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

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

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

Directory of Open Access Journals (Sweden)

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.

PEP-II Alignment

CERN Document Server

Gaydosh, M

2003-01-01

The PEP-II Asymmetric B-factory consists of two independent storage rings, one located atop the other in the 2200m-circumference PEP tunnel. The high-energy ring, which stores a 9-GeV electron beam, is an upgrade of the existing PEP collider. It re-utilizes all of the PEP magnets and incorporates a state-of-the-art copper vacuum chamber and a new RF system capable of supporting a one-amp stored beam. The low-energy ring, which stores 3.1-GeV positrons, is new construction. Injection is achieved by extracting electrons and positrons at collision energies from the SLC and transporting them each in a dedicated bypass line. The low-emittance SLC beams will be used for the injection process.

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.

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

Transduced PEP-1-ribosomal protein S3 (rpS3) ameliorates 12-O-tetradecanoylphorbol-13-acetate-induced inflammation in mice

International Nuclear Information System (INIS)

Ahn, Eun Hee; Kim, Dae Won; Kang, Hye Won; Shin, Min Jae; Won, Moo Ho; Kim, Joon; Kim, Dong Joon; Kwon, Oh-Shin; Kang, Tae-Cheon; Han, Kyu Hyung; Park, Jinseu; Eum, Won Sik; Choi, Soo Young

2010-01-01

This study investigated the preventive effect of ribosomal protein S3 (rpS3) on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ear edema in mice. A cell permeable expression vector PEP-1-rpS3 was constructed. Topical application of the vector markedly inhibited TPA-induced expression levels of cyclooxygenase-2 (COX-2) and pro-inflammatory cytokines. Application of PEP-1-rpS3 also resulted in a significant reduction in the activation of nuclear factor-kappa B (NF-kB) and mitogen-activated protein kinase (MAPK) in TPA-treated ears. These results indicate that PEP-1-rpS3 inhibits inflammatory response cytokines and enzymes by blocking NF-kB and MAPK, prompting the suggestion that PEP-1-rpS3 can be used as a therapeutic agent against skin inflammation.

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 ...

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

Can protein-fortified pasta serve as a meat substitute?

Science.gov (United States)

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

1982-01-01

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

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

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

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...

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

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

Pep for PEP-II

International Nuclear Information System (INIS)

Anon.

1995-01-01

The major B-factory project at the Stanford Linear Accelerator Center have(SLAC) is well underway and moving along smartly, en route to commencement of operations in September 1998. Called PEP-II, the new facility is a joint venture of three California laboratories: Lawrence Berkeley Laboratory (LBL), Lawrence Livermore Laboratory (LLNL) and SLAC. Housed at SLAC in the tunnels and buildings built for the original PEP electron-positron collider in the late 1970s, it involves no conventional civil engineering. In fact, PEP-II is a recycling project in more ways than one: for example, most of the original PEP magnets have been renovated for reuse in the PEP-II high-energy ring. While some of them require substantial rework (to change their length, for instance), many of them merely require repainting and remeasuring. The work of building the hardware is divided up among the three laboratories. LBL is primarily responsible for the low-energy ring; LLNL is building most of the interaction region, the complicated part where the high and low energy rings come together; and SLAC is responsible for the rest. Proposed by President Clinton as a ''presidential initiative'' (December 1993, page 2), the project was given a four-year funding profile. The total cost of $177 million, excluding the BaBar detector (September, page 16), was planned by the US government to be entirely provided during the present administration, the last increment coming in the final quarter of 1997. Happily, the first two increments have been forthcoming as planned and the third is faring well in US Congress. The PEP-II design is based on two intersecting storage rings, one carrying 9 GeV electrons and the other 3.1 GeV positrons, operating with high beam currents (a few amperes) to produce a luminosity of 3 x 10 33 per sq cm per s. The asymmetry in the energies of the colliding particles means that the centre-ofmass of the electron-positron annihilation system moves rapidly in the

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

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

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....

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

Design and alaysis of the PEP-II B-Factory HER QF5 quadrupole magnet

International Nuclear Information System (INIS)

Kendall, C.M.; Harvey, A.; Swan, J.; Yamamoto, R.; Yokota, T.; Tanabe, J.; Sullivan, M.; Wienands, U.

1997-01-01

The High Energy Ring (HER) in Stanford Linear Accelerator Center's PEP-II B-Factory employs two high field quality quadrupole magnets, labeled QF5, located in the Interaction Region (IR) symmetrically about the Interaction Point (IP), for final horizontal beam focusing. An asymmetric, septum, Collins quadrupole design is required for QF5 as a result of space constraints within the IR. Water cooled square hollow copper conductor is used in a two coil per pole configuration to develop the 61.7 kG/m and 82.2 kG/m gradients required for the HER 9 GeV and 12 GeV energy levels respectively. A 1.45 m long laminated iron core constructed in two halves with a 160 mm diameter aperture and pole tip shims shape the quadruple field. The QF5 field quality requirements include a multipole content of b n /b 2 ≤1 x 10 -4 for n = 3-15 at a radius of 78.1 mm. The QF5 quadrupole mechanical and magnetic design and analysis are presented

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.)

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

The Ustilago maydis effector Pep1 suppresses plant immunity by inhibition of host peroxidase activity.

Directory of Open Access Journals (Sweden)

Christoph Hemetsberger

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

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...

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

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

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.

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 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

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.

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.

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.

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

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.

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

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 sextupoles

International Nuclear Information System (INIS)

Brunk, W.O.

1976-10-01

The sextupole requirements of PEP are such that they represent a much larger proportion of the ring magnet cost than they did in SPEAR. A study is given of various fabrication techniques all pointed toward cost reduction without an undue sacrifice of function quality. The point of debarkation is the sextupole design as described in the PEP Conceptual Design Report. There are three main areas of inquiry, namely, pole tip contour, coil material and fabrication and yoke size

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...

The Danish PEP Registry

DEFF Research Database (Denmark)

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

2016-01-01

BACKGROUND: The risk of occupational exposures to blood cannot be eliminated completely and access to post-exposure prophylaxis (PEP) to prevent HIV transmission is important. However, PEP administration has been associated with frequent adverse effects, low compliance and difficulties to ensure ...

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

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

Determination of Free-Form and Peptide Bound Pyrraline in the Commercial Drinks Enriched with Different Protein Hydrolysates

Directory of Open Access Journals (Sweden)

Zhili Liang

2016-07-01

Full Text Available Pyrraline, a causative factor for the recent epidemics of diabetes and cardiovascular disease, is also employed as an indicator to evaluate heat damage and formation of advanced glycation end-products (AGEs in foods. Peptide-enriched drinks (PEDs are broadly consumed worldwide due to rapid rate of absorption and perceived health effects. It can be hypothesized that PED is an important source of pyrraline, especially peptide bound pyrraline (Pep-Pyr. In this study we determined free-form pyrraline (Free-Pyr and Pep-Pyr in drinks enriched with whey protein hydrolysate (WPH, soy protein hydrolysate (SPH and collagen protein hydrolysate (CPH. A detection method was developed using ultrahigh-performance liquid chromatography with UV-visible detector coupled with tandem mass spectrometry after solid-phase extraction (SPE. The SPE led to excellent recovery rates ranging between 93.2% and 98.5% and a high reproducibility with relative standard deviations (RSD of <5%. The limits of detection and quantification obtained were 30.4 and 70.3 ng/mL, respectively. Pep-Pyr was identified as the most abundant form (above 96 percent of total pyrraline, whereas Free-Pyr was present in a small proportion (less than four percent of total pyrraline. The results indicate that PED is an important extrinsic source of pyrraline, especially Pep-Pyr. As compared with CPH- and SPH-enriched drinks, WPH-enriched drinks contained high content of Pep-Pyr. The Pep-Pyr content is associated with the distribution of peptide lengths and the amino acid compositions of protein in PEDs.

PRAS40 and PRR5-like protein are new mTOR interactors that regulate apoptosis.

Directory of Open Access Journals (Sweden)

Kathrin Thedieck

Full Text Available TOR (Target of Rapamycin is a highly conserved protein kinase and a central controller of cell growth. TOR is found in two functionally and structurally distinct multiprotein complexes termed TOR complex 1 (TORC1 and TOR complex 2 (TORC2. In the present study, we developed a two-dimensional liquid chromatography tandem mass spectrometry (2D LC-MS/MS based proteomic strategy to identify new mammalian TOR (mTOR binding proteins. We report the identification of Proline-rich Akt substrate (PRAS40 and the hypothetical protein Q6MZQ0/FLJ14213/CAE45978 as new mTOR binding proteins. PRAS40 binds mTORC1 via Raptor, and is an mTOR phosphorylation substrate. PRAS40 inhibits mTORC1 autophosphorylation and mTORC1 kinase activity toward eIF-4E binding protein (4E-BP and PRAS40 itself. HeLa cells in which PRAS40 was knocked down were protected against induction of apoptosis by TNFalpha and cycloheximide. Rapamycin failed to mimic the pro-apoptotic effect of PRAS40, suggesting that PRAS40 mediates apoptosis independently of its inhibitory effect on mTORC1. Q6MZQ0 is structurally similar to proline rich protein 5 (PRR5 and was therefore named PRR5-Like (PRR5L. PRR5L binds specifically to mTORC2, via Rictor and/or SIN1. Unlike other mTORC2 members, PRR5L is not required for mTORC2 integrity or kinase activity, but dissociates from mTORC2 upon knock down of tuberous sclerosis complex 1 (TSC1 and TSC2. Hyperactivation of mTOR by TSC1/2 knock down enhanced apoptosis whereas PRR5L knock down reduced apoptosis. PRR5L knock down reduced apoptosis also in mTORC2 deficient cells. The above suggests that mTORC2-dissociated PRR5L may promote apoptosis when mTOR is hyperactive. Thus, PRAS40 and PRR5L are novel mTOR-associated proteins that control the balance between cell growth and cell death.

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.

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.

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-1-SIRT2 inhibits inflammatory response and oxidative stress-induced cell death via expression of antioxidant enzymes in murine macrophages.

Science.gov (United States)

Kim, Mi Jin; Kim, Dae Won; Park, Jung Hwan; Kim, Sang Jin; Lee, Chi Hern; Yong, Ji In; Ryu, Eun Ji; Cho, Su Bin; Yeo, Hyeon Ji; Hyeon, Jiye; Cho, Sung-Woo; Kim, Duk-Soo; Son, Ora; Park, Jinseu; Han, Kyu Hyung; Cho, Yoon Shin; Eum, Won Sik; Choi, Soo Young

2013-10-01

Sirtuin 2 (SIRT2), a member of the sirtuin family of proteins, plays an important role in cell survival. However, the biological function of SIRT2 protein is unclear with respect to inflammation and oxidative stress. In this study, we examined the protective effects of SIRT2 on inflammation and oxidative stress-induced cell damage using a cell permeative PEP-1-SIRT2 protein. Purified PEP-1-SIRT2 was transduced into RAW 264.7 cells in a time- and dose-dependent manner and protected against lipopolysaccharide- and hydrogen peroxide (H₂O₂)-induced cell death and cytotoxicity. Also, transduced PEP-1-SIRT2 significantly inhibited the expression of cytokines as well as the activation of NF-κB and mitogen-activated protein kinases (MAPKs). In addition, PEP-1-SIRT2 decreased cellular levels of reactive oxygen species (ROS) and of cleaved caspase-3, whereas it elevated the expression of antioxidant enzymes such as MnSOD, catalase, and glutathione peroxidase. Furthermore, topical application of PEP-1-SIRT2 to 12-O-tetradecanoylphorbol 13-acetate-treated mouse ears markedly inhibited expression levels of COX-2 and proinflammatory cytokines as well as the activation of NF-κB and MAPKs. These results demonstrate that PEP-1-SIRT2 inhibits inflammation and oxidative stress by reducing the levels of expression of cytokines and ROS, suggesting that PEP-1-SIRT2 may be a potential therapeutic agent for various disorders related to ROS, including skin inflammation. Copyright © 2013 Elsevier Inc. All rights reserved.

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

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.

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

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.

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.

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

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

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

Functional dissection of Streptococcus pyogenes M5 protein: the hypervariable region is essential for virulence.

Directory of Open Access Journals (Sweden)

Johan Waldemarsson

Full Text Available The surface-localized M protein of Streptococcus pyogenes is a major virulence factor that inhibits phagocytosis, as determined ex vivo. Because little is known about the role of M protein in vivo we analyzed the contribution of different M protein regions to virulence, using the fibrinogen (Fg-binding M5 protein and a mouse model of acute invasive infection. This model was suitable, because M5 is required for mouse virulence and binds mouse and human Fg equally well, as shown here. Mixed infection experiments with wild type bacteria demonstrated that mutants lacking the N-terminal hypervariable region (HVR or the Fg-binding B-repeat region were strongly attenuated, while a mutant lacking the conserved C-repeats was only slightly attenuated. Because the HVR of M5 is not required for phagocytosis resistance, our data imply that this HVR plays a major but unknown role during acute infection. The B-repeat region is required for phagocytosis resistance and specifically binds Fg, suggesting that it promotes virulence by binding Fg. However, B-repeat mutants were attenuated even in Fg-deficient mice, implying that the B-repeats may have a second function, in addition to Fg-binding. These data demonstrate that two distinct M5 regions, including the HVR, are essential to virulence during the early stages of an infection. In particular, our data provide the first in vivo evidence that the HVR of an M protein plays a major role in virulence, focusing interest on the molecular role of this region.

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

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.

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

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

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

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.

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.

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

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.

NMDA-induced potentiation of mGluR5 is mediated by activation of protein phosphatase 2B/calcineurin

Science.gov (United States)

Alagarsamy, Sudar; Saugstad, Julie; Warren, Lee; Mansuy, Isabelle M.; Gereau, Robert W.; Conn, P. Jeffrey

2010-01-01

Previous reports have shown that activation of N-methyl-D-aspartate (NMDA) receptors potentiates responses to activation of the group I metabotropic glutamate receptor mGluR5 by reversing PKC-mediated desensitization of this receptor. NMDA-induced reversal of mGluR5 desensitization is dependent on activation of protein phosphatases. However, the specific protein phosphatase involved and the precise mechanism by which NMDA receptor activation reduces mGluR desensitization are not known. We have performed a series of molecular, biochemical, and genetic studies to show that NMDA-induced regulation of mGluR5 is dependent on activation of calcium-dependent protein phosphatase 2B/calcineurin (PP2B/CaN). Furthermore, we report that purified calcineurin directly dephosphorylates the C-terminal tail of mGluR5 at sites that are phosphorylated by PKC. Finally, immunoprecipitation and GST fusion protein pull-down experiments reveal that calcineurin interacts with mGluR5, suggesting that these proteins could be colocalized in a signaling complex. Taken together with previous studies, these data suggest that activation of NMDA receptors leads to activation of calcineurin and that calcineurin modulates mGluR5 function by directly dephosphorylating mGluR5 at PKC sites that are involved in desensitization of this receptor. 2005 Elsevier Ltd. All rights reserved. PMID:16005030

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

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

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

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

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

Energy Technology Data Exchange (ETDEWEB)

Lee, Su Jin; Kang, Hyung Kyung [Department of Physiology, College of Medicine, Hallym University, Chunchon 200-702 (Korea, Republic of); Song, Dong Keun [Department of Pharmacology, College of Medicine, Hallym University, Chunchon 200-702 (Korea, Republic of); Eum, Won Sik; Park, Jinseu [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of); Choi, Soo Young, E-mail: sychoi@hallym.ac.kr [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of); Kwon, Hyeok Yil, E-mail: hykwon@hallym.ac.kr [Department of Physiology, College of Medicine, Hallym University, Chunchon 200-702 (Korea, Republic of)

2015-06-05

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

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

International Nuclear Information System (INIS)

Lee, Su Jin; Kang, Hyung Kyung; Song, Dong Keun; Eum, Won Sik; Park, Jinseu; Choi, Soo Young; Kwon, Hyeok Yil

2015-01-01

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

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.

Critical Role of PepT1 in Promoting Colitis-Associated Cancer and Therapeutic Benefits of the Anti-inflammatory PepT1-Mediated Tripeptide KPV in a Murine ModelSummary

Directory of Open Access Journals (Sweden)

Emilie Viennois

2016-05-01

Full Text Available Background & Aims: The human intestinal peptide transporter 1 (hPepT1, is expressed in the small intestine at low levels in the healthy colon and up-regulated during inflammatory bowel disease. hPepT1 plays a role in mouse colitis and human studies have shown that chronic intestinal inflammation leads to colorectal cancer (colitis-associated cancer; CAC. Hence, we assessed here the role of PepT1 in CAC. Methods: Mice with hPepT1 overexpression in intestinal epithelial cells (transgenic [TG] or PepT1 (PepT1-knockout [KO] deletion were used and CAC was induced by azoxymethane/dextran sodium sulfate. Results: TG mice had larger tumor sizes, increased tumor burdens, and increased intestinal inflammation compared with wild-type (WT mice. Conversely, tumor number and size and intestinal inflammation were decreased significantly in PepT1-KO mice. Proliferating crypt cells were increased in TG mice and decreased in PepT1-KO mice. Analysis of human colonic biopsy specimens showed increased expression of PepT1 in patients with colorectal cancer, suggesting that PepT1 might be targeted for the treatment of CAC. The use of an anti-inflammatory tripeptide Lys-Pro-Val (KPV transported by PepT1 was able to prevent carcinogenesis in WT mice. When administered to PepT1-KO mice, KPV did not trigger any of the inhibitory effect on tumorigenesis observed in WT mice. Conclusions: The observations that PepT1 was highly expressed in human colorectal tumor and that its overexpression and deletion in mice increased and decreased colitis-associated tumorigenesis, respectively, suggest that PepT1 is a potential therapeutic target for the treatment of colitis-associated tumorigenesis. Keywords: Colitis-Associated Cancer, Intestinal Inflammation, PepT1, KPV Peptide

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

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

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.

The anti-inflammatory effect of the synthetic antimicrobial peptide 19-2.5 in a murine sepsis model: a prospective randomized study

Science.gov (United States)

2013-01-01

Introduction Increasing rates of multi-resistant bacteria are a major problem in the treatment of critically ill patients. Furthermore, conventional antibiotics lead to the release of bacterial derived membrane parts initiating pro-inflammatory cascades with potential harm to the patient. Antimicrobial peptides (AMP) may kill bacteria without releasing pro-inflammatory factors. Thus, we compared three newly developed synthetic anti-lipopolysaccharide peptides (SALPs) with a broader range of efficacy to suppress cytokine release in plasma and CD14 mRNA expression in organ tissue in a murine, polymicrobial sepsis model. Methods A randomized, experimental trial was conducted in an animal research facility. Male NMRI mice (n = 90; 8- to 12-weeks old) were randomized to the following six groups: (i) sham operation and parenteral vehicle (NaCl 0.9%) administration (sham); (ii) cecal ligation and puncture (CLP) and vehicle infusion (sepsis-control), (iii) CLP and polymyxin B infusion (polyB), or (iv to vi) CLP and infusion of three different synthetic antimicrobial peptides Peptide 19-2.5 (Pep2.5), Peptide 19-4 (Pep4) or Peptide 19-8 (Pep8). All animals underwent arterial and venous catheterization for hemodynamic monitoring 48 hours prior to CLP or sham-operation. Physical appearance and behavior (activity), plasma cytokine levels, and CD14 mRNA expression in heart, lung, liver, spleen and kidney tissue were determined 24 hours after CLP or sham operation. Results Only Pep2.5 significantly enhanced the activity after CLP, whereas none of the therapeutic regimens elevated the mean arterial pressure or heart rate. The strongly elevated IL-6, IL-10 and monocyte chemoattractant protein serum levels in septic animals were significantly reduced after Pep2.5 administration (P < 0.001, P < 0.001, and P < 0.001, respectively). Similarly, Pep2.5 significantly reduced the sepsis-induced CD14 mRNA expression in heart (P = 0.003), lung (P = 0.008), and spleen tissue (P = 0.009) but

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

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.

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

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

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.

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

Science.gov (United States)

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

2007-01-01

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

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

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.

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.

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-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

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

Science.gov (United States)

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

2010-12-10

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

EFRT M-12 Issue Resolution: Solids Washing

Energy Technology Data Exchange (ETDEWEB)

Baldwin, David L.; Schonewill, Philip P.; Toth, James J.; Huckaby, James L.; Eslinger, Paul W.; Hanson, Brady D.; Kurath, Dean E.; Minette, Michael J.

2010-01-01

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, 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.

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

Post-Exposure Prophylaxis (PEP)

Science.gov (United States)

... Child Transmission of HIV Post-Exposure Prophylaxis (PEP) Pre-Exposure Prophylaxis (PrEP) HIV Treatment HIV Treatment: The Basics Just ... to HIV frequently. Another HIV prevention method, called pre-exposure prophylaxis or PrEP, is when people at high risk ...

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.

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

Differential between Protein and mRNA Expression of CCR7 and SSTR5 Receptors in Crohn's Disease Patients

Directory of Open Access Journals (Sweden)

Nathalie Taquet

2009-01-01

Full Text Available Crohn's disease (CD is a multifactorial chronic inflammatory bowel disease of unknown cause. The aim of the present study was to explore if mRNA over-expression of SSTR5 and CCR7 found in CD patients could be correlated to respective protein expression. When compared to healthy donors, SSTR5 was over-expressed 417 ± 71 times in CD peripheral blood mononuclear cells (PBMCs. Flow cytometry experiments showed no correlation between mRNA and protein expression for SSTR5 in PBMCs. In an attempt to find a reason of such a high mRNA expression, SSTR5 present on CD PBMCs were tested and found as biologically active as on healthy cells. In biopsies of CD intestinal tissue, SSTR5 was not over-expressed but CCR7, unchanged in PBMCs, was over-expressed by 10 ± 3 times in the lamina propria. Confocal microscopy showed a good correlation of CCR7 mRNA and protein expression in CD intestinal biopsies. Our data emphasize flow and image cytometry as impossible to circumvent in complement to molecular biology so to avoid false interpretation on receptor expressions. Once confirmed by further large-scale studies, our preliminary results suggest a role for SSTR5 and CCR7 in CD pathogenesis.

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

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

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

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

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...

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.

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

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

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

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.

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.

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%.

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.

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.

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)

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

Science.gov (United States)

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

2017-01-01

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

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.

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

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

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

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.)

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.

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

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.

Effects of positive expiratory pressure on pulmonary clearance of aerosolized technetium-99m-labeled diethylenetriaminepentaacetic acid in healthy individuals

Directory of Open Access Journals (Sweden)

Isabella Martins de Albuquerque

Full Text Available ABSTRACT Objective: To evaluate the effects of positive expiratory pressure (PEP on pulmonary epithelial membrane permeability in healthy subjects. Methods: We evaluated a cohort of 30 healthy subjects (15 males and 15 females with a mean age of 28.3 ± 5.4 years, a mean FEV1/FVC ratio of 0.89 ± 0.14, and a mean FEV1 of 98.5 ± 13.1% of predicted. Subjects underwent technetium-99m-labeled diethylenetriaminepentaacetic acid (99mTc-DTPA radioaerosol inhalation lung scintigraphy in two stages: during spontaneous breathing; and while breathing through a PEP mask at one of three PEP levels-10 cmH2O (n = 10, 15 cmH2O (n = 10, and 20 cmH2O (n = 10. The 99mTc-DTPA was nebulized for 3 min, and its clearance was recorded by scintigraphy over a 30-min period during spontaneous breathing and over a 30-min period during breathing through a PEP mask. Results: The pulmonary clearance of 99mTc-DTPA was significantly shorter when PEP was applied-at 10 cmH2O (p = 0.044, 15 cmH2O (p = 0.044, and 20 cmH2O (p = 0.004-in comparison with that observed during spontaneous breathing. Conclusions: Our findings indicate that PEP, at the levels tested, is able to induce an increase in pulmonary epithelial membrane permeability and lung volume in healthy subjects.

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.

Fragile X mental retardation protein recognizes a G quadruplex structure within the survival motor neuron domain containing 1 mRNA 5'-UTR.

Science.gov (United States)

McAninch, Damian S; Heinaman, Ashley M; Lang, Cara N; Moss, Kathryn R; Bassell, Gary J; Rita Mihailescu, Mihaela; Evans, Timothy L

2017-07-25

G quadruplex structures have been predicted by bioinformatics to form in the 5'- and 3'-untranslated regions (UTRs) of several thousand mature mRNAs and are believed to play a role in translation regulation. Elucidation of these roles has primarily been focused on the 3'-UTR, with limited focus on characterizing the G quadruplex structures and functions in the 5'-UTR. Investigation of the affinity and specificity of RNA binding proteins for 5'-UTR G quadruplexes and the resulting regulatory effects have also been limited. Among the mRNAs predicted to form a G quadruplex structure within the 5'-UTR is the survival motor neuron domain containing 1 (SMNDC1) mRNA, encoding a protein that is critical to the spliceosome. Additionally, this mRNA has been identified as a potential target of the fragile X mental retardation protein (FMRP), whose loss of expression leads to fragile X syndrome. FMRP is an RNA binding protein involved in translation regulation that has been shown to bind mRNA targets that form G quadruplex structures. In this study we have used biophysical methods to investigate G quadruplex formation in the 5'-UTR of SMNDC1 mRNA and analyzed its interactions with FMRP. Our results show that SMNDC1 mRNA 5'-UTR forms an intramolecular, parallel G quadruplex structure comprised of three G quartet planes, which is bound specifically by FMRP both in vitro and in mouse brain lysates. These findings suggest a model by which FMRP might regulate the translation of a subset of its mRNA targets by recognizing the G quadruplex structure present in their 5'-UTR, and affecting their accessibility by the protein synthesis machinery.

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%.

Structural basis for the inhibition of M1 family aminopeptidases by the natural product actinonin: Crystal structure in complex with E. coli aminopeptidase N.

Science.gov (United States)

Ganji, Roopa Jones; Reddi, Ravikumar; Gumpena, Rajesh; Marapaka, Anil Kumar; Arya, Tarun; Sankoju, Priyanka; Bhukya, Supriya; Addlagatta, Anthony

2015-05-01

Actinonin is a pseudotripeptide that displays a high affinity towards metalloproteases including peptide deformylases (PDFs) and M1 family aminopeptidases. PDF and M1 family aminopeptidases belong to thermolysin-metzincin superfamily. One of the major differences in terms of substrate binding pockets between these families is presence (in M1 aminopeptidases) or absence (in PDFs) of an S1 substrate pocket. The binding mode of actinonin to PDFs has been established previously; however, it is not clear how the actinonin, without a P1 residue, would bind to the M1 aminopeptidases. Here we describe the crystal structure of Escherichia coli aminopeptidase N (ePepN), a model protein of the M1 family aminopeptidases in complex with actinonin. For comparison we have also determined the structure of ePepN in complex with a well-known tetrapeptide inhibitor, amastatin. From the comparison of the actinonin and amastatin ePepN complexes, it is clear that the P1 residue is not critical as long as strong metal chelating head groups, like hydroxamic acid or α-hydroxy ketone, are present. Results from this study will be useful for the design of selective and efficient hydroxamate inhibitors against M1 family aminopeptidases. © 2015 The Protein Society.

A preliminary survey of M. hyopneumoniae virulence factors based on comparative genomic analysis

Directory of Open Access Journals (Sweden)

Henrique Bunselmeyer Ferreira

2007-01-01

Full Text Available Mycoplasma hyopneumoniae is the etiological agent of porcine enzootic pneumonia (PEP, a major problem for the pig industry. The mechanisms of M. hyopneumoniae pathogenicity allow to predict the existence of several classes of virulence factors, whose study has been essentially restricted to the characterization of adhesion-related and major antigenic proteins. The now available complete sequences of the genomes of two pathogenic and one non-pathogenic strain of M. hyopneumoniae allowed to use a comparative genomics approach to putatively identify virulence genes. In this preliminary survey, we were able to identify 118 CDSs encoding putative virulence factors, based on specific criteria ranging from predicted cell surface location or variation between strains to previous functional studies showing antigenicity or involvement in host-pathogen interaction. This survey is expected to serve as a first step towards the functional characterization of new virulence genes/proteins that will be important not only for a better comprehension of M. hyopneumoniae biology, but also for the development of new and improved protocols for PEP vaccination, diagnosis and treatment.

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

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

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

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

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

Characterization of a new M13 metallopeptidase from deep-sea Shewanella sp. E525-6 and mechanistic insight into its catalysis

Directory of Open Access Journals (Sweden)

Jin-Yu eYang

2016-01-01

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

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.

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 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

Effects of positive expiratory pressure on pulmonary clearance of aerosolized technetium-{sup 99m}-labeled diethylenetriaminepentaacetic acid in healthy individuals

Energy Technology Data Exchange (ETDEWEB)

Albuquerque, Isabella Martins de, E-mail: albuisa@gmail.com [Universidade Federal de Santa Maria (UFSM), Santa Maria, RS (Brazil). Departamento de Fisioterapia e Reabilitacao; Cardoso, Dannuey Machado; Paiva, Dulciane Nunes [Universidade de Santa Cruz do Sul, RS (Brazil); Masiero, Paulo Ricardo; Menna-Barreto, Sergio Saldanha [Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre (Brazil); Resqueti, Vanessa Regiane; Fregonezi, Guilherme Augusto de Freitas [Universidade Federal do Rio Grande do Norte (UFRN), Natal, RN (Brazil)

2016-11-15

Objective: To evaluate the effects of positive expiratory pressure (PEP) on pulmonary epithelial membrane permeability in healthy subjects. Methods: We evaluated a cohort of 30 healthy subjects (15 males and 15 females) with a mean age of 28.3 ± 5.4 years, a mean FEV{sub 1}/FVC ratio of 0.89 ± 0.14, and a mean FEV{sub 1} of 98.5 ± 13.1% of predicted. Subjects underwent technetium-99m labeled diethylenetriaminepentaacetic acid ({sup 99m}TcDTPA) radio aerosol inhalation lung scintigraphy in two stages: during spontaneous breathing; and while breathing through a PEP mask at one of three PEP levels—10 cmH{sub 2}O (n = 10), 15 cmH{sub 2}O (n = 10), and 20 cmH{sub 2}O (n = 10). The {sup 99m}Tc-DTPA was nebulized for 3 min, and its clearance was recorded by scintigraphy over a 30-min period during spontaneous breathing and over a 30-min period during breathing through a PEP mask. Results: The pulmonary clearance of {sup 99m}Tc-DTPA was significantly shorter when PEP was applied—at 10 cmH{sub 2}O (p = 0.044), 15 cmH{sub 2}O (p = 0.044), and 20 cmH{sub 2}O (p = 0.004) - in comparison with that observed during spontaneous breathing. Conclusions: Our findings indicate that PEP, at the levels tested, is able to induce an increase in pulmonary epithelial membrane permeability and lung volume in healthy subjects. (author)

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

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

Science.gov (United States)

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

2017-11-01

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

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.

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

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

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

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.

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

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.

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

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

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

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

Whey protein isolate improves acid and bile tolerances of Streptococcus thermophilus ST-M5 and Lactobacillus delbrueckii ssp. bulgaricus LB-12.

Science.gov (United States)

Vargas, Luis A; Olson, Douglas W; Aryana, Kayanush J

2015-04-01

Acid tolerance and bile tolerance are important probiotic characteristics. Whey proteins contain branched-chain amino acids, which play a role in muscle building and are popular among athletes. Increasing emphasis is being placed on diets containing less carbohydrate, less fat, and more protein. The effect of incremental additions of whey protein isolate (WPI) on probiotic characteristics of pure cultures is not known. The objective of this study was to determine the influence of added WPI on acid tolerance and bile tolerance of pure cultures of Streptococcus thermophilus ST-M5 and Lactobacillus bulgaricus LB-12. The WPI was used at 0 (control), 1, 2 and 3% (wt/vol). Assessment of acid tolerance was conducted on pure cultures at 30-min intervals for 2h of acid exposure and bile tolerance at 1-h intervals for 5h of bile exposure. Use of 1, 2, and 3% WPI improved acid tolerance of Strep. thermophilus ST-M5 and Lb. bulgaricus LB-12. The highest counts for acid tolerance of Strep. thermophilus ST-M5 and Lb. bulgaricus LB-12 were obtained when 3% WPI was used. Use of 2 and 3% WPI improved bile tolerance of Strep. thermophilus ST-M5 and Lb. bulgaricus LB-12 over 5h of bile exposure. The use of WPI is recommended to improve acid and bile tolerance of the yogurt culture bacteria Strep. thermophilus ST-M5 and Lb. bulgaricus LB-12. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Test results of distributed ion pump designs for the PEP-II Asymmetric B-Factory collider

Energy Technology Data Exchange (ETDEWEB)

Calderon, M.; Holdener, F.; Peterson, D. [Lawrence Livermore National Lab., CA (United States)] [and others

1994-07-01

The testing facility measurement methods and results of prototype distributed ion pump (DIP) designs for the PEP-II B-Factory High Energy Ring are presented. Two basic designs with 5- or 7-anode plates were tested at LLNL with penning cell sizes of 15, 18, and 21 mm. Direct comparison of 5- and 7-plate anodes with 18 mm holes shows increased pumping speed with the 7-plate design. The 5-plate, 18 mm and 7-plate, 15 mm designs both gave an average pumping speed of 135 1/s/m at 1 {times} 10{sup {minus}8} Torr nitrogen base pressure in a varying 0.18 T peak B-field. Comparison of the three hole sizes indicates that cells smaller than the 15 mm tested can be efficiently used to obtain higher pumping speeds for the same anode plate sizes used.

Test results of distributed ion pump designs for the PEP-II Asymmetric B-Factory collider

International Nuclear Information System (INIS)

Calderon, M.; Holdener, F.; Peterson, D.

1994-07-01

The testing facility measurement methods and results of prototype distributed ion pump (DIP) designs for the PEP-II B-Factory High Energy Ring are presented. Two basic designs with 5- or 7-anode plates were tested at LLNL with penning cell sizes of 15, 18, and 21 mm. Direct comparison of 5- and 7-plate anodes with 18 mm holes shows increased pumping speed with the 7-plate design. The 5-plate, 18 mm and 7-plate, 15 mm designs both gave an average pumping speed of 135 1/s/m at 1 x 10 -8 Torr nitrogen base pressure in a varying 0.18 T peak B-field. Comparison of the three hole sizes indicates that cells smaller than the 15 mm tested can be efficiently used to obtain higher pumping speeds for the same anode plate sizes used

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.

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

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.

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

Perception of Arabidopsis AtPep peptides, but not bacterial elicitors, accelerates starvation-induced senescence

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Kay eGully

2015-01-01

Full Text Available Members of the AtPep group of Arabidopsis endogenous peptides have frequently been reported to induce pattern-triggered immunity and to increase resistance to diverse pathogens by amplifying the innate immune response. Here, we made the surprising observation that dark-induced leaf senescence was accelerated by the presence of Peps. Adult leaves as well as leaf discs of Col-0 wild type plants showed a Pep-triggered early onset of chlorophyll breakdown and leaf yellowing whereas pepr1 pepr2 double mutant plants were insensitive. In addition, this response was dependent on ethylene signaling and inhibited by the addition of cytokinins. Notably, addition of the bacterial elicitors flg22 or elf18, both potent inducers of pattern-triggered immunity, did not provoke an early onset of leaf senescence.Continuous darkness leads to energy deprivation and starvation and therewith promotes leaf senescence. We found that continuous darkness also strongly induced PROPEP3 transcription. Moreover, Pep-perception led to a rapid induction of PAO, APG7 and APG8a, genes indispensable for chlorophyll degradation as well as autophagy, respectively, and all three hallmarks of starvation and senescence. Notably, addition of sucrose as a source of energy inhibited the Pep-triggered early onset of senescence. In conclusion, we report that Pep-perception accelerates dark/starvation-induced senescence via an early induction of chlorophyll degradation and autophagy. This represents a novel and unique characteristic of PEPR signaling, unrelated to pattern-triggered immunity.

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

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

Science.gov (United States)

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

2017-03-01

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

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

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

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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/

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

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

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

An RNA-binding protein, Qki5, regulates embryonic neural stem cells through pre-mRNA processing in cell adhesion signaling.

Science.gov (United States)

Hayakawa-Yano, Yoshika; Suyama, Satoshi; Nogami, Masahiro; Yugami, Masato; Koya, Ikuko; Furukawa, Takako; Zhou, Li; Abe, Manabu; Sakimura, Kenji; Takebayashi, Hirohide; Nakanishi, Atsushi; Okano, Hideyuki; Yano, Masato

2017-09-15

Cell type-specific transcriptomes are enabled by the action of multiple regulators, which are frequently expressed within restricted tissue regions. In the present study, we identify one such regulator, Quaking 5 (Qki5), as an RNA-binding protein (RNABP) that is expressed in early embryonic neural stem cells and subsequently down-regulated during neurogenesis. mRNA sequencing analysis in neural stem cell culture indicates that Qki proteins play supporting roles in the neural stem cell transcriptome and various forms of mRNA processing that may result from regionally restricted expression and subcellular localization. Also, our in utero electroporation gain-of-function study suggests that the nuclear-type Qki isoform Qki5 supports the neural stem cell state. We next performed in vivo transcriptome-wide protein-RNA interaction mapping to search for direct targets of Qki5 and elucidate how Qki5 regulates neural stem cell function. Combined with our transcriptome analysis, this mapping analysis yielded a bona fide map of Qki5-RNA interaction at single-nucleotide resolution, the identification of 892 Qki5 direct target genes, and an accurate Qki5-dependent alternative splicing rule in the developing brain. Last, our target gene list provides the first compelling evidence that Qki5 is associated with specific biological events; namely, cell-cell adhesion. This prediction was confirmed by histological analysis of mice in which Qki proteins were genetically ablated, which revealed disruption of the apical surface of the lateral wall in the developing brain. These data collectively indicate that Qki5 regulates communication between neural stem cells by mediating numerous RNA processing events and suggest new links between splicing regulation and neural stem cell states. © 2017 Hayakawa-Yano et al.; Published by Cold Spring Harbor Laboratory Press.

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.

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.)

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

Science.gov (United States)

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

2016-04-01

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

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.

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

Determination of a natural DNMT1 inhibitor, peperomin E, in rat plasma by UFLC-MS/MS and method application in a pharmacokinetic study.

Science.gov (United States)

Wang, Xin-Zhi; Wen, Hong-Mei; Chai, Chuan; Zhang, Wen-Ying; Gao, Ming; Liu, Rui; Wu, Hao; Liang, Jing-Yu

2017-08-01

Peperomin E (PepE), a naturally occurring secolignan isolated from Peperomia dindygulensis, has drawn much attention recently owing to its anticancer and DNA methyltransferase 1 (DNMT1) inhibitory activity. Here, a simple and sensitive ultra-fast liquid chromatography-tandem mass spectrometry method was developed and validated for the determination of PepE in rat plasma for the first time. Samples were prepared by simple protein precipitation. Separation was performed on an XBridge™ C 18 column using a mobile phase of acetonitrile and 0.1% (v/v) aqueous formic acid. PepE and the internal standard arctigenin were detected in a positive-ion mode using multiple reaction monitoring of the transitions at m/z 413.2 → 261.0 and 373.2 → 137.2, respectively. The calibration curve for PepE was linear over the range of concentrations of 1.46-6000 ng/mL, with a lower limit of quantitation of 1.46 ng/mL. Both intra- and interday precisions were within 11.05%, and the accuracy ranged from -11.5 to 5.51%. The extraction recovery and matrix effect were within acceptable limits. Stability tests showed that PepE remained stable throughout the analytical procedure. The validated method was then used to analyze the pharmacokinetics of PepE administered to rats orally (12.5 and 25 mg/kg) or intravenously (6.25 and 12.5 mg/kg). Copyright © 2017 John Wiley & Sons, Ltd.

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

The 0.3-kb fragment containing the R-U5-5'leader sequence of Friend murine leukemia virus influences the level of protein expression from spliced mRNA.

Science.gov (United States)

Choo, Yeng Cheng; Seki, Yohei; Machinaga, Akihito; Ogita, Nobuo; Takase-Yoden, Sayaka

2013-04-19

A neuropathogenic variant of Friend murine leukemia virus (Fr-MLV) clone A8 induces spongiform neurodegeneration when infected into neonatal rats. Studies with chimeras constructed from the A8 virus and the non-neuropathogenic Fr-MLV clone 57 identified a 0.3-kb KpnI-AatII fragment containing a R-U5-5'leader sequence as an important determinant for inducing spongiosis, in addition to the env gene of A8 as the primary determinant. This 0.3-kb fragment contains a 17-nucleotide difference between the A8 and 57 sequences. We previously showed that the 0.3-kb fragment influences expression levels of Env protein in both cultured cells and rat brain, but the corresponding molecular mechanisms are not well understood. Studies with expression vectors constructed from the full-length proviral genome of Fr-MLV that incorporated the luciferase (luc) gene instead of the env gene found that the vector containing the A8-0.3-kb fragment yielded a larger amount of spliced luc-mRNA and showed higher expression of luciferase when compared to the vector containing the 57-0.3-kb fragment. The amount of total transcripts from the vectors, the poly (A) tail length of their mRNAs, and the nuclear-cytoplasm distribution of luc-mRNA in transfected cells were also evaluated. The 0.3-kb fragment did not influence transcription efficiency, mRNA polyadenylation or nuclear export of luc-mRNA. Mutational analyses were carried out to determine the importance of nucleotides that differ between the A8 and 57 sequences within the 0.3-kb fragment. In particular, seven nucleotides upstream of the 5'splice site (5'ss) were found to be important in regulating the level of protein expression from spliced messages. Interestingly, these nucleotides reside within the stem-loop structure that has been speculated to limit the recognition of 5'ss. The 0.3-kb fragment containing the R-U5-5'leader sequence of Fr-MLV influences the level of protein expression from the spliced-mRNA by regulating the splicing

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

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

Cloning, Expression, Sequence Analysis and Homology Modeling of the Prolyl Endoprotease from Eurygaster integriceps Puton

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Ravi Chandra Yandamuri

2014-10-01

Full Text Available eurygaster integriceps Puton, commonly known as sunn pest, is a major pest of wheat in Northern Africa, the Middle East and Eastern Europe. This insect injects a prolyl endoprotease into the wheat, destroying the gluten. The purpose of this study was to clone the full length cDNA of the sunn pest prolyl endoprotease (spPEP for expression in E. coli and to compare the amino acid sequence of the enzyme to other known PEPs in both phylogeny and potential tertiary structure. Sequence analysis shows that the 5ꞌ UTR contains several putative transcription factor binding sites for transcription factors known to be expressed in Drosophila that might be useful targets for inhibition of the enzyme. The spPEP was first identified as a prolyl endoprotease by Darkoh et al., 2010. The enzyme is a unique serine protease of the S9A family by way of its substrate recognition of the gluten proteins, which are greater than 30 kD in size. At 51% maximum identity to known PEPs, homology modeling using SWISS-MODEL, the porcine brain PEP (PDB: 2XWD was selected in the database of known PEP structures, resulting in a predicted tertiary structure 99% identical to the porcine brain PEP structure. A Km for the recombinant spPEP was determined to be 210 ± 53 µM for the zGly-Pro-pNA substrate in 0.025 M ethanolamine, pH 8.5, containing 0.1 M NaCl at 37 °C with a turnover rate of 172 ± 47 µM Gly-Pro-pNA/s/µM of enzyme.

Combining protein-shelled platinum nanoparticles with graphene to build a bionanohybrid capacitor.

Science.gov (United States)

San, Boi Hoa; Kim, Jang Ah; Kulkarni, Atul; Moh, Sang Hyun; Dugasani, Sreekantha Reddy; Subramani, Vinod Kumar; Thorat, Nanasaheb D; Lee, Hyun Ho; Park, Sung Ha; Kim, Taesung; Kim, Kyeong Kyu

2014-12-23

The electronic properties of biomolecules and their hybrids with inorganic materials can be utilized for the fabrication of nanoelectronic devices. Here, we report the charge transport behavior of protein-shelled inorganic nanoparticles combined with graphene and demonstrate their possible application as a bionanohybrid capacitor. The conductivity of PepA, a bacterial aminopeptidase used as a protein shell (PS), and the platinum nanoparticles (PtNPs) encapsulated by PepA was measured using a field effect transistor (FET) and a graphene-based FET (GFET). Furthermore, we confirmed that the electronic properties of PepA-PtNPs were controlled by varying the size of the PtNPs. The use of two poly(methyl methacrylate) (PMMA)-coated graphene layers separated by PepA-PtNPs enabled us to build a bionanohybrid capacitor with tunable properties. The combination of bioinorganic nanohybrids with graphene is regarded as the cornerstone for developing flexible and biocompatible bionanoelectronic devices that can be integrated into bioelectric circuits for biomedical purposes.

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

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.

Control of beam size and polarization time in PEP

International Nuclear Information System (INIS)

Paterson, J.M.; Rees, J.R.; Wiedemann, H.

1975-07-01

In this report we describe a method of controlling beam size in which the focusing functions are not altered with beam energy but the curvature function is drastically altered in a few locations which comprise only a very small fraction of the circumference. As will be described in the following paper we are proposing to control the quantum excitation and radiation damping of the particles by means of special excitation magnets or /open quotes/wigglers/close quotes/. Since the mean square energy deviation and radial beam emittance are proportional approximately to E/sup 2//l angle/G/sup 3//r angle//l angle/G/sup 2//r angle//sup /minus/1 while the damping times are proportional to (E/sup 3//l angle/G/sup 2//r angle/)/sup /minus/1/, it is possible to achieve constant beam size in a constant focusing configuration while the damping times vary roughly as E/sup /minus/2/. In addition, it is possible to reduce the beam polarization time with these devices. A scheme for beam-size and damping control based on the same principle was described by M. Bassetti about a year ago, in which all of the storage-ring bending magnets were involved as wigglers, and a substantial increase in magnet cost resulted. The consequences for polarization times were not explored. The design formulae are derived and two specific applications to the PEP design in which the wigglers are installed in three of the six 5-m straight sections are described with attention given to practical magnet design, synchrotron radiation handling and other matters. 5 refs., 4 figs., 1 tab

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

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

Protein (Cyanobacteria): 553729681 [PGDBj - Ortholog DB

Lifescience Database Archive (English)

Full Text Available WP_023064372.1 ... 1117:4910 ... 1150:25585 1301283:43816 ... 28073:3666 118322:924 ... PEP-CTERM sorting , cyanoba...cterial subclass domain protein Lyngbya aestuarii MQNATIDGVYFVPEPFTILGTGTALGFGVLFKKESSKKRKKEKAKV

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

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

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.

mGlu5 Receptor Functional Interactions and Addiction

Directory of Open Access Journals (Sweden)

Robyn eBrown

2012-05-01

Full Text Available The idea of ‘receptor mosaics’ suggests that proteins can form complex and dynamic networks, with respect to time and protein make up, which has the potential to make significant contributions to the diversity and specificity of GPCR signalling, particularly in neuropharmacology, where a few key receptors have been implicated in multiple neurological and psychiatric disorders such as addiction. Metabotropic glutamate type 5 receptors (mGlu5 have been shown to heterodimerise and form complexes with other GPCRs including adenosine A2A and dopamine D2 receptors. mGlu5-containing complexes are found in the striatum, a region of the brain known to be critical for mediating the rewarding and incentive motivational properties of drugs of abuse. Indeed, initial studies indicate a role for mGlu5-containing complexes in rewarding and conditioned effects of drugs, as well as drug-seeking behaviour. This is consistent with the substantial influence that mGlu5 complexes appear to have on striatal function, regulating both GABAergic output of striatopallidal neurons and glutamatergic input from corticostriatal afferents. Given their discrete localization, mGlu5-containing complexes represent a novel way in which to minimize the off-target effects and therefore provide us with an exciting therapeutic avenue for drug discovery efforts. Indeed, the therapeutic targeting of receptor mosaics in a tissue specific or temporal manner (for example, a sub-population of receptors in a ‘pathological state’ has the potential to dramatically reduce detrimental side effects that may otherwise impair vital brain function.

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

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

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.

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 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

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

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.

The E5 Proteins

OpenAIRE

DiMaio, Daniel; Petti, Lisa

2013-01-01

The E5 proteins are short transmembrane proteins encoded by many animal and human papillomaviruses. These proteins display transforming activity in cultured cells and animals, and they presumably also play a role in the productive virus life cycle. The E5 proteins are thought to act by modulating the activity of cellular proteins. Here, we describe the biological activities of the best-studied E5 proteins and discuss the evidence implicating specific protein targets and pathways in mediating ...

Dynamic regulation of genome-wide pre-mRNA splicing and stress tolerance by the Sm-like protein LSm5 in Arabidopsis

KAUST Repository

Cui, Peng

2014-01-07

Background: Sm-like proteins are highly conserved proteins that form the core of the U6 ribonucleoprotein and function in several mRNA metabolism processes, including pre-mRNA splicing. Despite their wide occurrence in all eukaryotes, little is known about the roles of Sm-like proteins in the regulation of splicing.Results: Here, through comprehensive transcriptome analyses, we demonstrate that depletion of the Arabidopsis supersensitive to abscisic acid and drought 1 gene (SAD1), which encodes Sm-like protein 5 (LSm5), promotes an inaccurate selection of splice sites that leads to a genome-wide increase in alternative splicing. In contrast, overexpression of SAD1 strengthens the precision of splice-site recognition and globally inhibits alternative splicing. Further, SAD1 modulates the splicing of stress-responsive genes, particularly under salt-stress conditions. Finally, we find that overexpression of SAD1 in Arabidopsis improves salt tolerance in transgenic plants, which correlates with an increase in splicing accuracy and efficiency for stress-responsive genes.Conclusions: We conclude that SAD1 dynamically controls splicing efficiency and splice-site recognition in Arabidopsis, and propose that this may contribute to SAD1-mediated stress tolerance through the metabolism of transcripts expressed from stress-responsive genes. Our study not only provides novel insights into the function of Sm-like proteins in splicing, but also uncovers new means to improve splicing efficiency and to enhance stress tolerance in a higher eukaryote. 2014 Cui et al.; licensee BioMed Central Ltd.

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

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 .

Antimicrobial properties of two novel peptides derived from Theobroma cacao osmotin.

Science.gov (United States)

Falcao, Loeni L; Silva-Werneck, Joseilde O; Ramos, Alessandra de R; Martins, Natalia F; Bresso, Emmanuel; Rodrigues, Magali A; Bemquerer, Marcelo P; Marcellino, Lucilia H

2016-05-01

The osmotin proteins of several plants display antifungal activity, which can play an important role in plant defense against diseases. Thus, this protein can be useful as a source for biotechnological strategies aiming to combat fungal diseases. In this work, we analyzed the antifungal activity of a cacao osmotin-like protein (TcOsm1) and of two osmotin-derived synthetic peptides with antimicrobial features, differing by five amino acids residues at the N-terminus. Antimicrobial tests showed that TcOsm1 expressed in Escherichia coli inhibits the growth of Moniliophthora perniciosa mycelium and Pichia pastoris X-33 in vitro. The TcOsm1-derived peptides, named Osm-pepA (H-RRLDRGGVWNLNVNPGTTGARVWARTK-NH2), located at R23-K49, and Osm-pepB (H-GGVWNLNVNPGTTGARVWARTK-NH2), located at G28-K49, inhibited growth of yeasts (Saccharomyces cerevisiae S288C and Pichia pastoris X-33) and spore germination of the phytopathogenic fungi Fusarium f. sp. glycines and Colletotrichum gossypi. Osm-pepA was more efficient than Osm-pepB for S. cerevisiae (MIC=40μM and MIC=127μM, respectively), as well as for P. pastoris (MIC=20μM and MIC=127μM, respectively). Furthermore, the peptides presented a biphasic performance, promoting S. cerevisiae growth in doses around 5μM and inhibiting it at higher doses. The structural model for these peptides showed that the five amino acids residues, RRLDR at Osm-pepA N-terminus, significantly affect the tertiary structure, indicating that this structure is important for the peptide antimicrobial potency. This is the first report of development of antimicrobial peptides from T. cacao. Taken together, the results indicate that the cacao osmotin and its derived peptides, herein studied, are good candidates for developing biotechnological tools aiming to control phytopathogenic fungi. Copyright © 2016 Elsevier Inc. All rights reserved.

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

Expression, purification and crystallization of a lyssavirus matrix (M) protein

Energy Technology Data Exchange (ETDEWEB)

Assenberg, René [Division of Structural Biology and Oxford Protein Production Facility, The Henry Wellcome Building for Genomic Medicine, Oxford University, Roosevelt Drive, Oxford OX3 7BN (United Kingdom); Delmas, Olivier [UPRE Lyssavirus Dynamics and Host Adaptation, WHO Collaborating Centre for Reference and Research on Rabies, Institut Pasteur, 28 Rue du Docteur Roux, 75724 Paris CEDEX 15 (France); Graham, Stephen C.; Verma, Anil; Berrow, Nick; Stuart, David I.; Owens, Raymond J. [Division of Structural Biology and Oxford Protein Production Facility, The Henry Wellcome Building for Genomic Medicine, Oxford University, Roosevelt Drive, Oxford OX3 7BN (United Kingdom); Bourhy, Hervé [UPRE Lyssavirus Dynamics and Host Adaptation, WHO Collaborating Centre for Reference and Research on Rabies, Institut Pasteur, 28 Rue du Docteur Roux, 75724 Paris CEDEX 15 (France); Grimes, Jonathan M., E-mail: jonathan@strubi.ox.ac.uk [Division of Structural Biology and Oxford Protein Production Facility, The Henry Wellcome Building for Genomic Medicine, Oxford University, Roosevelt Drive, Oxford OX3 7BN (United Kingdom)

2008-04-01

The expression, purification and crystallization of the full-length matrix protein from three lyssaviruses is described. The matrix (M) proteins of lyssaviruses (family Rhabdoviridae) are crucial to viral morphogenesis as well as in modulating replication and transcription of the viral genome. To date, no high-resolution structural information has been obtained for full-length rhabdovirus M. Here, the cloning, expression and purification of the matrix proteins from three lyssaviruses, Lagos bat virus (LAG), Mokola virus and Thailand dog virus, are described. Crystals have been obtained for the full-length M protein from Lagos bat virus (LAG M). Successful crystallization depended on a number of factors, in particular the addition of an N-terminal SUMO fusion tag to increase protein solubility. Diffraction data have been recorded from crystals of native and selenomethionine-labelled LAG M to 2.75 and 3.0 Å resolution, respectively. Preliminary analysis indicates that these crystals belong to space group P6{sub 1}22 or P6{sub 5}22, with unit-cell parameters a = b = 56.9–57.2, c = 187.9–188.6 Å, consistent with the presence of one molecule per asymmetric unit, and structure determination is currently in progress.

Expression, purification and crystallization of a lyssavirus matrix (M) protein

International Nuclear Information System (INIS)

Assenberg, René; Delmas, Olivier; Graham, Stephen C.; Verma, Anil; Berrow, Nick; Stuart, David I.; Owens, Raymond J.; Bourhy, Hervé; Grimes, Jonathan M.

2008-01-01

The expression, purification and crystallization of the full-length matrix protein from three lyssaviruses is described. The matrix (M) proteins of lyssaviruses (family Rhabdoviridae) are crucial to viral morphogenesis as well as in modulating replication and transcription of the viral genome. To date, no high-resolution structural information has been obtained for full-length rhabdovirus M. Here, the cloning, expression and purification of the matrix proteins from three lyssaviruses, Lagos bat virus (LAG), Mokola virus and Thailand dog virus, are described. Crystals have been obtained for the full-length M protein from Lagos bat virus (LAG M). Successful crystallization depended on a number of factors, in particular the addition of an N-terminal SUMO fusion tag to increase protein solubility. Diffraction data have been recorded from crystals of native and selenomethionine-labelled LAG M to 2.75 and 3.0 Å resolution, respectively. Preliminary analysis indicates that these crystals belong to space group P6 1 22 or P6 5 22, with unit-cell parameters a = b = 56.9–57.2, c = 187.9–188.6 Å, consistent with the presence of one molecule per asymmetric unit, and structure determination is currently in progress

CCL5 promotes proliferation of MCF-7 cells through mTOR-dependent mRNA translation

International Nuclear Information System (INIS)

Murooka, Thomas T.; Rahbar, Ramtin; Fish, Eleanor N.

2009-01-01

The proliferative capacity of cancer cells is regulated by factors intrinsic to cancer cells and by secreted factors in the microenvironment. Here, we investigated the proto-oncogenic potential of the chemokine receptor, CCR5, in MCF-7 breast cancer cell lines. At physiological levels, CCL5, a ligand for CCR5, enhanced MCF-7.CCR5 proliferation. Treatment with the mTOR inhibitor, rapamycin, inhibited this CCL5-inducible proliferation. Because mTOR directly modulates mRNA translation, we investigated whether CCL5 activation of CCR5 leads to increased translation. CCL5 induced the formation of the eIF4F translation initiation complex through an mTOR-dependent process. Indeed, CCL5 initiated mRNA translation, shown by an increase in high-molecular-weight polysomes. Specifically, we show that CCL5 mediated a rapid up-regulation of protein expression for cyclin D1, c-Myc and Dad-1, without affecting their mRNA levels. Taken together, we describe a mechanism by which CCL5 influences translation of rapamycin-sensitive mRNAs, thereby providing CCR5-positive breast cancer cells with a proliferative advantage.

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.)

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

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.

Impact of food processing and simulated gastrointestinal digestion on gliadin immunoreactivity in rolls.

Science.gov (United States)

Brzozowski, Bartosz

2018-07-01

The enzymatic modification of wheat proteins during dough fermentation and its digestion as supported by peptidases of microbiological origin can result in the degradation of important peptides in the pathogenesis of coeliac disease. However, baking bread and the high temperature associated with this could change the physicochemical and immunological properties of proteins. Thermal changes in the spatial structure of proteins and their hydrolysis can lead to a masking or degrading of immunoreactive peptides. The addition of prolyl endopeptidase (PEP), comprising peptidases isolated from Lactobacillus acidophilus 5e2 (LA) or transglutaminase (TG) in the course of fermentation, decreases its immunoreactivity by 83.9%, 51.9% and 18.5%, respectively. An analysis of the fractional composition of gliadins revealed that γ- and ω-gliadins are the proteins most susceptible to enzymatic modification. Hydrolysis of wheat storage proteins with PEP and LA reduces the content of αβ-, γ- and ω-gliadins by 13.7%, 60.2% and 41.9% for PEP and by 22.1%, 43.5% and 36.9% for LA, respectively. Cross-linking of proteins with TG or their hydrolysis by PEP and LA peptidases during the process of forming wheat dough, followed by digesting bread samples with PEP and LA peptidases, decreases the immunoreactivity of bread hydrolysates from 2.4% to 0.02%. The content of peptide detected in polypeptide sequences is 263.4 ± 3.3, 30.9 ± 1.5 and 7.9 ± 0.4 mg kg -1 in samples of hydrolysates of bread digested with PEP, as produced from dough modified by TG, PEP and LA, respectively. Enzymatic pre-modification of proteins during the process of dough fermentation decreases their immunoreactive potential, such that fewer peptides recognised by R5 antibodies are released during the digestion process from the bread matrix. Immunoreactive peptides are degraded more effectively when digestive enzymes are supported by the addition of PEP. © 2017 Society of Chemical Industry. © 2017

The Rabies Virus L Protein Catalyzes mRNA Capping with GDP Polyribonucleotidyltransferase Activity.

Science.gov (United States)

Ogino, Minako; Ito, Naoto; Sugiyama, Makoto; Ogino, Tomoaki

2016-05-21

The large (L) protein of rabies virus (RABV) plays multiple enzymatic roles in viral RNA synthesis and processing. However, none of its putative enzymatic activities have been directly demonstrated in vitro. In this study, we expressed and purified a recombinant form of the RABV L protein and verified its guanosine 5'-triphosphatase and GDP polyribonucleotidyltransferase (PRNTase) activities, which are essential for viral mRNA cap formation by the unconventional mechanism. The RABV L protein capped 5'-triphosphorylated but not 5'-diphosphorylated RABV mRNA-start sequences, 5'-AACA(C/U), with GDP to generate the 5'-terminal cap structure G(5')ppp(5')A. The 5'-AAC sequence in the substrate RNAs was found to be strictly essential for RNA capping with the RABV L protein. Furthermore, site-directed mutagenesis showed that some conserved amino acid residues (G1112, T1170, W1201, H1241, R1242, F1285, and Q1286) in the PRNTase motifs A to E of the RABV L protein are required for cap formation. These findings suggest that the putative PRNTase domain in the RABV L protein catalyzes the rhabdovirus-specific capping reaction involving covalent catalysis of the pRNA transfer to GDP, thus offering this domain as a target for developing anti-viral agents.

Human HOXA5 homeodomain enhances protein transduction and its application to vascular inflammation

International Nuclear Information System (INIS)

Lee, Ji Young; Park, Kyoung sook; Cho, Eun Jung; Joo, Hee Kyoung; Lee, Sang Ki; Lee, Sang Do; Park, Jin Bong; Chang, Seok Jong; Jeon, Byeong Hwa

2011-01-01

Highlights: → We have developed an E. coli protein expression vector including human specific gene sequences for protein cellular delivery. → The plasmid was generated by ligation the nucleotides 770-817 of the homeobox A5 mRNA sequence. → HOXA5-APE1/Ref-1 inhibited TNF-alpha-induced monocyte adhesion to endothelial cells. → Human HOXA5-PTD vector provides a powerful research tools for uncovering cellular functions of proteins or for the generation of human PTD-containing proteins. -- Abstract: Cellular protein delivery is an emerging technique by which exogenous recombinant proteins are delivered into mammalian cells across the membrane. We have developed an Escherichia coli expression vector including human specific gene sequences for protein cellular delivery. The plasmid was generated by ligation the nucleotides 770-817 of the homeobox A5 mRNA sequence which was matched with protein transduction domain (PTD) of homeodomain protein A5 (HOXA5) into pET expression vector. The cellular uptake of HOXA5-PTD-EGFP was detected in 1 min and its transduction reached a maximum at 1 h within cell lysates. The cellular uptake of HOXA5-EGFP at 37 o C was greater than in 4 o C. For study for the functional role of human HOXA5-PTD, we purified HOXA5-APE1/Ref-1 and applied it on monocyte adhesion. Pretreatment with HOXA5-APE1/Ref-1 (100 nM) inhibited TNF-α-induced monocyte adhesion to endothelial cells, compared with HOXA5-EGFP. Taken together, our data suggested that human HOXA5-PTD vector provides a powerful research tools for uncovering cellular functions of proteins or for the generation of human PTD-containing proteins.

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 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

Immunodominant IgM and IgG Epitopes Recognized by Antibodies Induced in Enterovirus A71-Associated Hand, Foot and Mouth Disease Patients.

Directory of Open Access Journals (Sweden)

Kam Leng Aw-Yong

Full Text Available Enterovirus A71 (EV-A71 is one of the main causative agents of hand, foot and mouth disease (HFMD. Unlike other enteroviruses that cause HFMD, EV-A71 is more frequently associated with severe neurological complications and fatality. To date, no effective licensed antivirals are available to combat EV-A71 infection. Little is known about the immunogenicity of viral non-structural proteins in humans. Previous studies have mainly focused on characterization of epitopes of EV-A71 structural proteins by using immunized animal antisera. In this study, we have characterized human antibody responses against the structural and non-structural proteins of EV-A71. Each viral protein was cloned and expressed in either bacterial or mammalian systems, and tested with antisera by western blot. Results revealed that all structural proteins (VP1-4, and non-structural proteins 2A, 3C and 3D were targets of EV-A71 IgM, whereas EV-A71 IgG recognized all the structural and non-structural proteins. Sixty three synthetic peptides predicted to be immunogenic in silico were synthesized and used for the characterization of EV-A71 linear B-cell epitopes. In total, we identified 22 IgM and four IgG dominant epitopes. Synthetic peptide PEP27, corresponding to residues 142-156 of VP1, was identified as the EV-A71 IgM-specific immunodominant epitope. PEP23, mapped to VP1 41-55, was recognized as the EV-A71 IgG cross-reactive immunodominant epitope. The structural protein VP1 is the major immunodominant site targeted by anti-EV-A71 IgM and IgG antibodies, but epitopes against non-structural proteins were also detected. These data provide new understanding of the immune response to EV-A71 infection, which benefits the development of diagnostic tools, potential therapeutics and subunit vaccine candidates.

[A case of IgA2-lambda type M-protein that IgA concentration differs from the values of M-protein by serum protein electrophoresis].

Science.gov (United States)

Fukushima, M; Sugano, M; Ichikawa, T; Honda, T; Totsuka, M; Katsuyama, T; Fujita, K

2001-07-01

We report an IgA-lambda type M-protein in which the IgA concentration differed from the values of M-protein by serum protein electrophoresis found in a 53-year-old man with multiple myeloma. The M-protein value as determined by serum protein electrophoresis was 6,170 mg/dl. However, the serum IgA concentration was 3,052 mg/dl by turbidimetric immunoassay. Immuno-fixation electrophoresis using IgA subclass antisera revealed that this M-protein was the IgA2-lambda type. Western blotting analysis showed that the IgA2 molecules were composed of two approximately 68 kDa alpha 2 chains and two 28 kDa lambda chains. In addition the free lambda chain band was detected at the position of 28 kDa without 2-mercaptoethanol(2-ME) even though the patient IgA was purified. Since it is known that IgA2m(1) allotype easily release light chains from the IgA molecules in SDS-PAGE without 2-ME, we speculated that in this patient the IgA was the IgA2m(1) allotype. After peripheral blood stem cell transplantation(PBSCT), immunofixation electrophoresis of the patient serum revealed not only the bands of IgA2-lambda type M-protein, but also three bands of IgG1-kappa type M-protein in the gamma region.

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

Effects of a school-based sexuality education program on peer educators: the Teen PEP model

OpenAIRE

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

2014-01-01

This study evaluated the impact of the Teen Prevention Education Program (Teen PEP), a peer-led sexuality education program designed to prevent unintended pregnancy and sexually transmitted infections (STIs) including HIV among high school students. The study design was a quasi-experimental, nonrandomized design conducted from May 2007 to May 2008. The sample consisted of 96 intervention (i.e. Teen PEP peer educators) and 61 comparison students from five high schools in New Jersey. Baseline a...

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)

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

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...

The Rabies Virus L Protein Catalyzes mRNA Capping with GDP Polyribonucleotidyltransferase Activity

Directory of Open Access Journals (Sweden)

Minako Ogino

2016-05-01

Full Text Available The large (L protein of rabies virus (RABV plays multiple enzymatic roles in viral RNA synthesis and processing. However, none of its putative enzymatic activities have been directly demonstrated in vitro. In this study, we expressed and purified a recombinant form of the RABV L protein and verified its guanosine 5′-triphosphatase and GDP polyribonucleotidyltransferase (PRNTase activities, which are essential for viral mRNA cap formation by the unconventional mechanism. The RABV L protein capped 5′-triphosphorylated but not 5′-diphosphorylated RABV mRNA-start sequences, 5′-AACA(C/U, with GDP to generate the 5′-terminal cap structure G(5′ppp(5′A. The 5′-AAC sequence in the substrate RNAs was found to be strictly essential for RNA capping with the RABV L protein. Furthermore, site-directed mutagenesis showed that some conserved amino acid residues (G1112, T1170, W1201, H1241, R1242, F1285, and Q1286 in the PRNTase motifs A to E of the RABV L protein are required for cap formation. These findings suggest that the putative PRNTase domain in the RABV L protein catalyzes the rhabdovirus-specific capping reaction involving covalent catalysis of the pRNA transfer to GDP, thus offering this domain as a target for developing anti-viral agents.

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

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

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.

Tuning protein expression using synonymous codon libraries targeted to the 5' mRNA coding region

DEFF Research Database (Denmark)

Goltermann, Lise; Borch Jensen, Martin; Bentin, Thomas

2011-01-01

intermediate expression levels of green fluorescent protein in Escherichia coli. At least in one case, no apparent effect on protein stability was observed, pointing to RNA level effects as the principal reason for the observed expression differences. Targeting a synonymous codon library to the 5' coding...

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

Identification of a novel calcium binding motif based on the detection of sequence insertions in the animal peroxidase domain of bacterial proteins.

Science.gov (United States)

Santamaría-Hernando, Saray; Krell, Tino; Ramos-González, María-Isabel

2012-01-01

Proteins of the animal heme peroxidase (ANP) superfamily differ greatly in size since they have either one or two catalytic domains that match profile PS50292. The orf PP_2561 of Pseudomonas putida KT2440 that we have called PepA encodes a two-domain ANP. The alignment of these domains with those of PepA homologues revealed a variable number of insertions with the consensus G-x-D-G-x-x-[GN]-[TN]-x-D-D. This motif has also been detected in the structure of pseudopilin (pdb 3G20), where it was found to be involved in Ca(2+) coordination although a sequence analysis did not reveal the presence of any known calcium binding motifs in this protein. Isothermal titration calorimetry revealed that a peptide containing this consensus motif bound specifically calcium ions with affinities ranging between 33-79 µM depending on the pH. Microcalorimetric titrations of the purified N-terminal ANP-like domain of PepA revealed Ca(2+) binding with a K(D) of 12 µM and stoichiometry of 1.25 calcium ions per protein monomer. This domain exhibited peroxidase activity after its reconstitution with heme. These data led to the definition of a novel calcium binding motif that we have termed PERCAL and which was abundantly present in animal peroxidase-like domains of bacterial proteins. Bacterial heme peroxidases thus possess two different types of calcium binding motifs, namely PERCAL and the related hemolysin type calcium binding motif, with the latter being located outside the catalytic domains and in their C-terminal end. A phylogenetic tree of ANP-like catalytic domains of bacterial proteins with PERCAL motifs, including single domain peroxidases, was divided into two major clusters, representing domains with and without PERCAL motif containing insertions. We have verified that the recently reported classification of bacterial heme peroxidases in two families (cd09819 and cd09821) is unrelated to these insertions. Sequences matching PERCAL were detected in all kingdoms of life.

Identification of a novel calcium binding motif based on the detection of sequence insertions in the animal peroxidase domain of bacterial proteins.

Directory of Open Access Journals (Sweden)

Saray Santamaría-Hernando

Full Text Available Proteins of the animal heme peroxidase (ANP superfamily differ greatly in size since they have either one or two catalytic domains that match profile PS50292. The orf PP_2561 of Pseudomonas putida KT2440 that we have called PepA encodes a two-domain ANP. The alignment of these domains with those of PepA homologues revealed a variable number of insertions with the consensus G-x-D-G-x-x-[GN]-[TN]-x-D-D. This motif has also been detected in the structure of pseudopilin (pdb 3G20, where it was found to be involved in Ca(2+ coordination although a sequence analysis did not reveal the presence of any known calcium binding motifs in this protein. Isothermal titration calorimetry revealed that a peptide containing this consensus motif bound specifically calcium ions with affinities ranging between 33-79 µM depending on the pH. Microcalorimetric titrations of the purified N-terminal ANP-like domain of PepA revealed Ca(2+ binding with a K(D of 12 µM and stoichiometry of 1.25 calcium ions per protein monomer. This domain exhibited peroxidase activity after its reconstitution with heme. These data led to the definition of a novel calcium binding motif that we have termed PERCAL and which was abundantly present in animal peroxidase-like domains of bacterial proteins. Bacterial heme peroxidases thus possess two different types of calcium binding motifs, namely PERCAL and the related hemolysin type calcium binding motif, with the latter being located outside the catalytic domains and in their C-terminal end. A phylogenetic tree of ANP-like catalytic domains of bacterial proteins with PERCAL motifs, including single domain peroxidases, was divided into two major clusters, representing domains with and without PERCAL motif containing insertions. We have verified that the recently reported classification of bacterial heme peroxidases in two families (cd09819 and cd09821 is unrelated to these insertions. Sequences matching PERCAL were detected in all kingdoms of

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.

Selective translation of the measles virus nucleocapsid mRNA by La protein

Directory of Open Access Journals (Sweden)

Yoshihisa eInoue

2011-08-01

Full Text Available Measles, caused by measles virus (MeV infection, is the leading cause of death in children because of secondary infections attributable to MeV-induced immune suppression. Recently, we have shown that wild-type MeVs induce the suppression of protein synthesis in host cells (referred to as "shutoff" and that viral mRNAs are preferentially translated under shutoff conditions in infected cells. To determine the mechanism behind the preferential translation of viral mRNA, we focused on the 5 untranslated region (UTR of nucleocapsid (N mRNA. The La/SSB autoantigen (La was found to specifically bind to an N-5UTR probe. Recombinant La enhanced the translation of luciferase mRNA containing the N-5UTR (N-fLuc, and RNA interference of La suppressed N-fLuc translation. Furthermore, recombinant MeV lacking the La-binding motif in the N-5UTR displayed delayed viral protein synthesis and growth kinetics at an early phase of infection. These results suggest that La induced predominant translation of N mRNA via binding to its 5UTR under shutoff conditions. This is the first report on a cellular factor that specifically regulates paramyxovirus mRNA translation.

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.

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

Science.gov (United States)

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

2011-09-01

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

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.

Production of Polyclonal Antibodies to the Recombinant Potato virus M (PVM) Non-structural Triple Gene Block Protein 1 and Coat Protein

Czech Academy of Sciences Publication Activity Database

Čeřovská, Noemi; Moravec, Tomáš; Plchová, Helena; Hoffmeisterová, Hana; Dědič, P.

2012-01-01

Roč. 160, č. 5 (2012), s. 251-254 ISSN 0931-1785 R&D Projects: GA MŠk 1M06030 Institutional research plan: CEZ:AV0Z50380511 Keywords : Potato virus M * recombinant protein * coat protein Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.000, year: 2012

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.

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.

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.

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

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

Crimean-Congo Hemorrhagic Fever Virus Nucleocapsid Protein Augments mRNA Translation.

Science.gov (United States)

Jeeva, Subbiah; Cheng, Erdong; Ganaie, Safder S; Mir, Mohammad A

2017-08-01

Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne Nairovirus of the Bunyaviridae family, causing severe illness with high mortality rates in humans. Here, we demonstrate that CCHFV nucleocapsid protein (CCHFV-NP) augments mRNA translation. CCHFV-NP binds to the viral mRNA 5' untranslated region (UTR) with high affinity. It facilitates the translation of reporter mRNA both in vivo and in vitro with the assistance of the viral mRNA 5' UTR. CCHFV-NP equally favors the translation of both capped and uncapped mRNAs, demonstrating the independence of this translation strategy on the 5' cap. Unlike the canonical host translation machinery, inhibition of eIF4F complex, an amalgam of three initiation factors, eIF4A, eIF4G, and eIF4E, by the chemical inhibitor 4E1RCat did not impact the CCHFV-NP-mediated translation mechanism. However, the proteolytic degradation of eIF4G alone by the human rhinovirus 2A protease abrogated this translation strategy. Our results demonstrate that eIF4F complex formation is not required but eIF4G plays a critical role in this translation mechanism. Our results suggest that CCHFV has adopted a unique translation mechanism to facilitate the translation of viral mRNAs in the host cell cytoplasm where cellular transcripts are competing for the same translation apparatus. IMPORTANCE Crimean-Congo hemorrhagic fever, a highly contagious viral disease endemic to more than 30 countries, has limited treatment options. Our results demonstrate that NP favors the translation of a reporter mRNA harboring the viral mRNA 5' UTR. It is highly likely that CCHFV uses an NP-mediated translation strategy for the rapid synthesis of viral proteins during the course of infection. Shutdown of this translation mechanism might selectively impact viral protein synthesis, suggesting that an NP-mediated translation strategy is a target for therapeutic intervention against this viral disease. Copyright © 2017 American Society for Microbiology.

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...

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

5-Lipoxygenase-Activating Protein as a Modulator of Olanzapine-Induced Lipid Accumulation in Adipocyte

Directory of Open Access Journals (Sweden)

Svetlana Dzitoyeva

2013-01-01

Full Text Available Experiments were performed in 3T3-L1 preadipocytes differentiated in vitro into adipocytes. Cells were treated with olanzapine and a 5-lipoxygenase (5-LOX activating protein (FLAP inhibitor MK-886. Lipid content was measured using an Oil Red O assay; 5-LOX and FLAP mRNA content was measured using quantitative real-time PCR; the corresponding protein contents were measured using quantitative Western blot assay. Olanzapine did not affect the cell content of 5-LOX mRNA and protein; it decreased FLAP mRNA and protein content at day five but not 24 hours after olanzapine addition. In the absence of MK-886, low concentrations of olanzapine increased lipid content only slightly, whereas a 56% increase was induced by 50 μM olanzapine. A 5-day cotreatment with 10 μM MK-886 potentiated the lipid increasing action of low concentrations of olanzapine. In contrast, in the presence of 50 μM olanzapine nanomolar and low micromolar concentrations of MK-886 reduced lipid content. These data suggest that FLAP system in adipocytes is affected by olanzapine and that it may modify how these cells respond to the second-generation antipsychotic drugs (SGADs. Clinical studies could evaluate whether the FLAP/5-LOX system could play a role in setting a variable individual susceptibility to the metabolic side effects of SGADs.

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

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

Translational coregulation of 5′TOP mRNAs by TIA-1 and TIAR

Science.gov (United States)

Damgaard, Christian Kroun; Lykke-Andersen, Jens

2011-01-01

The response of cells to changes in their environment often requires coregulation of gene networks, but little is known about how this can occur at the post-transcriptional level. An important example of post-transcriptional coregulation is the selective translational regulation in response to growth conditions of mammalian mRNAs that encode protein biosynthesis factors and contain hallmark 5′-terminal oligopyrimidine tracts (5′TOP). However, the responsible trans-factors and the mechanism by which they coregulate 5′TOP mRNAs have remained elusive. Here we identify stress granule-associated TIA-1 and TIAR proteins as key factors in human 5′TOP mRNA regulation, which upon amino acid starvation assemble onto the 5′ end of 5′TOP mRNAs and arrest translation at the initiation step, as evidenced by TIA-1/TIAR-dependent 5′TOP mRNA translation repression, polysome release, and accumulation in stress granules. This requires starvation-mediated activation of the GCN2 (general control nonderepressible 2) kinase and inactivation of the mTOR (mammalian target of rapamycin) signaling pathway. Our findings provide a mechanistic explanation to the long-standing question of how the network of 5′TOP mRNAs are coregulated according to amino acid availability, thereby allowing redirection of limited resources to mount a nutrient deprivation response. This presents a fundamental example of how a group of mRNAs can be translationally coregulated in response to changes in the cellular environment. PMID:21979918

ZMS regulation of M2 muscarinic receptor mRNA stability requires protein factor

International Nuclear Information System (INIS)

Zhang Yongfang; Xia Zongqin; Hu Ya'er

2010-01-01

Aim The aim of this work is to study the elevation mechanism of ZMS on muscarinic M2 receptor mRNA expression. Methods Actinomycin D was added to cultured CHOm2 cells to stop the de novo synthesis of M2 receptor mRNA and samples were taken at various times to determine the time course of mRNA of M2 receptor with real-time quantitative RT-PCR. Half-life of M2 receptor mRNA and the effect of ZMS on the half-life was obtained from the slope of the exponential curves. Cycloheximide was added at 4 h prior to and 24 h after the addition of ZMS to examine the effect of de novo protein synthesis on the action of ZMS. Results The half-life of m2 mRNA was prolonged by ZMS treatment without cycloheximide (4.75±0.54 h and 2.13 h±0.23 h for ZMS and vehicle treated groups, respectively, P<0.05). When cycloheximide was added to the culture medium 4h prior to the addition of ZMS, the effect of ZMS in prolonging the half-life of m2 mRNA disappeared (3.06 h±0.23 h and 3.00 h±l.20 h for cells with and without ZMS, respectively). However, when the ZMS was added to the medium 24h prior to the addition of cycloheximide, the action of ZMS was not abolished by cycloheximide (half-life was 5.43 h±1.13 h and 2.46 h±0.09 h for cells with and without ZMS, respectively). Conclusion These data suggest that de novo protein synthesis was required for the increase in M2 mRNA stability induced by ZMS. (authors)

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.

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

Human cytomegalovirus TRS1 protein associates with the 7-methylguanosine mRNA cap and facilitates translation.

Science.gov (United States)

Ziehr, Benjamin; Lenarcic, Erik; Vincent, Heather A; Cecil, Chad; Garcia, Benjamin; Shenk, Thomas; Moorman, Nathaniel J

2015-06-01

Viruses rely on the host translation machinery for the synthesis of viral proteins. Human cells have evolved sensors that recognize viral RNAs and inhibit mRNA translation in order to limit virus replication. Understanding how viruses manipulate the host translation machinery to gain access to ribosomes and disable the antiviral response is therefore a critical aspect of the host/pathogen interface. In this study, we used a proteomics approach to identify human cytomegalovirus (HCMV) proteins that might contribute to viral mRNA translation. The HCMV TRS1 protein (pTRS1) associated with the 7-methylguanosine mRNA cap, increased the total level of protein synthesis, and colocalized with mRNAs undergoing translation initiation during infection. pTRS1 stimulated translation of a nonviral reporter gene and increased the translation of a reporter containing an HCMV 5' untranslated region (5'UTR) to a greater extent. The preferential effect of pTRS1 on translation of an mRNA containing a viral 5'UTR required the pTRS1 RNA and double-stranded RNA-dependent protein kinase (PKR)-binding domains, and was likely the result of PKR inhibition. However, pTRS1 also stimulated the total level of protein synthesis and translation directed by an HCMV 5'UTR in cells lacking PKR. Thus our results demonstrate that pTRS1 stimulates translation through both PKR-dependent and PKR-independent mechanisms. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Structure and expression of MHC class Ib genes of the central M region in rat and mouse: M4, M5, and M6.

Science.gov (United States)

Lambracht-Washington, Doris; Moore, Yuki F; Wonigeit, Kurt; Lindahl, Kirsten Fischer

2008-04-01

The M region at the telomeric end of the murine major histocompatibility complex (MHC) contains class I genes that are highly conserved in rat and mouse. We have sequenced a cosmid clone of the LEW rat strain (RT1 haplotype) containing three class I genes, RT1.M6-1, RT1.M4, and RT1.M5. The sequences of allelic genes of the BN strain (RT1n haplotype) were obtained either from cDNAs or genomic clones. For the coding parts of the genes few differences were found between the two RT1 haplotypes. In LEW, however, only RT1.M5 and RT1.M6 have open reading frames; whereas in BN all three genes were intact. In line with the findings in BN, transcription was found for all three rat genes in several tissues from strain Sprague Dawley. Protein expression in transfectants could be demonstrated for RT1.M6-1 using the monoclonal antibody OX18. By sequencing of transcripts obtained by RT-PCR, a second, transcribed M6 gene, RT1.M6-2, was discovered, which maps next to RT1.M6-1 outside of the region covered by the cosmid. In addition, alternatively spliced forms for RT1.M5 and RT1.M6 were detected. Of the orthologous mouse genes, H2-M4, H2-M5, and H2-M6, only H2-M5 has an open reading frame. Other important differences between the corresponding parts of the M region of the two species are insertion of long LINE repeats, duplication of RT1.M6, and the inversion of RT1.M5 in the rat. This demonstrates substantial evolutionary dynamics in this region despite conservation of the class I gene sequences themselves.

CYP3A5 mRNA degradation by nonsense-mediated mRNA decay.

Science.gov (United States)

Busi, Florent; Cresteil, Thierry

2005-09-01

The total CYP3A5 mRNA level is significantly greater in carriers of the CYP3A5*1 allele than in CYP3A5*3 homozygotes. Most of the CYP3A5*3 mRNA includes an intronic sequence (exon 3B) containing premature termination codons (PTCs) between exons 3 and 4. Two models were used to investigate the degradation of CYP3A5 mRNA: a CYP3A5 minigene consisting of CYP3A5 exons and introns 3 to 6 transfected into MCF7 cells, and the endogenous CYP3A5 gene expressed in HepG2 cells. The 3'-untranslated region g.31611C>T mutation has no effect on CYP3A5 mRNA decay. Splice variants containing exon 3B were more unstable than wild-type (wt) CYP3A5 mRNA. Cycloheximide prevents the recognition of PTCs by ribosomes: in transfected MCF7 and HepG2 cells, cycloheximide slowed down the degradation of exon 3B-containing splice variants, suggesting the participation of nonsense-mediated decay (NMD). When PTCs were removed from pseudoexon 3B or when UPF1 small interfering RNA was used to impair the NMD mechanism, the decay of the splice variant was reduced, confirming the involvement of NMD in the degradation of CYP3A5 splice variants. Induction could represent a source of variability for CYP3A5 expression and could modify the proportion of splice variants. The extent of CYP3A5 induction was investigated after exposure to barbiturates or steroids: CYP3A4 was markedly induced in a pediatric population compared with untreated neonates. However, no effect could be detected in either the total CYP3A5 RNA, the proportion of splice variant RNA, or the protein level. Therefore, in these carriers, induction is unlikely to switch on the phenotypic CYP3A5 expression in carriers of CYP3A5*3/*3.

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

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

Metabotropic Glutamate Receptor I (mGluR1) Antagonism Impairs Cocaine-Induced Conditioned Place Preference via Inhibition of Protein Synthesis

OpenAIRE

Yu, Fei; Zhong, Peng; Liu, Xiaojie; Sun, Dalong; Gao, Hai-qing; Liu, Qing-song

2013-01-01

Antagonism of group I metabotropic glutamate receptors (mGluR1 and mGluR5) reduces behavioral effects of drugs of abuse, including cocaine. However, the underlying mechanisms remain poorly understood. Activation of mGluR5 increases protein synthesis at synapses. Although mGluR5-induced excessive protein synthesis has been implicated in the pathology of fragile X syndrome, it remains unknown whether group I mGluR-mediated protein synthesis is involved in any behavioral effects of drugs of abus...

Sequence variability is correlated with weak immunogenicity in Streptococcus pyogenes M protein.

Science.gov (United States)

Lannergård, Jonas; Kristensen, Bodil M; Gustafsson, Mattias C U; Persson, Jenny J; Norrby-Teglund, Anna; Stålhammar-Carlemalm, Margaretha; Lindahl, Gunnar

2015-10-01

The M protein of Streptococcus pyogenes, a major bacterial virulence factor, has an amino-terminal hypervariable region (HVR) that is a target for type-specific protective antibodies. Intriguingly, the HVR elicits a weak antibody response, indicating that it escapes host immunity by two mechanisms, sequence variability and weak immunogenicity. However, the properties influencing the immunogenicity of regions in an M protein remain poorly understood. Here, we studied the antibody response to different regions of the classical M1 and M5 proteins, in which not only the HVR but also the adjacent fibrinogen-binding B repeat region exhibits extensive sequence divergence. Analysis of antisera from S. pyogenes-infected patients, infected mice, and immunized mice showed that both the HVR and the B repeat region elicited weak antibody responses, while the conserved carboxy-terminal part was immunodominant. Thus, we identified a correlation between sequence variability and weak immunogenicity for M protein regions. A potential explanation for the weak immunogenicity was provided by the demonstration that protease digestion selectively eliminated the HVR-B part from whole M protein-expressing bacteria. These data support a coherent model, in which the entire variable HVR-B part evades antibody attack, not only by sequence variability but also by weak immunogenicity resulting from protease attack. © 2015 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

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

Identification of the Calmodulin-Binding Domains of Fas Death Receptor.

Directory of Open Access Journals (Sweden)

Bliss J Chang

Full Text Available The extrinsic apoptotic pathway is initiated by binding of a Fas ligand to the ectodomain of the surface death receptor Fas protein. Subsequently, the intracellular death domain of Fas (FasDD and that of the Fas-associated protein (FADD interact to form the core of the death-inducing signaling complex (DISC, a crucial step for activation of caspases that induce cell death. Previous studies have shown that calmodulin (CaM is recruited into the DISC in cholangiocarcinoma cells and specifically interacts with FasDD to regulate the apoptotic/survival signaling pathway. Inhibition of CaM activity in DISC stimulates apoptosis significantly. We have recently shown that CaM forms a ternary complex with FasDD (2:1 CaM:FasDD. However, the molecular mechanism by which CaM binds to two distinct FasDD motifs is not fully understood. Here, we employed mass spectrometry, nuclear magnetic resonance (NMR, biophysical, and biochemical methods to identify the binding regions of FasDD and provide a molecular basis for the role of CaM in Fas-mediated apoptosis. Proteolytic digestion and mass spectrometry data revealed that peptides spanning residues 209-239 (Fas-Pep1 and 251-288 (Fas-Pep2 constitute the two CaM-binding regions of FasDD. To determine the molecular mechanism of interaction, we have characterized the binding of recombinant/synthetic Fas-Pep1 and Fas-Pep2 peptides with CaM. Our data show that both peptides engage the N- and C-terminal lobes of CaM simultaneously. Binding of Fas-Pep1 to CaM is entropically driven while that of Fas-Pep2 to CaM is enthalpically driven, indicating that a combination of electrostatic and hydrophobic forces contribute to the stabilization of the FasDD-CaM complex. Our data suggest that because Fas-Pep1 and Fas-Pep2 are involved in extensive intermolecular contacts with the death domain of FADD, binding of CaM to these regions may hinder its ability to bind to FADD, thus greatly inhibiting the initiation of apoptotic signaling

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

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

Science.gov (United States)

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

2018-04-20

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

UBL5 is essential for pre-mRNA splicing and sister chromatid cohesion in human cells

DEFF Research Database (Denmark)

Oka, Yasuyoshi; Varmark, Hanne; Vitting-Seerup, Kristoffer

2014-01-01

UBL5 is an atypical ubiquitin-like protein, whose function in metazoans remains largely unexplored. We show that UBL5 is required for sister chromatid cohesion maintenance in human cells. UBL5 primarily associates with spliceosomal proteins, and UBL5 depletion decreases pre-mRNA splicing efficien...

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

A Design Report of the Baseline for PEP-X: an Ultra-Low Emittance Storage Ring

Energy Technology Data Exchange (ETDEWEB)

Bane, Karl; Bertsche, Kirk; Cai, Yunhai; Chao, Alex; Corbett, Willian; Fox, John; Hettel, Robert; Huang, Xiaobiao; Huang, Zhirong; Ng, Cho-Kuen; Nosochkov, Yuri; Novokhatski, Sasha; Radedeau, Thomas; Raubenheimer, Tor; Rivetta, Claudio; Safranek, James; Seeman, John; Stohr, Joachim; Stupakov, Gennady; Wang, Lanfa; Wang, Min-Huey; /SLAC

2010-06-02

Over the past year, we have worked out a baseline design for PEP-X, as an ultra-low emittance storage ring that could reside in the existing 2.2-km PEPII tunnel. The design features a hybrid lattice with double bend achromat (DBA) cells in two arcs and theoretical minimum emittance (TME) cells in the remaining four arcs. Damping wigglers are used to reduce the horizontal emittance to 86 pm-rad at zero current for a 4.5 GeV electron beam. At a design current of 1.5 A, the horizontal emittance increases, due to intrabeam scattering, to 164 pm-rad when the vertical emittance is maintained at a diffraction limited 8 pm-rad. The baseline design will produce photon beams achieving a brightness of 10{sup 22} (ph/s/mm{sup 2}/mrad{sup 2}/0.1% BW) at 10 keV in a 3.5-m conventional planar undulator. Our study shows that an optimized lattice has adequate dynamic aperture, while accommodating a conventional off-axis injection system. In this report, we present the results of study, including the lattice properties, nonlinear dynamics, intra-beam scattering and Touschek lifetime, RF system, and collective instabilities. Finally, we discuss the possibility of partial lasing at soft X-ray wavelengths using a long undulator in a straight section.

Constitutive expression of a fungus-inducible carboxylesterase improves disease resistance in transgenic pepper plants.

Science.gov (United States)

Ko, Moonkyung; Cho, Jung Hyun; Seo, Hyo-Hyoun; Lee, Hyun-Hwa; Kang, Ha-Young; Nguyen, Thai Son; Soh, Hyun Cheol; Kim, Young Soon; Kim, Jeong-Il

2016-08-01

Resistance against anthracnose fungi was enhanced in transgenic pepper plants that accumulated high levels of a carboxylesterase, PepEST in anthracnose-susceptible fruits, with a concurrent induction of antioxidant enzymes and SA-dependent PR proteins. A pepper esterase gene (PepEST) is highly expressed during the incompatible interaction between ripe fruits of pepper (Capsicum annuum L.) and a hemibiotrophic anthracnose fungus (Colletotrichum gloeosporioides). In this study, we found that exogenous application of recombinant PepEST protein on the surface of the unripe pepper fruits led to a potentiated state for disease resistance in the fruits, including generation of hydrogen peroxide and expression of pathogenesis-related (PR) genes that encode mostly small proteins with antimicrobial activity. To elucidate the role of PepEST in plant defense, we further developed transgenic pepper plants overexpressing PepEST under the control of CaMV 35S promoter. Molecular analysis confirmed the establishment of three independent transgenic lines carrying single copy of transgenes. The level of PepEST protein was estimated to be approximately 0.002 % of total soluble protein in transgenic fruits. In response to the anthracnose fungus, the transgenic fruits displayed higher expression of PR genes, PR3, PR5, PR10, and PepThi, than non-transgenic control fruits did. Moreover, immunolocalization results showed concurrent localization of ascorbate peroxidase (APX) and PR3 proteins, along with the PepEST protein, in the infected region of transgenic fruits. Disease rate analysis revealed significantly low occurrence of anthracnose disease in the transgenic fruits, approximately 30 % of that in non-transgenic fruits. Furthermore, the transgenic plants also exhibited resistance against C. acutatum and C. coccodes. Collectively, our results suggest that overexpression of PepEST in pepper confers enhanced resistance against the anthracnose fungi by activating the defense signaling

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

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.

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

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.

Death of a dogma: eukaryotic mRNAs can code for more than one protein.

Science.gov (United States)

Mouilleron, Hélène; Delcourt, Vivian; Roucou, Xavier

2016-01-08

mRNAs carry the genetic information that is translated by ribosomes. The traditional view of a mature eukaryotic mRNA is a molecule with three main regions, the 5' UTR, the protein coding open reading frame (ORF) or coding sequence (CDS), and the 3' UTR. This concept assumes that ribosomes translate one ORF only, generally the longest one, and produce one protein. As a result, in the early days of genomics and bioinformatics, one CDS was associated with each protein-coding gene. This fundamental concept of a single CDS is being challenged by increasing experimental evidence indicating that annotated proteins are not the only proteins translated from mRNAs. In particular, mass spectrometry (MS)-based proteomics and ribosome profiling have detected productive translation of alternative open reading frames. In several cases, the alternative and annotated proteins interact. Thus, the expression of two or more proteins translated from the same mRNA may offer a mechanism to ensure the co-expression of proteins which have functional interactions. Translational mechanisms already described in eukaryotic cells indicate that the cellular machinery is able to translate different CDSs from a single viral or cellular mRNA. In addition to summarizing data showing that the protein coding potential of eukaryotic mRNAs has been underestimated, this review aims to challenge the single translated CDS dogma. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

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

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

Science.gov (United States)

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

2015-03-01

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

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

Recombinant HT{sub m4} gene, protein and assays

Science.gov (United States)

Lim, B.; Adra, C.N.; Lelias, J.M.

1996-09-03

The invention relates to a recombinant DNA molecule which encodes a HT{sub m4} protein, a transformed host cell which has been stably transfected with a DNA molecule which encodes a HT{sub m4} protein and a recombinant HT{sub m4} protein. The invention also relates to a method for detecting the presence of a hereditary atopy. 2 figs.

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

Selection of mRNA 5'-untranslated region sequence with high translation efficiency through ribosome display

International Nuclear Information System (INIS)

Mie, Masayasu; Shimizu, Shun; Takahashi, Fumio; Kobatake, Eiry

2008-01-01

The 5'-untranslated region (5'-UTR) of mRNAs functions as a translation enhancer, promoting translation efficiency. Many in vitro translation systems exhibit a reduced efficiency in protein translation due to decreased translation initiation. The use of a 5'-UTR sequence with high translation efficiency greatly enhances protein production in these systems. In this study, we have developed an in vitro selection system that favors 5'-UTRs with high translation efficiency using a ribosome display technique. A 5'-UTR random library, comprised of 5'-UTRs tagged with a His-tag and Renilla luciferase (R-luc) fusion, were in vitro translated in rabbit reticulocytes. By limiting the translation period, only mRNAs with high translation efficiency were translated. During translation, mRNA, ribosome and translated R-luc with His-tag formed ternary complexes. They were collected with translated His-tag using Ni-particles. Extracted mRNA from ternary complex was amplified using RT-PCR and sequenced. Finally, 5'-UTR with high translation efficiency was obtained from random 5'-UTR library

Affinity purification of human factor H on polypeptides derived from streptococcal m protein: enrichment of the Y402 variant.

Directory of Open Access Journals (Sweden)

O Rickard Nilsson

Full Text Available Recent studies indicate that defective activity of complement factor H (FH is associated with several human diseases, suggesting that pure FH may be used for therapy. Here, we describe a simple method to isolate human FH, based on the specific interaction between FH and the hypervariable region (HVR of certain Streptococcus pyogenes M proteins. Special interest was focused on the FH polymorphism Y402H, which is associated with the common eye disease age-related macular degeneration (AMD and has also been implicated in the binding to M protein. Using a fusion protein containing two copies of the M5-HVR, we found that the Y402 and H402 variants of FH could be efficiently purified by single-step affinity chromatography from human serum containing the corresponding protein. Different M proteins vary in their binding properties, and the M6 and M5 proteins, but not the M18 protein, showed selective binding of the FH Y402 variant. Accordingly, chromatography on a fusion protein derived from the M6-HVR allowed enrichment of the Y402 protein from serum containing both variants. Thus, the exquisite binding specificity of a bacterial protein can be exploited to develop a simple and robust procedure to purify FH and to enrich for the FH variant that protects against AMD.

Inhibition of translation by 7-methyl guanosine (m7G) nucleotide cap analogs with derivatized 5'-monophosphates

International Nuclear Information System (INIS)

Tahara, S.M.; Darzynkiewicz, E.; Ekiel, I.

1986-01-01

Recognition of the 5'-m 7 GpppN (cap) structure of eukaryote mRNA is an important step of translation initiation as shown by the potent inhibitory effect of m 7 G nucleotides on this process. A comparison of cap analogs as competitive inhibitors of initiation has allowed the authors to map probable protein-ligand contact points between the cap and cognate cap binding proteins (CBPs). Recently, several new derivatives of m 7 GMP (1) with modified phosphates were synthesized: m 7 G 5'-phosphite (2), m 7 G 5'-phosphoramidate (3), m 7 G 5'-methylphosphonate (4), and m 7 G 5'-phosphate-O-methyl ester (5). In addition, 7,8-dimethyl GMP (6) and 7-methyl 8-amino GMP (7) were synthesized. 6 and7 are primarily syn and anti respectively, relative to the glycosidic bond as shown by solution NMR studies. Inhibition by analogs on total translation in reticulocyte lysate and binding of mRNA to rabbit reticulocyte ribosomes was found to be: 1 = 3 > 5 > 4 > 2. The inhibitory activity of 3 was unexpected since it is isosteric with 4, however it suggested that electron configuration and/or the ability to form a hydrogen bond between protein and the phosphate moiety might be important for ligand binding. 7 was more inhibitory than 6. The latter two are isosteric therefore differences in electron delocalization and/or syn-anti conformation are likely to be the reason(s) for the observed difference

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

Dwarfism and impaired gut development in insulin-like growth factor II mRNA-binding protein 1-deficient mice

DEFF Research Database (Denmark)

Hansen, Thomas V O; Hammer, Niels A; Nielsen, Jacob

2004-01-01

Insulin-like growth factor II mRNA-binding protein 1 (IMP1) belongs to a family of RNA-binding proteins implicated in mRNA localization, turnover, and translational control. Mouse IMP1 is expressed during early development, and an increase in expression occurs around embryonic day 12.5 (E12.5). T...

ANP32B is a nuclear target of henipavirus M proteins.

Directory of Open Access Journals (Sweden)

Anja Bauer

Full Text Available Membrane envelopment and budding of negative strand RNA viruses (NSVs is mainly driven by viral matrix proteins (M. In addition, several M proteins are also known to be involved in host cell manipulation. Knowledge about the cellular targets and detailed molecular mechanisms, however, is poor for many M proteins. For instance, Nipah Virus (NiV M protein trafficking through the nucleus is essential for virus release, but nuclear targets of NiV M remain unknown. To identify cellular interactors of henipavirus M proteins, tagged Hendra Virus (HeV M proteins were expressed and M-containing protein complexes were isolated and analysed. Presence of acidic leucine-rich nuclear phosphoprotein 32 family member B (ANP32B in the complex suggested that this protein represents a direct or indirect interactor of the viral matrix protein. Over-expression of ANP32B led to specific nuclear accumulation of HeV M, providing a functional link between ANP32B and M protein. ANP32B-dependent nuclear accumulation was observed after plasmid-driven expression of HeV and NiV matrix proteins and also in NiV infected cells. The latter indicated that an interaction of henipavirus M protein with ANP32B also occurs in the context of virus replication. From these data we conclude that ANP32B is a nuclear target of henipavirus M that may contribute to virus replication. Potential effects of ANP32B on HeV nuclear shuttling and host cell manipulation by HeV M affecting ANP32B functions in host cell survival and gene expression regulation are discussed.

Evaluation of the in vivo binding of 99mTc-MDP on serum proteins

International Nuclear Information System (INIS)

Freitas, R.S.F.; Mattos, D.M.M.; Gomes, M.L.; Moreno, S.R.F.; Lima, E.A.C.; Dire, G.F.; Aleixo, L.C.M.; Lima Filho, G.L.; Bernardo-Filho, M.

2002-01-01

Aim: In the clinical application of technetium-99m-radiopharmaceuticals (99mTc) these agents are injected into the blood stream and they may bind reversibly and irreversibly to the blood proteins. To evaluate the protein binding of the radiopharmaceutical, the protein-bound 99mTc-radiopharmaceuticals must be separated from the free 99mTc-radiopharmaceuticals complexes. This has been accomplished by precipitation of the proteins. In this study, we have compared the results obtained with the evaluation of the binding of the radiopharmaceutical Tc-99m methylenediphosphonic acid (99mTc-MDP) on serum proteins using precipitation methods with TCA and AS. Material and Methods: 99mTc-MDP was administrated in Wistar rats and after 10 minutes blood was withdrawn and serum (S) isolated. Aliquots of S were precipitated with 1 ml of TCA or AS at various concentrations (0.1, 0.5, 1.0, 5.0, 10.0 and 20.0%) and soluble (SF) and insoluble fractions (IF) were separated. The samples (IF-S and SF-S) were counted in a well counter with NaI(TI)crystal. The percent of the radioactivity (%ATI) was determined in each fraction. Results: The results obtained with the comparison of the in vivo binding of 99mTc-MDP when the precipitation was performed with TCA showed that the %ATI was only statistically different (ANOVA, p<0.05) to the 20% TCA concentration. When various concentrations of AS were used no differences in the %ATI were found and the results were similar to the obtained with TCA, except to the concentration of 20%(TCA - 51.70 ± 10.19 and SA - 10.17 ± 0.98 %). Conclusion: It is possible to suggest that the different concentrations of the precipitating agents (TCA and AS) act, in general, on the same binding sites of the evaluate radiopharmaceutical to the proteins of the serum, except to concentration of 20%

Acute guttate psoriasis patients have positive streptococcus hemolyticus throat cultures and elevated antistreptococcal M6 protein titers.

Science.gov (United States)

Zhao, Guang; Feng, Xiaoling; Na, Aihua; Yongqiang, Jiang; Cai, Qing; Kong, Jian; Ma, Huijun

2005-02-01

To further study the role of Streptococci hemolyticus infection and streptococcal M6 protein in the pathogenesis of acute guttate psoriasis, streptococcal cultures were taken from the throats of 68 patients with acute guttate psoriasis. PCR technique was applied to detect M6 protein encoding DNA from those cultured streptococci. Pure M6 protein was obtained by Sephacry/S-200HR and Mono-Q chromatography from proliferated Streptococcus hemolyticus. Antistreptococcal M6 protein titers were measured in the serum of patients with acute guttate psoriasis, plaque psoriasis and healthy controls by ELISA. A high incidence of Streptococcus hemolyticus culture was observed in the guttate psoriatic group compared with the plaque psoriasis and control groups. Fourteen strains of Streptococcus hemolyticus were cultured from the throats of 68 acute guttate psoriasis patients. Of these, 5 strains contain DNA encoding the M6 protein gene as confirmed by PCR technique. More than 85% purification of M6 protein was obtained from Streptococcus pyogenes. Applying our pure M6 protein with the ELISA methods, we found that the titer of antistreptococcal M6 protein was significantly higher in the serum of guttate psoriasis patients than in the control or plaque psoriasis groups (P M6 protein in their sera.

The association of metabotropic glutamate receptor type 5 with the neuronal Ca2+-binding protein 2 modulates receptor function.

Science.gov (United States)

Canela, Laia; Fernández-Dueñas, Víctor; Albergaria, Catarina; Watanabe, Masahiko; Lluís, Carme; Mallol, Josefa; Canela, Enric I; Franco, Rafael; Luján, Rafael; Ciruela, Francisco

2009-10-01

Metabotropic glutamate (mGlu) receptors mediate in part the CNS effects of glutamate. These receptors interact with a large array of intracellular proteins in which the final role is to regulate receptor function. Here, using co-immunoprecipitation and pull-down experiments we showed a close and specific interaction between mGlu(5) receptor and NECAB2 in both transfected human embryonic kidney cells and rat hippocampus. Interestingly, in pull-down experiments increasing concentrations of calcium drastically reduced the ability of these two proteins to interact, suggesting that NECAB2 binds to mGlu(5) receptor in a calcium-regulated manner. Immunoelectron microscopy detection of NECAB2 and mGlu(5) receptor in the rat hippocampal formation indicated that both proteins are codistributed in the same subcellular compartment of pyramidal cells. In addition, the NECAB2/mGlu(5) receptor interaction regulated mGlu(5b)-mediated activation of both inositol phosphate accumulation and the extracellular signal-regulated kinase/mitogen-activated protein kinase pathway. Overall, these findings indicate that NECAB2 by its physical interaction with mGlu(5b) receptor modulates receptor function.

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.

Arabidopsis thaliana mTERF proteins: evolution and functional classification

Directory of Open Access Journals (Sweden)

Tatjana eKleine

2012-10-01

Full Text Available Organellar gene expression (OGE is crucial for plant development, photosynthesis and respiration, but our understanding of the mechanisms that control it is still relatively poor. Thus, OGE requires various nucleus-encoded proteins that promote transcription, splicing, trimming and editing of organellar RNAs, and regulate translation. In metazoans, proteins of the mitochondrial Transcription tERmination Factor (mTERF family interact with the mitochondrial chromosome and regulate transcriptional initiation and termination. Sequencing of the Arabidopsis thaliana genome led to the identification of a diversified MTERF gene family but, in contrast to mammalian mTERFs, knowledge about the function of these proteins in photosynthetic organisms is scarce. In this hypothesis article, I show that tandem duplications and one block duplication contributed to the large number of MTERF genes in A. thaliana, and propose that the expansion of the family is related to the evolution of land plants. The MTERF genes - especially the duplicated genes - display a number of distinct mRNA accumulation patterns, suggesting functional diversification of mTERF proteins to increase adaptability to environmental changes. Indeed, hypothetical functions for the different mTERF proteins can be predicted using co-expression analysis and gene ontology annotations. On this basis, mTERF proteins can be sorted into five groups. Members of the chloroplast and chloroplast-associated clusters are principally involved in chloroplast gene expression, embryogenesis and protein catabolism, while representatives of the mitochondrial cluster seem to participate in DNA and RNA metabolism in that organelle. Moreover, members of the mitochondrion-associated cluster and the low expression group may act in the nucleus and/or the cytosol. As proteins involved in OGE and presumably nuclear gene expression, mTERFs are ideal candidates for the coordination of the expression of organelle and nuclear

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.

A family of insulin-like growth factor II mRNA-binding proteins represses translation in late development

DEFF Research Database (Denmark)

Nielsen, J; Christiansen, J; Lykke-Andersen, J

1999-01-01

Insulin-like growth factor II (IGF-II) is a major fetal growth factor. The IGF-II gene generates multiple mRNAs with different 5' untranslated regions (5' UTRs) that are translated in a differential manner during development. We have identified a human family of three IGF-II mRNA-binding proteins.......5 followed by a decline towards birth, and, similar to IGF-II, IMPs are especially expressed in developing epithelia, muscle, and placenta in both mouse and human embryos. The results imply that cytoplasmic 5' UTR-binding proteins control IGF-II biosynthesis during late mammalian development....... and are homologous to the Xenopus Vera and chicken zipcode-binding proteins. IMP localizes to subcytoplasmic domains in a growth-dependent and cell-specific manner and causes a dose-dependent translational repression of IGF-II leader 3 -luciferase mRNA. Mouse IMPs are produced in a burst at embryonic day 12...

Antisense oligonucleotides targeting translation inhibitory elements in 5' UTRs can selectively increase protein levels.

Science.gov (United States)

Liang, Xue-Hai; Sun, Hong; Shen, Wen; Wang, Shiyu; Yao, Joyee; Migawa, Michael T; Bui, Huynh-Hoa; Damle, Sagar S; Riney, Stan; Graham, Mark J; Crooke, Rosanne M; Crooke, Stanley T

2017-09-19

A variety of diseases are caused by deficiencies in amounts or activity of key proteins. An approach that increases the amount of a specific protein might be of therapeutic benefit. We reasoned that translation could be specifically enhanced using trans-acting agents that counter the function of negative regulatory elements present in the 5' UTRs of some mRNAs. We recently showed that translation can be enhanced by antisense oligonucleotides (ASOs) that target upstream open reading frames. Here we report the amount of a protein can also be selectively increased using ASOs designed to hybridize to other translation inhibitory elements in 5' UTRs. Levels of human RNASEH1, LDLR, and ACP1 and of mouse ACP1 and ARF1 were increased up to 2.7-fold in different cell types and species upon treatment with chemically modified ASOs targeting 5' UTR inhibitory regions in the mRNAs encoding these proteins. The activities of ASOs in enhancing translation were sequence and position dependent and required helicase activity. The ASOs appear to improve the recruitment of translation initiation factors to the target mRNA. Importantly, ASOs targeting ACP1 mRNA significantly increased the level of ACP1 protein in mice, suggesting that this approach has therapeutic and research potentials. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

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

Human neuroglobin protein in cerebrospinal fluid

Directory of Open Access Journals (Sweden)

Whalen Gail

2005-02-01

Full Text Available Abstract Background Neuroglobin is a hexacoordinated member of the globin family of proteins. It is predominantly localized to various brain regions and retina where it may play a role in protection against ischemia and nitric oxide-induced neural injury. Cerebrospinal fluid was collected from 12 chronic regional or systemic pain and 5 control subjects. Proteins were precipitated by addition of 50% 0.2 N acetic acid, 50% ethanol, 0.02% sodium bisulfite. The pellet was extensively digested with trypsin. Peptides were separated by capillary liquid chromatography using a gradient from 95% water to 95% acetonitrile in 0.2% formic acid, and eluted through a nanoelectrospray ionization interface into a quadrapole – time-of-flight dual mass spectrometer (QToF2, Waters, Milford, MA. Peptides were sequenced (PepSeq, MassLynx v3.5 and proteins identified using MASCOT ®. Results Six different neuroglobin peptides were identified in various combinations in 3 of 9 female pain subjects, but none in male pain, or female or male control subjects. Conclusion This is the first description of neuroglobin in cerebrospinal fluid. The mechanism(s leading to its release in chronic pain states remain to be defined.

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

Design, Engineering and Application of an Amyloidogenic Protein, SBAFP-m1, for use in Nanotechnological Applications

Science.gov (United States)

Peralta, Maria del Refugio

Nanotechnology relies on collaborations across scientific disciplines such as physics, engineering, chemistry and biology. In nanotechnology, researchers manipulate molecules on the nanometer scale for various applications, ranging from tissue engineering, nanowire synthesis, and alternative energy devices. By utilizing various biological scaffolds, namely amyloid fibrils, the work of nanometer molecular control can be achieved through the use of self-assembly systems. Here, a systematic design scheme was developed to engineer protein based amyloid fibrils and was successfully applied to the design of two, unique self-assembled monomers, SBAFP-m1 and RGAFP-m1, from naturally occurring ice binding proteins found in insects and plants. A highly idealized, in-register dimer interface was designed and experimentally synthesized and demonstrated to form micron long amyloid fibrils (Chapter 2). The strength and resistance of the designer amyloid fibrils formed by SBAFP-m1 were probed in Chapter 3. Most notably, the ultimate tensile strength of SBAFP-m1 fibrils was experimentally determined to be 2.1 +/- 1.7 GPa, on par with that of naturally occurring amyloid fibrils in literature and steel. The fibrils were found to maintain their beta-sheet structure over a wide range of temperatures, from - 80 °C to 90 °C. Fibrils were resistant to common protein denaturants like 8M urea, 2.5 M guanidine hydrochloride, 2.5 M NaCl, organic solvents (methanol, ethanol, isopropanol and acetone), and across the pH range two to 11. SBAFP-m1 was mutated to add a 5x cysteine tag to the N-terminus, allowing for gold nanoparticle conjugation along the fibril axis (Chapter 4). The gold-conjugated fibrils were then enhanced with silver to produce nanowires. Various attempts to selectively synthesize heterogeneous fibrils from SBAFP-m1 mutants were attempted in Chapter 5. An attempt to de-stabilize the homogeneous fibril assembly through unfavorable homogeneous protein interactions was not

Recognition and cleavage of 5-methylcytosine DNA by bacterial SRA-HNH proteins

OpenAIRE

Han, Tiesheng; Yamada-Mabuchi, Megumu; Zhao, Gong; Li, Li; liu, Guang; Ou, Hong-Yu; Deng, Zixin; Zheng, Yu; He, Xinyi

2015-01-01

SET and RING-finger-associated (SRA) domain is involved in establishment and maintenance of DNA methylation in eukaryotes. Proteins containing SRA domains exist in mammals, plants, even microorganisms. It has been established that mammalian SRA domain recognizes 5-methylcytosine (5mC) through a base-flipping mechanism. Here, we identified and characterized two SRA domain-containing proteins with the common domain architecture of N-terminal SRA domain and C-terminal HNH nuclease domain, Sco533...

Detailed analysis of RNA-protein interactions within the bacterial ribosomal protein L5/5S rRNA complex.

Science.gov (United States)

Perederina, Anna; Nevskaya, Natalia; Nikonov, Oleg; Nikulin, Alexei; Dumas, Philippe; Yao, Min; Tanaka, Isao; Garber, Maria; Gongadze, George; Nikonov, Stanislav

2002-12-01

The crystal structure of ribosomal protein L5 from Thermus thermophilus complexed with a 34-nt fragment comprising helix III and loop C of Escherichia coli 5S rRNA has been determined at 2.5 A resolution. The protein specifically interacts with the bulged nucleotides at the top of loop C of 5S rRNA. The rRNA and protein contact surfaces are strongly stabilized by intramolecular interactions. Charged and polar atoms forming the network of conserved intermolecular hydrogen bonds are located in two narrow planar parallel layers belonging to the protein and rRNA, respectively. The regions, including these atoms conserved in Bacteria and Archaea, can be considered an RNA-protein recognition module. Comparison of the T. thermophilus L5 structure in the RNA-bound form with the isolated Bacillus stearothermophilus L5 structure shows that the RNA-recognition module on the protein surface does not undergo significant changes upon RNA binding. In the crystal of the complex, the protein interacts with another RNA molecule in the asymmetric unit through the beta-sheet concave surface. This protein/RNA interface simulates the interaction of L5 with 23S rRNA observed in the Haloarcula marismortui 50S ribosomal subunit.

Disruption of ten protease genes in the filamentous fungus Aspergillus oryzae highly improves production of heterologous proteins.

Science.gov (United States)

Yoon, Jaewoo; Maruyama, Jun-ichi; Kitamoto, Katsuhiko

2011-02-01

Proteolytic degradation by secreted proteases into the culture medium is one of the significant problems to be solved in heterologous protein production by filamentous fungi including Aspergillus oryzae. Double (tppA, and pepE) and quintuple (tppA, pepE, nptB, dppIV, and dppV) disruption of protease genes enhanced human lysozyme (HLY) and bovine chymosin (CHY) production by A. oryzae. In this study, we used a quintuple protease gene disruptant and performed successive rounds of disruption for five additional protease genes (alpA, pepA, AopepAa, AopepAd, and cpI), which were previously investigated by DNA microarray analyses for their expression. Gene disruption was performed by pyrG marker recycling with a highly efficient gene-targeting background (∆ligD) as previously reported. As a result, the maximum yields of recombinant CHY and HLY produced by a decuple protease gene disruptant were approximately 30% and 35%, respectively, higher than those produced by a quintuple protease gene disruptant. Thus, we successfully constructed a decuple protease gene disruptant possessing highly improved capability of heterologous protein production. This is the first report on decuple protease gene disruption that improved the levels of heterologous protein production by the filamentous fungus A. oryzae.

Enzymatic cyanide degradation by cell-free extract of Rhodococcus UKMP-5M.

Science.gov (United States)

Nallapan Maniyam, Maegala; Sjahrir, Fridelina; Latif Ibrahim, Abdul; Cass, Anthony E G

2015-01-01

The cell-free extract of locally isolated Rhodococcus UKMP-5M strain was used as an alternative to develop greener and cost effective cyanide removal technology. The present study aims to assess the viability of the cell-free extract to detoxify high concentrations of cyanide which is measured through the monitoring of protein concentration and specific cyanide-degrading activity. When cyanide-grown cells were subjected to grinding in liquid nitrogen which is relatively an inexpressive and fast cell disruption method, highest cyanide-degrading activity of 0.63 mM min(-1) mg(-1) protein was obtained in comparison to enzymatic lysis and agitation with fine glass beads. The cell-free extracts managed to degrade 80% of 20 mM KCN within 80 min and the rate of cyanide consumption increased linearly as the concentration of protein was raised. In both cases, the addition of co-factor was not required which proved to be advantageous economically. The successful formation of ammonia and formate as endproducts indicated that the degradation of cyanide by Rhodococcus UKMP-5M proceeded via the activity of cyanidase and the resulting non-toxic products are safe for disposal into the environment. Further verification with SDS-PAGE revealed that the molecular weight of the active enzyme was estimated to be 38 kDa, which is consistent with previously reported cyanidases. Thus, the utilization of cell-free extracts as an alternative to live microbial in cyanide degradation offers numerous advantageous such as the potential to tolerate and degrade higher concentration of cyanide and total reduction in the overall cost of operation since the requirement for nutrient support is irrelevant.

Protein Structure and the Sequential Structure of mRNA

DEFF Research Database (Denmark)

Brunak, Søren; Engelbrecht, Jacob

1996-01-01

entries in the Brookhaven Protein Data Bank produced 719 protein chains with matching mRNA sequence, amino acid sequence, and secondary structure assignment, By neural network analysis, we found strong signals in mRNA sequence regions surrounding helices and sheets, These signals do not originate from......A direct comparison of experimentally determined protein structures and their corresponding protein coding mRNA sequences has been performed, We examine whether real world data support the hypothesis that clusters of rare codons correlate with the location of structural units in the resulting...... protein, The degeneracy of the genetic code allows for a biased selection of codons which may control the translational rate of the ribosome, and may thus in vivo have a catalyzing effect on the folding of the polypeptide chain, A complete search for GenBank nucleotide sequences coding for structural...

Synthesis, Radiolabelling and In Vitro Characterization of the Gallium-68-, Yttrium-90- and Lutetium-177-Labelled PSMA Ligand, CHX-A''-DTPA-DUPA-Pep.

Science.gov (United States)

Baur, Benjamin; Solbach, Christoph; Andreolli, Elena; Winter, Gordon; Machulla, Hans-Jürgen; Reske, Sven N

2014-04-29

Since prostate-specific membrane antigen (PSMA) has been identified as a diagnostic target for prostate cancer, many urea-based small PSMA-targeting molecules were developed. First, the clinical application of these Ga-68 labelled compounds in positron emission tomography (PET) showed their diagnostic potential. Besides, the therapy of prostate cancer is a demanding field, and the use of radiometals with PSMA bearing ligands is a valid approach. In this work, we describe the synthesis of a new PSMA ligand, CHX-A''-DTPA-DUPA-Pep, the subsequent labelling with Ga-68, Lu-177 and Y-90 and the first in vitro characterization. In cell investigations with PSMA-positive LNCaP C4-2 cells, KD values of ≤14.67 ± 1.95 nM were determined, indicating high biological activities towards PSMA. Radiosyntheses with Ga-68, Lu-177 and Y-90 were developed under mild reaction conditions (room temperature, moderate pH of 5.5 and 7.4, respectively) and resulted in nearly quantitative radiochemical yields within 5 min.

Synthesis, Radiolabelling and In Vitro Characterization of the Gallium-68-, Yttrium-90- and Lutetium-177-Labelled PSMA Ligand, CHX-A''-DTPA-DUPA-Pep

Directory of Open Access Journals (Sweden)

Benjamin Baur

2014-04-01

Full Text Available Since prostate-specific membrane antigen (PSMA has been identified as a diagnostic target for prostate cancer, many urea-based small PSMA-targeting molecules were developed. First, the clinical application of these Ga-68 labelled compounds in positron emission tomography (PET showed their diagnostic potential. Besides, the therapy of prostate cancer is a demanding field, and the use of radiometals with PSMA bearing ligands is a valid approach. In this work, we describe the synthesis of a new PSMA ligand, CHX-A''-DTPA-DUPA-Pep, the subsequent labelling with Ga-68, Lu-177 and Y-90 and the first in vitro characterization. In cell investigations with PSMA-positive LNCaP C4-2 cells, KD values of ≤14.67 ± 1.95 nM were determined, indicating high biological activities towards PSMA. Radiosyntheses with Ga-68, Lu-177 and Y-90 were developed under mild reaction conditions (room temperature, moderate pH of 5.5 and 7.4, respectively and resulted in nearly quantitative radiochemical yields within 5 min.

Diabetes alters KIF1A and KIF5B motor proteins in the hippocampus.

Directory of Open Access Journals (Sweden)

Filipa I Baptista

Full Text Available Diabetes mellitus is the most common metabolic disorder in humans. Diabetic encephalopathy is characterized by cognitive and memory impairments, which have been associated with changes in the hippocampus, but the mechanisms underlying those impairments triggered by diabetes, are far from being elucidated. The disruption of axonal transport is associated with several neurodegenerative diseases and might also play a role in diabetes-associated disorders affecting nervous system. We investigated the effect of diabetes (2 and 8 weeks duration on KIF1A, KIF5B and dynein motor proteins, which are important for axonal transport, in the hippocampus. The mRNA expression of motor proteins was assessed by qRT-PCR, and also their protein levels by immunohistochemistry in hippocampal slices and immunoblotting in total extracts of hippocampus from streptozotocin-induced diabetic and age-matched control animals. Diabetes increased the expression and immunoreactivity of KIF1A and KIF5B in the hippocampus, but no alterations in dynein were detected. Since hyperglycemia is considered a major player in diabetic complications, the effect of a prolonged exposure to high glucose on motor proteins, mitochondria and synaptic proteins in hippocampal neurons was also studied, giving particular attention to changes in axons. Hippocampal cell cultures were exposed to high glucose (50 mM or mannitol (osmotic control; 25 mM plus 25 mM glucose for 7 days. In hippocampal cultures incubated with high glucose no changes were detected in the fluorescence intensity or number of accumulations related with mitochondria in the axons of hippocampal neurons. Nevertheless, high glucose increased the number of fluorescent accumulations of KIF1A and synaptotagmin-1 and decreased KIF5B, SNAP-25 and synaptophysin immunoreactivity specifically in axons of hippocampal neurons. These changes suggest that anterograde axonal transport mediated by these kinesins may be impaired in hippocampal

A Mycobacterium leprae Hsp65 mutant as a candidate for mitigating lupus aggravation in mice.

Directory of Open Access Journals (Sweden)

Eliana B Marengo

Full Text Available Hsp60 is an abundant and highly conserved family of intracellular molecules. Increased levels of this family of proteins have been observed in the extracellular compartment in chronic inflammation. Administration of M. leprae Hsp65 [WT] in [NZBxNZW]F(1 mice accelerates the Systemic Lupus Erythematosus [SLE] progression whereas the point mutated K(409A Hsp65 protein delays the disease. Here, the biological effects of M. leprae Hsp65 Leader pep and K(409A pep synthetic peptides, which cover residues 352-371, are presented. Peptides had immunomodulatory effects similar to that observed with their respective proteins on survival and the combined administration of K(409A+Leader pep or K(409A pep+WT showed that the mutant forms were able to inhibit the deleterious effect of WT on mortality, indicating the neutralizing potential of the mutant molecules in SLE progression. Molecular modeling showed that replacing Lysine by Alanine affects the electrostatic potential of the 352-371 region. The number of interactions observed for WT is much higher than for Hsp65 K(409A and mouse Hsp60. The immunomodulatory effects of the point-mutated protein and peptide occurred regardless of the catalytic activity. These findings may be related to the lack of effect on survival when F(1 mice were inoculated with Hsp60 or K(409A pep. Our findings indicate the use of point-mutated Hsp65 molecules, such as the K(409A protein and its corresponding peptide, that may minimize or delay the onset of SLE, representing a new approach to the treatment of autoimmune diseases.

General Model for Retroviral Capsid Pattern Recognition by TRIM5 Proteins.

Science.gov (United States)

Wagner, Jonathan M; Christensen, Devin E; Bhattacharya, Akash; Dawidziak, Daria M; Roganowicz, Marcin D; Wan, Yueping; Pumroy, Ruth A; Demeler, Borries; Ivanov, Dmitri N; Ganser-Pornillos, Barbie K; Sundquist, Wesley I; Pornillos, Owen

2018-02-15

Restriction factors are intrinsic cellular defense proteins that have evolved to block microbial infections. Retroviruses such as HIV-1 are restricted by TRIM5 proteins, which recognize the viral capsid shell that surrounds, organizes, and protects the viral genome. TRIM5α uses a SPRY domain to bind capsids with low intrinsic affinity ( K D of >1 mM) and therefore requires higher-order assembly into a hexagonal lattice to generate sufficient avidity for productive capsid recognition. TRIMCyp, on the other hand, binds HIV-1 capsids through a cyclophilin A domain, which has a well-defined binding site and higher affinity ( K D of ∼10 μM) for isolated capsid subunits. Therefore, it has been argued that TRIMCyp proteins have dispensed with the need for higher-order assembly to function as antiviral factors. Here, we show that, consistent with its high degree of sequence similarity with TRIM5α, the TRIMCyp B-box 2 domain shares the same ability to self-associate and facilitate assembly of a TRIMCyp hexagonal lattice that can wrap about the HIV-1 capsid. We also show that under stringent experimental conditions, TRIMCyp-mediated restriction of HIV-1 is indeed dependent on higher-order assembly. Both forms of TRIM5 therefore use the same mechanism of avidity-driven capsid pattern recognition. IMPORTANCE Rhesus macaques and owl monkeys are highly resistant to HIV-1 infection due to the activity of TRIM5 restriction factors. The rhesus macaque TRIM5α protein blocks HIV-1 through a mechanism that requires self-assembly of a hexagonal TRIM5α lattice around the invading viral core. Lattice assembly amplifies very weak interactions between the TRIM5α SPRY domain and the HIV-1 capsid. Assembly also promotes dimerization of the TRIM5α RING E3 ligase domain, resulting in synthesis of polyubiquitin chains that mediate downstream steps of restriction. In contrast to rhesus TRIM5α, the owl monkey TRIM5 homolog, TRIMCyp, binds isolated HIV-1 CA subunits much more tightly

Proteomic analysis reveals differential accumulation of small heat shock proteins and late embryogenesis abundant proteins between ABA-deficient mutant vp5 seeds and wild-type Vp5 seeds in maize

Directory of Open Access Journals (Sweden)

Xiaolin eWu

2015-01-01

Full Text Available ABA is a major plant hormone that plays important roles during many phases of plant life cycle, including seed development, maturity and dormancy, and especially the acquisition of desiccation tolerance. Understanding of the molecular basis of ABA-mediated plant response to stress is of interest not only in basic research on plant adaptation but also in applied research on plant productivity. Maize mutant viviparous-5 (vp5, deficient in ABA biosynthesis in seeds, is a useful material for studying ABA-mediated response in maize. Due to carotenoid deficiency, vp5 endosperm is white, compared to yellow Vp5 endosperm. However, the background difference at proteome level between vp5 and Vp5 seeds is unclear. This study aimed to characterize proteome alterations of maize vp5 seeds and to identify ABA-dependent proteins during seed maturation. We compared the embryo and endosperm proteomes of vp5 and Vp5 seeds by gel-based proteomics. Up to 46 protein spots, most in embryos, were found to be differentially accumulated between vp5 and Vp5. The identified proteins included small heat shock proteins (sHSPs, late embryogenesis abundant (LEA proteins, stress proteins, storage proteins and enzymes among others. However, EMB564, the most abundant LEA protein in maize embryo, accumulated in comparable levels between vp5 and Vp5 embryos, which contrasted to previously characterized, greatly lowered expression of emb564 mRNA in vp5 embryos. Moreover, LEA proteins and sHSPs displayed differential accumulations in vp5 embryos: six out of eight identified LEA proteins decreased while nine sHSPs increased in abundance. Finally, we discussed the possible causes of global proteome alterations, especially the observed differential accumulation of identified LEA proteins and sHSPs in vp5 embryos. The data derived from this study provides new insight into ABA-dependent proteins and ABA-mediated response during maize seed maturation.

The nuclear import of ribosomal proteins is regulated by mTOR

Science.gov (United States)

Kazyken, Dubek; Kaz, Yelimbek; Kiyan, Vladimir; Zhylkibayev, Assylbek A.; Chen, Chien-Hung; Agarwal, Nitin K.; Sarbassov, Dos D.

2014-01-01

Mechanistic target of rapamycin (mTOR) is a central component of the essential signaling pathway that regulates cell growth and proliferation by controlling anabolic processes in cells. mTOR exists in two distinct mTOR complexes known as mTORC1 and mTORC2 that reside mostly in cytoplasm. In our study, the biochemical characterization of mTOR led to discovery of its novel localization on nuclear envelope where it associates with a critical regulator of nuclear import Ran Binding Protein 2 (RanBP2). We show that association of mTOR with RanBP2 is dependent on the mTOR kinase activity that regulates the nuclear import of ribosomal proteins. The mTOR kinase inhibitors within thirty minutes caused a substantial decrease of ribosomal proteins in the nuclear but not cytoplasmic fraction. Detection of a nuclear accumulation of the GFP-tagged ribosomal protein rpL7a also indicated its dependence on the mTOR kinase activity. The nuclear abundance of ribosomal proteins was not affected by inhibition of mTOR Complex 1 (mTORC1) by rapamycin or deficiency of mTORC2, suggesting a distinctive role of the nuclear envelope mTOR complex in the nuclear import. Thus, we identified that mTOR in association with RanBP2 mediates the active nuclear import of ribosomal proteins. PMID:25294810

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.

Processing of the glycosomal matrix-protein import receptor PEX5 of Trypanosoma brucei

International Nuclear Information System (INIS)

Gualdrón-López, Melisa; Michels, Paul A.M.

2013-01-01

Highlights: ► Most eukaryotic cells have a single gene for the peroxin PEX5. ► PEX5 is sensitive to in vitro proteolysis in distantly related organisms. ► TbPEX5 undergoes N-terminal truncation in vitro and possibly in vivo. ► Truncated TbPEX5 is still capable of binding PTS1-containing proteins. ► PEX5 truncation is physiologically relevant or an evolutionary conserved artifact. -- Abstract: Glycolysis in kinetoplastid protists such as Trypanosoma brucei is compartmentalized in peroxisome-like organelles called glycosomes. Glycosomal matrix-protein import involves a cytosolic receptor, PEX5, which recognizes the peroxisomal-targeting signal type 1 (PTS1) present at the C-terminus of the majority of matrix proteins. PEX5 appears generally susceptible to in vitro proteolytic processing. On western blots of T. brucei, two PEX5 forms are detected with apparent M r of 100 kDa and 72 kDa. 5′-RACE-PCR showed that TbPEX5 is encoded by a unique transcript that can be translated into a protein of maximally 72 kDa. However, recombinant PEX5 migrates aberrantly in SDS–PAGE with an apparent M r of 100 kDa, similarly as observed for the native peroxin. In vitro protease susceptibility analysis of native and 35 S-labelled PEX5 showed truncation of the 100 kDa form at the N-terminal side by unknown parasite proteases, giving rise to the 72 kDa form which remains functional for PTS1 binding. The relevance of these observations is discussed

Processing of the glycosomal matrix-protein import receptor PEX5 of Trypanosoma brucei

Energy Technology Data Exchange (ETDEWEB)

Gualdrón-López, Melisa [Research Unit for Tropical Diseases, de Duve Institute, Université catholique de Louvain, Brussels (Belgium); Michels, Paul A.M., E-mail: paul.michels@uclouvain.be [Research Unit for Tropical Diseases, de Duve Institute, Université catholique de Louvain, Brussels (Belgium)

2013-02-01

Highlights: ► Most eukaryotic cells have a single gene for the peroxin PEX5. ► PEX5 is sensitive to in vitro proteolysis in distantly related organisms. ► TbPEX5 undergoes N-terminal truncation in vitro and possibly in vivo. ► Truncated TbPEX5 is still capable of binding PTS1-containing proteins. ► PEX5 truncation is physiologically relevant or an evolutionary conserved artifact. -- Abstract: Glycolysis in kinetoplastid protists such as Trypanosoma brucei is compartmentalized in peroxisome-like organelles called glycosomes. Glycosomal matrix-protein import involves a cytosolic receptor, PEX5, which recognizes the peroxisomal-targeting signal type 1 (PTS1) present at the C-terminus of the majority of matrix proteins. PEX5 appears generally susceptible to in vitro proteolytic processing. On western blots of T. brucei, two PEX5 forms are detected with apparent M{sub r} of 100 kDa and 72 kDa. 5′-RACE-PCR showed that TbPEX5 is encoded by a unique transcript that can be translated into a protein of maximally 72 kDa. However, recombinant PEX5 migrates aberrantly in SDS–PAGE with an apparent M{sub r} of 100 kDa, similarly as observed for the native peroxin. In vitro protease susceptibility analysis of native and {sup 35}S-labelled PEX5 showed truncation of the 100 kDa form at the N-terminal side by unknown parasite proteases, giving rise to the 72 kDa form which remains functional for PTS1 binding. The relevance of these observations is 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

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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

Targeting mGlu5 Metabotropic Glutamate Receptors in the Treatment of Cognitive Dysfunction in a Mouse Model of Phenylketonuria

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Francesca Nardecchia

2018-03-01

Full Text Available We studied group-I metabotropic glutamate (mGlu receptors in Pahenu2 (ENU2 mice, which mimic the genetics and neurobiology of human phenylketonuria (PKU, a metabolic disorder characterized, if untreated, by autism, and intellectual disability (ID. Male ENU2 mice showed increased mGlu5 receptor protein levels in the hippocampus and corpus striatum (but not in the prefrontal cortex whereas the transcript of the mGlu5 receptor was unchanged. No changes in mGlu1 receptor mRNA and protein levels were found in any of the three brain regions of ENU2 mice. We extended the analysis to Homer proteins, which act as scaffolds by linking mGlu1 and mGlu5 receptors to effector proteins. Expression of the long isoforms of Homer was significantly reduced in the hippocampus of ENU2 mice, whereas levels of the short Homer isoform (Homer 1a were unchanged. mGlu5 receptors were less associated to immunoprecipitated Homer in the hippocampus of ENU2 mice. The lack of mGlu5 receptor-mediated long-term depression (LTD in wild-type mice (of BTBR strain precluded the analysis of hippocampal synaptic plasticity in ENU2 mice. We therefore performed a behavioral analysis to examine whether pharmacological blockade of mGlu5 receptors could correct behavioral abnormalities in ENU2 mice. Using the same apparatus we sequentially assessed locomotor activity, object exploration, and spatial object recognition (spatial novelty test after displacing some of the objects from their original position in the arena. Systemic treatment with the mGlu5 receptor antagonist, MPEP (20 mg/kg, i.p., had a striking effect in the spatial novelty test by substantially increasing the time spent in exploring the displaced objects in ENU2 mice (but not in wild-type mice. These suggest a role for mGlu5 receptors in the pathophysiology of ID in PKU and suggest that, also in adult untreated animals, cognitive dysfunction may be improved by targeting these receptors with an appropriate therapy.

Metabotropic glutamate receptor I (mGluR1) antagonism impairs cocaine-induced conditioned place preference via inhibition of protein synthesis.

Science.gov (United States)

Yu, Fei; Zhong, Peng; Liu, Xiaojie; Sun, Dalong; Gao, Hai-Qing; Liu, Qing-Song

2013-06-01

Antagonism of group I metabotropic glutamate receptors (mGluR1 and mGluR5) reduces behavioral effects of drugs of abuse, including cocaine. However, the underlying mechanisms remain poorly understood. Activation of mGluR5 increases protein synthesis at synapses. Although mGluR5-induced excessive protein synthesis has been implicated in the pathology of fragile X syndrome, it remains unknown whether group I mGluR-mediated protein synthesis is involved in any behavioral effects of drugs of abuse. We report that group I mGluR agonist DHPG induced more pronounced initial depression of inhibitory postsynaptic currents (IPSCs) followed by modest long-term depression (I-LTD) in dopamine neurons of rat ventral tegmental area (VTA) through the activation of mGluR1. The early component of DHPG-induced depression of IPSCs was mediated by the cannabinoid CB1 receptors, while DHPG-induced I-LTD was dependent on protein synthesis. Western blotting analysis indicates that mGluR1 was coupled to extracellular signal-regulated kinase (ERK) and mammalian target of rapamycin (mTOR) signaling pathways to increase translation. We also show that cocaine conditioning activated translation machinery in the VTA via an mGluR1-dependent mechanism. Furthermore, intra-VTA microinjections of mGluR1 antagonist JNJ16259685 and protein synthesis inhibitor cycloheximide significantly attenuated or blocked the acquisition of cocaine-induced conditioned place preference (CPP) and activation of translation elongation factors. Taken together, these results suggest that mGluR1 antagonism inhibits de novo protein synthesis; this effect may block the formation of cocaine-cue associations and thus provide a mechanism for the reduction in CPP to cocaine.

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

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.)

Characterization of an M-Cluster-Substituted Nitrogenase VFe Protein.

Science.gov (United States)

Rebelein, Johannes G; Lee, Chi Chung; Newcomb, Megan; Hu, Yilin; Ribbe, Markus W

2018-03-13

The Mo- and V-nitrogenases are two homologous members of the nitrogenase family that are distinguished mainly by the presence of different heterometals (Mo or V) at their respective cofactor sites (M- or V-cluster). However, the V-nitrogenase is ~600-fold more active than its Mo counterpart in reducing CO to hydrocarbons at ambient conditions. Here, we expressed an M-cluster-containing, hybrid V-nitrogenase in Azotobacter vinelandii and compared it to its native, V-cluster-containing counterpart in order to assess the impact of protein scaffold and cofactor species on the differential reactivities of Mo- and V-nitrogenases toward CO. Housed in the VFe protein component of V-nitrogenase, the M-cluster displayed electron paramagnetic resonance (EPR) features similar to those of the V-cluster and demonstrated an ~100-fold increase in hydrocarbon formation activity from CO reduction, suggesting a significant impact of protein environment on the overall CO-reducing activity of nitrogenase. On the other hand, the M-cluster was still ~6-fold less active than the V-cluster in the same protein scaffold, and it retained its inability to form detectable amounts of methane from CO reduction, illustrating a fine-tuning effect of the cofactor properties on this nitrogenase-catalyzed reaction. Together, these results provided important insights into the two major determinants for the enzymatic activity of CO reduction while establishing a useful framework for further elucidation of the essential catalytic elements for the CO reactivity of nitrogenase. IMPORTANCE This is the first report on the in vivo generation and in vitro characterization of an M-cluster-containing V-nitrogenase hybrid. The "normalization" of the protein scaffold to that of the V-nitrogenase permits a direct comparison between the cofactor species of the Mo- and V-nitrogenases (M- and V-clusters) in CO reduction, whereas the discrepancy between the protein scaffolds of the Mo- and V-nitrogenases (MoFe and VFe

Preferential 5-Methylcytosine Oxidation in the Linker Region of Reconstituted Positioned Nucleosomes by Tet1 Protein.

Science.gov (United States)

Kizaki, Seiichiro; Zou, Tingting; Li, Yue; Han, Yong-Woon; Suzuki, Yuki; Harada, Yoshie; Sugiyama, Hiroshi

2016-11-07

Tet (ten-eleven translocation) family proteins oxidize 5-methylcytosine (mC) to 5-hydroxymethylcytosine (hmC), 5-formylcytosine (fC), and 5-carboxycytosine (caC), and are suggested to be involved in the active DNA demethylation pathway. In this study, we reconstituted positioned mononucleosomes using CpG-methylated 382 bp DNA containing the Widom 601 sequence and recombinant histone octamer, and subjected the nucleosome to treatment with Tet1 protein. The sites of oxidized methylcytosine were identified by bisulfite sequencing. We found that, for the oxidation reaction, Tet1 protein prefers mCs located in the linker region of the nucleosome compared with those located in the core region. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Intrinsic resistance to aminoglycosides in Enterococcus faecium is conferred by the 16S rRNA m5C1404-specific methyltransferase EfmM

DEFF Research Database (Denmark)

Galimand, Marc; Schmitt, Emmanuelle; Panvert, Michel

2011-01-01

methyltransferase, as well as by the previously characterized aac(6')-Ii that encodes a 6'-N-aminoglycoside acetyltransferase. Inactivation of efmM in E. faecium increases susceptibility to the aminoglycosides kanamycin and tobramycin, and, conversely, expression of a recombinant version of efmM in Escherichia coli...... confers resistance to these drugs. The EfmM protein shows significant sequence similarity to E. coli RsmF (previously called YebU), which is a 5-methylcytidine (m(5)C) methyltransferase modifying 16S rRNA nucleotide C1407. The target for EfmM is shown by mass spectrometry to be a neighboring 16S r...

Human trabecular meshwork cells express BMP antagonist mRNAs and proteins.

Science.gov (United States)

Tovar-Vidales, Tara; Fitzgerald, Ashley M; Clark, Abbot F

2016-06-01

Glaucoma patients have elevated aqueous humor and trabecular meshwork (TM) levels of transforming growth factor-beta2 (TGF-β2). TGF-β2 has been associated with increased extracellular matrix (ECM) deposition (i.e. fibronectin), which is attributed to the increased resistance of aqueous humor outflow through the TM. We have previously demonstrated that bone morphogenetic protein (BMP) 4 selectively counteracts the profibrotic effect of TGF-β2 with respect to ECM synthesis in the TM, and this action is reversed by the BMP antagonist gremlin. Thus, the BMP and TGF-β signaling pathways antagonize each other's antifibrotic and profibrotic roles. The purpose of this study was to determine whether cultured human TM cells: (a) express other BMP antagonists including noggin, chordin, BMPER, BAMBI, Smurf1 and 2, and (b) whether expression of these proteins is regulated by exogenous TGF-β2 treatment. Primary human trabecular meshwork (TM) cells were grown to confluency and treated with TGF-β2 (5 ng/ml) for 24 or 48 h in serum-free medium. Untreated cell served as controls. qPCR and Western immunoblots (WB) determined that human TM cells expressed mRNAs and proteins for the BMP antagonist proteins: noggin, chordin, BMPER, BAMBI, and Smurf1/2. Exogenous TGF-β2 decreased chordin, BMPER, BAMBI, and Smurf1 mRNA and protein expression. In contrast, TGF-β2 increased secreted noggin and Smurf2 mRNA and protein levels. BMP antagonist members are expressed in the human TM. These molecules may be involved in the normal function of the TM as well as TM pathogenesis. Altered expression of BMP antagonist members may lead to functional changes in the human TM. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

Genome-wide mRNA processing in methanogenic archaea reveals post-transcriptional regulation of ribosomal protein synthesis.

Science.gov (United States)

Qi, Lei; Yue, Lei; Feng, Deqin; Qi, Fengxia; Li, Jie; Dong, Xiuzhu

2017-07-07

Unlike stable RNAs that require processing for maturation, prokaryotic cellular mRNAs generally follow an 'all-or-none' pattern. Herein, we used a 5΄ monophosphate transcript sequencing (5΄P-seq) that specifically captured the 5΄-end of processed transcripts and mapped the genome-wide RNA processing sites (PSSs) in a methanogenic archaeon. Following statistical analysis and stringent filtration, we identified 1429 PSSs, among which 23.5% and 5.4% were located in 5΄ untranslated region (uPSS) and intergenic region (iPSS), respectively. A predominant uridine downstream PSSs served as a processing signature. Remarkably, 5΄P-seq detected overrepresented uPSS and iPSS in the polycistronic operons encoding ribosomal proteins, and the majority upstream and proximal ribosome binding sites, suggesting a regulatory role of processing on translation initiation. The processed transcripts showed increased stability and translation efficiency. Particularly, processing within the tricistronic transcript of rplA-rplJ-rplL enhanced the translation of rplL, which can provide a driving force for the 1:4 stoichiometry of L10 to L12 in the ribosome. Growth-associated mRNA processing intensities were also correlated with the cellular ribosomal protein levels, thereby suggesting that mRNA processing is involved in tuning growth-dependent ribosome synthesis. In conclusion, our findings suggest that mRNA processing-mediated post-transcriptional regulation is a potential mechanism of ribosomal protein synthesis and stoichiometry. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Analysis of protein-protein docking decoys using interaction fingerprints: application to the reconstruction of CaM-ligand complexes

Directory of Open Access Journals (Sweden)

Uchikoga Nobuyuki

2010-05-01

Full Text Available Abstract Background Protein-protein docking for proteins with large conformational changes was analyzed by using interaction fingerprints, one of the scales for measuring similarities among complex structures, utilized especially for searching near-native protein-ligand or protein-protein complex structures. Here, we have proposed a combined method for analyzing protein-protein docking by taking large conformational changes into consideration. This combined method consists of ensemble soft docking with multiple protein structures, refinement of complexes, and cluster analysis using interaction fingerprints and energy profiles. Results To test for the applicability of this combined method, various CaM-ligand complexes were reconstructed from the NMR structures of unbound CaM. For the purpose of reconstruction, we used three known CaM-ligands, namely, the CaM-binding peptides of cyclic nucleotide gateway (CNG, CaM kinase kinase (CaMKK and the plasma membrane Ca2+ ATPase pump (PMCA, and thirty-one structurally diverse CaM conformations. For each ligand, 62000 CaM-ligand complexes were generated in the docking step and the relationship between their energy profiles and structural similarities to the native complex were analyzed using interaction fingerprint and RMSD. Near-native clusters were obtained in the case of CNG and CaMKK. Conclusions The interaction fingerprint method discriminated near-native structures better than the RMSD method in cluster analysis. We showed that a combined method that includes the interaction fingerprint is very useful for protein-protein docking analysis of certain cases.

The Human Splicing Factor ASF/SF2 can Specifically Recognize Pre-mRNA 5' Splice Sites

Science.gov (United States)

Zuo, Ping; Manley, James L.

1994-04-01

ASF/SF2 is a human protein previously shown to function in in vitro pre-mRNA splicing as an essential factor necessary for all splices and also as an alternative splicing factor, capable of switching selection of 5' splice sites. To begin to study the protein's mechanism of action, we have investigated the RNA binding properties of purified recombinant ASF/SF2. Using UV crosslinking and gel shift assays, we demonstrate that the RNA binding region of ASF/SF2 can interact with RNA in a sequence-specific manner, recognizing the 5' splice site in each of two different pre-mRNAs. Point mutations in the 5' splice site consensus can reduce binding by as much as a factor of 100, with the largest effects observed in competition assays. These findings support a model in which ASF/SF2 aids in the recognition of pre-mRNA 5' splice sites.

Bioactive Peptides from Angelica sinensis Protein Hydrolyzate Delay Senescence in Caenorhabditis elegans through Antioxidant Activities

Directory of Open Access Journals (Sweden)

Qiangqiang Wang

2016-01-01

Full Text Available Since excessive reactive oxygen species (ROS is known to be associated with aging and age-related diseases, strategies modulating ROS level and antioxidant defense systems may contribute to the delay of senescence. Here we show that the protein hydrolyzate from Angelica sinensis was capable of increasing oxidative survival of the model animal Caenorhabditis elegans intoxicated by paraquat. The hydrolyzate was then fractionated by ultrafiltration, and the antioxidant fraction (<3 kDa was purified by gel filtration to obtain the antioxidant A. sinensis peptides (AsiPeps, which were mostly composed of peptides with <20 amino acid residues. Further studies demonstrate that AsiPeps were able to reduce the endogenous ROS level, increase the activities of the antioxidant enzymes superoxide dismutase and catalase, and decrease the content of the lipid peroxidation product malondialdehyde in nematodes treated with paraquat or undergoing senescence. AsiPeps were also shown to reduce age pigments accumulation and extend lifespan but did not affect the food-intake behavior of the nematodes. Taken together, our results demonstrate that A. sinensis peptides (AsiPeps are able to delay aging process in C. elegans through antioxidant activities independent of dietary restriction.

Holographic cosmology from a system of M2–M5 branes

International Nuclear Information System (INIS)

Sepehri, Alireza; Faizal, Mir; Setare, Mohammad Reza; Ali, Ahmed Farag

2016-01-01

In this paper, we analyze the holographic cosmology using a M2–M5 brane configuration. In this configuration, a M2-brane will be placed in between a M5-brane and an anti-M5-brane. The M2-brane will act as a channel for energy to flow from an anti-M5-brane to a M5-brane, and this will increase the degrees of freedom on the M5-brane causing inflation. The inflation will end when the M5-brane and anti-M5-brane get separated. However, at a later stage the distance between the M5-brane and the anti-M5-bran can reduce and this will cause the formation of tachyonic states. These tachyonic states will again open a bridge between the M5-branes and the anti-M5-branes, which will cause further acceleration of the universe.

Holographic cosmology from a system of M2–M5 branes

Energy Technology Data Exchange (ETDEWEB)

Sepehri, Alireza, E-mail: alireza.sepehri@uk.ac.ir [Faculty of Physics, Shahid Bahonar University, P.O. Box 76175, Kerman (Iran, Islamic Republic of); Research Institute for Astronomy and Astrophysics of Maragha (RIAAM), Maragha (Iran, Islamic Republic of); Faizal, Mir, E-mail: f2mir@uwaterloo.ca [Department of Physics and Astronomy, University of Waterloo, Waterloo, ON, N2L 3G1 (Canada); Setare, Mohammad Reza, E-mail: rezakord@ipm.ir [Department of Science, Campus of Bijar, University of Kurdistan, Bijar (Iran, Islamic Republic of); Ali, Ahmed Farag, E-mail: afali@fsu.edu [Department of Physics, Florida State University, Tallahassee, FL 32306 (United States); Department of Physics, Faculty of Science, Benha University, Benha 13518 (Egypt)

2016-05-15

In this paper, we analyze the holographic cosmology using a M2–M5 brane configuration. In this configuration, a M2-brane will be placed in between a M5-brane and an anti-M5-brane. The M2-brane will act as a channel for energy to flow from an anti-M5-brane to a M5-brane, and this will increase the degrees of freedom on the M5-brane causing inflation. The inflation will end when the M5-brane and anti-M5-brane get separated. However, at a later stage the distance between the M5-brane and the anti-M5-bran can reduce and this will cause the formation of tachyonic states. These tachyonic states will again open a bridge between the M5-branes and the anti-M5-branes, which will cause further acceleration of the universe.

mKikGR, a monomeric photoswitchable fluorescent protein.

Directory of Open Access Journals (Sweden)

Satoshi Habuchi

Full Text Available The recent demonstration and utilization of fluorescent proteins whose fluorescence can be switched on and off has greatly expanded the toolkit of molecular and cell biology. These photoswitchable proteins have facilitated the characterization of specifically tagged molecular species in the cell and have enabled fluorescence imaging of intracellular structures with a resolution far below the classical diffraction limit of light. Applications are limited, however, by the fast photobleaching, slow photoswitching, and oligomerization typical for photoswitchable proteins currently available. Here, we report the molecular cloning and spectroscopic characterization of mKikGR, a monomeric version of the previously reported KikGR that displays high photostability and switching rates. Furthermore, we present single-molecule imaging experiments that demonstrate that individual mKikGR proteins can be localized with a precision of better than 10 nanometers, suggesting their suitability for super-resolution imaging.

Interactions of cullin3/KCTD5 complexes with both cytoplasmic and nuclear proteins: Evidence for a role in protein stabilization

Energy Technology Data Exchange (ETDEWEB)

Rutz, Natalja; Heilbronn, Regine; Weger, Stefan, E-mail: stefan.weger@charite.de

2015-08-28