of these peptides as well as a hybrid construct, DD13-RIP, for their ability to inhibit bacterial proliferation and suppress quorum sensing in vitro and for their efficacy in preventing staphylococcal infection in a rat graft infection model with methicillin-resistant Staphylococcus aureus (MRSA) or S. epidermidis (MRSE). In vitro, proliferation assays demonstrated that RIP had no inhibitory effect, while DD13-RIP and DD13 were equally effective, and that the chimeric peptide but not DD13 was slightly more effective than RIP in inhibiting RNA III synthesis, a regulatory RNA molecule important for staphylococcal pathogenesis. In vivo, the three peptides reduced graft-associated bacterial load in a dose-dependent manner, but the hybrid peptide was most potent in totally preventing staphylococcal infections at the lowest dose. In addition, each of the peptides acted synergistically with antibiotics. The data indicate that RIP and DD13 act in synergy by attacking bacteria simultaneously by two different mechanisms. Such a chimeric peptide may be useful for coating medical devices to prevent drug-resistant staphylococcal infections. PMID:15215107

Pregnenolone co-treatment partially restores steroidogenesis, but does not prevent growth inhibition and increased atresia in mouse ovarian antral follicles treated with mono-hydroxy methoxychlor

International Nuclear Information System (INIS)

Craig, Zelieann R.; Hannon, Patrick R.; Flaws, Jodi A.

2013-01-01

Mono-hydroxy methoxychlor (mono-OH MXC) is a metabolite of the pesticide, methoxychlor (MXC). Although MXC is known to decrease antral follicle numbers, and increase follicle death in rodents, not much is known about the ovarian effects of mono-OH MXC. Previous studies indicate that mono-OH MXC inhibits mouse antral follicle growth, increases follicle death, and inhibits steroidogenesis in vitro. Further, previous studies indicate that CYP11A1 expression and production of progesterone (P 4 ) may be the early targets of mono-OH MXC in the steroidogenic pathway. Thus, this study tested whether supplementing pregnenolone, the precursor of progesterone and the substrate for HSD3B, would prevent decreased steroidogenesis, inhibited follicle growth, and increased follicle atresia in mono-OH MXC-treated follicles. Mouse antral follicles were exposed to vehicle (dimethylsulfoxide), mono-OH MXC (10 μg/mL), pregnenolone (1 μg/mL), or mono-OH MXC and pregnenolone together for 96 h. Levels of P 4 , androstenedione (A), testosterone (T), estrone (E 1 ), and 17β-estradiol (E 2 ) in media were determined, and follicles were processed for histological evaluation of atresia. Pregnenolone treatment alone stimulated production of all steroid hormones except E 2 . Mono-OH MXC-treated follicles had decreased sex steroids, but when given pregnenolone, produced levels of P 4 , A, T, and E 1 that were comparable to those in vehicle-treated follicles. Pregnenolone treatment did not prevent growth inhibition and increased atresia in mono-OH MXC-treated follicles. Collectively, these data support the idea that the most upstream effect of mono-OH MXC on steroidogenesis is by reducing the availability of pregnenolone, and that adding pregnenolone may not be sufficient to prevent inhibited follicle growth and survival. - Highlights: • Mono-OH MXC inhibited antral follicle steroidogenesis, growth, and survival. • Pregnenolone partially restored steroidogenesis in mono-OH MXC

Pregnenolone co-treatment partially restores steroidogenesis, but does not prevent growth inhibition and increased atresia in mouse ovarian antral follicles treated with mono-hydroxy methoxychlor

Energy Technology Data Exchange (ETDEWEB)

Craig, Zelieann R., E-mail: zelieann@illinois.edu; Hannon, Patrick R., E-mail: phannon2@illinois.edu; Flaws, Jodi A., E-mail: jflaws@illinois.edu

2013-11-01

Mono-hydroxy methoxychlor (mono-OH MXC) is a metabolite of the pesticide, methoxychlor (MXC). Although MXC is known to decrease antral follicle numbers, and increase follicle death in rodents, not much is known about the ovarian effects of mono-OH MXC. Previous studies indicate that mono-OH MXC inhibits mouse antral follicle growth, increases follicle death, and inhibits steroidogenesis in vitro. Further, previous studies indicate that CYP11A1 expression and production of progesterone (P{sub 4}) may be the early targets of mono-OH MXC in the steroidogenic pathway. Thus, this study tested whether supplementing pregnenolone, the precursor of progesterone and the substrate for HSD3B, would prevent decreased steroidogenesis, inhibited follicle growth, and increased follicle atresia in mono-OH MXC-treated follicles. Mouse antral follicles were exposed to vehicle (dimethylsulfoxide), mono-OH MXC (10 μg/mL), pregnenolone (1 μg/mL), or mono-OH MXC and pregnenolone together for 96 h. Levels of P{sub 4}, androstenedione (A), testosterone (T), estrone (E{sub 1}), and 17β-estradiol (E{sub 2}) in media were determined, and follicles were processed for histological evaluation of atresia. Pregnenolone treatment alone stimulated production of all steroid hormones except E{sub 2}. Mono-OH MXC-treated follicles had decreased sex steroids, but when given pregnenolone, produced levels of P{sub 4}, A, T, and E{sub 1} that were comparable to those in vehicle-treated follicles. Pregnenolone treatment did not prevent growth inhibition and increased atresia in mono-OH MXC-treated follicles. Collectively, these data support the idea that the most upstream effect of mono-OH MXC on steroidogenesis is by reducing the availability of pregnenolone, and that adding pregnenolone may not be sufficient to prevent inhibited follicle growth and survival. - Highlights: • Mono-OH MXC inhibited antral follicle steroidogenesis, growth, and survival. • Pregnenolone partially restored steroidogenesis

Improvement of PEP-II Linear Optics with a MIA-Derived Virtual Accelerator

International Nuclear Information System (INIS)

Cerio, B.; Colgate U.

2006-01-01

In several past studies, model independent analysis, in conjunction with a virtual accelerator model, has been successful in improving PEP-II linear geometric optics. In many cases, optics improvement yielded an increase in machine luminosity. In this study, an updated characterization of linear optics is presented. With the PEP-II beam position monitor (BPM) system, four independent beam centroid orbits were extracted and used to determine phase advances and linear Green's functions among BPM locations. A magnetic lattice model was then constructed with a singular value decomposition-enhanced least-square fitting of phase advances and Green's functions, which are functions of quadrupole strengths, sextupole feed-downs, as well as BPM errors, to the corresponding measured quantities. The fitting process yielded a machine model that matched the measured linear optics of the real machine and was therefore deemed the virtual accelerator. High beta beat, as well as linear coupling, was observed in both LER and HER of the virtual accelerator. Since there was higher beta beating in LER, focus was shifted to the improvement of this ring. By adjusting select quadrupoles of the virtual LER and fitting the resulting beta functions and phase advances to those of the desired lattice, the average beta beat of the virtual machine was effectively reduced. The new magnet configuration was dialed into LER on August 10, 2006, and beta beat was reduced by a factor of three. After fine tuning HER to match the improved LER for optimal collision, a record peak luminosity of 12.069 x 10 33 cm -2 s -1 was attained on August 16, 2006

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.

Science.gov (United States)

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

Progress on PEP-II injection R ampersand D

International Nuclear Information System (INIS)

Bloom, E.; Bulos, F.; Fieguth, T.; Godfrey, G.; Loew, G.; Miller, R.

1993-06-01

The R ampersand D program described in this paper focuses on an improvement of the SLAC linac designed to extract and study a 9 GeV electron beam under stringent control of energy, energy spread, emittance, optical parameters, and timing. The extraction system begins with an on-axis pulsed magnet, followed by a magnetic lattice and diagnostic equipment required for the measurement and optimization of the above beam qualities. Design, construction, and installation of this system is the first step in the development of the overall PEP-II e ± injection system. This system is required to fill 1658 bunches of 9 GeV electrons (0.99A stored) and 3.1 GeV positrons (2.14A stored) in two separate rings in a total of about 6 minutes from zero ring current (i.e., full-fill mode, 0 to 100%) or in about 3 minutes from 80% ring current (i.e., topping-off mode, 80 to 100%). This unprecedented rate of filling can be met by a judicious use of the SLC linac, damping rings, and positron source

Progress on PEP-II injection R ampersand D

International Nuclear Information System (INIS)

Bloom, E.; Bulos, F.; Fieguth, T.; Godfrey, G.; Loew, G.; Miller, R.

1993-01-01

The R ampersand D program described in this paper focuses on an improvement of the SLAC linac designed to extract and study a 9 GeV electron beam under stringent control of energy, energy spread, emittance, optical parameters, and timing. The extraction system begins with an on-axis pulsed magnet, followed by a magnetic lattice and diagnostic equipment required for the measurement and optimization of the above beam qualities. Design, construction, and installation of this system is the first step in the development of the overall PEP-II e ± injection system. This system is required to fill 1658 bunches of 9 GeV electrons (0.99A stored) and 3.1 GeV positrons (2.14A stored) in two separate rings in a total of about 6 minutes from zero ring current (i.e., full-fill mode, 0 to 100%) or in about 3 minutes from 80% ring current (i.e., topping-off mode, 80 to 100%). This unprecedented rate of filling can be met by a judicious use of the SLC linac, damping rings, and positron source

Design of traveling wave windows for the PEP-II RF coupling network

International Nuclear Information System (INIS)

Kroll, N.M.; Ng, C.K.; Judkins, J.; Neubauer, M.

1995-05-01

The waveguide windows in the PEP-II RF coupling network have to withstand high power of 500 kW. Traveling wave windows have lower power dissipation than conventional self-matched windows, thus rendering the possibility of less stringent mechanical design. The traveling wave behavior is achieved by providing a reflecting iris on each side of the window, and depending on the configuration of the irises, traveling wave windows are characterized as inductive or capacitive types. A numerical design procedure using MAFIA has been developed for traveling wave windows. The relative advantages of inductive and capacitive windows are discussed. Furthermore, the issues of bandwidth and multipactoring are also addressed

Prevention of formation of acid drainage from high-sulfur coal refuse by inhibition of iron- and sulfur-oxidizing microorganisms. II. Inhibition in run of mine refuse under simulated field conditions

Energy Technology Data Exchange (ETDEWEB)

Dugan, P.R.

1987-01-01

The combination of sodium lauryl sulfate and benzoic acid effectively inhibits iron- and sulfur-oxidizing bacteria in coal refuse and prevents the conversion of iron pyrite to sulfate, ferric iron, and sulfuric acid, thereby significantly reducing the formation of acidic drainage from coal refuse. The inhibitors were effective in a concentration of 1.1. mg/kg refuse, and data indicate that the SLS was in excess of the concentration required. The treatment was compatible with the use of lime for neutralization of acid present prior to inhibition of its formation.

A new class of synthetic anti-lipopolysaccharide peptides inhibits influenza A virus replication by blocking cellular attachment.

Science.gov (United States)

Hoffmann, Julia; Schneider, Carola; Heinbockel, Lena; Brandenburg, Klaus; Reimer, Rudolph; Gabriel, Gülsah

2014-04-01

Influenza A viruses are a continuous threat to human health as illustrated by the 2009 H1N1 pandemic. Since circulating influenza virus strains become increasingly resistant against currently available drugs, the development of novel antivirals is urgently needed. Here, we have evaluated a recently described new class of broad-spectrum antiviral peptides (synthetic anti-lipopolysaccharide peptides; SALPs) for their potential to inhibit influenza virus replication in vitro and in vivo. We found that particularly SALP PEP 19-2.5 shows high binding affinities for the influenza virus receptor molecule, N-Acetylneuraminic acid, leading to impaired viral attachment and cellular entry. As a result, replication of several influenza virus subtypes (H7N7, H3N2 and 2009 pandemic H1N1) was strongly reduced. Furthermore, mice co-treated with PEP 19-2.5 were protected against an otherwise 100% lethal H7N7 influenza virus infection. These findings show that SALPs exhibit antiviral activity against influenza viruses by blocking virus attachment and entry into host cells. Thus, SALPs present a new class of broad-spectrum antiviral peptides for further development for influenza virus therapy. Copyright © 2014 Elsevier B.V. All rights reserved.

The neuroprotective efficacy of cell-penetrating peptides TAT, penetratin, Arg-9, and Pep-1 in glutamic acid, kainic acid, and in vitro ischemia injury models using primary cortical neuronal cultures.

Science.gov (United States)

Meloni, Bruno P; Craig, Amanda J; Milech, Nadia; Hopkins, Richard M; Watt, Paul M; Knuckey, Neville W

2014-03-01

Cell-penetrating peptides (CPPs) are small peptides (typically 5-25 amino acids), which are used to facilitate the delivery of normally non-permeable cargos such as other peptides, proteins, nucleic acids, or drugs into cells. However, several recent studies have demonstrated that the TAT CPP has neuroprotective properties. Therefore, in this study, we assessed the TAT and three other CPPs (penetratin, Arg-9, Pep-1) for their neuroprotective properties in cortical neuronal cultures following exposure to glutamic acid, kainic acid, or in vitro ischemia (oxygen-glucose deprivation). Arg-9, penetratin, and TAT-D displayed consistent and high level neuroprotective activity in both the glutamic acid (IC50: 0.78, 3.4, 13.9 μM) and kainic acid (IC50: 0.81, 2.0, 6.2 μM) injury models, while Pep-1 was ineffective. The TAT-D isoform displayed similar efficacy to the TAT-L isoform in the glutamic acid model. Interestingly, Arg-9 was the only CPP that displayed efficacy when washed-out prior to glutamic acid exposure. Neuroprotection following in vitro ischemia was more variable with all peptides providing some level of neuroprotection (IC50; Arg-9: 6.0 μM, TAT-D: 7.1 μM, penetratin/Pep-1: >10 μM). The positive control peptides JNKI-1D-TAT (JNK inhibitory peptide) and/or PYC36L-TAT (AP-1 inhibitory peptide) were neuroprotective in all models. Finally, in a post-glutamic acid treatment experiment, Arg-9 was highly effective when added immediately after, and mildly effective when added 15 min post-insult, while the JNKI-1D-TAT control peptide was ineffective when added post-insult. These findings demonstrate that different CPPs have the ability to inhibit neurodamaging events/pathways associated with excitotoxic and ischemic injuries. More importantly, they highlight the need to interpret neuroprotection studies when using CPPs as delivery agents with caution. On a positive note, the cytoprotective properties of CPPs suggests they are ideal carrier molecules to

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

Science.gov (United States)

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.

Secondary Electron Emission Yields from PEP-II Accelerator Materials

International Nuclear Information System (INIS)

Kirby, Robert E.

2000-01-01

The PEP-II B-Factory at SLAC operates with aluminum alloy and copper vacuum chambers, having design positron and electron beam currents of 2 and 1 A, respectively. Titanium nitride coating of the aluminum vacuum chamber in the arcs of the positron ring is needed in order to reduce undesirable electron-cloud effects. The total secondary electron emission yield of TiN-coated aluminum alloy has been measured after samples of beam chamber material were exposed to air and again after electron-beam bombardment, as a function of incident electron beam angle and energy. The results may be used to simulate and better understand electron-cloud effects under actual operating conditions. We also present yield measurements for other accelerator materials because new surface effects are expected to arise as beam currents increase. Copper, in particular, is growing in popularity for its good thermal conductivity and self-radiation-shielding properties. The effect of electron bombardment, ''conditioning'', on the yield of TiN and copper is shown

Sensitivity of the PEP beam transport line to perturbations

International Nuclear Information System (INIS)

Peterson, J.M.; Brown, K.L.

1979-03-01

The sensitivity of a beam-transport line to various perturbations determines the extent to which one can simplify component design and relax tolerances. For the PEP injection lines, effects of various fabrication errors, magnet misalignments, and residual gas scattering were studied. Using the TURTLE ray-tracing program, it is found that magnetic-field errors corresponding to a relative sextupole strength in the dipoles of 0.5% and/or a relative sextupole or octupole strength in the quadrupoles of 5% are permissible. This allows relatively loose tolerances in magnet fabrication. Transverse misalignment of a quadrupole by a distance x causes the beam centroid to be displaced downstream by as much as 5x. This requires a quadrupole alignment accuracy of +- 0.5 mm or better. No compensation for the earth's field is necessary because an integral number of optical wavelengths and a short wavelength were used for the design. Analysis shows that beam broadening from multiple coulomb scattering is insignificant for pressures of less than 1/10 torr

Higher order mode damping studies on the PEP-II B-Factory RF cavity

International Nuclear Information System (INIS)

Rimmer, R.; Goldberg, D.; Lambertson, G.; Voelker, F.; Ko, K.; Kroll, N.; Pendleton, R.; Schwarz, H.; Adams, F.; De Jong, M.

1992-03-01

We describe studies of the higher-order-mode (HOM) properties of the prototype 476 MHz RF cavity for the proposed PEP-II B-Factory and a waveguide damping scheme to reduce possible HOM-driven coupled-bunch beam instability growth. Numerical studies include modelling of the HOM spectrum using MAFIA and ARGUS, and calculation of the loaded Q's of the damped modes using data from these codes and the Kroll-Yu method. We discuss briefly the experimental investigations of the modes, which will be made in a full-size low-power test cavity, using probes, wire excitation and bead perturbation methods

High-power RF cavity R ampersand D for the PEP-II B Factory

International Nuclear Information System (INIS)

Rimmer, R.; Lambertson, G.; Hodgson, J.

1994-06-01

We describe the development of a high-power test model of the 476 MHz RF cavity for the PEP-II B Factory. This cavity is designed to demonstrate the feasibility of a high-power design with higher-order mode (HOM) damping waveguides and the fabrication technologies involved, and it can also be used to evaluate aperture or loop couplers and various RF windows. Changes to the RF design to reduce peak surface heating are discussed and results of finite-element analyses of temperature and stress are presented. Fabrication methods for the prototype and subsequent production cavities are discussed

Developing Novel PepT1-Targeted Modulators for Inflammatory Bowel Disease (IBD) Therapy

Science.gov (United States)

2016-10-01

physiological roles. PepT1 is found in the small intestine where it absorbs dietary degradation products and therapeutic agents such as antibiotics ...results provide a framework for developing more potent ligands in various cellular and animal IBD models, directly addressing Aims 2 and 3 of our... Products …………………………………….………….……………4 7. Participants & Other Collaborating Organizations…….…………….5 8. Special Reporting Requirements…………..………………………5 9

HyPEP-FY 07 Annual Report: A Hydrogen Production Plant Efficiency Calculation Program

Energy Technology Data Exchange (ETDEWEB)

Chang Oh

2007-09-01

The Very High Temperature Gas-Cooled Reactor (VHTR) coupled to the High Temperature Steam Electrolysis (HTSE) process is one of two reference integrated systems being investigated by the U.S. Department of Energy and Idaho National Laboratory for the production of hydrogen. In this concept the VHTR outlet temperature of 900 °C provides thermal energy and high efficiency electricity for the electrolysis of steam in the HTSE process. In the second reference system the Sulfur Iodine (SI) process is coupled to the VHTR to produce hydrogen thermochemically. In the HyPEP project we are investigating and characterizing these two reference systems with respect to production, operability, and safety performance criteria. Under production, plant configuration and working fluids are being studied for their effect on efficiency. Under operability, control strategies are being developed with the goal of maintaining equipment within operating limits while meeting changes in demand. Safety studies are to investigate plant response for equipment failures. Specific objectives in FY07 were (1) to develop HyPEP Beta and verification and validation (V&V) plan, (2) to perform steady state system integration, (3) to perform parametric studies with various working fluids and power conversion unit (PCU) configurations, (4) the study of design options such as pressure, temperature, etc. (5) to develop a control strategy and (6) to perform transient analyses for plant upsets, control strategy, etc for hydrogen plant with PCU. This report describes the progress made in FY07 in each of the above areas. (1) The HyPEP code numeric scheme and Graphic User Interface have been tested and refined since the release of the alpha version a year ago. (2) The optimal size and design condition for the intermediate heat exchanger, one of the most important components for integration of the VHTR and HTSE plants, was estimated. (3) Efficiency calculations were performed for a variety of working fluids for

Polysaccharides from Wolfberry Prevents Corticosterone-Induced Inhibition of Sexual Behavior and Increases Neurogenesis

Science.gov (United States)

Lau, Benson Wui-Man; Lee, Jada Chia-Di; Li, Yue; Fung, Sophia Man-Yuk; Sang, Yan-Hua; Shen, Jiangang; Chang, Raymond Chuen-Chung; So, Kwok-Fai

2012-01-01

Lycium barbarum, commonly known as wolfberry, has been used as a traditional Chinese medicine for the treatment of infertility and sexual dysfunction. However, there is still a scarcity of experimental evidence to support the pro-sexual effect of wolfberry. The aim of this study is to determine the effect of Lycium barbarum polysaccharides (LBP) on male sexual behavior of rats. Here we report that oral feeding of LBP for 21 days significantly improved the male copulatory performance including increase of copulatory efficiency, increase of ejaculation frequency and shortening of ejaculation latency. Furthermore, sexual inhibition caused by chronic corticosterone was prevented by LBP. Simultaneously, corticosterone suppressed neurogenesis in subventricular zone and hippocampus in adult rats, which could be reversed by LBP. The neurogenic effect of LBP was also shown in vitro. Significant correlation was found between neurogenesis and sexual performance, suggesting that the newborn neurons are associated with reproductive successfulness. Blocking neurogenesis in male rats abolished the pro-sexual effect of LBP. Taken together, these results demonstrate the pro-sexual effect of LBP on normal and sexually-inhibited rats, and LBP may modulate sexual behavior by regulating neurogenesis. PMID:22523540

Current perspectives in HIV post-exposure prophylaxis

Directory of Open Access Journals (Sweden)

Sultan B

2014-10-01

Full Text Available Binta Sultan,1,2 Paul Benn,1 Laura Waters1 1Department of Genitourinary Medicine, Mortimer Market Centre, Central and North West London NHS Foundation Trust, London, UK; 2Centre for Sexual Health and HIV Research, University College London, London, UK Abstract: The incidence of human immunodeficiency virus (HIV infection continues to rise among core groups and efforts to reduce the numbers of new infections are being redoubled. Post-exposure prophylaxis (PEP is the use of short-term antiretroviral therapy (ART to reduce the risk of acquisition of HIV infection following exposure. Current guidelines recommend a 28-day course of ART within 36–72 hours of exposure to HIV. As long as individuals continue to be exposed to HIV there will be a role for PEP in the foreseeable future. Nonoccupational PEP, the vast majority of which is for sexual exposure (PEPSE, has a significant role to play in HIV prevention efforts. Awareness of PEP and its availability for both clinicians and those who are eligible to receive it are crucial to ensure that PEP is used to its full potential in any HIV prevention strategy. In this review, we provide current evidence for the use of PEPSE, assessment of the risk of HIV transmission, indications for PEP, drug regimens, and management of patients started on PEP. We summarize national and international guidelines for the use of PEPSE. We explore the place of PEP within the wider strategy of reducing HIV incidence rates in the era of treatment as prevention and pre-exposure prophylaxis. We also consider the implications of recent data from interventional and observational studies demonstrating significant reductions in the risk of HIV transmission within a serodiscordant relationship if the HIV-positive partner is taking effective ART upon PEP guidelines. Keywords: post-exposure prophylaxis, pre-exposure prophylaxis, treatment as prevention, human immunodeficiency virus

Several hPepT1-transported drugs are substrates of the Escherichia coli proton-coupled oligopeptide transporter YdgR

DEFF Research Database (Denmark)

Prabhala, Bala K; Aduri, Nanda G; Iqbal, Mazhar

2017-01-01

transported by hPepT1. The transport of these drugs was evaluated using the prototypical POT YdgR from E. coli. The transport studies were pursued through combining cell-based assays with liquid chromatography-tandem mass spectrometric (LC-MS/MS) analysis. These investigations revealed that YdgR from E. coli...

Soluble FGFR4 extracellular domain inhibits FGF19-induced activation of FGFR4 signaling and prevents nonalcoholic fatty liver disease

Energy Technology Data Exchange (ETDEWEB)

Chen, Qiang [State Key Laboratory of Stress Cell Biology, School of Life Sciences, Xiamen University, Xiamen (China); The First Affiliated Hospital of Xiamen University, Xiamen (China); Jiang, Yuan; An, Yuan; Zhao, Na; Zhao, Yang [State Key Laboratory of Stress Cell Biology, School of Life Sciences, Xiamen University, Xiamen (China); Yu, Chundong, E-mail: cdyu@xmu.edu.cn [State Key Laboratory of Stress Cell Biology, School of Life Sciences, Xiamen University, Xiamen (China)

2011-06-17

Highlights: {yields} Soluble FGFR4 extracellular domain (FGFR4-ECD) was effectively expressed. {yields} FGFR4-ECD inhibited FGF19-induced activation of FGFR4 signaling. {yields} FGFR4-ECD reduced palmitic acid-induced steatosis of HepG2 cells. {yields} FGFR4-ECD reduced tetracycline-induced fatty liver in mice. {yields} FGFR4-ECD partially restored tetracycline-repressed PPAR{alpha} expression. -- Abstract: Fibroblast growth factor receptor 4 (FGFR4) is a transmembrane tyrosine kinase receptor that plays a crucial role in the regulation of hepatic bile acid and lipid metabolism. FGFR4 underlies high-fat diet-induced hepatic steatosis, suggesting that inhibition of FGFR4 activation may be an effective way to prevent or treat nonalcoholic fatty liver disease (NAFLD). To determine whether neutralization of FGFR4 ligands by soluble FGFR4 extracellular domain (FGFR4-ECD) can inhibit the activation of FGFR4, we constructed FGFR4-ECD expression vector and showed that FGFR4-ECD was effectively expressed in cells and secreted into culture medium. FGFR4-ECD inhibited FGF19-induced activation of FGFR4 signaling and reduced steatosis of HepG2 induced by palmitic acid in vitro. Furthermore, in a tetracycline-induced fatty liver model, expression of FGFR4-ECD in mouse liver reduced the accumulation of hepatic lipids and partially restored the expression of peroxisome proliferator-activated receptor {alpha} (PPAR{alpha}), which promotes the mitochondrial fatty acid beta-oxidation but is repressed by tetracycline. Taken together, these results demonstrate that FGFR4-ECD can block FGFR4 signaling and prevent hepatic steatosis, highlighting the potential value of inhibition of FGFR4 signaling as a method for therapeutic intervention against NAFLD.

Soluble FGFR4 extracellular domain inhibits FGF19-induced activation of FGFR4 signaling and prevents nonalcoholic fatty liver disease

International Nuclear Information System (INIS)

Chen, Qiang; Jiang, Yuan; An, Yuan; Zhao, Na; Zhao, Yang; Yu, Chundong

2011-01-01

Highlights: → Soluble FGFR4 extracellular domain (FGFR4-ECD) was effectively expressed. → FGFR4-ECD inhibited FGF19-induced activation of FGFR4 signaling. → FGFR4-ECD reduced palmitic acid-induced steatosis of HepG2 cells. → FGFR4-ECD reduced tetracycline-induced fatty liver in mice. → FGFR4-ECD partially restored tetracycline-repressed PPARα expression. -- Abstract: Fibroblast growth factor receptor 4 (FGFR4) is a transmembrane tyrosine kinase receptor that plays a crucial role in the regulation of hepatic bile acid and lipid metabolism. FGFR4 underlies high-fat diet-induced hepatic steatosis, suggesting that inhibition of FGFR4 activation may be an effective way to prevent or treat nonalcoholic fatty liver disease (NAFLD). To determine whether neutralization of FGFR4 ligands by soluble FGFR4 extracellular domain (FGFR4-ECD) can inhibit the activation of FGFR4, we constructed FGFR4-ECD expression vector and showed that FGFR4-ECD was effectively expressed in cells and secreted into culture medium. FGFR4-ECD inhibited FGF19-induced activation of FGFR4 signaling and reduced steatosis of HepG2 induced by palmitic acid in vitro. Furthermore, in a tetracycline-induced fatty liver model, expression of FGFR4-ECD in mouse liver reduced the accumulation of hepatic lipids and partially restored the expression of peroxisome proliferator-activated receptor α (PPARα), which promotes the mitochondrial fatty acid beta-oxidation but is repressed by tetracycline. Taken together, these results demonstrate that FGFR4-ECD can block FGFR4 signaling and prevent hepatic steatosis, highlighting the potential value of inhibition of FGFR4 signaling as a method for therapeutic intervention against NAFLD.

Aldose reductase inhibition prevents allergic airway remodeling through PI3K/AKT/GSK3β pathway in mice.

Directory of Open Access Journals (Sweden)

Umesh C S Yadav

Full Text Available Long-term and unresolved airway inflammation and airway remodeling, characteristic features of chronic asthma, if not treated could lead to permanent structural changes in the airways. Aldose reductase (AR, an aldo-sugar and lipid aldehyde metabolizing enzyme, mediates allergen-induced airway inflammation in mice, but its role in the airway remodeling is not known. In the present study, we have examined the role of AR on airway remodeling using ovalbumin (OVA-induced chronic asthma mouse model and cultured human primary airway epithelial cells (SAECs and mouse lung fibroblasts (mLFs.Airway remodeling in chronic asthma model was established in mice sensitized and challenged twice a week with OVA for 6 weeks. AR inhibitor, fidarestat, was administered orally in drinking water after first challenge. Inflammatory cells infiltration in the lungs and goblet cell metaplasia, airway thickening, collagen deposition and airway hyper-responsiveness (AHR in response to increasing doses of methacholine were assessed. The TGFβ1-induced epithelial-mesenchymal transition (EMT in SAECs and changes in mLFs were examined to investigate AR-mediated molecular mechanism(s of airway remodeling.In the OVA-exposed mice for 6 wks inflammatory cells infiltration, levels of inflammatory cytokines and chemokines, goblet cell metaplasia, collagen deposition and AHR were significantly decreased by treatment with AR inhibitor, fidarestat. Further, inhibition of AR prevented TGFβ1-induced altered expression of E-cadherin, Vimentin, Occludin, and MMP-2 in SAECs, and alpha-smooth muscle actin and fibronectin in mLFs. Further, in SAECs, AR inhibition prevented TGFβ1- induced activation of PI3K/AKT/GSK3β pathway but not the phosphorylation of Smad2/3.Our results demonstrate that allergen-induced airway remodeling is mediated by AR and its inhibition blocks the progression of remodeling via inhibiting TGFβ1-induced Smad-independent and PI3K/AKT/GSK3β-dependent pathway.

Nicorandil prevents right ventricular remodeling by inhibiting apoptosis and lowering pressure overload in rats with pulmonary arterial hypertension.

Directory of Open Access Journals (Sweden)

Xiang-Rong Zuo

Full Text Available BACKGROUND: Most of the deaths among patients with severe pulmonary arterial hypertension (PAH are caused by progressive right ventricular (RV pathological remodeling, dysfunction, and failure. Nicorandil can inhibit the development of PAH by reducing pulmonary artery pressure and RV hypertrophy. However, whether nicorandil can inhibit apoptosis in RV cardiomyocytes and prevent RV remodeling has been unclear. METHODOLOGY/PRINCIPAL FINDINGS: RV remodeling was induced in rats by intraperitoneal injection of monocrotaline (MCT. RV systolic pressure (RVSP was measured at the end of each week after MCT injection. Blood samples were drawn for brain natriuretic peptide (BNP ELISA analysis. The hearts were excised for histopathological, ultrastructural, immunohistochemical, and Western blotting analyses. The MCT-injected rats exhibited greater mortality and less weight gain and showed significantly increased RVSP and RV hypertrophy during the second week. These worsened during the third week. MCT injection for three weeks caused pathological RV remodeling, characterized by hypertrophy, fibrosis, dysfunction, and RV mitochondrial impairment, as indicated by increased levels of apoptosis. Nicorandil improved survival, weight gain, and RV function, ameliorated RV pressure overload, and prevented maladaptive RV remodeling in PAH rats. Nicorandil also reduced the number of apoptotic cardiomyocytes, with a concomitant increase in Bcl-2/Bax ratio. 5-hydroxydecanoate (5-HD reversed these beneficial effects of nicorandil in MCT-injected rats. CONCLUSIONS/SIGNIFICANCE: Nicorandil inhibits PAH-induced RV remodeling in rats not only by reducing RV pressure overload but also by inhibiting apoptosis in cardiomyocytes through the activation of mitochondrial ATP-sensitive K(+ (mitoK(ATP channels. The use of a mitoK(ATP channel opener such as nicorandil for PAH-associated RV remodeling and dysfunction may represent a new therapeutic strategy for the amelioration of RV

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

Science.gov (United States)

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.

Beam-beam dynamics during the injection process at the PEP-II B-Factory

International Nuclear Information System (INIS)

Chin, Yong Ho.

1991-10-01

This paper is concerned with beam-beam effects during the injection process at the proposed asymmetric SLAC/LBL/LLNL B-Factory based on PEP (PEP-2). For symmetric colliders, the primary source of the beam-beam effect is the head-on collision at the interaction point (IP), and this effect can be mitigated by separating the beams during the injection process. For an asymmetric collider, which intrinsically consists of two separate rings, the bunches not only collide at the IP but experience a long-range beam-beam force on the way into and out of the IP region. These collisions are called ''parasitic crossings (PC).'' The parasitic crossings emerge as a potential source of far stronger beam-beam impact during the injection process for the following reason. In the proposed injection scheme of the APIARY-6.3d design, the bunches are injected horizontally into the two rings with large horizontal offset of 8σ Ox sptm where σ Ox sptm is the nominal horizontal storage ring beam size at the end of the septum magnet. Then, the injected beam starts to travel around the ring oscillating horizontally. For the sake of discussion, let us assume that the beam in the other ring has already been fully stored. When the injected beam arrives at the 1st PC, where the two nominal orbits are separated horizontally by about 7.6 times the nominal horizontal beam size of the low energy ring, it may pass through the other beam far more closely than at the nominal separation distance, or it may even strike the other beam head-on

Low energy ring lattice of the PEP-II asymmetric B-Factory

International Nuclear Information System (INIS)

Cai, Y.; Donald, M.; Helm, R.; Irwin, J.; Nosochkov, Y.; Ritson, D.M.; Yan, Y.

1995-01-01

Developing a lattice that contains a very low beta value at the interaction point (IP) and has adequate dynamic aperture is one of the major challenges in designing the PEP-II asymmetric B-factory. For the Low Energy Ring (LER) the authors have studied several different chromatic correction schemes since the conceptual design report (CDR). Based on these studies, a hybrid solution with local and semi-local chromatic sextupoles has been selected as the new baseline lattice to replace the local scheme in the CDR. The new design simplifies the interaction region (IR) and reduces the number of sextupoles in the arcs. Arc sextupoles are paired at π phase difference and are not interleaved. In this paper the authors describe the baseline lattice with the emphasis on the lattice changes made since the CDR

DIDS prevents ischemic membrane degradation in cultured hippocampal neurons by inhibiting matrix metalloproteinase release.

Directory of Open Access Journals (Sweden)

Matthew E Pamenter

prevented stimulus-evoked release of von Willebrand Factor from human umbilical vein endothelial cells. We conclude that DIDS inhibits MMP exocytosis and through this mechanism preserves neuronal membrane integrity during pathological stress.

Commissioning experience with the PEP-II low-level RF system

International Nuclear Information System (INIS)

Corredoura, P.; Allison, S.; Claus, R.; Ross, W.; Sapozhnikov, L.; Schwarz, H.D.; Tighe, R.; Yee, C.; Ziomek, C.

1997-05-01

The low-level RF system for PEP-II is a modular design housed in a VXI environment and supported by EPICS. All signal processing and control is done at baseband using in-phase and quadrature (IQ) techniques. Remotely configurable RF feedback loops are used to control coupled-bunch instabilities driven by the accelerating mode of the RF cavities. A programmable DSP based feedback loop is implemented to control phase variations across the klystron due to the required adjustment of the cathode voltage to limit cathode power dissipation. The DSP loop also adaptively cancels modulations caused by klystron power supply ripple at selected power line harmonics between 60 Hz and 10 kHz. The system contains a built-in baseband network analyzer which allows remote measurement of the RF feedback loop transfer functions and automated configuration of these loops. This paper presents observations and measured data from the system

Extracellular cystatin SN and cathepsin B prevent cellular senescence by inhibiting abnormal glycogen accumulation.

Science.gov (United States)

Oh, Sang-Seok; Park, Soojong; Lee, Ki-Won; Madhi, Hamadi; Park, Sae Gwang; Lee, Hee Gu; Cho, Yong-Yeon; Yoo, Jiyun; Dong Kim, Kwang

2017-04-06

Cystatin SN (CST1), a known inhibitor of cathepsin B (CatB), has important roles in tumor development. Paradoxically, CatB is a member of the cysteine cathepsin family that acts in cellular processes, such as tumor development and invasion. However, the relationship between CST1 and CatB, and their roles in tumor development are poorly understood. In this study, we observed that the knockdown of CST1 induced the activity of senescence-associated β-galactosidase, a marker of cellular senescence, and expression of senescence-associated secretory phenotype genes, including interleukin-6 and chemokine (C-C motif) ligand 20, in MDA-MB-231 and SW480 cancer cells. Furthermore, CST1 knockdown decreased extracellular CatB activity, and direct CatB inhibition, using specific inhibitors or shCatB, induced cellular senescence. Reconstitution of CST1 restored CatB activity and inhibited cellular senescence in CST1 knockdown cells. CST1 knockdown or CatB inhibition increased glycogen synthase (GS) kinase 3β phosphorylation at serine 9, resulting in the activation of GS and the induction of glycogen accumulation associated with cellular senescence. Importantly, CST1 knockdown suppressed cancer cell proliferation, soft agar colony growth and tumor growth in a xenograft model. These results indicate that CST1-mediated extracellular CatB activity enhances tumor development by preventing cellular senescence. Our findings suggest that antagonists of CST1 or inhibitors of CatB are potential anticancer agents.

A Fungus-Inducible Pepper Carboxylesterase Exhibits Antifungal Activity by Decomposing the Outer Layer of Fungal Cell Walls.

Science.gov (United States)

Seo, Hyo-Hyoun; Park, Ae Ran; Lee, Hyun-Hwa; Park, Sangkyu; Han, Yun-Jeong; Hoang, Quyen T N; Choi, Gyung Ja; Kim, Jin-Cheol; Kim, Young Soon; Kim, Jeong-Il

2018-05-01

Colletotrichum species are major fungal pathogens that cause devastating anthracnose diseases in many economically important crops. In this study, we observed the hydrolyzing activity of a fungus-inducible pepper carboxylesterase (PepEST) on cell walls of C. gloeosporioides, causing growth retardation of the fungus by blocking appressorium formation. To determine the cellular basis for the growth inhibition, we observed the localization of PepEST on the fungus and found the attachment of the protein on surfaces of conidia and germination tubes. Moreover, we examined the decomposition of cell-wall materials from the fungal surface after reaction with PepEST, which led to the identification of 1,2-dithiane-4,5-diol (DTD) by gas chromatography mass spectrometry analysis. Exogenous DTD treatment did not elicit expression of defense-related genes in the host plant but did trigger the necrosis of C. gloeosporioides. Furthermore, the DTD compound displayed protective effects on pepper fruits and plants against C. gloeosporioides and C. coccodes, respectively. In addition, DTD was also effective in preventing other diseases, such as rice blast, tomato late blight, and wheat leaf rust. Therefore, our results provide evidence that PepEST is involved in hydrolysis of the outmost layer of the fungal cell walls and that DTD has antifungal activity, suggesting an alternative strategy to control agronomically important phytopathogens.

A New Chicane Experiment In PEP-II to Test Mitigations of the Electron Cloud Effect for Linear Colliders

International Nuclear Information System (INIS)

Pivi, M

2008-01-01

Beam instability caused by the electron cloud has been observed in positron and proton storage rings, and it is expected to be a limiting factor in the performance of future colliders [1-3]. The effect is expected to be particularly severe in magnetic field regions. To test possible mitigation methods in magnetic fields, we have installed a new 4-dipole chicane experiment in the PEP-II Low Energy Ring (LER) at SLAC with both bare and TiN-coated aluminum chambers. In particular, we have observed a large variation of the electron flux at the chamber wall as a function of the chicane dipole field. We infer this is a new high order resonance effect where the energy gained by the electrons in the positron beam depends on the phase of the electron cyclotron motion with respect to the bunch crossing, leading to a modulation of the secondary electron production. Presumably the cloud density is modulated as well and this resonance effect could be used to reduce its magnitude in future colliders. We present the experimental results obtained during January 2008 until the April final shut-down of the PEP-II machine

NecroX-7 prevents oxidative stress-induced cardiomyopathy by inhibition of NADPH oxidase activity in rats

Energy Technology Data Exchange (ETDEWEB)

Park, Joonghoon; Park, Eok; Ahn, Bong-Hyun; Kim, Hyoung Jin [LG Life Sciences Ltd., R and D Park, Daejeon, 305-380 (Korea, Republic of); Park, Ji-hoon [Department of Biochemistry, School of Medicine, Chungnam National University, Daejeon, 301-747 (Korea, Republic of); Koo, Sun Young; Kwak, Hyo-Shin; Park, Heui Sul; Kim, Dong Wook; Song, Myoungsub; Yim, Hyeon Joo; Seo, Dong Ook [LG Life Sciences Ltd., R and D Park, Daejeon, 305-380 (Korea, Republic of); Kim, Soon Ha, E-mail: shakim@lgls.com [LG Life Sciences Ltd., R and D Park, Daejeon, 305-380 (Korea, Republic of)

2012-08-15

Oxidative stress is one of the causes of cardiomyopathy. In the present study, NecroXs, novel class of mitochondrial ROS/RNS scavengers, were evaluated for cardioprotection in in vitro and in vivo model, and the putative mechanism of the cardioprotection of NecroX-7 was investigated by global gene expression profiling and subsequent biochemical analysis. NecroX-7 prevented tert-butyl hydroperoxide (tBHP)-induced death of H9C2 rat cardiomyocytes at EC{sub 50} = 0.057 μM. In doxorubicin (DOX)-induced cardiomyopathy in rats, NecroX-7 significantly reduced the plasma levels of creatine kinase (CK-MB) and lactate dehydrogenase (LDH) which were increased by DOX treatment (p < 0.05). Microarray analysis revealed that 21 genes differentially expressed in tBHP-treated H9C2 cells were involved in ‘Production of reactive oxygen species’ (p = 0.022), and they were resolved by concurrent NecroX-7 treatment. Gene-to-gene networking also identified that NecroX-7 relieved cell death through Ncf1/p47phox and Rac2 modulation. In subsequent biochemical analysis, NecroX-7 inhibited NADPH oxidase (NOX) activity by 53.3% (p < 0.001). These findings demonstrate that NecroX-7, in part, provides substantial protection of cardiomyopathy induced by tBHP or DOX via NOX-mediated cell death. -- Highlights: ► NecroX-7 prevented tert-butyl hydroperoxide-induced in vitro cardiac cell death. ► NecroX-7 ameliorated doxorubicin-induced in vivo cardiomyopathy. ► NecroX-7 prevented oxidative stress and necrosis-enriched transcriptional changes. ► NecroX-7 effectively inhibited NADPH oxidase activation. ► Cardioprotection of Necro-7 was brought on by modulation of NADPH oxidase activity.

Lithium prevents early cytosolic calcium increase and secondary injurious calcium overload in glycolytically inhibited endothelial cells

Energy Technology Data Exchange (ETDEWEB)

Bosche, Bert, E-mail: bert.bosche@uk-essen.de [Department of Neurology, University of Duisburg-Essen (Germany); Max Planck Institute for Neurological Research with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne (Germany); Schäfer, Matthias, E-mail: matthias.schaefer@sanofi.com [Institute of Physiology, Justus-Liebig-University Giessen (Germany); Graf, Rudolf, E-mail: rudolf.graf@nf.mpg.de [Max Planck Institute for Neurological Research with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne (Germany); Härtel, Frauke V., E-mail: frauke.haertel@tu-dresden.de [Institute of Physiology, Medical Faculty Carl Gustav Carus, Technical University Dresden (Germany); Schäfer, Ute, E-mail: ute.schaefer@medunigraz.at [Research Unit for Experimental Neurotraumatology, Medical University of Graz (Austria); Noll, Thomas, E-mail: thomas.noll@tu-dresden.de [Institute of Physiology, Medical Faculty Carl Gustav Carus, Technical University Dresden (Germany)

2013-05-03

Highlights: •We investigate free calcium as a central signalling element in endothelial cells. •Inhibition of glycolysis with 2-deoxy-D-glucose reduces cellular ATP. •This manoeuvre leads to a biphasic increase and overload of free calcium. •Pre-treatment with lithium for 24 h abolishes both phases of the calcium increase. •This provides a new strategy to protect endothelial calcium homeostasis and barrier function. -- Abstract: Cytosolic free calcium concentration ([Ca{sup 2+}]{sub i}) is a central signalling element for the maintenance of endothelial barrier function. Under physiological conditions, it is controlled within narrow limits. Metabolic inhibition during ischemia/reperfusion, however, induces [Ca{sup 2+}]{sub i} overload, which results in barrier failure. In a model of cultured porcine aortic endothelial monolayers (EC), we addressed the question of whether [Ca{sup 2+}]{sub i} overload can be prevented by lithium treatment. [Ca{sup 2+}]{sub i} and ATP were analysed using Fura-2 and HPLC, respectively. The combined inhibition of glycolytic and mitochondrial ATP synthesis by 2-desoxy-D-glucose (5 mM; 2-DG) plus sodium cyanide (5 mM; NaCN) caused a significant decrease in cellular ATP content (14 ± 1 nmol/mg protein vs. 18 ± 1 nmol/mg protein in the control, n = 6 culture dishes, P < 0.05), an increase in [Ca{sup 2+}]{sub i} (278 ± 24 nM vs. 71 ± 2 nM in the control, n = 60 cells, P < 0.05), and the formation of gaps between adjacent EC. These observations indicate that there is impaired barrier function at an early state of metabolic inhibition. Glycolytic inhibition alone by 10 mM 2-DG led to a similar decrease in ATP content (14 ± 2 nmol/mg vs. 18 ± 1 nmol/mg in the control, P < 0.05) with a delay of 5 min. The [Ca{sup 2+}]{sub i} response of EC was biphasic with a peak after 1 min (183 ± 6 nM vs. 71 ± 1 nM, n = 60 cells, P < 0.05) followed by a sustained increase in [Ca{sup 2+}]{sub i}. A 24-h pre-treatment with 10 mM of lithium

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

Science.gov (United States)

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

2017-03-01

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

The PEP II injection kicker system

International Nuclear Information System (INIS)

Pappas, G.C.; Donaldson, A.R.; Williams, D.

1997-07-01

PEP II or the B Factory consists of two asymmetric storage rings. The injection energy for electrons is 9 GeV, while that for positrons is 3.1 GeV. The bend angle into the high energy ring (HER) is 0.35 m-rad, and the angle into the low energy ring (LER) is 0.575 m-rad. The magnetic length for the HER kicker is 0.85 m, and 0.55 m for the LER kicker. The field produced by the magnet is therefore 123.5 G for the HER, and 132 G for the LER. Each ring has a kicker magnet upstream of the injection line which is used to distort the orbit of the stored beam. An identical magnet downstream of the injection line is used to restore the orbit of the stored beam and inject the incoming beam. The two magnets are driven in parallel by the modulator. The apeture of the magnets is 3.86x3.46 cm (HxV). Therefore the current required to drive the HER is 863 A, while for the LER it is 756 A. The inductance of the magnet is approximately 1.4 uH/m. The current pulse is a critically damped sinusoid with a rise time of less than 300 ns. A kicker system has been designed which can be used for injection of both beams by varying the charge of voltage. The modulator uses a conjugate circuit to match the impedance of the magnet, and coupling to the beam chamber

Trickle-Charge: a New Operational Mode for PEP-II

International Nuclear Information System (INIS)

Kozanecki, W.; Colocho, W.S.; Decker, F.-J.; Ecklund, S.; Fisher, A.S.; Iverson, R.H.; O'Grady, C.; Seeman, J.; Sullivan, M.K.; Turner, J.L.; Weaver, M.; Wienands, U.; SLAC

2005-01-01

In regular top-up-and-coast operation, PEP-II average luminosity is about 70-75% of the peak luminosity due to detector ramp-down and ramp-up times plus the time it takes to top-up both beams. We recently commissioned a new operational mode where the Low Energy Ring is injected continuously without ramping down the detector. The benefits--increased luminosity lifetime and roughly half the number of top-ups per shift--were expected to give an increase in delivered luminosity of about 15% at the same peak luminosity; this was confirmed in test runs. In routine trickle operation, however, it appears that the increase in delivered luminosity is more than twice that due to an increase in availability credited to the more stable operating conditions during trickle operation. Further gains were made when continuous injection was extended to the high energy ring as well. In this paper we will present our operational experience as well as some of the diagnostics we use to monitor and maintain tuning of the machine in order to control injection background and protect the detector

PEP-II Large Power Supplies Rebuild Program at SLAC

CERN Document Server

de Lira, Antonio C; Lipari, James J; da Silva Rafael, Fernando

2005-01-01

At PEP-II, seven large power supplies (LGPS) are used to power quad magnets in the electron-positron collider region. The LGPS ratings range from 72kW to 270kW, and were installed in 1997. They are unipolar off-line switch mode supplies, with a 6 pulse bridge rectifying 480VAC, 3-phase input power to yield 650VDC unregulated. This unregulated 650VDC is then input into one (or two) IGBT H-bridges, which convert the DC into PWM 16 kHz square wave AC. This high frequency AC drives the primary side of a step-down transformer followed by rectifiers and low pass filters. Over the years, these LGPS have presented many problems mainly in their control circuits, making it difficult to troubleshoot and affecting the overall accelerator availability. A redesign/rebuilding program for these power supplies was established under the coordination of the Power Conversion Department at SLAC. During the 2004 accelerator summer shutdown all the control circuits in these supplies were redesigned and replaced. A new PWM control b...

Lattice Effects Due to High Currents in PEP-II

International Nuclear Information System (INIS)

Decker, F.-J.; Smith, H.; Turner, J.L.; SLAC

2005-01-01

The very high beam currents in the PEP-II B-Factory have caused many expected and unexpected effects: Synchrotron light fans move the beam pipe and cause dispersion; higher order modes cause excessive heating, e-clouds around the positron beam blow up its beam size. Here we describe an effect where the measured dispersion of the beam in the Low Energy Ring (LER) is different at high and at low beam currents. The dispersion was iteratively lowered by making anti-symmetric orbit bumps in many sextupole duplets, checking each time with a dispersion measurement where a dispersive kick is generated. This can be done parasitically during collisions. It was a surprise when checking the low current characterization data that there is a change. Subsequent high and low current measurements confirmed the effect. One source was believed to be located far away from any synchrotron radiation in the middle of a straight (PR12), away from sextupoles and skew quadrupoles and created a dispersion wave of about 70 mm at high current while at low current it is negligible

Delphinidin prevents high glucose-induced cell proliferation and collagen synthesis by inhibition of NOX-1 and mitochondrial superoxide in mesangial cells

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Seung Eun Song

2016-04-01

Full Text Available This study examined the effect of delphinidin on high glucose-induced cell proliferation and collagen synthesis in mesangial cells. Glucose dose-dependently (5.6–25 mM increased cell proliferation and collagen I and IV mRNA levels, whereas pretreatment with delphinidin (50 μM prevented cell proliferation and the increased collagen mRNA levels induced by high glucose (25 mM. High glucose increased reactive oxygen species (ROS generation, and this was suppressed by pretreating delphinidin or the antioxidant N-acetyl cysteine. NADPH oxidase (NOX 1 was upregulated by high glucose, but pretreatment with delphinidin abrogated this upregulation. Increased mitochondrial superoxide by 25 mM glucose was also suppressed by delphinidin. The NOX inhibitor apocynin and mitochondria-targeted antioxidant Mito TEMPO inhibited ROS generation and cell proliferation induced by high glucose. Phosphorylation of extracellular signal regulated kinase (ERK1/2 was increased by high glucose, which was suppressed by delphinidin, apocynin or Mito TEMPO. Furthermore, PD98059 (an ERK1/2 inhibitor prevented the high glucose-induced cell proliferation and increased collagen mRNA levels. Transforming growth factor (TGF-β protein levels were elevated by high glucose, and pretreatment with delphinidin or PD98059 prevented this augmentation. These results suggest that delphinidin prevents high glucose-induced cell proliferation and collagen synthesis by inhibition of NOX-1 and mitochondrial superoxide in mesangial cells.

ZAP study of collective effects in PEP: 9 x 9 collider optics

International Nuclear Information System (INIS)

Corbett, W.J.

1990-02-01

In this note, single and multi-bunch collective instabilities are considered for PEP operating a 9 x 9 bunch configuration. The lattice is based on a vertically separated beam 'pretzel' design which allows for collisions at the TPC (IR2) only. Threshold current levels and linear instability growth rates are calculated with the storage ring design code 'ZAP'. Single bunch instabilities should not be a problem for total circulating currents of 100mA (18 bunches, 5.6mA/bunch). Coupled-bunch growth rate calculations are based on a line broadening technique for the higher-order cavity modes. In the longitudinal case, feedback will be required. For the transverse coupled bunch instabilities, growth rates are about 5 times less. 14 refs., 5 figs

Psychoeducation with problem-solving (PEPS) therapy for adults with personality disorder: a pragmatic randomised controlled trial to determine the clinical effectiveness and cost-effectiveness of a manualised intervention to improve social functioning.

Science.gov (United States)

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

2016-07-01

If effective, less intensive treatments for people with personality disorder have the potential to serve more people. To compare the clinical effectiveness and cost-effectiveness of psychoeducation with problem-solving (PEPS) therapy plus usual treatment against usual treatment alone in improving social problem-solving with adults with personality disorder. Multisite two-arm, parallel-group, pragmatic randomised controlled superiority trial. Community mental health services in three NHS trusts in England and Wales. Community-dwelling adults with any personality disorder recruited from community mental health services. Up to four individual sessions of psychoeducation, a collaborative dialogue about personality disorder, followed by 12 group sessions of problem-solving therapy to help participants learn a process for solving interpersonal problems. The primary outcome was measured by the Social Functioning Questionnaire (SFQ). Secondary outcomes were service use (general practitioner records), mood (measured via the Hospital Anxiety and Depression Scale) and client-specified three main problems rated by severity. We studied the mechanism of change using the Social Problem-Solving Inventory. Costs were identified using the Client Service Receipt Inventory and quality of life was identified by the European Quality of Life-5 Dimensions questionnaire. Research assistants blinded to treatment allocation collected follow-up information. There were 739 people referred for the trial and 444 were eligible. More adverse events in the PEPS arm led to a halt to recruitment after 306 people were randomised (90% of planned sample size); 154 participants received PEPS and 152 received usual treatment. The mean age was 38 years and 67% were women. Follow-up at 72 weeks after randomisation was completed for 62% of participants in the usual-treatment arm and 73% in the PEPS arm. Intention-to-treat analyses compared individuals as randomised, regardless of treatment received or

Low-energy solar neutrino spectroscopy with Borexino. Towards the detection of the solar pep and CNO neutrino flux

Energy Technology Data Exchange (ETDEWEB)

Maneschg, Werner

2011-05-11

Borexino is a large-volume organic liquid scintillator detector of unprecedented high radiopurity which has been designed for low-energy neutrino spectroscopy in real time. Besides the main objective of the experiment, the measurement of the solar {sup 7}Be neutrino flux, Borexino also aims at detecting solar neutrinos from the pep fusion process and from the CNO cycle. The detectability of these neutrinos is strictly connected to a successful rejection of all relevant background components. The identification and reduction of these background signals is the central subject of this dissertation. In the first part, contaminants induced by cosmic-ray muons and muon showers were analyzed. The dominant background is the cosmogenic radioisotope {sup 11}C. Its rate is {proportional_to}10 times higher than the expected combined pep and CNO neutrino rate in the preferred energy window of observation at [0.8,1.3] MeV. Since {sup 11}C is mostly produced under the release of a free neutron, {sup 11}C can be tagged with a threefold coincidence (TFC) consisting of the muon signal, the neutron capture and the subsequent {sup 11}C decay. By optimizing the TFC method and other rejection techniques, a {sup 11}C rejection efficiency of 80% was achieved. This led to a neutrino-to-background ratio of 1:1.7, whereby 61% of statistics is lost. The second part of the work concerns the study of the external background. Especially long-range 2.6 MeV gamma rays from {sup 208}Tl decays in the outer detector parts can reach the scintillator in the innermost region of the detector. For the determination of the resultant spectral shape, a custom-made {proportional_to}5 MBq {sup 228}Th source was produced and an external calibration was carried out for the first time. The obtained calibration data and the achieved {sup 11}C rejection efficiency will allow for the direct detection of solar pep and possibly also CNO neutrinos with Borexino. (orig.)

Low-energy solar neutrino spectroscopy with Borexino. Towards the detection of the solar pep and CNO neutrino flux

International Nuclear Information System (INIS)

Maneschg, Werner

2011-01-01

Borexino is a large-volume organic liquid scintillator detector of unprecedented high radiopurity which has been designed for low-energy neutrino spectroscopy in real time. Besides the main objective of the experiment, the measurement of the solar 7 Be neutrino flux, Borexino also aims at detecting solar neutrinos from the pep fusion process and from the CNO cycle. The detectability of these neutrinos is strictly connected to a successful rejection of all relevant background components. The identification and reduction of these background signals is the central subject of this dissertation. In the first part, contaminants induced by cosmic-ray muons and muon showers were analyzed. The dominant background is the cosmogenic radioisotope 11 C. Its rate is ∝10 times higher than the expected combined pep and CNO neutrino rate in the preferred energy window of observation at [0.8,1.3] MeV. Since 11 C is mostly produced under the release of a free neutron, 11 C can be tagged with a threefold coincidence (TFC) consisting of the muon signal, the neutron capture and the subsequent 11 C decay. By optimizing the TFC method and other rejection techniques, a 11 C rejection efficiency of 80% was achieved. This led to a neutrino-to-background ratio of 1:1.7, whereby 61% of statistics is lost. The second part of the work concerns the study of the external background. Especially long-range 2.6 MeV gamma rays from 208 Tl decays in the outer detector parts can reach the scintillator in the innermost region of the detector. For the determination of the resultant spectral shape, a custom-made ∝5 MBq 228 Th source was produced and an external calibration was carried out for the first time. The obtained calibration data and the achieved 11 C rejection efficiency will allow for the direct detection of solar pep and possibly also CNO neutrinos with Borexino. (orig.)

Syringic Acid Extracted from Herba dendrobii Prevents Diabetic Cataract Pathogenesis by Inhibiting Aldose Reductase Activity

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Xiaoyong Wei

2012-01-01

Full Text Available Objective. Effects of Syringic acid (SA extracted from dendrobii on diabetic cataract (DC pathogenesis were explored. Methods. Both in vitro and in vivo DC lens models were established using D-gal, and proliferation of HLEC exposed to SA was determined by MMT assay. After 60-day treatment with SA, rat lens transparency was observed by anatomical microscopy using a slit lamp. SA protein targets were extracted and isolated using 2-DE and MALDI TOF/TOF. AR gene expression was investigated using qRT-PCR. Interaction sites and binding characteristics were determined by molecule-docking techniques and dynamic models. Results. Targeting AR, SA provided protection from D-gal-induced damage by consistently maintaining lens transparency and delaying lens turbidity development. Inhibition of AR gene expression by SA was confirmed by qRT-PCR. IC50 of SA for inhibition of AR activity was 213.17 μg/mL. AR-SA binding sites were Trp111, His110, Tyr48, Trp20, Trp79, Leu300, and Phe122. The main binding modes involved hydrophobic interactions and hydrogen bonding. The stoichiometric ratio of non-covalent bonding between SA and AR was 1.0 to 13.3. Conclusion. SA acts to prevent DC in rat lenses by inhibiting AR activity and gene expression, which has potential to be developed into a novel drug for therapeutic management of DC.

Measurements of a Fast Vertical Instability in the PEP-II HER

International Nuclear Information System (INIS)

Matter, Regina S.

2000-01-01

The HER beam current was limited to tens of mA by a strong vertical coupled bunch instability during PEP-II commissioning in July '98. In the absence of transverse feedback, vertical oscillations were seen to be unstable at currents as low as 5 mA. The instability has been observed by using the HER longitudinal feedback electronics to digitize and store the vertical beam signal used for transverse feedback. This note presents measurements of modal growth and damping rates at two different vacuum pressures for 291 bunch uniform fills as well as 100 and 150 bunch train measurements. In some cases the unstable modes maintain a constant residual amplitude when feedback is on, and exhibit nonlinear behavior when feedback is switched off. Knowledge of the shape, speed and spectral location of the modal transients should help in diagnosing the cause of instability

A failure of matrix metalloproteinase inhibition in the prevention of rat intracranial aneurysm formation

International Nuclear Information System (INIS)

Kaufmann, T.J.; Kallmes, D.F.; Marx, W.F.

2006-01-01

We tested the hypothesis that nonspecific matrix metalloproteinase (MMP) inhibition with doxycycline would decrease the incidence of intracranial aneurysm formation in a rat aneurysm model. We performed common carotid artery ligation on 96 Long-Evans rats. A treatment group of 48 animals was chosen at random to receive oral doxycycline (3 mg/kg) in addition to standard rat chow, and the control group of 48 animals received standard rat chow only. The major circle of Willis arteries was dissected at 1 year following carotid ligation, and the proportions of animals with aneurysms were compared between groups using Fisher's exact test. Four animals given oral doxycycline and ten control animals expired before 1 year. Of the examined animals, eight saccular intracranial aneurysms were found in 8 of 45 animals which had received doxycycline (17.8%) and seven saccular intracranial aneurysms were found in 7 of 37 control animals (18.9%). There was no significant difference in aneurysm formation between the doxycycline-treated and control groups (P=0.894). Nonspecific MMP inhibition with doxycycline is not effective in preventing intracranial aneurysm formation in a rat model. (orig.)

Does rectal indomethacin eliminate the need for prophylactic pancreatic stent placement in patients undergoing high-risk ERCP? Post hoc efficacy and cost-benefit analyses using prospective clinical trial data.

Science.gov (United States)

Elmunzer, B Joseph; Higgins, Peter D R; Saini, Sameer D; Scheiman, James M; Parker, Robert A; Chak, Amitabh; Romagnuolo, Joseph; Mosler, Patrick; Hayward, Rodney A; Elta, Grace H; Korsnes, Sheryl J; Schmidt, Suzette E; Sherman, Stuart; Lehman, Glen A; Fogel, Evan L

2013-03-01

A recent large-scale randomized controlled trial (RCT) demonstrated that rectal indomethacin administration is effective in addition to pancreatic stent placement (PSP) for preventing post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) in high-risk cases. We performed a post hoc analysis of this RCT to explore whether rectal indomethacin can replace PSP in the prevention of PEP and to estimate the potential cost savings of such an approach. We retrospectively classified RCT subjects into four prevention groups: (1) no prophylaxis, (2) PSP alone, (3) rectal indomethacin alone, and (4) the combination of PSP and indomethacin. Multivariable logistic regression was used to adjust for imbalances in the prevalence of risk factors for PEP between the groups. Based on these adjusted PEP rates, we conducted an economic analysis comparing the costs associated with PEP prevention strategies employing rectal indomethacin alone, PSP alone, or the combination of both. After adjusting for risk using two different logistic regression models, rectal indomethacin alone appeared to be more effective for preventing PEP than no prophylaxis, PSP alone, and the combination of indomethacin and PSP. Economic analysis revealed that indomethacin alone was a cost-saving strategy in 96% of Monte Carlo trials. A prevention strategy employing rectal indomethacin alone could save approximately $150 million annually in the United States compared with a strategy of PSP alone, and $85 million compared with a strategy of indomethacin and PSP. This hypothesis-generating study suggests that prophylactic rectal indomethacin could replace PSP in patients undergoing high-risk ERCP, potentially improving clinical outcomes and reducing healthcare costs. A RCT comparing rectal indomethacin alone vs. indomethacin plus PSP is needed.

CopA3 Peptide Prevents Ultraviolet-Induced Inhibition of Type-I Procollagen and Induction of Matrix Metalloproteinase-1 in Human Skin Fibroblasts

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Dong-Hee Kim

2014-05-01

Full Text Available Ultraviolet (UV exposure is well-known to induce premature aging, which is mediated by matrix metalloproteinase-1 (MMP-1 activity. A 9-mer peptide, CopA3 (CopA3 was synthesized from a natural peptide, coprisin, which is isolated from the dung beetle Copris tripartitus. As part of our continuing search for novel bioactive natural products, CopA3 was investigated for its in vitro anti-skin photoaging activity. UV-induced inhibition of type-I procollagen and induction of MMP-1 were partially prevented in human skin fibroblasts by CopA3 peptide in a dose-dependent manner. At a concentration of 25 μM, CopA3 nearly completely inhibited MMP-1 expression. These results suggest that CopA3, an insect peptide, is a potential candidate for the prevention and treatment of skin aging.

Diagnostic and Prevention Approach in Post Endoscopic Retrograde Cholangiopancreatography Pancreatitis

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Stella Ilone

2016-12-01

Full Text Available Obstructive jaundice (icterus was an emergency situation in gastroenterology. Endoscopic retrograde cholangiopancreatography (ERCP was a nonsurgical approach to release obstruction, mostly in common bile duct. Nowadays, this procedure was become frequently used in daily practice, but several complications also emerging. One of the severe complication was Post-ERCP Pancreatitis (PEP. Since it has a high mortality and morbidity, and also reduce patient quality of life, several approaches have been developed to reduce its incidence. In general, approaches consist of patient identification, efficient procedure, until pharmacological agent prevention. Although there were still contradiction among these, careful approach should be considered for each patients for a better outcomes.

Bilirubin prevents acute DSS-induced colitis by inhibiting leukocyte infiltration and suppressing upregulation of inducible nitric oxide synthase.

Science.gov (United States)

Zucker, Stephen D; Vogel, Megan E; Kindel, Tammy L; Smith, Darcey L H; Idelman, Gila; Avissar, Uri; Kakarlapudi, Ganesh; Masnovi, Michelle E

2015-11-15

Bilirubin is thought to exert anti-inflammatory effects by inhibiting vascular cell adhesion molecule-1 (VCAM-1)-dependent leukocyte migration and by suppressing the expression of inducible nitric oxide synthase (iNOS). As VCAM-1 and iNOS are important mediators of tissue injury in the dextran sodium sulfate (DSS) murine model of inflammatory colitis, we examined whether bilirubin prevents colonic injury in DSS-treated mice. Male C57BL/6 mice were administered 2.5% DSS in the drinking water for 7 days, while simultaneously receiving intraperitoneal injections of bilirubin (30 mg/kg) or potassium phosphate vehicle. Disease activity was monitored, peripheral blood counts and serum nitrate levels were determined, and intestinal specimens were analyzed for histological injury, leukocyte infiltration, and iNOS expression. The effect of bilirubin on IL-5 production by HSB-2 cells and on Jurkat cell transendothelial migration also was determined. DSS-treated mice that simultaneously received bilirubin lost less body weight, had lower serum nitrate levels, and exhibited reduced disease severity than vehicle-treated animals. Concordantly, histopathological analyses revealed that bilirubin-treated mice manifested significantly less colonic injury, including reduced infiltration of eosinophils, lymphocytes, and monocytes, and diminished iNOS expression. Bilirubin administration also was associated with decreased eosinophil and monocyte infiltration into the small intestine, with a corresponding increase in peripheral blood eosinophilia. Bilirubin prevented Jurkat migration but did not alter IL-5 production. In conclusion, bilirubin prevents DSS-induced colitis by inhibiting the migration of leukocytes across the vascular endothelium and by suppressing iNOS expression. Copyright © 2015 the American Physiological Society.

Limited access to HIV prevention in French prisons (ANRS PRI2DE: implications for public health and drug policy

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Blanche Jerôme

2011-05-01

Full Text Available Abstract Background Overpopulation, poor hygiene and disease prevention conditions in prisons are major structural determinants of increased infectious risk within prison settings but evidence-based national and WHO guidelines provide clear indications on how to reduce this risk. We sought to estimate the level of infectious risk by measuring how French prisons adhere to national and WHO guidelines. Methods A nationwide survey targeting the heads of medical (all French prisons and psychiatric (26 French prisons units was conducted using a postal questionnaire and a phone interview mainly focusing on access to prevention interventions, i.e. bleach, opioid substitution treatment (OST, HBV vaccination and post-exposure prophylaxis (PEP for French prisoners. Two scores were built reflecting adherence to national and WHO international guidelines, ranging from 0 (no adherence to 10 (maximum adherence and 0 to 9 respectively. Results A majority (N = 113 (66% of the 171 prisons answered the questionnaires, representing 74% coverage (46,786 prisoners of the French prison population: 108 were medical units and 12 were psychiatric units. Inmate access to prevention was poor. The median[IQR] score measuring adherence to national guidelines was quite low (4.5[2.5; 5.5] but adherence to WHO guidelines was even lower 2.5[1.5; 3.5]; PEP was absent despite reported risky practices. Unsuitable OST delivery practices were frequently observed. Conclusions A wide gap exists between HIV prevention policies and their application in prisons. Similar assessments in other countries may be needed to guide a global policy reform in prison settings. Adequate funding together with innovative interventions able to remove structural and ideological barriers to HIV prevention are now needed to motivate those in charge of prison health, to improve their working environment and to relieve French prisoners from their currently debilitating conditions.

mTOR pathway inhibition prevents neuroinflammation and neuronal death in a mouse model of cerebral palsy.

Science.gov (United States)

Srivastava, Isha N; Shperdheja, Jona; Baybis, Marianna; Ferguson, Tanya; Crino, Peter B

2016-01-01

Mammalian target of rapamycin (mTOR) pathway signaling governs cellular responses to hypoxia and inflammation including induction of autophagy and cell survival. Cerebral palsy (CP) is a neurodevelopmental disorder linked to hypoxic and inflammatory brain injury however, a role for mTOR modulation in CP has not been investigated. We hypothesized that mTOR pathway inhibition would diminish inflammation and prevent neuronal death in a mouse model of CP. Mouse pups (P6) were subjected to hypoxia-ischemia and lipopolysaccharide-induced inflammation (HIL), a model of CP causing neuronal injury within the hippocampus, periventricular white matter, and neocortex. mTOR pathway inhibition was achieved with rapamycin (an mTOR inhibitor; 5mg/kg) or PF-4708671 (an inhibitor of the downstream p70S6kinase, S6K, 75 mg/kg) immediately following HIL, and then for 3 subsequent days. Phospho-activation of the mTOR effectors p70S6kinase and ribosomal S6 protein and expression of hypoxia inducible factor 1 (HIF-1α) were assayed. Neuronal cell death was defined with Fluoro-Jade C (FJC) and autophagy was measured using Beclin-1 and LC3II expression. Iba-1 labeled, activated microglia were quantified. Neuronal death, enhanced HIF-1α expression, and numerous Iba-1 labeled, activated microglia were evident at 24 and 48 h following HIL. Basal mTOR signaling, as evidenced by phosphorylated-S6 and -S6K levels, was unchanged by HIL. Rapamycin or PF-4,708,671 treatment significantly reduced mTOR signaling, neuronal death, HIF-1α expression, and microglial activation, coincident with enhanced expression of Beclin-1 and LC3II, markers of autophagy induction. mTOR pathway inhibition prevented neuronal death and diminished neuroinflammation in this model of CP. Persistent mTOR signaling following HIL suggests a failure of autophagy induction, which may contribute to neuronal death in CP. These results suggest that mTOR signaling may be a novel therapeutic target to reduce neuronal cell death in

Meson and baryon correlation studies using the PEP-TPC/2γ Facility

International Nuclear Information System (INIS)

Ronan, M.T.

1991-03-01

Results on vector meson, and strange and charmed-baryon production are presented for data taken during the period 1982--1986 using the TPC/2γ detector at PEP. Vector mesons (ρ 0 , K * and φ) with 0, 1 and 2 strange quarks are used to obtain redundant measures of strange-quark suppression and of the vector to pseudoscalar ratio in hadronization. Measurements of the production rates of Λ, Ξ - , Ω and Ξ *0 hyperons and for the Λ c and of rapidity correlations between Λ bar Λ pairs provide sensitive tests of baryon production in fragmentation models. In addition, two- and three-particle correlations between like sign pions provide further evidence for the Bose-Einstein effect in e + e - interactions including the relativistic motion of particle sources. 9 refs., 7 figs

Pharmacological approach to acute pancreatitis

DEFF Research Database (Denmark)

Bang, U.C.; Semb, S.; Nøjgaard, Camilla

2008-01-01

The aim of the present review is to summarize the current knowledge regarding pharmacological prevention and treatment of acute pancreatitis (AP) based on experimental animal models and clinical trials. Somatostatin (SS) and octreotide inhibit the exocrine production of pancreatic enzymes and may...... be useful as prophylaxis against post endoscopic retrograde cholangiopancreatography pancreatitis (PEP). The protease inhibitor gabexate mesilate (GM) is used routinely as treatment to AP in some countries, but randomized clinical trials and a meta-analysis do not support this practice. Nitroglycerin (NGL...

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

Science.gov (United States)

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.

Novel Synthetic, Host-defense Peptide Protects Against Organ Injury/Dysfunction in a Rat Model of Severe Hemorrhagic Shock.

Science.gov (United States)

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.

Inhibition of the Rho/ROCK pathway prevents neuronal degeneration in vitro and in vivo following methylmercury exposure

International Nuclear Information System (INIS)

Fujimura, Masatake; Usuki, Fusako; Kawamura, Miwako; Izumo, Shuji

2011-01-01

Methylmercury (MeHg) is an environmental neurotoxicant which induces neuropathological changes in both the central nervous and peripheral sensory nervous systems. Our recent study demonstrated that down-regulation of Ras-related C3 botulinum toxin substrate 1 (Rac1), which is known to promote neuritic extension, preceded MeHg-induced damage in cultured cortical neurons, suggesting that MeHg-mediated axonal degeneration is due to the disturbance of neuritic extension. Therefore we hypothesized that MeHg-induced axonal degeneration might be caused by neuritic extension/retraction incoordination. This idea brought our attention to the Ras homolog gene (Rho)/Rho-associated coiled coil-forming protein kinase (ROCK) pathway because it has been known to be associated with the development of axon and apoptotic neuronal cell death. Here we show that inhibition of the Rho/ROCK pathway prevents MeHg-intoxication both in vitro and in vivo. A Rho inhibitor, C3 toxin, and 2 ROCK inhibitors, Fasudil and Y-27632, significantly protected against MeHg-induced axonal degeneration and apoptotic neuronal cell death in cultured cortical neuronal cells exposed to 100 nM MeHg for 3 days. Furthermore, Fasudil partially prevented the loss of large pale neurons in dorsal root ganglia, axonal degeneration in dorsal spinal root nerves, and vacuolar degeneration in the dorsal columns of the spinal cord in MeHg-intoxicated model rats (20 ppm MeHg in drinking water for 28 days). Hind limb crossing sign, a characteristic MeHg-intoxicated sign, was significantly suppressed in this model. The results suggest that inhibition of the Rho/ROCK pathway rescues MeHg-mediated neuritic extension/retraction incoordination and is effective for the prevention of MeHg-induced axonal degeneration and apoptotic neuronal cell death.

Prevention of post endoscopic retrograde cholangiopancreatography pancreatitis

Directory of Open Access Journals (Sweden)

Nalini M Guda

2012-01-01

Full Text Available Post ERCP pancreatitis (PEP is a common problem. Knowledge of patient and procedure related risk factors along with appropriate measures aimed at reduction of risk have been successful in reducing both the incidence and the severity. Prophylactic pancreatic duct stenting has definitely reduced the incidence and the severity of PEP in high risk patients. There are some emerging data on the use of non steroidal anti inflammatory agents though this is not widely adapted in practice. Key is to avoid procedures with marginal indications and use of non invasive/less invasive procedures.

Interaction between the effects of pepleomycin with lidocaine and radiation on cultured Chinese hamster V79 cells

International Nuclear Information System (INIS)

Shimada, Yuji

1989-01-01

The interaction of the cytotoxicities in combination use of lidocaine (LID), pepleomycin (PEP) and radiation in combined treatment was studied using Chinese hamster V79 cells by colony forming assay. LID showed no cytotoxic effect up to 12 mM when it was employed alone. However selective enhancement of the PEP cytotoxic effect appeared when the drugs were used simultaneously. The mechanism of this enhancing effect was thought to involve inhibition by LID of the repair of the cells from PEP potentially lethal damage. LID showed no enhancing effect on the radiation cytotoxicity when the agents were used simultaneously. Only an additive effect appeared when PEP and radiation were employed simultaneously. An interactive effect appeared when LID, PEP and radiation were used simultaneously, although this effect was not so significant. The enhancement ratio of PEP with LID on radiation was 1.58. The fundamental mechanism of enhancement of cytotoxic effect of LID on PEP and the interactive relationship among LID, PEP and radiation are analyzed and discussed. (author)

Inhibition of Matrix Metalloproteinase Activity Prevents Increases in Myocardial Tumor Necrosis Factor-α

Science.gov (United States)

Murray, David B.; Levick, Scott P; Brower, Gregory L.; Janicki, Joseph S.

2010-01-01

Aim TNF-α is known to cause adverse myocardial remodeling. While we have previously shown a role for cardiac mast cells in mediating myocardial TNF-α, matrix metalloproteinases (MMP) activation of TNF-α may also be contributory. We sought to determine the relative roles of MMPs and cardiac mast cells in the activation of TNF-α in the hearts of rats subjected to chronic volume overload. Methods Interventions with the broad spectrum MMP inhibitor, GM6001, or the mast cell stabilizer, nedocromil, were performed in the rat aortocaval fistula (ACF) model of volume overload. Results Myocardial TNF-α levels were significantly increased in the ACF. This increase was prevented by MMP inhibition with GM6001 (p ≤ 0.001 vs. ACF). Conversely, myocardial TNF-α levels were increased in the ACF + nedocromil treated fistula groups (p ≤ 0.001 vs. sham). The degradation of interstitial collagen volume fraction seen in the untreated ACF group was prevented in both the GM6001 and nedocromil treated hearts. Significant increases in LV myocardial ET-1 levels also occurred in the ACF group at 3 days post-fistula. Whereas administration of GM6001 significantly attenuated this increase, mast cell stabilization with nedocromil markedly exacerbated the increase, producing ET-1 levels 6.5 fold and 2 fold greater than that in the sham-operated control and ACF group, respectively. Conclusion The efficacy of the MMP inhibitor, GM6001, to prevent increased levels of myocardial TNF-α is indicative of MMP-mediated cleavage of latent extracellular membrane bound TNF-α protein as the primary source of bioactive TNF-α in the myocardium of the volume-overload heart. PMID:20403361

Nurturing the Continuum of HIV Testing, Treatment and Prevention Matrix Cascade in Reducing HIV Transmission.

Science.gov (United States)

Yah, Clarence S

2017-11-01

Despite the shift in antiretroviral therapy (ARVs) eligibility cascade from CD4 ≤ 200 to CD4 ≤ 350 to CD4 ≤ 500 mm 3 , HIV related morbidity and mortality continue to escalate annually, as do HIV infections. The new paradigm of treatment for all HIV positives individual irrespective of CD4 count may significantly reduce HIV and related illnesses. The author assumes that all HIV infected partners should be eligible for HIV treatment and care, irrespective of CD4 count. A second assumption is that high risk HIV negative partners have free access to continuum of HIV pre-exposure prophylaxis (PrEP), post exposure prophylaxis (PEP) and other prevention packages. A literature review search was used to extract evidence-based ARVs-HIV treatment and prevention interventions among HIV positives and high risk partners respectively. Only articles published in English and indexed in journal nuclei were used for the study. The information was used to nurture understanding of HIV treatment and prevention approaches as well as HIV incidence multiplier effect among HIV serodiscordant partners. The imputed HIV incident reference was assumed at 1.2 per 100 person-years (2). This was based on the imputation that retention in care, adherence and other predetermined factors are functions of an effective health care delivery system. The model showed a reduced HIV transmission from 1.2 per 100 person-years to 1.032 per 100 person-years in 6 months. The average threshold period of HIV suppressed partners on ARVs to an undetectable level. The combined multiplier protective-effect probability of transmitting HIV from HIV positive partners on ARVs-suppressed viremic load to HIV negative partners on PrEP/PEP-prevention was detected at 86. The model showed a significant reduction in HIV incidence. Placing serodiscordant sexual partners in HIV treatment and prevention plays a significant role in reducing and controlling HIV infection. Therefore, the policy of enrolling all HIV positives

Inhibiting the inevitable

DEFF Research Database (Denmark)

Shashoua, Yvonne

2006-01-01

conservation is to ‘buy time’ for the object. Inhibitive conservation of plastics involves the removal or reduction of factors causing or accelerating degradation including light, oxygen, acids, relative humidity and acidic breakdown products. Specific approaches to conservation have been developed......Once plastics objects are registered in museum collections, the institution becomes responsible for their long term preservation, until the end of their useful lifetime. Plastics appear to deteriorate faster than other materials in museum collections and have a useful lifetime between 5 and 25...... years. Preventive or inhibitive conservation involves controlling the environments in which objects are placed during storage and display, with the aim of slowing the major deterioration reactions. Once in progress, degradation of plastics cannot be stopped or reversed, so the aim of preventive...

Prevention of wear particle-induced osteolysis by a novel V-ATPase inhibitor saliphenylhalamide through inhibition of osteoclast bone resorption.

Directory of Open Access Journals (Sweden)

An Qin

Full Text Available Wear particle-induced peri-implant loosening (Aseptic prosthetic loosening is one of the most common causes of total joint arthroplasty. It is well established that extensive bone destruction (osteolysis by osteoclasts is responsible for wear particle-induced peri-implant loosening. Thus, inhibition of osteoclastic bone resorption should prevent wear particle induced osteolysis and may serve as a potential therapeutic avenue for prosthetic loosening. Here, we demonstrate for the first time that saliphenylhalamide, a new V-ATPase inhibitor attenuates wear particle-induced osteolysis in a mouse calvarial model. In vitro biochemical and morphological assays revealed that the inhibition of osteolysis is partially attributed to a disruption in osteoclast acidification and polarization, both a prerequisite for osteoclast bone resorption. Interestingly, the V-ATPase inhibitor also impaired osteoclast differentiation via the inhibition of RANKL-induced NF-κB and ERK signaling pathways. In conclusion, we showed that saliphenylhalamide affected multiple physiological processes including osteoclast differentiation, acidification and polarization, leading to inhibition of osteoclast bone resorption in vitro and wear particle-induced osteolysis in vivo. The results of the study provide proof that the new generation V-ATPase inhibitors, such as saliphenylhalamide, are potential anti-resorptive agents for treatment of peri-implant osteolysis.

Comparison of q anti qg and q anti qγ events in e+e- annihilation at PEP

International Nuclear Information System (INIS)

Hofmann, W.

1986-07-01

In comparing the particle flow in the event plane of three-jet (q anti qg) events and of radiative annihilation events (q anti qγ) for similar kinematic configurations, two PEP experiments find a significant decrease in particle density in the angular region opposite to the gluon jet in q anti qg events, relative to the particle density in the region opposite to the photon in q anti qγ events. The effect is predicted both by QCD and by phenomenological string models. 5 refs., 5 figs

Alzheimer's Disease Brain-Derived Amyloid-{beta}-Mediated Inhibition of LTP In Vivo Is Prevented by Immunotargeting Cellular Prion Protein.

LENUS (Irish Health Repository)

Barry, Andrew E

2011-05-18

Synthetic amyloid-β protein (Aβ) oligomers bind with high affinity to cellular prion protein (PrP(C)), but the role of this interaction in mediating the disruption of synaptic plasticity by such soluble Aβ in vitro is controversial. Here we report that intracerebroventricular injection of Aβ-containing aqueous extracts of Alzheimer\\'s disease (AD) brain robustly inhibits long-term potentiation (LTP) without significantly affecting baseline excitatory synaptic transmission in the rat hippocampus in vivo. Moreover, the disruption of LTP was abrogated by immunodepletion of Aβ. Importantly, intracerebroventricular administration of antigen-binding antibody fragment D13, directed to a putative Aβ-binding site on PrP(C), prevented the inhibition of LTP by AD brain-derived Aβ. In contrast, R1, a Fab directed to the C terminus of PrP(C), a region not implicated in binding of Aβ, did not significantly affect the Aβ-mediated inhibition of LTP. These data support the pathophysiological significance of SDS-stable Aβ dimer and the role of PrP(C) in mediating synaptic plasticity disruption by soluble Aβ.

Ketogenic Diet Improves Brain Ischemic Tolerance and Inhibits NLRP3 Inflammasome Activation by Preventing Drp1-Mediated Mitochondrial Fission and Endoplasmic Reticulum Stress

Directory of Open Access Journals (Sweden)

Min Guo

2018-03-01

Full Text Available Background: Neuroprotective effects of ketogenic diets (KD have been reported in stroke models, and nucleotide-binding domain (NOD-like receptor protein 3 (NLRP3 inflammasome has also been implicated in the pathogenesis of stroke. This study aimed to investigate the effects of KD on NLRP3 inflammasome and explore the potential molecular mechanisms.Methods: In in vivo study, mice were fed with KD for 3 weeks and then subjected to middle cerebral artery occlusion/reperfusion (MCAO/R-injury. In in vitro study, SH-SY-5Y cells were treated with β-hydroxybutyrate (BHB followed by oxygen–glucose deprivation/reoxygenation (OGD/R. NLRP3 inflammasome activation and related regulatory mechanisms were evaluated.Results: Mice fed with KD had increased tolerance to MCAO/R. KD inhibited endoplasmic reticulum (ER stress and suppressed TXNIP/NLRP3 inflammasome activation in the brain. The in vitro study showed BHB (10 mM prevented the mitochondrial translocation of dynamin-related protein 1 (Drp1 to inhibit mitochondrial fission. Furthermore, BHB decreased reactive oxygen species (ROS generation, inhibited ROS-NLRP3 pathway in OGD/R-treated cells, and suppressed ER stress-induced NLRP3 inflammasome activation.Conclusions: KD may suppress ER stress and protect mitochondrial integrity by suppressing the mitochondrial translocation of Drp1 to inhibit NLRP3 inflammasome activation, thus exerting neuroprotective effects. Our findings provide evidence for the potential application of KD in the prevention of ischemic stroke.

Inhibition of FoxO transcriptional activity prevents muscle fiber atrophy during cachexia and induces hypertrophy

Science.gov (United States)

Reed, Sarah A.; Sandesara, Pooja B.; Senf, Sarah M.; Judge, Andrew R.

2012-01-01

Cachexia is characterized by inexorable muscle wasting that significantly affects patient prognosis and increases mortality. Therefore, understanding the molecular basis of this muscle wasting is of significant importance. Recent work showed that components of the forkhead box O (FoxO) pathway are increased in skeletal muscle during cachexia. In the current study, we tested the physiological significance of FoxO activation in the progression of muscle atrophy associated with cachexia. FoxO-DNA binding dependent transcription was blocked in the muscles of mice through injection of a dominant negative (DN) FoxO expression plasmid prior to inoculation with Lewis lung carcinoma cells or the induction of sepsis. Expression of DN FoxO inhibited the increased mRNA levels of atrogin-1, MuRF1, cathepsin L, and/or Bnip3 and inhibited muscle fiber atrophy during cancer cachexia and sepsis. Interestingly, during control conditions, expression of DN FoxO decreased myostatin expression, increased MyoD expression and satellite cell proliferation, and induced fiber hypertrophy, which required de novo protein synthesis. Collectively, these data show that FoxO-DNA binding-dependent transcription is necessary for normal muscle fiber atrophy during cancer cachexia and sepsis, and further suggest that basal levels of FoxO play an important role during normal conditions to depress satellite cell activation and limit muscle growth.—Reed, S. A., Sandesara, P. B., Senf, S. F., Judge, A. R. Inhibition of FoxO transcriptional activity prevents muscle fiber atrophy during cachexia and induces hypertrophy. PMID:22102632

Safflower bud inhibits RANKL-induced osteoclast differentiation and prevents bone loss in ovariectomized mice.

Science.gov (United States)

Choi, Joo-Hee; Lim, Seul-Ki; Kim, Dong-Il; Park, Min-Jung; Kim, Young-Kuk; Lee, An-Chul; Kim, Young-Min; Yang, Soo-Jin; Park, Jong-Hwan

2017-10-15

The powder and extract of safflower seeds are known to be effective in the prevention of bone loss in ovariectomized animals. However, the inhibitory effect and molecular mechanisms of safflower bud (SB), the germinated safflower, on bone destruction is unclear. The present study was designed to investigate the inhibitory effect and molecular mechanism of SB on osteoclastic differentiation and on bone loss in ovarietomized (OVX) mice. Osteoclastogenesis was determined by TRAP staining, F-actin ring formation, and bone resorption assay. NF-κB and MAPKs activation was analyzed by transfection assay and Western blot, respectively. Real-time PCR was performed to examine the expression of osteoclastogenesis-related genes. Histological changes, increases in TRAP-positive cells, and cathepsin K expression were examined in the metaphysis of OVX mice. Density of bone marrow was evaluated by µCT. SB inhibited the RANKL-induced differentiation of BMDMs into osteoclasts in a dose-dependent manner. F-actin ring formation and bone resorption were also reduced by SB in RANKL-treated BMDMs. In addition, SB decreased the activation of NF-κB and MAPKs and the expression of osteoclastogenesis-related genes in BMDMs treated with RANKL. Feeding of SB-included diet prevented bone loss in OVX mice. The number of TRAP-positive cells and level of protein expression of cathepsin K was reduced and bone mineral density was increased in the metaphysis of mice fed SB compared with OVX mice. These findings suggest that SB can be a preventive and therapeutic candidate for destructive bone diseases. Copyright © 2017. Published by Elsevier GmbH.

Rosetta FlexPepDock ab-initio: simultaneous folding, docking and refinement of peptides onto their receptors.

Science.gov (United States)

Raveh, Barak; London, Nir; Zimmerman, Lior; Schueler-Furman, Ora

2011-04-29

Flexible peptides that fold upon binding to another protein molecule mediate a large number of regulatory interactions in the living cell and may provide highly specific recognition modules. We present Rosetta FlexPepDock ab-initio, a protocol for simultaneous docking and de-novo folding of peptides, starting from an approximate specification of the peptide binding site. Using the Rosetta fragments library and a coarse-grained structural representation of the peptide and the receptor, FlexPepDock ab-initio samples efficiently and simultaneously the space of possible peptide backbone conformations and rigid-body orientations over the receptor surface of a given binding site. The subsequent all-atom refinement of the coarse-grained models includes full side-chain modeling of both the receptor and the peptide, resulting in high-resolution models in which key side-chain interactions are recapitulated. The protocol was applied to a benchmark in which peptides were modeled over receptors in either their bound backbone conformations or in their free, unbound form. Near-native peptide conformations were identified in 18/26 of the bound cases and 7/14 of the unbound cases. The protocol performs well on peptides from various classes of secondary structures, including coiled peptides with unusual turns and kinks. The results presented here significantly extend the scope of state-of-the-art methods for high-resolution peptide modeling, which can now be applied to a wide variety of peptide-protein interactions where no prior information about the peptide backbone conformation is available, enabling detailed structure-based studies and manipulation of those interactions. © 2011 Raveh et al.

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

Science.gov (United States)

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 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.

Transport of the photodynamic therapy agent 5-aminolevulinic acid by distinct H+-coupled nutrient carriers coexpressed in the small intestine.

Science.gov (United States)

Anderson, Catriona M H; Jevons, Mark; Thangaraju, Muthusamy; Edwards, Noel; Conlon, Nichola J; Woods, Steven; Ganapathy, Vadivel; Thwaites, David T

2010-01-01

5-Aminolevulinic acid (ALA) is a prodrug used in photodynamic therapy, fluorescent diagnosis, and fluorescent-guided resection because it leads to accumulation of the photosensitizer protoporphyrin IX (PpIX) in tumor tissues. ALA has good oral bioavailability, but high oral doses are required to obtain selective PpIX accumulation in colonic tumors because accumulation is also observed in normal gut mucosa. Structural similarities between ALA and GABA led us to test the hypothesis that the H(+)-coupled amino acid transporter PAT1 (SLC36A1) will contribute to luminal ALA uptake. Radiolabel uptake and electrophysiological measurements identified PAT1-mediated H(+)-coupled ALA symport after heterologous expression in Xenopus oocytes. The selectivity of the nontransported inhibitors 5-hydroxytryptophan and 4-aminomethylbenzoic acid for, respectively, PAT1 and the H(+)-coupled di/tripeptide transporter PepT1 (SLC15A1) were examined. 5-Hydroxytryptophan selectively inhibited PAT1-mediated amino acid uptake across the brush-border membrane of the human intestinal (Caco-2) epithelium whereas 4-aminomethylbenzoic acid selectively inhibited PepT1-mediated dipeptide uptake. The inhibitory effects of 5-hydroxytryptophan and 4-aminomethylbenzoic acid were additive, demonstrating that both PAT1 and PepT1 contribute to intestinal transport of ALA. This is the first demonstration of overlap in substrate specificity between these distinct transporters for amino acids and dipeptides. PAT1 and PepT1 expression was monitored by reverse transcriptase-polymerase chain reaction using paired samples of normal and cancer tissue from human colon. mRNA for both transporters was detected. PepT1 mRNA was increased 2.3-fold in cancer tissues. Thus, increased PepT1 expression in colonic cancer could contribute to the increased PpIX accumulation observed. Selective inhibition of PAT1 could enhance PpIX loading in tumor tissue relative to that in normal tissue.

The proposed injection system for an asymmetric B Factory in the PEP tunnel

International Nuclear Information System (INIS)

Bloom, E.; Bulos, F.; Loew, G.; Miller, R.; Sukiennicki, B.; Mattison, T.; Barletta, W.

1991-01-01

The proposed asymmetric energy B Factory to be built in the PEP tunnel at SLAC will require a highly effective and profuse source of low emittance electron and positron bunches. The B Factory will consist of two rings of equal size, a 9 GeV electron ring and a 3.1 GeV positron ring, each with 1658 bunches with total circulating currents of 1.5 and 2.1 amperes respectively. As the luminosity lifetime of the collider is expected to be about two hours, the injector should be capable of filling the rings in a small fraction of an hour. It turns out that with some simple modifications, the SLC linac with its damping rings and positron source is ideally suited to fulfill this function effectively. The overall injection system is described

Prevention Strategies Against HIV Transmission: A Proactive Approach.

Science.gov (United States)

Carrion, Antonio J; Miles, Jovan D; Mosley, Juan F; Smith, Lillian L; Prather, April S; Gurley, Marcus M; Phan, Linh D; Everton, Emily C

2018-02-01

Human immunodeficiency virus (HIV) has now transformed into a manageable chronic condition. Highly active antiretroviral therapy (HAART) has proven efficacious at controlling the disease progression. Based on compelling evidence, the Department of Health and Human Services (DHHS) and the Infectious Disease Society of America (IDSA) developed guidelines for the management of persons infected with HIV. However, there are approximately 50 000 new cases of HIV in the United States each year. In this article, we review proactive methods to reduce the transmission of HIV, which include reinforcing patient education, gel-coated condoms that destroy HIV, HIV vaccinations, and adequately utilizing pre-exposure prophylaxis (PrEP), and post-exposure prophylaxis (PEP). Further development and consistent utilization of innovative prevention tools can significantly reduce the incidence of HIV infections regardless of HIV status.

Inhibition of Plant-Pathogenic Bacteria by Short Synthetic Cecropin A-Melittin Hybrid Peptides

OpenAIRE

Ferre, Rafael; Badosa, Esther; Feliu, Lidia; Planas, Marta; Montesinos, Emili; Bardají, Eduard

2006-01-01

Short peptides of 11 residues were synthesized and tested against the economically important plant pathogenic bacteria Erwinia amylovora, Pseudomonas syringae, and Xanthomonas vesicatoria and compared to the previously described peptide Pep3 (WKLFKKILKVL-NH2). The antimicrobial activity of Pep3 and 22 analogues was evaluated in terms of the MIC and the 50% effective dose (ED50) for growth. Peptide cytotoxicity against human red blood cells and peptide stability toward protease degradation wer...

cAMP prevents TNF-induced apoptosis through inhibiting DISC complex formation in rat hepatocytes

International Nuclear Information System (INIS)

Bhattacharjee, Rajesh; Xiang, Wenpei; Wang, Yinna; Zhang, Xiaoying; Billiar, Timothy R.

2012-01-01

complex upon the binding of TNF to TNFR1. In conclusion, our study shows that cAMP prevents TNF + ActD-induced apoptosis in rat hepatocytes by inhibiting DISC complex formation.

cAMP prevents TNF-induced apoptosis through inhibiting DISC complex formation in rat hepatocytes

Energy Technology Data Exchange (ETDEWEB)

Bhattacharjee, Rajesh [Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA 15213 (United States); Xiang, Wenpei [Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA 15213 (United States); Family Planning Research Institute, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People' s Republic of China (China); Wang, Yinna [Vascular Medicine Institute, University of Pittsburgh School of Medicine, 10051-5A BST 3, 3501 Fifth Avenue, Pittsburgh, PA 15261 (United States); Zhang, Xiaoying [Department of Medicine/Endocrinology Division, University of Pittsburgh Medical Center, 200 Lothrop St., Pittsburgh, PA 15213 (United States); Billiar, Timothy R., E-mail: billiartr@upmc.edu [Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA 15213 (United States)

2012-06-22

that cAMP exerts its affect at the proximal level of TNF signaling by inhibiting the formation of the DISC complex upon the binding of TNF to TNFR1. In conclusion, our study shows that cAMP prevents TNF + ActD-induced apoptosis in rat hepatocytes by inhibiting DISC complex formation.

Taurine Pretreatment Prevents Isoflurane-Induced Cognitive Impairment by Inhibiting ER Stress-Mediated Activation of Apoptosis Pathways in the Hippocampus in Aged Rats.

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Zhang, Yanan; Li, Dongliang; Li, Haiou; Hou, Dailiang; Hou, Jingdong

2016-10-01

Isoflurane, a commonly used inhalation anesthetic, may induce neurocognitive deficits, especially in elderly patients after surgery. Recent study demonstrated that isoflurane caused endoplasmic reticulum (ER) stress and subsequent neuronal apoptosis in the brain, contributing to cognitive deficits. Taurine, a major intracellular free amino acid, has been shown to inhibit ER stress and neuronal apoptosis in several neurological disorders. Here, we examined whether taurine can prevent isoflurane-induced ER stress and cognitive impairment in aged rats. Thirty minutes prior to a 4-h 1.3 % isoflurane exposure, aged rats were treated with vehicle or taurine at low, middle and high doses. Aged rats without any treatment served as control. The brains were harvested 6 h after isoflurane exposure for molecular measurements, and behavioral study was performed 2 weeks later. Compared with control, isoflurane increased expression of hippocampal ER stress biomarkers including glucose-regulated protein 78, phosphorylated (P-) inositol-requiring enzyme 1, P-eukaryotic initiation factor 2-α (EIF2α), activating transcription factor 4 (ATF-4), cleaved ATF-6 and C/EBP homologous protein, along with activation of apoptosis pathways as indicated by decreased B cell lymphoma 2 (BCL-2)/BCL2-associated X protein, increased expressions of cytochrome-c and cleaved caspase-3. Taurine pretreatment dose-dependently inhibited isoflurane-induced increase in expression of ER stress biomarkers except for P-EIF2α and ATF-4, and reversed isoflurane-induced changes in apoptosis-related proteins. Moreover, isoflurane caused spatial working memory deficits in aged rats, which were prevented by taurine pretreatment. The results indicate that taurine pretreatment prevents anesthetic isoflurane-induced cognitive impairment by inhibiting ER stress-mediated activation of apoptosis pathways in the hippocampus in aged rats.

Effect of Chemical Prevention Drugs-based MicroRNAs and Their Target Genes 
on Tumor Inhibition

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Yanhui JIANG

2015-04-01

Full Text Available Chemopreventive drugs including natural chemopreventive drugs and synthetic chemopreventive drugs, it not only can prevent cancer, can also play a role in tumor treatment. MicroRNAs (miRNAs is a kind of short chains of non-coding RNA, regulating the expression of many genes through the way of degradation of mRNA or inhibitting mRNA translation. In recent years, more and more studies have shown that chemopreventive drugs through influence the expression of miRNAs and their target genes play a role in the prevention and treatment in a variety of tumors, and chemopreventive drugs on the experimental study of miRNAs and their target genes in tumor have demonstrated a good safety and efficacy. Effect on chemopreventive drugs-based microRNAs and their target genes into cancer cells will be expected as a new starting point for cancer research. The thesis expounds and analyzes between the natural chemopreventive drugs and synthetic chemopreventive drugs and miRNAs and their target genes in tumor research progress.

A search for supersymmetric electrons with the Mark II detector at PEP (Positron Electron Project)

Energy Technology Data Exchange (ETDEWEB)

LeClaire, B.W.

1987-10-01

An experimental search for selectrons, the supersymmetric partner of the electron, has been performed at the PEP storage ring at SLAC using the Mark II detector. The experimental search done was based upon hypothetical reaction in e/sup +/e/sup -/ interactions at PEP center of mass energies of 29 GeV. In this reaction the selectrons, e-tilde, are assumed produced by the interaction of one of initial state electrons with a photon radiated from the other initial state electron. This latter electron is assumed to continue down the beam pipe undetected. The photon and electron then produce a selectron and a photino, ..gamma..-tilde, in the supersymmetric analog of Compton scattering. The photino is assumed to be the lightest supersymmetric particle, and as such, does not interact in the detector, thereby escaping detection very much like a neutrino. The selectron is assumed to immediately decay into an electron and photino. This electron is produced with large p perpendicular with respect to the beam pipe, since it must balance the transverse momentum carried off by the photinos. Thus, the experimental signature of the process is a single electron in the detector with a large unbalanced tranverse momentum. No events of this type were observed in the original search of 123 pb/sup -1/ of data, resulting in a cross section limit of less than 2.4 x 10/sup -2/ pb (at the 95% CL) within the detector acceptance. This cross section upper limit applies to any process which produces anomalous single electron events with missing transverse momentum. When interpreted as a supersymmetry search it results in a lower selectron mass limit of 22.2 GeV/c/sup 2/ for the case of massless photinos. Limits for non-zero mass photinos have been calculated. 87 refs., 67 figs., 17 tabs.

A search for supersymmetric electrons with the Mark II detector at PEP [Positron Electron Project

International Nuclear Information System (INIS)

LeClaire, B.W.

1987-10-01

An experimental search for selectrons, the supersymmetric partner of the electron, has been performed at the PEP storage ring at SLAC using the Mark II detector. The experimental search done was based upon hypothetical reaction in e + e - interactions at PEP center of mass energies of 29 GeV. In this reaction the selectrons, e, are assumed produced by the interaction of one of initial state electrons with a photon radiated from the other initial state electron. This latter electron is assumed to continue down the beam pipe undetected. The photon and electron then produce a selectron and a photino, γ, in the supersymmetric analog of Compton scattering. The photino is assumed to be the lightest supersymmetric particle, and as such, does not interact in the detector, thereby escaping detection very much like a neutrino. The selectron is assumed to immediately decay into an electron and photino. This electron is produced with large p perpendicular with respect to the beam pipe, since it must balance the transverse momentum carried off by the photinos. Thus, the experimental signature of the process is a single electron in the detector with a large unbalanced tranverse momentum. No events of this type were observed in the original search of 123 pb -1 of data, resulting in a cross section limit of less than 2.4 x 10 -2 pb (at the 95% CL) within the detector acceptance. This cross section upper limit applies to any process which produces anomalous single electron events with missing transverse momentum. When interpreted as a supersymmetry search it results in a lower selectron mass limit of 22.2 GeV/c 2 for the case of massless photinos. Limits for non-zero mass photinos have been calculated. 87 refs., 67 figs., 17 tabs

Development of a movable plunger tuner for the high-power RF cavity for the PEP-II B-factory

International Nuclear Information System (INIS)

Schwarz, H.D.; Fant, K.; Judkins, J.G.

1997-05-01

A 10 cm diameter by 5 cm travel plunger tuner was developed for the PEP-II RF copper cavity system. The single cell cavity including the tuner is designed to operate up to 150 kW of dissipated RF power are specially placed 8.5 cm away from the inside wall of the cavity to avoid fundamental and higher order mode resonances. The spring fingers are made of dispersion-strengthened copper to accommodate relatively high heating. The design, alignment, testing and performance of the tuner is described

The PEP [positron-electron-proton] electron-positron ring: An update

International Nuclear Information System (INIS)

1975-03-01

The first stage of the positron-electron-protron (PEP) colliding-beam system, which has been under joint study by a Lawrence Berkeley Laboratory--Stanford Linear Accelerator Center team for the past two years, will be the electron-positron storage ring. The physics justification for the e + e/sup /minus// ring is summarized briefly and the proposed facility is described. The ring will have six arcs having gross radii of about 220 m and six interaction regions located at the centers of straight sections about 130 m long. The longitudinal distance left free for experimental apparatus around the interaction regions was set provisionally at 20 m. The range of operating beam energies will be from 5 GeV to 15 GeV. The design luminosity at 15 GeV will be 10 32 cm/sup /minus/2/s/sup /minus/1/, and the luminosity will vary approximately as the square of the beam energy. Alternative methods under consideration for adjusting the beam cross section are discussed. The designs of the storage ring subsystems and of the conventional facilities including the experimental halls at the interaction regions are described. 7 figs., 3 tabs

The Association between Endometriomas and Ovarian Cancer: Preventive Effect of Inhibiting Ovulation and Menstruation during Reproductive Life.

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Grandi, Giovanni; Toss, Angela; Cortesi, Laura; Botticelli, Laura; Volpe, Annibale; Cagnacci, Angelo

2015-01-01

Although endometriosis frequently involves multiple sites in the pelvis, malignancies associated with this disease are mostly confined to the ovaries, evolving from an endometrioma. Endometriomas present a 2-3-fold increased risk of transformation in clear-cell, endometrioid, and possibly low-grade serous ovarian cancers, but not in mucinous ovarian cancers. These last cancers are, in some aspects, different from the other epithelial ovarian cancers, as they do not appear to be decreased by the inhibition of ovulation and menstruation. The step by step process of transformation from typical endometrioma, through atypical endometrioma, finally to ovarian cancer seems mainly related to oxidative stress, inflammation, hyperestrogenism, and specific molecular alterations. Particularly, activation of oncogenic KRAS and PI3K pathways and inactivation of tumor suppressor genes PTEN and ARID1A are suggested as major pathogenic mechanisms for endometriosis associated clear-cell and endometrioid ovarian cancer. Both the risk for endometriomas and their associated ovarian cancers seems to be highly and similarly decreased by the inhibition of ovulation and retrograde menstruation, suggesting a common pathogenetic mechanism and common possible preventive strategies during reproductive life.

Delivering health information about self-medication to older adults: use of touchscreen-equipped notebook computers.

Science.gov (United States)

Neafsey, P J; Strickler, Z; Shellman, J; Padula, A T

2001-11-01

Preventing Drug Interactions in Active Older Adults is an educational intervention to prevent prescription and over-the-counter (OTC) drug and alcohol interactions in active, community-living older adults. The objectives of the program are to increase older adults' knowledge of potential interactions of prescription medications with OTC drugs and alcohol and to increase their confidence (self-efficacy) about how to avoid such interactions. An interactive multimedia computer software program (Personal Education Program or PEP) was designed for the learning styles and psychomotor skills of older adults. Focus groups of older adults evaluated PEP components in a formative manner during development. The program content dealing with antacids, calcium supplements, and acid reducers was pilot tested with 60 older adults recruited from local senior centers. Participants used the PEP on notebook computers equipped with infrared-sensitive touchscreens. Users of PEP had greater knowledge and self-efficacy scores than controls. Participants indicated a high degree of satisfaction with the PEP and reported their intent to make specific changes in self-medication behaviors.

Virulent poxviruses inhibit DNA sensing by preventing STING activation.

Science.gov (United States)

Georgana, Iliana; Sumner, Rebecca P; Towers, Greg J; Maluquer de Motes, Carlos

2018-02-28

Cytosolic recognition of DNA has emerged as a critical cellular mechanism of host immune activation upon pathogen invasion. The central cytosolic DNA sensor cGAS activates STING, which is phosphorylated, dimerises and translocates from the ER to a perinuclear region to mediate IRF-3 activation. Poxviruses are dsDNA viruses replicating in the cytosol and hence likely to trigger cytosolic DNA sensing. Here we investigated the activation of innate immune signalling by 4 different strains of the prototypic poxvirus vaccinia virus (VACV) in a cell line proficient in DNA sensing. Infection with the attenuated VACV strain MVA activated IRF-3 via cGAS and STING, and accordingly STING dimerised and was phosphorylated during MVA infection. Conversely, VACV strains Copenhagen and Western Reserve inhibited STING dimerisation and phosphorylation during infection and in response to transfected DNA and cGAMP, thus efficiently suppressing DNA sensing and IRF-3 activation. A VACV deletion mutant lacking protein C16, thought to be the only viral DNA sensing inhibitor acting upstream of STING, retained the ability to block STING activation. Similar inhibition of DNA-induced STING activation was also observed for cowpox and ectromelia viruses. Our data demonstrate that virulent poxviruses possess mechanisms for targeting DNA sensing at the level of the cGAS-STING axis and that these mechanisms do not operate in replication-defective strains such as MVA. These findings shed light on the role of cellular DNA sensing in poxvirus-host interactions and will open new avenues to determine its impact on VACV immunogenicity and virulence. IMPORTANCE Poxviruses are dsDNA viruses infecting a wide range of vertebrates and include the causative agent of smallpox (variola virus) and its vaccine vaccinia virus (VACV). Despite smallpox eradication VACV remains of interest as a therapeutic. Attenuated strains are popular vaccine candidates, whereas replication-competent strains are emerging as

Several hPepT1-transported drugs are substrates of the Escherichia coli proton-coupled oligopeptide transporter YdgR.

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Prabhala, Bala K; Aduri, Nanda G; Iqbal, Mazhar; Rahman, Moazur; Gajhede, Michael; Hansen, Paul R; Mirza, Osman

2017-06-01

Proton-dependent oligopeptide transporters (POTs) are secondary active transporters found in all kingdoms of life. POTs utilize the proton electrochemical gradient for the uptake of nutrient dipeptides and tripeptides. The human POT hPepT1 is known to transport a number of drugs. As part of ongoing studies on substrate specificities of POTs from Escherichia coli, our aim in this study was to investigate whether bacterial POTs could also transport these drugs. For this, we selected the common orally administered drugs sulpiride, bestatin, valacyclovir, ampicillin and oseltamivir, that are all transported by hPepT1. The transport of these drugs was evaluated using the prototypical POT YdgR from E. coli. The transport studies were pursued through combining cell-based assays with liquid chromatography-tandem mass spectrometric (LC-MS/MS) analysis. These investigations revealed that YdgR from E. coli is able to transport five (sulpiride, bestatin, valacyclovir, ampicillin and oseltamivir) drugs. Furthermore, cells not overexpressing YdgR were also able to transport these drugs in a POT-like manner. Orthologues of YdgR are found in several species in the gut microbiome; hence, our findings could have implications for further understanding about the interaction between gut microbes and orally administered drugs. Copyright © 2017 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Herencia de la resistencia al virus del mosaico deformante del pimentón PepDMV en Capsicum Inheritance of resistance to the deforming pepper mosaic virus, PepDMV, in Capsicum

Directory of Open Access Journals (Sweden)

Mario Augusto García Dávila

2009-10-01

Full Text Available En busca de determinar el modo de herencia de la resistencia en tres materiales resistentes, se hicieron cruzamientos hacia tres líneas susceptibles. Se siguió el método del retrocruzamiento propuesto por Warner (1952 fundamentado en el modelo matemático de Fisher Immer y Tedin (1932 descrito con detalle por Mater (1949 y Jenkins (1982, 1984 en el cual se descompone la varianza genética en tres componentes: aditiva, dominancia y epistática. El modelo del retrocruzamiento incluye los dos parentales, el hibrido de la primera generación y la autofecunfación de la F1 para formar la población F2 y las retrocruzas hacia ambos padres. Las poblaciones fueron evaluadas a resistencia al virus del mosaico del pimentón PepDMV en condiciones de invernadero. Los resultados mostraron que el modelo aditivodominancia explicó la resistencia en los híbridos formados entre materiales resistentes y susceptibles. Los genes con acción heredable transmiten a la descendencia el efecto de resistencia. La ganancia de la resistencia viral se da por la presencia de parentales resistentes.With the aim to determine the mode of inheritance in three resistant materials, crosses were performed towards three susceptible lines. We followed the backcrossing method used by Warner (1952, based on the mathematical model of Fisher Immer and tedin (1932, described in detail by Mater (1949 and Jenkins (1982, 1984. In this method the genetic variance is partitioned into three components: additive, dominant and epistatic. The backcross method includes the two parents, the F1 hybrid, and the self-pollination of the F1 to form the F2 population, and the backcrosses to both parents. The populations were evaluated for resistance to the pepper mosaic virusPepDMV in greenhouse conditions. The results showed that the model additive-dominant explained the resistance in the hybrids formed between resistant and susceptible material. The genes with heritable action transmit to their

Comparing Provider and Client Preferences for HIV Prevention Services in South Africa among Men Who Have Sex with Men.

Science.gov (United States)

Shaver, John; Sullivan, Patrick; Siegler, Aaron; de Voux, Alex; Phaswana-Mafuya, Nancy; Bekker, Linda-Gail; Baral, Stefan D; Wirtz, Andrea L; Beyrer, Chris; Brown, Ben; Stephenson, Rob

Combination prevention efforts are now recommended toward reducing HIV incidence among men who have sex with men (MSM). Understanding the perceptions of both MSM and service providers is critical to informing the development of prevention packages and ultimately improving intervention effectiveness. This study assessed the preferences of MSM and health service providers in the administration of HIV-prevention efforts. Qualitative data were gathered from a series of separate MSM and health care provider focus groups in 2 South African cities. Participants discussed HIV-prevention services and MSM client experiences within South Africa and identified the 3 most important clinic characteristics and 3 most important HIV-prevention services for MSM clients. Priorities indicated by both MSM and health care providers were confidentiality of visit, friendly staff, and condoms, while discrepancies existed between MSM and providers regarding provider consistency and the provision of pre-exposure prophylaxis/post-exposure prophylaxis (PrEP/PEP) and lubricant as prevention methods. Effective interventions must address these discrepancies through the design of intervention and provider training to optimally accommodate MSM.

Synthesis and labelling of Df-DUPA-Pep with gallium-68 and zirconium-89 as new PSMA ligands

International Nuclear Information System (INIS)

Benjamin Baur; Ehab Al-Momani; Noeen Malik; Hans-Juergen Machulla; Reske, S.N.; Christoph Solbach; Elena Andreolli; University of Milano-Bicocca, Milan

2014-01-01

Prostate-specific membrane antigen (PSMA) is a cell surface protein that is overexpressed in prostate cancer. Due to the specificity of expression of PSMA, numerous urea-based ligands have been synthesized until now. In the current study, we describe the coupling of the chelator desferrioxamine to DUPA-Pep and the subsequent labelling with Ga-68 and Zr-89 as new PSMA ligands. The labelling step is performed at room temperature and pH 7.5. In both radiosyntheses, the RCYs were higher than 95 % within 10 min, making dispensable any further purification and providing the radiotracers directly applicable for further utilization. (author)

Curcumin synergizes with resveratrol to inhibit colon cancer.

Science.gov (United States)

Majumdar, Adhip P N; Banerjee, Sanjeev; Nautiyal, Jyoti; Patel, Bhaumik B; Patel, Vaishali; Du, Jianhua; Yu, Yingjie; Elliott, Althea A; Levi, Edi; Sarkar, Fazlul H

2009-01-01

Development and progression of many malignancies, including colorectal cancer, are associated with activation of multiple signaling pathways. Therefore, inhibition of these signaling pathways with noncytotoxic natural products represents a logical preventive and/or therapeutic approach for colon cancer. Curcumin and resveratrol, both of which inhibit the growth of transformed cells and colon carcinogenesis, were selected to examine whether combining them would be an effective preventive and/or therapeutic strategy for colon cancer. Indeed, the combination of curcumin and resveratrol was found to be more effective in inhibiting growth of p53-positive (wt) and p53-negative colon cancer HCT-116 cells in vitro and in vivo in SCID xenografts of colon cancer HCT-116 (wt) cells than either agent alone. Analysis by Calcusyn software showed synergism between curcumin and resveratrol. The inhibition of tumors in response to curcumin and/or resveratrol was associated with the reduction in proliferation and stimulation of apoptosis accompanied by attenuation of NF-kappaB activity. In vitro studies have further demonstrated that the combinatorial treatment caused a greater inhibition of constitutive activation of EGFR and its family members as well as IGF-1R. Our current data suggest that the combination of curcumin and resveratrol could be an effective preventive/therapeutic strategy for colon cancer.

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

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