Indications for a critical point in the phase diagram for hot and dense nuclear matter

NASA Astrophysics Data System (ADS)

Lacey, Roy A.

2016-12-01

Two-pion interferometry measurements are studied for a broad range of collision centralities in Au+Au (√{sNN} = 7.7- 200 GeV) and Pb+Pb (√{sNN} = 2.76 TeV) collisions. They indicate non-monotonic excitation functions for the Gaussian emission source radii difference (Rout -Rside), suggestive of reaction trajectories which spend a fair amount of time near a soft point in the equation of state (EOS) that coincides with the critical end point (CEP). A Finite-Size Scaling (FSS) analysis of these excitation functions, provides further validation tests for the CEP. It also indicates a second order phase transition at the CEP, and the values Tcep ∼ 165 MeV and μBcep ∼ 95 MeV for its location in the (T ,μB)-plane of the phase diagram. The static critical exponents (ν ≈ 0.66 and γ ≈ 1.2) extracted via the same FSS analysis, place this CEP in the 3D Ising model (static) universality class. A Dynamic Finite-Size Scaling analysis of the excitation functions, gives the estimate z ∼ 0.87 for the dynamic critical exponent, suggesting that the associated critical expansion dynamics is dominated by the hydrodynamic sound mode.

Cep55 overexpression causes male-specific sterility in mice by suppressing Foxo1 nuclear retention through sustained activation of PI3K/Akt signaling.

PubMed

Sinha, Debottam; Kalimutho, Murugan; Bowles, Josephine; Chan, Ai-Leen; Merriner, D Jo; Bain, Amanda L; Simmons, Jacinta L; Freire, Raimundo; Lopez, J Alejandro; Hobbs, Robin M; O'Bryan, Moira K; Khanna, Kum Kum

2018-04-17

Spermatogenesis is a dynamic process involving self-renewal and differentiation of spermatogonial stem cells, meiosis, and ultimately, the differentiation of haploid spermatids into sperm. Centrosomal protein (CEP)-55 is necessary for somatic cell abscission during cytokinesis. It facilitates equal segregation of cytoplasmic contents between daughter cells by recruiting endosomal sorting complex required for transport machinery (ESCRT) at the midbody. In germ cells, CEP55, in partnership with testes expressed-14 protein (TEX14), has also been shown to be an integral component of intercellular bridge before meiosis. Various in vitro studies have demonstrated a role for CEP55 in multiple cancers and other diseases. However, its oncogenic potential in vivo remains elusive. To investigate, we generated ubiquitously overexpressing Cep55 transgenic mice ( Cep55 Tg/Tg ) aiming to characterize its oncogenic role in cancer. Unexpectedly, we found that Cep55 Tg/Tg male mice were sterile and had severe and progressive defects in spermatogenesis related to spermatogenic arrest and lack of spermatids in the testes. In this study, we characterized this male-specific phenotype and showed that excessively high levels of Cep55 results in hyperactivation of PI3K/protein kinase B (Akt) signaling in testis. In line with this finding, we observed increased phosphorylation of forkhead box protein O1 (FoxO1), and suppression of its nuclear retention, along with the relative enrichment of promyelocytic leukemia zinc finger (PLZF) -positive cells. Independently, we observed that Cep55 amplification favored upregulation of ret ( Ret) proto-oncogene and glial-derived neurotrophic factor family receptor α-1 ( Gfra1). Consistent with these data, we observed selective down-regulation of genes associated with germ cell differentiation in Cep55-overexpressing testes at postnatal day 10, including early growth response-4 ( Egr4) and spermatogenesis and oogenesis specific basic helix-loop-helix-1 ( Sohlh1). Thus, Cep55 amplification leads to a shift toward the initial maintenance of undifferentiated spermatogonia and ultimately results in progressive germ cell loss. Collectively, our findings demonstrate that Cep55 overexpression causes change in germ cell proportions and manifests as a Sertoli cell only tubule phenotype, similar to that seen in many azoospermic men.-Sinha, D., Kalimutho, M., Bowles, J., Chan, A.-L., Merriner, D. J., Bain, A. L., Simmons, J. L., Freire, R., Lopez, J. A., Hobbs, R. M., O'Bryan, M. K., Khanna, K. K. Cep55 overexpression causes male-specific sterility in mice by suppressing Foxo1 nuclear retention through sustained activation of PI3K/Akt signaling.

Carrier-envelope phase dependence of the directional fragmentation and hydrogen migration in toluene in few-cycle laser fields.

PubMed

Li, Hui; Kling, Nora G; Förg, Benjamin; Stierle, Johannes; Kessel, Alexander; Trushin, Sergei A; Kling, Matthias F; Kaziannis, Spyros

2016-07-01

The dissociative ionization of toluene initiated by a few-cycle laser pulse as a function of the carrier envelope phase (CEP) is investigated using single-shot velocity map imaging. Several ionic fragments, CH3 (+), H2 (+), and H3 (+), originating from multiply charged toluene ions present a CEP-dependent directional emission. The formation of H2 (+) and H3 (+) involves breaking C-H bonds and forming new bonds between the hydrogen atoms within the transient structure of the multiply charged precursor. We observe appreciable intensity-dependent CEP-offsets. The experimental data are interpreted with a mechanism that involves laser-induced coupling of vibrational states, which has been found to play a role in the CEP-control of molecular processes in hydrocarbon molecules, and appears to be of general importance for such complex molecules.

Experimental demonstration of photon upconversion via cooperative energy pooling

DOE PAGES

Weingarten, Daniel H.; LaCount, Michael D.; van de Lagemaat, Jao; ...

2017-03-15

Photon upconversion is a fundamental interaction of light and matter that has applications in fields ranging from bioimaging to microfabrication. However, all photon upconversion methods demonstrated thus far involve challenging aspects, including requirements of high excitation intensities, degradation in ambient air, requirements of exotic materials or phases, or involvement of inherent energy loss processes. Here we experimentally demonstrate a mechanism of photon upconversion in a thin film, binary mixture of organic chromophores that provides a pathway to overcoming the aforementioned disadvantages. This singlet-based process, called Cooperative Energy Pooling (CEP), utilizes a sensitizer-acceptor design in which multiple photoexcited sensitizers resonantly andmore » simultaneously transfer their energies to a higher-energy state on a single acceptor. Data from this proof-of-concept implementation is fit by a proposed model of the CEP process. As a result, design guidelines are presented to facilitate further research and development of more optimized CEP systems.« less

Experimental demonstration of photon upconversion via cooperative energy pooling

PubMed Central

Weingarten, Daniel H.; LaCount, Michael D.; van de Lagemaat, Jao; Rumbles, Garry; Lusk, Mark T.; Shaheen, Sean E.

2017-01-01

Photon upconversion is a fundamental interaction of light and matter that has applications in fields ranging from bioimaging to microfabrication. However, all photon upconversion methods demonstrated thus far involve challenging aspects, including requirements of high excitation intensities, degradation in ambient air, requirements of exotic materials or phases, or involvement of inherent energy loss processes. Here we experimentally demonstrate a mechanism of photon upconversion in a thin film, binary mixture of organic chromophores that provides a pathway to overcoming the aforementioned disadvantages. This singlet-based process, called Cooperative Energy Pooling (CEP), utilizes a sensitizer-acceptor design in which multiple photoexcited sensitizers resonantly and simultaneously transfer their energies to a higher-energy state on a single acceptor. Data from this proof-of-concept implementation is fit by a proposed model of the CEP process. Design guidelines are presented to facilitate further research and development of more optimized CEP systems. PMID:28294129

Experimental demonstration of photon upconversion via cooperative energy pooling

NASA Astrophysics Data System (ADS)

Weingarten, Daniel H.; Lacount, Michael D.; van de Lagemaat, Jao; Rumbles, Garry; Lusk, Mark T.; Shaheen, Sean E.

2017-03-01

Photon upconversion is a fundamental interaction of light and matter that has applications in fields ranging from bioimaging to microfabrication. However, all photon upconversion methods demonstrated thus far involve challenging aspects, including requirements of high excitation intensities, degradation in ambient air, requirements of exotic materials or phases, or involvement of inherent energy loss processes. Here we experimentally demonstrate a mechanism of photon upconversion in a thin film, binary mixture of organic chromophores that provides a pathway to overcoming the aforementioned disadvantages. This singlet-based process, called Cooperative Energy Pooling (CEP), utilizes a sensitizer-acceptor design in which multiple photoexcited sensitizers resonantly and simultaneously transfer their energies to a higher-energy state on a single acceptor. Data from this proof-of-concept implementation is fit by a proposed model of the CEP process. Design guidelines are presented to facilitate further research and development of more optimized CEP systems.

Carrier-envelope phase dependence of the directional fragmentation and hydrogen migration in toluene in few-cycle laser fields

PubMed Central

Li, Hui; Kling, Nora G.; Förg, Benjamin; Stierle, Johannes; Kessel, Alexander; Trushin, Sergei A.; Kling, Matthias F.; Kaziannis, Spyros

2016-01-01

The dissociative ionization of toluene initiated by a few-cycle laser pulse as a function of the carrier envelope phase (CEP) is investigated using single-shot velocity map imaging. Several ionic fragments, CH3+, H2+, and H3+, originating from multiply charged toluene ions present a CEP-dependent directional emission. The formation of H2+ and H3+ involves breaking C-H bonds and forming new bonds between the hydrogen atoms within the transient structure of the multiply charged precursor. We observe appreciable intensity-dependent CEP-offsets. The experimental data are interpreted with a mechanism that involves laser-induced coupling of vibrational states, which has been found to play a role in the CEP-control of molecular processes in hydrocarbon molecules, and appears to be of general importance for such complex molecules. PMID:26958589

Influence of the carrier-envelope phase of few-cycle pulses on ponderomotive surface-plasmon electron acceleration.

PubMed

Irvine, S E; Dombi, P; Farkas, Gy; Elezzabi, A Y

2006-10-06

Control over basic processes through the electric field of a light wave can lead to new knowledge of fundamental light-matter interaction phenomena. We demonstrate, for the first time, that surface-plasmon (SP) electron acceleration can be coherently controlled through the carrier-envelope phase (CEP) of an excitation optical pulse. Analysis indicates that the physical origin of the CEP sensitivity arises from the electron's ponderomotive interaction with the oscillating electromagnetic field of the SP wave. The ponderomotive electron acceleration mechanism provides sensitive (nJ energies), high-contrast, single-shot CEP measurement capability of few-cycle laser pulses.

An anomalous extinction law in the Cep OB3b young cluster: Evidence for dust processing during gas dispersal

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

Allen, Thomas S.; Prchlik, Jakub J.; Megeath, S. Thomas

We determine the extinction law through Cep OB3b, a young cluster of 3000 stars undergoing gas dispersal. The extinction is measured toward 76 background K giants identified with MMT/Hectospec spectra. Color excess ratios were determined toward each of the giants using V and R photometry from the literature, g, r, i, and z photometry from the Sloan Digital Sky Survey and J, H, and K{sub s} photometry from the Two Micron All Sky Survey. These color excess ratios were then used to construct the extinction law through the dusty material associated with Cep OB3b. The extinction law through Cep OB3bmore » is intermediate between the R{sub V} = 3.1 and R{sub V} = 5 laws commonly used for the diffuse atomic interstellar medium and dense molecular clouds, respectively. The dependence of the extinction law on line-of-sight A{sub V} is investigated and we find the extinction law becomes shallower for regions with A{sub V} > 2.5 mag. We speculate that the intermediate dust law results from dust processing during the dispersal of the molecular cloud by the cluster.« less

Phosphorylation of the centrosomal protein, Cep169, by Cdk1 promotes its dissociation from centrosomes in mitosis.

PubMed

Mori, Yusuke; Inoue, Yoko; Taniyama, Yuki; Tanaka, Sayori; Terada, Yasuhiko

2015-12-25

Cep169 is a centrosomal protein conserved among vertebrates. In our previous reports, we showed that mammalian Cep169 interacts and collaborates with CDK5RAP2 to regulate microtubule (MT) dynamics and stabilization. Although Cep169 is required for MT regulation, its precise cellular function remains largely elusive. Here we show that Cep169 associates with centrosomes during interphase, but dissociates from these structures from the onset of mitosis, although CDK5RAP2 (Cep215) is continuously located at the centrosomes throughout cell cycle. Interestingly, treatment with purvalanol A, a Cdk1 inhibitor, nearly completely blocked the dissociation of Cep169 from centrosomes during mitosis. In addition, mass spectrometry analyses identified 7 phosphorylated residues of Cep169 corresponding to consensus phosphorylation sequence for Cdk1. These data suggest that the dissociation of Cep169 from centrosomes is controlled by Cdk1/Cyclin B during mitosis, and that Cep169 might regulate MT dynamics of mitotic spindle. Copyright © 2015 Elsevier Inc. All rights reserved.

Coherent and incoherent contributions to the carrier-envelope phase control of wave packet localization in quantum double wells

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

Hader, K.; Engel, V., E-mail: voen@phys-chemie.uni-wuerzburg.de

2014-05-14

We study laser excitation processes in a double well potential. The possibility to influence localization via the carrier-envelope phase (CEP) of a laser pulse is investigated for various situations which differ in the nature of the initial state prior to the laser interactions. In more detail, the CEP-dependence of asymmetries in the case where initially the system is described by localized wave packets, eigenstates, or incoherent mixtures are calculated and interpreted within time-dependent perturbation theory. It is investigated which contributions to the asymmetry exist and how they can be modified to reveal a more or less pronounced CEP-effect.

Coherent and incoherent contributions to the carrier-envelope phase control of wave packet localization in quantum double wells.

PubMed

Hader, K; Engel, V

2014-05-14

We study laser excitation processes in a double well potential. The possibility to influence localization via the carrier-envelope phase (CEP) of a laser pulse is investigated for various situations which differ in the nature of the initial state prior to the laser interactions. In more detail, the CEP-dependence of asymmetries in the case where initially the system is described by localized wave packets, eigenstates, or incoherent mixtures are calculated and interpreted within time-dependent perturbation theory. It is investigated which contributions to the asymmetry exist and how they can be modified to reveal a more or less pronounced CEP-effect.

Functional C-TERMINALLY ENCODED PEPTIDE (CEP) plant hormone domains evolved de novo in the plant parasite Rotylenchulus reniformis.

PubMed

Eves-Van Den Akker, Sebastian; Lilley, Catherine J; Yusup, Hazijah B; Jones, John T; Urwin, Peter E

2016-10-01

Sedentary plant-parasitic nematodes (PPNs) induce and maintain an intimate relationship with their host, stimulating cells adjacent to root vascular tissue to re-differentiate into unique and metabolically active 'feeding sites'. The interaction between PPNs and their host is mediated by nematode effectors. We describe the discovery of a large and diverse family of effector genes, encoding C-TERMINALLY ENCODED PEPTIDE (CEP) plant hormone mimics (RrCEPs), in the syncytia-forming plant parasite Rotylenchulus reniformis. The particular attributes of RrCEPs distinguish them from all other CEPs, regardless of origin. Together with the distant phylogenetic relationship of R. reniformis to the only other CEP-encoding nematode genus identified to date (Meloidogyne), this suggests that CEPs probably evolved de novo in R. reniformis. We have characterized the first member of this large gene family (RrCEP1), demonstrating its significant up-regulation during the plant-nematode interaction and expression in the effector-producing pharyngeal gland cell. All internal CEP domains of multi-domain RrCEPs are followed by di-basic residues, suggesting a mechanism for cleavage. A synthetic peptide corresponding to RrCEP1 domain 1 is biologically active and capable of up-regulating plant nitrate transporter (AtNRT2.1) expression, whilst simultaneously reducing primary root elongation. When a non-CEP-containing, syncytia-forming PPN species (Heterodera schachtii) infects Arabidopsis in a CEP-rich environment, a smaller feeding site is produced. We hypothesize that CEPs of R. reniformis represent a two-fold adaptation to sustained biotrophy in this species: (i) increasing host nitrate uptake, whilst (ii) limiting the size of the syncytial feeding site produced. © 2016 The Authors. Molecular Plant Pathology Published by British Society for Plant Pathology and John Wiley & Sons Ltd.

CEP genes regulate root and shoot development in response to environmental cues and are specific to seed plants.

PubMed

Delay, Christina; Imin, Nijat; Djordjevic, Michael A

2013-12-01

The manifestation of repetitive developmental programmes during plant growth can be adjusted in response to various environmental cues. During root development, this means being able to precisely control root growth and lateral root development. Small signalling peptides have been found to play roles in many aspects of root development. One member of the CEP (C-TERMINALLY ENCODED PEPTIDE) gene family has been shown to arrest root growth. Here we report that CEP genes are widespread among seed plants but are not present in land plants that lack true branching roots or root vasculature. We have identified 10 additional CEP genes in Arabidopsis. Expression analysis revealed that CEP genes are regulated by environmental cues such as nitrogen limitation, increased salt levels, increased osmotic strength, and increased CO2 levels in both roots and shoots. Analysis of synthetic CEP variants showed that both peptide sequence and modifications of key amino acids affect CEP biological activity. Analysis of several CEP over-expression lines revealed distinct roles for CEP genes in root and shoot development. A cep3 knockout mutant showed increased root and shoot growth under a range of abiotic stress, nutrient, and light conditions. We demonstrate that CEPs are negative regulators of root development, slowing primary root growth and reducing lateral root formation. We propose that CEPs are negative regulators that mediate environmental influences on plant development.

Abnormal neuronal response to rectal and anal stimuli in patients treated with primary radiotherapy for anal cancer.

PubMed

Haas, Susanne; Faaborg, Pia; Gram, Mikkel; Lundby, Lilli; Brock, Christina; Drewes, Anbjørn M; Laurberg, Søren; Krogh, Klaus; Christensen, Peter

2018-04-26

Sphincter-sparing radiotherapy or chemoradiation (RT/CRT) have become the standard treatments for most patients with anal cancer. Unfortunately, long-term survivors often suffer from severe bowel symptoms indicating sensory dysfunction. The aim of the present study was to characterize the sensory pathways of the brain-gut axis after radiotherapy for anal cancer. Cortical evoked potentials (CEPs) were recorded during repeated, rapid balloon distensions of the rectum and anal canal in 13 patients with anal cancer treated with radiotherapy or chemoradiation and in 17 healthy volunteers. Latencies and amplitudes of rectal CEPs were compared between the groups. CEPs from both rectal and anal distensions were examined using single sweep spectral band analysis to determine the relative amplitude of five spectral bands as a proxy of neuronal processing. Groups were comparable by age (62.4 ± 7.8 vs 58.9 ± 8.9, p < 0.32) and gender. Patients had a mean Wexner fecal incontinence score of 5.5 (±3.8) and median LARS Score of 29 (0-39). Rectal CEP latencies were prolonged in patients (F = 11.7; p < 0.001), whereas amplitudes were similar (F = 0.003; p = 0.96). Spectral analysis of CEPs from rectal distensions showed significant differences between groups in theta (4-8 Hz), alpha (8-12 Hz), beta (12-32 Hz) and gamma (32-70 Hz) bands (all p < 0.001) and CEPs from anal distensions showed significant differences in the alpha, beta and gamma bands (all p ≤ 0.002). Patients treated with RT/CRT for anal cancer have impaired ano-rectal sensory pathways and abnormal cortical processing. This may play a central role for the pathogenesis of late proctopathy. Copyright © 2018 Elsevier B.V. All rights reserved.

Solution NMR studies of the plant peptide hormone CEP inform function.

PubMed

Bobay, Benjamin G; DiGennaro, Peter; Scholl, Elizabeth; Imin, Nijat; Djordjevic, Michael A; Mck Bird, David

2013-12-11

The C-terminally Encoded Peptide (CEP) family of regulatory peptides controls root development in vascular plants. Here, we present the first NMR structures of CEP. We show that root-knot nematode (RKN: Meloidogyne spp.) also encodes CEP, presumably to mimic plant CEP as part of their stereotypic, parasitic interaction with vascular plants. Molecular dynamics simulations of plant- and nematode-encoded CEP displaying known posttranslational modifications (PTM) provided insight into the structural effects of PTM and the conformational plasticity and rigidity of CEP. Potential mechanisms of action are discussed with respect to the structure and sampling of conformational space. © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Saturation mutagenesis of a CepR binding site as a means to identify new quorum-regulated promoters in Burkholderia cenocepacia

USDA-ARS?s Scientific Manuscript database

Burkholderia cenocepacia, an opportunistic pathogen of humans, encodes the CepI and CepR proteins, which resemble the LuxI and LuxR quorum sensing proteins of Vibrio fischeri. CepI directs the synthesis of octanoylhomoserine lactone (OHL), while CepR is an OHL dependent transcription factor. In pr...

Centriolar satellites assemble centrosomal microcephaly proteins to recruit CDK2 and promote centriole duplication

PubMed Central

Kodani, Andrew; Yu, Timothy W; Johnson, Jeffrey R; Jayaraman, Divya; Johnson, Tasha L; Al-Gazali, Lihadh; Sztriha, Lāszló; Partlow, Jennifer N; Kim, Hanjun; Krup, Alexis L; Dammermann, Alexander; Krogan, Nevan J; Walsh, Christopher A; Reiter, Jeremy F

2015-01-01

Primary microcephaly (MCPH) associated proteins CDK5RAP2, CEP152, WDR62 and CEP63 colocalize at the centrosome. We found that they interact to promote centriole duplication and form a hierarchy in which each is required to localize another to the centrosome, with CDK5RAP2 at the apex, and CEP152, WDR62 and CEP63 at sequentially lower positions. MCPH proteins interact with distinct centriolar satellite proteins; CDK5RAP2 interacts with SPAG5 and CEP72, CEP152 with CEP131, WDR62 with MOONRAKER, and CEP63 with CEP90 and CCDC14. These satellite proteins localize their cognate MCPH interactors to centrosomes and also promote centriole duplication. Consistent with a role for satellites in microcephaly, homozygous mutations in one satellite gene, CEP90, may cause MCPH. The satellite proteins, with the exception of CCDC14, and MCPH proteins promote centriole duplication by recruiting CDK2 to the centrosome. Thus, centriolar satellites build a MCPH complex critical for human neurodevelopment that promotes CDK2 centrosomal localization and centriole duplication. DOI: http://dx.doi.org/10.7554/eLife.07519.001 PMID:26297806

Three close binaries in different evolutionary stages in the old open cluster NGC 188

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

Zhu, L. Y.; Qian, S. B.; Liu, L.

2014-02-01

NGC 188 is a good laboratory for studying the formation and evolution of W UMa type contact binaries due to its rich populations of them. We present a detailed photometric study of three short-period close binaries, EP Cep, ES Cep, and V369 Cep, in the old open cluster NGC 188 based on our two-set photometric observations. We discovered that both EP Cep and ES Cep are shallow-contact binaries with continuously decreasing periods. The difference is in their mass ratios. EP Cep has an extremely low-mass ratio, q = 0.15, while ES Cep has a relatively high-mass ratio, q = 0.69,more » indicating that they lie in different evolutionary stages. ES Cep is likely a newly formed contact binary via a Case A mass transfer, while EP Cep is an evolved system and may be on the oscillations caused by the combined effect of the thermal relaxation oscillation and the variable angular momentum loss. For another system, V369 Cep, we found that it is a primary-filling near-contact binary. Both the semidetached configuration and the continuous decrease in the orbital period indicate that it is undergoing a mass transfer from the primary component to the secondary one. This conclusion is in agreement with the excess luminosity seen in the light curves on the ingress of the secondary minimum produced by the impact of the mass transfer. All of the results suggest that V369 Cep is evolving into contact, and a shallow-contact high-mass ratio system similar to ES Cep will be formed. Then, it will evolve into a low-mass ratio contact binary just like EP Cep, and finally merge into a rapidly rotating single star.« less

General Theory of Carrier-Envelope Phase Effects

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

Roudnev, V.; Esry, B. D.

2007-11-30

We present a general framework for understanding carrier-envelope phase (CEP) effects in a quantum system interacting with an intense, short laser pulse. We establish a simple connection between the CEP and the wave function that can be exploited to obtain the full CEP dependence of an observable given the wave function at a single CEP. Within this framework, all CEP effects are interpreted as interference between different photon amplitudes which, in turn, can be used to put limits on the pulse lengths and intensities required to see significant CEP effects.

Cep152 interacts with Plk4 and is required for centriole duplication

PubMed Central

Hatch, Emily M.; Kulukian, Anita; Holland, Andrew J.; Cleveland, Don W.

2010-01-01

Centrioles are microtubule-based structures that organize the centrosome and nucleate cilia. Centrioles duplicate once per cell cycle, and duplication requires Plk4, a member of the Polo-like kinase family; however, the mechanism linking Plk4 activity and centriole formation is unknown. In this study, we show in human and frog cells that Plk4 interacts with the centrosome protein Cep152, the orthologue of Drosophila melanogaster Asterless. The interaction requires the N-terminal 217 residues of Cep152 and the crypto Polo-box of Plk4. Cep152 and Plk4 colocalize at the centriole throughout the cell cycle. Overexpression of Cep152 (1–217) mislocalizes Plk4, but both Cep152 and Plk4 are able to localize to the centriole independently of the other. Depletion of Cep152 prevents both normal centriole duplication and Plk4-induced centriole amplification and results in a failure to localize Sas6 to the centriole, an early step in duplication. Cep152 can be phosphorylated by Plk4 in vitro, suggesting that Cep152 acts with Plk4 to initiate centriole formation. PMID:21059850

The IL-8 Protease SpyCEP/ScpC of Group A Streptococcus Promotes Resistance to Neutrophil Killing

PubMed Central

Zinkernagel, Annelies S.; Timmer, Anjuli M.; Pence, Morgan A.; Locke, Jeffrey B.; Buchanan, John T.; Turner, Claire E.; Mishalian, Inbal; Sriskandan, Shiranee; Hanski, Emanuel; Nizet, Victor

2009-01-01

SUMMARY Interleukin-8 (IL-8) promotes neutrophil-mediated host defense through its chemoattractant and immunostimulatory activities. The Group A Streptococcus (GAS) protease SpyCEP (also called ScpC) cleaves IL-8, and SpyCEP expression is strongly upregulated in vivo in the M1T1 GAS strains associated with life-threatening systemic disease including necrotizing fasciitis. Coupling allelic replacement with heterologous gene expression, we show that SpyCEP is necessary and sufficient for IL-8 degradation. SpyCEP decreased IL-8-dependent neutrophil endothelial transmigration and bacterial killing, the latter by reducing neutrophil extracellular trap formation. The knockout mutant lacking SpyCEP was attenuated for virulence in murine infection models, and SpyCEP expression conferred protection to coinfecting bacteria. We also show that the zoonotic pathogen Streptococcus iniae possesses a functional homolog of SpyCEP (Cepl) that cleaves IL-8, promotes neutrophil resistance, and contributes to virulence. By inactivating the multifunctional host defense peptide IL-8, the SpyCEP protease impairs neutrophil clearance mechanisms, contributing to the pathogenesis of invasive streptococcal infection. PMID:18692776

Subfemtosecond directional control of chemical processes in molecules

NASA Astrophysics Data System (ADS)

Alnaser, Ali S.; Litvinyuk, Igor V.

2017-02-01

Laser pulses with a waveform-controlled electric field and broken inversion symmetry establish the opportunity to achieve directional control of molecular processes on a subfemtosecond timescale. Several techniques could be used to break the inversion symmetry of an electric field. The most common ones include combining a fundamental laser frequency with its second harmonic or with higher -frequency pulses (or pulse trains) as well as using few-cycle pulses with known carrier-envelope phase (CEP). In the case of CEP, control over chemical transformations, typically occurring on a timescale of many femtoseconds, is driven by much faster sub-cycle processes of subfemtosecond to few-femtosecond duration. This is possible because electrons are much lighter than nuclei and fast electron motion is coupled to the much slower nuclear motion. The control originates from populating coherent superpositions of different electronic or vibrational states with relative phases that are dependent on the CEP or phase offset between components of a two-color pulse. In this paper, we review the recent progress made in the directional control over chemical processes, driven by intense few-cycle laser pulses a of waveform-tailored electric field, in different molecules.

Measuring the absolute carrier-envelope phase of many-cycle laser fields

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

Tzallas, P.; Skantzakis, E.; Charalambidis, D.

2010-12-15

The carrier-envelope phase (CEP) of high-peak-power, many-cycle laser fields becomes a crucial parameter when such fields are used, in conjunction with polarization gating techniques, in isolated attosecond (asec) pulse generation. However, its measurement has not been achieved so far. We demonstrate a physical process sensitive to the CEP value of such fields and describe a method for its online shot-to-shot monitoring. This work paves the way for the exploitation of energetic isolated asec pulses in studies of nonlinear extreme ultraviolet (XUV) processes and XUV-pump-XUV-probe experiments with asec resolutions.

MRI Quantification of Human Spine Cartilage Endplate Geometry: Comparison With Age, Degeneration, Level, and Disc Geometry

PubMed Central

DeLucca, John F.; Peloquin, John M.; Smith, Lachlan J.; Wright, Alexander C.; Vresilovic, Edward J.; Elliott, Dawn M.

2017-01-01

Geometry is an important indicator of disc mechanical function and degeneration. While the geometry and associated degenerative changes in the nucleus pulposus and the annulus fibrosus are well-defined, the geometry of the cartilage endplate (CEP) and its relationship to disc degeneration are unknown. The objectives of this study were to quantify CEP geometry in three dimensions using an MRI FLASH imaging sequence and evaluate relationships between CEP geometry and age, degeneration, spinal level, and overall disc geometry. To do so, we assessed the MRI-based measurements for accuracy and repeatability. Next, we measured CEP geometry across a larger sample set and correlated CEP geometric parameters to age, disc degeneration, level, and disc geometry. The MRI-based measures resulted in thicknesses (0.3–1 mm) that are comparable to prior measurements of CEP thickness. CEP thickness was greatest at the anterior/posterior (A/P) margins and smallest in the center. The CEP A/P thickness, axial area, and lateral width decreased with age but were not related to disc degeneration. Age-related, but not degeneration-related, changes in geometry suggest that the CEP may not follow the progression of disc degeneration. Ultimately, if the CEP undergoes significant geometric changes with aging and if these can be related to low back pain, a clinically feasible translation of the FLASH MRI-based measurement of CEP geometry presented in this study may prove a useful diagnostic tool. PMID:27232974

Midbody Targeting of the ESCRT Machinery by a Noncanonical Coiled Coil in CEP55

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

Lee, Hyung Ho; Elia, Natalie; Ghirlando, Rodolfo

2008-11-14

The ESCRT (endosomal sorting complex required for transport) machinery is required for the scission of membrane necks in processes including the budding of HIV-1 and cytokinesis. An essential step in cytokinesis is recruitment of the ESCRT-I complex and the ESCRT-associated protein ALIX to the midbody (the structure that tethers two daughter cells) by the protein CEP55. Biochemical experiments show that peptides from ALIX and the ESCRT-I subunit TSG101 compete for binding to the ESCRT and ALIX-binding region (EABR) of CEP55. We solved the crystal structure of EABR bound to an ALIX peptide at a resolution of 2.0 angstroms. The structuremore » shows that EABR forms an aberrant dimeric parallel coiled coil. Bulky and charged residues at the interface of the two central heptad repeats create asymmetry and a single binding site for an ALIX or TSG101 peptide. Both ALIX and ESCRT-I are required for cytokinesis, which suggests that multiple CEP55 dimers are required for function.« less

A primary microcephaly protein complex forms a ring around parental centrioles.

PubMed

Sir, Joo-Hee; Barr, Alexis R; Nicholas, Adeline K; Carvalho, Ofelia P; Khurshid, Maryam; Sossick, Alex; Reichelt, Stefanie; D'Santos, Clive; Woods, C Geoffrey; Gergely, Fanni

2011-10-09

Autosomal recessive primary microcephaly (MCPH) is characterized by a substantial reduction in prenatal human brain growth without alteration of the cerebral architecture and is caused by biallelic mutations in genes coding for a subset of centrosomal proteins. Although at least three of these proteins have been implicated in centrosome duplication, the nature of the centrosome dysfunction that underlies the neurodevelopmental defect in MCPH is unclear. Here we report a homozygous MCPH-causing mutation in human CEP63. CEP63 forms a complex with another MCPH protein, CEP152, a conserved centrosome duplication factor. Together, these two proteins are essential for maintaining normal centrosome numbers in cells. Using super-resolution microscopy, we found that CEP63 and CEP152 co-localize in a discrete ring around the proximal end of the parental centriole, a pattern specifically disrupted in CEP63-deficient cells derived from patients with MCPH. This work suggests that the CEP152-CEP63 ring-like structure ensures normal neurodevelopment and that its impairment particularly affects human cerebral cortex growth.

The centrosomal component CEP161 of Dictyostelium discoideum interacts with the Hippo signaling pathway

PubMed Central

Sukumaran, Salil K.; Blau-Wasser, Rosemarie; Rohlfs, Meino; Gallinger, Christoph; Schleicher, Michael; Noegel, Angelika A

2015-01-01

CEP161 is a novel component of the Dictyostelium discoideum centrosome which was identified as binding partner of the pericentriolar component CP250. Here we show that the amino acids 1-763 of the 1381 amino acids CEP161 are sufficient for CP250 binding, centrosomal targeting and centrosome association. Analysis of AX2 cells over-expressing truncated and full length CEP161 proteins revealed defects in growth and development. By immunoprecipitation experiments we identified the Hippo related kinase SvkA (Hrk-svk) as binding partner for CEP161. Both proteins colocalize at the centrosome. In in vitro kinase assays the N-terminal domain of CEP161 (residues 1-763) inhibited the kinase activity of Hrk-svk. A comparison of D. discoideum Hippo kinase mutants with mutants overexpressing CEP161 polypeptides revealed similar defects. We propose that the centrosomal component CEP161 is a novel player in the Hippo signaling pathway and affects various cellular properties through this interaction. PMID:25607232

The Cysteine Protease CEP1, a Key Executor Involved in Tapetal Programmed Cell Death, Regulates Pollen Development in Arabidopsis[W][OPEN

PubMed Central

Zhang, Dandan; Liu, Di; Lv, Xiaomeng; Wang, Ying; Xun, Zhili; Liu, Zhixiong; Li, Fenglan; Lu, Hai

2014-01-01

Tapetal programmed cell death (PCD) is a prerequisite for pollen grain development in angiosperms, and cysteine proteases are the most ubiquitous hydrolases involved in plant PCD. We identified a papain-like cysteine protease, CEP1, which is involved in tapetal PCD and pollen development in Arabidopsis thaliana. CEP1 is expressed specifically in the tapetum from stages 5 to 11 of anther development. The CEP1 protein first appears as a proenzyme in precursor protease vesicles and is then transported to the vacuole and transformed into the mature enzyme before rupture of the vacuole. cep1 mutants exhibited aborted tapetal PCD and decreased pollen fertility with abnormal pollen exine. A transcriptomic analysis revealed that 872 genes showed significantly altered expression in the cep1 mutants, and most of them are important for tapetal cell wall organization, tapetal secretory structure formation, and pollen development. CEP1 overexpression caused premature tapetal PCD and pollen infertility. ELISA and quantitative RT-PCR analyses confirmed that the CEP1 expression level showed a strong relationship to the degree of tapetal PCD and pollen fertility. Our results reveal that CEP1 is a crucial executor during tapetal PCD and that proper CEP1 expression is necessary for timely degeneration of tapetal cells and functional pollen formation. PMID:25035401

The cysteine protease CEP1, a key executor involved in tapetal programmed cell death, regulates pollen development in Arabidopsis.

PubMed

Zhang, Dandan; Liu, Di; Lv, Xiaomeng; Wang, Ying; Xun, Zhili; Liu, Zhixiong; Li, Fenglan; Lu, Hai

2014-07-01

Tapetal programmed cell death (PCD) is a prerequisite for pollen grain development in angiosperms, and cysteine proteases are the most ubiquitous hydrolases involved in plant PCD. We identified a papain-like cysteine protease, CEP1, which is involved in tapetal PCD and pollen development in Arabidopsis thaliana. CEP1 is expressed specifically in the tapetum from stages 5 to 11 of anther development. The CEP1 protein first appears as a proenzyme in precursor protease vesicles and is then transported to the vacuole and transformed into the mature enzyme before rupture of the vacuole. cep1 mutants exhibited aborted tapetal PCD and decreased pollen fertility with abnormal pollen exine. A transcriptomic analysis revealed that 872 genes showed significantly altered expression in the cep1 mutants, and most of them are important for tapetal cell wall organization, tapetal secretory structure formation, and pollen development. CEP1 overexpression caused premature tapetal PCD and pollen infertility. ELISA and quantitative RT-PCR analyses confirmed that the CEP1 expression level showed a strong relationship to the degree of tapetal PCD and pollen fertility. Our results reveal that CEP1 is a crucial executor during tapetal PCD and that proper CEP1 expression is necessary for timely degeneration of tapetal cells and functional pollen formation. © 2014 American Society of Plant Biologists. All rights reserved.

Cepharanthine attenuates lipopolysaccharide-induced mice mastitis by suppressing the NF-κB signaling pathway.

PubMed

Ershun, Zhou; Yunhe, Fu; Zhengkai, Wei; Yongguo, Cao; Naisheng, Zhang; Zhengtao, Yang

2014-04-01

Cepharanthine (CEP), a biscoclaurine alkaloid isolated from Stephania cepharantha Hayata, has been reported to have potent anti-inflammatory properties. However, the anti-inflammatory effects of CEP on a mouse model of lipopolysaccharide (LPS)-induced mastitis and its underlying molecular mechanisms remain to be elucidated. The purpose of the present study was to investigate the effects of CEP on LPS-induced mouse mastitis. The mouse model of mastitis was induced by inoculation of LPS through the canals of the mammary gland. CEP was administered intraperitoneally at 1 h before and 12 h after induction of LPS. The results show that CEP significantly attenuates the infiltration of neutrophils, suppresses myeloperoxidase activity, and reduces the levels of TNF-α, IL-1β, and IL-6 in LPS-induced mouse mastitis. Furthermore, CEP inhibited the phosphorylation of NF-κB p65 subunit and the degradation of its inhibitor IκBα. All the results suggest that CEP exerts potent anti-inflammatory effects on LPS-induced mouse mastitis. Accordingly, CEP might be a potential therapeutic agent for mastitis.

Cep55 regulates embryonic growth and development by promoting Akt stability in zebrafish.

PubMed

Jeffery, Jessie; Neyt, Christine; Moore, Wade; Paterson, Scott; Bower, Neil I; Chenevix-Trench, Georgia; Verkade, Heather; Hogan, Benjamin M; Khanna, Kum Kum

2015-05-01

CEP55 was initially described as a centrosome- and midbody-associated protein and a key mediator of cytokinesis. More recently, it has been implicated in PI3K/AKT pathway activation via an interaction with the catalytic subunit of PI3K. However, its role in embryonic development is unknown. Here we describe a cep55 nonsense mutant zebrafish with which we can study the in vivo physiologic role of Cep55. Homozygous mutants underwent extensive apoptosis by 24 hours postfertilization (hpf) concomitant with cell cycle defects, and heterozygous carriers were indistinguishable from their wild-type siblings. A similar phenotype was also observed in zebrafish injected with a cep55 morpholino, suggesting the mutant is a cep55 loss-of-function model. Further analysis revealed that Akt was destabilized in the homozygous mutants, which partially phenocopied Akt1 and Akt2 knockdown. Expression of either constitutively activated PIK3CA or AKT1 could partially rescue the homozygous mutants. Consistent with a role for Cep55 in regulation of Akt stability, treatment with proteasome inhibitor, MG132, partially rescued the homozygous mutants. Taken together, these results provide the first description of Cep55 in development and underline the importance of Cep55 in the regulation of Pi3k/Akt pathway and in particular Akt stability. © FASEB.

Reversing resistance to vascular-disrupting agents by blocking late mobilization of circulating endothelial progenitor cells.

PubMed

Taylor, Melissa; Billiot, Fanny; Marty, Virginie; Rouffiac, Valérie; Cohen, Patrick; Tournay, Elodie; Opolon, Paule; Louache, Fawzia; Vassal, Gilles; Laplace-Builhé, Corinne; Vielh, Philippe; Soria, Jean-Charles; Farace, Françoise

2012-05-01

The prevailing concept is that immediate mobilization of bone marrow-derived circulating endothelial progenitor cells (CEP) is a key mechanism mediating tumor resistance to vascular-disrupting agents (VDA). Here, we show that administration of VDA to tumor-bearing mice induces 2 distinct peaks in CEPs: an early, unspecific CEP efflux followed by a late yet more dramatic tumor-specific CEP burst that infiltrates tumors and is recruited to vessels. Combination with antiangiogenic drugs could not disrupt the early peak but completely abrogated the late VDA-induced CEP burst, blunted bone marrow-derived cell recruitment to tumors, and resulted in striking antitumor efficacy, indicating that the late CEP burst might be crucial to tumor recovery after VDA therapy. CEP and circulating endothelial cell kinetics in VDA-treated patients with cancer were remarkably consistent with our preclinical data. These findings expand the current understanding of vasculogenic "rebounds" that may be targeted to improve VDA-based strategies. Our findings suggest that resistance to VDA therapy may be strongly mediated by late, rather than early, tumor-specific recruitment of CEPs, the suppression of which resulted in increased VDA-mediated antitumor efficacy. VDA-based therapy might thus be significantly enhanced by combination strategies targeting late CEP mobilization. © 2012 AACR

G4CEP: A G4 theory modification by including pseudopotential for molecules containing first-, second- and third-row representative elements

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

Silva, Cleuton de Souza; Instituto de Ciências Exatas e Tecnologia, Universidade Federal do Amazonas, Campus de Itacoatiara, 69100-021 Itacoatiara, Amazonas; Pereira, Douglas Henrique

2016-05-28

The G4CEP composite method was developed from the respective G4 all-electron version by considering the implementation of compact effective pseudopotential (CEP). The G3/05 test set was used as reference to benchmark the adaptation by treating in this work atoms and compounds from the first and second periods of the periodic table, as well as representative elements of the third period, comprising 440 thermochemical data. G4CEP has not reached a so high level of accuracy as the G4 all-electron theory. G4CEP presented a mean absolute error around 1.09 kcal mol{sup −1}, while the original method presents a deviation corresponding to 0.83more » kcal mol{sup −1}. The similarity of the optimized molecular geometries between G4 and G4CEP indicates that the core-electron effects and basis set adjustments may be pointed out as a significant factor responsible for the large discrepancies between the pseudopotential results and the experimental data, or even that the all-electron calculations are more efficient either in its formulation or in the cancellation of errors. When the G4CEP mean absolute error (1.09 kcal mol{sup −1}) is compared to 1.29 kcal mol{sup −1} from G3CEP, it does not seem so efficient. However, while the G3CEP uncertainty is ±4.06 kcal mol{sup −1}, the G4CEP deviation is ±2.72 kcal mol{sup −1}. Therefore, the G4CEP theory is considerably more reliable than any previous combination of composite theory and pseudopotential, particularly for enthalpies of formation and electron affinities.« less

Evaluation of intervertebral disc cartilaginous endplate structure using magnetic resonance imaging.

PubMed

Moon, Sung M; Yoder, Jonathon H; Wright, Alexander C; Smith, Lachlan J; Vresilovic, Edward J; Elliott, Dawn M

2013-08-01

The cartilaginous endplate (CEP) is a thin layer of hyaline cartilage positioned between the vertebral endplate and nucleus pulposus (NP) that functions both as a mechanical barrier and as a gateway for nutrient transport into the disc. Despite its critical role in disc nutrition and degeneration, the morphology of the CEP has not been well characterized. The objective of this study was to visualize and report observations of the CEP three-dimensional morphology, and quantify CEP thickness using an MRI FLASH (fast low-angle shot) pulse sequence. MR imaging of ex vivo human cadaveric lumbar spine segments (N = 17) was performed in a 7T MRI scanner with sequence parameters that were selected by utilizing high-resolution T1 mapping, and an analytical MRI signal model to optimize image contrast between CEP and NP. The CEP thickness at five locations along the mid-sagittal AP direction (center, 5 mm, 10 mm off-center towards anterior and posterior) was measured, and analyzed using two-way ANOVA and a post hoc Bonferonni test. For further investigation, six in vivo volunteers were imaged with a similar sequence in a 3T MRI scanner. In addition, decalcified and undecalcified histology was performed, which confirmed that the FLASH sequence successfully detected the CEP. CEP thickness determined by MRI in the mid-sagittal plane across all lumbar disc levels and locations was 0.77 ± 0.24 mm ex vivo. The CEP thickness was not different across disc levels, but was thinner toward the center of the disc. This study demonstrates the potential of MRI FLASH imaging for structural quantification of the CEP geometry, which may be developed as a technique to evaluate changes in the CEP with disc degeneration in future applications.

G4CEP: A G4 theory modification by including pseudopotential for molecules containing first-, second- and third-row representative elements.

PubMed

Silva, Cleuton de Souza; Pereira, Douglas Henrique; Custodio, Rogério

2016-05-28

The G4CEP composite method was developed from the respective G4 all-electron version by considering the implementation of compact effective pseudopotential (CEP). The G3/05 test set was used as reference to benchmark the adaptation by treating in this work atoms and compounds from the first and second periods of the periodic table, as well as representative elements of the third period, comprising 440 thermochemical data. G4CEP has not reached a so high level of accuracy as the G4 all-electron theory. G4CEP presented a mean absolute error around 1.09 kcal mol(-1), while the original method presents a deviation corresponding to 0.83 kcal mol(-1). The similarity of the optimized molecular geometries between G4 and G4CEP indicates that the core-electron effects and basis set adjustments may be pointed out as a significant factor responsible for the large discrepancies between the pseudopotential results and the experimental data, or even that the all-electron calculations are more efficient either in its formulation or in the cancellation of errors. When the G4CEP mean absolute error (1.09 kcal mol(-1)) is compared to 1.29 kcal mol(-1) from G3CEP, it does not seem so efficient. However, while the G3CEP uncertainty is ±4.06 kcal mol(-1), the G4CEP deviation is ±2.72 kcal mol(-1). Therefore, the G4CEP theory is considerably more reliable than any previous combination of composite theory and pseudopotential, particularly for enthalpies of formation and electron affinities.

The relationship of physical and chemical conditions of CEP diluent with egg yolk addition to bull spermatozoa quality before and after storage at temperaturof 4-5°C

NASA Astrophysics Data System (ADS)

Ducha, N.; Hariani, D.; Budijastuti, W.

2018-01-01

Storage of semen requires diluent to dilute semen and maintain sperm quality. One of the diluent for bull semen was CEP. The purpose of this study was to assess the association of bull spermatozoa quality with the physical and chemical conditions of CEP diluents with the addition of egg yolk before and after the storage process. The study used Limousin bull with 5 replications. The quality of spermatozoa included motility and viability. Physical and chemical conditions included the pH and osmolarity of the diluent. The motility of spermatozoa was observed under a light microscope with 200 X magnification at 37°C by two people. The viability of spermatozoa was observed under a light microscope with 400 X magnification with nigrosine eosin staining. Data were analyzed with ANOVA and continued Duncan’s test. Dilution pH was measured using pH indicator paper ranging from 6-8. The osmolarity of the diluent was measured by electrical osmolarity. The results showed that the addition of egg yolk in the CEP diluent decreased the pH and increased osmolartitas, but the quality of spermatozoa can be kept up to 8 days of storage. The conclusion in this study was the addition of egg yolk in the CEP diluent provided physical and chemical conditions that can maintain the quality of spermatozoa during storage at a temperature of 4-5 ° C.

Human Cartilage Endplate Permeability Varies with Degeneration and Intervertebral Disc Site

PubMed Central

DeLucca, John F.; Cortes, Daniel H.; Jacobs, Nathan T.; Vresilovic, Edward J.; Duncan, Randall L.; Elliott, Dawn M.

2016-01-01

Despite the critical functions the human cartilage endplate (CEP) plays in the intervertebral disc, little is known about its structural and mechanical properties and their changes with degeneration. Quantifying these changes with degeneration is important for understanding how the CEP contributes to the function and pathology of the disc. Therefore the objectives of this study were to quantify the effect of disc degeneration on human CEP mechanical properties, determine the influence of superior and inferior disc site on mechanics and composition, and simulate the role of collagen fibers in CEP and disc mechanics using a validated finite element model. Confined compression data and biochemical composition data were used in a biphasic-swelling model to calculate compressive extrafibrillar elastic and permeability properties. Tensile properties were obtained by applying published tensile test data to an ellipsoidal fiber distribution. Results showed that with degeneration CEP permeability decreased 50–60% suggesting that transport is inhibited in the degenerate disc. CEP fibers are organized parallel to the vertebrae and nucleus pulposus and may contribute to large shear strains (0.1–0.2) and delamination failure of the CEP commonly seen in herniated disc tissue. Fiber-reinforcement also reduces CEP axial strains thereby enhancing fluid flux by a factor of 1.8. Collectively, these results suggest that the structure and mechanics of the CEP may play critical roles in the solute transport and disc mechanics. PMID:26874969

The Community Eligibility Provision (CEP): "What Does It Mean for Your School or Local Educational Agency?

ERIC Educational Resources Information Center

US Department of Agriculture, 2015

2015-01-01

The Community Eligibility Provision (CEP) is a non-pricing meal service option for schools and school districts in low-income areas. CEP allows the nation's highest poverty schools and districts to serve breakfast and lunch at no cost to all enrolled students without collecting household applications. Instead, schools that adopt CEP are reimbursed…

Enabling interspecies epigenomic comparison with CEpBrowser.

PubMed

Cao, Xiaoyi; Zhong, Sheng

2013-05-01

We developed the Comparative Epigenome Browser (CEpBrowser) to allow the public to perform multi-species epigenomic analysis. The web-based CEpBrowser integrates, manages and visualizes sequencing-based epigenomic datasets. Five key features were developed to maximize the efficiency of interspecies epigenomic comparisons. CEpBrowser is a web application implemented with PHP, MySQL, C and Apache. URL: http://www.cepbrowser.org/.

Long-term maintenance of the carrier-envelope phase coherence of a femtosecond laser.

PubMed

Kim, Eok Bong; Lee, Jae-Hwan; Lee, Won-Kyu; Luu, Tran Trung; Nam, Chang Hee

2010-12-06

The long-term carrier-envelope phase (CEP) coherence of a femtosecond laser with same pulse-to-pulse CEP value, obtained using the direct locking method, is demonstrated by employing a quasi-common-path interferometer (QPI). For the evaluation of the CEP stability, the phase noise properties of a femtosecond laser with the CEP stabilized using a QPI are compared with those obtained using a Mach-Zehnder f-2f interferometer, for which the phase power spectral density and the Allan deviation were calculated from the beat signals of the interferometers. With the improved CEP stability, the long-term CEP coherent signal with an accumulated phase noise well below 1 radian can be maintained for more than 56 hours, i.e., the CEP coherence is preserved without a phase cycle slip for more than 1.6 × 10(13) pulses at a repetition rate of 80 MHz. The relative stability is also estimated to be approximately 1.4 × 10(-22) at a central wavelength of 790 nm.

High passive CEP stability from a few-cycle, tunable NOPA-DFG system for observation of CEP-effects in photoemission.

PubMed

Vogelsang, Jan; Robin, Jörg; Piglosiewicz, Björn; Manzoni, Cristian; Farinello, Paolo; Melzer, Stefan; Feru, Philippe; Cerullo, Giulio; Lienau, Christoph; Groß, Petra

2014-10-20

The investigation of fundamental mechanisms taking place on a femtosecond time scale is enabled by ultrafast pulsed laser sources. Here, the control of pulse duration, center wavelength, and especially the carrier-envelope phase has been shown to be of essential importance for coherent control of high harmonic generation and attosecond physics and, more recently, also for electron photoemission from metallic nanostructures. In this paper we demonstrate the realization of a source of 2-cycle laser pulses tunable between 1.2 and 2.1 μm, and with intrinsic CEP stability. The latter is guaranteed by difference frequency generation between the output pulse trains of two noncollinear optical parametric amplifier stages that share the same CEP variations. The CEP stability is better than 50 mrad over 20 minutes, when averaging over 100 pulses. We demonstrate the good CEP stability by measuring kinetic energy spectra of photoemitted electrons from a single metal nanostructure and by observing a clear variation of the electron yield with the CEP.

Synthesis and application of Pb-MCM-41/ZnNiO2 as a novel mesoporous nanocomposite adsorbent for the decontamination of chloroethyl phenyl sulfide (CEPS)

NASA Astrophysics Data System (ADS)

Sadeghi, Meysam; Yekta, Sina; Ghaedi, Hamed

2017-04-01

In the current research, MCM-41 was successfully prepared by the sol-gel method and lead ions (Pb2+) were loaded in the synthesized MCM-41 mesoporous structure to prepare Pb-MCM-41. The ZnO-NiO nanoparticles (ZnNiO2 NPs) as a type of bimetallic oxides were then dispersed and deposited on the surface of Pb-MCM-41 through indirect method to gain the final Pb-MCM-41/ZnNiO2 nanocomposite adsorbent. The characterization study of samples carried out by SEM-EDAX, AFM, XRD and FTIR techniques. Pb-MCM-41/ZnNiO2 nanocomposite as a destructive adsorbent has been proposed for the first time for the decontamination process of chloroethyl phenyl sulfide (CEPS), a mimic of bis(chloroethyl) sulfide (i.e. sulfur mustard), and were confirmed using GC-FID, GC-MS and FTIR instruments. Besides, the effect of different experimental parameters including contact time, catalyst dose and initial concentration of CEPS on the decontamination efficiency of this agent simulant were also perused. The GC-FID analysis results verified that the maximum decontamination of CEPS was more than 90% yield. The parameters such as: contact time (240 min), adsorbent dose (0.4 g/L), and initial concentration (10 mg/L) were investigated and considered as optimized conditions for the noted reaction. Moreover, the reaction kinetic information was surveyed by employing first order model. The values of the rate constant (k) and half-life (t1/2) were determined as 0.0128 min-1 and 54.1406 min, and 0.0012 min-1 and 577.5 min for CEPS and its hydrolysis/elimination products, respectively. Data demonstrates the role of the hydrolysis and elimination products, i.e. hydroxy ethyl phenyl sulfide (HEPS) and phenyl vinyl sulfide (PVS) in the reaction of CEPS with Pb-MCM-41/ZnNiO2 nanocomposite and GC-MS analysis was exerted to identify and quantify simulant destruction products. It was clarified that Pb-MCM-41/ZnNiO2 nanocomposite gains a high capacity and potential for the effective decontamination of CEPS.

Why Schools Do Not Release ASVAB Scores to Military Recruiters

DTIC Science & Technology

2012-06-08

Career and Technical Education DoD Department of Defense FERPA Family Education Records Protection Act GA Grad...incorporated the CEP. Since the adaptation of career clusters in Career and Technical Education (CTE), a venture funded by the states and the federal...available from career and technical education websites. The ASVAB CEP website provides the ASVAB CEP Fact Sheet and Overview of the ASVAB CEP.

3D Ultrashort TE MRI for Evaluation of Cartilaginous Endplate of Cervical Disk In Vivo: Feasibility and Correlation With Disk Degeneration in T2-Weighted Spin-Echo Sequence.

PubMed

Kim, Yeo Ju; Cha, Jang Gyu; Shin, Yoon Sang; Chaudhari, Akshay S; Suh, Young Ju; Hwan Yoon, Seung; Gold, Garry E

2018-05-01

The purpose of this study was to evaluate the feasibility of 3D ultrashort TE (UTE) MRI in depicting the cartilaginous endplate (CEP) and its abnormalities and to investigate the association between CEP abnormalities and disk degeneration on T2-weighted spin-echo (SE) MR images in cervical disks in vivo. Eight healthy volunteers and 70 patients were examined using 3-T MRI with the 3D UTE cones trajectory technique (TR/TE, 16.1/0.032, 6.6). In the volunteer study, quantitative and qualitative assessments of CEP depiction were conducted for the 3D UTE and T2-weighted SE imaging. In the patient study, CEP abnormalities were analyzed. Intersequence agreement between the images obtained with the first-echo 3D UTE sequence and the images created by subtracting the second-echo from the first-echo 3D UTE sequence (subtracted 3D UTE) and the intraobserver and interobserver agreements for 3D UTE overall were also tested. The CEP abnormalities on the 3D UTE images correlated with the Miyazaki grading of the T2-weighted SE images. In the volunteer study, the CEP was well visualized on 3D UTE images but not on T2-weighted SE images (p < 0.001). In the patient study, for evaluation of CEP abnormalities, intersequence agreements were substantial to almost perfect, intraobserver agreements were substantial to almost perfect, and interobserver agreements were moderate to substantial (p < 0.001). All of the CEP abnormalities correlated with the Miyazaki grade with statistical significance (p < 0.001). Three-dimensional UTE MRI feasibly depicts the CEP and CEP abnormalities, which may be associated with the severity of disk degeneration on T2-weighted SE MRI.

Effective Social Media Practices for Communicating Climate Change Science to Community Leaders

NASA Astrophysics Data System (ADS)

Estrada, M.; DeBenedict, C.; Bruce, L.

2016-12-01

Climate Education Partners (CEP) uses an action research approach to increase climate knowledge and informed decision-making among key influential (KI) leaders in San Diego county. Social media has been one method for disseminating knowledge. During CEP's project years, social media use has proliferated. To capitalize on this trend, CEP iteratively developed a strategic method to engage KIs. First, as with all climate education, CEP identified the audience. Three primary Facebook and Twitter audiences were CEP's internal team, local KIs, and strategic partner organizations. Second, post contents were chosen based on interest to CEP key audiences and followed CEP's communications message triangle, which incorporates the Tripartite Integration Model of Social Influence (TIMSI). This message triangle focuses on San Diegan's valued quality of life, future challenges we face due to the changing climate, and ways in which we are working together to protect our quality of life for future generations. Third, an editorial calendar was created to carefully time posts, which capitalize on when target audiences were using social media most and to maintain consistency. The results of these three actions were significant. Results attained utilizing Facebook and Twitter data, which tracks post reach, total followers/likes, and engagement (likes, comments, mentions, shares). For example we found that specifically mentioning KIs resulted in more re-tweets and resulted in reaching a broader audience. Overall, data shows that CEP's reach to audiences of like-minded individuals and organizations now extends beyond CEP's original local network and reached more than 20,000 accounts on Twitter this year (compared with 460 on Twitter the year before). In summary, through posting and participating in the online conversation strategically, CEP disseminated key educational climate resources and relevant climate change news to educate and engage target audience and amplify our work.

Classification of Lactococcus lactis cell envelope proteinase based on gene sequencing, peptides formed after hydrolysis of milk, and computer modeling.

PubMed

Børsting, M W; Qvist, K B; Brockmann, E; Vindeløv, J; Pedersen, T L; Vogensen, F K; Ardö, Y

2015-01-01

Lactococcus lactis strains depend on a proteolytic system for growth in milk to release essential AA from casein. The cleavage specificities of the cell envelope proteinase (CEP) can vary between strains and environments and whether the enzyme is released or bound to the cell wall. Thirty-eight Lc. lactis strains were grouped according to their CEP AA sequences and according to identified peptides after hydrolysis of milk. Finally, AA positions in the substrate binding region were suggested by the use of a new CEP template based on Streptococcus C5a CEP. Aligning the CEP AA sequences of 38 strains of Lc. lactis showed that 21 strains, which were previously classified as group d, could be subdivided into 3 groups. Independently, similar subgroupings were found based on comparison of the Lc. lactis CEP AA sequences and based on normalized quantity of identified peptides released from αS1-casein and β-casein. A model structure of Lc. lactis CEP based on the crystal structure of Streptococcus C5a CEP was used to investigate the AA positions in the substrate-binding region. New AA positions were suggested, which could be relevant for the cleavage specificity of CEP; however, these could only explain 2 out of 3 found subgroups. The third subgroup could be explained by 1 to 5 AA positions located opposite the substrate binding region. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Human cartilage endplate permeability varies with degeneration and intervertebral disc site.

PubMed

DeLucca, John F; Cortes, Daniel H; Jacobs, Nathan T; Vresilovic, Edward J; Duncan, Randall L; Elliott, Dawn M

2016-02-29

Despite the critical functions the human cartilage endplate (CEP) plays in the intervertebral disc, little is known about its structural and mechanical properties and their changes with degeneration. Quantifying these changes with degeneration is important for understanding how the CEP contributes to the function and pathology of the disc. Therefore the objectives of this study were to quantify the effect of disc degeneration on human CEP mechanical properties, determine the influence of superior and inferior disc site on mechanics and composition, and simulate the role of collagen fibers in CEP and disc mechanics using a validated finite element model. Confined compression data and biochemical composition data were used in a biphasic-swelling model to calculate compressive extrafibrillar elastic and permeability properties. Tensile properties were obtained by applying published tensile test data to an ellipsoidal fiber distribution. Results showed that with degeneration CEP permeability decreased 50-60% suggesting that transport is inhibited in the degenerate disc. CEP fibers are organized parallel to the vertebrae and nucleus pulposus and may contribute to large shear strains (0.1-0.2) and delamination failure of the CEP commonly seen in herniated disc tissue. Fiber-reinforcement also reduces CEP axial strains thereby enhancing fluid flux by a factor of 1.8. Collectively, these results suggest that the structure and mechanics of the CEP may play critical roles in the solute transport and disc mechanics. Copyright © 2016 Elsevier Ltd. All rights reserved.

Decoy receptor 3 down-regulates centrosomal protein 70 kDa specifically in rheumatoid synovial fibroblasts.

PubMed

Fukuda, Koji; Miura, Yasushi; Maeda, Toshihisa; Hayashi, Shinya; Kuroda, Ryosuke

2018-03-01

Decoy receptor 3 (DcR3) competitively binds to Fas ligand, lymphotoxin-related inducible ligand that competes for glycoprotein D binding to herpes virus entry mediator on T cells (LIGHT) and TNF-like ligand 1A (TL1A), thereby preventing their effects. Using a microarray assay, we previously newly identified centrosomal protein 70 kDa (CEP70) as one of the genes whose expression in fibroblast-like synoviocytes from patients with rheumatoid arthritis (RA-FLS) is reduced by DcR3. Here, we investigated the significance of DcR3 regulation of CEP70 for RA-FLS. Synovial samples were obtained from RA patients who had never been treated with biologics and from osteoarthritis (OA) patients. CEP70 mRNA expression was quantified using RT-qPCR analysis. CEP70 protein expression was assessed using immunohistochemical and western blot analyses. CEP70 was expressed predominantly in the superficial lining layer in RA synovial tissue. CEP70 expression was dose-dependently downregulated by DcR3-Fc in RA-FLS but was not downregulated in OA-FLS. TL1A antibody prevented the DcR3-Fc inhibitory effects on CEP70 expression in RA-FLS. These results indicated that DcR3 reduces CEP70 expression in RA-FLS by binding to membrane-bound TL1A and may suppress RA-FLS proliferation. The reduction in CEP70 expression by DcR3/TL1A signaling may control the hyperplasia of RA synovium.

An inherited genetic variant in CEP72 promoter predisposes to vincristine-induced peripheral neuropathy in adults with acute lymphoblastic leukemia

PubMed Central

Stock, Wendy; Diouf, Barthelemy; Crews, Kristine R.; Pei, Deqing; Cheng, Cheng; Laumann, Kristina; Mandrekar, Sumithra J.; Luger, Selina; Advani, Anjali; Stone, Richard M.; Larson, Richard A.; Evans, William E.

2016-01-01

Peripheral neuropathy is a major toxicity of vincristine, yet no strategies exist for identifying at-risk adult patients. We used a case-control design of 48 adults receiving protocol therapy for acute lymphoblastic leukemia (ALL) who developed vincristine-induced neuropathy (NCI Grade 2-4) during treatment, and 48 matched controls who did not develop grade 2-4 neuropathy. Peripheral neuropathy was prospectively graded by NCI criteria. CEP72 promoter genotype (rs924607) was determined using PCR based SNP genotyping. Frequency of the CEP72 T/T genotype was higher in cases (31% vs 10%, p=0.0221) and the incidence of vincristine-induced neuropathy (grades 2-4) was significantly higher in patients homozygous for the CEP72 T/T genotype. 75% of the 20 patients homozygous for the CEP72 T allele developed grade 2-4 neuropathy, compared to 44% of patients with CEP72 CC or CT genotype (p=0.0221). The CEP72 polymorphism can identify adults at increased risk of vincristine-induced peripheral neuropathy. PMID:27618250

Synthesis and structural characterization of carboxyethylpyrrole-modified proteins: mediators of age-related macular degeneration.

PubMed

Lu, Liang; Gu, Xiaorong; Hong, Li; Laird, James; Jaffe, Keeve; Choi, Jaewoo; Crabb, John; Salomon, Robert G

2009-11-01

Protein modifications in which the epsilon-amino group of lysyl residues is incorporated into a 2-(omega-carboxyethyl)pyrrole (CEP) are mediators of age-related macular degeneration (AMD). They promote both angiogenesis into the retina ('wet AMD') and geographic retinal atrophy ('dry AMD'). Blood levels of CEPs are biomarkers for clinical prognosis of the disease. To enable mechanistic studies of their role in promoting AMD, for example, through the activation of B- and T-cells, interaction with receptors, or binding with complement proteins, we developed an efficient synthesis of CEP derivatives, that is especially effective for proteins. The structures of tryptic peptides derived from CEP-modified proteins were also determined. A key finding is that 4,7-dioxoheptanoic acid 9-fluorenylmethyl ester reacts with primary amines to provide 9-fluorenylmethyl esters of CEP-modified proteins that can be deprotected in situ with 1,8-diazabicyclo[5.4.0]undec-7-ene without causing protein denaturation. The introduction of multiple CEP-modifications with a wide variety of CEP:protein ratios is readily achieved using this strategy.

An amorphous silicon photodiode with 2 THz gain-bandwidth product based on cycling excitation process

NASA Astrophysics Data System (ADS)

Yan, Lujiang; Yu, Yugang; Zhang, Alex Ce; Hall, David; Niaz, Iftikhar Ahmad; Raihan Miah, Mohammad Abu; Liu, Yu-Hsin; Lo, Yu-Hwa

2017-09-01

Since impact ionization was observed in semiconductors over half a century ago, avalanche photodiodes (APDs) using impact ionization in a fashion of chain reaction have been the most sensitive semiconductor photodetectors. However, APDs have relatively high excess noise, a limited gain-bandwidth product, and high operation voltage, presenting a need for alternative signal amplification mechanisms of superior properties. As an amplification mechanism, the cycling excitation process (CEP) was recently reported in a silicon p-n junction with subtle control and balance of the impurity levels and profiles. Realizing that CEP effect depends on Auger excitation involving localized states, we made the counter intuitive hypothesis that disordered materials, such as amorphous silicon, with their abundant localized states, can produce strong CEP effects with high gain and speed at low noise, despite their extremely low mobility and large number of defects. Here, we demonstrate an amorphous silicon low noise photodiode with gain-bandwidth product of over 2 THz, based on a very simple structure. This work will impact a wide range of applications involving optical detection because amorphous silicon, as the primary gain medium, is a low-cost, easy-to-process material that can be formed on many kinds of rigid or flexible substrates.

Characterization of Phenotypic and Transcriptional Differences in Human Pluripotent Stem Cells under 2D and 3D Culture Conditions.

PubMed

Kamei, Ken-Ichiro; Koyama, Yoshie; Tokunaga, Yumie; Mashimo, Yasumasa; Yoshioka, Momoko; Fockenberg, Christopher; Mosbergen, Rowland; Korn, Othmar; Wells, Christine; Chen, Yong

2016-11-01

Human pluripotent stem cells hold great promise for applications in drug discovery and regenerative medicine. Microfluidic technology is a promising approach for creating artificial microenvironments; however, although a proper 3D microenvironment is required to achieve robust control of cellular phenotypes, most current microfluidic devices provide only 2D cell culture and do not allow tuning of physical and chemical environmental cues simultaneously. Here, the authors report a 3D cellular microenvironment plate (3D-CEP), which consists of a microfluidic device filled with thermoresponsive poly(N-isopropylacrylamide)-β-poly(ethylene glycol) hydrogel (HG), which enables systematic tuning of both chemical and physical environmental cues as well as in situ cell monitoring. The authors show that H9 human embryonic stem cells (hESCs) and 253G1 human induced pluripotent stem cells in the HG/3D-CEP system maintain their pluripotent marker expression under HG/3D-CEP self-renewing conditions. Additionally, global gene expression analyses are used to elucidate small variations among different test environments. Interestingly, the authors find that treatment of H9 hESCs under HG/3D-CEP self-renewing conditions results in initiation of entry into the neural differentiation process by induction of PAX3 and OTX1 expression. The authors believe that this HG/3D-CEP system will serve as a versatile platform for developing targeted functional cell lines and facilitate advances in drug screening and regenerative medicine. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Prediction of retail beef yield and fat content from live animal and carcass measurements in Nellore cattle.

PubMed

Sakamoto, L S; Mercadante, M E Z; Bonilha, S F M; Branco, R H; Bonilha, E F M; Magnani, E

2014-11-01

Data from 156 Nellore males were used to develop equations for the prediction of retail beef yield and carcass fat content, expressed as kilograms and as a percentage, from live animal and carcass measurements. Longissimus muscle area and backfat and rump fat thickness were measured by ultrasound up to 5 d before slaughter and fasted live weight was determined 1 d before slaughter. The same traits were obtained after slaughter. The carcass edible portion (CEP in kg and CEP% in percentage; n = 116) was calculated by the sum of the edible portions of primal cuts: hindquarter, forequarter, and spare ribs. Trimmable fat from the carcass boning process, with the standardization of about 3 mm of fat on retail beef, was considered to be representative of carcass fat content. Most of the variation in CEP was explained by fasted live weight or carcass weight (R(2) of 0.92 and 0.96); the same occurred for CEP% (R(2) of 0.15 and 0.13), and for CEP, the inclusion of LM area and fat thickness reduced the equation bias (lower value of Mallow's Cp statistics). For trimmable fat, most variation could be explained by weight or rump fat thickness. In general, the equations developed from live animal measurements showed a predictive power similar to the equations using carcass measurements. In all cases, the traits expressed as kilograms were better predicted (R(2) of 0.39 to 0.96) than traits expressed as a percentage (R(2) of 0.08 to 0.42).

Basal exon skipping and genetic pleiotropy: A predictive model of disease pathogenesis.

PubMed

Drivas, Theodore G; Wojno, Adam P; Tucker, Budd A; Stone, Edwin M; Bennett, Jean

2015-06-10

Genetic pleiotropy, the phenomenon by which mutations in the same gene result in markedly different disease phenotypes, has proven difficult to explain with traditional models of disease pathogenesis. We have developed a model of pleiotropic disease that explains, through the process of basal exon skipping, how different mutations in the same gene can differentially affect protein production, with the total amount of protein produced correlating with disease severity. Mutations in the centrosomal protein of 290 kDa (CEP290) gene are associated with a spectrum of phenotypically distinct human diseases (the ciliopathies). Molecular biologic examination of CEP290 transcript and protein expression in cells from patients carrying CEP290 mutations, measured by quantitative polymerase chain reaction and Western blotting, correlated with disease severity and corroborated our model. We show that basal exon skipping may be the mechanism underlying the disease pleiotropy caused by CEP290 mutations. Applying our model to a different disease gene, CC2D2A (coiled-coil and C2 domains-containing protein 2A), we found that the same correlations held true. Our model explains the phenotypic diversity of two different inherited ciliopathies and may establish a new model for the pathogenesis of other pleiotropic human diseases. Copyright © 2015, American Association for the Advancement of Science.

Cytoskeleton disorder and cell cycle arrest may be associated with the alteration of protein CEP135 by microgravity

NASA Astrophysics Data System (ADS)

Hang, Xiaoming; Sun, Yeqing; Wu, Di; Li, Yixiao; Liu, Zhiyuan

In the past decades, alterations in the morphology, cytoskeleton and cell cycle have been observed in cells in vitro under microgravity conditions. But the underlying mechanisms are not absolutely identified yet. Our previous study on proteomic and microRNA expression profiles of zebrafish embryos exposed to simulated-microgravity has demonstrated a serial of microgravity-sensitive molecules. Centrosomal protein of 135 kDa (CEP135) was found down-regulated, but the mRNA expression level of it was up-regulated in zebrafish embryos after simulated-microgravity. However, the functional study on CEP135 is very limited and it has not been cloned in zebrafish till now. In this study, we try to determine whether the cytoskeleton disorder and cell cycle arrest is associated with the alteration of CEP135 by microgravity. Full-length cDNA of cep135 gene was firstly cloned from mitosis phase of ZF4. The sequence was analyzed and the phylogenetic tree was constructed based on the similarity to other species. Zebrafish embryonic cell line ZF4 were exposed to simulated microgravity for 24 and 48 hours, using a rotary cell culture system (RCCS) designed by NASA. Quantitative analysis by western blot showed that CEP135 expression level was significantly decreased two times after 24 hour simulated microgravity. Cell cycle detection by flow cytometer indicated ZF4 cells were blocked in G1 phase after 24 and 48 hour simulated microgravity. Moreover, double immunostained ZF4 cells with anti-tubulin and anti-CEP135antibodies demonstrated simulated microgravity could lead to cytoskeleton disorder and CEP135 abnormality. Further investigations are currently being carried out to determine whether knockdown and over-expression of CEP135 will modulate cytoskeleton and cell cycle. In vitro data in combination within vivo results might, at least in part, explain the dramatic effects of microgravity. Key Words: microgravity; CEP135; Cytoskeleton disorder; G1 arrest; ZF4 cell line

CEP-26401 (irdabisant), a potent and selective histamine H₃ receptor antagonist/inverse agonist with cognition-enhancing and wake-promoting activities.

PubMed

Raddatz, Rita; Hudkins, Robert L; Mathiasen, Joanne R; Gruner, John A; Flood, Dorothy G; Aimone, Lisa D; Le, Siyuan; Schaffhauser, Hervé; Duzic, Emir; Gasior, Maciej; Bozyczko-Coyne, Donna; Marino, Michael J; Ator, Mark A; Bacon, Edward R; Mallamo, John P; Williams, Michael

2012-01-01

CEP-26401 [irdabisant; 6-{4-[3-((R)-2-methyl-pyrrolidin-1-yl)-propoxy]-phenyl}-2H-pyridazin-3-one HCl] is a novel, potent histamine H₃ receptor (H₃R) antagonist/inverse agonist with drug-like properties. High affinity of CEP-26401 for H₃R was demonstrated in radioligand binding displacement assays in rat brain membranes (K(i) = 2.7 ± 0.3 nM) and recombinant rat and human H₃R-expressing systems (K(i) = 7.2 ± 0.4 and 2.0 ± 1.0 nM, respectively). CEP-26401 displayed potent antagonist and inverse agonist activities in [³⁵S]guanosine 5'-O-(γ-thio)triphosphate binding assays. After oral dosing of CEP-26401, occupancy of H₃R was estimated by the inhibition of ex vivo binding in rat cortical slices (OCC₅₀ = 0.1 ± 0.003 mg/kg), and antagonism of the H₃R agonist R-α-methylhistamine- induced drinking response in the rat dipsogenia model was demonstrated in a similar dose range (ED₅₀ = 0.06 mg/kg). CEP-26401 improved performance in the rat social recognition model of short-term memory at doses of 0.01 to 0.1 mg/kg p.o. and was wake-promoting at 3 to 30 mg/kg p.o. In DBA/2NCrl mice, CEP-26401 at 10 and 30 mg/kg i.p. increased prepulse inhibition (PPI), whereas the antipsychotic risperidone was effective at 0.3 and 1 mg/kg i.p. Coadministration of CEP-26401 and risperidone at subefficacious doses (3 and 0.1 mg/kg i.p., respectively) increased PPI. These results demonstrate potent behavioral effects of CEP-26401 in rodent models and suggest that this novel H₃R antagonist may have therapeutic utility in the treatment of cognitive and attentional disorders. CEP-26401 may also have therapeutic utility in treating schizophrenia or as adjunctive therapy to approved antipsychotics.

CEP152 is a genome maintenance protein disrupted in Seckel syndrome

PubMed Central

Kalay, Ersan; Yigit, Gökhan; Aslan, Yakup; Brown, Karen E; Pohl, Esther; Bicknell, Louise S; Kayserili, Hülya; Li, Yun; Tüysüz, Beyhan; Nürnberg, Gudrun; Kiess, Wieland; Koegl, Manfred; Baessmann, Ingelore; Buruk, Kurtulus; Toraman, Bayram; Kayipmaz, Saadettin; Kul, Sibel; Ikbal, Mevlit; Turner, Daniel J; Taylor, Martin S; Aerts, Jan; Scott, Carol; Milstein, Karen; Dollfus, Helene; Wieczorek, Dagmar; Brunner, Han G; Hurles, Matthew; Jackson, Andrew P; Rauch, Anita; Nürnberg, Peter; Karagüzel, Ahmet; Wollnik, Bernd

2012-01-01

Functional impairment of DNA damage response pathways leads to increased genomic instability. Here we describe the centrosomal protein CEP152 as a new regulator of genomic integrity and cellular response to DNA damage. Using homozygosity mapping and exome sequencing, we identified CEP152 mutations in Seckel syndrome and showed that impaired CEP152 function leads to accumulation of genomic defects resulting from replicative stress through enhanced activation of ATM signaling and increased H2AX phosphorylation. PMID:21131973

CEP250 mutations associated with mild cone-rod dystrophy and sensorineural hearing loss in a Japanese family.

PubMed

Kubota, Daiki; Gocho, Kiyoko; Kikuchi, Sachiko; Akeo, Keiichiro; Miura, Masahiro; Yamaki, Kunihiko; Takahashi, Hiroshi; Kameya, Shuhei

2018-05-02

CEP250 encodes the C-Nap1 protein which belongs to the CEP family of proteins. C-Nap1 has been reported to be expressed in the photoreceptor cilia and is known to interact with other ciliary proteins. Mutations of CEP250 cause atypical Usher syndrome which is characterized by early-onset sensorineural hearing loss (SNHL) and a relatively mild retinitis pigmentosa. This study tested the hypothesis that the mild cone-rod dystrophy (CRD) and SNHL in a non-consanguineous Japanese family was caused by CEP250 mutations. Detailed ophthalmic and auditory examinations were performed on the proband and her family members. Whole exome sequencing (WES) was used on the DNA obtained from the proband. Electrophysiological analysis revealed a mild CRD in two family members. Adaptive optics (AO) imaging showed reduced cone density around the fovea. Auditory examinations showed a slight SNHL in both patients. WES of the proband identified compound heterozygous variants c.361C>T, p.R121*, and c.562C>T, p.R188* in CEP250. The variants were found to co-segregate with the disease in five members of the family. The variants of CEP250 are both null variants and according to American College of Medical Genetics and Genomics (ACMG) standards and guideline, these variants are classified into the very strong category (PVS1). The criteria for both alleles will be pathogenic. Our data indicate that mutations of CEP250 can cause mild CRD and SNHL in Japanese patients. Because the ophthalmological phenotypes were very mild, high-resolution retinal imaging analysis, such as AO, will be helpful in diagnosing CEP250-associated disease.

RsaM: a transcriptional regulator of Burkholderia spp. with novel fold

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

Michalska, Karolina; Chhor, Gekleng; Clancy, Shonda

2014-07-04

Burkholderia cepacia complex (Bcc) is a set of closely related bacterial species that are notorious pathogens of cystic fibrosis patients, responsible for life-threatening lung infections. Expression of several virulence factors of Bcc is controlled by a mechanism known as quorum sensing (QS). QS is a means of bacterial communication used to coordinate gene expression in a cell-density-dependent manner. The system involves the production of diffusible signaling molecules (N-acyl-L-homoserine lactones, AHLs), that bind to cognate transcriptional regulators and influence their ability to regulate gene expression. One such system that is highly conserved in Bcc consists of CepI and CepR. CepI ismore » AHL synthase, while CepR is an AHL-dependent transcription factor. In most members of the Bcc group, the cepI and cepR genes are divergently transcribed and separated by additional genes. One of them, bcam1869, encodes the BcRsaM protein, which was recently postulated to modulate the abundance or activity of CepI or CepR. Here we show the crystal structure of BcRsaM from B. cenocepacia J2315. It is a single-domain protein with unique topology and presents a novel fold. The protein is a dimer in the crystal and in solution. This regulator has no known DNA binding motifs and direct binding of BcRsaM to the cepI promoter could not be detected in in vitro assays. Therefore, we propose that the modulatory action of RsaM might result from interactions with other components of the QS machinery rather than from direct association with the DNA promoter.« less

Simulated-microgravity induced G2/M arrest in zebrafish embryonic cell is regulated by dre-miR-22a and its target cep135

NASA Astrophysics Data System (ADS)

Hang, Xiaoming; Sun, Yeqing; Wu, Di; Li, Yixiao; Wang, Ruonan

2016-07-01

Microgravity has been recognized as a major environmental factor that can induce a number of adverse effects such as bone loss, skeletal muscle atrophy, cardiovascular problems and immune system dysregulation, etc. The underlying mechanisms are not absolutely identified yet. Our previous study demonstrated centrosomal protein of 135 kDa (CEP135) might be a microgravity sensitive molecule. In this study, the expression and regulation of CEP135 and its possible roles in cell cycle regulation under simulated microgravity (SMG) condition were investigated. SMG can induce significant increasing of cep135 in zebrafish embryos, detected by both in situ hybridization and RT-qPCR, while CEP135 protein level was significantly decreased, tested by western blot. The similar results were also obtained in zebrafish embryonic cells (ZF4) exposed to SMG. Accordingly, the expression level of dre-miR-22a, which might be the potential miRNA for targeting cep135, was significantly increased in SMG exposed ZF4 cells. By combining the results obtained from transfection and dual luciferase reporter assay, we firstly confirmed that dre-miR-22a regulated the expression of cep135 in ZF4 cells. Further investigation on cell cycle demonstrated SMG induced a significant arrest in G2/M phase. Transfection of dre-miR-22a also induced G2/M arrest in ZF4 cells. These results suggest that SMG induced G2/M arrest in ZF4 cells is via cep135, while dre-miR-22a plays a key role in modulating this effect. Key Words: Simulated-microgravity; cep135; dre-miR-22a; G2/M arrest; zebrafish embryonic cell

CEP63 deficiency promotes p53-dependent microcephaly and reveals a role for the centrosome in meiotic recombination.

PubMed

Marjanović, Marko; Sánchez-Huertas, Carlos; Terré, Berta; Gómez, Rocío; Scheel, Jan Frederik; Pacheco, Sarai; Knobel, Philip A; Martínez-Marchal, Ana; Aivio, Suvi; Palenzuela, Lluís; Wolfrum, Uwe; McKinnon, Peter J; Suja, José A; Roig, Ignasi; Costanzo, Vincenzo; Lüders, Jens; Stracker, Travis H

2015-07-09

CEP63 is a centrosomal protein that facilitates centriole duplication and is regulated by the DNA damage response. Mutations in CEP63 cause Seckel syndrome, a human disease characterized by microcephaly and dwarfism. Here we demonstrate that Cep63-deficient mice recapitulate Seckel syndrome pathology. The attrition of neural progenitor cells involves p53-dependent cell death, and brain size is rescued by the deletion of p53. Cell death is not the result of an aberrant DNA damage response but is triggered by centrosome-based mitotic errors. In addition, Cep63 loss severely impairs meiotic recombination, leading to profound male infertility. Cep63-deficient spermatocytes display numerical and structural centrosome aberrations, chromosome entanglements and defective telomere clustering, suggesting that a reduction in centrosome-mediated chromosome movements underlies recombination failure. Our results provide novel insight into the molecular pathology of microcephaly and establish a role for the centrosome in meiotic recombination.

CEP63 deficiency promotes p53-dependent microcephaly and reveals a role for the centrosome in meiotic recombination

PubMed Central

Marjanović, Marko; Sánchez-Huertas, Carlos; Terré, Berta; Gómez, Rocío; Scheel, Jan Frederik; Pacheco, Sarai; Knobel, Philip A.; Martínez-Marchal, Ana; Aivio, Suvi; Palenzuela, Lluís; Wolfrum, Uwe; McKinnon, Peter J.; Suja, José A.; Roig, Ignasi; Costanzo, Vincenzo; Lüders, Jens; Stracker, Travis H.

2015-01-01

CEP63 is a centrosomal protein that facilitates centriole duplication and is regulated by the DNA damage response. Mutations in CEP63 cause Seckel syndrome, a human disease characterized by microcephaly and dwarfism. Here we demonstrate that Cep63 deficient mice recapitulate Seckel syndrome pathology. The attrition of neural progenitor cells involves p53-dependent cell death and brain size is rescued by the deletion of p53. Cell death is not the result of an aberrant DNA damage response but is triggered by centrosome-based mitotic errors. In addition, Cep63 loss severely impairs meiotic recombination, leading to profound male infertility. Cep63 deficient spermatocytes display numerical and structural centrosome aberrations, chromosome entanglements and defective telomere clustering, suggesting that a reduction in centrosome-mediated chromosome movements underlies recombination failure. Our results provide novel insight into the molecular pathology of microcephaly and establish a role for the centrosome in meiotic recombination. PMID:26158450

STED nanoscopy of the centrosome linker reveals a CEP68-organized, periodic rootletin network anchored to a C-Nap1 ring at centrioles.

PubMed

Vlijm, Rifka; Li, Xue; Panic, Marko; Rüthnick, Diana; Hata, Shoji; Herrmannsdörfer, Frank; Kuner, Thomas; Heilemann, Mike; Engelhardt, Johann; Hell, Stefan W; Schiebel, Elmar

2018-03-06

The centrosome linker proteins C-Nap1, rootletin, and CEP68 connect the two centrosomes of a cell during interphase into one microtubule-organizing center. This coupling is important for cell migration, cilia formation, and timing of mitotic spindle formation. Very little is known about the structure of the centrosome linker. Here, we used stimulated emission depletion (STED) microscopy to show that each C-Nap1 ring at the proximal end of the two centrioles organizes a rootletin ring and, in addition, multiple rootletin/CEP68 fibers. Rootletin/CEP68 fibers originating from the two centrosomes form a web-like, interdigitating network, explaining the flexible nature of the centrosome linker. The rootletin/CEP68 filaments are repetitive and highly ordered. Staggered rootletin molecules (N-to-N and C-to-C) within the filaments are 75 nm apart. Rootletin binds CEP68 via its C-terminal spectrin repeat-containing region in 75-nm intervals. The N-to-C distance of two rootletin molecules is ∼35 to 40 nm, leading to an estimated minimal rootletin length of ∼110 nm. CEP68 is important in forming rootletin filaments that branch off centrioles and to modulate the thickness of rootletin fibers. Thus, the centrosome linker consists of a vast network of repeating rootletin units with C-Nap1 as ring organizer and CEP68 as filament modulator. Copyright © 2018 the Author(s). Published by PNAS.

Molded Communication Earplugs in Military Aviation.

PubMed

Lahtinen, Taija M M; Leino, Tuomo K

2015-09-01

Radio communication remains important for the delivery of safety-critical information in military aviation. Pilots are exposed to high noise levels. Noise attenuation provided by certain helmets is not sufficient, and resulting noise exposure can deteriorate operational effectiveness and flight safety. A need for hearing protection that enables efficient communication is obvious, especially for fighter and helicopter pilots. One possible solution for this issue is molded communication earplugs (m-CEP). Data about the advantages and disadvantages of m-CEPs are limited. To determine the usage rates, advantages, disadvantages and pilot opinions about m-CEPs, an anonymous survey study including 31 questions was conducted in fighter, fighter trainer, helicopter, and transport aircraft units of the Finnish Defense Forces. Of the pilots who responded, 136 (93%) had used or tried m-CEPs and 90 (62%) were currently using them. There are many benefits to m-CEPs: they seem to enhance experienced speech intelligibility, since 85% of the pilots who had experience about them reported improved speech intelligibility under difficult hearing conditions, and 93% would recommend them to other pilots. It seems m-CEPs provide equal benefits to pilots with and without current hearing problems. They were also considered better than previously used hearing protectors. Still, problems were common: 82% of the pilots reported m-CEP related drawbacks, of which technical problems and discomfort issues were the most prevalent. Most military pilots hold a positive opinion on m-CEPs and are willing to recommend their use. Technical problems and discomfort issues are, however, relatively common.

Congenital extrahepatic portosystemic shunt: an underdiagnosed but treatable cause of hepatopulmonary syndrome.

PubMed

Fu, Lijun; Wang, Qian; Wu, Jinjin; Guo, Ying; Huang, Meirong; Liu, Tingliang; Chen, Qimin; Li, Fen

2016-02-01

Congenital extrahepatic portosystemic shunt (CEPS) is a rare malformation of the mesenteric vasculature, which may lead to severe complications. In this report, we describe a case series of three children with type II CEPS (presenting as hypoxemia) and hepatopulmonary syndrome (HPS). The first patient was a 4-year-old male who did not receive any specific treatment and subsequently died of brain abscess 5 years after the diagnosis. The second patient was a 10-year-old female with a 5-year history of cyanosis and dyspnea on exertion. She had partial regression of hypoxemia and improved exercise tolerance at 8 months after a surgical shunt closure. The third patient was a 4-year-old male with a 3-year history of cyanosis and decreased exercise tolerance. He had full regression of hypoxemia at 3 months after a transcatheter shunt closure. These results indicate that CEPS may present in children with unexplained hypoxemia, which may lead to devastating clinical consequences. Closure of portosystemic shunts may result in resolution of HPS in type II CEPS and the length of period for resolution varies depending on the severity of HPS. Congenital extrahepatic portosystemic shunt (CEPS) is a rare cause of hepatopulmonary syndrome (HPS). There have been few reports in the literature about the management and outcome of HPS in children with CEPS. CEPS may present in children with unexplained hypoxemia, which may lead to devastating clinical consequences. Closure of portosystemic shunts may result in resolution of HPS in type II CEPS.

Spindle formation in the mouse embryo requires Plk4 in the absence of centrioles.

PubMed

Coelho, Paula A; Bury, Leah; Sharif, Bedra; Riparbelli, Maria G; Fu, Jingyan; Callaini, Giuliano; Glover, David M; Zernicka-Goetz, Magdalena

2013-12-09

During the first five rounds of cell division in the mouse embryo, spindles assemble in the absence of centrioles. Spindle formation initiates around chromosomes, but the microtubule nucleating process remains unclear. Here we demonstrate that Plk4, a protein kinase known as a master regulator of centriole formation, is also essential for spindle assembly in the absence of centrioles. Depletion of maternal Plk4 prevents nucleation and growth of microtubules and results in monopolar spindle formation. This leads to cytokinesis failure and, consequently, developmental arrest. We show that Plk4 function depends on its kinase activity and its partner protein, Cep152. Moreover, tethering Cep152 to cellular membranes sequesters Plk4 and is sufficient to trigger spindle assembly from ectopic membranous sites. Thus, the Plk4-Cep152 complex has an unexpected role in promoting microtubule nucleation in the vicinity of chromosomes to mediate bipolar spindle formation in the absence of centrioles. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Diverse Peptide Hormones Affecting Root Growth Identified in the Medicago truncatula Secreted Peptidome.

PubMed

Patel, Neha; Mohd-Radzman, Nadiatul A; Corcilius, Leo; Crossett, Ben; Connolly, Angela; Cordwell, Stuart J; Ivanovici, Ariel; Taylor, Katia; Williams, James; Binos, Steve; Mariani, Michael; Payne, Richard J; Djordjevic, Michael A

2018-01-01

Multigene families encoding diverse secreted peptide hormones play important roles in plant development. A need exists to efficiently elucidate the structures and post-translational-modifications of these difficult-to-isolate peptide hormones in planta so that their biological functions can be determined. A mass spectrometry and bioinformatics approach was developed to comprehensively analyze the secreted peptidome of Medicago hairy root cultures and xylem sap. We identified 759 spectra corresponding to the secreted products of twelve peptide hormones including four CEP ( C -TERMINALLY E NCODED P EPTIDE), two CLE ( CL V3/ E NDOSPERM SURROUNDING REGION RELATED) and six XAP ( X YLEM SAP A SSOCIATED P EPTIDE) peptides. The MtCEP1, MtCEP2, MtCEP5 and MtCEP8 peptides identified differed in post-translational-modifications. Most were hydroxylated at conserved proline residues but some MtCEP1 derivatives were tri-arabinosylated. In addition, many CEP peptides possessed unexpected N - and C -terminal extensions. The pattern of these extensions suggested roles for endo- and exoproteases in CEP peptide maturation. Longer than expected, hydroxylated and homogeneously modified mono- and tri-arabinosylated CEP peptides corresponding to their in vivo structures were chemically synthesized to probe the effect of these post-translational-modifications on function. The ability of CEP peptides to elevate root nodule number was increased by hydroxylation at key positions. MtCEP1 peptides with N -terminal extensions or with tri-arabinosylation modification, however, were unable to impart increased nodulation. The MtCLE5 and MtCLE17 peptides identified were of precise size, and inhibited main root growth and increased lateral root number. Six XAP peptides, each beginning with a conserved DY sulfation motif, were identified including MtXAP1a, MtXAP1b, MtXAP1c, MtXAP3, MtXAP5 and MtXAP7. MtXAP1a and MtXAP5 inhibited lateral root emergence. Transcriptional analyses demonstrated peptide hormone gene expression in the root vasculature and tip. Since hairy roots can be induced on many plants, their corresponding root cultures may represent ideal source materials to efficiently identify diverse peptide hormones in vivo in a broad range of species. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

New image-processing and noise-reduction software reduces radiation dose during complex endovascular procedures.

PubMed

Kirkwood, Melissa L; Guild, Jeffrey B; Arbique, Gary M; Tsai, Shirling; Modrall, J Gregory; Anderson, Jon A; Rectenwald, John; Timaran, Carlos

2016-11-01

A new proprietary image-processing system known as AlluraClarity, developed by Philips Healthcare (Best, The Netherlands) for radiation-based interventional procedures, claims to lower radiation dose while preserving image quality using noise-reduction algorithms. This study determined whether the surgeon and patient radiation dose during complex endovascular procedures (CEPs) is decreased after the implementation of this new operating system. Radiation dose to operators, procedure type, reference air kerma, kerma area product, and patient body mass index were recorded during CEPs on two Philips Allura FD 20 fluoroscopy systems with and without Clarity. Operator dose during CEPs was measured using optically stimulable, luminescent nanoDot (Landauer Inc, Glenwood, Ill) detectors placed outside the lead apron at the left upper chest position. nanoDots were read using a microStar ii (Landauer Inc) medical dosimetry system. For the CEPs in the Clarity group, the radiation dose to surgeons was also measured by the DoseAware (Philips Healthcare) personal dosimetry system. Side-by-side measurements of DoseAware and nanoDots allowed for cross-calibration between systems. Operator effective dose was determined using a modified Niklason algorithm. To control for patient size and case complexity, the average fluoroscopy dose rate and the dose per radiographic frame were adjusted for body mass index differences and then compared between the groups with and without Clarity by procedure. Additional factors, for example, physician practice patterns, that may have affected operator dose were inferred by comparing the ratio of the operator dose to procedural kerma area product with and without Clarity. A one-sided Wilcoxon rank sum test was used to compare groups for radiation doses, reference air kermas, and operating practices for each procedure type. The analysis included 234 CEPs; 95 performed without Clarity and 139 with Clarity. Practice patterns of operators during procedures with and without Clarity were not significantly different. For all cases, procedure radiation dose to the patient and the primary and assistant operators were significantly decreased in the Clarity group by 60% compared with the non-Clarity group. By procedure type, fluorography dose rates decreased from 44% for fenestrated endovascular repair and up to 70% with lower extremity interventions. Fluoroscopy dose rates also significantly decreased, from about 37% to 47%, depending on procedure type. The AlluraClarity system reduces the patient and primary operator's radiation dose by more than half during CEPs. This feature appears to be an effective tool in lowering the radiation dose while maintaining image quality. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Cold-evoked potentials - Ready for clinical use?

PubMed

Hüllemann, P; Nerdal, A; Binder, A; Helfert, S; Reimer, M; Baron, R

2016-11-01

Cold-evoked potentials (CEPs) are known to assess the integrity of A-delta fibres and the spinothalamic tract. Nevertheless, the clinical value was not investigated previously. The aim of this study was to measure CEPs in 16 healthy subjects from the face, hand and foot sole and to investigate whether CEPs reliably detect A-delta fibre abnormalities. Swift cold stimuli were applied to the skin with a commercially available thermode, which cooled down from 30 to 25 °C in approximately 0.5 s. CEP latencies (N1, N2 and P2) and amplitudes (N1, N2/P2) were recorded with EEG. Reversible A-fibre function loss was induced by applying a selective A-fibre block at the superficial radial nerve. In all 16 subjects CEPs could be recorded from all locations; N2, P2 mean latencies were 276.4 ± 38.9 and 389.8 ± 52.5 (face), 318.6 ± 31.6 ms and 477.7 ± 43.6 (hand), and 627.6 ± 84.4 and 774.2 ± 94.0 (foot sole). N2/P2 amplitudes were 10.7 ± 4.1, 11.3 ± 4.1 and 7.5 ± 4.1 μV. During A-fibre block no CEPs were detectable in the grand average, which restored 10 min after block removal. CEPs were reliably recorded in healthy subjects at the hand, face and foot. Experimentally induced reversible A-delta fibre function loss was detected by CEPs. Functional recovery was assessed as well. This study is basis for further CEP evaluation studies and might be the first step for implementing CEPs in clinical routine for the early diagnosis of small-fibre disease. WHAT DOES THIS STUDY ADD?: Cold-evoked potentials are capable of reliably measuring A-delta fibre integrity, loss of function and functional recovery in healthy subjects, which is an essential prerequisite for diagnostic use in patients with small-fibre disease. © 2016 European Pain Federation - EFIC®.

Mechanisms for the cooling of the central eastern Pacific

NASA Astrophysics Data System (ADS)

Liu, Chunlei; Allan, Richard

2017-04-01

The sea surface temperature variation over the Central Eastern Pacific (CEP) controls the global mean surface temperature variation (Kosaka and Xie, 2013). The regional cooling over CEP is directly linked to the surface warming slowdown in last twenty years. It is important to understand the mechanisms of the CEP cooling in the warming climate in order to have a robust prediction of the future climate change. Previous studies showed the CEP cooling is related to the pronounced strengthening in Pacific trade winds over the past two decades, which is sufficient to account for the cooling of the CEP and a substantial slowdown in surface warming through increased subsurface ocean heat uptake in the Pacific shallow overturning cells and equatorial upwelling in the CEP (England et al., 2014). By analysing the cloud data, Zhou et al. (2016) showed the increase of the lower cloud cover (LCC) over the CEP area contributed to the cooling, resulting in positive local feedback and negative global feedback. Using the data from observations, ERA-Interim reanalysis and atmospheric climate simulations, our study shows that the increasing Latent Heat (LH) also plays an important role in the CEP cooling (Liu et al., 2015). After the sensitivity test using the bulk formula, it showed that both wind and total column water vapour content contribute to the cooling trends of the SST in CEP. The observed trends of the wind and LH in CEP also confirmed this. England et al. (2014) Recent intensification of wind-driven circulation in the Pacific and the ongoing warming hiatus, Nat. Clim. Change, 4, 222-227, doi:10.1038/nclimate2106. Kosaka, Y., and S. P. Xie (2013), Recent global-warming hiatus tied to equatorial Pacific surface cooling, Nature, 501, 403-407, doi:10.1038/nature12534. Liu et al. (2015) Combining satellite observations and reanalysis energy transports to estimate global net surface energy fluxes 1985-2012. J. Geophys. Res. , Atmospheres. ISSN 2169-8996 doi: 10.1002/2015JD023264. Zhou et al. (2016) Impact of decadal cloud variations on the Earth's energy budget, Nature Geoscience 9, 871-874 (2016) doi:10.1038/ngeo2828.

Conserving analyst attention units: use of multi-agent software and CEP methods to assist information analysis

NASA Astrophysics Data System (ADS)

Rimland, Jeffrey; McNeese, Michael; Hall, David

2013-05-01

Although the capability of computer-based artificial intelligence techniques for decision-making and situational awareness has seen notable improvement over the last several decades, the current state-of-the-art still falls short of creating computer systems capable of autonomously making complex decisions and judgments in many domains where data is nuanced and accountability is high. However, there is a great deal of potential for hybrid systems in which software applications augment human capabilities by focusing the analyst's attention to relevant information elements based on both a priori knowledge of the analyst's goals and the processing/correlation of a series of data streams too numerous and heterogeneous for the analyst to digest without assistance. Researchers at Penn State University are exploring ways in which an information framework influenced by Klein's (Recognition Primed Decision) RPD model, Endsley's model of situational awareness, and the Joint Directors of Laboratories (JDL) data fusion process model can be implemented through a novel combination of Complex Event Processing (CEP) and Multi-Agent Software (MAS). Though originally designed for stock market and financial applications, the high performance data-driven nature of CEP techniques provide a natural compliment to the proven capabilities of MAS systems for modeling naturalistic decision-making, performing process adjudication, and optimizing networked processing and cognition via the use of "mobile agents." This paper addresses the challenges and opportunities of such a framework for augmenting human observational capability as well as enabling the ability to perform collaborative context-aware reasoning in both human teams and hybrid human / software agent teams.

Intratumor heterogeneity predicts metastasis of triple-negative breast cancer.

PubMed

Yang, Fang; Wang, Yucai; Li, Quan; Cao, Lulu; Sun, Zijia; Jin, Juan; Fang, Hehui; Zhu, Aiyu; Li, Yan; Zhang, Wenwen; Wang, Yanru; Xie, Hui; Gustafsson, Jan-Åke; Wang, Shui; Guan, Xiaoxiang

2017-09-01

Even with the identical clinicopathological features, the ability for metastasis is vastly different among triple-negative breast cancer (TNBC) patients. Intratumor heterogeneity (ITH), which is common in breast cancer, may be a key mechanism leading to the tumor progression. In this study, we studied whether a quantitative genetic definition of ITH can predict clinical outcomes in patients with TNBC. We quantified ITH by calculating Shannon index, a measure of diversity in a population, based on Myc, epidermal growth factor receptor/centromeric probe 7 (EGFR/CEP7) and cyclin D1/centromeric probe 11 (CCND1/CEP11) copy number variations (CNVs) in 300 cells at three different locations of a tumor. Among 75 TNBC patients, those who developed metastasis had significantly higher ITH, that is Shannon indices of EGFR/CEP7 and CCND1/CEP11 CNVs. Higher Shannon indices of EGFR/CEP7 and CCND1/CEP11 CNVs were significantly associated with the development of metastasis and were predictive of significantly worse metastasis-free survival (MFS). Regional heterogeneity, defined as the difference in copy numbers of Myc, EGFR or CCND1 at different locations, was found in 52 patients. However, the presence of regional heterogeneity did not correlate with metastasis or MFS. Our findings demonstrate that higher ITH of EGFR/CEP7 and CCND1/CEP11 CNVs is predictive of metastasis and is associated with significantly worse MFS in TNBC patients, suggesting that ITH is a very promising novel prognostic factor in TNBC. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Pulsating Stars in the ASAS-3 Database. I. beta Cephei Stars

NASA Astrophysics Data System (ADS)

Pigulski, A.

2005-06-01

We present results of an analysis of the ASAS-3 data for short-period variables from the recently published catalog of over 38000 stars. Using the data available in the literature we verify the results of the automatic classification related to \\beta Cep pulsators. In particular, we find that 14 stars in the catalog can be classified unambiguously as new beta Cep stars. By means of periodogram analysis we derive the frequencies and amplitudes of the excited modes. The main modes in the new beta Cep stars have large semi-amplitudes, between 35 and 80 mmag. Up to four modes were found in some stars. Two (maybe three) new beta Cep stars are members of southern young open clusters: ASAS 164409-4719.1 belongs to NGC 6200, ASAS 164630-4701.2 is a member of Hogg 22, and ASAS 164939-4431.7 could be a member of NGC 6216. We also analyze the photometry of four known beta Cep stars in the ASAS-3 catalog, namely IL Vel, NSV 24078, V1449 Aql and SY Equ. Finally, we discuss the distribution of beta Cep stars in the Galaxy.

Circulating Endothelial Cells and Endothelial Progenitor Cells in Pediatric Sepsis.

PubMed

Zahran, Asmaa Mohamad; Elsayh, Khalid Ibrahim; Mohamad, Ismail Lotfy; Hassan, Gamal Mohamad; Abdou, Madleen Adel A

2016-03-01

The aim of the study was to measure the number of circulating endothelial cells (CECs) and circulating endothelial progenitor cells (CEPs) in pediatric patients with sepsis and correlating it with the severity of the disease and its outcome. The study included 19 children with sepsis, 26 with complicated sepsis, and 30 healthy controls. The patients were investigated within 48 hours of pediatric intensive care unit admission together with flow cytometric detection of CECs and CEPs. The levels of both CECs and CEPs were significantly higher in patient with sepsis and complicated sepsis than the controls. The levels of CECs were higher in patients with complicated sepsis, whereas the levels of CEPs were lower in patients with complicated sepsis. Comparing the survival and nonsurvival septic patients, the levels of CEPs were significantly higher in the survival than in nonsurvival patients, whereas the levels of CECs were significantly lower in the survival than in nonsurvival patients. Serum albumin was higher in survival than in nonsurvival patients. Estimation of CECs and CEPs and their correlation with other parameters such as serum albumen could add important information regarding prognosis in septic pediatric patients.

Disease-Associated Mutations in CEP120 Destabilize the Protein and Impair Ciliogenesis.

PubMed

Joseph, Nimesh; Al-Jassar, Caezar; Johnson, Christopher M; Andreeva, Antonina; Barnabas, Deepak D; Freund, Stefan M V; Gergely, Fanni; van Breugel, Mark

2018-05-29

Ciliopathies are a group of genetic disorders caused by a failure to form functional cilia. Due to a lack of structural information, it is currently poorly understood how ciliopathic mutations affect protein functionality to give rise to the underlying disease. Using X-ray crystallography, we show that the ciliopathy-associated centriolar protein CEP120 contains three C2 domains. The point mutations V194A and A199P, which cause Joubert syndrome (JS) and Jeune asphyxiating thoracic dystrophy (JATD), respectively, both reduce the thermostability of the second C2 domain by targeting residues that point toward its hydrophobic core. Genome-engineered cells homozygous for these mutations have largely normal centriole numbers but show reduced CEP120 levels, compromised recruitment of distal centriole markers, and deficient cilia formation. Our results provide insight into the disease mechanism of two ciliopathic mutations in CEP120, identify putative binding partners of CEP120 C2B, and suggest a complex genotype-phenotype relation of the CEP120 ciliopathy alleles. Copyright © 2018 MRC Laboratory of Molecular Biology. Published by Elsevier Inc. All rights reserved.

Pannus overgrowth after mitral valve replacement with a Carpentier-Edwards pericardial bioprosthesis.

PubMed

Oda, Takeshi; Kato, Seiya; Tayama, Eiki; Fukunaga, Shuji; Akashi, Hidetoshi; Aoyagi, Shigeaki

2009-01-01

A Carpentier-Edwards pericardial (CEP) bioprosthesis was explanted from an 81-year-old woman due to nonstructural dysfunction 9 years after mitral valve replacement. The nonstructural dysfunction produced severe regurgitation in the mitral position. During the surgery, excessive pannus overgrowth was seen on the left ventricular side of the CEP bioprosthesis. Pannus overgrowth was prominent on one leaflet. That leaflet was stiff and shortened due to the excessive overgrowth of pannus. In this patient, the distortion of one leaflet was the main reason for transvalvular leakage of the CEP bioprosthesis in the mitral position. A new CEP bioprosthesis was implanted in the mitral position. Pathological analysis revealed fibrotic pannus with a small amount of cellular material over the leaflets of the resected CEP valve. This change was marked on the distorted leaflet.

Sensitive frequency dependence of the carrier-envelope phase effect on bound-bound transitions: An interference perspective

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

Peng Dian; Fu Panming; Wang Bingbing

2010-11-15

We investigate numerically with Hylleraas coordinates the frequency dependence of the carrier-envelope phase (CEP) effect on bound-bound transitions of helium induced by an ultrashort laser pulse of a few cycles. We find that the CEP effect is very sensitive to the carrier frequency of the laser pulse, occurring regularly even at far-off-resonance frequencies. By analyzing a two-level model, we find that the CEP effect can be attributed to the quantum interference between neighboring multiphoton transition pathways, which is made possible by the broadened spectrum of the ultrashort laser pulse. A general picture is developed along this line to understand themore » sensitivity of the CEP effect to the laser's carrier frequency. Multilevel influence on the CEP effect is also discussed.« less

The C-terminal region of A-kinase anchor protein 350 (AKAP350A) enables formation of microtubule-nucleation centers and interacts with pericentriolar proteins.

PubMed

Kolobova, Elena; Roland, Joseph T; Lapierre, Lynne A; Williams, Janice A; Mason, Twila A; Goldenring, James R

2017-12-15

Microtubules in animal cells assemble (nucleate) from both the centrosome and the cis-Golgi cisternae. A-kinase anchor protein 350 kDa (AKAP350A, also called AKAP450/CG-NAP/AKAP9) is a large scaffolding protein located at both the centrosome and Golgi apparatus. Previous findings have suggested that AKAP350 is important for microtubule dynamics at both locations, but how this scaffolding protein assembles microtubule nucleation machinery is unclear. Here, we found that overexpression of the C-terminal third of AKAP350A, enhanced GFP-AKAP350A(2691-3907), induces the formation of multiple microtubule-nucleation centers (MTNCs). Nevertheless, these induced MTNCs lacked "true" centriole proteins, such as Cep135. Mapping analysis with AKAP350A truncations demonstrated that AKAP350A contains discrete regions responsible for promoting or inhibiting the formation of multiple MTNCs. Moreover, GFP-AKAP350A(2691-3907) recruited several pericentriolar proteins to MTNCs, including γ-tubulin, pericentrin, Cep68, Cep170, and Cdk5RAP2. Proteomic analysis indicated that Cdk5RAP2 and Cep170 both interact with the microtubule nucleation-promoting region of AKAP350A, whereas Cep68 interacts with the distal C-terminal AKAP350A region. Yeast two-hybrid assays established a direct interaction of Cep170 with AKAP350A. Super-resolution and deconvolution microscopy analyses were performed to define the association of AKAP350A with centrosomes, and these studies disclosed that AKAP350A spans the bridge between centrioles, co-localizing with rootletin and Cep68 in the linker region. siRNA-mediated depletion of AKAP350A caused displacement of both Cep68 and Cep170 from the centrosome. These results suggest that AKAP350A acts as a scaffold for factors involved in microtubule nucleation at the centrosome and coordinates the assembly of protein complexes associating with the intercentriolar bridge.

Validation and Trustworthiness of Multiscale Models of Cardiac Electrophysiology

PubMed Central

Pathmanathan, Pras; Gray, Richard A.

2018-01-01

Computational models of cardiac electrophysiology have a long history in basic science applications and device design and evaluation, but have significant potential for clinical applications in all areas of cardiovascular medicine, including functional imaging and mapping, drug safety evaluation, disease diagnosis, patient selection, and therapy optimisation or personalisation. For all stakeholders to be confident in model-based clinical decisions, cardiac electrophysiological (CEP) models must be demonstrated to be trustworthy and reliable. Credibility, that is, the belief in the predictive capability, of a computational model is primarily established by performing validation, in which model predictions are compared to experimental or clinical data. However, there are numerous challenges to performing validation for highly complex multi-scale physiological models such as CEP models. As a result, credibility of CEP model predictions is usually founded upon a wide range of distinct factors, including various types of validation results, underlying theory, evidence supporting model assumptions, evidence from model calibration, all at a variety of scales from ion channel to cell to organ. Consequently, it is often unclear, or a matter for debate, the extent to which a CEP model can be trusted for a given application. The aim of this article is to clarify potential rationale for the trustworthiness of CEP models by reviewing evidence that has been (or could be) presented to support their credibility. We specifically address the complexity and multi-scale nature of CEP models which makes traditional model evaluation difficult. In addition, we make explicit some of the credibility justification that we believe is implicitly embedded in the CEP modeling literature. Overall, we provide a fresh perspective to CEP model credibility, and build a depiction and categorisation of the wide-ranging body of credibility evidence for CEP models. This paper also represents a step toward the extension of model evaluation methodologies that are currently being developed by the medical device community, to physiological models. PMID:29497385

LONG-TERM LIGHT CURVE OF HIGHLY VARIABLE PROTOSTELLAR STAR GM CEP

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

Xiao Limin; Kroll, Peter; Henden, Arne A.

2010-04-15

We present data from the archival plates at Harvard College Observatory and Sonneberg Observatory showing the field of the solar-type pre-main-sequence star GM Cep. A total of 186 magnitudes of GM Cep have been measured on these archival plates, with 176 in blue sensitivity, six in visible, and four in red. We combine our data with data from the literature and from the American Association of Variable Star Observers to depict the long-term light curves of GM Cep in both B and V wavelengths. The light curves span from 1895 until now, with two densely sampled regions (1935-1945 in themore » B band, and 2006 until now in the V band). The long-term light curves do not show any fast rise behavior as predicted by an accretion mechanism. Both the light curves and the magnitude histograms confirm the conclusion that the light curves are dominated by dips (possibly from extinction) superposed on some quiescence state, instead of outbursts caused by accretion flares. Our result excludes the possibility of GM Cep being a FUor, EXor, or McNeil's Nebula-type star. Several special cases of T Tauri stars were checked, but none of these light curves were compatible with that of GM Cep. The lack of periodicity in the light curve excludes the possibility of GM Cep being a KH 15D system.« less

Carrier-envelope phase-dependent ionization of Xe in intense, ultrafast (two-cycle) laser fields

NASA Astrophysics Data System (ADS)

Vasa, Parinda; Dharmadhikari, Aditya K.; Mathur, Deepak

2018-01-01

We report an experimental study that shows the dependence of the tunnel ionization of Xe by two-cycle, intense, near infrared light on the carrier-envelope-phase (CEP) of incident laser pulses. At low values of the optical field (E), the ionization yield is found to be maximum for cos-like pulses; the CEP dependence of the ion yield becomes stronger for higher charge states. At higher E-values, the CEP dependence either washes out or flips. A simple phenomenological model is used to confirm that our results fall within the ambit of the current understanding of ionization dynamics in strong, ultrashort optical fields. In the observed tunnel ionization of Xe, CEP effects appear to persist for longer, eight-cycle, pulses. Electron rescattering is observed to play a relatively unimportant role in the observed CEP dependence. These results provide fresh perspectives in the ionization mechanisms of multielectron systems in the few-cycle regime.

Automated Image Analysis of HER2 Fluorescence In Situ Hybridization to Refine Definitions of Genetic Heterogeneity in Breast Cancer Tissue

PubMed Central

Radziuviene, Gedmante; Rasmusson, Allan; Augulis, Renaldas; Lesciute-Krilaviciene, Daiva; Laurinaviciene, Aida; Clim, Eduard

2017-01-01

Human epidermal growth factor receptor 2 gene- (HER2-) targeted therapy for breast cancer relies primarily on HER2 overexpression established by immunohistochemistry (IHC) with borderline cases being further tested for amplification by fluorescence in situ hybridization (FISH). Manual interpretation of HER2 FISH is based on a limited number of cells and rather complex definitions of equivocal, polysomic, and genetically heterogeneous (GH) cases. Image analysis (IA) can extract high-capacity data and potentially improve HER2 testing in borderline cases. We investigated statistically derived indicators of HER2 heterogeneity in HER2 FISH data obtained by automated IA of 50 IHC borderline (2+) cases of invasive ductal breast carcinoma. Overall, IA significantly underestimated the conventional HER2, CEP17 counts, and HER2/CEP17 ratio; however, it collected more amplified cells in some cases below the lower limit of GH definition by manual procedure. Indicators for amplification, polysomy, and bimodality were extracted by factor analysis and allowed clustering of the tumors into amplified, nonamplified, and equivocal/polysomy categories. The bimodality indicator provided independent cell diversity characteristics for all clusters. Tumors classified as bimodal only partially coincided with the conventional GH heterogeneity category. We conclude that automated high-capacity nonselective tumor cell assay can generate evidence-based HER2 intratumor heterogeneity indicators to refine GH definitions. PMID:28752092

Automated Image Analysis of HER2 Fluorescence In Situ Hybridization to Refine Definitions of Genetic Heterogeneity in Breast Cancer Tissue.

PubMed

Radziuviene, Gedmante; Rasmusson, Allan; Augulis, Renaldas; Lesciute-Krilaviciene, Daiva; Laurinaviciene, Aida; Clim, Eduard; Laurinavicius, Arvydas

2017-01-01

Human epidermal growth factor receptor 2 gene- (HER2-) targeted therapy for breast cancer relies primarily on HER2 overexpression established by immunohistochemistry (IHC) with borderline cases being further tested for amplification by fluorescence in situ hybridization (FISH). Manual interpretation of HER2 FISH is based on a limited number of cells and rather complex definitions of equivocal, polysomic, and genetically heterogeneous (GH) cases. Image analysis (IA) can extract high-capacity data and potentially improve HER2 testing in borderline cases. We investigated statistically derived indicators of HER2 heterogeneity in HER2 FISH data obtained by automated IA of 50 IHC borderline (2+) cases of invasive ductal breast carcinoma. Overall, IA significantly underestimated the conventional HER2, CEP17 counts, and HER2/CEP17 ratio; however, it collected more amplified cells in some cases below the lower limit of GH definition by manual procedure. Indicators for amplification, polysomy, and bimodality were extracted by factor analysis and allowed clustering of the tumors into amplified, nonamplified, and equivocal/polysomy categories. The bimodality indicator provided independent cell diversity characteristics for all clusters. Tumors classified as bimodal only partially coincided with the conventional GH heterogeneity category. We conclude that automated high-capacity nonselective tumor cell assay can generate evidence-based HER2 intratumor heterogeneity indicators to refine GH definitions.

The Art of Living Together: Reducing Stereotyping and Prejudicial Attitudes through the Arab-Jewish Class Exchange Program (CEP)

ERIC Educational Resources Information Center

Berger, Rony; Abu-Raiya, Hisham; Gelkopf, Marc

2015-01-01

This study evaluated the efficacy of a newly developed Arab-Jewish Class Exchange Program (CEP) in reducing stereotyping and prejudicial attitudes between Israeli-Jewish and Israeli-Palestinian children. The CEP builds on the core principles of contact theory and is designed to help participants cultivate empathy and tolerance toward the other.…

The Creation of Multimedia Resources to Support the Gaelic Athletic Association (GAA) Coach Education Programme (CEP)

ERIC Educational Resources Information Center

Crotty, Yvonne; D'Arcy, Jimmy; Sweeney, David

2016-01-01

The Gaelic Athletic Association (GAA) is an Irish amateur sporting and cultural organisation. It represents in excess of 20,000 teams nationwide and is committed to supporting the development of players and coaches through its Coach Education Programme (CEP). A strategic goal of the CEP is to supplement the traditional field based coach education…

The test about blood serum capabilities in maintaining the quality of bull spermatozoa during storage in cep diluent at refrigerator temperature

NASA Astrophysics Data System (ADS)

Ducha, Nur

2018-03-01

The storage of spermatozoa requires a protective material from cold shock events and the presence of free radicals.In CEP diluent contain BSA, that was used as spermatozoa protection. This study aim was to examine the ability of cow blood serum in replacing BSA as spermatozoa protective in CEP diluent. Fresh semen from Limousin bull was diluted with CEP diluent + BSA as control, in the treatment group were CEP without BSA, but replaced with 3%, 5%, and 7% serum from fresh blood. Spermatozoa quality tests included motility and viability. The motility of spermatozoa was observed by two people using a light microscope with 200 X magnification at temperature of 37°C. The method of viability observation was eosin nigrosin staining, and observed under a light microscope with 400 X magnification. The results showed that the replacement of cow blood serum with various concentrations gave different effects on the quality of spermatozoa. The best motility and viability of the treatment group was at serum concentrations of 5% after eight days storage and was not significantly different from the controls. The conclusion in this study was cow blood serum can replace BSA in CEP diluents.

High glucose-induced excessive reactive oxygen species promote apoptosis through mitochondrial damage in rat cartilage endplate cells.

PubMed

Jiang, Zengxin; Lu, Wei; Zeng, Qingmin; Li, Defang; Ding, Lei; Wu, Jingping

2018-04-16

Diabetes mellitus (DM) is an important factor in intervertebral disc degeneration (IDD). Apoptosis of cartilage endplate (CEP) cells is one of the initiators of IDD. However, the effects of high glucose on CEP cells are still unknown. Therefore, we conducted the present study to evaluate the effects of high glucose on CEP cells and to identify the mechanisms of those effects. Rat CEP cells were isolated and cultured in 10% foetal bovine serum (FBS, normal control) or high-glucose medium (10% FBS + 0.1 M glucose or 10% FBS + 0.2 M glucose, experimental conditions) for 1 or 3 days. In addition, CEP cells were treated with 0.2 M glucose for 3 days in the presence or absence of alpha-lipoic acid (ALA, 0.15 M). Flow cytometry was performed to identify and quantify the degree of apoptosis. The expression of reactive oxygen species (ROS) was assessed by flow cytometry, and mitochondrial damage (mitochondrial membrane potential) was assessed by fluorescence microscopy. Furthermore, the expression levels of cleaved caspase-3, cleaved caspase-9, Bcl-2, Bax, and cytochrome c were evaluated by Western blotting. High glucose significantly increased apoptosis and ROS accumulation in CEP cells in a dose- and time-dependent manner. Meanwhile, a disrupted mitochondrial membrane potential was detected in rat CEP cells cultured in the two high glucose concentrations. Incubating in high glucose enhanced the expression levels of cleaved caspase-3, cleaved caspase-9, Bax, and cytochrome c but decreased the level of the anti-apoptotic protein Bcl-2. ALA inhibited the expression of cleaved caspase-3, cleaved caspase-9, Bax, and cytochrome c but enhanced the expression of Bcl-2. ALA also prevented disruption of the mitochondrial membrane potential in CEP cells. This study demonstrates that high glucose-induced excessive reactive oxygen species promote mitochondrial damage, thus causing apoptosis in rat CEP cells in a dose- and time-dependent manner. ALA could prevent mitochondrial damage and apoptosis caused by high glucose in CEP cells. The results suggest that appropriate blood glucose control may be the key to preventing IDD in diabetic patients. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Participation in Training for Depression Care Quality Improvement: A Randomized Trial of Community Engagement or Technical Support.

PubMed

Chung, Bowen; Ngo, Victoria K; Ong, Michael K; Pulido, Esmeralda; Jones, Felica; Gilmore, James; Stoker-Mtume, Norma; Johnson, Megan; Tang, Lingqi; Wells, Kenneth Brooks; Sherbourne, Cathy; Miranda, Jeanne

2015-08-01

Community engagement and planning (CEP) could improve dissemination of depression care quality improvement in underresourced communities, but whether its effects on provider training participation differ from those of standard technical assistance, or resources for services (RS), is unknown. This study compared program- and staff-level participation in depression care quality improvement training among programs enrolled in CEP, which trained networks of health care and social-community agencies jointly, and RS, which provided technical support to individual programs. Matched programs from health care and social-community service sectors in two communities were randomly assigned to RS or CEP. Data were from 1,622 eligible staff members from 95 enrolled programs. Primary outcomes were any staff trained (for programs) and total hours of training (for staff). Secondary staff-level outcomes were hours of training in specific depression collaborative care components. CEP programs were more likely than RS programs to participate in any training (p=.006). Within health care sectors, CEP programs were more likely than RS programs to participate in training (p=.016), but within social-community sectors, there was no difference in training by intervention. Among staff who participated in training, mean training hours were greater among CEP programs versus RS programs for any type of training (p<.001) and for training related to each component of depression care (p<.001) except medication management. CEP may be an effective strategy to promote staff participation in depression care improvement efforts in underresourced communities.

Antisense Oligonucleotide-Based Splicing Correction in Individuals with Leber Congenital Amaurosis due to Compound Heterozygosity for the c.2991+1655A>G Mutation in CEP290.

PubMed

Duijkers, Lonneke; van den Born, L Ingeborgh; Neidhardt, John; Bax, Nathalie M; Pierrache, Laurence H M; Klevering, B Jeroen; Collin, Rob W J; Garanto, Alejandro

2018-03-07

Leber congenital amaurosis (LCA) is a rare inherited retinal disorder affecting approximately 1:50,000 people worldwide. So far, mutations in 25 genes have been associated with LCA, with CEP290 (encoding the Centrosomal protein of 290 kDa) being the most frequently mutated gene. The most recurrent LCA-causing CEP290 mutation, c.2991+1655A>G, causes the insertion of a pseudoexon into a variable proportion of CEP290 transcripts. We previously demonstrated that antisense oligonucleotides (AONs) have a high therapeutic potential for patients homozygously harbouring this mutation, although to date, it is unclear whether rescuing one single allele is enough to restore CEP290 function. Here, we assessed the AON efficacy at RNA, protein and cellular levels in samples that are compound heterozygous for this mutation, together with a protein-truncating mutation in CEP290 . We demonstrate that AONs can efficiently restore splicing and increase protein levels. However, due to a high variability in ciliation among the patient-derived cell lines, the efficacy of the AONs was more difficult to assess at the cellular level. This observation points towards the importance of the severity of the second allele and possibly other genetic variants present in each individual. Overall, AONs seem to be a promising tool to treat CEP290 -associated LCA, not only in homozygous but also in compound heterozygous carriers of the c.2991+1655A>G variant.

76 FR 59240 - Airworthiness Directives; Empresa Brasileira de Aeronáutica S.A. (EMBRAER) Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-26

... Support, Av. Brig. Faria Lima, 2170, Sao Jose dos Campos-SP, CEP: 12227-901--PO Box: 36/2, Brasil.... Brig. Faria Lima, 2170, Sao Jose dos Campos--SP, CEP: 12227-901--PO Box: 36/2, Brasil; telephone: ++55... dos Campos--SP, CEP: 12227-901--PO Box: 36/2, Brasil; telephone: ++55 12 3927-5383; fax: ++55 12 3927...

Circulating Endothelial Progenitor Cells in Castration Resistant Prostate Cancer: A Randomized, Controlled, Biomarker Study

PubMed Central

Fuereder, Thorsten; Wacheck, Volker; Strommer, Sabine; Horak, Peter; Gerschpacher, Marion; Lamm, Wolfgang; Kivaranovic, Danijel; Krainer, Michael

2014-01-01

Background Endothelial progenitor cells (CEPs) and circulating endothelial cells (CECs) are potential biomarkers of response to anti-angiogenic treatment regimens. In the current study, we investigated the effect of docetaxel and sunitinib on CEP/CEC kinetics and clinical response in castration resistant prostate cancer (CRPC) patients. Patients and methods Chemonaive patients with CRPC were enrolled in this study to receive either sunitinib (37.5 mg/d), in combination with docetaxel (75 mg/m2) or docetaxel alone. CEP and CEC kinetics were analyzed for every cycle. The primary objective was to compare CEP/CEC pharmacodynamics between both treatment arms. We also investigated if CEC/CEP spikes, induced by MTD docetaxel, are suppressed by sunitinib in patients treated with docetaxel/sunitinib relative to docetaxel monotherapy. Results A total of 27 patients were enrolled. We observed a significant increase of CEP/CEC (total/viable) counts over time within each cycle (coefficients 0.29233, 0.22092 and 0.26089, respectively; p<0.001). However, no differences between the treatment groups, in terms of CEP and CEC kinetics, were detected. In the docetaxel monotherapy arm 4 (30%) patients responded to therapy with a 50% PSA decline, while 9 (64%) patients showed a PSA decline in the combination group (n.s.). The median PFS in the docetaxel monotherapy group was 3.1 months (2.6–3.6 months, 95% CI) and 6.2 months (4.9–7.4 months, 95% CI; p = 0.062) in the combination arm. Sunitinib/docetaxel was reasonably well tolerated and toxicity manageable. Conclusion In summary, no significant differences in CEC and CEP kinetics between the treatment arms were observed, although a highly significant increase of CEPs/CECs within each cycle over time was detected. These results mirror the challenge we have to face when employing anti-angiogenic strategies in CRPC. Additional preclinical research is needed to elucidate the underlying molecular mechanisms. However, docetaxel/sunitinib therapy resulted in a better response in terms of PSA decline and a trend towards improved PFS. Trial Registery clinicaltrialsregister.eu EudraCT 2007-003705-27 PMID:24755958

MKS5 and CEP290 Dependent Assembly Pathway of the Ciliary Transition Zone

PubMed Central

Li, Chunmei; Kennedy, Julie; Garcia-Gonzalo, Francesc R.; Romani, Marta; De Mori, Roberta; Bruel, Ange-Line; Gaillard, Dominique; Doray, Bérénice; Lopez, Estelle; Rivière, Jean-Baptiste; Faivre, Laurence; Thauvin-Robinet, Christel; Reiter, Jeremy F.; Blacque, Oliver E.; Valente, Enza Maria; Leroux, Michel R.

2016-01-01

Cilia have a unique diffusion barrier (“gate”) within their proximal region, termed transition zone (TZ), that compartmentalises signalling proteins within the organelle. The TZ is known to harbour two functional modules/complexes (Meckel syndrome [MKS] and Nephronophthisis [NPHP]) defined by genetic interaction, interdependent protein localisation (hierarchy), and proteomic studies. However, the composition and molecular organisation of these modules and their links to human ciliary disease are not completely understood. Here, we reveal Caenorhabditis elegans CEP-290 (mammalian Cep290/Mks4/Nphp6 orthologue) as a central assembly factor that is specific for established MKS module components and depends on the coiled coil region of MKS-5 (Rpgrip1L/Rpgrip1) for TZ localisation. Consistent with a critical role in ciliary gate function, CEP-290 prevents inappropriate entry of membrane-associated proteins into cilia and keeps ARL-13 (Arl13b) from leaking out of cilia via the TZ. We identify a novel MKS module component, TMEM-218 (Tmem218), that requires CEP-290 and other MKS module components for TZ localisation and functions together with the NPHP module to facilitate ciliogenesis. We show that TZ localisation of TMEM-138 (Tmem138) and CDKL-1 (Cdkl1/Cdkl2/Cdkl3/Cdlk4 related), not previously linked to a specific TZ module, similarly depends on CEP-290; surprisingly, neither TMEM-138 or CDKL-1 exhibit interdependent localisation or genetic interactions with core MKS or NPHP module components, suggesting they are part of a distinct, CEP-290-associated module. Lastly, we show that families presenting with Oral-Facial-Digital syndrome type 6 (OFD6) have likely pathogenic mutations in CEP-290-dependent TZ proteins, namely Tmem17, Tmem138, and Tmem231. Notably, patient fibroblasts harbouring mutated Tmem17, a protein not yet ciliopathy-associated, display ciliogenesis defects. Together, our findings expand the repertoire of MKS module-associated proteins—including the previously uncharacterised mammalian Tmem80—and suggest an MKS-5 and CEP-290-dependent assembly pathway for building a functional TZ. PMID:26982032

Nature of shocks revealed by SOFIA OI observations in the Cepheus E protostellar outflow

NASA Astrophysics Data System (ADS)

Gusdorf, A.; Anderl, S.; Lefloch, B.; Leurini, S.; Wiesemeyer, H.; Güsten, R.; Benedettini, M.; Codella, C.; Godard, B.; Gómez-Ruiz, A. I.; Jacobs, K.; Kristensen, L. E.; Lesaffre, P.; Pineau des Forêts, G.; Lis, D. C.

2017-06-01

Context. Protostellar jets and outflows are key features of the star-formation process, and primary processes of the feedback of young stars on the interstellar medium. Understanding the underlying shocks is necessary to explain how jet and outflow systems are launched, and to quantify their chemical and energetic impacts on the surrounding medium. Aims: We performed a high-spectral resolution study of the [OI]63μm emission in the outflow of the intermediate-mass Class 0 protostar Cep E-mm. The goal is to determine the structure of the outflow, to constrain the chemical conditions in the various components, and to understand the nature of the underlying shocks, thus probing the origin of the mass-loss phenomenon. Methods: We present observations of the O I 3P1 → 3P2, OH between 2Π1/2J = 3/2 and J = 1/2 at 1837.8 GHz, and CO (16-15) lines with the GREAT receiver onboard SOFIA towards three positions in the Cep E protostellar outflow: Cep E-mm (the driving protostar), Cep E-BI (in the southern lobe), and Cep E-BII (the terminal position in the southern lobe). Results: The CO (16-15) line is detected at all three positions. The [OI]63μm line is detected in Cep E-BI and BII, whereas the OH line is not detected. In Cep E-BII, we identify three kinematical components in O I and CO. These were already detected in CO transitions and relate to spatial components: the jet, the HH377 terminal bow-shock, and the outflow cavity. We measure line temperature and line integrated intensity ratios for all components. The O I column density is higher in the outflow cavity than in the jet, which itself is higher than in the terminal shock. The terminal shock is the region where the abundance ratio of O I to CO is the lowest (about 0.2), whereas the jet component is atomic (N(O I)/N(CO) 2.7). In the jet, we compare the [OI]63μm observations with shock models that successfully fit the integrated intensity of 10 CO lines. We find that these models most likely do not fit the [OI]63μm data. Conclusions: The high intensity of O I emission points towards the propagation of additional dissociative or alternative FUV-irradiated shocks, where the illumination comes from the shock itself. A picture emerges from the sample of low-to-high mass protostellar outflows, where similar observations have been performed, with the effects of illumination increasing with the mass of the protostar. These findings need confirmation with more observational constraints and a larger sample. This article uses Herschel-PACS data; Herschel is an ESA space observatory with science instruments provided by European-led Principal Investigator consortia and with important participation from NASA.All spectra shown in Fig. 2 are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (http://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/602/A8

A ubiquitin carboxyl extension protein secreted from a plant-parasitic nematode Globodera rostochiensis is cleaved in planta to promote plant parasitism.

PubMed

Chronis, Demosthenis; Chen, Shiyan; Lu, Shunwen; Hewezi, Tarek; Carpenter, Sara C D; Loria, Rosemary; Baum, Thomas J; Wang, Xiaohong

2013-04-01

Nematode effector proteins originating from esophageal gland cells play central roles in suppressing plant defenses and in formation of the plant feeding cells that are required for growth and development of cyst nematodes. A gene (GrUBCEP12) encoding a unique ubiquitin carboxyl extension protein (UBCEP) that consists of a signal peptide for secretion, a mono-ubiquitin domain, and a 12 amino acid carboxyl extension protein (CEP12) domain was cloned from the potato cyst nematode Globodera rostochiensis. This GrUBCEP12 gene was expressed exclusively within the nematode's dorsal esophageal gland cell, and was up-regulated in the parasitic second-stage juvenile, correlating with the time when feeding cell formation is initiated. We showed that specific GrUBCEP12 knockdown via RNA interference reduced nematode parasitic success, and that over-expression of the secreted Gr(Δ) (SP) UBCEP12 protein in potato resulted in increased nematode susceptibility, providing direct evidence that this secreted effector is involved in plant parasitism. Using transient expression assays in Nicotiana benthamiana, we found that Gr(Δ) (SP) UBCEP12 is processed into free ubiquitin and a CEP12 peptide (GrCEP12) in planta, and that GrCEP12 suppresses resistance gene-mediated cell death. A target search showed that expression of RPN2a, a gene encoding a subunit of the 26S proteasome, was dramatically suppressed in Gr(Δ) (SP) UBCEP12 but not GrCEP12 over-expression plants when compared with control plants. Together, these results suggest that, when delivered into host plant cells, Gr(Δ) (SP) UBCEP12 becomes two functional units, one acting to suppress plant immunity and the other potentially affecting the host 26S proteasome, to promote feeding cell formation. © 2013 The Authors The Plant Journal © 2013 Blackwell Publishing Ltd.

The role of operative intervention in management of congenital extrahepatic portosystemic shunt.

PubMed

Sanada, Yukihiro; Urahashi, Taizen; Ihara, Yoshiyuki; Wakiya, Taiichi; Okada, Noriki; Yamada, Naoya; Egami, Satoshi; Hishikawa, Shuji; Kawano, Youichi; Ushijima, Kentaro; Otomo, Shinya; Sakamoto, Koichi; Nakata, Manabu; Yasuda, Yoshikazu; Mizuta, Koichi

2012-03-01

Congenital extrahepatic portosystemic shunt (CEPS) is a rare venous malformation in which mesenteric venous blood drains directly into the systemic circulation. It is still a matter of debate whether conservative or operative strategies should be used to treat symptomatic CEPS. The aim of this study was to evaluate the role of operative intervention in the management of CEPS. Between June 2004 and August 2010, 6 consecutive patients with symptomatic CEPS were treated in our department. There were 3 male and 3 female patients, with a median age of 3.5 years (range, 1-8). Their demographic, clinical, and laboratory data were analyzed. All patients were scheduled to undergo shunt ligation or liver transplantation (LT). Living donor LT was carried out in 4 patients, and shunt ligation in 2. After a median follow-up of 25 months, all the patients are alive currently with marked relief of symptoms. Shunt ligation or LT for symptomatic CEPS is potentially curative. Crown Copyright © 2012. Published by Mosby, Inc. All rights reserved.

Nanoscale electron manipulation in metals with intense THz electric fields

NASA Astrophysics Data System (ADS)

Takeda, Jun; Yoshioka, Katsumasa; Minami, Yasuo; Katayama, Ikufumi

2018-03-01

Improved control over the electromagnetic properties of metals on a nanoscale is crucial for the development of next-generation nanoelectronics and plasmonic devices. Harnessing the terahertz (THz)-electric-field-induced nonlinearity for the motion of electrons is a promising method of manipulating the local electromagnetic properties of metals, while avoiding undesirable thermal effects and electronic transitions. In this review, we demonstrate the manipulation of electron delocalization in ultrathin gold (Au) films with nanostructures, by intense THz electric-field transients. On increasing the electric-field strength of the THz pulses, the transmittance in the THz-frequency region abruptly decreases around the percolation threshold. The observed THz-electric-field-induced nonlinearity is analysed, based on the Drude-Smith model. The results suggest that ultrafast electron delocalization occurs by electron tunnelling across the narrow insulating bridge between the Au nanostructures, without material breakdown. In order to quantitatively discuss the tunnelling process, we perform scanning tunnelling microscopy with carrier-envelope phase (CEP)-controlled single-cycle THz electric fields. By applying CEP-controlled THz electric fields to the 1 nm nanogap between a metal nanotip and graphite sample, many electrons could be coherently driven through the quantum tunnelling process, either from the nanotip to the sample or vice versa. The presented concept, namely, electron tunnelling mediated by CEP-controlled single-cycle THz electric fields, can facilitate the development of nanoscale electron manipulation, applicable to next-generation ultrafast nanoelectronics and plasmonic devices.

Ribosome Synthesis and MAPK Activity Modulate Ionizing Radiation-Induced Germ Cell Apoptosis in Caenorhabditis elegans

PubMed Central

Eberhard, Ralf; Stergiou, Lilli; Hofmann, E. Randal; Hofmann, Jen; Haenni, Simon; Teo, Youjin; Furger, André; Hengartner, Michael O.

2013-01-01

Synthesis of ribosomal RNA by RNA polymerase I (RNA pol I) is an elemental biological process and is key for cellular homeostasis. In a forward genetic screen in C. elegans designed to identify DNA damage-response factors, we isolated a point mutation of RNA pol I, rpoa-2(op259), that leads to altered rRNA synthesis and a concomitant resistance to ionizing radiation (IR)-induced germ cell apoptosis. This weak apoptotic IR response could be phenocopied when interfering with other factors of ribosome synthesis. Surprisingly, despite their resistance to DNA damage, rpoa-2(op259) mutants present a normal CEP-1/p53 response to IR and increased basal CEP-1 activity under normal growth conditions. In parallel, rpoa-2(op259) leads to reduced Ras/MAPK pathway activity, which is required for germ cell progression and physiological germ cell death. Ras/MAPK gain-of-function conditions could rescue the IR response defect in rpoa-2(op259), pointing to a function for Ras/MAPK in modulating DNA damage-induced apoptosis downstream of CEP-1. Our data demonstrate that a single point mutation in an RNA pol I subunit can interfere with multiple key signalling pathways. Ribosome synthesis and growth-factor signalling are perturbed in many cancer cells; such an interplay between basic cellular processes and signalling might be critical for how tumours evolve or respond to treatment. PMID:24278030

Social influence on temptation: perceived descriptive norms, temptation and restraint, and problem drinking among college students

PubMed Central

Rinker, Dipali Venkataraman; Neighbors, Clayton

2013-01-01

Temptation and restraint have long been associated with problematic drinking. Among college students, social norms are one of the strongest predictors of problematic drinking. To date, no studies have examined the association between temptation and restraint and perceived descriptive norms on drinking and alcohol-related problems among college students. The purpose of this study was to examine whether perceived descriptive norms moderated the relationship between temptation and restraint and drinking outcomes among college students. Participants were 1,095 college students from a large, public, culturally-diverse, southern university who completed an online survey about drinking behaviors and related attitudes. Drinks per week and alcohol-related problems were examined as a function of perceived descriptive norms, Cognitive Emotional Preoccupation (CEP) (temptation), and Cognitive Behavioral Control (CBC) (restraint). Additionally, drinking outcomes were examined as a function of the two-way interactions between CEP and perceived descriptive norms and CBC and perceived descriptive norms. Results indicated that CEP and perceived descriptive norms were associated with drinking outcomes. CBC was not associated with drinking outcomes. Additionally, perceived descriptive norms moderated the association between CEP and drinks per week and CEP and alcohol-related problems. There was a positive association between CEP and drinks per week and CEP and alcohol-related problems, especially for those higher on perceived descriptive norms. College students who are very tempted to drink may drink more heavily and experience alcohol-related problems more frequently if they have greater perceptions that the typical student at their university/college drinks a lot. PMID:24064190

Social influence on temptation: perceived descriptive norms, temptation and restraint, and problem drinking among college students.

PubMed

Rinker, Dipali Venkataraman; Neighbors, Clayton

2013-12-01

Temptation and restraint have long been associated with problematic drinking. Among college students, social norms are one of the strongest predictors of problematic drinking. To date, no studies have examined the association between temptation and restraint and perceived descriptive norms on drinking and alcohol-related problems among college students. The purpose of this study was to examine whether perceived descriptive norms moderated the relationship between temptation and restraint and drinking outcomes among college students. Participants were 1095 college students from a large, public, culturally-diverse, southern university who completed an online survey about drinking behaviors and related attitudes. Drinks per week and alcohol-related problems were examined as a function of perceived descriptive norms, Cognitive Emotional Preoccupation (CEP) (temptation), and Cognitive Behavioral Control (CBC) (restraint). Additionally, drinking outcomes were examined as a function of the two-way interactions between CEP and perceived descriptive norms and CBC and perceived descriptive norms. Results indicated that CEP and perceived descriptive norms were associated with drinking outcomes. CBC was not associated with drinking outcomes. Additionally, perceived descriptive norms moderated the association between CEP and drinks per week and CEP and alcohol-related problems. There was a positive association between CEP and drinks per week and CEP and alcohol-related problems, especially for those higher on perceived descriptive norms. College students who are very tempted to drink may drink more heavily and experience alcohol-related problems more frequently if they have greater perceptions that the typical student at their university/college drinks a lot. © 2013.

Analysis of Substrates of Protein Kinase C Isoforms in Human Breast Cells By The Traceable Kinase Method

PubMed Central

Chen, Xiangyu; Zhao, Xin; Abeyweera, Thushara P.; Rotenberg, Susan A.

2012-01-01

A previous report (Biochemistry 46: 2364–2370, 2007) described the application of The Traceable Kinase Method to identify substrates of PKCα in non-transformed human breast MCF-10A cells. Here, a non-radioactive variation of this method compared the phospho-protein profiles of three traceable PKC isoforms (α, δ and ζ) for the purpose of identifying novel, isoform-selective substrates. Each FLAG-tagged traceable kinase was expressed and co-immunoprecipitated along with high affinity substrates. The isolated kinase and its associated substrates were subjected to an in vitro phosphorylation reaction with traceable kinase-specific N6-phenyl-ATP, and the resulting phospho-proteins were analyzed by Western blot with an antibody that recognizes the phosphorylated PKC consensus site. Phospho-protein profiles generated by PKC-α and -δ were similar and differed markedly from that of PKC-ζ. Mass spectrometry of selected bands revealed known PKC substrates and several potential substrates that included the small GTPase-associated effector protein Cdc42 effector protein-4 (CEP4). Of those potential substrates tested, only CEP4 was phosphorylated by pure PKC-α, –δ, and −ζ isoforms in vitro, and by endogenous PKC isoforms in MCF-10A cells treated with DAG-lactone, a membrane permeable PKC activator. Under these conditions, the stoichiometry of CEP4 phosphorylation was 3.2 ± 0.5 (mol phospho-CEP4/mol CEP4). Following knock-down with isoform-specific shRNA-encoding plasmids, phosphorylation of CEP4 was substantially decreased in response to silencing of each of the three isoforms (PKC–α, –δ, or –ζ), whereas testing of kinase-dead mutants supported a role for only PKC-α and –δ in CEP4 phosphorylation. These findings identify CEP4 as a novel intracellular PKC substrate that is phosphorylated by multiple PKC isoforms. PMID:22897107

Ultrashort polarization-tailored bichromatic fields from a CEP-stable white light supercontinuum.

PubMed

Kerbstadt, Stefanie; Timmer, Daniel; Englert, Lars; Bayer, Tim; Wollenhaupt, Matthias

2017-05-29

We apply ultrafast polarization shaping to an ultrabroadband carrier envelope phase (CEP) stable white light supercontinuum to generate polarization-tailored bichromatic laser fields of low-order frequency ratio. The generation of orthogonal linearly and counter-rotating circularly polarized bichromatic fields is achieved by introducing a composite polarizer in the Fourier plane of a 4 f polarization shaper. The resulting Lissajous- and propeller-type polarization profiles are characterized experimentally by cross-correlation trajectories. The scheme provides full control over all bichromatic parameters and allows for individual spectral phase modulation of both colors. Shaper-based CEP control and the generation of tailored bichromatic fields is demonstrated. These bichromatic CEP-stable polarization-shaped ultrashort laser pulses provide a versatile class of waveforms for coherent control experiments.

CEP72-ROS1: A novel ROS1 oncogenic fusion variant in lung adenocarcinoma identified by next-generation sequencing.

PubMed

Zhu, You-Cai; Zhou, Yue-Fen; Wang, Wen-Xian; Xu, Chun-Wei; Zhuang, Wu; Du, Kai-Qi; Chen, Gang

2018-05-01

ROS1 rearrangement is a validated therapeutic driver gene in non-small cell lung cancer (NSCLC) and represents a small subset (1-2%) of NSCLC. A total of 17 different fusion partner genes of ROS1 in NSCLC have been reported. The multi-targeted MET/ALK/ROS1 tyrosine kinase inhibitor (TKI) crizotinib has demonstrated remarkable efficacy in ROS1-rearranged NSCLC. Consequently, ROS1 detection assays include fluorescence in situ hybridization, immunohistochemistry, and real-time PCR. Next-generation sequencing (NGS) assay covers a range of fusion genes and approaches to discover novel receptor-kinase rearrangements in lung cancer. A 63-year-old male smoker with stage IV NSCLC (TxNxM1) was detected with a novel ROS1 fusion. Histological examination of the tumor showed lung adenocarcinoma. NGS analysis of the hydrothorax cellblocks revealed a novel CEP72-ROS1 rearrangement. This novel CEP72-ROS1 fusion variant is generated by the fusion of exons 1-11 of CEP72 on chromosome 5p15 to exons 23-43 of ROS1 on chromosome 6q22. The predicted CEP72-ROS1 protein product contains 1202 amino acids comprising the N-terminal amino acids 594-647 of CEP72 and C-terminal amino acid 1-1148 of ROS1. CEP72-ROS1 is a novel ROS1 fusion variant in NSCLC discovered by NGS and could be included in ROS1 detection assay, such as reverse transcription PCR. Pleural effusion samples show good diagnostic performance in clinical practice. © 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Expression of miR-625 and Fas in cervical vertebral cartilage endplate.

PubMed

Zhan, Beilei; Zhan, Yan; Wang, Wei; Zhan, Yunzhong; Liu, Bingsheng

2018-01-01

The aim of the present study was to assess miR-625 and Fas expression in normal and degenerative cervical cartilage endplate (CEP) tissues. Following biof-informatics analysis, the Fas gene was predicted to be one of the targets of miR-625. Quantitative PCR (qPCR) and western blotting were used to detect miR-625 and Fas expression in normal and degenerative CEP. A luciferase reporter assay was used to identify whether miR-625 could directly target the 3' untranslated region (3'-UTR) of Fas. Lentiviral overexpression and/or inhibition vectors of miR-625 (pre-miR-625)/antigomiR-625 were constructed to determine whether overexpression or inhibition of miR-625 could affect Fas and B-cell lymphoma 2 (Bcl-2) expression in cartilaginous endplate cells (CECs) and tissues. qPCR analysis demonstrated that miR-625 expression in degenerative CEP was significantly lower than in normal CEP tissue, while the production of Fas in degenerated CEP was significantly higher. Results from western blotting also showed a significant increase in Fas expression in degenerative CEP. miR-625 can bind directly to the 3'-UTR of the Fas gene. However, this inhibition was attenuated by a target mutation in the miR-625-binding site of the 3'-UTR of Fas mRNA. In addition, following transfection of CECs with pre-miR-625 and antigomiR-625, expression of Fas significantly decreased and increased, respectively, and Bcl-2 expression was upregulated and downregulated, respectively. Upregulation of miR-625 can inhibit Fas expression and further affect Bcl-2 expression in CEP degeneration, suggesting that miR-625-mediated inhibition of the Fas gene is important in cervical degeneration.

CEP72‐ROS1: A novel ROS1 oncogenic fusion variant in lung adenocarcinoma identified by next‐generation sequencing

PubMed Central

Zhu, You‐cai; Zhou, Yue‐fen; Zhuang, Wu; Du, Kai‐qi; Chen, Gang

2018-01-01

ROS1 rearrangement is a validated therapeutic driver gene in non‐small cell lung cancer (NSCLC) and represents a small subset (1–2%) of NSCLC. A total of 17 different fusion partner genes of ROS1 in NSCLC have been reported. The multi‐targeted MET/ALK/ROS1 tyrosine kinase inhibitor (TKI) crizotinib has demonstrated remarkable efficacy in ROS1‐rearranged NSCLC. Consequently, ROS1 detection assays include fluorescence in situ hybridization, immunohistochemistry, and real‐time PCR. Next‐generation sequencing (NGS) assay covers a range of fusion genes and approaches to discover novel receptor‐kinase rearrangements in lung cancer. A 63‐year‐old male smoker with stage IV NSCLC (TxNxM1) was detected with a novel ROS1 fusion. Histological examination of the tumor showed lung adenocarcinoma. NGS analysis of the hydrothorax cellblocks revealed a novel CEP72‐ROS1 rearrangement. This novel CEP72‐ROS1 fusion variant is generated by the fusion of exons 1–11 of CEP72 on chromosome 5p15 to exons 23–43 of ROS1 on chromosome 6q22. The predicted CEP72‐ROS1 protein product contains 1202 amino acids comprising the N‐terminal amino acids 594–647 of CEP72 and C‐terminal amino acid 1‐1148 of ROS1. CEP72‐ROS1 is a novel ROS1 fusion variant in NSCLC discovered by NGS and could be included in ROS1 detection assay, such as reverse transcription PCR. Pleural effusion samples show good diagnostic performance in clinical practice. PMID:29517860

Congenital extrahepatic portosystemic venous shunt: imaging features.

PubMed

Kandpal, H; Sharma, R; Arora, N K; Gupta, S D

2007-09-01

Congenital extrahepatic portosystemic venous shunt (CEPS) is a rare anomaly. It causes metabolic derangements and is often associated with liver tumours and other anomalies. Imaging plays an important role in the diagnosis of CEPS. However, it may be misleading in determining the type of shunt. We present a six-year-old girl with CEPS to illustrate the importance of histology in determining the presence of portal veins in the portal triad, which were too small to be seen on imaging.

High-speed carrier-envelope phase drift detection of amplified laser pulses.

PubMed

Fordell, T; Miranda, M; Arnold, C L; L'Huillier, A

2011-11-21

An instrument for measuring carrier-envelope phase (CEP) drift of amplified femtosecond laser pulses at repetition rates up to the 100-kHz regime is presented. The device can be used for real-time pulse labeling and it could also enable single-loop CEP control of future high-repetition rate laser amplifiers. The scheme is demonstrated by measuring the CEP drift of a 1-kHz source. © 2011 Optical Society of America

Phase control of attosecond pulses in a train

NASA Astrophysics Data System (ADS)

Guo, Chen; Harth, Anne; Carlström, Stefanos; Cheng, Yu-Chen; Mikaelsson, Sara; Mårsell, Erik; Heyl, Christoph; Miranda, Miguel; Gisselbrecht, Mathieu; Gaarde, Mette B.; Schafer, Kenneth J.; Mikkelsen, Anders; Mauritsson, Johan; Arnold, Cord L.; L'Huillier, Anne

2018-02-01

Ultrafast processes in matter can be captured and even controlled by using sequences of few-cycle optical pulses, which need to be well characterized, both in amplitude and phase. The same degree of control has not yet been achieved for few-cycle extreme ultraviolet pulses generated by high-order harmonic generation (HHG) in gases, with duration in the attosecond range. Here, we show that by varying the spectral phase and carrier-envelope phase (CEP) of a high-repetition rate laser, using dispersion in glass, we achieve a high degree of control of the relative phase and CEP between consecutive attosecond pulses. The experimental results are supported by a detailed theoretical analysis based upon the semi-classical three-step model for HHG.

Turning the LHC ring into a new physics search machine

NASA Astrophysics Data System (ADS)

Orava, Risto

2017-03-01

The LHC Collider Ring is proposed to be turned into an ultimate automatic search engine for new physics in four consecutive phases: (1) Searches for heavy particles produced in Central Exclusive Process (CEP): pp → p + X + p based on the existing Beam Loss Monitoring (BLM) system of the LHC; (2) Feasibility study of using the LHC Ring as a gravitation wave antenna; (3) Extensions to the current BLM system to facilitate precise registration of the selected CEP proton exit points from the LHC beam vacuum chamber; (4) Integration of the BLM based event tagging system together with the trigger/data acquisition systems of the LHC experiments to facilitate an on-line automatic search machine for the physics of tomorrow.

A POSSIBLE DETECTION OF OCCULTATION BY A PROTO-PLANETARY CLUMP IN GM Cephei

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

Chen, W. P.; Hu, S. C.-L.; Guo, J. K.

2012-06-01

GM Cephei (GM Cep), in the young ({approx}4 Myr) open cluster Trumpler 37, has been known to be an abrupt variable and to have a circumstellar disk with a very active accretion. Our monitoring observations in 2009-2011 revealed that the star showed sporadic flare events, each with a brightening of {approx}< 0.5 mag lasting for days. These brightening events, associated with a color change toward blue, should originate from increased accretion activity. Moreover, the star also underwent a brightness drop of {approx}1 mag lasting for about a month, during which time the star became bluer when fainter. Such brightness dropsmore » seem to have a recurrence timescale of a year, as evidenced in our data and the photometric behavior of GM Cep over a century. Between consecutive drops, the star brightened gradually by about 1 mag and became blue at peak luminosity. We propose that the drop is caused by the obscuration of the central star by an orbiting dust concentration. The UX Orionis type of activity in GM Cep therefore exemplifies the disk inhomogeneity process in transition between the grain coagulation and the planetesimal formation in a young circumstellar disk.« less

Conserved molecular interactions in centriole-to-centrosome conversion.

PubMed

Fu, Jingyan; Lipinszki, Zoltan; Rangone, Hélène; Min, Mingwei; Mykura, Charlotte; Chao-Chu, Jennifer; Schneider, Sandra; Dzhindzhev, Nikola S; Gottardo, Marco; Riparbelli, Maria Giovanna; Callaini, Giuliano; Glover, David M

2016-01-01

Centrioles are required to assemble centrosomes for cell division and cilia for motility and signalling. New centrioles assemble perpendicularly to pre-existing ones in G1-S and elongate throughout S and G2. Fully elongated daughter centrioles are converted into centrosomes during mitosis to be able to duplicate and organize pericentriolar material in the next cell cycle. Here we show that centriole-to-centrosome conversion requires sequential loading of Cep135, Ana1 (Cep295) and Asterless (Cep152) onto daughter centrioles during mitotic progression in both Drosophila melanogaster and human. This generates a molecular network spanning from the inner- to outermost parts of the centriole. Ana1 forms a molecular strut within the network, and its essential role can be substituted by an engineered fragment providing an alternative linkage between Asterless and Cep135. This conserved architectural framework is essential for loading Asterless or Cep152, the partner of the master regulator of centriole duplication, Plk4. Our study thus uncovers the molecular basis for centriole-to-centrosome conversion that renders daughter centrioles competent for motherhood.

Carrier-envelope-phase stabilized terawatt class laser at 1 kHz with a wavelength tunable option

DOE PAGES

Langdon, Benjamin; Garlick, Jonathan; Ren, Xiaoming; ...

2015-02-12

We demonstrate a chirped-pulse-amplified Ti:Sapphire laser system operating at 1 kHz, with 20 mJ pulse energy, 26 femtosecond pulse duration (0.77 terawatt), and excellent long term carrier-envelope-phase (CEP) stability. A new vibrational damping technique is implemented to significantly reduce vibrational noise on both the laser stretcher and compressor, thus enabling a single-shot CEP noise value of 250 mrad RMS over 1 hour and 300 mrad RMS over 9 hours. This is, to the best of our knowledge, the best long term CEP noise ever reported for any terawatt class laser. This laser is also used to pump a white-light-seeded opticalmore » parametric amplifier, producing 6 mJ of total energy in the signal and idler with 18 mJ of pumping energy. Due to preservation of the CEP in the white-light generated signal and passive CEP stability in the idler, this laser system promises synthesized laser pulses spanning multi-octaves of bandwidth at an unprecedented energy scale.« less

Impact of the Career Explorers Program on High School Students' Perceptions of the Pharmacy Profession

PubMed Central

Stensland, Sheri L.; Warholak, Terri L.; Mattingly, Lisa

2008-01-01

Objective To determine the effect of a 5-week Career Explorers Program (CEP) on high school students' perceptions of pharmacists' characteristics, duties, and training. Methods A 16-item survey instrument with attitudinal, frequency, and relative quantity response options was completed by all CEP students on the first and last day of the program. The survey assessed students' attitudes concerning pharmacist characteristics, duties, and training. Results All students who participated in the CEP in 2003 completed the survey instrument (n = 50). Seventy percent of respondents' answers to the attitudinal subscale questions significantly changed from preassessment to postassessment. Conclusion A 5-week CEP provided high school students with more realistic perceptions of pharmacists' roles, duties, and training before the students entered the pharmacy program. PMID:18698385

The Discovery of Carboxyethylpyrroles (CEPs): Critical Insights into AMD, Autism, Cancer, and Wound Healing from Basic Research on the Chemistry of Oxidized Phospholipids

PubMed Central

Salomon, Robert G.; Hong, Li; Hollyfield, Joe G.

2011-01-01

Basic research, exploring the hypothesis that 2-(ω-carboxyethyl)pyrrole (CEP) modifications of proteins are generated nonenzymatically in vivo is delivering a bonanza of molecular mechanistic insights into age-related macular degeneration, autism, cancer, and wound healing. CEPs are produced through covalent modification of protein lysyl ε-amino groups by γ-hydroxyalkenal phospholipids that are formed by oxidative cleavage of docosahexaenate-containing phospholipids. Chemical synthesis of CEP-modified proteins and the production of highly specific antibodies that recognize them preceded and facilitated their detection in vivo and enabled exploration of their biological occurrence and activities. This investigational approach –from the chemistry of biomolecules to disease phenotype – is proving to be remarkably productive. PMID:21875030

Distinctive proteolytic activity of cell envelope proteinase of Lactobacillus helveticus isolated from airag, a traditional Mongolian fermented mare's milk.

PubMed

Miyamoto, Mari; Ueno, Hiroshi M; Watanabe, Masayuki; Tatsuma, Yumi; Seto, Yasuyuki; Miyamoto, Taku; Nakajima, Hadjime

2015-03-16

Airag is a traditional fermented milk of Mongolia that is usually made from raw mare's milk. Lactobacillus helveticus is one of the lactic acid bacteria most frequently isolated from airag. In this study, we investigated the genetic and physiological characteristics of L. helveticus strains isolated from airag and clarified their significance in airag by comparing them with strains from different sources. Six strains of L. helveticus were isolated from five home-made airag samples collected from different regions of Mongolia. The optimal temperature for acidification in skim milk was 30 to 35°C for all the Mongolian strains, which is lower than those for the reference strains (JCM 1554 and JCM 1120(T)) isolated from European cheeses. All of the strains had a prtH1-like gene encoding a variant type of cell envelope proteinase (CEP). The CEP amino acid sequence in Snow Brand Typeculture (SBT) 11087 isolated from airag shared 71% identity with PrtH of L. helveticus CNRZ32 (AAD50643.1) but 98% identity with PrtH of Lactobacillus kefiranofaciens ZW3 (AEG40278.1) isolated from a traditional fermented milk in Tibet. The proteolytic activities of the CEP from SBT11087 on artificial substrate (N-succinyl-Ala-Ala-Pro-Phe-p-nitroanilide) and pure casein were measured using an intact-cell degradation assay. The activity of the CEP from SBT11087 was observed to be weak and exhibited a lower optimal temperature (40°C) than those from the reference strains (45-50°C). The specificity of the SBT11087 CEP for αS1-casein was typical of the CEPs previously reported in L. helveticus, as determined through the degradation profiles obtained through gel electrophoresis and mass spectrometry analyses. In contrast, the degradation profile of β-casein revealed that the CEP of SBT11087 primarily hydrolyzes its C-terminal domain and hydrolyzed nine of the 16 cleavage sites shared among the CEPs of other L. helveticus strains. Thus, the CEP of SBT11087 is distinct from those from previously reported L. helveticus strains in terms of its optimal temperature and its degradation of β-casein. Therefore, the Mongolian L. helveticus strains differ from other strains of the species in different collections and are specifically suited for the natural lactic acid bacterial population in airag. Copyright © 2014 Elsevier B.V. All rights reserved.

Brief Report: An Observational Measure of Empathy for Autism Spectrum--A Preliminary Study of the Development and Reliability of the Client Emotional Processing Scale

ERIC Educational Resources Information Center

Robinson, Anna; Elliott, Robert

2016-01-01

People with autism spectrum disorder (ASD), can have difficulties in emotion processing, including recognising their own and others' emotions, leading to problems in emotion regulation and interpersonal relating. This study reports the development and piloting of the Client Emotional Processing Scale-Autism Spectrum (CEPS-AS), a new observer…

From bipolar to quadrupolar - The collimation processes of the Cepheus A outflow

NASA Technical Reports Server (NTRS)

Torrelles, Jose M.; Verdes-Montenegro, Lourdes; Ho, Paul T. P.; Rodriguez, Luis F.; Canto, Jorge

1993-01-01

Results of new K-band observations of the (1, 1) and (2, 2) ammonia lines toward Cepheus A are reported. The lines are mapped with approximately 2 arcsec of angular resolution and 0.3 km/s of velocity resolution. A sensitivity of 10 mJy has been achieved. The observations reveal details of the spatial and kinematics structure of the ambient high-density gas. It is suggested that the interstellar high-density gas is diverting and redirecting the outflow in the sense that the quadrupolar structure of the molecular outflow is produced by the interaction with the ammonia condensationss, with Cep A-1 and Cep A-3 splitting in two halves, respectively the blue- and redshifted lobes of an east-west bipolar molecular outflow.

Improving carrier-envelope phase stability in optical parametric chirped-pulse amplifiers by control of timing jitter.

PubMed

Hädrich, S; Rothhardt, J; Krebs, M; Demmler, S; Limpert, J; Tünnermann, A

2012-12-01

It is shown that timing jitter in optical parametric chirped-pulse amplification induces spectral drifts that transfer to carrier-envelope phase (CEP) instabilities via dispersion. Reduction of this effect requires temporal synchronization, which is realized with feedback obtained from the angularly dispersed idler. Furthermore, a novel method to measure the CEP drifts by utilizing parasitic second harmonic generation within parametric amplifiers is presented. Stabilization of the timing allows the obtainment of a CEP stability of 86 mrad over 40 min at 150 kHz repetition rate.

Leber Congenital Amaurosis Associated with Mutations in CEP290, Clinical Phenotype, and Natural History in Preparation for Trials of Novel Therapies.

PubMed

Sheck, Leo; Davies, Wayne I L; Moradi, Phillip; Robson, Anthony G; Kumaran, Neruban; Liasis, Alki C; Webster, Andrew R; Moore, Anthony T; Michaelides, Michel

2018-06-01

To investigate and describe in detail the demographics, functional and anatomic characteristics, and clinical course of Leber congenital amaurosis (LCA) associated with mutations in the CEP290 gene (LCA-CEP290) in a large cohort of adults and children. Retrospective case series. Patients with mutations in CEP290 identified at a single UK referral center. Review of case notes and results of retinal imaging (color fundus photography, fundus autofluorescence [FAF] imaging, OCT), electrophysiologic assessment, and molecular genetic testing. Molecular genetic testing, clinical findings including visual acuity and retinal imaging, and electrophysiologic assessment. Forty patients with LCA-CEP290 were identified. The deep intronic mutation c.2991+1655 A>G was the most common disease-causing variant (23/40 patients) identified in the compound heterozygous state in 20 patients (50%) and homozygous in 2 patients (5%). Visual acuity (VA) varied from 6/9 to no perception of light, and only 2 of 12 patients with longitudinal VA data showed deterioration in VA in their better-seeing eye over time. A normal fundus was found at diagnosis in younger patients (mean age, 1.9 years), with older patients showing white flecks (mean age, 5.9 years) or pigmentary retinopathy (mean age, 21.7 years). Eleven of 12 patients (92%) with OCT imaging had preservation of foveal architecture. Ten of 12 patients (83%) with FAF imaging had a perifoveal hyperautofluorescent ring. Having 2 nonsense CEP290 mutations was associated with worse final VA and the presence of nonocular features. Detailed analysis of the clinical phenotype of LCA-CEP290 in a large cohort confirms that there is a window of opportunity in childhood for therapeutic intervention based on relative structural preservation in the central cone-rich retina in a significant proportion of patients, with the majority harboring the deep intronic variant potentially tractable to several planned gene editing approaches. Copyright © 2018 American Academy of Ophthalmology. All rights reserved.

Cycling excitation process: An ultra efficient and quiet signal amplification mechanism in semiconductor

NASA Astrophysics Data System (ADS)

Liu, Yu-Hsin; Yan, Lujiang; Zhang, Alex Ce; Hall, David; Niaz, Iftikhar Ahmad; Zhou, Yuchun; Sham, L. J.; Lo, Yu-Hwa

2015-08-01

Signal amplification, performed by transistor amplifiers with its merit rated by the efficiency and noise characteristics, is ubiquitous in all electronic systems. Because of transistor thermal noise, an intrinsic signal amplification mechanism, impact ionization was sought after to complement the limits of transistor amplifiers. However, due to the high operation voltage (30-200 V typically), low power efficiency, limited scalability, and, above all, rapidly increasing excess noise with amplification factor, impact ionization has been out of favor for most electronic systems except for a few applications such as avalanche photodetectors and single-photon Geiger detectors. Here, we report an internal signal amplification mechanism based on the principle of the phonon-assisted cycling excitation process (CEP). Si devices using this concept show ultrahigh gain, low operation voltage, CMOS compatibility, and, above all, quantum limit noise performance that is 30 times lower than devices using impact ionization. Established on a unique physical effect of attractive properties, CEP-based devices can potentially revolutionize the fields of semiconductor electronics.

Carrier-envelope-phase control of asymmetries in the multiphoton ionization of xenon atoms by ultrashort bichromatic fields

NASA Astrophysics Data System (ADS)

Kerbstadt, S.; Pengel, D.; Englert, L.; Bayer, T.; Wollenhaupt, M.

2018-06-01

We report on bichromatic multiphoton ionization of xenon atoms (Xe) to demonstrate carrier-envelope-phase (CEP) control of lateral asymmetries in the photoelectron momentum distribution. In the experiments, we employ a 4 f polarization pulse shaper to sculpture bichromatic fields with commensurable center frequencies ω1:ω2=7 :8 from an over-octave-spanning CEP-stable white light supercontinuum by spectral amplitude and phase modulation. The bichromatic fields are spectrally tailored to induce controlled interferences of 7- vs 8-photon quantum pathways in the 5 P3 /2 ionization continuum of Xe. The CEP sensitivity of the asymmetric final-state wave function arises from coherent superposition of continuum states with opposite parity. Our results demonstrate that shaper-generated bichromatic fields with tailored center frequency ratio are a suitable tool to localize CEP-sensitive asymmetries in a specific photoelectron kinetic-energy window.

Indian hedgehog contributes to human cartilage endplate degeneration.

PubMed

Wang, Shaowei; Yang, Kun; Chen, Shuai; Wang, Jiying; Du, Guoqing; Fan, Shunwu; Wei, Lei

2015-08-01

To determine the role of Indian hedgehog (Ihh) signaling in human cartilage endplate (CEP) degeneration. CEP-degenerated tissues from patients with Modic I or II changes (n = 9 and 45, respectively) and normal tissues from vertebral burst fracture patients (n = 17) were collected. Specimens were either cut into slices for organ culture ex vivo or digested to isolate chondrocytes for cell culture in vitro. Ihh expression and the effect of Ihh on cartilage degeneration were determined by investigating degeneration markers in this study. Ihh expression and cartilage degeneration markers significantly increased in the Modic I and II groups. The expression of cartilage degeneration markers was positively correlated with degeneration severity. Gain-of-function for Ihh promoted expression of cartilage degeneration markers in vitro, while loss-of-function for Ihh inhibited their expression both in vitro and ex vivo. These findings demonstrated that Ihh promotes CEP degeneration. Blocking Ihh pathway has potential clinical usage for attenuating CEP degeneration.

Corruption Early Prevention: Decision Support System for President of the Republic of Indonesia

NASA Astrophysics Data System (ADS)

Sasmoko; Widhoyoko, S. A.; Ariyanto, S.; Indrianti, Y.; Noerlina; Muqsith, A. M.; Alamsyah, M.

2017-01-01

Corruption is an extraordinary crime, and then the prevention must also be extraordinary, simultaneously (national) in the form of early warning that involves all elements; government, industry, and society. To realize it the system needs to be built which in this study is called the Corruption Early Prevention (CEP) as a Decision Support System for President of the Republic of Indonesia. This study aims to examine 1) how is the construct of the Corruption Early Prevention as a Decision Support System for President of the Republic of Indonesia?, and 2) how is the design form of the system of Corruption Early Prevention as a Decision Support System for President of Republic of Indonesia? The research method is using Neuro-Research which is the collaboration of qualitative and quantitative research methods and the model development of Information Technology (IT). The research found that: 1) the construct of CEP is theoretically feasible, valid and reliable by content to be developed in the context of the prevention of corruption in Indonesia as an early prevention system that diagnoses Indonesia simultaneously and in real time, and 2) the concept of system design and business process of CEP is predicted to be realized in the IT-based program.

Locating the QCD critical end point through peaked baryon number susceptibilities along the freeze-out line

NASA Astrophysics Data System (ADS)

Li, Zhibin; Chen, Yidian; Li, Danning; Huang, Mei

2018-01-01

We investigate the baryon number susceptibilities up to fourth order along different freeze-out lines in a holographic QCD model with a critical end point (CEP), and we propose that the peaked baryon number susceptibilities along the freeze-out line can be used as a clean signature to locate the CEP in the QCD phase diagram. On the temperature and baryon chemical potential plane, the cumulant ratio of the baryon number susceptibilities (up to fourth order) forms a ridge along the phase boundary, and develops a sword-shaped “mountain” standing upright around the CEP in a narrow and oblate region. The measurement of baryon number susceptibilities from heavy-ion collision experiments is along the freeze-out line. If the freeze-out line crosses the foot of the CEP mountain, then one can observe the peaked baryon number susceptibilities along the freeze-out line, and the kurtosis of the baryon number distributions has the highest magnitude. The data from the first phase of the beam energy scan program at the Relativistic Heavy Ion Collider indicates that there should be a peak of the kurtosis of the baryon number distribution at a collision energy of around 5 GeV, which suggests that the freeze-out line crosses the foot of the CEP mountain and the summit of the CEP should be located nearby, around a collision energy of 3-7 GeV. Supported by NSFC (11275213, and 11261130311) (CRC 110 by DFG and NSFC), CAS key project KJCX2-EW-N01, and Youth Innovation Promotion Association of CAS

Towards Hybrid Online On-Demand Querying of Realtime Data with Stateful Complex Event Processing

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

Zhou, Qunzhi; Simmhan, Yogesh; Prasanna, Viktor K.

Emerging Big Data applications in areas like e-commerce and energy industry require both online and on-demand queries to be performed over vast and fast data arriving as streams. These present novel challenges to Big Data management systems. Complex Event Processing (CEP) is recognized as a high performance online query scheme which in particular deals with the velocity aspect of the 3-V’s of Big Data. However, traditional CEP systems do not consider data variety and lack the capability to embed ad hoc queries over the volume of data streams. In this paper, we propose H2O, a stateful complex event processing framework,more » to support hybrid online and on-demand queries over realtime data. We propose a semantically enriched event and query model to address data variety. A formal query algebra is developed to precisely capture the stateful and containment semantics of online and on-demand queries. We describe techniques to achieve the interactive query processing over realtime data featured by efficient online querying, dynamic stream data persistence and on-demand access. The system architecture is presented and the current implementation status reported.« less

Responding to Community Needs.

ERIC Educational Resources Information Center

Salinas, Alicia M.

This paper outlines the development process of a Comprehensive Education Plan (CEP) for one Texas school district. The Center for the Management of Innovation in Multicultural Education (MIME) is assisting the Edcouch-Elsa Independent School District to develop a comprehensive plan that will answer the whole community's educational needs. The…

Carrier-envelope phase control of carrier-wave Rabi flopping in asymmetric semiparabolic quantum well.

PubMed

Zhang, Chaojin; Song, Xiaohong; Yang, Weifeng; Xu, Zhizhan

2008-02-04

We investigate the carrier-wave Rabi flopping effects in an asymmetric semiparabolic semiconductor quantum well (QW) with few-cycle pulse. It is found that higher spectral components of few-cycle ultrashort pulses in the semiparabolic QW depend crucially on the carrier-envelope phase (CEP) of the few-cycle ultrashort pulses: continuum and distinct peaks can be achieved by controlling the CEP. Our results demonstrate that by adjusting the CEP of few-cycle ultrashort pulses, the intersubband dynamics in the asymmetric semiparabolic QW can be controlled in an ultrashort timescale with moderate laser intensity.

Robust generation of isolated attosecond pulse against the variation of carrier envelope phase of driving laser pulses

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

Zou Pu; Zeng Zhinan; Zheng Yinghui

2010-11-15

We propose a scheme for generating isolated attosecond pulse (IAP) via high-order harmonic generation in gases using a chirped two-color laser field of multicycle duration. In contrast to previous techniques where the stable carrier-envelope phase (CEP) of the driving laser pulses is a prerequisite for IAP generation, the proposed scheme is robust against the large variation of CEP. We show the generation of IAP with an intensity fluctuation less than 50% and an intensity contrast ratio higher than 5:1 when the CEP shift is as large as 1.35{pi}.

Cervical enamel projections in unusual locations: a case report and mini-review.

PubMed

Chan, Hsun-Liang; Oh, Tae-Ju; Bashutski, Jill; Fu, Jia-Hui; Wang, Hom-Lay

2010-05-01

Periodontitis is primarily a bacteria-induced disease that can be modified by tooth-related local factors. Cervical enamel projections (CEPs) are a common tooth anomaly that can act as contributing factors in the development of periodontitis. They are most commonly found at the buccal surfaces of mandibular molars. A 57-year-old female was referred to our clinic for treatment of chronic periodontitis. A clinical examination revealed moderate attachment loss that was localized to the palatal side of the maxillary second molars. The rest of the dentition was less affected, with a diagnosis of generalized slight chronic periodontitis. An initial non-surgical periodontal treatment was provided followed by apically positioned flap surgery in the maxillary right and left posterior areas. At the time of surgery, CEPs were found where the periodontium was most affected. Because surgical intervention exposed the CEPs, they were not removed. After the active therapy, which resulted in inflammation resolution and maintainable probing depths, the patient was placed on a 3-month recall for periodontal maintenance. CEPs were found in an unusual location on the palatal roots of maxillary second molars. The findings of this case report confirm the role of CEPs as a local contributing factor in localized chronic periodontitis.

Cervical enamel projections in unusual locations: A case report and mini-review.

PubMed

Chan, Hsun-Liang; Oh, Tae-Ju; Bashutski, Jill; Fu, Jia-Hui; Wang, Hom-Lay

2010-02-02

Background: Periodontitis is primarily a bacteria-induced disease that can be modified by tooth-related local factors. Cervical enamel projections (CEPs) are a common tooth anomaly that can act as a contributing factor in the development of periodontitis. They are most commonly found at the buccal surfaces of mandibular molars. Methods: A 57-year-old female was referred to our clinic for treatment of chronic periodontitis. Clinical examination revealed moderate attachment loss that was localized to the palatal side of the maxillary secondary molars. The rest of the dentition was less affected, with a diagnosis of generalized slight chronic periodontitis. Initial non-surgical periodontal treatment was provided, followed by apically positioned flap surgery in the maxillary right and left posterior areas. At the time of surgery, CEPs were found where the periodontium was most affected. Results: Due to the fact that surgical intervention exposed the CEPs, they were not removed. After the active therapy, which resulted in inflammation resolution and maintainable probing depth, the patient was placed on a three-month recall for periodontal maintenance. Conclusions: This case report presents CEPs in an unusual location in the palatal roots of maxillary secondary molars. CEPs confirm their role as a local contributing factor in localized chronic periodontitis.

Zoledronic acid induces a significant decrease of circulating endothelial cells and circulating endothelial precursor cells in the early prostate cancer neoadjuvant setting.

PubMed

Santini, Daniele; Zoccoli, Alice; Gregorj, Chiara; Di Cerbo, Melania; Iuliani, Michele; Pantano, Francesco; Zamarchi, Rita; Sergi, Federico; Flammia, Gerardo; Buscarini, Maurizio; Rizzo, Sergio; Cicero, Giuseppe; Russo, Antonio; Vincenzi, Bruno; Avvisati, Giuseppe; Tonini, Giuseppe

2013-01-01

Published data demonstrated that zoledronic acid (ZOL) exhibits antiangiogenetic effects. A promising tool for monitoring antiangiogenic therapies is the measurement of circulating endothelial cells (CECs) and circulating endothelial precursor cells (CEPs) in the peripheral blood of patients. Our aim was to investigate the effects of ZOL on levels of CECs and CEPs in localized prostate cancer. Ten consecutive patients with a histologic diagnosis of low-risk prostate adenocarcinoma were enrolled and received an intravenous infusion of ZOL at baseline (T0), 28 days (T28) and 56 days (T56). Blood samples were collected at the following times: T0 (before the first infusion of ZOL), T3 (72 h after the first dose), T28, T56 (both just before the ZOL infusion) and T84 (28 days after the last infusion of ZOL) and CEC/CEP levels were directly quantified by flow cytometry at all these time points. Our analyses highlighted a significant reduction of mean percentage of CECs and CEPs after initiation of ZOL treatment [p = 0.014 (at day 3) and p = 0.012 (at day 84), respectively]. These preliminary results demonstrate that ZOL could exert an antiangiogenic effect in early prostate cancer through CEP and CEC modulation.

'Too-much-of-a-good-thing'? The role of advanced eco-learning and contingency factors on the relationship between corporate environmental and financial performance.

PubMed

Latan, Hengky; Chiappetta Jabbour, Charbel Jose; Lopes de Sousa Jabbour, Ana Beatriz; Renwick, Douglas William Scott; Wamba, Samuel Fosso; Shahbaz, Muhammad

2018-08-15

Inspired by the natural-resource-based view (NRBV) theory, we attempt to shed light on a controversy which has been persistent over the last decade, concerning the relationship between corporate environmental performance (CEP) and corporate financial performance (CFP). Using the 'too-much-of-a-good-thing' (TMGT) concept, which suggests that "too much can be worse than too little," we link mixed results and consider the roles of advanced eco-learning and contingency factors in influencing the CEP-CFP relationship. Based on a sample composed of ISO 14001 certified companies in Indonesia, and analyzing the data using consistent Partial Least Squares (PLSc), we found that: the CEP-CFP relationship follows an inverted U-shape; advanced eco-learning is a significant predictor of the CEP-CFP relationship, meaning that organizations able to develop higher eco-learning capability will be better able to identify the ideal boundaries of investment in environmental performance without reducing their financial performance; and that contingency factors such as environmental strategy and firm size have a significant role in influencing the CEP-CFP relationship. The study's limitations, implications for practitioners and a future research agenda are also detailed. Copyright © 2018 Elsevier Ltd. All rights reserved.

PULSAR: A High-Repetition-Rate, High-Power, CE Phase-Locked Laser for the J.R. Macdonald Laboratory at Kansas State University

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

Ben-Itzhak, Itzik; Carnes, Kevin D.; Cocke, C. Lew

2014-05-09

This instrumentation grant funded the development and installation of a state-of-the-art laser system to be used for the DOE funded research at the J.R. Macdonald Laboratory at Kansas State University. Specifically, we purchased a laser based on the KMLABs Red-Dragon design, which has a high repetition rate of 10-20 kHz crucial for multi-parameter coincidence measurements conducted in our lab. This laser system is carrier-envelope phase (CEP) locked and provides pulses as short as 21 fs directly from the amplifier (see details below). In addition, we have developed a pulse compression setup that provides sub 5 fs pulses and a CEPmore » tagging capability that allows for long measurements of CEP dependent processes.« less

Low-dose metronomic cyclophosphamide combined with vascular disrupting therapy induces potent antitumor activity in preclinical human tumor xenograft models.

PubMed

Daenen, Laura G; Shaked, Yuval; Man, Shan; Xu, Ping; Voest, Emile E; Hoffman, Robert M; Chaplin, David J; Kerbel, Robert S

2009-10-01

Vascular disrupting agents preferentially target the established but abnormal tumor vasculature, resulting in extensive intratumoral hypoxia and cell death. However, a rim of viable tumor tissue remains from which angiogenesis-dependent regrowth can occur, in part through the mobilization and tumor colonization of circulating endothelial progenitor cells (CEP). Cotreatment with an agent that blocks CEPs, such as a vascular endothelial growth factor pathway-targeting biological antiangiogenic drug, results in enhanced antitumor efficacy. We asked whether an alternative therapeutic modality, low-dose metronomic chemotherapy, could achieve the same result given its CEP-targeting effects. We studied the combination of the vascular disrupting agent OXi4503 with daily administration of CEP-inhibiting, low-dose metronomic cyclophosphamide to treat primary orthotopic tumors with the use of the 231/LM2-4 breast cancer cell line and MeWo melanoma cell line. In addition, CEP mobilization and various tumor characteristics were assessed. We found that daily p.o. low-dose metronomic cyclophosphamide was capable of preventing the CEP spike and tumor colonization induced by OXi4503. This was associated with a decrease in the tumor rim and marked suppression of primary 231/LM2-4 growth in nude as well as severe combined immunodeficient mice. Similar results were found in MeWo-bearing nude mice. The delay in tumor growth was accompanied by significant decreases in microvessel density, perfusion, and proliferation, and a significant increase in tumor cell apoptosis. No overt toxicity was observed. The combination of OXi4503 and metronomic chemotherapy results in prolonged tumor control, thereby expanding the list of therapeutic agents that can be successfully integrated with metronomic low-dose chemotherapy.

prtH2, Not prtH, Is the Ubiquitous Cell Wall Proteinase Gene in Lactobacillus helveticus▿

PubMed Central

Genay, M.; Sadat, L.; Gagnaire, V.; Lortal, S.

2009-01-01

Lactobacillus helveticus strains possess an efficient proteolytic system that releases peptides which are essential for lactobacillus growth in various fermented dairy products and also affect textural properties or biological activities. Cell envelope proteinases (CEPs) are bacterial enzymes that hydrolyze milk proteins. In the case of L. helveticus, two CEPs with low percentages of amino acid identity have been described, i.e., PrtH and PrtH2. However, the distribution of the genes that encode CEPs still remains unclear, rendering it difficult to further control the formation of particular peptides. This study evaluated the diversity of genes that encode CEPs in a collection of strains of L. helveticus isolated from various biotopes, both in terms of the presence or absence of these genes and in terms of nucleotide sequence, and studied their transcription in dairy matrices. After defining three sets of primers for both the prtH and prtH2 genes, we studied the distribution of the genes by using PCR and Southern blotting experiments. The prtH2 gene was ubiquitous in the 29 strains of L. helveticus studied, whereas only 18 of them also exhibited the prtH gene. Sequencing of a 350-bp internal fragment of these genes revealed the existence of intraspecific diversity. Finally, expression of these two CEP-encoding genes was followed during the growth in dairy matrices of two strains, ITG LH77 and CNRZ32, which possess one and two CEP-encoding genes, respectively. Both genes were shown to be expressed by L. helveticus at each stage of growth in milk and at different stages of mini-Swiss-type cheese making and ripening. PMID:19286786

The Secret Lives of Cepheids: δ Cep—The Prototype of a New Class of Pulsating X-Ray Variable Stars

NASA Astrophysics Data System (ADS)

Engle, Scott G.; Guinan, Edward F.; Harper, Graham M.; Cuntz, Manfred; Remage Evans, Nancy; Neilson, Hilding R.; Fawzy, Diaa E.

2017-03-01

From our Secret Lives of Cepheids program, the prototype Classical Cepheid, δ Cep, is found to be an X-ray source with periodic pulsation-modulated X-ray variations. This finding complements our earlier reported phase-dependent FUV-UV emissions of the star that increase ˜10-20 times with highest fluxes at ˜ 0.90{--}0.95φ , just prior to maximum brightness. Previously δ Cep was found as potentially X-ray variable, using XMM-Newton observations. Additional phase-constrained data were secured with Chandra near X-ray emission peak, to determine if the emission and variability were pulsation-phase-specific to δ Cep and not transient or due to a possible coronally active, cool companion. The Chandra data were combined with prior XMM-Newton observations, and were found to very closely match the previously observed X-ray behavior. From the combined data set, a ˜4 increase in X-ray flux is measured, reaching a peak {L}{{X}} = 1.7 × 1029 erg s-1 near 0.45ϕ. The precise X-ray flux phasing with the star’s pulsation indicates that the emissions arise from the Cepheid and not from a companion. However, it is puzzling that the maximum X-ray flux occurs ˜0.5ϕ (˜3 days) later than the FUV-UV maximum. There are several other potential Cepheid X-ray detections with properties similar to δ Cep, and comparable X-ray variability is indicated for two other Cepheids: β Dor and V473 Lyr. X-ray generating mechanisms in δ Cep and other Cepheids are discussed. If additional Cepheids are confirmed to show phased X-ray variations, then δ Cep will be the prototype of a new class of pulsation-induced X-ray variables.

Diesel-Enriched Particulate Matter Functionally Activates Human Dendritic Cells

PubMed Central

Porter, Michael; Karp, Matthew; Killedar, Smruti; Bauer, Stephen M.; Guo, Jia; Williams, D'Ann; Breysse, Patrick; Georas, Steve N.; Williams, Marc A.

2007-01-01

Epidemiologic studies have associated exposure to airborne particulate matter (PM) with exacerbations of asthma. It is unknown how different sources of PM affect innate immunity. We sought to determine how car- and diesel exhaust–derived PM affects dendritic cell (DC) activation. DC development was modeled using CD34+ hematopoietic progenitors. Airborne PM was collected from exhaust plenums of Fort McHenry Tunnel providing car-enriched particles (CEP) and diesel-enriched particles (DEP). DC were stimulated for 48 hours with CEP, DEP, CD40-ligand, or lipopolysaccharide. DC activation was assessed by flow cytometry, enzyme-linked immunosorbent assay, and standard culture techniques. DEP increased uptake of fluorescein isothiocyanate–dextran (a model antigen) by DC. Diesel particles enhanced cell-surface expression of co-stimulatory molecules (e.g., CD40 [P < 0.01] and MHC class II [P < 0.01]). By contrast, CEP poorly affected antigen uptake and expression of cell surface molecules, and did not greatly affect cytokine secretion by DC. However, DEP increased production of TNF, IL-6, and IFN-γ (P < 0.01), IL-12 (P < 0.05), and vascular endothelial growth factor (P < 0.001). In co-stimulation assays of PM-exposed DC and alloreactive CD4+ T cells, both CEP and DEP directed a Th2-like pattern of cytokine production (e.g., enhanced IL-13 and IL-18 and suppressed IFN-γ production). CD4+ T cells were not functionally activated on exposure to either DEP or CEP. Car- and diesel-enriched particles exert a differential effect on DC activation. Our data support the hypothesis that DEP (and to a lesser extent CEP) regulate important functional aspects of human DC, supporting an adjuvant role for this material. PMID:17630318

Geophysical Investigation Along the Great Miami River From New Miami to Charles M. Bolton Well Field, Cincinnati, Ohio

USGS Publications Warehouse

Sheets, R.A.; Dumouchelle, D.H.

2009-01-01

Three geophysical profiling methods were tested to help characterize subsurface materials at selected transects along the Great Miami River, in southwestern Ohio. The profiling methods used were continuous seismic profiling (CSP), continuous resistivity profiling (CRP), and continuous electromagnetic profiling (CEP). Data were collected with global positioning systems to spatially locate the data along the river. The depth and flow conditions of the Great Miami River limited the amount and quality of data that could be collected with the CSP and CRP methods. Data from the CSP were generally poor because shallow reflections (less than 5 meters) were mostly obscured by strong multiple reflections and deep reflections (greater than 5 meters) were sparse. However, modeling of CRP data indicated broad changes in subbottom geology, primarily below about 3 to 5 meters. Details for shallow electrical conductivity (resistivity) (less than 3 meters) were limited because of the 5-meter electrode spacing used for the surveys. For future studies of this type, a cable with 3-meter electrode spacing (or perhaps even 1-meter spacing) might best be used in similar environments to determine shallow electrical properties of the stream-bottom materials. CEP data were collected along the entire reach of the Great Miami River. The CRP and CEP data did not correlate well, but the CRP electrode spacing probably limited the correlation. Middle-frequency (3,510 hertz) and high-frequency (15,030 hertz) CEP data were correlated to water depth. Low-frequency (750 hertz) CEP data indicate shallow (less than 5-meter) changes in electrical conductivity. Given the variability in depth and flow conditions on a river such as the Great Miami, the CEP method worked better than either the CSP or CRP methods.

Basal exon skipping and nonsense-associated altered splicing allows bypassing complete CEP290 loss-of-function in individuals with unusually mild retinal disease.

PubMed

Barny, Iris; Perrault, Isabelle; Michel, Christel; Soussan, Mickael; Goudin, Nicolas; Rio, Marlène; Thomas, Sophie; Attié-Bitach, Tania; Hamel, Christian; Dollfus, Hélène; Kaplan, Josseline; Rozet, Jean-Michel; Gerard, Xavier

2018-05-16

CEP290 mutations cause a spectrum of ciliopathies from Leber congenital amaurosis type 10 (LCA10) to embryo-lethal Meckel syndrome (MKS). Using panel-based molecular diagnosis testing for inherited retinal diseases, we identified two individuals with some preserved vision despite biallelism for presumably truncating CEP290 mutations. The first one carried a homozygous 1 base-pair deletion in exon 17, introducing a premature termination codon (PTC) in exon 18 (c.1666del; p.Ile556Phefs*17). mRNA analysis revealed a basal exon skipping (BES) of exon 18, providing mutant cells with the ability to escape protein truncation, while disrupting the reading frame in controls. The second individual harbored compound heterozygous nonsense mutations in exon 8 (c.508A>T, p.Lys170*) and exon 32 (c.4090G>T, p.Glu1364*), respectively. Some CEP290 lacking exon 8 were detected in mutant fibroblasts but not in controls whereas some skipping of exon 32 occurred in both lines, but with higher amplitude in the mutant. Considering that the deletion of either exon maintains the reading frame in either line, skipping in mutant cells likely involves nonsense-associated altered splicing (NAS) alone (exon 8), or with BES (exon 32). Skipping of PTC-containing exons in mutant cells allowed production of CEP290 isoforms with preserved ability to assemble into a high molecular weight complex and to interact efficiently with proteins important for cilia formation and intraflagellar trafficking. In contrast, studying LCA10 and MKS fibroblasts we show moderate to severe cilia alterations, providing support for a correlation between disease severity and the ability of cells to express shortened, yet functional, CEP290 isoforms.

Advancing Diversity in Higher Education

ERIC Educational Resources Information Center

Turner, Caroline S.

2013-01-01

This special section of the "Journal of Diversity in Higher Education" ("JDHE") on "Advancing Diversity in Higher Education" emerged from the 2012 Association for the Study of Higher Education Council on Ethnic Participation (ASHE-CEP) Pre-Conference Forum. CEP, a standing committee of ASHE, partnered with the…

New insights into the near-IR spectroscopy of the young variable PV Cep

NASA Astrophysics Data System (ADS)

Lorenzetti, D.; Giannini, T.; Antoniucci, S.; Kopatskaya, E. N.; Larionov, V.; Arkharov, A. A.; Di Paola, A.; Nisini, B.

2015-08-01

During our EXor monitoring programme dubbed EXORCISM (EXOR OptiCal and Infrared Systematic Monitoring - Antoniucci et al. 2013 PPVI, Lorenzetti et al. 2007 ApJ 665, 1182), we have been observing the variable source PV Cep (ATel #1256; #1607).

Stabilization of cartwheel-less centrioles for duplication requires CEP295-mediated centriole to centrosome conversion

PubMed Central

Izquierdo, Denisse; Wang, Won-Jing; Uryu, Kunihiro; Tsou, Meng-Fu Bryan

2014-01-01

SUMMARY Vertebrate centrioles lose their geometric scaffold, the cartwheel, during mitosis, concurrently with gaining the ability to recruit the pericentriolar material (PCM) and thereby function as the centrosome. Cartwheel removal has recently been implicated in centriole duplication, but whether “cartwheel-less” centrioles are intrinsically stable, or must be maintained through other modifications remains unclear. Here, we identify a newborn centriole-enriched protein, KIAA1731/CEP295, specifically mediating centriole-to-centrosome conversion but dispensable for cartwheel removal. In the absence of CEP295, centrioles form in S/G2 phase, and lose their associated cartwheel in mitosis, but cannot be converted to centrosomes, uncoupling the two events. Strikingly, centrioles devoid of both the PCM and cartwheel progressively lose centriolar components, whereas centrioles associating with either the cartwheel or PCM alone can exist stably. Thus, cartwheel removal can have grave repercussions to centriole stability, and centriole-to-centrosome conversion mediated by CEP295 must occur in parallel to maintain cartwheel-less centrioles for duplication. PMID:25131205

p53/CEP-1 Increases or Decreases Lifespan, Depending on Level of Mitochondrial Bioenergetic Stress

PubMed Central

Ventura, Natascia; Rea, Shane L.; Schiavi, Alfonso; Torgovnick, Alessandro; Testi, Roberto; Johnson, Thomas E.

2009-01-01

SUMMARY Mitochondrial pathologies underlie a number of life-shortening diseases in humans. In the nematode Caenorhabditis elegans, severely reduced expression of mitochondrial proteins involved in electron transport chain-mediated energy production also leads to pathological phenotypes, including arrested development and/or shorter life; in sharp contrast, mild suppression of these same proteins extends lifespan. Here we show that the C. elegans p53 ortholog cep-1 mediates these opposite effects. We find that cep-1 is required to extend longevity in response to mild suppression of several bioenergetically relevant mitochondrial proteins, including frataxin - the protein defective in patients with Friedreich’s Ataxia. Importantly we show that cep-1 also mediates both the developmental arrest and life shortening induced by severe mitochondrial stress. Our findings support an evolutionarily conserved function for p53 in modulating organismal responses to mitochondrial dysfunction and suggest that metabolic checkpoint responses may play a role in longevity control and in human mitochondrial-associated diseases. PMID:19416129

Evaluating Candidate Principal Surrogate Endpoints

PubMed Central

Gilbert, Peter B.; Hudgens, Michael G.

2009-01-01

Summary Frangakis and Rubin (2002, Biometrics 58, 21–29) proposed a new definition of a surrogate endpoint (a “principal” surrogate) based on causal effects. We introduce an estimand for evaluating a principal surrogate, the causal effect predictiveness (CEP) surface, which quantifies how well causal treatment effects on the biomarker predict causal treatment effects on the clinical endpoint. Although the CEP surface is not identifiable due to missing potential outcomes, it can be identified by incorporating a baseline covariate(s) that predicts the biomarker. Given case–cohort sampling of such a baseline predictor and the biomarker in a large blinded randomized clinical trial, we develop an estimated likelihood method for estimating the CEP surface. This estimation assesses the “surrogate value” of the biomarker for reliably predicting clinical treatment effects for the same or similar setting as the trial. A CEP surface plot provides a way to compare the surrogate value of multiple biomarkers. The approach is illustrated by the problem of assessing an immune response to a vaccine as a surrogate endpoint for infection. PMID:18363776

Tank binding kinase 1 is a centrosome-associated kinase necessary for microtubule dynamics and mitosis

PubMed Central

Pillai, Smitha; Nguyen, Jonathan; Johnson, Joseph; Haura, Eric; Coppola, Domenico; Chellappan, Srikumar

2015-01-01

TANK Binding Kinase 1 (TBK1) is a non-canonical IκB kinase that contributes to KRAS-driven lung cancer. Here we report that TBK1 plays essential roles in mammalian cell division. Specifically, levels of active phospho-TBK1 increase during mitosis and localize to centrosomes, mitotic spindles and midbody, and selective inhibition or silencing of TBK1 triggers defects in spindle assembly and prevents mitotic progression. TBK1 binds to the centrosomal protein CEP170 and to the mitotic apparatus protein NuMA, and both CEP170 and NuMA are TBK1 substrates. Further, TBK1 is necessary for CEP170 centrosomal localization and binding to the microtubule depolymerase Kif2b, and for NuMA binding to dynein. Finally, selective disruption of the TBK1–CEP170 complex augments microtubule stability and triggers defects in mitosis, suggesting that TBK1 functions as a mitotic kinase necessary for microtubule dynamics and mitosis. PMID:26656453

G3(MP2)-CEP theory and applications for compounds containing atoms from representative first, second and third row elements of the periodic table.

PubMed

Pereira, Douglas Henrique; Rocha, Carlos Murilo Romero; Morgon, Nelson Henrique; Custodio, Rogério

2015-08-01

The compact effective potential (CEP) pseudopotential was adapted to the G3(MP2) theory, herein referred to as G3(MP2)-CEP, and applied to the calculation of enthalpies of formation, ionization energies, atomization energies, and electron and proton affinities for 446 species containing elements of the 1st, 2nd, and 3rd rows of the periodic table. A total mean absolute deviation of 1.67 kcal mol(-1) was achieved with G3(MP2)-CEP, compared with 1.47 kcal mol(-1) for G3(MP2). Electron affinities and enthalpies of formation are the properties exhibiting the lowest deviations with respect to the original G3(MP2) theory. The use of pseudopotentials and composite theories in the framework of the G3 theory is feasible and compatible with the all electron approach. Graphical Abstract Application of composite methods in high-level ab initio calculations.

Carrier Envelope Phase Effect of a Long Duration Pulse in the Low Frequency Region

NASA Astrophysics Data System (ADS)

Zhao, Xi; Yang, Yu-Jun; Liu, Xue-Shen; Wang, Bing-Bing

2014-04-01

Using the characteristic of small energy difference between two high Rydberg states, we theoretically investigate the carrier envelope phase (CEP) effect in a bound-bound transition of an atom in a low-frequency long laser pulse with tens of optical cycles. Particularly, we first prepare a Rydberg state of a hydrogen-like atom by a laser field with the resonant frequency between this state and the ground state. Then by using a low-frequency long laser pulse interacting with this Rydberg atom, we calculate the population of another Rydberg state nearby this Rydberg state at the end of the laser pulse and find that the population changes dramatically with the CEP of the low-frequency pulse. This CEP effect is attributed to the interference between the positive-frequency and negative-frequency components in one-photon transition. These results may provide a method to measure the CEP value of a long laser pulse with low frequency.

Massive hemorrhage after Kasai portoenterostomy in a patient with a congenital extrahepatic portosystemic shunt, malrotation and a double aortic arch: report of a case.

PubMed

Takazawa, Shinya; Uchida, Hiroo; Kawashima, Hiroshi; Tanaka, Yujiro; Sato, Kaori; Jimbo, Takahiro; Deie, Kyoichi; Koiwai, Kazuki; Nomura, Koji; Iwanaka, Tadashi

2014-08-01

A newborn female was transferred to our hospital presenting with severe respiratory distress. She underwent tracheal intubation and nasogastric tubing. Investigations revealed a congenital extrahepatic portosystemic shunt (CEPS) type 1, biliary atresia, heterotaxia, polysplenia, malrotation and a double aortic arch (DAA). She underwent the Kasai portoenterostomy and the Ladd procedure when she was 29 days old. On postoperative day 20, she developed sudden hematemesis with bright red blood. Endoscopy showed massive bleeding from an esophageal ulcer, and endoscopic therapy was performed successfully. During left thoracotomy, an aortoesophageal fistula (AEF) was detected and repaired by direct suturing. The postoperative course was uneventful. CEPS type 1 is commonly associated with other congenital malformations; however, there have been no previous reports of an association between CEPS and DAA. Nasogastric tube insertion in a patient with DAA can result in catastrophic AEF. The treatment strategy should be carefully considered in patients with CEPS type 1 and multiple congenital fetal anomalies.

The Abernethy malformation-myriad imaging manifestations of a single entity.

PubMed

Ghuman, Samarjit S; Gupta, Saumya; Buxi, T B S; Rawat, Kishan S; Yadav, Anurag; Mehta, Naimish; Sud, Seema

2016-01-01

Abernethy malformation, also known as congenital extrahepatic portosystemic shunts (CEPS) is a rare clinical entity and manifests with different clinical symptoms. CEPS are abnormalities of vascular development where there is shunting of portal blood into the systemic venous system. Multidetector computed tomography (MDCT) is a fast and effective modality for evaluation of CEPS. CT displays all the information desired by the surgeon as well as the clinician including the anatomy of the splenic and superior mesenteric veins, size and site of the shunt, presence or absence of the portal vein radicles, and helps to plan the therapy and even the follow-up of these patients. Contrast-enhanced magnetic resonance imaging (MRI) has also emerged as a promising tool for the evaluation of liver lesions associated with the malformation. The Radiologist should be aware of the various imaging appearances of this entity including its complications. In this article, we describe the imaging appearances of CEPS, their complications, and their imaging appearances on CT and MRI. We have also described various associated anomalies.

The Abernethy malformation—myriad imaging manifestations of a single entity

PubMed Central

Ghuman, Samarjit S; Gupta, Saumya; Buxi, T B S; Rawat, Kishan S; Yadav, Anurag; Mehta, Naimish; Sud, Seema

2016-01-01

Abernethy malformation, also known as congenital extrahepatic portosystemic shunts (CEPS) is a rare clinical entity and manifests with different clinical symptoms. CEPS are abnormalities of vascular development where there is shunting of portal blood into the systemic venous system. Multidetector computed tomography (MDCT) is a fast and effective modality for evaluation of CEPS. CT displays all the information desired by the surgeon as well as the clinician including the anatomy of the splenic and superior mesenteric veins, size and site of the shunt, presence or absence of the portal vein radicles, and helps to plan the therapy and even the follow-up of these patients. Contrast-enhanced magnetic resonance imaging (MRI) has also emerged as a promising tool for the evaluation of liver lesions associated with the malformation. The Radiologist should be aware of the various imaging appearances of this entity including its complications. In this article, we describe the imaging appearances of CEPS, their complications, and their imaging appearances on CT and MRI. We have also described various associated anomalies. PMID:27857464

Asterless is required for centriole length control and sperm development

PubMed Central

Galletta, Brian J.; Jacobs, Katherine C.; Fagerstrom, Carey J.

2016-01-01

Centrioles are the foundation of two organelles, centrosomes and cilia. Centriole numbers and functions are tightly controlled, and mutations in centriole proteins are linked to a variety of diseases, including microcephaly. Loss of the centriole protein Asterless (Asl), the Drosophila melanogaster orthologue of Cep152, prevents centriole duplication, which has limited the study of its nonduplication functions. Here, we identify populations of cells with Asl-free centrioles in developing Drosophila tissues, allowing us to assess its duplication-independent function. We show a role for Asl in controlling centriole length in germline and somatic tissue, functioning via the centriole protein Cep97. We also find that Asl is not essential for pericentriolar material recruitment or centrosome function in organizing mitotic spindles. Lastly, we show that Asl is required for proper basal body function and spermatid axoneme formation. Insights into the role of Asl/Cep152 beyond centriole duplication could help shed light on how Cep152 mutations lead to the development of microcephaly. PMID:27185836

Quantum control of molecular fragmentation in strong laser fields

NASA Astrophysics Data System (ADS)

Zohrabi, Mohammad

Present advances in laser technology allow the production of ultrashort (<˜5 fs, approaching single cycle at 800 nm), intense tabletop laser pulses. At these high intensities laser-matter interactions cannot be described with perturbation theory since multiphoton processes are involved. This is in contrast to photodissociation by the absorption of a single photon, which is well described by perturbation theory. For example, at high intensities (<˜5x1013 W/cm2) the fragmentation of molecular hydrogen ions has been observed via the absorption of three or more photons. In another example, an intriguing dissociation mechanism has been observed where molecular hydrogen ions seem to fragment by apparently absorbing no photons. This is actually a two photon process, photoabsorption followed by stimulated emission, resulting in low energy fragments. We are interested in exploring these kinds of multiphoton processes. Our research group has studied the dynamics and control of fragmentation induced by strong laser fields in a variety of molecular targets. The main goal is to provide a basic understanding of fragmentation mechanisms and possible control schemes of benchmark systems such as H2+. This knowledge is further extended to more complex systems like the benchmark H3+ polyatomic and other molecules. In this dissertation, we report research based on two types of experiments. In the first part, we describe laser-induced fragmentation of molecular ion-beam targets. In the latter part, we discuss the formation of highly-excited neutral fragments from hydrogen molecules using ultrashort laser pulses. In carrying out these experiments, we have also extended experimental techniques beyond their previous capabilities. We have performed a few experiments to advance our understanding of laser-induced fragmentation of molecular-ion beams. For instance, we explored vibrationally resolved spectra of O2+ dissociation using various wavelengths. We observed a vibrational suppression effect in the dissociation spectra due to the small magnitude of the dipole transition moment, which depends on the photon energy --- a phenomenon known as Cooper minima. By changing the laser wavelength, the Cooper minima shift, a fact that was used to identify the dissociation pathways. In another project, we studied the carrier-envelope phase (CEP) dependences of highly-excited fragments from hydrogen molecules. General CEP theory predicts a CEP dependence in the total dissociation yield due to the interference of dissociation pathways differing by an even net number of photons, and our measurements are consistent with this prediction. Moreover, we were able to extract the difference in the net number of photons involved in the interfering pathways by using a Fourier analysis. In terms of our experimental method, we have implemented a pump-probe style technique on a thin molecular ion-beam target and explored the feasibility of such experiments. The results presented in this work should lead to a better understanding of the dynamics and control in molecular fragmentation induced by intense laser fields.

PHOTOMETRIC ANALYSIS OF HS Aqr, EG Cep, VW LMi, AND DU Boo

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

Djurasevic, G.; Latkovic, O.; Bastuerk, Oe.

2013-03-15

We analyze new multicolor light curves for four close late-type binaries: HS Aqr, EG Cep, VW LMi, and DU Boo, in order to determine the orbital and physical parameters of the systems and estimate the distances. The analysis is done using the modeling code of G. Djurasevic, and is based on up-to-date measurements of spectroscopic elements. All four systems have complex, asymmetric light curves that we model by including bright or dark spots on one or both components. Our findings indicate that HS Aqr and EG Cep are in semi-detached, while VW LMi and DU Boo are in overcontact configurations.

Circular Probable Error for Circular and Noncircular Gaussian Impacts

DTIC Science & Technology

2012-09-01

1M simulated impacts ph(k)=mean(imp(:,1).^2+imp(:,2).^2<=CEP^2); % hit frequency on CEP end phit (j)=mean(ph...avg 100 hit frequencies to “incr n” end % GRAPHICS plot(i, phit ,’r-’); % error exponent versus Ph estimate

[Congenital portosystemic shunt. The Abernethy malformation].

PubMed

Avila, L F; Luis, A L; Encinas, J L; Hernández, F; Olivares, P; Fernández Cuadrado, J; Hierro, L; Jara, P; López Santamaría, M; Tovar, J A

2006-10-01

Congenital portosystemic shunt (CEPS) is a rare condition that was first reported by John Abernethy in 1793. Two types of CEPS are described: type I (side to end anastomosis) or congenital absence of the portal vein, and type II (side to side anastomosis) with portal vein supply partially conserved. Type I CEPS is usually seen in girls and associates multiple malformations as polysplenia, malrotation, and cardiac anomalies. Type II is even rarer with no sex preference and no malformations associated. Hepatic encephalopathy is a common complication of both types in adulthood. Liver transplantation is the only effective treatment for symptomatic type I CEPS. A therapeutic approach for type II could be surgical closure of the shunt. To analyse our experience in diagnosis and management of portosystemic shunts. We report 4 cases of CEPS (3 type I and 1 type II) diagnosed between January-1997 and March-2005 in our department. We present 4 patients with ages at diagnosis ranging from 0 to 28 months, 3 type I CEPS (2 boys and 1 girl) and 1 boy type II. The type I girl was prenatally diagnosed at 12 weeks of gestation. Initial clinical signs in type 1 boys were splenomegaly and hypersplenism, both with normal pondo-statural growth. No polysplenia or cardiac anomalies were assessed. One of them presented mild developmental delay, dismorphic features and facial telangiectasias. He had normal coagulation tests with chronic hepatic dysfunction (high transaminases) and regenerative nodular lesions were seen by imaging techniques. The other type I patient had hypoprothrombinemia, tendency to capillary bleeding (haematomas and epistaxis) with preserved liver function. Both patients have developed mild portal hypertension and present steatosis signs at liver biopsy. The type I girl presents a 21 trisomy and associates a cardiac anomaly (interauricular communication). Her hepatic function test are normal but liver calcifications can be seen by ultrasound. Type II child associates hypospadias but he has no clinical sigh or symptom related to the shunt. In our three cases diagnosis was suggested by conventional and Doppler ultrasound and confirmed by angio-resonance imaging. All our patients are included in a meticulous clinical and radiological follow-up with no need of surgical treatment for the shunt until now. Although diagnosis of these malformations could be casual we have to think about CEPS in children presenting unspecific liver disease. Magnetic angio-resonance imaging is actually the best diagnosis methods for CEPS. These patients have a high risk for developing hepatic encephalopathy and portal hypertension, so a careful follow-up is required although surgery is not usually needed until adulthood.

Effects and possible mechanisms of simulated-microgravity on zebrafish embryonic cell

NASA Astrophysics Data System (ADS)

Hang, Xiaoming; Sun, Yeqing; Wu, Di; Li, Yixiao; Wang, Ruonan

2016-07-01

Cellular level studies are helpful for revealing the underlying mechanisms of microgravity effects on living organisms. Many cell types, ranging from bacteria to mammalian cells, are sensitive to the microgravity environment. In this study, zebrafish embryonic cells (ZF4) were exposed to simulated-microgravity (SMG) for different times to investigate the effects and possible mechanisms of microgravity on fibroblasts. A significant arrest in G2/M phase was detected in ZF4 cells after 24 or 48 hour of SMG exposure, respectively. The mRNA levels of G2/M phase regulators cyclinB1 and cdc2 were significantly decreased, while wee1 was significantly increased. Additionally, CEP135, a core centrosome protein throughout the cell cycle, seems to play a key role in modulating this effect. Quantitative analysis showed that cep135 expression was significantly increased, while CEP135 protein expression level was significantly decreased two times after SMG. Further investigation demonstrated the transfection of dre-miR-22a, a miRNA for targeting cep135, also induced G2/M arrest in ZF4 cells. These results suggest that SMG induced G2/M arrest in ZF4 cells may due to the regulation of dre-miR-22a and its target cep135. Key Words: Simulated-microgravity; zebrafish embryonic cell; G2/M arrest; molecular mechanism

Stress-Induced Sleep After Exposure to Ultraviolet Light Is Promoted by p53 in Caenorhabditis elegans.

PubMed

DeBardeleben, Hilary K; Lopes, Lindsey E; Nessel, Mark P; Raizen, David M

2017-10-01

Stress-induced sleep (SIS) in Caenorhabditis elegans is important for restoration of cellular homeostasis and is a useful model to study the function and regulation of sleep. SIS is triggered when epidermal growth factor (EGF) activates the ALA neuron, which then releases neuropeptides to promote sleep. To further understand this behavior, we established a new model of SIS using irradiation by ultraviolet C (UVC) light. While UVC irradiation requires ALA signaling and leads to a sleep state similar to that induced by heat and other stressors, it does not induce the proteostatic stress seen with heat exposure. Based on the known genotoxic effects of UVC irradiation, we tested two genes, atl-1 and cep-1 , which encode proteins that act in the DNA damage response pathway. Loss-of-function mutants of atl-1 had no defect in UVC-induced SIS but a partial loss-of-function mutant of cep-1 , gk138 , had decreased movement quiescence following UVC irradiation. Germline ablation experiments and tissue-specific RNA interference experiments showed that cep-1 is required somatically in neurons for its effect on SIS. The cep-1 ( gk138 ) mutant suppressed body movement quiescence controlled by EGF, indicating that CEP-1 acts downstream or in parallel to ALA activation to promote quiescence in response to ultraviolet light. Copyright © 2017 by the Genetics Society of America.

77 FR 39159 - Airworthiness Directives; Empresa Brasileria de Aeronáutica S.A. (EMBRAER) Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-02

... Lima, 2170, S[atilde]o Jos[eacute] dos Campos--SP, CEP: 12227-901--PO Box 36/2, BRASIL; fax ++55 12.... Brigadeiro Faria Lima, 2170, S[atilde]o Jos[eacute] dos Campos--SP, CEP: 12227-901--P.O. Box 36/2, BRASIL...

76 FR 444 - Airworthiness Directives; Empresa Brasileira de Aeronautica S.A. (EMBRAER) Model EMB-500 Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-05

.... Farina Lima, 2170, Sao Jose dos Campos--SP, CEP: 12227-901--PO Box: 38/2, BRASIL, telephone: ++55 12 3927... Campos--SP, CEP: 12227-901--PO Box: 38/2, BRASIL, telephone: ++55 12 3927-5383; fax: ++55 12 3927-2610; E...

76 FR 40286 - Airworthiness Directives; Empresa Brasileira de Aeronáutica S.A. (EMBRAER) Model EMB-505 Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-08

..., Sao Jose dos Campos--SP, CEP: 12227-901--PO Box: 36/2, BRASIL; telephone: ++55 12 3927-5383; fax: ++55... Campos--SP, CEP: 12227-901--PO Box: 36/2, BRASIL; telephone: ++55 12 3927-5383; fax: ++55 12 3927-2619; E...

75 FR 68684 - Airworthiness Directives; Empresa Brasileira de Aeronautica S.A. (EMBRAER) Model EMB-500 Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-09

..., Sao Jose dos Campos--SP, CEP: 12227-901--P.O. Box: 38/2, BRASIL, telephone: ++55 12 3927-5383; fax... Support, Av. Brig. Farina Lima, 2170, Sao Jose dos Campos--SP, CEP: 12227-901--P.O. Box: 38/2, BRASIL...

MIT Clean Energy Prize: Final Technical Report May 12, 2010 - May 11, 2011

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

Snyder, Chris; Campbell, Georgina; Salony, Jason

2011-08-09

The MIT Clean Energy Prize (MIT CEP) is a venture creation and innovation competition to encourage innovation in the energy space, specifically with regard to clean energy. The Competition invited student teams from any US university to submit student-led ventures that demonstrate a high potential of successfully making clean energy more affordable, with a positive impact on the environment. By focusing on student ventures, the MIT CEP aims to educate the next generation of clean energy entrepreneurs. Teams receive valuable mentoring and hard deadlines that complement the cash prize to accelerate development of ventures. The competition is a year-long educationalmore » process that culminates in the selection of five category finalists and a Grand Prize winner and the distribution of cash prizes to each of those teams. Each entry was submitted in one of five clean energy categories: Renewables, Clean Non-Renewables, Energy Efficiency, Transportation, and Deployment.« less

Cycling excitation process: An ultra efficient and quiet signal amplification mechanism in semiconductor

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

Liu, Yu-Hsin; Yan, Lujiang; Zhang, Alex Ce

2015-08-03

Signal amplification, performed by transistor amplifiers with its merit rated by the efficiency and noise characteristics, is ubiquitous in all electronic systems. Because of transistor thermal noise, an intrinsic signal amplification mechanism, impact ionization was sought after to complement the limits of transistor amplifiers. However, due to the high operation voltage (30-200 V typically), low power efficiency, limited scalability, and, above all, rapidly increasing excess noise with amplification factor, impact ionization has been out of favor for most electronic systems except for a few applications such as avalanche photodetectors and single-photon Geiger detectors. Here, we report an internal signal amplification mechanismmore » based on the principle of the phonon-assisted cycling excitation process (CEP). Si devices using this concept show ultrahigh gain, low operation voltage, CMOS compatibility, and, above all, quantum limit noise performance that is 30 times lower than devices using impact ionization. Established on a unique physical effect of attractive properties, CEP-based devices can potentially revolutionize the fields of semiconductor electronics.« less

Noncanonical control of C. elegans germline apoptosis by the insulin/IGF-1 and Ras/MAPK signaling pathways.

PubMed

Perrin, A J; Gunda, M; Yu, B; Yen, K; Ito, S; Forster, S; Tissenbaum, H A; Derry, W B

2013-01-01

The insulin/IGF-1 pathway controls a number of physiological processes in the nematode worm Caenorhabditis elegans, including development, aging and stress response. We previously found that the Akt/PKB ortholog AKT-1 dampens the apoptotic response to genotoxic stress in the germline by negatively regulating the p53-like transcription factor CEP-1. Here, we report unexpected rearrangements to the insulin/IGF-1 pathway, whereby the insulin-like receptor DAF-2 and 3-phosphoinositide-dependent protein kinase PDK-1 oppose AKT-1 to promote DNA damage-induced apoptosis. While DNA damage does not affect phosphorylation at the PDK-1 site Thr350/Thr308 of AKT-1, it increased phosphorylation at Ser517/Ser473. Although ablation of daf-2 or pdk-1 completely suppressed akt-1-dependent apoptosis, the transcriptional activation of CEP-1 was unaffected, suggesting that daf-2 and pdk-1 act independently or downstream of cep-1 and akt-1. Ablation of the akt-1 paralog akt-2 or the downstream target of the insulin/IGF-1 pathway daf-16 (a FOXO transcription factor) restored sensitivity to damage-induced apoptosis in daf-2 and pdk-1 mutants. In addition, daf-2 and pdk-1 mutants have reduced levels of phospho-MPK-1/ERK in their germ cells, indicating that the insulin/IGF-1 pathway promotes Ras signaling in the germline. Ablation of the Ras effector gla-3, a negative regulator of mpk-1, restored sensitivity to apoptosis in daf-2 mutants, suggesting that gla-3 acts downstream of daf-2. In addition, the hypersensitivity of let-60/Ras gain-of-function mutants to damage-induced apoptosis was suppressed to wild-type levels by ablation of daf-2. Thus, insulin/IGF-1 signaling selectively engages AKT-2/DAF-16 to promote DNA damage-induced germ cell apoptosis downstream of CEP-1 through the Ras pathway.

W UMa Type Eclipsing Binary VW Cep

NASA Astrophysics Data System (ADS)

Kang, Bong-Seok; Lee, Yong-Sam; Jeong, Jang-Hae

2000-06-01

A total of 1,018 observations (509 in B, 509 in V ) of the eclipsing binary VW Cep was made during 7 nights from April through May in 1999 at Sobaeksan Optical Astronomy Observatory, using the CCD camera attached to the 61cm telescope. A time of minimum light of HJD2451327.2282 was determined from our data, and we constructed BV light curves with the data. Using Wilson-Devinney's binary model, we analized the light curves. The absolute dimension of M1 = 0.95Msolar, M2 = 0.33Msolar, R1 = 1.02Rsolar, R2 = 0.66Rsolar of the VW Cep system were derived from our light curve solution and Kaszas et al. (1998) spectroscoppic rsult.

Experimental observation of carrier-envelope-phase effects by multicycle pulses

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

Jha, Pankaj K.; Scully, Marlan O.; Mechanical and Aerospace Engineering and the Princeton Institute for the Science and Technology of Materials, Princeton University, Princeton, New Jersey 08544

2011-03-15

We present an experimental and theoretical study of carrier-envelope-phase (CEP) effects on the population transfer between two bound atomic states interacting with pulses consisting of many cycles. Using intense radio-frequency pulse with Rabi frequency of the order of the atomic transition frequency, we investigate the influence of the CEP on the control of phase-dependent multiphoton transitions between the Zeeman sublevels of the ground state of {sup 87}Rb. Our scheme has no limitation on the duration of the pulses. Extending the CEP control to longer pulses creates interesting possibilities to generate pulses with accuracy that is better than the period ofmore » optical oscillations.« less

Stabilization and control of the carrier-envelope phase of high-power femtosecond laser pulses using the direct locking technique.

PubMed

Imran, Tayyab; Lee, Yong S; Nam, Chang H; Hong, Kyung-Han; Yu, Tae J; Sung, Jae H

2007-01-08

We have stabilized and electronically controlled the carrier-envelope phase (CEP) of high-power femtosecond laser pulses, generated in a grating-based chirped-pulse amplification kHz Ti:sapphire laser, using the direct locking technique [Opt. Express 13, 2969 (2005)] combined with a slow feedback loop. An f-2f spectral interferometer has shown the CEP stabilities of 1.2 rad with the direct locking loop applied to the oscillator and of 180 mrad with an additional slow feedback loop, respectively. The electronic CEP modulations that can be easily realized in the direct locking loop are also demonstrated with the amplified pulses.

Clinical Overestimation of HER2 Positivity in Early Estrogen and Progesterone Receptor–Positive Breast Cancer and the Value of Molecular Subtyping Using BluePrint

PubMed Central

Langenhoven, Lizanne; Grant, Kathleen A.; van der Merwe, Lize; Kotze, Maritha J.

2017-01-01

Purpose Human epidermal growth factor receptor 2 (HER2) positivity is an important prognostic and predictive indicator in breast cancer. HER2 status is determined by immunohistochemistry and fluorescent in situ hybridization (FISH), which are potentially inaccurate techniques as a result of several technical factors, polysomy of chromosome 17, and amplification or overexpression of CEP17 (centromeric probe for chromosome 17) and/or HER2. In South Africa, HER2-positive tumors are excluded from a MammaPrint (MP; Agendia BV, Amsterdam, Netherlands) pretest algorithm. Clinical HER2 status has been reported to correlate poorly with molecular subtype. The aim of this study was to investigate the correlation of clinical HER2 status with BluePrint (BP) molecular subtyping. Methods Clinico-pathologic and genomic information was extracted from a prospectively collected central MP database containing records of 256 estrogen receptor–positive and/or progesterone receptor–positive tumors. Twenty-one tumors considered HER2 positive on immunohistochemistry or FISH were identified for this study. Results The median age of patients was 56 years (range, 34 to 77 years), with a median tumor size of 16 mm (3 to 27 mm). Four (19%) tumors were confirmed HER2-enriched subtype, six (29%) were luminal A, and 11 (52%) were luminal B. The positive predictive values of HER2/CEP17 ratio ≥ 2 and HER2 copy number ≥ 6 were only 29% and 40%, respectively. The differences in means for HER2/CEP17 ratio were significant between BP HER2-enriched versus luminal (P = .0249; 95% CI, 0.12 to 1.21) and MP high-risk versus low-risk tumors (P = .0002; 95% CI, 0.40 to 1.06). Conclusion Of the 21 tumors considered clinically HER2 positive, only four were HER2-enriched subtype with BP, indicating an overestimation of HER2 positivity. FISH testing has a poor positive predictive value. PMID:28831439

Clinical Overestimation of HER2 Positivity in Early Estrogen and Progesterone Receptor-Positive Breast Cancer and the Value of Molecular Subtyping Using BluePrint.

PubMed

Myburgh, Ettienne J; Langenhoven, Lizanne; Grant, Kathleen A; van der Merwe, Lize; Kotze, Maritha J

2017-08-01

Human epidermal growth factor receptor 2 (HER2) positivity is an important prognostic and predictive indicator in breast cancer. HER2 status is determined by immunohistochemistry and fluorescent in situ hybridization (FISH), which are potentially inaccurate techniques as a result of several technical factors, polysomy of chromosome 17, and amplification or overexpression of CEP17 (centromeric probe for chromosome 17) and/or HER2. In South Africa, HER2-positive tumors are excluded from a MammaPrint (MP; Agendia BV, Amsterdam, Netherlands) pretest algorithm. Clinical HER2 status has been reported to correlate poorly with molecular subtype. The aim of this study was to investigate the correlation of clinical HER2 status with BluePrint (BP) molecular subtyping. Clinico-pathologic and genomic information was extracted from a prospectively collected central MP database containing records of 256 estrogen receptor-positive and/or progesterone receptor-positive tumors. Twenty-one tumors considered HER2 positive on immunohistochemistry or FISH were identified for this study. The median age of patients was 56 years (range, 34 to 77 years), with a median tumor size of 16 mm (3 to 27 mm). Four (19%) tumors were confirmed HER2-enriched subtype, six (29%) were luminal A, and 11 (52%) were luminal B. The positive predictive values of HER2/CEP17 ratio ≥ 2 and HER2 copy number ≥ 6 were only 29% and 40%, respectively. The differences in means for HER2/CEP17 ratio were significant between BP HER2-enriched versus luminal ( P = .0249; 95% CI, 0.12 to 1.21) and MP high-risk versus low-risk tumors ( P = .0002; 95% CI, 0.40 to 1.06). Of the 21 tumors considered clinically HER2 positive, only four were HER2-enriched subtype with BP, indicating an overestimation of HER2 positivity. FISH testing has a poor positive predictive value.

High-Performance Cricket Coaches' Perceptions of an Educationally Informed Coach Education Programme

ERIC Educational Resources Information Center

Galvan, Hugh; Fyall, Glenn; Culpan, Ian

2012-01-01

This paper reports and discusses the findings of a research project that investigated the recently conceptualized and implemented New Zealand Cricket, Level 3, high-performance coach education programme (CEP). A qualitative methodology was employed to gather data from six coaches involved in the CEP. In particular the researchers sought the…

Community Eligibility Provision Evaluation. Nutrition Assistance Program Report

ERIC Educational Resources Information Center

Logan, Christopher W.; Connor, Patty; Harvill, Eleanor L.; Harkness, Joseph; Nisar, Hiren; Checkoway, Amy; Peck, Laura R.; Shivji, Azim; Bein, Edwin; Levin, Marjorie; Enver, Ayesha

2014-01-01

Section 104(a) of the Healthy, Hunger Free Kids Act (HHFKA) of 2010 made the Community Eligibility Provision (CEP) available to Local Educational Agencies (LEAs) and schools in high poverty areas. Under the CEP, families are not required to submit applications for free or reducedprice (FRP) meals, and schools must provide free lunch and breakfast…

Stabilization of cartwheel-less centrioles for duplication requires CEP295-mediated centriole-to-centrosome conversion.

PubMed

Izquierdo, Denisse; Wang, Won-Jing; Uryu, Kunihiro; Tsou, Meng-Fu Bryan

2014-08-21

Vertebrate centrioles lose their geometric scaffold, the cartwheel, during mitosis, concurrently with gaining the ability to recruit the pericentriolar material (PCM) and thereby function as the centrosome. Cartwheel removal has recently been implicated in centriole duplication, but whether "cartwheel-less" centrioles are intrinsically stable or must be maintained through other modifications remains unclear. Here, we identify a newborn centriole-enriched protein, KIAA1731/CEP295, specifically mediating centriole-to-centrosome conversion but dispensable for cartwheel removal. In the absence of CEP295, centrioles form in the S/G2 phase and lose their associated cartwheel in mitosis but cannot be converted to centrosomes, uncoupling the two events. Strikingly, centrioles devoid of both the PCM and the cartwheel progressively lose centriolar components, whereas centrioles associating with either the cartwheel or PCM alone can exist stably. Thus, cartwheel removal can have grave repercussions to centriole stability, and centriole-to-centrosome conversion mediated by CEP295 must occur in parallel to maintain cartwheel-less centrioles for duplication. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Osteoconduction of impacted porous titanium particles with a calcium-phosphate coating is comparable to osteoconduction of impacted allograft bone particles: in vivo study in a nonloaded goat model.

PubMed

Walschot, Lucas H B; Aquarius, René; Schreurs, Barend W; Verdonschot, Nico; Buma, Pieter

2012-08-01

Impaction grafting restores bone defects in hip arthroplasty. Defects are reconstructed with bone particles (BoP) as substitute materials with adequate mechanical and biological properties are not yet available. Ceramic particles (CeP) have mechanical drawbacks as opposed to porous titanium particles (TiP). In this in vivo study, bone ingrowth and bone volume in coated and noncoated TiP were compared to porous biphasic calcium-phospate CeP and allograft BoP. Coatings consisted of silicated calcium-phosphate and carbonated apatite. Materials were implanted in goats and impacted in cylindrical defects (diameter 8 mm) in the cancellous bone of the femur. On the basis of fluorochrome labeling and histology, bone ingrowth distance was measured at 4, 8, and 12 weeks. Cross-sectional bone area was measured at 12 weeks. TiP created a coherent matrix of entangled particles. CeP pulverized and were noncoherent. Bone ingrowth in TiP improved significantly by the coatings to levels comparable to BoP and CeP. Cross-sectional bone area was smaller in CeP and TiP compared to BoP. The osteoconductive properties of impacted TiP with a calcium-phosphate coating are comparable to impacted allograft bone and impacted biphasic ceramics. A more realistic loaded in vivo study should prove that coated TiP is an attractive alternative to allograft bone. Copyright © 2012 Wiley Periodicals, Inc.

Better Federal Policies Leading to Better Schools

ERIC Educational Resources Information Center

Kober, Nancy; Jennings, Jack; Peltason, Jody

2010-01-01

Two years ago, the Center on Education Policy (CEP), an independent nonprofit organization known for its comprehensive studies of No Child Left Behind Act (NCLB) and related issues, began a research-based review of the federal role. As part of this process, the authors examined an extensive body of research from a wide range of sources. They also…

Community Eligibility Provision Evaluation: Year 3 Addendum. Nutrition Assistance Program Report

ERIC Educational Resources Information Center

Harkness, Joseph; Logan, Christopher W.; Shivji, Azim; Nisar, Hiren; Connor, Patty

2015-01-01

Section 104(a) of the Healthy, Hunger Free Kids Act (HHFKA) of 2010 made the Community Eligibility Provision (CEP) available to Local Educational Agencies (LEAs) and schools in high poverty areas. Under the CEP, families are not required to submit applications for free or reduced-price meals, and schools must provide free lunch and breakfast to…

State High School Exit Exams: A Policy in Transition

ERIC Educational Resources Information Center

McIntosh, Shelby

2012-01-01

Since 2002, the Center on Education Policy (CEP) at The George Washington University, a national advocate for public education and improving public schools, has been studying state high school exit examinations--tests students must pass to receive a high school diploma. This year marks the 11th year CEP has reported on exit exams in order to help…

Cancer Education Program Evaluation: A Responsive Approach to Planning an Evaluation and Initial Results.

ERIC Educational Resources Information Center

Pearsol, James A.

This paper describes evaluation planning for the Cancer Education Program (CEP) at Ohio State University (OSU). The three-year OSU CEP project was designed as a multidisciplinary cancer education program. A responsive method, which trades off some measurement precision in order to increase the usefulness of the findings, was employed in the…

Nonsequential double ionization channels control of Ar with few-cycle elliptically polarized laser pulse by carrier-envelope-phase.

PubMed

Ben, Shuai; Wang, Tian; Xu, Tongtong; Guo, Jing; Liu, Xueshen

2016-04-04

The carrier-envelop-phase (CEP) dependence of nonsequential double ionization (NSDI) of atomic Ar with few-cycle elliptically polarized laser pulse is investigated using 2D classical ensemble method. We distinguish two particular recollision channels in NSDI, which are recollision-impact ionization (RII) and recollision-induced excitation with subsequent ionization (RESI). We separate the RII and RESI channels according to the delay time between recollision and final double ionization. By tracing the history of the trajectories, we find the electron correlation spectra as well as the competition between the two channels are sensitively dependent on the laser field CEP. Finally, control can be achieved between the two channels by varying the CEP.

Attosecond pulse carrier-envelope phase effects on ionized electron momentum and energy distributions

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

Peng, L.-Y.; Starace, Anthony F.

2007-10-15

We analyze carrier-envelope phase (CEP) effects on electron wave-packet momentum and energy spectra produced by one or two few-cycle attosecond xuv pulses. The few-cycle attosecond pulses are assumed to have arbitrary phases. We predict CEP effects on ionized electron wave-packet momentum distributions produced by attosecond pulses having durations comparable to those obtained by Sansone et al. [Science 314, 443 (2006)]. The onset of significant CEP effects is predicted to occur for attosecond pulse field strengths close to those possible with current experimental capabilities. Our results are based on single-active-electron solutions of the three-dimensional, time-dependent Schroedinger equation including atomic potentials appropriatemore » for the H and He atoms.« less

Recycling of mixed wastes using Quantum-CEP{trademark}

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

Sameski, B.

1997-02-01

The author describes the process that M4 Environmental Management, Inc., is commercializing for the treatment of mixed wastes. He summarizes the types of wastes which the process can be applied to, the products which come out of the process, and examples of various waste streams which have been processed. The process is presently licensed to treat mixed wastes and the company has in place contracts for such services. The process uses a molten metal bath to catalyze reactions which break the incoming products down to an atomic level, and allow different process steams to be tapped at the output end.

Why Rules Matter in Complex Event Processing...and Vice Versa

NASA Astrophysics Data System (ADS)

Vincent, Paul

Many commercial and research CEP solutions are moving beyond simple stream query languages to more complete definitions of "process" and thence to "decisions" and "actions". And as capabilities increase in event processing capabilities, there is an increasing realization that the humble "rule" is as relevant to the event cloud as it is to specific services. Less obvious is how much event processing has to offer the process and rule execution and management technologies. Does event processing change the way we should manage businesses, processes and services, together with their embedded (and hopefully managed) rulesets?

MYC gene amplification is a rare event in atypical fibroxanthoma and pleomorphic dermal sarcoma

PubMed Central

Bach, Marisa; Kind, Peter; Helbig, Doris; Quaas, Alexander; Utikal, Jochen; Marx, Alexander; Gaiser, Maria Rita

2018-01-01

Atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) are rare malignancies typically occurring in elderly patients and predominantly located in skin regions exposed to UV-light. Thus, a role of UV-radiation-induced damage for AFX and PDS tumorigenesis has been postulated. MYC gene amplification has been demonstrated as a distinctive feature of radiation-induced angiosarcoma. In order to investigate whether chronic exposure to UV-light might also lead to MYC copy number changes, 51 AFX and 24 PDS samples were retrospectively analyzed for MYC amplification by fluorescence in situ hybridization using a MYC and a CEP8 gene probe. Of the 44 analyzable AFX samples, one case showed MYC amplification (defined as a MYC/CEP8 ratio ≥2.0), whereas 13 cases demonstrated low level copy number gains (defined as MYC/CEP8 ratio ≥ 1.2−< 2.0). MYC amplification was seen in an AFX sample of extraordinary tumor thickness of 17.5 mm (vs. median 3.25 mm for all samples). Of the 24 PDS cases, five specimen demonstrated MYC low level copy number gains. Immunohistochemically, neither the AFX nor the PDS cases showed MYC protein expression. In summary, these findings rule out that MYC amplification is a major genetic driver in the process of AFX or PDS tumorigenesis. However, MYC amplification may occur as a late event during AFX development and hence might only be detectable in advanced, thick lesions. PMID:29765529

MYC gene amplification is a rare event in atypical fibroxanthoma and pleomorphic dermal sarcoma.

PubMed

Gaiser, Timo; Hirsch, Daniela; Orouji, Azadeh; Bach, Marisa; Kind, Peter; Helbig, Doris; Quaas, Alexander; Utikal, Jochen; Marx, Alexander; Gaiser, Maria Rita

2018-04-20

Atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) are rare malignancies typically occurring in elderly patients and predominantly located in skin regions exposed to UV-light. Thus, a role of UV-radiation-induced damage for AFX and PDS tumorigenesis has been postulated. MYC gene amplification has been demonstrated as a distinctive feature of radiation-induced angiosarcoma. In order to investigate whether chronic exposure to UV-light might also lead to MYC copy number changes, 51 AFX and 24 PDS samples were retrospectively analyzed for MYC amplification by fluorescence in situ hybridization using a MYC and a CEP8 gene probe. Of the 44 analyzable AFX samples, one case showed MYC amplification (defined as a MYC /CEP8 ratio ≥2.0), whereas 13 cases demonstrated low level copy number gains (defined as MYC /CEP8 ratio ≥ 1.2-< 2.0). MYC amplification was seen in an AFX sample of extraordinary tumor thickness of 17.5 mm (vs. median 3.25 mm for all samples). Of the 24 PDS cases, five specimen demonstrated MYC low level copy number gains. Immunohistochemically, neither the AFX nor the PDS cases showed MYC protein expression. In summary, these findings rule out that MYC amplification is a major genetic driver in the process of AFX or PDS tumorigenesis. However, MYC amplification may occur as a late event during AFX development and hence might only be detectable in advanced, thick lesions.

Assessment of G3(MP2)//B3 theory including a pseudopotential for molecules containing first-, second-, and third-row representative elements

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

Rocha, Carlos Murilo Romero; Morgon, Nelson Henrique; Custodio, Rogério, E-mail: roger@iqm.unicamp.br

2013-11-14

G3(MP2)//B3 theory was modified to incorporate compact effective potential (CEP) pseudopotentials, providing a theoretical alternative referred to as G3(MP2)//B3-CEP for calculations involving first-, second-, and third-row representative elements. The G3/05 test set was used as a standard to evaluate the accuracy of the calculated properties. G3(MP2)//B3-CEP theory was applied to the study of 247 standard enthalpies of formation, 104 ionization energies, 63 electron affinities, 10 proton affinities, and 22 atomization energies, comprising 446 experimental energies. The mean absolute deviations compared with the experimental data for all thermochemical results presented an accuracy of 1.4 kcal mol{sup −1} for G3(MP2)//B3 and 1.6more » kcal mol{sup −1} for G3(MP2)//B3-CEP. Approximately 75% and 70% of the calculated properties are found with accuracy between ±2 kcal mol{sup −1} for G3(MP2)//B3 and G3(MP2)//B3-CEP, respectively. Considering a confidence interval of 95%, the results may oscillate between ±4.2 kcal mol{sup −1} and ±4.6 kcal mol{sup −1}, respectively. The overall statistical behavior indicates that the calculations using pseudopotential present similar behavior with the all-electron theory. Of equal importance to the accuracy is the CPU time, which was reduced by between 10% and 40%.« less

Development and studies on a compact electron cyclotron resonance plasma source

NASA Astrophysics Data System (ADS)

Ganguli, A.; Tarey, R. D.; Arora, N.; Narayanan, R.

2016-04-01

It is well known that electron cyclotron resonance (ECR) produced plasmas are efficient, high-density plasma sources and have many industrial applications. The concept of a portable compact ECR plasma source (CEPS) would thus become important from an application point of view. This paper gives details of such a CEPS that is both portable and easily mountable on a chamber of any size. It uses a fully integrated microwave line operating at 2.45 GHz, up to 800 W, cw. The required magnetic field is produced by a set of suitably designed NdFeB ring magnets; the device has an overall length of  ≈60 cm and weighs  ≈14 kg including the permanent magnets. The CEPS was attached to a small experimental chamber to judge its efficacy for plasma production. In the pressure range of 0.5-10 mTorr and microwave power of  ≈400-500 W the experiments indicate that the CEPS is capable of producing high-density plasma (≈9  ×  1011-1012 cm-3) with bulk electron temperature in the range  ≈2-3 eV. In addition, a warm electron population with density and temperature in the range ≈7  ×  108-109 cm-3 and  ≈45-80 eV, respectively has been detected. This warm population plays an important role at high pressures in maintaining the high-density plasma, when plasma flow from the CEPS into the test chamber is strongly affected.

Successful preemptive surgical division of type 2-congenital extrahepatic portosystemic shunt in children.

PubMed

Nii, Akira; Takehara, Hiro-o; Kuyama, Hisako; Shimada, Mitsuo

2009-02-01

A congenital extrahepatic portosystemic shunt (CEPS) is a rare abnormality. The shunts are classified into 2 types. Of these, a type 2-shunt is a side-to-side one, which may be treated by a simple shunt division. The aim of this retrospective study was to clarify the effects of a surgical shunt division on 4 children with type 2-CEPS. Between June 2002 and June 2008, 4 children with type 2-CEPS underwent a surgical shunt division. Various clinical factors of each patient, including shunt types, shut ratios evaluated by portal scintigraphy using (123)I-iodoamphetamine, serum levels of ammonia and total bile acids before and after surgery were evaluated. Two children had a conventional open surgery and the other two had a laparoscopic surgery. The serum levels of ammonia as well as total bile acids of these children decreased significantly to the normal levels within a month after the surgical shunt divisions. All the children had a better clinical course. A shunt division, especially by laparoscopic surgery, is an effective therapy for type 2-CEPS. To the best of our knowledge by reviewing literatures, our cases are the youngest ones treated by laparoscopic shunt division.

Identification of quorum sensing-controlled genes in Burkholderia ambifaria

PubMed Central

Chapalain, Annelise; Vial, Ludovic; Laprade, Natacha; Dekimpe, Valérie; Perreault, Jonathan; Déziel, Eric

2013-01-01

The Burkholderia cepacia complex (Bcc) comprises strains with a virulence potential toward immunocompromised patients as well as plant growth–promoting rhizobacteria (PGPR). Owing to the link between quorum sensing (QS) and virulence, most studies among Bcc species have been directed toward QS of pathogenic bacteria. We have investigated the QS of B. ambifaria, a PGPR only infrequently recovered from patients. The cepI gene, responsible for the synthesis of the main signaling molecule N-octanoylhomoserine lactone (C8-HSL), was inactivated. Phenotypes of the B. ambifaria cepI mutant we observed, such as increased production of siderophores and decreased proteolytic and antifungal activities, are in agreement with those of other Bcc cepI mutants. The cepI mutant was then used as background strain for a whole-genome transposon-insertion mutagenesis strategy, allowing the identification of 20 QS-controlled genes, corresponding to 17 loci. The main functions identified are linked to antifungal and antimicrobial properties, as we have identified QS-controlled genes implicated in the production of pyrrolnitrin, burkholdines (occidiofungin-like molecules), and enacyloxins. This study provides insights in the QS-regulated functions of a PGPR, which could lead to beneficial potential biotechnological applications. PMID:23382083

Common Ground - Kansas Climate and Energy Project Connects with the Heartland

ScienceCinema

None

2018-01-11

In 2010, Lawrence Berkeley National Laboratory (LBNL) electricity-market, policy and consumer behavior expert Merrian Fuller singled out a small environmental organization in Kansas-- the Climate and Energy Project (CEP)-- as an outstanding example of how you change behavior on energy efficiency and reduce carbon emissions through an apolitical emphasis on heartland values. In the summer of 2011, a team from LBNL, seeking to capture what Fuller had featured in her report Driving Demand for Home Energy Improvement, visited Kansas. Speaking with CEP's Nancy Jackson and Dorothy Barnett, as well as farmers, small business owners, politicians and others, the team produced this video, which shows how and why CEP has become an inspiration to other environmental organizations that are seeking to change behavior where climate-change skepticism abounds.

Waveform-controlled terahertz radiation from the air filament produced by few-cycle laser pulses.

PubMed

Bai, Ya; Song, Liwei; Xu, Rongjie; Li, Chuang; Liu, Peng; Zeng, Zhinan; Zhang, Zongxin; Lu, Haihe; Li, Ruxin; Xu, Zhizhan

2012-06-22

Waveform-controlled terahertz (THz) radiation is of great importance due to its potential application in THz sensing and coherent control of quantum systems. We demonstrated a novel scheme to generate waveform-controlled THz radiation from air plasma produced when carrier-envelope-phase (CEP) stabilized few-cycle laser pulses undergo filamentation in ambient air. We launched CEP-stabilized 10 fs-long (~1.7 optical cycles) laser pulses at 1.8 μm into air and found that the generated THz waveform can be controlled by varying the filament length and the CEP of driving laser pulses. Calculations using the photocurrent model and including the propagation effects well reproduce the experimental results, and the origins of various phase shifts in the filament are elucidated.

75 FR 973 - Certain Welded Stainless Steel Pipes From the Republic of Korea: Preliminary Results of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-07

... same LOT as CEP. Sales are made at different LOTs if they are made at different marketing stages (or... marketing. Id; see also Notice of Final Determination of Sales at Less than Fair Value: Certain Cut-to...). In order to determine whether the home market sales were at different stages in the marketing process...

Capability Engineering Process (CEP) Foundations - Version 2

DTIC Science & Technology

2006-03-02

R& D /Ops Research, Infrastructure & Organization, Qoncepts, Doctrine & Collective Training, IT Infrastructure , Equipment, Supplies and Services...les investissements strategiques requis pour repondre it une lacune en matiere de capacite. Ce processus est elabore dans la cadre du projet de...ainsi que six (6) buts secondaires servent it positionner Ie PIC comme un processus interne aux activites de planification axee sur les capacites

Characterization of the mature cell surface proteinase of Lactobacillus delbrueckii subsp. lactis CRL 581.

PubMed

Villegas, Josefina M; Brown, Lucía; Savoy de Giori, Graciela; Hebert, Elvira M

2015-05-01

The cell envelope-associated proteinase (CEP) of Lactobacillus delbrueckii subsp. lactis CRL 581 (PrtL) has an essential role in bacterial growth, contributes to the flavor and texture development of fermented products, and can release bioactive health-beneficial peptides during milk fermentation. The genome of L. delbrueckii subsp. lactis CRL 581 possesses only one gene that encodes PrtL, which consists of 1924 amino acids and is a multidomain protein anchored to the cell via its W domain. PrtL was extracted from the cell under high ionic strength conditions using NaCl, suggesting an electrostatic interaction between the proteinase and the cell envelope. The released PrtL was purified and biochemically characterized; its activity was maximal at temperatures between 37 and 40 °C and at pH between 7 and 8. Under optimal conditions, PrtL exhibited higher affinity for succinyl-alanyl-alanyl-prolyl-phenylalanine-p-nitroanilide than for succinyl-alanyl-glutamyl-prolyl-phenylalanine-p-nitroanilide, while methoxy-succinyl-arginyl-prolyl-tyrosyl-p-nitroanilide was not degraded. A similar α- and β-casein degradation pattern was observed with the purified and the cell envelope-bound proteinase. Finally, on the basis of its specificity towards caseins and the unique combination of amino acids at residues thought to be involved in substrate specificity, PrtL can be classified as a representative of a new group of CEP.

Contact binary stars. I - An X-ray survey

NASA Technical Reports Server (NTRS)

Cruddace, R. G.; Dupree, A. K.

1984-01-01

X-ray emission from a contact binary star was first detected by the HEAO 1 satellite in 1977. Spectroscopic observations of 44i Boo and VW Cep by IUE established the presence of high-temperature chromospheric and transition region emission lines in the spectra of these stars. The HEAO 1 and IUE results implied that the processes causing X-ray emission from VW Cep might be similar to those energizing the solar corona, and that X-ray emission might be a common occurrence among contact binary stars. A series of observations of these stars was, therefore, conducted with the aid of the HEAO 2 (Einstein) Observatory. The present investigation is concerned with the results of these observations, giving attention to their implications with respect to the nature of contact binary stars. The results are compared with similar HEAO 2 studies of coronal X-ray sources in the local region of the Galaxy, in the Hyades, and other rapidly rotating systems.

Abnormal Condition Monitoring of Workpieces Based on RFID for Wisdom Manufacturing Workshops.

PubMed

Zhang, Cunji; Yao, Xifan; Zhang, Jianming

2015-12-03

Radio Frequency Identification (RFID) technology has been widely used in many fields. However, previous studies have mainly focused on product life cycle tracking, and there are few studies on real-time status monitoring of workpieces in manufacturing workshops. In this paper, a wisdom manufacturing model is introduced, a sensing-aware environment for a wisdom manufacturing workshop is constructed, and RFID event models are defined. A synthetic data cleaning method is applied to clean the raw RFID data. The Complex Event Processing (CEP) technology is adopted to monitor abnormal conditions of workpieces in real time. The RFID data cleaning method and data mining technology are examined by simulation and physical experiments. The results show that the synthetic data cleaning method preprocesses data well. The CEP based on the Rifidi(®) Edge Server technology completed abnormal condition monitoring of workpieces in real time. This paper reveals the importance of RFID spatial and temporal data analysis in real-time status monitoring of workpieces in wisdom manufacturing workshops.

Abnormal Condition Monitoring of Workpieces Based on RFID for Wisdom Manufacturing Workshops

PubMed Central

Zhang, Cunji; Yao, Xifan; Zhang, Jianming

2015-01-01

Radio Frequency Identification (RFID) technology has been widely used in many fields. However, previous studies have mainly focused on product life cycle tracking, and there are few studies on real-time status monitoring of workpieces in manufacturing workshops. In this paper, a wisdom manufacturing model is introduced, a sensing-aware environment for a wisdom manufacturing workshop is constructed, and RFID event models are defined. A synthetic data cleaning method is applied to clean the raw RFID data. The Complex Event Processing (CEP) technology is adopted to monitor abnormal conditions of workpieces in real time. The RFID data cleaning method and data mining technology are examined by simulation and physical experiments. The results show that the synthetic data cleaning method preprocesses data well. The CEP based on the Rifidi® Edge Server technology completed abnormal condition monitoring of workpieces in real time. This paper reveals the importance of RFID spatial and temporal data analysis in real-time status monitoring of workpieces in wisdom manufacturing workshops. PMID:26633418

Precise and long-term stabilization of the carrier-envelope phase of femtosecond laser pulses using an enhanced direct locking technique.

PubMed

Yu, Tae Jun; Hong, Kyung-Han; Choi, Hyun-Gyug; Sung, Jae Hee; Choi, Il Woo; Ko, Do-Kyeong; Lee, Jongmin; Kim, Junwon; Kim, Dong Eon; Nam, Chang Hee

2007-06-25

We demonstrate a long-term operation with reduced phase noise in the carrier-envelope-phase (CEP) stabilization process by employing a double feedback loop and an improved signal detection in the direct locking technique [Opt. Express 13, 2969 (2005)]. A homodyne balanced detection method is employed for efficiently suppressing the dc noise in the f-2f beat signal, which is converted into the CEP noise in the direct locking loop working at around zero carrier-envelope offset frequency (f(ceo)). In order to enhance the long-term stability, we have used the double feedback scheme that modulates both the oscillator pump power for a fast control and the intracavity-prism insertion depth for a slow and high-dynamic-range control. As a result, the in-loop phase jitter is reduced from 50 mrad of the previous result to 29 mrad, corresponding to 13 as in time scale, and the long-term stable operation is achieved for more than 12 hours.

Evaluation of Motor Gasoline Stability

DTIC Science & Technology

1990-12-01

CAMPINNE AIR POLLUTION CONTROL I LABORATOIRE MECANIQUE TRANSPORT 2565 PLYMOUTH ROAD AVENUE DE LA RENAISSANCE, 3D ANN ARBOR MI 48105 B-1040 BRUSSELS 5...CUARTEL GENERAL DEL EJERCITO ATTN: MR K LAURINSEN ATTN: MAJ M ENGO NOGUES GADHOLTVEJ 11 DIVISION DE LOGISTICA (DIAM/LABCAMVE) DK-9900 FREDERIKSHAVN...Gum for Typical Civilian Gasolines Transported by CEPS and F-46 Gasolines Stored by CEPS ...................................... 47 B. Potential Gum

State Test Score Trends through 2007-08, Part 6: Has Progress Been Made in Raising Achievement for English Language Learners?

ERIC Educational Resources Information Center

Chudowsky, Naomi; Chudowsky, Victor

2010-01-01

This report by the Center on Education Policy (CEP), an independent nonprofit organization, examines progress in raising achievement for English language learners. It also describes the factors that make it difficult to accurately assess what ELLs know and can do. The data for this analysis were collected by CEP with technical support from the…

[(Modic) signal alterations of vertebral endplates and their correlation to a minimally invasive treatment of lumbar disc herniation using epidural injections].

PubMed

Liphofer, J P; Theodoridis, T; Becker, G T; Koester, O; Schmid, G

2006-11-01

To study the influence of (Modic) signal alterations (SA) of the cartilage endplate (CEP) of vertebrae L3-S1 on the outcome of an in-patient minimally invasive treatment (MIT) using epidural injections on patients with lumbar disc herniation (LDH). The MR images of 59 consecutive patients with LDH within segments L3/L4 - L5/S1 undergoing in-patient minimally invasive treatment with epidural injections were evaluated in a clinical study. The (Modic) signal alterations of the CEP were recorded using T1- and T2-weighted sagittal images. On the basis of the T2-weighted sagittal images, the extension and distribution of the SA were measured by dividing each CEP into 9 areas. The outcome of the MIT was recorded using the Oswestry Disability Index (ODI) before and after therapy and in a 3-month follow-up. Within a subgroup of patients (n = 35), the distribution and extension of the signal alterations were correlated with the development of the ODI. Segments with LDH showed significantly more (p < 0.001) SA of the CEP than segments without LDH. Although the extension of the SA was not dependent on sex, it did increase significantly with age (p = 0.017). The outcome after MIT did not depend on the sex and age of the patients nor on the type of LDH. The SA extension tended to have a negative correlation with the outcome after MIT after 3 months (p = 0.071). A significant negative correlation could be established between the SA extension in the central section of the upper endplate and the outcome after 3 months (p = 0.019). 1. Lumbar disc herniation is clearly associated with the prevalence of (Modic) signal alterations. 2. Extensive signal alterations tend to correlate with a negative outcome of an MIT using epidural injections. 3. Such SA in the central portion of the upper CEP correlate significantly with a negative treatment result. 4. The central portion of the upper CEP being extensively affected by (Modic) SA is a negative predictor for the success of a minimally invasive pain therapy.

Updated 2013 College of American Pathologists/American Society of Clinical Oncology (CAP/ASCO) guideline recommendations for human epidermal growth factor receptor 2 (HER2) fluorescent in situ hybridization (FISH) testing increase HER2 positive and HER2 equivocal breast cancer cases; retrospective study of HER2 FISH results of 836 invasive breast cancers.

PubMed

Singh, Kamaljeet; Tantravahi, Umadevi; Lomme, Michele M; Pasquariello, Terese; Steinhoff, Margaret; Sung, C James

2016-06-01

For dual probe HER2 FISH assay, the 2013 CAP/ASCO guideline recommendations lowered the HER2/CEP17 ratio cut off for HER2 amplification to ≥2.0 and introduced an average HER2 copy number criterion for HER2 amplification (≥6.0/cell) and HER2 equivocal categories (≥4 and <6/cell). The HER2/CEP17 equivocal category is eliminated. The aim of this study is to assess the impact of 2013 HER2 FISH testing guideline recommendations update on the assignment of HER2 status with dual probe HER2 FISH assay. Dual probe HER2 FISH assay results on breast cancers from 09/2009 to 07/2015 that underwent reflex HER2 FISH testing after equivocal HER2 (2+) immunohistochemistry (IHC) were reviewed. HER2 copy number, CEP17 signals, and HER2/CEP ratios were noted. HER2 status was assigned as HER2 negative (HER2-), HER2 equivocal (HER2e), and HER2 amplified (HER2+) by applying both 2007 and 2013 CAP/ASCO HER2 FISH guideline recommendations and results were compared. New guidelines reclassified HER2 FISH status in a significant proportion of cases (8.3 %, 69/836; p = .021). There were 22 (2.6 %) more HER2+, 17 (2.1 %) more HER2e, and 39 (4.1 %) fewer HER2- tumors. Change of HER2 status correlated significantly with ≥3 CEP17 signals (38 vs. 2 %; p < .001). The 2013 CAP/ASCO guideline recommendations for HER2 FISH testing by dual probe assay increased the HER2 amplified and HER2 equivocal tumors. Increase in HER2 equivocal tumors would potentially increase the frequency of repeat HER2 testing. Tumors with ≥3 CEP17 signals, so-called chromosome 17 polysomy, are more likely to be impacted and classified as HER2 equivocal.

Mutations in CEP78 Cause Cone-Rod Dystrophy and Hearing Loss Associated with Primary-Cilia Defects.

PubMed

Nikopoulos, Konstantinos; Farinelli, Pietro; Giangreco, Basilio; Tsika, Chrysanthi; Royer-Bertrand, Beryl; Mbefo, Martial K; Bedoni, Nicola; Kjellström, Ulrika; El Zaoui, Ikram; Di Gioia, Silvio Alessandro; Balzano, Sara; Cisarova, Katarina; Messina, Andrea; Decembrini, Sarah; Plainis, Sotiris; Blazaki, Styliani V; Khan, Muhammad Imran; Micheal, Shazia; Boldt, Karsten; Ueffing, Marius; Moulin, Alexandre P; Cremers, Frans P M; Roepman, Ronald; Arsenijevic, Yvan; Tsilimbaris, Miltiadis K; Andréasson, Sten; Rivolta, Carlo

2016-09-01

Cone-rod degeneration (CRD) belongs to the disease spectrum of retinal degenerations, a group of hereditary disorders characterized by an extreme clinical and genetic heterogeneity. It mainly differentiates from other retinal dystrophies, and in particular from the more frequent disease retinitis pigmentosa, because cone photoreceptors degenerate at a higher rate than rod photoreceptors, causing severe deficiency of central vision. After exome analysis of a cohort of individuals with CRD, we identified biallelic mutations in the orphan gene CEP78 in three subjects from two families: one from Greece and another from Sweden. The Greek subject, from the island of Crete, was homozygous for the c.499+1G>T (IVS3+1G>T) mutation in intron 3. The Swedish subjects, two siblings, were compound heterozygotes for the nearby mutation c.499+5G>A (IVS3+5G>A) and for the frameshift-causing variant c.633delC (p.Trp212Glyfs(∗)18). In addition to CRD, these three individuals had hearing loss or hearing deficit. Immunostaining highlighted the presence of CEP78 in the inner segments of retinal photoreceptors, predominantly of cones, and at the base of the primary cilium of fibroblasts. Interaction studies also showed that CEP78 binds to FAM161A, another ciliary protein associated with retinal degeneration. Finally, analysis of skin fibroblasts derived from affected individuals revealed abnormal ciliary morphology, as compared to that of control cells. Altogether, our data strongly suggest that mutations in CEP78 cause a previously undescribed clinical entity of a ciliary nature characterized by blindness and deafness but clearly distinct from Usher syndrome, a condition for which visual impairment is due to retinitis pigmentosa. Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Endothelial trans-differentiation in glioblastoma recurring after radiotherapy.

PubMed

De Pascalis, Ivana; Morgante, Liliana; Pacioni, Simone; D'Alessandris, Quintino Giorgio; Giannetti, Stefano; Martini, Maurizio; Ricci-Vitiani, Lucia; Malinverno, Matteo; Dejana, Elisabetta; Larocca, Luigi M; Pallini, Roberto

2018-04-30

We hypothesized that in glioblastoma recurring after radiotherapy, a condition whereby the brain endothelium undergoes radiation-induced senescence, tumor cells with endothelial phenotype may be relevant for tumor neovascularization. Matched glioblastoma samples obtained at primary surgery and at surgery for tumor recurrence after radiotherapy, all expressing epidermal growth factor receptor variant III (EGFRvIII), were assessed by a technique that combines fluorescent in situ hybridization (FISH) for the EGFR/CEP7 chromosomal probe with immunostaining for endothelial cells (CD31) and activated pericytes (α Smooth Muscle Actin). Five EGFRvIII-expressing paired primary/recurrent glioblastoma samples, in which the tumor cells showed EGFR/CEP7 amplification, were then assessed by CD31 and α Smooth Muscle Actin immunofluorescence. In glomeruloid bodies, the ratio between CD31+ cells with amplified EGFR/CEP7 signal and the total CD31+ cells was 0.23 ± 0.09 (mean ± sem) and 0.63 ± 0.07 in primary tumors and in recurrent ones, respectively (p < 0.002, Student-t test). In capillaries, the ratio of CD31+ cells with amplified EGFR/CEP7 over the total CD31+ cells lining the capillary lumen was 0.21 ± 0.06 (mean ± sem) and 0.42 ± 0.07 at primary surgery and at recurrence, respectively (p < 0.005, Student-t test). Expression of α Smooth Muscle Actin by cells with EGFR/CEP7 amplification was not observed. Then, in glioblastoma recurring after radiotherapy, where the brain endothelium suffers from radiation-induced cell senescence, tumor-derived endothelium plays a role in neo-vascularization.

Discovery Of An Infrared Bow Shock Associated With Delta Cephei

NASA Astrophysics Data System (ADS)

Remage Evans, Nancy; Marengo, M.; Barmby, P.; Matthews, L. D.; Bono, G.; Welch, D. L.; Romaniello, M.; Huelsman, D.; Su, K. Y. L.; Fazio, G.

2010-05-01

We have obtained Spitzer Infrared Array Camera (IRAC) and Multiband Infrared Photometer for Spitzer (MIPS) observations of a sample of classical Cepheids both to derive infrared Leavitt Laws (Period-Luminosity Relations) and to look for evidence of mass loss in the spectral energy distributions. The MIPS 24 and 70 micron images of Delta Cep were particularly striking, since they show an arc of emission offset about an arcmin from Delta Cep. The emission is shaped like a bow shock and is aligned with the space motion of the Cepheid, implying it is physically related to the star. Bow shock structures of this kind can be formed when ram pressure of the ambient ISM balances the wind from a mass-losing star, raising the intriguing possibility that delta Cep is undergoing mass-loss during the Cepheid phase. Circumstellar emission is not a general feature of our Cepheid observations, but 2 unusual circumstances may make it visible around Delta Cep. If the Cepheid was already surrounded by interstellar matter, mass loss from the star could have created the bow shock. Second, Delta Cep has a physical companion 40" to the South, HD 213317, itself a binary. This B7-8 III-IV star is hot enough that it may produce infrared emission by heating dust within the ejected material. This work is based on observations made with the Spitzer Space Telescope, which is operated by the Jet Propulsion Laboratory, California Institute of Technology under NASA contract 1407. P. B. and D. W. both acknowledge research support through Discovery Grants from the Natural Sciences and Engineering Research Council of Canada. N. R. E. acknowledges support from the Chandra X-Ray Center grant NAS8-03060.

Tumor Content Chart-Assisted HER2/CEP17 Digital PCR Analysis of Gastric Cancer Biopsy Specimens.

PubMed

Matsusaka, Keisuke; Ishikawa, Shumpei; Nakayama, Atsuhito; Ushiku, Tetsuo; Nishimoto, Aiko; Urabe, Masayuki; Kaneko, Nobuyuki; Kunita, Akiko; Kaneda, Atsushi; Aburatani, Hiroyuki; Fujishiro, Mitsuhiro; Seto, Yasuyuki; Fukayama, Masashi

2016-01-01

Evaluating HER2 gene amplification is an essential component of therapeutic decision-making for advanced or metastatic gastric cancer. A simple method that is applicable to small, formalin-fixed, paraffin-embedded biopsy specimens is desirable as an adjunct to or as a substitute for currently used HER2 immunohistochemistry and in situ hybridization protocols. In this study, we developed a microfluidics-based digital PCR method for determining HER2 and chromosome 17 centromere (CEP17) copy numbers and estimating tumor content ratio (TCR). The HER2/CEP17 ratio is determined by three variables-TCR and absolute copy numbers of HER2 and CEP17-by examining tumor cells; only the ratio of the latter two can be obtained by digital PCR using the whole specimen without purifying tumor cells. TCR was determined by semi-automatic image analysis. We developed a Tumor Content chart, which is a plane of rectangular coordinates consisting of HER2/CEP17 digital PCR data and TCR that delineates amplified, non-amplified, and equivocal areas. By applying this method, 44 clinical gastric cancer biopsy samples were classified as amplified (n = 13), non-amplified (n = 25), or equivocal (n = 6). By comparison, 11 samples were positive, 11 were negative, and 22 were equivocally immunohistochemistry. Thus, our novel method reduced the number of equivocal samples from 22 to 6, thereby obviating the need for confirmation by fluorescence or dual-probe in situ hybridization to < 30% of cases. Tumor content chart-assisted digital PCR analysis is also applicable to multiple sites in surgically resected tissues. These results indicate that this analysis is a useful alternative to HER2 immunohistochemistry in gastric cancers that can serve as a basis for the automated evaluation of HER2 status.

A homozygous nonsense CEP250 mutation combined with a heterozygous nonsense C2orf71 mutation is associated with atypical Usher syndrome.

PubMed

Khateb, Samer; Zelinger, Lina; Mizrahi-Meissonnier, Liliana; Ayuso, Carmen; Koenekoop, Robert K; Laxer, Uri; Gross, Menachem; Banin, Eyal; Sharon, Dror

2014-07-01

Usher syndrome (USH) is a heterogeneous group of inherited retinitis pigmentosa (RP) and sensorineural hearing loss (SNHL) caused by mutations in at least 12 genes. Our aim is to identify additional USH-related genes. Clinical examination included visual acuity test, funduscopy and electroretinography. Genetic analysis included homozygosity mapping and whole exome sequencing (WES). A combination of homozygosity mapping and WES in a large consanguineous family of Iranian Jewish origin revealed nonsense mutations in two ciliary genes: c.3289C>T (p.Q1097*) in C2orf71 and c.3463C>T (p.R1155*) in centrosome-associated protein CEP250 (C-Nap1). The latter has not been associated with any inherited disease and the c.3463C>T mutation was absent in control chromosomes. Patients who were double homozygotes had SNHL accompanied by early-onset and severe RP, while patients who were homozygous for the CEP250 mutation and carried a single mutant C2orf71 allele had SNHL with mild retinal degeneration. No ciliary structural abnormalities in the respiratory system were evident by electron microscopy analysis. CEP250 expression analysis of the mutant allele revealed the generation of a truncated protein lacking the NEK2-phosphorylation region. A homozygous nonsense CEP250 mutation, in combination with a heterozygous C2orf71 nonsense mutation, causes an atypical form of USH, characterised by early-onset SNHL and a relatively mild RP. The severe retinal involvement in the double homozygotes indicates an additive effect caused by nonsense mutations in genes encoding ciliary proteins. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Tumor Content Chart-Assisted HER2/CEP17 Digital PCR Analysis of Gastric Cancer Biopsy Specimens

PubMed Central

Matsusaka, Keisuke; Ishikawa, Shumpei; Nakayama, Atsuhito; Ushiku, Tetsuo; Nishimoto, Aiko; Urabe, Masayuki; Kaneko, Nobuyuki; Kunita, Akiko; Kaneda, Atsushi; Aburatani, Hiroyuki; Fujishiro, Mitsuhiro; Seto, Yasuyuki; Fukayama, Masashi

2016-01-01

Evaluating HER2 gene amplification is an essential component of therapeutic decision-making for advanced or metastatic gastric cancer. A simple method that is applicable to small, formalin-fixed, paraffin-embedded biopsy specimens is desirable as an adjunct to or as a substitute for currently used HER2 immunohistochemistry and in situ hybridization protocols. In this study, we developed a microfluidics-based digital PCR method for determining HER2 and chromosome 17 centromere (CEP17) copy numbers and estimating tumor content ratio (TCR). The HER2/CEP17 ratio is determined by three variables—TCR and absolute copy numbers of HER2 and CEP17—by examining tumor cells; only the ratio of the latter two can be obtained by digital PCR using the whole specimen without purifying tumor cells. TCR was determined by semi-automatic image analysis. We developed a Tumor Content chart, which is a plane of rectangular coordinates consisting of HER2/CEP17 digital PCR data and TCR that delineates amplified, non-amplified, and equivocal areas. By applying this method, 44 clinical gastric cancer biopsy samples were classified as amplified (n = 13), non-amplified (n = 25), or equivocal (n = 6). By comparison, 11 samples were positive, 11 were negative, and 22 were equivocally immunohistochemistry. Thus, our novel method reduced the number of equivocal samples from 22 to 6, thereby obviating the need for confirmation by fluorescence or dual-probe in situ hybridization to < 30% of cases. Tumor content chart-assisted digital PCR analysis is also applicable to multiple sites in surgically resected tissues. These results indicate that this analysis is a useful alternative to HER2 immunohistochemistry in gastric cancers that can serve as a basis for the automated evaluation of HER2 status. PMID:27119558

CC2D2A Is Mutated in Joubert Syndrome and Interacts with the Ciliopathy-Associated Basal Body Protein CEP290

PubMed Central

Gorden, Nicholas T.; Arts, Heleen H.; Parisi, Melissa A.; Coene, Karlien L.M.; Letteboer, Stef J.F.; van Beersum, Sylvia E.C.; Mans, Dorus A.; Hikida, Abigail; Eckert, Melissa; Knutzen, Dana; Alswaid, Abdulrahman F.; Özyurek, Hamit; Dibooglu, Sel; Otto, Edgar A.; Liu, Yangfan; Davis, Erica E.; Hutter, Carolyn M.; Bammler, Theo K.; Farin, Frederico M.; Dorschner, Michael; Topçu, Meral; Zackai, Elaine H.; Rosenthal, Phillip; Owens, Kelly N.; Katsanis, Nicholas; Vincent, John B.; Hildebrandt, Friedhelm; Rubel, Edwin W.; Raible, David W.; Knoers, Nine V.A.M.; Chance, Phillip F.; Roepman, Ronald; Moens, Cecilia B.; Glass, Ian A.; Doherty, Dan

2008-01-01

Joubert syndrome and related disorders (JSRD) are primarily autosomal-recessive conditions characterized by hypotonia, ataxia, abnormal eye movements, and intellectual disability with a distinctive mid-hindbrain malformation. Variable features include retinal dystrophy, cystic kidney disease, and liver fibrosis. JSRD are included in the rapidly expanding group of disorders called ciliopathies, because all six gene products implicated in JSRD (NPHP1, AHI1, CEP290, RPGRIP1L, TMEM67, and ARL13B) function in the primary cilium/basal body organelle. By using homozygosity mapping in consanguineous families, we identify loss-of-function mutations in CC2D2A in JSRD patients with and without retinal, kidney, and liver disease. CC2D2A is expressed in all fetal and adult tissues tested. In ciliated cells, we observe localization of recombinant CC2D2A at the basal body and colocalization with CEP290, whose cognate gene is mutated in multiple hereditary ciliopathies. In addition, the proteins can physically interact in vitro, as shown by yeast two-hybrid and GST pull-down experiments. A nonsense mutation in the zebrafish CC2D2A ortholog (sentinel) results in pronephric cysts, a hallmark of ciliary dysfunction analogous to human cystic kidney disease. Knockdown of cep290 function in sentinel fish results in a synergistic pronephric cyst phenotype, revealing a genetic interaction between CC2D2A and CEP290 and implicating CC2D2A in cilium/basal body function. These observations extend the genetic spectrum of JSRD and provide a model system for studying extragenic modifiers in JSRD and other ciliopathies. PMID:18950740

Effect of carbohydrate and protein solutions consumed during a moderate-intensity exercise on post-exercise appetite.

PubMed

Sun, Feng-Hua; Si, Gang-Yan

2017-10-01

This study aimed to investigate whether co-ingestion of carbohydrate and protein during exercise affect the post-exercise ad libitum food intake. Twelve healthy active male participants (mean±SD, age: 20±1; height: 176±6cm; weight: 63.6±5.3kg; VO 2peak : 51.2±7.1ml/kg/min) completed three main experimental trials in a randomized cross-over design. In each trial, the participants completed 1h of ergometer cycling at 60% VO 2peak , followed by 2h recovery. The participants were required to consume one of three solutions every 15min during exercise: distilled water (DW), carbohydrate-electrolyte solution (CE), and carbohydrate-electrolyte-protein solution (CEP). The energy was matched between the two latter solutions. The CHO-to-protein ratio in CEP was 2:1. At the end of recovery period, participants were provided with pizza lunch ad libitum, and the amount consumed was recorded. Several subjective feelings, appetite scores and blood glucose were determined during the experimental trials. No differences were found in either the amount of consumed pizza (DW vs. CE vs. CEP: 607±128 vs. 592±119 vs. 599±125g, P=0.845) or the appetite score before pizza was consumed (DW vs. CE vs. CEP: 14±9 vs. 12±14 vs. 14±10, P=0.357) among the three trials. The blood glucose concentrations during exercise were higher in the CE and CEP trials than in the DW trial. In conclusion, different solutions consumed during a 1h moderate-intensity exercise in the present study did not affect post-exercise appetite. Copyright © 2017 Elsevier Inc. All rights reserved.

Endoplasmic Reticulum Stress as a Mediator of Neurotoxin-Induced Dopamine Neuron Death

DTIC Science & Technology

2006-07-01

reversible reduction in choline acetyl- transferase concentration in rat hypoglossal nucleus after hypoglossal nerve transection. Nature 275, 324–325...cally, analogs were evaluated for their ability to enhance choline acetyltransferase (ChAT) activity in embryonic rat spinal cord and basal forebrain...of ibotenate, CEP1347 protected basal forebrain cholinergic neurons.102 In a model of apoptosis induced in auditory hair cells by noise trauma, CEP1347

Numerical Simulation of Ultra-Fast Pulse Propagation in Two-Photon Absorbing Medium

DTIC Science & Technology

2011-08-01

physical problems including coherent- and incoherent regimes of optical power limiting, saturation, CEP effects, soliton formation etc. It can be also...coherent- and incoherent regimes of optical power limiting, saturation, CEP effects, electromagnetically induced transparency, soliton formation etc...experimental data ( dark blue); Upper panel - 1PA spectrum; Lower panel - 2PA cross section spectrum. The parameter values used are shown in Table 1. 10

Grism compressor for carrier-envelope phase-stable millijoule-energy chirped pulse amplifier lasers featuring bulk material stretcher.

PubMed

Ricci, A; Jullien, A; Forget, N; Crozatier, V; Tournois, P; Lopez-Martens, R

2012-04-01

We demonstrate compression of amplified carrier-envelope phase (CEP)-stable laser pulses using paired transmission gratings and high-index prisms, or grisms, with chromatic dispersion matching that of a bulk material pulse stretcher. Grisms enable the use of larger bulk stretching factors and thereby higher energy pulses with lower B-integral in a compact amplifier design suitable for long-term CEP control.

Public Schools and the Original Federal Land Grant Program. A Background Paper from the Center on Education Policy

ERIC Educational Resources Information Center

Usher, Alexandra

2011-01-01

This background paper from the Center on Education Policy (CEP) examines the origins, history, and evolution of federal land grants for public schools, as well as their significance as an early example of the federal role in education. It is intended to serve as a more detailed companion to another CEP paper, "Get the Federal Government Out of…

[Influence of tobacco smoking on lipase activity in patients with pancreatitis].

PubMed

Sliwińska-Mossoń, Mariola; Milnerowicz, Halina

2005-01-01

The aim of this study is to prove the influence of tobacco smoking on lipase activity in the blood of smoking and non-smoking health persons and in smoking and non-smoking patients with diagnosed acute (AP), chronic exaggerated (CEP) and chronic pancreatitis (CP). The blood has been collected from 28 healthy persons and 55 patients with AP, CEP and CP. The enzyme activity has been determined using the colorimetric method with substrate 1,2-odilauryl-rac-glycero-3-glutaric acid -(6-methylresorufin) ester. The exposures to tobacco smoke have been examined on the basic of concentration of cotinine in the serum of patients. The highest lipase activity has been found in smoking patients with CEP. It has been noted that the serum lipase activity is significantly higher in smoking and healthy persons (p<0,05) then in non-smoking and healthy patients. However no significant differences have been found between the lipase activity in smoking patients with CP and non-smoking patients with CP. Smoking patients with AP and CEP have been found to have a significantly increased enzyme activity (p>0.01; p>0.05 respectively) when compared to non-smoking patients. Results of examination indicate that tobacco smoking has a significant influence on exocrine function of pancreas.

A six-colour flow cytometric method for simultaneous detection of cell phenotype and apoptosis of circulating endothelial cells.

PubMed

Mariucci, S; Rovati, B; Chatzileontiadou, S; Bencardino, K; Manzoni, M; Delfanti, S; Danova, M

2009-01-01

Blood circulating endothelial cells (CECs), with their resting and activated subsets, (rCECs and aCECs) and circulating progenitors cells (CEPs) are two extremely rare cell populations that are important in tissue vascularization. Their number and function are modulated in diseases involving vascular injury, such as human tumours. Although a consensus on the phenotypic definition of endothelial cells, as well as on the optimal enumeration technique, is still lacking, the number of clinical studies based on assessment of these cells is rapidly expanding, as well as the analytical methods employed. The present study aimed to develop a rapid and sensitive flow cytometric method of quantifying and characterizing CECs (with both their subsets and the apoptotic fraction) and CEPs. We analysed peripheral blood samples from 21 subjects with a six-colour flow cytometric approach allowing detection of the cell phenotype of CECs and CEPs using a monoclonal antibodies panel and a dedicated gating strategy. Apoptotic CECs were detected with Annexin V and dead cells with 7-amino-actinomycin D staining. The described technique proved to be a new, reliable, tool increasing our knowledge of the biology of CECs and CEPs and can readily be applied in the study of many pathological conditions characterized by endothelial damage.

The Utrecht questionnaire (U-CEP) measuring knowledge on clinical epidemiology proved to be valid.

PubMed

Kortekaas, Marlous F; Bartelink, Marie-Louise E L; de Groot, Esther; Korving, Helen; de Wit, Niek J; Grobbee, Diederick E; Hoes, Arno W

2017-02-01

Knowledge on clinical epidemiology is crucial to practice evidence-based medicine. We describe the development and validation of the Utrecht questionnaire on knowledge on Clinical epidemiology for Evidence-based Practice (U-CEP); an assessment tool to be used in the training of clinicians. The U-CEP was developed in two formats: two sets of 25 questions and a combined set of 50. The validation was performed among postgraduate general practice (GP) trainees, hospital trainees, GP supervisors, and experts. Internal consistency, internal reliability (item-total correlation), item discrimination index, item difficulty, content validity, construct validity, responsiveness, test-retest reliability, and feasibility were assessed. The questionnaire was externally validated. Internal consistency was good with a Cronbach alpha of 0.8. The median item-total correlation and mean item discrimination index were satisfactory. Both sets were perceived as relevant to clinical practice. Construct validity was good. Both sets were responsive but failed on test-retest reliability. One set took 24 minutes and the other 33 minutes to complete, on average. External GP trainees had comparable results. The U-CEP is a valid questionnaire to assess knowledge on clinical epidemiology, which is a prerequisite for practicing evidence-based medicine in daily clinical practice. Copyright © 2016 Elsevier Inc. All rights reserved.

On-chip learning of hyper-spectral data for real time target recognition

NASA Technical Reports Server (NTRS)

Duong, T. A.; Daud, T.; Thakoor, A.

2000-01-01

As the focus of our present paper, we have used the cascade error projection (CEP) learning algorithm (shown to be hardware-implementable) with on-chip learning (OCL) scheme to obtain three orders of magnitude speed-up in target recognition compared to software-based learning schemes. Thus, it is shown, real time learning as well as data processing for target recognition can be achieved.

VizieR Online Data Catalog: Eclipsing times of BE Cep (Dai+, 2012)

NASA Astrophysics Data System (ADS)

Dai, H.-F.; Yang, Y.-G.; Hu, S.-M.; Guo, D.-F.

2012-03-01

New CCD observations of BE Cep were carried out from 2008 to 2011, using the 1.0m Cassegrain telescope at the Weihai Astronomical Observatory (WHAO) of Shandong University, the 85cm telescope and the 60cm telescope at the Xinglong station (XLs) of National Astronomical Observatories of China (NAOC), and the 1.56m telescope at the Sheshan Station of Shanghai Astronomical Observatory (SHAO). (2 data files).

Secure Transaction Protocol for CEPS Compliant EPS in Limited Connectivity Environment

NASA Astrophysics Data System (ADS)

Devane, Satish; Phatak, Deepak

Common Electronic Purse Specification (CEPS) used by European countries, elaborately defines the transaction between customer’s CEP card and merchant’s point of sales (POS) terminal. However it merely defines the specification to transfer the transactions between the Merchant and Merchant Acquirer (MA). This paper proposes a novel approach by introducing an entity, mobile merchant acquirer (MMA) which is a trusted agent of MA and principally works on man in middle concept, but facilitates remote two fold mutual authentication and secure transaction transfer between Merchant and MA through MMA. This approach removes the bottle-neck of connectivity issues between Merchant and MA in limited connectivity environment. The proposed protocol ensures the confidentiality, integrity and money atomicity of transaction batch. The proposed protocol has been verified for correctness by Spin, a model checker and security properties of the protocol have been verified by avispa.

Detection of cephradine through the electrochemical study of the degradation product of cephradine

NASA Astrophysics Data System (ADS)

Jiang, Qingfeng; Ying, Yibin; Wang, Jianping; Ye, Zunzhong; Li, Yanbin

2005-11-01

The degradation product of cephradine(CEP), a broad spectrum antibiotic, with NaOH was studied in solution by Cyclic Voltammetry and Differential Pulse Voltammetry at a three electrode system (Gold working electrode, Hg/HgCl reference electrode and Platinum counter electrode). Our experiment was based on that the R-SH in degradation product could cause a deoxidization peak at gold working electrode. The response was optimized with respect to accumulation time, ionic strength, drug concentration, reproducibility and other variables. We found that the degradation product of CEP in Na2HPO4-NaH2PO4 buffer could cause a sensitive deoxidization peak at -0.68V. A linear dependence of peak currents on the concentration was observed in the range of 10-7 - 10-6 mol/L, with a detection limit of 0.5*10-7mol/L. This method can achieve satisfactory results in the application of detecting human-made CEP.

On-target diagnosing of few-cycle pulses by high-order-harmonic generation

NASA Astrophysics Data System (ADS)

Brambila, Danilo S.; Husakou, Anton; Ivanov, Misha; Zhavoronkov, Nickolai

2017-12-01

We propose an approach to determine the residual phase distortion directly in the interaction region of few-cycle laser radiation with a gaseous target. We describe how the spectra of the generated high harmonics measured as a function of externally introduced dispersion into the driving few-cycle laser pulse can be used to decode small amounts of second- and third-order spectral phase, including the sign. The diagnosis is based on the analysis of several key features in the high-harmonic spectrum: the depth of spectral modulation, the position of the cutoff, and the symmetry of the spectrum with respect to the introduced dispersion. The approach is applicable to pulses without carrier-envelope phase (CEP) stabilization. Surprisingly, we find that for nearly-single-cycle pulses with nonstabilized CEP, deep spectral modulations in the harmonic spectra emerge for positively rather than negatively chirped pulses, in contrast to the case of CEP-stabilized pulses.

Préparation chimique et propriétés optiques de CeP 5O 14 triclinique

NASA Astrophysics Data System (ADS)

Rzaigui, Mohamed; Ariguib, N´jia Kbir

1985-01-01

Crystals of a new cerium(III)-ultraphosphate form, CeP 5O 14, have been grown from CeCl 3 · 7H 2O and NH 4H 2PO 4. Synthesis and structural characterization by X-ray diffraction and ir absorption spectroscopy are given. The new CeP 5O 14 crystallizes in a triclinic unit cell, P1, with parameters: a = 9.229(2), b = 8.879(1), c = 7.201(1) (Å), α = 110.27(1), β = 102.75(1), γ = 82.13(1)°, Z = 2, and D x = 3.20. This compound is piezoelectric and has no known structural analog. The excitation and emission spectrum of this Ce-ultraphosphate variety are reported. This material emits strongly in the near-uv. The emission band peaks at 322 nm and decays, at first, with τ 1 = 14 nsec, then, with τ 2 = 60 nsec.

Multiple critical endpoints in magnetized three flavor quark matter

NASA Astrophysics Data System (ADS)

Ferreira, Márcio; Costa, Pedro; Providência, Constança

2018-01-01

The magnetized phase diagram for three-flavor quark matter is studied within the Polyakov extended Nambu-Jona-Lasinio model. The order parameters are analyzed with special emphasis on the strange quark condensate. We show that the presence of an external magnetic field induces several critical endpoints (CEPs) in the strange sector, which arise due to the multiple phase transitions that the strange quark undergoes. The spinodal and binodal regions of the phase transitions are shown to increase with external magnetic field strength. The influence of strong magnetic fields on the isentropic trajectories around the several CEPs is analyzed. A focusing effect is observed on the region towards the CEPs that are related with the strange quark phase transitions. Compared to the chiral transitions, the deconfinement transition turns out to be less sensitive to the external magnetic field and the crossover nature is preserved over the whole phase diagram.

Carrier-envelope phase-dependent field-free molecular orientation

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

Shu Chuancun; Yuan Kaijun; Hu Wenhui

2009-07-15

We present a strategy to achieve carrier-envelope phase-dependent field-free molecular orientation with the use of carrier-envelope phase (CEP) stabilization and asymmetric few-cycle terahertz (THz) laser pulses. The calculations are performed on the LiH molecule by an exact solution of the full time-dependent Schroedinger equation including both the vibrational and the rotational degrees of freedom. Our calculations show that an efficient field-free molecular orientation can be obtained even at considerable temperatures. Moreover, we find a simple dependence of the field-free orientation on the CEP, which implies that the CEP becomes an important parameter for control of molecular orientation. More importantly, themore » realization of this scenario is appealing based on the fact that the intense few-cycle THz pulse with duration as short as a few optical cycles is available as a research tool.« less

Hierarchical assembly of centriole subdistal appendages via centrosome binding proteins CCDC120 and CCDC68.

PubMed

Huang, Ning; Xia, Yuqing; Zhang, Donghui; Wang, Song; Bao, Yitian; He, Runsheng; Teng, Junlin; Chen, Jianguo

2017-04-19

In animal cells, the centrosome is the main microtubule-organizing centre where microtubules are nucleated and anchored. The centriole subdistal appendages (SDAs) are the key structures that anchor microtubules in interphase cells, but the composition and assembly mechanisms of SDAs are not well understood. Here, we reveal that centrosome-binding proteins, coiled-coil domain containing (CCDC) 120 and CCDC68 are two novel SDA components required for hierarchical SDA assembly in human cells. CCDC120 is anchored to SDAs by ODF2 and recruits CEP170 and Ninein to the centrosome through different coiled-coil domains at its N terminus. CCDC68 is a CEP170-interacting protein that competes with CCDC120 in recruiting CEP170 to SDAs. Furthermore, CCDC120 and CCDC68 are required for centrosome microtubule anchoring. Our findings elucidate the molecular basis for centriole SDA hierarchical assembly and microtubule anchoring in human interphase cells.

Association of levels of antibodies against citrullinated cyclic peptides and citrullinated α-enolase in chronic and aggressive periodontitis as a risk factor of Rheumatoid arthritis: a case control study.

PubMed

Reichert, Stefan; Schlumberger, Wolfgang; Dähnrich, Cornelia; Hornig, Nora; Altermann, Wolfgang; Schaller, Hans-Günter; Schulz, Susanne

2015-08-29

Periodontal disease could be a risk factor for rheumatoid arthritis (RA). It is assumed that the bacterial strain Porphyromonas gingivalis mediates citrullination of host peptides and thereby the generation of RA-associated autoantibodies in genetically predisposed individuals. For that reason non-RA individuals who suffered from generalized aggressive (GAgP, N = 51) and generalized chronic periodontitis (GChP, N = 50) were investigated regarding the occurrence of antibodies against citrullinated cyclic peptides (anti-CCP) and citrullinated α-enolase peptide-1 (anti-CEP-1) in comparison to non-RA non-periodontitis controls (N = 89). Furthermore, putative associations between infections with five periodontopathic bacteria or expression of certain human leucocyte antigens (HLA) to these autoantibodies were investigated. The presence of anti-CCP and anti-CEP-1 in plasma samples was conducted with enzyme linked immunosorbent assay. Subgingival plaque specimens were taken from the deepest pocket of each quadrant and pooled. For detection of DNA of five periodontopathic bacteria PCR with sequence specific oligonucleotides was carried out. Low resolution HLA typing was carried out with PCR with sequence specific primers. Differences between patients and controls were assessed using Chi square test with Yates correction or Fisher`s exact test if the expected number n in one group was <5. Two patients with GAgP (3.9%), no patient with GChP and two controls (2.2%, pFisher = 0.662) were positive for anti-CEP-1 whereas no study participant was anti-CCP positive. Individuals with P. gingivalis were slightly more often anti-CEP-1 positive in comparison to individuals without P. gingivalis (3.2 vs. 1.1%, pFisher = 0.366). Carrier of HLA-DQB1*06 or the HLA combination DRB1*13; DRB3*; DQB1*06 were slightly more anti-CEP-1 positive (6.1 and 4.3%) than no carriers (0.7 and 0%, pFisher 0.053). GAgP and GChP and the presence of periodontopathic bacteria are not associated with an increased risk for occurrence of anti-CCP and anti-CEP-1 autoantibodies. The putative relationship between periodontitis and RA should be investigated in further studies.

Russia and the Iranian Nuclear Program: Replay or Breakthrough? (Strategic Perspectives, no. 9)

DTIC Science & Technology

2012-03-01

Interfax– AVN Online, February 17, 2009, CEP20090217950042. 6 “Delivery of S–300 Air Defense Systems to Iran Could Be Postponed,” Interfax– AVN Online...analysis/20111115/168714032.html>. 5 “Hostilities against Iran would have unpredictable consequences—Lavrov (Part 2),” Interfax– AVN Online, November 7...Force, Death of Civilians in Iran,” Interfax– AVN Online, June 26, 2009, CEP20090626950139. This was a far cry from American reaction. Several days

CEP populations observed by ISEE 1

NASA Astrophysics Data System (ADS)

Whitaker, Katherine E.; Chen, Jiasheng; Fritz, Theodore A.

2006-12-01

Observations on October 30, 1978 show the ISEE 1 spacecraft passing though the high-altitude dayside northern cusp region from roughly 16:00 to 18:30 UT, during a slow solar wind period (~380 km/s). More than two orders of magnitude enhancements of the cusp energetic particle (CEP) fluxes are observed along with a depressed and turbulent local magnetic field and both ionospheric and solar wind plasma. The clock angle of the local magnetic field is different from that of the IMF, implying that the spacecraft was indeed inside the magnetosphere. The observed variations of the pitch angle distributions provide a unique opportunity to determine the structure of the cusp. The CEP fluxes were measured at about 8.5 hours MLT when the IMF had both an 8-10 nT duskward and southward component. The dawnside location of the cusp under these IMF conditions is unexpected by the existing models. No obvious time-energy dispersion is measured for the CEP fluxes. The time evolution of the phase space density as the spacecraft crossed the cusp boundary layer exhibits a positive gradient pointed to the high-altitude cusp, indicating a probable cusp source of the energetic particles. Through a careful analysis of the data available, we report the first detailed study of the equatorial orbiting ISEE 1 spacecraft passing through the high altitude cusp region.

Transcription factors CEP-1/p53 and CEH-23 collaborate with AAK-2/AMPK to modulate longevity in Caenorhabditis elegans.

PubMed

Chang, Hsin-Wen; Pisano, Steve; Chaturbedi, Amaresh; Chen, Jennifer; Gordon, Sarah; Baruah, Aiswarya; Lee, Siu Sylvia

2017-08-01

A decline in mitochondrial electron transport chain (ETC) function has long been implicated in aging and various diseases. Recently, moderate mitochondrial ETC dysfunction has been found to prolong lifespan in diverse organisms, suggesting a conserved and complex role of mitochondria in longevity determination. Several nuclear transcription factors have been demonstrated to mediate the lifespan extension effect associated with partial impairment of the ETC, suggesting that compensatory transcriptional response to be crucial. In this study, we showed that the transcription factors CEP-1/p53 and CEH-23 act through a similar mechanism to modulate longevity in response to defective ETC in Caenorhabditis elegans. Genomewide gene expression profiling comparison revealed a new link between these two transcription factors and AAK-2/AMP kinase (AMPK) signaling. Further functional analyses suggested that CEP-1/p53 and CEH-23 act downstream of AAK-2/AMPK signaling and CRTC-1 transcriptional coactivator to promote stress resistance and lifespan. As AAK-2, CEP-1, and CEH-23 are all highly conserved, our findings likely provide important insights for understanding the organismal adaptive response to mitochondrial dysfunction in diverse organisms and will be relevant to aging and pathologies with a mitochondrial etiology in human. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Theoretical study on the antitumor properties of Ru(II) complexes containing 2-pyridyl, 2-pyridine-4-carboxylic acid ligands

NASA Astrophysics Data System (ADS)

Erkan kariper, Sultan; Sayin, Koray; Karakaş, Duran

2017-12-01

[Ru(bipy)2(CppH)]2+(1), [Ru(bipy)2(Cpp-NH-Hex-COOH)]2+(2), [Ru(dppz)2(CppH)]2+(3) and [Ru(dppz)2(Cpp-NH-Hex-COOH)]2+(4) were calculated by Hartree-Fock (HF), Density Functional Theory (DFT) hybrid B3LYP and Moller-Plesset Perturbation (MPn n = 2,3) theory method and CEP-4G, CEP-31G, CEP-121G, LANL2DZ, LANL2MB, SDD basic sets and a mixed basic set with the keyword GEN in gas phase and water. Structure parameters obtained from optimized structures were compared with experimental parameters. M062X/(6-31G(d))(CEP-4G) level was taken into account for the most appropriate calculation level. IR, UV-VIS and NMR spectrums were examined for structural characterization. The optimal structure was identified via structure parameters, IR, UV-VIS and NMR spectrums. For the most compatible structure, the highest molecular orbital energy (EHOMO) which one of the most effective chemical determiners on the antitumor activity of the complexes, the lowest molecular orbital energy (ELUMO), LUMO-HOMO energy gap, hardness (η), softness (σ), electronegativity (χ), chemical potential (μ), electrophilicity index (ω), molar volume (V), dipole moment (DM), total negative charge (TNC), enthalpy (H), entropy (S) and total energy (E) were calculated. The causes of anticancer activity of the complexes have been studied.

Clinical and radiologic manifestations of congenital extrahepatic portosystemic shunts: a comprehensive review.

PubMed

Alonso-Gamarra, Eduardo; Parrón, Manuel; Pérez, Ana; Prieto, Consuelo; Hierro, Loreto; López-Santamaría, Manuel

2011-01-01

Congenital extrahepatic portosystemic shunt (CEPS) is a rare condition in which the portomesenteric blood drains into a systemic vein, bypassing the liver through a complete or partial shunt. Most often, the diagnosis is made primarily with Doppler ultrasonography. Computed tomographic angiography and magnetic resonance angiography are used for further classification of the shunt and assessment of accompanying anomalies. Conventional angiography is necessary when results of the other tests disagree or are inconclusive. CEPS is classified into two types according to the pattern of anastomoses between the portal vein and systemic vein. In type 1, intrahepatic portal venous supply is absent; in type 2, intrahepatic portal venous supply is preserved. Type 1 usually occurs in girls with associated malformations, such as situs ambiguous with polysplenia and congenital heart defects. Associated anomalies are less frequent in type 2, and symptoms usually develop later without a gender preference. Hepatic encephalopathy and liver dysfunction are possible complications of both types and usually develop during adulthood. Both types are also associated with regenerative hepatic nodules. The clinical setting and imaging appearance of these nodules can help one avoid misdiagnosis. Definitive treatment of CEPS is determined by the type of shunt. Liver transplantation is the only effective treatment for symptomatic type 1 CEPS; surgical closure or embolization of the shunt is the therapeutic approach for type 2. Copyright © RSNA, 2011.

Effect of cassava bioethanol by-product and crude palm oil in Brahman x Thai native yearling heifer cattle diets: I. Nutrient digestibility and growth performance.

PubMed

Phoemchalard, Chirasak; Uriyapongson, Suthipong; Berg, Eric Paul

2014-04-01

The effects of cassava bioethanol by-product (CEP) and crude palm oil (CPO) on feed intake, nutrient digestibility, and growth performance of yearling heifers were investigated in a 150-day feeding trial. Eighteen, crossbred heifers (Brahman x Thai native) were randomly allotted according to 2 × 3 factorial arrangement. Low or high levels of CEP (15 or 30% of concentrate, LCEP, or HCEP) were basal treatments and 0, 2, and 4% CPO were daily top-dressed. Concentrate was supplemented at 1.75% of body weight (BW) and rice straw offered ad libitum. CEP level had no significance on feed intake. CPO increased roughage intake, concentrate intake, and total feed intake when expressed as %BW/d (P < 0.01) and as metabolic BW (kg(0.75)/d, P < 0.05). Intakes of dry matter (DM), organic matter (OM), and crude protein (CP) were similar (P > 0.05). Intake of fat increased with higher levels of CPO (P < 0.001). The DM, OM, CP, and EE digestibility of cattle-fed HCEP was lower than LCEP, but adding 4% CPO increased digestibility. Growth performance was similar for all diets (P > 0.05). We concluded that CEP can be used up to 30% in the diet, with or without additional fat inclusion.

Performance tests of the 5 TW, 1 kHz, passively CEP-stabilized ELI-ALPS SYLOS few-cycle laser system (Conference Presentation)

NASA Astrophysics Data System (ADS)

Stanislauskas, Tomas; Budriūnas, Rimantas; Veitas, Gediminas; Gadonas, Darius; Adamonis, Jonas; Aleknavičius, Aidas; Masian, Gžegož; Kuprionis, Zenonas; Hoff, Dominik; Paulus, Gerhard G.; Börzsönyi, Ádám.; Toth, Szabolcs; Kovacs, Mate; Csontos, János; López-Martens, Rodrigo; Osvay, Károly

2017-05-01

ELI-ALPS in Hungary, one of the three pillars of the Extreme Light Infrastructure, aims at providing diverse light sources, including energetic attosecond pulses at the highest possible repetition rates. One of the main laser systems for driving plasma and gas-based HHG stages, is a state-of-the-art 1 kHz few-cycle laser called SYLOS. Targeted pulse parameters are an energy of 100 mJ and a duration shorter than two optical cycles (<6 fs), with outstanding energy, phase and pointing stability as well as high spatiotemporal quality. The first phase of the laser system has already set a new standard in kHz laser system engineering and technology. The performance and reliability of the SYLOS laser have been consistently tested over the course of a six-month trial period. During this time the system was running at least 8 hours a day at full power for more than 5 months. The current output parameters are 5 TW peak power, 45 mJ pulse energy with 9 fs duration and 300 mrad CEP stability, while the spectrum spans over 300 nm around 840 nm central wavelength. The layout follows the general scheme NOPCPA architecture with a passively CEP-stabilized front-end. The pulses are negatively chirped for the amplification process and compressed by a combination of large aperture bulk glass blocks and positively chirped mirrors under vacuum conditions at the output. During the trial period, the laser system demonstrated outstanding reliability. Daily startup and shutdown procedures take only a few minutes, and the command-control system enables pulse parameters to be modified instantly. Controlling the delays of individual NOPCPA stages makes it possible to tailor the output spectrum of the pulses and tune the central wavelength between 770 nm and 940 nm. We performed several experimental tests to find out the pulse characteristics. Pulse duration was verified with Wizzler, chirp-scan, autocorrelation methods and a stereo-ATI independently. All of them confirmed the sub-9 fs pulse duration. We recorded the long-term waveform and pointing stabilities of the beam in order to find out the effect of the temperature load on optical elements. Excluding a short initial warm up time, stable signals were observed in general. The in-loop and out-of-loop CEP stability was cross-checked between f-to-2f and stereo-ATI devices. Moreover, the inherent CEP stability of the system without feedback loop was also found to be surprisingly robust thanks to the passive CEP stabilization of the front-end. The polarization contrast was better than 1000:1. The temporal contrast was also measured independently with Sequoia and Tundra cross-correlators, and on the ns scale with a fast photodiode and GHz oscilloscope as well. Results showed that the pulse pedestal generally consists of parametric superfluorescence below the 1E-7 level and about 100 ps long, well in accordance with the pump duration. Delaying the pump pulse allows us to shift the seed pulse to the front and reach a pre-pulse pedestal below 1E-11 at 30 ps before the pulse peak. Detailed findings on all the examined pulse characteristics of the SYLOS laser will be reported in this presentation.

Plasma Protein Pentosidine and Carboxymethyllysine, Biomarkers for Age-related Macular Degeneration*

PubMed Central

Ni, Jiaqian; Yuan, Xianglin; Gu, Jiayin; Yue, Xiuzhen; Gu, Xiaorong; Nagaraj, Ram H.; Crabb, John W.

2009-01-01

Age-related macular degeneration (AMD) causes severe vision loss in the elderly; early identification of AMD risk could help slow or prevent disease progression. Toward the discovery of AMD biomarkers, we quantified plasma protein Nε-carboxymethyllysine (CML) and pentosidine from 58 AMD and 32 control donors. CML and pentosidine are advanced glycation end products that are abundant in Bruch membrane, the extracellular matrix separating the retinal pigment epithelium from the blood-bearing choriocapillaris. We measured CML and pentosidine by LC-MS/MS and LC-fluorometry, respectively, and found higher mean levels of CML (∼54%) and pentosidine (∼64%) in AMD (p < 0.0001) relative to normal controls. Plasma protein fructosyl-lysine, a marker of early glycation, was found by amino acid analysis to be in equal amounts in control and non-diabetic AMD donors, supporting an association between AMD and increased levels of CML and pentosidine independent of other diseases like diabetes. Carboxyethylpyrrole (CEP), an oxidative modification from docosahexaenoate-containing lipids and also abundant in AMD Bruch membrane, was elevated ∼86% in the AMD cohort, but autoantibody titers to CEP, CML, and pentosidine were not significantly increased. Compellingly higher mean levels of CML and pentosidine were present in AMD plasma protein over a broad age range. Receiver operating curves indicate that CML, CEP adducts, and pentosidine alone discriminated between AMD and control subjects with 78, 79, and 88% accuracy, respectively, whereas CML in combination with pentosidine provided ∼89% accuracy, and CEP plus pentosidine provided ∼92% accuracy. Pentosidine levels appeared slightly altered in AMD patients with hypertension and cardiovascular disease, indicating further studies are warranted. Overall this study supports the potential utility of plasma protein CML and pentosidine as biomarkers for assessing AMD risk and susceptibility, particularly in combination with CEP adducts and with concurrent analyses of fructosyl-lysine to detect confounding factors. PMID:19435712

The Frequency of Autoimmune N-Methyl-D-Aspartate Receptor Encephalitis Surpasses That of Individual Viral Etiologies in Young Individuals Enrolled in the California Encephalitis Project

PubMed Central

Sheriff, Heather; Dalmau, Josep; Tilley, Drake H.; Glaser, Carol A.

2012-01-01

Background. In 2007, the California Encephalitis Project (CEP), which was established to study the epidemiology of encephalitis, began identifying cases of anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis. Increasing numbers of anti-NMDAR encephalitis cases have been identified at the CEP, and this form rivals commonly known viral etiologies as a causal agent. We report here the relative frequency and differences among encephalitides caused by anti-NMDAR and viral etiologies within the CEP experience. Methods. Demographic, frequency, and clinical data from patients with anti-NMDAR encephalitis are compared with those with viral encephalitic agents: enterovirus, herpes simplex virus type 1 (HSV-1), varicella-zoster virus (VZV), and West Nile virus (WNV). All examined cases presented to the CEP between September 2007 and February 2011 and are limited to individuals aged ≤30 years because of the predominance of anti-NMDAR encephalitis in this group. The diagnostic costs incurred in a single case are also included. Results. Anti-NMDAR encephalitis was identified >4 times as frequently as HSV-1, WNV, or VZV and was the leading entity identified in our cohort. We found that 65% of anti-NMDAR encephalitis occurred in patients aged ≤18 years. This disorder demonstrated a predilection, which was not observed with viral etiologies, for females (P < .01). Seizures, language dysfunction, psychosis, and electroencephalographic abnormalities were significantly more frequent in patients with anti-NMDAR encephalitis (P < .05), and autonomic instability occurred exclusively in this group. Discussion. Anti-NMDAR encephalitis rivals viral etiologies as a cause of encephalitis within the CEP cohort. This entity deserves a prominent place on the encephalitic differential diagnosis to avoid unnecessary diagnostic and treatment costs, and to permit a more timely treatment. PMID:22281844

Utility of Alternate, Noncentromeric Chromosome 17 Reference Probe for Human Epidermal Growth Factor Receptor Fluorescence In Situ Hybridization Testing in Breast Cancer Cases.

PubMed

Pai, Trupti; Shet, Tanuja; Patil, Asawari; Shetty, Omshree; Singh, Angad; Desai, Sangeeta B

2018-05-01

Context PathVysion-a US Food and Drug Administration-approved dual-probe human epidermal growth factor receptor ( HER2) fluorescence in situ hybridization (FISH) assay-provides the HER2: CEP17 ratio, a centromeric enumeration probe ratio for determining HER2 status in breast cancers. However, pericentromeric amplifications might then skew the HER2: CEP17 ratio, underestimating the HER2 status, which calls into question the use of CEP17 as the reference probe. Objective To analyze the utility of a noncentromeric chromosome 17 reference locus ( D17S122) to assess HER2 gene status in cases showing "nonclassical" FISH patterns with the CEP17 probe. Design The HER2 status of breast cancers accessioned in the years 2015-2017, displaying "nonclassical" or "equivocal" results by the PathVysion (Abbott Molecular Inc, Des Plaines, Illinois) HER2 DNA Probe Kit were reflex tested using an alternate FISH probe (ZytoLight SPEC/D17S122, ZytoVision, Bremerhaven, Germany) and interpreted with American Society of Clinical Oncology/College of American Pathologists 2013 guidelines. Results Of 37 cases, 17 were FISH equivocal. With the alternate D17S122 probe, 13 (76.4%) were reclassified as amplified, 3 (17.6%) as nonamplified, and a single case retained an equivocal result. Of the 17 cases with a chromosome 17 polysomy pattern, disomy, polysomy, and monosomy patterns were seen with 14 cases, 2 cases, and 1 case, respectively. Within the 17 cases with polysomy pattern, 3 (17.6%) demonstrated an unusual colocalization pattern of HER2 and CEP17, which was not observed with the alternate probe. Conclusions The denominator-stable alternate probe is a useful adjunct in the diagnostic armamentarium to analyze HER2 status in cases with FISH equivocal and complex patterns.

Simultaneous Presence of PrtH and PrtH2 Proteinases in Lactobacillus helveticus Strains Improves Breakdown of the Pure αs1-Casein▿ †

PubMed Central

Sadat-Mekmene, L.; Jardin, J.; Corre, C.; Mollé, D.; Richoux, R.; Delage, M.-M.; Lortal, S.; Gagnaire, V.

2011-01-01

Lactobacillus helveticus can possess one or two cell envelope proteinases (CEPs), called PrtH2 and PrtH. The aim of this work was to explore the diversity of 15 strains of L. helveticus, isolated from various origins, in terms of their proteolytic activities and specificities on pure caseins or on milk casein micelles. CEP activity differed 14-fold when the strains were assayed on a synthetic substrate, but no significant differences were detected between strains possessing one or two CEPs. No correlation was observed between the proteolytic activities of the strains and their rates of acidification in milk. The kinetics of hydrolysis of purified αs1- and β-casein by L. helveticus whole cells was monitored using Tris-Tricine sodium dodecyl sulfate (SDS) electrophoresis, and for four strains, the peptides released were identified using mass spectrometry. While rapid hydrolysis of pure β-casein was observed for all strains, the hydrolysis kinetics of αs1-casein was the only criterion capable of distinguishing between the strains based on the number of CEPs. Fifty-four to 74 peptides were identified for each strain. When only PrtH2 was present, 22 to 30% of the peptides originated from αs1-casein. The percentage increased to 41 to 49% for strains in which both CEPs were expressed. The peptide size ranged from 6 to 33 amino acids, revealing a broad range of cleavage specificities, involving all classes of amino acids (Leu, Val, Ala, Ile, Glu, Gln, Lys, Arg, Met, and Pro). Regions resistant to proteolysis were identified in both caseins. When strains were grown in milk, a drastic reduction in the number of peptides was observed, reflecting changes in accessibility and/or peptide assimilation during growth. PMID:21037305

Mid-term haemodynamic and clinical results after aortic valve replacement using the Freedom Solo stentless bioprosthesis versus the Carpentier Edwards Perimount stented bioprosthesis.

PubMed

van der Straaten, Ellen P J; Rademakers, Leonard M; van Straten, Albert H M; Houterman, Saskia; Tan, M Erwin S H; Soliman Hamad, Mohamed A

2016-04-01

The aim of this study was to investigate the mid-term haemodynamic and clinical results after aortic valve replacement (AVR) using the Sorin Freedom Solo (SFS) stentless bioprosthesis, compared with the standard Carpentier Edwards Perimount (CEP) stented bioprosthesis. In this retrospective cohort study of prospectively collected data, 116 patients were included in the SFS group (53 males; median age 74 years, range 56-85 years), and 122 patients in the CEP group (85 males; median age 73 years, range 43-88 years) between July 2007 and January 2013. Echocardiography was performed at 6 weeks after surgery in our centre, and the most recent echocardiography (in our centre or in referring cardiology departments) was requested. Between September 2013 and April 2014, all patients were called by the same researcher to gain clinical follow-up data. Mid-term mortality was 16.4% in the SFS group (19 patients) and 21.3% in the CEP group (26 patients); (P = 0.3). The mean transvalvular gradient was 7.4 ± 3.1 mmHg in the SFS group, and 11.6 ± 3.2 mmHg in the CEP group at 6 weeks postoperatively (P < 0.001). When stratified by labelled valve size, mean gradients were significantly lower in the SFS group for every size (P ≤ 0.03). After 3.3 ± 1.4 years of follow-up, the mean gradient was still significantly lower in the SFS group than that in the CEP group (P < 0.001). Clinical follow-up showed relatively low complication rates. These data suggest that the Sorin Freedom Solo stentless bioprosthesis is as safe as the Carpentier Edwards bioprosthesis, and provides better short- and mid-term haemodynamic performance than the Carpentier Edwards bioprosthesis. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Centrobin-centrosomal protein 4.1-associated protein (CPAP) interaction promotes CPAP localization to the centrioles during centriole duplication.

PubMed

Gudi, Radhika; Zou, Chaozhong; Dhar, Jayeeta; Gao, Qingshen; Vasu, Chenthamarakshan

2014-05-30

Centriole duplication is the process by which two new daughter centrioles are generated from the proximal end of preexisting mother centrioles. Accurate centriole duplication is important for many cellular and physiological events, including cell division and ciliogenesis. Centrosomal protein 4.1-associated protein (CPAP), centrosomal protein of 152 kDa (CEP152), and centrobin are known to be essential for centriole duplication. However, the precise mechanism by which they contribute to centriole duplication is not known. In this study, we show that centrobin interacts with CEP152 and CPAP, and the centrobin-CPAP interaction is critical for centriole duplication. Although depletion of centrobin from cells did not have an effect on the centriolar levels of CEP152, it caused the disappearance of CPAP from both the preexisting and newly formed centrioles. Moreover, exogenous expression of the CPAP-binding fragment of centrobin also caused the disappearance of CPAP from both the preexisting and newly synthesized centrioles, possibly in a dominant negative manner, thereby inhibiting centriole duplication and the PLK4 overexpression-mediated centrosome amplification. Interestingly, exogenous overexpression of CPAP in the centrobin-depleted cells did not restore CPAP localization to the centrioles. However, restoration of centrobin expression in the centrobin-depleted cells led to the reappearance of centriolar CPAP. Hence, we conclude that centrobin-CPAP interaction is critical for the recruitment of CPAP to procentrioles to promote the elongation of daughter centrioles and for the persistence of CPAP on preexisting mother centrioles. Our study indicates that regulation of CPAP levels on the centrioles by centrobin is critical for preserving the normal size, shape, and number of centrioles in the cell. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Translational aspects of rectal evoked potentials: a comparative study in rats and humans

PubMed Central

Nissen, Thomas Dahl; Graversen, Carina; Coen, Steven J.; Hultin, Leif; Aziz, Qasim; Lykkesfeldt, Jens; Drewes, Asbjørn Mohr

2013-01-01

Inconsistencies between species has stunted the progress of developing new analgesics. To increase the success of translating results between species, improved comparable models are required. Twelve rats received rectal balloon distensions on 2 different days separated by 24.3 (SD 24.6) days. Rectal balloon distensions were also performed in 18 humans (mean age: 34 yr; range: 21–56 yr; 12 men) on two separate occasions, separated by 9.3 (SD 5.5) days. In rats, cerebral evoked potentials (CEPs) were recorded by use of implanted skull-electrodes to distension pressure of 80 mmHg. In humans surface electrodes and individualized pressure, corresponding to pain detection threshold, were used. Comparison of morphology was assessed by wavelet analysis. Within- and between-day reproducibility was assessed in terms of latencies, amplitudes, and frequency content. In rats CEPs showed triphasic morphology. No differences in latencies, amplitudes, and power distribution were seen within or between days (all P ≥ 0.5). Peak-to-peak amplitude between the first positive and negative potential were the most reproducible characteristic within and between days (evaluated by intraclass correlation coefficients, ICC) (ICC = 0.99 and ICC = 9.98, respectively). In humans CEPs showed a triphasic morphology. No differences in latencies, amplitudes, or power distribution were seen within or between days (all P ≥ 0.2). Latency to the second negative potential (ICC = 0.98) and the second positive potential (ICC = 0.95) was the most reproducible characteristic within and between days. A unique and reliable translational platform was established assessing visceral sensitivity in rats and humans, which may improve the translational process of developing new drugs targeting visceral pain. PMID:23703652

Breast cancer evaluation by fluorescent dot detection using combined mathematical morphology and multifractal techniques

PubMed Central

2011-01-01

Background Fluorescence in situ hybridization (FISH) is very accurate method for measuring HER2 gene copies, as a sign of potential breast cancer. This method requires small tissue samples, and has a high sensitivity to detect abnormalities from a histological section. By using multiple colors, this method allows the detection of multiple targets simultaneously. The target parts in the cells become visible as colored dots. The HER-2 probes are visible as orange stained spots under a fluorescent microscope while probes for centromere 17 (CEP-17), the chromosome on which the gene HER-2/neu is located, are visible as green spots. Methods The conventional analysis involves the scoring of the ratio of HER-2/neu over CEP 17 dots within each cell nucleus and then averaging the scores for a number of 60 cells. A ratio of 2.0 of HER-2/neu to CEP 17 copy number denotes amplification. Several methods have been proposed for the detection and automated evaluation (dot counting) of FISH signals. In this paper the combined method based on the mathematical morphology (MM) and inverse multifractal (IMF) analysis is suggested. Similar method was applied recently in detection of microcalcifications in digital mammograms, and was very successful. Results The combined MM using top-hat and bottom-hat filters, and the IMF method was applied to FISH images from Molecular Biology Lab, Department of Pathology, Wielkoposka Cancer Center, Poznan. Initial results indicate that this method can be applied to FISH images for the evaluation of HER2/neu status. Conclusions Mathematical morphology and multifractal approach are used for colored dot detection and counting in FISH images. Initial results derived on clinical cases are promising. Note that the overlapping of colored dots, particularly red/orange dots, needs additional improvements in post-processing. PMID:21489192

Centrobin-Centrosomal Protein 4.1-associated Protein (CPAP) Interaction Promotes CPAP Localization to the Centrioles during Centriole Duplication*

PubMed Central

Gudi, Radhika; Zou, Chaozhong; Dhar, Jayeeta; Gao, Qingshen; Vasu, Chenthamarakshan

2014-01-01

Centriole duplication is the process by which two new daughter centrioles are generated from the proximal end of preexisting mother centrioles. Accurate centriole duplication is important for many cellular and physiological events, including cell division and ciliogenesis. Centrosomal protein 4.1-associated protein (CPAP), centrosomal protein of 152 kDa (CEP152), and centrobin are known to be essential for centriole duplication. However, the precise mechanism by which they contribute to centriole duplication is not known. In this study, we show that centrobin interacts with CEP152 and CPAP, and the centrobin-CPAP interaction is critical for centriole duplication. Although depletion of centrobin from cells did not have an effect on the centriolar levels of CEP152, it caused the disappearance of CPAP from both the preexisting and newly formed centrioles. Moreover, exogenous expression of the CPAP-binding fragment of centrobin also caused the disappearance of CPAP from both the preexisting and newly synthesized centrioles, possibly in a dominant negative manner, thereby inhibiting centriole duplication and the PLK4 overexpression-mediated centrosome amplification. Interestingly, exogenous overexpression of CPAP in the centrobin-depleted cells did not restore CPAP localization to the centrioles. However, restoration of centrobin expression in the centrobin-depleted cells led to the reappearance of centriolar CPAP. Hence, we conclude that centrobin-CPAP interaction is critical for the recruitment of CPAP to procentrioles to promote the elongation of daughter centrioles and for the persistence of CPAP on preexisting mother centrioles. Our study indicates that regulation of CPAP levels on the centrioles by centrobin is critical for preserving the normal size, shape, and number of centrioles in the cell. PMID:24700465

Acidogenic fermentation of iron-enhanced primary sedimentation sludge under different pH conditions for production of volatile fatty acids.

PubMed

Lin, Lin; Li, Xiao-Yan

2018-03-01

Iron-based chemically enhanced primary sedimentation (CEPS) is increasingly adopted for wastewater treatment in mega cities, producing a large amount of sludge (Fe-sludge) with a high content of organics for potential organic resource recovery. In this experimental study, acidogenic fermentation was applied treat FeCl 3 -based CEPS sludge for production of volatile fatty acids (VFAs) at different pHs. Batch fermentation tests on the Fe-sludge with an organic content of 10 g-COD/L showed that the maximum VFAs production reached 2782.2 mg-COD/L in the reactor without pH control, and it reached 688.4, 3095.3, and 2603.7 mg-COD/L in reactors with pHs kept at 5.0, 6.0 and 8.0, respectively. Analysis of the acidogenesis kinetics and enzymatic activity indicated that the alkaline pH could accelerate the rate of organic hydrolysis but inhibited the further organic conversion to VFAs. In semi-continuous sludge fermentation tests, the VFAs yield in the pH6 reactor was 20% higher than that in the control reactor without pH regulation, while the VFAs yield in the pH8 reactor was 10% lower than the control. Illumina MiSeq sequencing revealed that key functional microorganisms known for effective sludge fermentation, including Bacteroidia and Erysipelotrichi, were enriched in the pH6 reactor with an enhanced VFAs production, while Clostridia became more abundant in the pH8 reactor to stand the unfavorable pH condition. The research presented acidogenic fermentation as an effective process for CEPS sludge treatment and organic resource recovery and provided the first insight into the related microbial community dynamics. Copyright © 2017 Elsevier Ltd. All rights reserved.

Design Issues for Helmet-Mounted Display Systems for Rotary-Wing Aviation.

DTIC Science & Technology

1998-07-01

have been examined (Mozo and Murphy, 1997a; Mozo, Murphy, and Ribera , 1995) and have been determined to be within a manageable range. The device also...usefulness for the helicopter environment ( Ribera and Mozo, undated). SI results of SPH-4B with and without ANR and CEP used in the "normal" verses "waivered...USAARL Report No. 97-36. Mozo, B. T., Murphy, B. A., and Ribera , J. E. 1995. User acceptability and comfort of the Communications Earplug (CEP) when

HER2/CEP17 Ratios and Clinical Outcome in HER2-Positive Early Breast Cancer Undergoing Trastuzumab-Containing Therapy.

PubMed

Stocker, Albina; Hilbers, Marie-Luise; Gauthier, Claire; Grogg, Josias; Kullak-Ublick, Gerd A; Seifert, Burkhardt; Varga, Zsuzsanna; Trojan, Andreas

2016-01-01

Adjuvant therapy comprising the HER2 receptor antagonist trastuzumab is associated with a significant improvement in disease-free and overall survival as compared to chemotherapy alone in localized HER2-positive breast cancer (BC). However, a subset of HER2-positive tumors seems to respond less favorably to trastuzumab. Various mechanisms have been proposed for trastuzumab resistance, such as high HER2 to Chromosome 17 FISH (HER2/CEP17) ratios and the possibility that single agent trastuzumab may not suffice to efficiently block HER2 downstream signaling thresholds. In a retrospective analysis we evaluated whether HER2/CEP17 ratios might have an impact on disease-free survival (DFS). Clinical records of Stage I-III BC patients with HER2-positive tumors were reviewed at our institution from 2007-2013. We analyzed demographics, tumor characteristics including tumor size and grade, lymph node involvement and estrogen receptor expression as well as treatment with respect to chemotherapeutic regimens from the clinical charts. HER2/CEP17 ratios were determined by routine pathology analysis using in situ fluorescent hybridization (FISH). Upon statistical preview we defined three groups of HER2 amplification based on FISH ratio (2.2 to 4, >4 to 8, >8), in order to evaluate an association between HER2 gene amplification and DFS with trastuzumab containing therapies. DFS was analyzed using Cox-regression. A total of 332 patients with HER2-positive BC were reviewed. Median age was 54 (range 23-89) years. The majority of tumors were classified T1 (50%) or T2 (39%), node negative (52%) and of high grade G3 histology (70%). We identified 312 (94%) tumors as immunohistochemistry (IHC) score 3+ and HER2/CEP17 ratios were available from 278 patients (84%). 30% (N = 84) had tumors with high HER2/CEP17 ratios (>8). Univariate analysis found no correlation between outcome, age, histological grade, sequence as well as anthracycline content of chemotherapy. However, a prognostic impact was detected for tumor size (p = 0.02), nodal status (p<0.01), proliferation index (p<0.01), level (≥20%) of estrogen receptor expression (p = 0.03) and neoadjuvant therapeutic setting (p = 0.03), respectively. Importantly, univariate and multivariable analysis revealed that standard trastuzumab containing chemotherapy resulted in impaired disease free survival among tumors with FISH ratio >8 (p<0.01). Although less pronounced, a similar association was found also with respect to high HER2 gene copy numbers (>12) and DFS (p = 0.01). In early BC patients, tumors with high HER2 amplification ratios (>8), may less likely respond to standard trastuzumab-containing therapies. Although, we obtained a similar effect for high HER2 gene copy numbers, this provides only an indirect speculation and not a proof that high HER2/CEP17 ratios may induce HER2 resistance.

HER2/CEP17 Ratios and Clinical Outcome in HER2-Positive Early Breast Cancer Undergoing Trastuzumab-Containing Therapy

PubMed Central

Stocker, Albina; Hilbers, Marie-Luise; Gauthier, Claire; Grogg, Josias; Kullak-Ublick, Gerd A.; Seifert, Burkhardt; Varga, Zsuzsanna

2016-01-01

Background Adjuvant therapy comprising the HER2 receptor antagonist trastuzumab is associated with a significant improvement in disease-free and overall survival as compared to chemotherapy alone in localized HER2-positive breast cancer (BC). However, a subset of HER2-positive tumors seems to respond less favorably to trastuzumab. Various mechanisms have been proposed for trastuzumab resistance, such as high HER2 to Chromosome 17 FISH (HER2/CEP17) ratios and the possibility that single agent trastuzumab may not suffice to efficiently block HER2 downstream signaling thresholds. In a retrospective analysis we evaluated whether HER2/CEP17 ratios might have an impact on disease-free survival (DFS). Methods Clinical records of Stage I-III BC patients with HER2-positive tumors were reviewed at our institution from 2007–2013. We analyzed demographics, tumor characteristics including tumor size and grade, lymph node involvement and estrogen receptor expression as well as treatment with respect to chemotherapeutic regimens from the clinical charts. HER2/CEP17 ratios were determined by routine pathology analysis using in situ fluorescent hybridization (FISH). Upon statistical preview we defined three groups of HER2 amplification based on FISH ratio (2.2 to 4, >4 to 8, >8), in order to evaluate an association between HER2 gene amplification and DFS with trastuzumab containing therapies. DFS was analyzed using Cox-regression. Results A total of 332 patients with HER2-positive BC were reviewed. Median age was 54 (range 23–89) years. The majority of tumors were classified T1 (50%) or T2 (39%), node negative (52%) and of high grade G3 histology (70%). We identified 312 (94%) tumors as immunohistochemistry (IHC) score 3+ and HER2/CEP17 ratios were available from 278 patients (84%). 30% (N = 84) had tumors with high HER2/CEP17 ratios (>8). Univariate analysis found no correlation between outcome, age, histological grade, sequence as well as anthracycline content of chemotherapy. However, a prognostic impact was detected for tumor size (p = 0.02), nodal status (p<0.01), proliferation index (p<0.01), level (≥20%) of estrogen receptor expression (p = 0.03) and neoadjuvant therapeutic setting (p = 0.03), respectively. Importantly, univariate and multivariable analysis revealed that standard trastuzumab containing chemotherapy resulted in impaired disease free survival among tumors with FISH ratio >8 (p<0.01). Although less pronounced, a similar association was found also with respect to high HER2 gene copy numbers (>12) and DFS (p = 0.01). Conclusions In early BC patients, tumors with high HER2 amplification ratios (>8), may less likely respond to standard trastuzumab-containing therapies. Although, we obtained a similar effect for high HER2 gene copy numbers, this provides only an indirect speculation and not a proof that high HER2/CEP17 ratios may induce HER2 resistance. PMID:27463363

Lack of Evidence That Male Fetal Microchimerism is Present in Endometriosis

PubMed Central

Fassbender, Amelie; Debiec-Rychter, Maria; Bree, Rieta Van; Vermeesch, Joris Robert; Meuleman, Christel; Tomassetti, Carla; Peeraer, Karen; D’Hooghe, Thomas; Lebovic, Dan I.

2015-01-01

Introduction: Fetal microchimerism has been implicated in the etiology of autoimmune diseases. This study was done to test the hypothesis that male fetal microchimerism is present in eutopic and ectopic endometrium (EM) obtained from women with endometriosis but not in eutopic EM from women without endometriosis. Methods: A total of 31 patients were selected, including women with endometriosis (paired eutopic and ectopic EM; n = 19) and women without endometriosis (eutopic EM; n = 12). Tricolor interphase fluorescence in situ hybridization analysis was performed by cohybridization of CEP Y SpectrumAqua and CEP X SpectrumGreen (SG)/CEP Y SpectrumOrange probes. Results: Ectopic EM from women with endometriosis had 75% XX chromosomes (double SG signals) and 25% X chromosomes (single SG signal). Y chromosomes were not observed in any of the eutopic/ectopic endometrial tissues from cases or controls. Conclusions: We were unable to confirm our hypothesis that male fetal microchimerism is present in eutopic and/or ectopic EM obtained from women with endometriosis. PMID:25749809

DEZ ANOS DE EXPERIÊNCIA DO COMITÊ DE ÉTICA EM PESQUISA DA SECRETARIA DE SAÚDE DO DISTRITO FEDERAL, BRASIL

PubMed Central

Novaes, Maria Rita C. G.; Guilhem, Dirce; Lolas, Fernando

2009-01-01

O objetivo deste artigo é relatar a experiência do Comitê de Ética em Pesquisa da Secretaria de Estado de Saúde do Distrito Federal (CEP/SES/DF) Brasil, durante o período de 10 anos a partir de sua fundação. Trata-se de uma avaliação descritiva e documental, na modalidade estudo de caso, utilizando-se a totalidade de projetos protocolados no CEP/SES/DF (N° 052/08) nesse período. As pendências mais freqüentes dos projetos foram: termo de consentimento livre e esclarecido (30%), folha de rosto (25%), metodologia (20%), curriculum vitae (12%), planilha de orçamento (9%), outros (4%). O relato das atividades do CEP/SES/DF no período de 10 anos revelou, através de sua produtividade, a legitimidade do processo de análise ética dos protocolos visando à proteção dos participantes da pesquisa. PMID:19888441

A new exact method for line radiative transfer

NASA Astrophysics Data System (ADS)

Elitzur, Moshe; Asensio Ramos, Andrés

2006-01-01

We present a new method, the coupled escape probability (CEP), for exact calculation of line emission from multi-level systems, solving only algebraic equations for the level populations. The CEP formulation of the classical two-level problem is a set of linear equations, and we uncover an exact analytic expression for the emission from two-level optically thick sources that holds as long as they are in the `effectively thin' regime. In a comparative study of a number of standard problems, the CEP method outperformed the leading line transfer methods by substantial margins. The algebraic equations employed by our new method are already incorporated in numerous codes based on the escape probability approximation. All that is required for an exact solution with these existing codes is to augment the expression for the escape probability with simple zone-coupling terms. As an application, we find that standard escape probability calculations generally produce the correct cooling emission by the CII 158-μm line but not by the 3P lines of OI.

X-ray crystal structures of the pheromone-binding domains of two quorum-hindered transcription factors, YenR of Yersinia enterocolitica and CepR2 of Burkholderia cenocepacia: KIM et al.

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

Kim, Youngchang; Chhor, Gekleng; Tsai, Ching-Sung

The ability of LuxR-type proteins to regulate transcription is controlled by bacterial pheromones, N-acylhomoserine lactones (AHLs). Most LuxR-family proteins require their cognate AHLs for activity, and some of them require AHLs for folding and stability, and for protease-resistance. However, a few members of this family are able to fold, dimerize, bind DNA, and regulate transcription in the absence of AHLs; moreover, these proteins are antagonized by their cognate AHLs. One such protein is YenR of Yersinia enterocolitica, which is antagonized by N-3-oxohexanoyl-l-homoserine lactone (OHHL). This pheromone is produced by the OHHL synthase, a product of the adjacent yenI gene. Anothermore » example is CepR2 of Burkholderia cenocepacia, which is antagonized by N-octanoyl-l-homoserine lactone (OHL), whose synthesis is directed by the cepI gene of the same bacterium. Here, we describe the high-resolution crystal structures of the AHL binding domains of YenR and CepR2. YenR was crystallized in the presence and absence of OHHL. While this ligand does not cause large scale changes in the YenR structure, it does alter the orientation of several highly conserved YenR residues within and near the pheromone-binding pocket, which in turn caused a significant movement of a surface-exposed loop.« less

Vascular Endothelial Growth Factor and Angiopoietin-1 Stimulate Postnatal Hematopoiesis by Recruitment of Vasculogenic and Hematopoietic Stem Cells

PubMed Central

Hattori, Koichi; Dias, Sergio; Heissig, Beate; Hackett, Neil R.; Lyden, David; Tateno, Masatoshi; Hicklin, Daniel J.; Zhu, Zhenping; Witte, Larry; Crystal, Ronald G.; Moore, Malcolm A.S.; Rafii, Shahin

2001-01-01

Tyrosine kinase receptors for angiogenic factors vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang-1) are expressed not only by endothelial cells but also by subsets of hematopoietic stem cells (HSCs). To further define their role in the regulation of postnatal hematopoiesis and vasculogenesis, VEGF and Ang-1 plasma levels were elevated by injecting recombinant protein or adenoviral vectors expressing soluble VEGF165, matrix-bound VEGF189, or Ang-1 into mice. VEGF165, but not VEGF189, induced a rapid mobilization of HSCs and VEGF receptor (VEGFR)2+ circulating endothelial precursor cells (CEPs). In contrast, Ang-1 induced delayed mobilization of CEPs and HSCs. Combined sustained elevation of Ang-1 and VEGF165 was associated with an induction of hematopoiesis and increased marrow cellularity followed by proliferation of capillaries and expansion of sinusoidal space. Concomitant to this vascular remodeling, there was a transient depletion of hematopoietic activity in the marrow, which was compensated by an increase in mobilization and recruitment of HSCs and CEPs to the spleen resulting in splenomegaly. Neutralizing monoclonal antibody to VEGFR2 completely inhibited VEGF165, but not Ang-1–induced mobilization and splenomegaly. These data suggest that temporal and regional activation of VEGF/VEGFR2 and Ang-1/Tie-2 signaling pathways are critical for mobilization and recruitment of HSCs and CEPs and may play a role in the physiology of postnatal angiogenesis and hematopoiesis. PMID:11342585

HEATING 7. 1 user's manual

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

Childs, K.W.

1991-07-01

HEATING is a FORTRAN program designed to solve steady-state and/or transient heat conduction problems in one-, two-, or three- dimensional Cartesian, cylindrical, or spherical coordinates. A model may include multiple materials, and the thermal conductivity, density, and specific heat of each material may be both time- and temperature-dependent. The thermal conductivity may be anisotropic. Materials may undergo change of phase. Thermal properties of materials may be input or may be extracted from a material properties library. Heating generation rates may be dependent on time, temperature, and position, and boundary temperatures may be time- and position-dependent. The boundary conditions, which maymore » be surface-to-boundary or surface-to-surface, may be specified temperatures or any combination of prescribed heat flux, forced convection, natural convection, and radiation. The boundary condition parameters may be time- and/or temperature-dependent. General graybody radiation problems may be modeled with user-defined factors for radiant exchange. The mesh spacing may be variable along each axis. HEATING is variably dimensioned and utilizes free-form input. Three steady-state solution techniques are available: point-successive-overrelaxation iterative method with extrapolation, direct-solution (for one-dimensional or two-dimensional problems), and conjugate gradient. Transient problems may be solved using one of several finite-difference schemes: Crank-Nicolson implicit, Classical Implicit Procedure (CIP), Classical Explicit Procedure (CEP), or Levy explicit method (which for some circumstances allows a time step greater than the CEP stability criterion). The solution of the system of equations arising from the implicit techniques is accomplished by point-successive-overrelaxation iteration and includes procedures to estimate the optimum acceleration parameter.« less

CEP78 is mutated in a distinct type of Usher syndrome.

PubMed

Fu, Qing; Xu, Mingchu; Chen, Xue; Sheng, Xunlun; Yuan, Zhisheng; Liu, Yani; Li, Huajin; Sun, Zixi; Li, Huiping; Yang, Lizhu; Wang, Keqing; Zhang, Fangxia; Li, Yumei; Zhao, Chen; Sui, Ruifang; Chen, Rui

2017-03-01

Usher syndrome is a genetically heterogeneous disorder featured by combined visual impairment and hearing loss. Despite a dozen of genes involved in Usher syndrome having been identified, the genetic basis remains unknown in 20-30% of patients. In this study, we aimed to identify the novel disease-causing gene of a distinct subtype of Usher syndrome. Ophthalmic examinations and hearing tests were performed on patients with Usher syndrome in two consanguineous families. Target capture sequencing was initially performed to screen causative mutations in known retinal disease-causing loci. Whole exome sequencing (WES) and whole genome sequencing (WGS) were applied for identifying novel disease-causing genes. RT-PCR and Sanger sequencing were performed to evaluate the splicing-altering effect of identified CEP78 variants. Patients from the two independent families show a mild Usher syndrome phenotype featured by juvenile or adult-onset cone-rod dystrophy and sensorineural hearing loss. WES and WGS identified two homozygous rare variants that affect mRNA splicing of a ciliary gene CEP78 . RT-PCR confirmed that the two variants indeed lead to abnormal splicing, resulting in premature stop of protein translation due to frameshift. Our results provide evidence that CEP78 is a novel disease-causing gene for Usher syndrome, demonstrating an additional link between ciliopathy and Usher protein network in photoreceptor cells and inner ear hair cells. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Drosophila Ana1 is required for centrosome assembly and centriole elongation

PubMed Central

Saurya, Saroj; Roque, Hélio; Novak, Zsofia A.; Wainman, Alan; Aydogan, Mustafa G.; Volanakis, Adam; Sieber, Boris; Pinto, David Miguel Susano

2016-01-01

ABSTRACT Centrioles organise centrosomes and cilia, and these organelles have an important role in many cell processes. In flies, the centriole protein Ana1 is required for the assembly of functional centrosomes and cilia. It has recently been shown that Cep135 (also known as Bld10) initially recruits Ana1 to newly formed centrioles, and that Ana1 then recruits Asl (known as Cep152 in mammals) to promote the conversion of these centrioles into centrosomes. Here, we show that ana1 mutants lack detectable centrosomes in vivo, that Ana1 is irreversibly incorporated into centrioles during their assembly and appears to play a more important role in maintaining Asl at centrioles than in initially recruiting Asl to centrioles. Unexpectedly, we also find that Ana1 promotes centriole elongation in a dose-dependent manner: centrioles are shorter when Ana1 dosage is reduced and are longer when Ana1 is overexpressed. This latter function of Ana1 appears to be distinct from its role in centrosome and cilium function, as a GFP–Ana1 fusion lacking the N-terminal 639 amino acids of the protein can support centrosome assembly and cilium function but cannot promote centriole over-elongation when overexpressed. PMID:27206860

Use of Modal Acoustic Emission to Monitor Damage Progression in Carbon Fiber/Epoxy Tows and Implications for Composite Structures

NASA Technical Reports Server (NTRS)

Waller, Jess M.; Saulsberry, Regor L.; Nichols, Charles T.; Wentzel, Daniel J.

2010-01-01

This slide presentation reviews the use of Modal Acoustic Emission to monitor damage progression to carbon fiber/epoxy tows. There is a risk for catastrophic failure of composite overwrapped pressure vessels (COPVs) due to burst-before-leak (BBL) stress rupture (SR) failure of carbon-epoxy (C/Ep) COPVs. A lack of quantitative nondestructive evaluation (NDE) is causing problems in current and future spacecraft designs. It is therefore important to develop and demonstrate critical NDE that can be implemented during stages of the design process since the observed rupture can occur with little of no advanced warning. Therefore a program was required to develop quantitative acoustic emission (AE) procedures specific to C/Ep overwraps, but which also have utility for monitoring damage accumulation in composite structure in general, and to lay the groundwork for establishing critical thresholds for accumulated damage in composite structures, such as COPVs, so that precautionary or preemptive engineering steps can be implemented to minimize of obviate the risk of catastrophic failure. A computed Felicity Ratio (FR) coupled with fast Fourier Transform (FFT) frequency analysis shows promise as an analytical pass/fail criterion. The FR analysis and waveform and FFT analysis are reviewed

The atmosphere, the p-factor and the bright visible circumstellar environment of the prototype of classical Cepheids δ Cep

NASA Astrophysics Data System (ADS)

Nardetto, Nicolas; Poretti, Ennio; Mérand, Antoine; Anderson, Richard I.; Fokin, Andrei; Fouqué, Pascal; Gallenne, Alexandre; Gieren, Wolfgang; Graczyk, Dariusz; Kervella, Pierre; Mathias, Philippe; Mourard, Denis; Neilson, Hilding; Pietrzynski, Grzegorz; Pilecki, Bogumil; Rainer, Monica; Storm, Jesper

2017-09-01

Even ≃ 16000 cycles after its discovery by John Goodricke in 1783, δ Cep, the prototype of classical Cepheids, is still studied intensively in order to better understand its atmospheric dynamical structure and its environment. Using HARPS-N spectroscopic measurements, we have measured the atmospheric velocity gradient of δ Cep for the first time and we confirm the decomposition of the projection factor, a subtle physical quantity limiting the Baade-Wesselink (BW) method of distance determination. This decomposition clarifies the physics behind the projection factor and will be useful to interpret the hundreds of p-factors that will come out from the next Gaia release. Besides, VEGA/CHARA interferometric observations of the star revealed a bright visible circumstellar environment contributing to about 7% to the total flux. Better understanding the physics of the pulsation and the environment of Cepheids is necessary to improve the BW method of distance determination, a robust tool to reach Cepheids in the MilkyWay, and beyond, in the Local Group.

[Circulating endothelial cells: biomarkers for monitoring activity of antiangiogenic therapy].

PubMed

Farace, Françoise; Bidart, Jean-Michel

2007-07-01

Tumor vessel formation is largely dependent on the recruitment of endothelial cells. Rare in healthy individuals, circulating endothelial cells (CEC) are shed from vessel walls and enter the circulation reflecting endothelial damage or dysfunction. Increased numbers of CEC have been documented in different types of cancer. Recent studies have suggested the role for CEC in tumor angiogenesis, but whose presence could also reflect normal endothelium perturbation in cancer. Originating from the bone marrow rather than from vessel walls, endothelial progenitor cells (EPC) are mobilized following tissue ischemia and may be recruited to complement local angiogenesis supplied by existing endothelium. Recently, studies in mouse models suggest that the circulating fraction of endothelial progenitors (CEP) is involved in tumor angiogenesis but their contribution is less clear in humans. The detection of CEC and CEP is difficult and impeded by the rarity of these cells. They may have important clinical implication as novel biomarkers susceptible to predict more efficiently and rapidly the therapeutic response to anti-angiogenic treatments. However, a methodological consensus would be necessary in order to correctly evaluate the clinical interest of CEC and CEP in patients.

Phase- and intensity-resolved measurements of above threshold ionization by few-cycle pulses

NASA Astrophysics Data System (ADS)

Kübel, M.; Arbeiter, M.; Burger, C.; Kling, Nora G.; Pischke, T.; Moshammer, R.; Fennel, T.; Kling, M. F.; Bergues, B.

2018-07-01

We investigate the carrier-envelope phase (CEP) and intensity dependence of the longitudinal momentum distribution of photoelectrons resulting from above threshold ionization of argon by few-cycle laser pulses. The intensity of the pulses with a center wavelength of 750 nm is varied in a range between 0.7 × 1014 and 5.5× {10}14 {{W}} {cm}}-2. Our measurements reveal a prominent maximum in the CEP-dependent asymmetry at photoelectron energies of 2 U P (U P being the ponderomotive potential), that is persistent over the entire intensity range. Further local maxima are observed around 0.3 and 0.8 U P. The experimental results are in good agreement with theoretical results obtained by solving the three-dimensional time-dependent Schrödinger equation. We show that for few-cycle pulses, the amplitude of the CEP-dependent asymmetry provides a reliable measure for the peak intensity on target. Moreover, the measured asymmetry amplitude exhibits an intensity-dependent interference structure at low photoelectron energy, which could be used to benchmark model potentials for complex atoms.

Effect of cassava bioethanol by-product and crude palm oil in Brahman x Thai native yearling heifer cattle diets: II. Carcass characteristics and meat quality.

PubMed

Phoemchalard, Chirasak; Uriyapongson, Suthipong

2015-12-01

This experiment was conducted to determine the effects of cassava bioethanol by-product (CEP) and crude palm oil (CPO) on the carcass characteristics and meat quality of yearling heifer cattle. Eighteen crossbred Brahman × Thai heifers were randomly allotted to 2 × 3 factorial arrangement consisting of two levels of CEP (15 or 30 %, LCEP or HCEP) and 3 levels of CPO (0, 2, and 4 %). The results obtained showed that lean meat was greater (P < 0.05) in HCEP-fed cattle, but bone percentage and lean/bone ratio were less (P < 0.05) than LCEP-fed cattle. Carcass fat (P < 0.05) and fat content (P < 0.01) were significantly increased with levels of dietary CPO. Diets with 4 % CPO supplementation had better effects on redness (a*, P < 0.01) and chroma (C*, P < 0.001) values. In conclusion, up to 30 % CEP can be used to improve lean carcass and 4 % CPO can improve the redness of the meat.

Association of an inherited genetic variant with vincristine-related peripheral neuropathy in children with acute lymphoblastic leukemia

PubMed Central

Diouf, Barthelemy; Crews, Kristine R.; Lew, Glen; Pei, Deqing; Cheng, Cheng; Bao, Ju; Zheng, Jie J.; Yang, Wenjian; Fan, Yiping; Wheeler, Heather E.; Wing, Claudia; Delaney, Shannon M.; Komatsu, Masaaki; Paugh, Steven W.; McCorkle, Joseph Robert; Lu, Xiaomin; Winick, Naomi J.; Carroll, William L.; Loh, Mignon L.; Hunger, Stephen P.; Devidas, Meenakshi; Pui, Ching-Hon; Dolan, M. Eileen; Relling, Mary V.; Evans, William E.

2015-01-01

Importance With cure rates of childhood acute lymphoblastic leukemia (ALL) exceeding 85%, there is compelling need to mitigate treatment toxicities that can compromise quality of life. Peripheral neuropathy is the major dose-limiting toxicity of the microtubule inhibitor vincristine, an anticancer agent given to every child with ALL. Objective Identify genetic germline variants associated with the occurrence or severity of vincristine-induced peripheral neuropathy in children with ALL. Design, Setting and Participants All patients had been enrolled in one of two prospective clinical trials for childhood ALL that included treatment with 36–39 doses of vincristine. Genome-wide single nucleotide polymorphism (SNP) analysis and vincristine-induced peripheral neuropathy were assessed in all patients from whom DNA was available (n=321 patients); 222 patients (median age at 6.0 years, range 0.1–18.8 years) enrolled between 1994–1998 on the St. Jude Children’s Research Hospital protocol Total XIIIB (St. Jude cohort) with toxicity followed through January 2001, and 99 patients (median age 11.4 years, range 3.0–23.8 years) enrolled between 2007–2010 on the Children’s Oncology Group protocol AALL0433 (COG cohort) with toxicity followed through May 2011. Human leukemia cells and induced pluripotent stem cell neurons were used to assess the effects of lower CEP72 expression on vincristine sensitivity. Exposures Treatment with vincristine at a dosage of 1.5 or 2.0 mg/m2 as a component of protocol directed chemotherapy for childhood ALL. Main Outcomes and Measures Vincristine-induced peripheral neuropathy was assessed at each clinic visit using the National Cancer Institute Common Terminology Criteria for Adverse Events and prospectively graded as mild (grade 1), moderate (grade 2), serious/disabling (grade 3), or life-threatening (grade 4). Results Grade 2–4 vincristine-induced neuropathy during continuation therapy occurred in 28.8% of patients (n=64 of 222) in the St. Jude cohort and in 22.2% of patients (n=22 of 99) in the COG cohort. A SNP in the promoter region of the CEP72 gene, which encodes a centrosomal protein involved in microtubule formation, had a significant association with vincristine neuropathy (meta p =6.3 × 10−9). This SNP had a minor allele frequency of 37% (235/642), with 50 of 321 patients (16%, 95% CI 11.6%–19.5%) homozygous for the risk allele (TT at rs924607). Among patients with the high-risk CEP72 genotype (TT at rs924607), 28 of 50 patients (56%, 95% CI 41.2–70.0) developed at least one episode of grade 2–4 neuropathy, a higher rate than in patients with the CEP72 CC or CT genotype (58 of 271 patients; 21.4%, 95% CI 16.9–26.7); p=2.4×10−6. The severity (grade) of neuropathy was greater (2.4-fold by Poisson regression (p<0.0001), 2.7-fold based on mean grade of neuropathy (1.23 [95% CI 0.74 – 1.72] versus 0.45 [95% CI 0.3 – 0.6]; t test p=0.004)) in patients homozygous for the CEP72 risk allele (TT genotype), compared to patients with the CC or CT genotype. The CEP72 promoter SNP was shown to create a binding site for a transcriptional repressor causing lower mRNA expression, and reducing CEP72 expression in human neurons and leukemia cells increased their sensitivity to vincristine. Conclusions In this preliminary study of children with ALL, an inherited polymorphism in the promoter region of CEP72 was associated with increased risk and severity of vincristine-related peripheral neuropathy. If replicated in additional populations, this finding may provide a basis for safer dosing of this widely prescribed anticancer agent. PMID:25710658

Double life of centrioles: CP110 in the spotlight.

PubMed

Bettencourt-Dias, Mónica; Carvalho-Santos, Zita

2008-01-01

Centrioles lead an important double life: they can give rise to the centrosome or convert to basal bodies and template cilia. Little is known about the control of centriole fate. Spektor and colleagues have now identified a centriolar complex, composed of CP110 and CEP97, which inhibits centriole to basal body conversion, preventing cilia formation. This work paves the way to understanding centriole and cilia biogenesis, which are two processes misregulated in human diseases, such as cancer and polycystic kidney disease.

Vaporous Hydrogen Peroxide (VHP) Decontamination of a C-141B Starlifter Aircraft: Validation of VHP and Modified VHP (mVHP) Fumigation Decontamination Process via VHP-Sensor, Biological Indicator, and HD Simulant in a Large-Scale Environment

DTIC Science & Technology

2007-03-01

Geobacillus stearothermophilus biological indicator (BI) strips and coupons of three aircraft related surface materials contaminated with the same type...Starlifter Aircraft BIs Geobacillus stearothermophilus mVHP system Vaporizer modules Coupons HD Ammonia Computational flow dynamics CARC CEPS 16. SECURITY...21 18. G. stearothermophilus ATCC 7953VHP Exposure Test Results ..................... 33 19. Vapor Cup

Magnetization at high pressure in CeP

NASA Astrophysics Data System (ADS)

Naka, T.; Matsumoto, T.; Okayama, Y.; Môri, N.; Haga, Y.; Suzuki, T.

1995-02-01

We have investigated the pressure dependence of magnetization below 60 K up to 1.6 GPa in the low-carrier concentration system CeP showing two step transitions at T = TL and TH under high pressure. At high pressure, M( P, T) exhibits a maximum at around the lower transition temperature TL. This behavior implies that the magnetic state changes at TL. The pressure dependence of isothermal magnetization M( P) is different above and below TL. In fact, M( P) below TL exhibits a maximum at around 1.4 GPa, whereas M( P) above TL increases steeply with pressure up to 1.6 GPa.

Carrier-envelope phase stabilization and control using a transmission grating compressor and an AOPDF.

PubMed

Canova, Lorenzo; Chen, Xiaowei; Trisorio, Alexandre; Jullien, Aurélie; Assion, Andreas; Tempea, Gabriel; Forget, Nicolas; Oksenhendler, Thomas; Lopez-Martens, Rodrigo

2009-05-01

Carrier-envelope phase (CEP) stabilization of a femtosecond chirped-pulse amplification system featuring a compact transmission grating compressor is demonstrated. The system includes two amplification stages and routinely generates phase-stable (approximately 250 mrad rms) 2 mJ, 25 fs pulses at 1 kHz. Minimizing the optical pathway in the compressor enables phase stabilization without feedback control of the grating separation or beam pointing. We also demonstrate for the first time to the best of our knowledge, out-of-loop control of the CEP using an acousto-optic programmable dispersive filter inside the laser chain.

Real-Time Adaptive Color Segmentation by Neural Networks

NASA Technical Reports Server (NTRS)

Duong, Tuan A.

2004-01-01

Artificial neural networks that would utilize the cascade error projection (CEP) algorithm have been proposed as means of autonomous, real-time, adaptive color segmentation of images that change with time. In the original intended application, such a neural network would be used to analyze digitized color video images of terrain on a remote planet as viewed from an uninhabited spacecraft approaching the planet. During descent toward the surface of the planet, information on the segmentation of the images into differently colored areas would be updated adaptively in real time to capture changes in contrast, brightness, and resolution, all in an effort to identify a safe and scientifically productive landing site and provide control feedback to steer the spacecraft toward that site. Potential terrestrial applications include monitoring images of crops to detect insect invasions and monitoring of buildings and other facilities to detect intruders. The CEP algorithm is reliable and is well suited to implementation in very-large-scale integrated (VLSI) circuitry. It was chosen over other neural-network learning algorithms because it is better suited to realtime learning: It provides a self-evolving neural-network structure, requires fewer iterations to converge and is more tolerant to low resolution (that is, fewer bits) in the quantization of neural-network synaptic weights. Consequently, a CEP neural network learns relatively quickly, and the circuitry needed to implement it is relatively simple. Like other neural networks, a CEP neural network includes an input layer, hidden units, and output units (see figure). As in other neural networks, a CEP network is presented with a succession of input training patterns, giving rise to a set of outputs that are compared with the desired outputs. Also as in other neural networks, the synaptic weights are updated iteratively in an effort to bring the outputs closer to target values. A distinctive feature of the CEP neural network and algorithm is that each update of synaptic weights takes place in conjunction with the addition of another hidden unit, which then remains in place as still other hidden units are added on subsequent iterations. For a given training pattern, the synaptic weight between (1) the inputs and the previously added hidden units and (2) the newly added hidden unit is updated by an amount proportional to the partial derivative of a quadratic error function with respect to the synaptic weight. The synaptic weight between the newly added hidden unit and each output unit is given by a more complex function that involves the errors between the outputs and their target values, the transfer functions (hyperbolic tangents) of the neural units, and the derivatives of the transfer functions.

Comparing the health state preferences of older persons, informal caregivers and healthcare professionals: a vignette study.

PubMed

Hofman, Cynthia S; Makai, Peter; Blom, Jeanet W; Boter, Han; Buurman, Bianca M; Olde Rikkert, Marcel G M; Donders, Rogier; Melis, René J F

2015-01-01

The Older Persons and Informal Caregivers Survey-Minimum Dataset (TOPICS-MDS) collects uniform information from research projects funded under the Dutch National Care for the Elderly Programme. To compare the effectiveness of these projects a preference-weighted outcome measure that combined multidimensional TOPICS-MDS outcomes into a composite endpoint (TOPICS-CEP) was developed based on the health state preferences of older persons and informal caregivers. To derive preference weights for TOPICS-CEP's components based on health state preferences of healthcare professionals and to investigate whether these weights differ between disciplines and differ from those of older persons and informal caregivers. Vignette studies were conducted. Participants assessed the general wellbeing of older persons described in vignettes on a scale (0-10). Mixed linear analyses were used to obtain and compare the preference weights of the eight TOPICS-CEP components: morbidities, functional limitations, emotional wellbeing, pain experience, cognitive problems, social functioning, self-perceived health, and self-perceived quality of life (QOL). Overall, 330 healthcare professionals, 124 older persons and 76 informal caregivers participated. The preference weights were not significantly different between disciplines. However, the professionals' preference weights differed significantly from those of older persons and informal caregivers. Morbidities and functional limitations were given more weight by older persons and informal caregivers than by healthcare professionals [difference between preference weights: 0.12 and 0.07] while the opposite was true for pain experience, social functioning, and self-perceived QOL [difference between preference weights: 0.13, 0.15 and 0.26]. It is important to recognize the discrepancies between the health state preferences of various stakeholders to (1) correctly interpret results when studying the effectiveness of interventions in elderly care and (2) establish appropriate healthcare policies. Furthermore, we should strive to include older persons in our decision making process through a shared decision making approach.

Establishing a composite endpoint for measuring the effectiveness of geriatric interventions based on older persons' and informal caregivers' preference weights: a vignette study.

PubMed

Hofman, Cynthia S; Makai, Peter; Boter, Han; Buurman, Bianca M; de Craen, Anton J M; Olde Rikkert, Marcel G M; Donders, Rogier A R T; Melis, René J F

2014-04-18

The Older Persons and Informal Caregivers Survey Minimal Dataset's (TOPICS-MDS) questionnaire which measures relevant outcomes for elderly people was successfully incorporated into over 60 research projects of the Dutch National Care for the Elderly Programme. A composite endpoint (CEP) for this instrument would be helpful to compare effectiveness of the various intervention projects. Therefore, our aim is to establish a CEP for the TOPICS-MDS questionnaire, based on the preferences of elderly persons and informal caregivers. A vignette study was conducted with 200 persons (124 elderly and 76 informal caregivers) as raters. The vignettes described eight TOPICS-MDS outcomes of older persons (morbidity, functional limitations, emotional well-being, pain experience, cognitive functioning, social functioning, self-perceived health and self-perceived quality of life) and the raters assessed the general well-being (GWB) of these vignette cases on a numeric rating scale (0-10). Mixed linear regression analyses were used to derive the preference weights of the TOPICS-MDS outcomes (dependent variable: GWB scores; fixed factors: the eight outcomes; unstandardized coefficients: preference weights). The mixed regression model that combined the eight outcomes showed that the weights varied from 0.01 for social functioning to 0.16 for self-perceived health. A model that included "informal caregiver" showed that the interactions between this variable and each of the eight outcomes were not significant (p > 0.05). A preference-weighted CEP for TOPICS-MDS questionnaire was established based on the preferences of older persons and informal caregivers. With this CEP optimal comparing the effectiveness of interventions in older persons can be realized.

Arima syndrome caused by CEP290 specific variant and accompanied with pathological cilium; clinical comparison with Joubert syndrome and its related diseases.

PubMed

Itoh, Masayuki; Ide, Shuhei; Iwasaki, Yuji; Saito, Takashi; Narita, Keishi; Dai, Hongmei; Yamakura, Shinji; Furue, Takeki; Kitayama, Hirotsugu; Maeda, Keiko; Takahashi, Eihiko; Matsui, Kiyoshi; Goto, Yu-Ichi; Takeda, Sen; Arima, Masataka

2018-04-01

Arima syndrome (AS) is a rare disease and its clinical features mimic those of Joubert syndrome or Joubert syndrome-related diseases (JSRD). Recently, we clarified the AS diagnostic criteria and its severe phenotype. However, genetic evidence of AS remains unknown. We explored causative genes of AS and compared the clinical and genetic features of AS with the other JSRD. We performed genetic analyses of 4 AS patients of 3 families with combination of whole-exome sequencing and Sanger sequencing. Furthermore, we studied cell biology with the cultured fibroblasts of 3 AS patients. All patients had a specific homozygous variant (c.6012-12T>A, p.Arg2004Serfs*7) or compound heterozygous variants (c.1711+1G>A; c.6012-12T>A, p.Gly570Aspfs*19;Arg2004Serfs*7) in centrosomal protein 290 kDa (CEP290) gene. These unique variants lead to abnormal splicing and premature termination. Morphological analysis of cultured fibroblasts from AS patients revealed a marked decrease of the CEP290-positive cell number with significantly longer cilium and naked and protruded ciliary axoneme without ciliary membrane into the cytoplasm. AS resulted in cilia dysfunction from centrosome disruption. The unique variant of CEP290 could be strongly linked to AS pathology. Here, we provided AS specific genetic evidence, which steers the structure and functions of centrosome that is responsible for normal ciliogenesis. This is the first report that has demonstrated the molecular basis of Arima syndrome. Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Identification and Genetic Characterization of a Novel Proteinase, PrtR, from the Human Isolate Lactobacillus rhamnosus BGT10

PubMed Central

Pastar, Irena; Tonic, Ivana; Golic, Natasa; Kojic, Milan; van Kranenburg, Richard; Kleerebezem, Michiel; Topisirovic, Ljubisa; Jovanovic, Goran

2003-01-01

A novel proteinase, PrtR, produced by the human vaginal isolate Lactobacillus rhamnosus strain BGT10 was identified and genetically characterized. The prtR gene and flanking regions were cloned and sequenced. The deduced amino acid sequence of PrtR shares characteristics that are common for other cell envelope proteinases (CEPs) characterized to date, but in contrast to the other cell surface subtilisin-like serine proteinases, it has a smaller and somewhat different B domain and lacks the helix domain, and the anchor domain has a rare sorting signal sequence. Furthermore, PrtR lacks the insert domain, which otherwise is situated inside the catalytic serine protease domain of all CEPs, and has a different cell wall spacer (W) domain similar to that of the cell surface antigen I and II polypeptides expressed by oral and vaginal streptococci. Moreover, the PrtR W domain exhibits significant sequence homology to the consensus sequence that has been shown to be the hallmark of human intestinal mucin protein. According to its αS1- and β-casein cleavage efficacy, PrtR is an efficient proteinase at pH 6.5 and is distributed throughout all L. rhamnosus strains tested. Proteinase extracts of the BGT10 strain obtained with Ca2+-free buffer at pH 6.5 were proteolytically active. The prtR promoter-like sequence was determined, and the minimal promoter region was defined by use of prtR-gusA operon fusions. The prtR expression is Casitone dependent, emphasizing that nitrogen depletion elevates its transcription. This is in correlation with the catalytic activity of the PrtR proteinase. PMID:14532028

Evidence of the presence of a Be circumstelar disk in the Be/X-ray binaries KS 1947+ 300 and Cep X-4

NASA Astrophysics Data System (ADS)

Ozbey-Arabaci, M.; Camero-Arranz, A.; Fabregat, J.; Ozcan, H. Bilal; Peris, V.

2014-06-01

We report on photometric and spectroscopic optical observations of the Be/X-ray binaries KS 1947+300 and Cep X-4, obtained with the TUG Faint Object Spectrograph and Camera (TFOSC) mounted on the focal plane of the 1.5-m Russian-Turkish Telescope (RTT150) at T & Uuml;B & #304TAK National Observatory (Antalya, Turkey) between 2014 June 18-20 (MJD 56826.933-56828.067), and with the spectrograph located at the 51-cm telescope of the Observatorio de Aras de los Olmos of the University of Valencia on 2014 June 3 (MJD 56811.097). ...

What's Right with Kansas? (LBNL Science at the Theater)

ScienceCinema

Fuller, Merrian; Jackson, Nancy

2018-06-20

On Monday, Oct. 3 at 7 p.m. in Berkeley's Repertory Theater, the Lab presented "What's Right with Kansas," an evening of conversation with the Kansas-based Climate and Energy Project's founder and board chair, Nancy Jackson, and Berkeley Lab scientist Merrian Fuller, an electricity-market, policy and consumer behavior expert. Berkeley Lab will also debut its video "Common Ground," which showcases how CEP has become a Kansas mainstay and an inspiration to environmental organizations across the country. In a state rife with climate-change skepticism, CEP has changed behavior, and some minds, by employing rural values of thrift, independence, conservation, and friendly competition to promote energy efficiency.

Cubesat Application for Planetary Entry (CAPE) Missions: Micro-Return Capsule (MIRCA)

NASA Technical Reports Server (NTRS)

Esper, Jaime

2016-01-01

The Cubesat Application for Planetary Entry Missions (CAPE) concept describes a high-performing Cubesat system which includes a propulsion module and miniaturized technologies capable of surviving atmospheric entry heating, while reliably transmitting scientific and engineering data. The Micro Return Capsule (MIRCA) is CAPE's first planetary entry probe flight prototype. Within this context, this paper briefly describes CAPE's configuration and typical operational scenario, and summarizes ongoing work on the design and basic aerodynamic characteristics of the prototype MIRCA vehicle. CAPE not only opens the door to new planetary mission capabilities, it also offers relatively low-cost opportunities especially suitable to university participation. In broad terms, CAPE consists of two main functional components: the "service module" (SM), and "CAPE's entry probe" (CEP). The SM contains the subsystems necessary to support vehicle targeting (propulsion, ACS, computer, power) and the communications capability to relay data from the CEP probe to an orbiting "mother-ship". The CEP itself carries the scientific instrumentation capable of measuring atmospheric properties (such as density, temperature, composition), and embedded engineering sensors for Entry, Descent, and Landing (EDL). The first flight of MIRCA was successfully completed on 10 October 2015 as a "piggy-back" payload onboard a NASA stratospheric balloon launched from Ft. Sumner, NM.

Survey Development to Assess College Students' Perceptions of the Campus Environment.

PubMed

Sowers, Morgan F; Colby, Sarah; Greene, Geoffrey W; Pickett, Mackenzie; Franzen-Castle, Lisa; Olfert, Melissa D; Shelnutt, Karla; Brown, Onikia; Horacek, Tanya M; Kidd, Tandalayo; Kattelmann, Kendra K; White, Adrienne A; Zhou, Wenjun; Riggsbee, Kristin; Yan, Wangcheng; Byrd-Bredbenner, Carol

2017-11-01

We developed and tested a College Environmental Perceptions Survey (CEPS) to assess college students' perceptions of the healthfulness of their campus. CEPS was developed in 3 stages: questionnaire development, validity testing, and reliability testing. Questionnaire development was based on an extensive literature review and input from an expert panel to establish content validity. Face validity was established with the target population using cognitive interviews with 100 college students. Concurrent-criterion validity was established with in-depth interviews (N = 30) of college students compared to surveys completed by the same 30 students. Surveys completed by college students from 8 universities (N = 1147) were used to test internal structure (factor analysis) and internal consistency (Cronbach's alpha). After development and testing, 15 items remained from the original 48 items. A 5-factor solution emerged: physical activity (4 items, α = .635), water (3 items, α = .773), vending (2 items, α = .680), healthy food (2 items, α = .631), and policy (2 items, α = .573). The mean total score for all universities was 62.71 (±11.16) on a 100-point scale. CEPS appears to be a valid and reliable tool for assessing college students' perceptions of their health-related campus environment.

Evidence of The Importance of Philosophy of Science Course On Undergraduate Level

NASA Astrophysics Data System (ADS)

Suyono

2018-01-01

This study aimed to describe academic impact of Philosophy of Science course in change of students’ conceptions on the Nature of science (NOS) before and after attending the course. This study followed one group pretest-posttest design. Treatment in this study was Philosophy of Science course for one semester. Misconception diagnostic tests of the NOS had been developed by Suyono et al. (2015) equipped with Certainty of Response Index (CRI). It consists of 15 concept questions about the NOS. The number of students who were tested on Chemistry Education Program (CEP) and Chemistry Program (CP) respectively 42 and 45 students. This study shows that after the learning of Philosophy of Science course happened: (1) the decrease of the number of misconception students on the NOS from 47.47 to 19.20% in CEP and from 47.47 to 18.18% in CP and (2) the decrease in the number of concepts that understood as misconception by the large number of students from 11 to 2 concepts on the CEP and from 10 to 2 concepts on CP. Therefore, the existence of Philosophy of Science course has a positive academic impact on students from both programs on undergraduate level.

Constraints on the magnitude of the deglacial migration of the ITCZ in the Central Equatorial Pacific Ocean

NASA Astrophysics Data System (ADS)

Reimi, Maria A.; Marcantonio, Franco

2016-11-01

Accurate paleo-latitudinal reconstructions of the Intertropical Convergence Zone (ITCZ) are necessary for understanding tropical hydroclimate and atmospheric circulation. Paleoclimate models and records suggest that as global temperatures increase, the ITCZ should migrate towards the warmer hemisphere. Many uncertainties remain regarding the magnitude of this migration, and few studies have focused on the Central Equatorial Pacific (CEP). Here, we use eolian dust records recovered from three locations in the CEP to address changes in dust provenance across the paleo ITCZ since the last glacial maximum (LGM). Radiogenic isotope compositions of Nd and Pb show that dust delivered to the CEP was sourced mainly from two regions: East Asia and South America. From these data we deduced that since Marine Oxygen Isotope Stage 2 (MIS2) the ITCZ has migrated north to its modern position, being displaced by as much as 7°, to as little as 2.5°. We find that the ITCZ migrated further north during the early Holocene (∼9 kyr), reaching its position furthest north during the mid-Holocene warm interval (∼7 kyr), based on an increase in South American dust at the northernmost sites.

EM Cep: The Be Star

NASA Astrophysics Data System (ADS)

Kochiashvili, N.; Kochiashvili, I.; Natsvlishvili, R.; Vardosanidze, M.; Beradze, S.

2017-07-01

On the basis of UBVR photometric data, obtained in the Abastumani Observatory during 1991-1999, very interesting and unusual flare of EM Cep has been revealed. Duration of the flare was over two hours. We estimated the percentage of brightness increase during the flare and brightness decrease of the corresponding anti- flare and the minimum amount of the lost mass during this event. We have solved the light curves of the star using the Wilson-Devinney code. But the resulting fraction of calculated brightness of the companion star was not in accordance with spectral data. Then we decided to check the idea of a pulsating single star using new spectral data. Together with our Buyrakan colleagues we obtained and analyzed spectra of the star. We could not find spectral lines of a companion star or any traces of the radial velocities using this data. Hence, we concluded that we need the higher resolution spectra for final resolution of the matter. On the basis of the latest spectral data of Bulgarian astronomers they concluded that EM Cep is a single star. This makes it possible to suggest, that the question of stellar pulsation could be solved using additional photometric observations.

Mutations in CDK5RAP2 cause Seckel syndrome.

PubMed

Yigit, Gökhan; Brown, Karen E; Kayserili, Hülya; Pohl, Esther; Caliebe, Almuth; Zahnleiter, Diana; Rosser, Elisabeth; Bögershausen, Nina; Uyguner, Zehra Oya; Altunoglu, Umut; Nürnberg, Gudrun; Nürnberg, Peter; Rauch, Anita; Li, Yun; Thiel, Christian Thomas; Wollnik, Bernd

2015-09-01

Seckel syndrome is a heterogeneous, autosomal recessive disorder marked by prenatal proportionate short stature, severe microcephaly, intellectual disability, and characteristic facial features. Here, we describe the novel homozygous splice-site mutations c.383+1G>C and c.4005-9A>G in CDK5RAP2 in two consanguineous families with Seckel syndrome. CDK5RAP2 (CEP215) encodes a centrosomal protein which is known to be essential for centrosomal cohesion and proper spindle formation and has been shown to be causally involved in autosomal recessive primary microcephaly. We establish CDK5RAP2 as a disease-causing gene for Seckel syndrome and show that loss of functional CDK5RAP2 leads to severe defects in mitosis and spindle organization, resulting in cells with abnormal nuclei and centrosomal pattern, which underlines the important role of centrosomal and mitotic proteins in the pathogenesis of the disease. Additionally, we present an intriguing case of possible digenic inheritance in Seckel syndrome: A severely affected child of nonconsanguineous German parents was found to carry heterozygous mutations in CDK5RAP2 and CEP152. This finding points toward a potential additive genetic effect of mutations in CDK5RAP2 and CEP152.

Mutations in CDK5RAP2 cause Seckel syndrome

PubMed Central

Yigit, Gökhan; Brown, Karen E; Kayserili, Hülya; Pohl, Esther; Caliebe, Almuth; Zahnleiter, Diana; Rosser, Elisabeth; Bögershausen, Nina; Uyguner, Zehra Oya; Altunoglu, Umut; Nürnberg, Gudrun; Nürnberg, Peter; Rauch, Anita; Li, Yun; Thiel, Christian Thomas; Wollnik, Bernd

2015-01-01

Seckel syndrome is a heterogeneous, autosomal recessive disorder marked by prenatal proportionate short stature, severe microcephaly, intellectual disability, and characteristic facial features. Here, we describe the novel homozygous splice-site mutations c.383+1G>C and c.4005-9A>G in CDK5RAP2 in two consanguineous families with Seckel syndrome. CDK5RAP2 (CEP215) encodes a centrosomal protein which is known to be essential for centrosomal cohesion and proper spindle formation and has been shown to be causally involved in autosomal recessive primary microcephaly. We establish CDK5RAP2 as a disease-causing gene for Seckel syndrome and show that loss of functional CDK5RAP2 leads to severe defects in mitosis and spindle organization, resulting in cells with abnormal nuclei and centrosomal pattern, which underlines the important role of centrosomal and mitotic proteins in the pathogenesis of the disease. Additionally, we present an intriguing case of possible digenic inheritance in Seckel syndrome: A severely affected child of nonconsanguineous German parents was found to carry heterozygous mutations in CDK5RAP2 and CEP152. This finding points toward a potential additive genetic effect of mutations in CDK5RAP2 and CEP152. PMID:26436113

Community Engagement Compared With Technical Assistance to Disseminate Depression Care Among Low-Income, Minority Women: A Randomized Controlled Effectiveness Study

PubMed Central

Sherbourne, Cathy; Chung, Bowen; Tang, Lingqi; Wright, Aziza L.; Whittington, Yolanda; Wells, Kenneth; Miranda, Jeanne

2016-01-01

Objectives. To compare the effectiveness of a (CEP) versus a technical assistance approach (Resources for Services, or RS) to disseminate depression care for low-income ethnic minority women. Methods. We conducted secondary analyses of intervention effects for largely low-income, minority women subsample (n = 595; 45.1% Latino and 45.4% African American) in a matched, clustered, randomized control trial conducted in 2 low-resource communities in Los Angeles, California, between 2010 and 2012. Outcomes assessed included mental health, socioeconomic factors, and service use at 6- and 12-month follow-up. Results. Although we found no intervention difference for depressive symptoms, there were statistically significant effects for mental health quality of life, resiliency, homelessness risk, and financial difficulties at 6 months, as well as missed work days, self-efficacy, and care barriers at 12 months favoring CEP relative to RS. CEP increased use of outpatient substance abuse services and faith-based depression visits at 6 months. Conclusions. Engaging health care and social community programs may offer modest improvements on key functional and socioeconomic outcomes, reduce care barriers, and increase engagement in alternative depression services for low-income, predominantly ethnic minority women. PMID:27552274

The role of liver transplantation for congenital extrahepatic portosystemic shunt.

PubMed

Sakamoto, Seisuke; Shigeta, Takanobu; Fukuda, Akinari; Tanaka, Hideaki; Nakazawa, Atsuko; Nosaka, Shunsuke; Uemoto, Shinji; Kasahara, Mureo

2012-06-27

Congenital extrahepatic portosystemic shunt (CEPS) is reported more frequently because of advances in imaging techniques. Liver transplantation (LT) is a therapeutic option, although the indications for LT are still controversial. This study reviewed 34 cases of LT for CEPS, including 30 cases reported in the English medical literature and the patients treated in our department, to collect the clinical data associated with LT. The median age at diagnosis and LT was 3.7 and 6.8 years, respectively. Hepatic encephalopathy, including persistent hyperammonemia, was the most common indication of LT. Pulmonary complications, including hepatopulmonary syndrome and pulmonary hypertension, were the second most common indications of LT, and those patients underwent LT soon after the diagnosis. Although a shunt directly draining into the inferior vena cava was the most common type and managed by a simple direct anastomosis of the portal vein at LT, some cases required the modification of the portal vein reconstruction, such as interposition. Thirty patients were alive with a median follow-up period of 18 months. LT for CEPS showed an excellent outcome. The development of pulmonary complications is an early indication for LT. Precise planning of portal vein reconstruction is required before LT.

HARPS-N high spectral resolution observations of Cepheids I. The Baade-Wesselink projection factor of δ Cep revisited

NASA Astrophysics Data System (ADS)

Nardetto, N.; Poretti, E.; Rainer, M.; Fokin, A.; Mathias, P.; Anderson, R. I.; Gallenne, A.; Gieren, W.; Graczyk, D.; Kervella, P.; Mérand, A.; Mourard, D.; Neilson, H.; Pietrzynski, G.; Pilecki, B.; Storm, J.

2017-01-01

Context. The projection factor p is the key quantity used in the Baade-Wesselink (BW) method for distance determination; it converts radial velocities into pulsation velocities. Several methods are used to determine p, such as geometrical and hydrodynamical models or the inverse BW approach when the distance is known. Aims: We analyze new HARPS-N spectra of δ Cep to measure its cycle-averaged atmospheric velocity gradient in order to better constrain the projection factor. Methods: We first apply the inverse BW method to derive p directly from observations. The projection factor can be divided into three subconcepts: (1) a geometrical effect (p0); (2) the velocity gradient within the atmosphere (fgrad); and (3) the relative motion of the optical pulsating photosphere with respect to the corresponding mass elements (fo-g). We then measure the fgrad value of δ Cep for the first time. Results: When the HARPS-N mean cross-correlated line-profiles are fitted with a Gaussian profile, the projection factor is pcc-g = 1.239 ± 0.034(stat.) ± 0.023(syst.). When we consider the different amplitudes of the radial velocity curves that are associated with 17 selected spectral lines, we measure projection factors ranging from 1.273 to 1.329. We find a relation between fgrad and the line depth measured when the Cepheid is at minimum radius. This relation is consistent with that obtained from our best hydrodynamical model of δ Cep and with our projection factor decomposition. Using the observational values of p and fgrad found for the 17 spectral lines, we derive a semi-theoretical value of fo-g. We alternatively obtain fo-g = 0.975 ± 0.002 or 1.006 ± 0.002 assuming models using radiative transfer in plane-parallel or spherically symmetric geometries, respectively. Conclusions: The new HARPS-N observations of δ Cep are consistent with our decomposition of the projection factor. The next step will be to measure p0 directly from the next generation of visible interferometers. With these values in hand, it will be possible to derive fo-g directly from observations. Table A.1 is also available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (http://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/597/A73

Precise calibration of few-cycle laser pulses with atomic hydrogen

NASA Astrophysics Data System (ADS)

Wallace, W. C.; Kielpinski, D.; Litvinyuk, I. V.; Sang, R. T.

2017-12-01

Interaction of atoms and molecules with strong electric fields is a fundamental process in many fields of research, particularly in the emerging field of attosecond science. Therefore, understanding the physics underpinning those interactions is of significant interest to the scientific community. One crucial step in this understanding is accurate knowledge of the few-cycle laser field driving the process. Atomic hydrogen (H), the simplest of all atomic species, plays a key role in benchmarking strong-field processes. Its wide-spread use as a testbed for theoretical calculations allows the comparison of approximate theoretical models against nearly-perfect numerical solutions of the three-dimensional time-dependent Schrödinger equation. Until recently, relatively little experimental data in atomic H was available for comparison to these models, and was due mostly due to the difficulty in the construction and use of atomic H sources. Here, we review our most recent experimental results from atomic H interaction with few-cycle laser pulses and how they have been used to calibrate important laser pulse parameters such as peak intensity and the carrier-envelope phase (CEP). Quantitative agreement between experimental data and theoretical predictions for atomic H has been obtained at the 10% uncertainty level, allowing for accurate laser calibration intensity at the 1% level. Using this calibration in atomic H, both accurate CEP data and an intensity calibration standard have been obtained Ar, Kr, and Xe; such gases are in common use for strong-field experiments. This calibration standard can be used by any laboratory using few-cycle pulses in the 1014 W cm-2 intensity regime centered at 800 nm wavelength to accurately calibrate their peak laser intensity to within few-percent precision.

Thermal decomposition kinetics of hydrazinium cerium 2,3-Pyrazinedicarboxylate hydrate: a new precursor for CeO2.

PubMed

Premkumar, Thathan; Govindarajan, Subbiah; Coles, Andrew E; Wight, Charles A

2005-04-07

The thermal decomposition kinetics of N(2)H(5)[Ce(pyrazine-2,3-dicarboxylate)(2)(H(2)O)] (Ce-P) have been studied by thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC), for the first time; TGA analysis reveals an oxidative decomposition process yielding CeO(2) as the final product with an activation energy of approximately 160 kJ mol(-1). This complex may be used as a precursor to fine particle cerium oxides due to its low temperature of decomposition.

Drosophila Ana1 is required for centrosome assembly and centriole elongation.

PubMed

Saurya, Saroj; Roque, Hélio; Novak, Zsofia A; Wainman, Alan; Aydogan, Mustafa G; Volanakis, Adam; Sieber, Boris; Pinto, David Miguel Susano; Raff, Jordan W

2016-07-01

Centrioles organise centrosomes and cilia, and these organelles have an important role in many cell processes. In flies, the centriole protein Ana1 is required for the assembly of functional centrosomes and cilia. It has recently been shown that Cep135 (also known as Bld10) initially recruits Ana1 to newly formed centrioles, and that Ana1 then recruits Asl (known as Cep152 in mammals) to promote the conversion of these centrioles into centrosomes. Here, we show that ana1 mutants lack detectable centrosomes in vivo, that Ana1 is irreversibly incorporated into centrioles during their assembly and appears to play a more important role in maintaining Asl at centrioles than in initially recruiting Asl to centrioles. Unexpectedly, we also find that Ana1 promotes centriole elongation in a dose-dependent manner: centrioles are shorter when Ana1 dosage is reduced and are longer when Ana1 is overexpressed. This latter function of Ana1 appears to be distinct from its role in centrosome and cilium function, as a GFP-Ana1 fusion lacking the N-terminal 639 amino acids of the protein can support centrosome assembly and cilium function but cannot promote centriole over-elongation when overexpressed. © 2016. Published by The Company of Biologists Ltd.

Genome-wide comparative analysis of papain-like cysteine protease family genes in castor bean and physic nut.

PubMed

Zou, Zhi; Huang, Qixing; Xie, Guishui; Yang, Lifu

2018-01-10

Papain-like cysteine proteases (PLCPs) are a class of proteolytic enzymes involved in many plant processes. Compared with the extensive research in Arabidopsis thaliana, little is known in castor bean (Ricinus communis) and physic nut (Jatropha curcas), two Euphorbiaceous plants without any recent whole-genome duplication. In this study, a total of 26 or 23 PLCP genes were identified from the genomes of castor bean and physic nut respectively, which can be divided into nine subfamilies based on the phylogenetic analysis: RD21, CEP, XCP, XBCP3, THI, SAG12, RD19, ALP and CTB. Although most of them harbor orthologs in Arabidopsis, several members in subfamilies RD21, CEP, XBCP3 and SAG12 form new groups or subgroups as observed in other species, suggesting specific gene loss occurred in Arabidopsis. Recent gene duplicates were also identified in these two species, but they are limited to the SAG12 subfamily and were all derived from local duplication. Expression profiling revealed diverse patterns of different family members over various tissues. Furthermore, the evolution characteristics of PLCP genes were also compared and discussed. Our findings provide a useful reference to characterize PLCP genes and investigate the family evolution in Euphorbiaceae and species beyond.

Structural centrosome aberrations sensitize polarized epithelia to basal cell extrusion.

PubMed

Ganier, Olivier; Schnerch, Dominik; Nigg, Erich A

2018-06-01

Centrosome aberrations disrupt tissue architecture and may confer invasive properties to cancer cells. Here we show that structural centrosome aberrations, induced by overexpression of either Ninein-like protein (NLP) or CEP131/AZI1, sensitize polarized mammalian epithelia to basal cell extrusion. While unperturbed epithelia typically dispose of damaged cells through apical dissemination into luminal cavities, certain oncogenic mutations cause a switch in directionality towards basal cell extrusion, raising the potential for metastatic cell dissemination. Here we report that NLP-induced centrosome aberrations trigger the preferential extrusion of damaged cells towards the basal surface of epithelial monolayers. This switch in directionality from apical to basal dissemination coincides with a profound reorganization of the microtubule cytoskeleton, which in turn prevents the contractile ring repositioning that is required to support extrusion towards the apical surface. While the basal extrusion of cells harbouring NLP-induced centrosome aberrations requires exogenously induced cell damage, structural centrosome aberrations induced by excess CEP131 trigger the spontaneous dissemination of dying cells towards the basal surface from MDCK cysts. Thus, similar to oncogenic mutations, structural centrosome aberrations can favour basal extrusion of damaged cells from polarized epithelia. Assuming that additional mutations may promote cell survival, this process could sensitize epithelia to disseminate potentially metastatic cells. © 2018 The Authors.

A search for T Tauri stars and related objects: Archival photometry of candidate variables in V733 Cep field

NASA Astrophysics Data System (ADS)

Jurdana-Šepić, R.; Poljančić Beljan, I.

Searching for T Tauri stars or related early type variables we carried out a BVRI photometric measurements of five candidates with positions within the field of the pre-main sequence object V733 Cephei (Persson's star) located in the dark cloud L1216 near to Cepheus OB3 Association: VES 946, VES 950, NSV 14333, NSV 25966 and V385 Cep. Their magnitudes are determined on the plates from Asiago Observatory historical photographic archive exposed 1971 - 1978. We provide finding charts for program stars and comparison sequence stars, magnitude estimations, magnitude mean values and BVR_cI_c light curves of program stars.

Single-shot detection and direct control of carrier phase drift of midinfrared pulses.

PubMed

Manzoni, Cristian; Först, Michael; Ehrke, Henri; Cavalleri, Andrea

2010-03-01

We introduce a scheme for single-shot detection and correction of the carrier-envelope phase (CEP) drift of femtosecond pulses at mid-IR wavelengths. Difference frequency mixing between the mid-IR field and a near-IR gate pulse generates a near-IR frequency-shifted pulse, which is then spectrally interfered with a replica of the gate pulse. The spectral interference pattern contains shot-to-shot information of the CEP of the mid-IR field, and it can be used for simultaneous correction of its slow drifts. We apply this technique to detect and compensate long-term phase drifts at 17 microm wavelength, reducing fluctuations to only 110 mrad over hours of operation.

Evidence for using Monte Carlo calculated wall attenuation and scatter correction factors for three styles of graphite-walled ion chamber.

PubMed

McCaffrey, J P; Mainegra-Hing, E; Kawrakow, I; Shortt, K R; Rogers, D W O

2004-06-21

The basic equation for establishing a 60Co air-kerma standard based on a cavity ionization chamber includes a wall correction term that corrects for the attenuation and scatter of photons in the chamber wall. For over a decade, the validity of the wall correction terms determined by extrapolation methods (K(w)K(cep)) has been strongly challenged by Monte Carlo (MC) calculation methods (K(wall)). Using the linear extrapolation method with experimental data, K(w)K(cep) was determined in this study for three different styles of primary-standard-grade graphite ionization chamber: cylindrical, spherical and plane-parallel. For measurements taken with the same 60Co source, the air-kerma rates for these three chambers, determined using extrapolated K(w)K(cep) values, differed by up to 2%. The MC code 'EGSnrc' was used to calculate the values of K(wall) for these three chambers. Use of the calculated K(wall) values gave air-kerma rates that agreed within 0.3%. The accuracy of this code was affirmed by its reliability in modelling the complex structure of the response curve obtained by rotation of the non-rotationally symmetric plane-parallel chamber. These results demonstrate that the linear extrapolation technique leads to errors in the determination of air-kerma.

Cascade Error Projection with Low Bit Weight Quantization for High Order Correlation Data

NASA Technical Reports Server (NTRS)

Duong, Tuan A.; Daud, Taher

1998-01-01

In this paper, we reinvestigate the solution for chaotic time series prediction problem using neural network approach. The nature of this problem is such that the data sequences are never repeated, but they are rather in chaotic region. However, these data sequences are correlated between past, present, and future data in high order. We use Cascade Error Projection (CEP) learning algorithm to capture the high order correlation between past and present data to predict a future data using limited weight quantization constraints. This will help to predict a future information that will provide us better estimation in time for intelligent control system. In our earlier work, it has been shown that CEP can sufficiently learn 5-8 bit parity problem with 4- or more bits, and color segmentation problem with 7- or more bits of weight quantization. In this paper, we demonstrate that chaotic time series can be learned and generalized well with as low as 4-bit weight quantization using round-off and truncation techniques. The results show that generalization feature will suffer less as more bit weight quantization is available and error surfaces with the round-off technique are more symmetric around zero than error surfaces with the truncation technique. This study suggests that CEP is an implementable learning technique for hardware consideration.

EE Cep observations requested for upcoming eclipse

NASA Astrophysics Data System (ADS)

Waagen, Elizabeth O.

2014-07-01

The AAVSO requests observations for the upcoming eclipse of EE Cephei, a long-period eclipsing variable. EE Cep has a period of 2,050 days, and shows strong variations in the eclipse light curve from one event to the next. Observations are needed to study the morphology of the upcoming eclipse, which will be used to better understand the shape of the eclipsing disk and how it precesses. Mid-eclipse is predicted to be August 23, 2014, but the early stages of the eclipse may begin as much as a month earlier. EE Cep is being observed by a number of amateur and professional astronomers using multiple telescopes at multiple wavelengths. Among these is a collaboration (see https://sites.google.com/site/eecep2014campaign/) headed by Cezary Galan at the Nicolaus Copernicus Astronomical Center in Poland; several individual AAVSO observers are already participating in this effort. The AAVSO is not currently a partner in that campaign, but all data submitted to the AAVSO will be publicly available. The AAVSO strongly encourages observers to begin following this star now, and to continue observations into October 2014 at least. Finder charts with sequence may be created using the AAVSO Variable Star Plotter (http://www.aavso.org/vsp). Observations should be submitted to the AAVSO International Database. See full Alert Notice for more details and observations.

Attosecond Pulse Carrier-Envelope Phase Effects: Roles of Frequency, Intensity and an Additional IR Pulse

NASA Astrophysics Data System (ADS)

Pronin, Evgeny A.; Peng, Liang-You; Starace, Anthony F.

2008-05-01

The effects of the carrier-envelope phase (CEP) of a few-cycle attosecond pulse on ionized electron momentum and energy spectra are analyzed, both with and without an additional few-cycle IR pulse [1, 2]. In the absence of an IR pulse, the CEP-induced asymmetries in the ionized electron momentum distributions are shown to vary as the 3/2 power of the attosecond pulse intensity. These asymmetries are also found to satisfy an approximate scaling law involving the frequency and intensity of the attosecond pulse. In the presence of even a very weak IR pulse, the attosecond pulse CEP-induced asymmetries are found to be significantly augmented. In addition, for higher IR laser intensities, we observe for low electron energies peaks separated by the IR photon energy in one electron momentum direction along the laser polarization axis; in the opposite direction, we find structured peaks that are spaced by twice the IR photon energy. Possible physical mechanisms for such asymmetric, low-energy structures in the ionized electron momentum distribution are proposed. Our results are based on single-active-electron solutions of the 3D TDSE for H and He. [1] Peng LY, Pronin EA, and Starace AF, New J. Phys. 10, xxx (2008); [2] Peng LY, Starace AF, Phys. Rev. A 76, 043401 (2007)

Mutation analysis of Leber congenital amaurosis‑associated genes in patients with retinitis pigmentosa.

PubMed

Shen, Tao; Guan, Liping; Li, Shiqiang; Zhang, Jianguo; Xiao, Xueshan; Jiang, Hui; Yang, Jianhua; Guo, Xiangming; Wang, Jun; Zhang, Qingjiong

2015-03-01

The genetic defects underlying approximately half of all retinitis pigmentosa (RP) cases are unknown. A number of genes responsible for Leber congenital amaurosis (LCA) may also cause RP when they are mutated. Our previous study revealed that variants in the most frequently mutated nine exons accounted for approximately half of the mutations detected in a cohort of patients with LCA. The aim of the present study was to detect mutations in LCA-associated genes in patients with RP using two different strategies. Sanger sequencing was used to screen mutations in the nine exons in 293 patients with RP and exome sequencing was used to detect variants in 12 LCA-associated genes in 157 of the 293 patients with RP and then to validate the variants by Sanger sequencing. Potential pathogenic mutations were identified in four patients with early onset RP, including homozygous CRB1 mutations in two patients, compound heterozygous CRB1 mutations in one patient and compound heterozygous CEP290 mutations in one patient. The present study indicated that mutations in CEP290 may also be associated with RP but not with LCA. With the exception of CEP290, the remaining 11 genes known to be associated with LCA but not with RP are unlikely to be a common cause of RP.

PVO / NGO initiatives, Latin America. Grupo pela VIDDA, Brazil.

PubMed

1996-01-01

"VIDDA" is a Portuguese acronym representing enhancement, integration, and dignity of people living with HIV/AIDS (PWAs). The groups are composed of people infected with HIV, their friends, relatives, lovers, and anyone who feels that his or her everyday life has been affected by the epidemic. They hope that through solidarity they can respond to the difficult situation facing people who are HIV positive in Brazil. Grupo pela VIDDA seeks to raise the consciousness of the government and the society and force them to take responsibility for the epidemic. Their fundamental objective is to fight for PWAs to have a full range of civil rights. "This is a fight that we have in common with all the Brazilian people who are searching for democracy, the right to work, and access to good health services," states a Grupo pela VIDDA brochure. Through their network they provide accurate and current information, counseling, legal assistance, and sponsor support groups. For more information, please contact Grupo pela VIDDA, Rua General Jardim, 556 CEP 01223-010, Cx Postal 54063, CEP 01296, Sao Paulo SP, tel/fax: +55 11 258 7729; or Rua 7 de Setembro, 48 12 andar CEP 20050-000, tel: +55 21 224 1654, fax: +55 21 294 5602. There are also offices in Curitiba, Goiania, Niteroi, Recife, and Vitoria. full text

Analytical description of generation of the residual current density in the plasma produced by a few-cycle laser pulse

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

Silaev, A. A., E-mail: silaev@appl.sci-nnov.ru; Vvedenskii, N. V., E-mail: vved@appl.sci-nnov.ru; University of Nizhny Novgorod, Nizhny Novgorod 603950

2015-05-15

When a gas is ionized by a few-cycle laser pulse, some residual current density (RCD) of free electrons remains in the produced plasma after the passage of the laser pulse. This quasi-dc RCD is an initial impetus to plasma polarization and excitation of the plasma oscillations which can radiate terahertz (THz) waves. In this work, the analytical model for calculation of RCD excited by a few-cycle laser pulse is developed for the first time. The dependences of the RCD on the carrier-envelope phase (CEP), wavelength, duration, and intensity of the laser pulse are derived. It is shown that maximum RCDmore » corresponding to optimal CEP increases with the laser pulse wavelength, which indicates the prospects of using mid-infrared few-cycle laser pulses in the schemes of generation of high-power THz pulses. Analytical formulas for optimal pulse intensity and maximum efficiency of excitation of the RCD are obtained. Basing on numerical solution of the 3D time-dependent Schrödinger equation for hydrogen atoms, RCD dependence on CEP is calculated in a wide range of wavelengths. High accuracy of analytical formulas is demonstrated at the laser pulse parameters which correspond to the tunneling regime of ionization.« less

Poly (ADP-ribose) polymerase inhibitor CEP-8983 synergizes with bendamustine in chronic lymphocytic leukemia cells in vitro

PubMed Central

Dilley, Robert L.; Poh, Weijie; Gladstone, Douglas E.; Herman, James G.; Showel, Margaret M.; Karp, Judith E.; McDevitt, Michael A.; Pratz, Keith W.

2014-01-01

DNA repair aberrations and associated chromosomal instability is a feature of chronic lymphocytic leukemia (CLL). To evaluate if DNA repair insufficiencies are related to methylation changes, we examined the methylation of nine promoter regions of DNA repair proteins by bisulfide sequencing in 26 CLL primary samples and performed quantitative PCR on a subset of samples to examine BRCA1 expression. We also investigated if changes in cytogenetic or expression level of DNA repair proteins led to changes in sensitivity to a novel PARP inhibitor, CEP-8983, alone and in combination with bendamustine. No changes in promoter methylation were identified in BRCA1, BRCA2, FANC-C, FANC-F, FANC-L, ATM, MGMT, hMLH1 and H2AX except for two cases of minor BRCA1 hypermethylation. CLL samples appeared to have reduced BRCA1 mRNA expression uniformly in comparison to non-malignant lymphocytes irrespective of promoter hypermethylation. CEP-8983 displayed single agent cytotoxicity and the combination with bendamustine demonstrated synergistic cytotoxicity in the majority of CLL samples. These results were consistent across cytogenetic subgroups, including 17p deleted and previously treated patients. Our results provide rationale for further exploration of the combination of a PARP inhibitor and DNA damaging agents as a novel therapeutic strategy in CLL. PMID:24439051

Inter-Tropical Convergence Zone Shifts During the Last Glacial Cycle Near the Line Islands Ridge.

NASA Astrophysics Data System (ADS)

Reimi Sipala, M. A.; Marcantonio, F.

2015-12-01

This research focuses on the shift in the inter-tropical convergence zone (ITCZ) during the last glacial cycle. Deep sea sediments from the Central Equatorial Pacific (CEP) are used to quantify and isolate the sources and sinks of atmospheric dust. Dust records and influences climate affecting a wide range of process from Earth's Albedo to carbon export. Our aim is to determine the provenance of windblown dust deposited in the CEP near the Line Islands Ridge using radiogenic Nd and Pb isotopes, and to infer the location of the ITCZ and the changes of atmospheric transport through ice-age climate transitions. We focus on three cores from the CEP, along a meridional transect at approximately 160° W --- 0° 28' N (ML1208-17PC), 4° 41' N (ML1208-31BB), and 7 ° 2'N (ML1208-31BB). Radiogenic isotopes (Sr, Nd, Pb) have been successfully used to distinguish between different potential dust sources in the aluminosilicates fractions of Pacific Sediments. Our preliminary data suggest that the equatorial core (17PC) predominantly receives its dust from South America and South American volcanics South America (206Pb/204Pb = 18.62, 207Pb/204Pb = 15.63, 208Pb/204Pb = 38.62; ; ɛNd = ~ -5). The middle core, which more closely reflects the modern position of the ITCZ, has varied dust provenance through time, at times consistent with Asian Loess (average ratios are 206Pb/204Pb = 18.88, 207Pb/204Pb = 15.69, 208Pb/204Pb = 39.06; ɛNd = ~ -7) and Asian Volcanics (ɛNd = ~-1) suggesting a shift in the ITCZ south of 4N before the LGM. Our results for the most northern core are forthcoming. Prior to Holocene time, the changes in Pb isotope ratios in both cores appear to be in anti-phase; the northern core becomes less radiogenic up to the LGM, while the southern core becomes more radiogenic. This is potentially due to a weakening of the ITCZ during glacial times. A secondary aim of this work is to determine if the ITCZ migrated further south than core 17PC during Heinrich stage II.

Estimate of Cost-Effective Potential for Minimum Efficiency Performance Standards in 13 Major World Economies Energy Savings, Environmental and Financial Impacts

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

Letschert, Virginie E.; Bojda, Nicholas; Ke, Jing

2012-07-01

This study analyzes the financial impacts on consumers of minimum efficiency performance standards (MEPS) for appliances that could be implemented in 13 major economies around the world. We use the Bottom-Up Energy Analysis System (BUENAS), developed at Lawrence Berkeley National Laboratory (LBNL), to analyze various appliance efficiency target levels to estimate the net present value (NPV) of policies designed to provide maximum energy savings while not penalizing consumers financially. These policies constitute what we call the “cost-effective potential” (CEP) scenario. The CEP scenario is designed to answer the question: How high can we raise the efficiency bar in mandatory programsmore » while still saving consumers money?« less

Phase-dependent above-barrier ionization of excited-state electrons.

PubMed

Yang, Weifeng; Song, Xiaohong; Chen, Zhangjin

2012-05-21

The carrier-envelope phase (CEP)-dependent above-barrier ionization (ABI) has been investigated in order to probe the bound-state electron dynamics. It is found that when the system is initially prepared in the excited state, the ionization yield asymmetry between left and right sides can occur both in low-energy and high-energy parts of the photoelectron spectra. Moreover, in electron momentum map, a new interference effect along the direction perpendicular to the laser polarization is found. We show that this interference is related to the competition among different excited states. The interference effect is dependent on CEPs of few-cycle probe pulses, which can be used to trace the superposition information and control the electron wave packet of low excited states.

Electron Localization in Molecular Fragmentation of H{sub 2} by Carrier-Envelope Phase Stabilized Laser Pulses

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

Kremer, Manuel; Fischer, Bettina; Feuerstein, Bernold

2009-11-20

Fully differential data for H{sub 2} dissociation in ultrashort (6 fs, 760 nm), linearly polarized, intense (0.44 PW/cm{sup 2}) laser pulses with a stabilized carrier-envelope phase (CEP) were recorded with a reaction microscope. Depending on the CEP, the molecular orientation, and the kinetic energy release (KER), we find asymmetric proton emission at low KERs (0-3 eV), basically predicted by Roudnev and Esry, and much stronger than reported by Kling et al. Wave packet propagation calculations reproduce the salient features and discard, together with the observed KER-independent electron asymmetry, the first ionization step to be the reason for the asymmetric protonmore » emission.« less

Distribution of the 3.1 micron feature in Cepheus A

NASA Technical Reports Server (NTRS)

Hodapp, Klaus-Werner; Eiroa, Carlos

1989-01-01

Near-IR absorption features produced by core-mantle dust grains are observed in many protostellar objects. The high spatial resolution observations (less or equal to 3 in.) could be helpful to monitor the expected changes of the features. Cep A/IRS 6 is a suitable candidate to carry out such a kind of study. It is located in an active star formation region and consists of a young object associated with an extended reflection nebula. The ice feature was observed in four positions of Cep A/IRS 6 with a 2.7 in. aperture. The observations were carried out at the IRTF using the cooled grating array spectrometer CGAS. The 2.4 to 3.8 micron spectra of two positions are presented.

Automated processing of fluorescence in-situ hybridization slides for HER2 testing in breast and gastro-esophageal carcinomas.

PubMed

Tafe, Laura J; Allen, Samantha F; Steinmetz, Heather B; Dokus, Betty A; Cook, Leanne J; Marotti, Jonathan D; Tsongalis, Gregory J

2014-08-01

HER2 fluorescence in-situ hybridization (FISH) is used in breast and gastro-esophageal carcinoma for determining HER2 gene amplification and patients' eligibility for HER2 targeted therapeutics. Traditional manual processing of the FISH slides is labor intensive because of multiple steps that require hands on manipulation of the slides and specifically timed intervals between steps. This highly manual processing also introduces inter-run and inter-operator variability that may affect the quality of the FISH result. Therefore, we sought to incorporate an automated processing instrument into our FISH workflow. Twenty-six cases including breast (20) and gastro-esophageal (6) cancer comprising 23 biopsies and three excision specimens were tested for HER2 FISH (Pathvysion, Abbott) using the Thermobrite Elite (TBE) system (Leica). Up to 12 slides can be run simultaneously. All cases were previously tested by the Pathvysion HER2 FISH assay with manual preparation. Twenty cells were counted by two observers for each case; five cases were tested on three separate runs by different operators to evaluate the precision and inter-operator variability. There was 100% concordance in the scoring between the manual and TBE methods as well as among the five cases that were tested on three runs. Only one case failed due to poor probe hybridization. In total, seven cases were positive for HER2 amplification (HER2:CEP17 ratio >2.2) and the remaining 19 were negative (HER2:CEP17 ratio <1.8) utilizing the 2007 ASCO/CAP scoring criteria. Due to the automated denaturation and hybridization, for each run, there was a reduction in labor of 3.5h which could then be dedicated to other lab functions. The TBE is a walk away pre- and post-hybridization system that automates FISH slide processing, improves work flow and consistency and saves approximately 3.5h of technologist time. The instrument has a small footprint thus occupying minimal counter space. TBE processed slides performed exceptionally well in comparison to the manual technique with no disagreement in HER2 amplification status. Copyright © 2014 Elsevier Inc. All rights reserved.

Outbursts from the Transient X-Ray Pulsar Cep X-4 (GS 2138+56)

NASA Technical Reports Server (NTRS)

Wilson, Colleen A.; Finger, Mark H.; Scott, D. Matthew

1997-01-01

Cep X-4 was discovered with the Orbiting Solar Observatory (OSO) 7 Satellite in 1973 June-July, but no pulsations were detected. In March 1988, an additional outburst was observed with Gingaq. Pulsations at a period of 66.2490 +/- .0001 s were detected during a month long outburst which peaked at about 100 mCrab (1-20 keV) in early April 1988. The source apparently did not appear again until June 1993 when it was detected by Roentgen Satellite (ROSAT) and Burst and Transient Source Experiment (BATSE). Pulsations at a period of 66.2499 +/- .0007 s were detected by BATSE. The outburst lasted about two weeks and had a peak pulsed flux of 15-20 mCrab (20-50 keV). In July 1997, BATSE and the All-Sky Monitor (ASM) on Rossi X-ray Timing Explorer (RXTE) observed a new outburst from Cep X-4. Pulsations at a period of 66.2743 +/- 0.0005 s were detected by BATSE. This outburst lasted about 2 weeks and peaked at a pulsed flux of about 10-15 mCrab (20-50 keV). Results of a search of BATSE data for additional outbursts will be presented. Pulse frequency and flux histories will be presented and compared to the flux history from the RXTE ASM. Implications of the apparent spin-down between outbursts will be discussed.

Poly(ADP-ribose) polymerase inhibitor CEP-8983 synergizes with bendamustine in chronic lymphocytic leukemia cells in vitro.

PubMed

Dilley, Robert L; Poh, Weijie; Gladstone, Douglas E; Herman, James G; Showel, Margaret M; Karp, Judith E; McDevitt, Michael A; Pratz, Keith W

2014-03-01

DNA repair aberrations and associated chromosomal instability is a feature of chronic lymphocytic leukemia (CLL). To evaluate if DNA repair insufficiencies are related to methylation changes, we examined the methylation of nine promoter regions of DNA repair proteins by bisulfide sequencing in 26 CLL primary samples and performed quantitative PCR on a subset of samples to examine BRCA1 expression. We also investigated if changes in cytogenetic or expression level of DNA repair proteins led to changes in sensitivity to a novel PARP inhibitor, CEP-8983, alone and in combination with bendamustine. No changes in promoter methylation were identified in BRCA1, BRCA2, FANC-C, FANC-F, FANC-L, ATM, MGMT, hMLH1 and H2AX except for two cases of minor BRCA1 hypermethylation. CLL samples appeared to have reduced BRCA1 mRNA expression uniformly in comparison to non-malignant lymphocytes irrespective of promoter hypermethylation. CEP-8983 displayed single agent cytotoxicity and the combination with bendamustine demonstrated synergistic cytotoxicity in the majority of CLL samples. These results were consistent across cytogenetic subgroups, including 17p deleted and previously treated patients. Our results provide rationale for further exploration of the combination of a PARP inhibitor and DNA damaging agents as a novel therapeutic strategy in CLL. Copyright © 2013 Elsevier Ltd. All rights reserved.

Polarization gating of high harmonic generation in the water window

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

Li, Jie; Ren, Xiaoming; Yin, Yanchun

2016-06-06

We implement the polarization gating (PG) technique with a two-cycle, 1.7 μm driving field to generate an attosecond supercontinuum extending to the water window spectral region. The ellipticity dependence of the high harmonic yield over a photon energy range much broader than previous work is measured and compared with a semi-classical model. When PG is applied, the carrier-envelope phase (CEP) is swept to study its influence on the continuum generation. PG with one-cycle (5.7 fs) and two-cycle (11.3 fs) delay are tested, and both give continuous spectra spanning from 50 to 450 eV under certain CEP values, strongly indicating the generation ofmore » isolated attosecond pulses in the water window region.« less

Optical spectrum variations of IL Cep A

NASA Astrophysics Data System (ADS)

Ismailov, N. Z.; Khalilov, O. V.; Bakhaddinova, G. R.

2016-02-01

The results of many-year uniform spectroscopic observations of the Herbig Ae/Be star IL Cep A are presented. Its Hα line has either a single or a barely resolved two-component emission profile. The H β emission line is clearly divided into two components with a deep central absorption. Smooth variations of the observed parameters of individual spectral lines over nine years are observed. The He I λ5876 Å line has a complex absorption profile, probably with superposed emission components. The NaI D1, D2 doublet exhibits weak changes due to variations in the circumstellar envelope. The variations observed in the stellar spectrum can be explained by either binarity or variations of the magnetic field in the stellar disk. Difficulties associated with both these possibilities are discussed.

[The French medecine pricing committee and the medicine economic policy: Rules and competences].

PubMed

Giorgi, D

2017-09-01

The French medicine pricing committee (CEPS), a governmental and inter-institutional body exercises essential competences for the regulation of the economy of the reimbursable drugs in France. It provides a good example of administered price regulation. It also supervises the proper use of products (control of promotion, conventional control of sales volumes). Finally, it regulates the annual envelope of drug expenditures by means of discounts paid by pharmaceutical companies. The article presents the legal criteria and the doctrine of price setting used in France. It details the types of market access contracts concluded by the CEPS. It specifies the conditions governing the annual envelope of expenditures on reimbursable medicines. Copyright © 2017 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.

[An educational software development proposal for nursing in neonatal cardiopulmonary resuscitation].

PubMed

Rodrigues, Rita de Cassia Vieira; Peres, Heloisa Helena Ciqueto

2013-02-01

The objective of this study was to develop an educational software program for nursing continuing education. This program was intended to incorporate applied methodological research that used the learning management system methodology created by Galvis Panqueva in association with contextualized instructional design for software design. As a result of this study, we created a computerized educational product (CEP) called ENFNET. This study describes all the necessary steps taken during its development. The creation of a CEP demands a great deal of study, dedication and investment as well as the necessity of specialized technical personnel to construct it. At the end of the study, the software was positively evaluated and shown to be a useful strategy to help users in their education, skills development and professional training.

A sudden brightness decrease of the young pre-MS object GM Cep

NASA Astrophysics Data System (ADS)

Munari, U.; Castellani, F.; Giannini, T.; Antoniucci, S.; Lorenzetti, D.

2017-11-01

In the framework of our EXor monitoring programme dubbed EXORCISM (EXOR OptiCal and Infrared Systematic Monitoring - Antoniucci et al. 2013 PPVI, Lorenzetti et al. 2007 ApJ 665, 1182; Lorenzetti et al. 2009 ApJ 693, 1056), we observed a new fading of the optical brightness of the Young Stellar Object (YSO) GM Cep (d=870 pc). This is a well studied variable (Semkov & Peneva 2012 APSS,338,95; Ibryamov et al. 2015 PASA,32,11; Xiao, Kroll, & Henden 2010 AJ, 139, 1527; Sicilia-Aguilar et al. 2008 ApJ,673,382-3) whose light-curve is dominated by recurrent brightness dims, interpreted as non-periodical eclipse events due to orbiting dust structures that move along the line of sight (UXor-type variability - Grinin 1988).

Co-evolutionary constraints of globular proteins correlate with their folding rates.

PubMed

Mallik, Saurav; Kundu, Sudip

2015-08-04

Folding rates (lnkf) of globular proteins correlate with their biophysical properties, but relationship between lnkf and patterns of sequence evolution remains elusive. We introduce 'relative co-evolution order' (rCEO) as length-normalized average primary chain separation of co-evolving pairs (CEPs), which negatively correlates with lnkf. In addition to pairs in native 3D contact, indirectly connected and structurally remote CEPs probably also play critical roles in protein folding. Correlation between rCEO and lnkf is stronger in multi-state proteins than two-state proteins, contrasting the case of contact order (co), where stronger correlation is found in two-state proteins. Finally, rCEO, co and lnkf are fitted into a 3D linear correlation. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

EE Cep Winks in Full Color

NASA Astrophysics Data System (ADS)

Walker, Gary E.

2015-01-01

We observe the long period (5.6 years) Eclipsing Binary Variable Star EE Cep during it's 2014 eclipse. It was observed on every clear night from the Maria Mitchell Observatory as well as remote sites for a total of 25 nights. Each night consisted of a detailed time series in BVRI looking for short term variations for a total of >9000 observations. The data was transformed to the Standard System. In addition, a time series was captured during the night of the eclipse. This data provides an alternate method to determine Time of Minimum than traditionally performed. The TOM varied with color. Several strong correlations are seen between colors substantiating the detection of variations on a time scale of hours. The long term light curve shows 5 interesting and different Phases with different characteristics.

Proceedings of RIKEN BNL Resarch Center Workshop: Fluctuations, Correlations and RHIC Low Energy Runs

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

Karsch, F.; Kojo, T.; Mukherjee, S.

Most of our visible universe is made up of hadronic matter. Quantum Chromodynamics (QCD) is the theory of strong interaction that describes the hadronic matter. However, QCD predicts that at high enough temperatures and/or densities ordinary hadronic matter ceases to exist and a new form of matter is created, the so-called Quark Gluon Plasma (QGP). Non-perturbative lattice QCD simulations shows that for high temperature and small densities the transition from the hadronic to the QCD matter is not an actual phase transition, rather it takes place via a rapid crossover. On the other hand, it is generally believed that atmore » zero temperature and high densities such a transition is an actual first order phase transition. Thus, in the temperature-density phase diagram of QCD, the first order phase transition line emanating from the zero temperature high density region ends at some higher temperature where the transition becomes a crossover. The point at which the first order transition line turns into a crossover is a second order phase transition point belonging to three dimensional Ising universality class. This point is known as the QCD Critical End Point (CEP). For the last couple of years the Relativistic Heavy Ion Collider (RHIC) at Brookhaven National Laboratory has been performing experiments at lower energies in search of the elusive QCD CEP. In general critical behaviors are manifested through appearance of long range correlations and increasing fluctuations associated with the presence of mass-less modes in the vicinity of a second order phase transition. Experimental signatures of the CEP are likely to be found in observables related to fluctuations and correlations. Thus, one of the major focuses of the RHIC low energy scan program is to measure various experimental observables connected to fluctuations and correlations. On the other hand, with the start of the RHIC low energy scan program, a flurry of activities are taking place to provide solid theoretical background for the search of the CEP using observables related to fluctuations and correlations. While new data are pouring in from the RHIC low energy scan program, many recent advances have also been made in the phenomenological and lattice gauge theory sides in order to have a better theoretical understanding of the wealth of new data. This workshop tried to create a synergy between the experimental, phenomenological and lattice QCD aspects of the fluctuation and correlation related studies of the RHIC low energy scan program. The workshop brought together all the leading experts from related fields under the same forum to share new ideas among themselves in order to streamline the continuing search of CEP in the RHIC low energy scan program.« less

Thromboembolic adverse event study of combined estrogen-progestin preparations using Japanese Adverse Drug Event Report database

PubMed Central

Hasegawa, Shiori; Matsui, Toshinobu; Hane, Yuuki; Abe, Junko; Hatahira, Haruna; Motooka, Yumi; Sasaoka, Sayaka; Fukuda, Akiho; Naganuma, Misa; Hirade, Kouseki; Takahashi, Yukiko; Kinosada, Yasutomi

2017-01-01

Combined estrogen-progestin preparations (CEPs) are associated with thromboembolic (TE) side effects. The aim of this study was to evaluate the incidence of TE using the Japanese Adverse Drug Event Report (JADER) database. Adverse events recorded from April 2004 to November 2014 in the JADER database were obtained from the Pharmaceuticals and Medical Devices Agency (PMDA) website (www.pmda.go.jp). We calculated the reporting odds ratios (RORs) of suspected CEPs, analyzed the time-to-onset profile, and assessed the hazard type using Weibull shape parameter (WSP). Furthermore, we used the applied association rule mining technique to discover undetected relationships such as the possible risk factors. The total number of reported cases in the JADER contained was 338,224. The RORs (95% confidential interval, CI) of drospirenone combined with ethinyl estradiol (EE, Dro-EE), norethisterone with EE (Ne-EE), levonorgestrel with EE (Lev-EE), desogestrel with EE (Des-EE), and norgestrel with EE (Nor-EE) were 56.2 (44.3–71.4), 29.1 (23.5–35.9), 42.9 (32.3–57.0), 44.7 (32.7–61.1), and 38.6 (26.3–56.7), respectively. The medians (25%–75%) of the time-to-onset of Dro-EE, Ne-EE, Lev-EE, Des-EE, and Nor-EE were 150.0 (75.3–314.0), 128.0 (27.0–279.0), 204.0 (44.0–660.0), 142.0 (41.3–344.0), and 16.5 (8.8–32.0) days, respectively. The 95% CIs of the WSP-β for Ne-EE, Lev-EE, and Nor-EE were lower and excluded 1. Association rule mining indicated that patients with anemia had a potential risk of developing a TE when using CEPs. Our results suggest that it is important to monitor patients administered CEP for TE. Careful observation is recommended, especially for those using Nor-EE, and this information may be useful for efficient therapeutic planning. PMID:28732067

The secret lives of Cepheids: evolutionary changes and pulsation-induced shock heating in the prototype classical Cepheid δ Cep

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

Engle, Scott G.; Guinan, Edward F.; Harper, Graham M.

Over the past decade, the Secret Lives of Cepheids (SLiC) program has been carried out at Villanova University to study aspects and behaviors of classical Cepheids that are still not well understood. In this, the first of several planned papers on program Cepheids, we report the current results for δ Cep, the Cepheid prototype. Ongoing photometry has been obtained to search for changes in the pulsation period, light-curve morphology, and amplitude. Combining our photometry with the times of maximum light compilation by Berdnikov et al. returns a small period change of dP/dt ≈–0.1006 ± 0.0002 s yr{sup -1}. There ismore » also evidence for a gradual light amplitude increase of ∼0.011 mag (V band) and ∼0.012 mag (B band) per decade over the last ∼50 years. In addition, Hubble Space Telescope (HST) Cosmic Origins Spectrograph (COS) UV spectrophotometry and XMM-Newton X-ray data were carried out to investigate the high-temperature plasmas present above the Cepheid photospheres. In total, from the five visits (eight exposures) with XMM-Newton, δ Cep is found to be a soft X-ray source (L {sub X} (0.3-2 keV) ≈4.5-13 × 10{sup 28} erg s{sup -1}) with peak flux at kT = 0.6-0.9 keV. The X-ray activity is found to vary, possibly in phase with the stellar pulsations. From 2010-2013, nine observations of δ Cep were carried out with HST-COS. The UV emissions are also variable and well phased with the stellar pulsations. Maximum UV line emissions occur near, or slightly before, maximum optical light, varying by as much as 20 times. This variability shows that pulsation-induced shock heating plays a significant role in Cepheid atmospheres, possibly in addition to a quiescent, magnetic heating. The results of this study show Cepheid atmospheres to be rather complex and dynamic.« less

Reach of Individuals at Risk for Cardiovascular Disease by Proactive Recruitment Strategies in General Practices, Job Centers, and Health Insurance.

PubMed

Guertler, Diana; Meyer, Christian; Dörr, Marcus; Braatz, Janina; Weymar, Franziska; John, Ulrich; Freyer-Adam, Jennis; Ulbricht, Sabina

2017-02-01

Reach of individuals at risk for cardiovascular disease (CVD) constitutes a major determinant of the population impact of preventive effort. This study compares three proactive recruitment strategies regarding their reach of individuals with CVD risk factors. Individuals aged 40-65 years were invited to a two-stage cardio-preventive program including an on-site health screening and a cardiovascular examination program (CEP) using face-to-face recruitment in general practices (n = 671), job centers (n = 1049), and mail invitations from health insurance (n = 894). The recruitment strategies were compared regarding the following: (1) participation rate; (2) participants' characteristics, i.e., socio-demographics, self-reported health, and CVD risk factors (smoking, physical activity, fruit/vegetable consumption, body mass index, blood pressure, high-density lipoprotein, triglycerides, and glycated hemoglobin); and (3) participation factors, i.e., differences between participants and non-participants. Screening participation rates were 56.0, 32.8, and 23.5 % for the general practices, the job centers, and the health insurance, respectively. Among eligible individuals for the CEP, respectively, 80.3, 65.5, and 96.1 % participated in the CEP. Job center clients showed the lowest socio-economic status and the most adverse CVD risk pattern. Being female predicted screening participation across all strategies (OR = 1.45, 95 % CI 1.07-1.98; OR = 1.34, 95 % CI 1.04-1.74; OR = 1.62, 95 % CI 1.16-2.27). Age predicted screening participation only within health insurance (OR = 1.04, 95 % CI 1.01-1.06). Within the general practices and the job centers, CEP participants were less likely to be smokers than non-participants (OR = 0.49, 95 % CI 0.26-0.94; OR = 0.42, 95 % CI 0.20-0.89). The recruitment in general practices yielded the highest reach. However, job centers may be useful to reduce health inequalities induced by social gradient.

Spectral and Photometric Data of Be Star, EM Cep

NASA Astrophysics Data System (ADS)

Kochiashvili, Nino; Natsvilishvili, Rezo; Kochiashvili, Ia; Vardosanidze, Manana; Beradze, Sopia; Pannicke, Anna

The subject of investigation in this project is a Be spectral type giant variable star EM Cep. It was established that the star has a double nature: 1. when emission lines are seen in its spectrum and 2. when only absorption lines are observable and emission lines are not seen. This means that the star is not always in Be state. Be state continues existing during a few months. EM Cep shows flare activity too. The causes of photometric and spectral variability are to be established. The existence of different mechanisms, which provokes Be phenomenon, is possible. The character of light curves' variability gives us possibility to propose that it is not excluded that the star could be a short-period Cepheid of λ Eri type. However, we do not have sufficient data to exclude its binarity. On the basis of the observations carried out at Abastumani observatory, the light curve with two minima and two maxima were revealed, but these data, too accord with the half-period - we can also consider a light curve with one minimum and one maximum. Both cases suggest a good agreement with the characters of variability. For the case of binarity in Abastumani observatory, a set of orbital elements by using the Wilson-Devinney code is already obtained. The elements correspond to the model of acceptable, real close binary star. However, notwithstanding this situation, the true nature of the star is not established for the moment. To solve this problem, we need to get high-resolution spectral data, when by using radial velocity curves, it would be possible to answer the question of binarity of the star. It is not excluded to reveal spectral lines of the second component in case of binarity of the star. Since 2014, we have renewed UBVRI photometric observations of EM Cep in Abastumani using a 48-cm telescope with CCD device. Spectral observations are made in Azerbaijan, Shamakhy Observatory. Our German Colleagues have been observing the star since March of 2017 at the Observatory of the Jena University. We plan to carry out a joint analysis of the observations of the three observatories to explain the observational peculiarities of the star.

Congenital Erythropoietic Porphyria (CEP)

MedlinePlus

... can be severe and such patients require periodic transformations to maintain sufficient red blood cells. In severely ... DAY FOR PATIENTS! date: Dec 9, 2017 PATIENT EDUCATION AND SUPPORT MEETING - ATLANTA » More upcoming events Athi ...

Laser phase control of high-order harmonic generation at large internuclear distance: the H+ -H2+ system.

PubMed

Bandrauk, André D; Barmaki, Samira; Kamta, Gerard Lagmago

2007-01-05

Exact (Born-Oppenheimer) 3-D numerical solutions of the time-dependent Schrödinger equation are obtained for the one electron linear H+-H2+ atom-molecule system at large internuclear distance R in interaction with two-cycles intense (I>10(14) W cm(-2)) 800 nm laser pulses. High-order harmonic generation (HHG) spectra are obtained with an energy cutoff larger than the atomic maximum of I(p)+3U(p), where I(p) is the ionization potential and U(p) is the ponderomotive energy. At large R, this extended cutoff is shown to be related to the nature of electron transfer, whose direction is shown to depend critically on the carrier-envelope phase (CEP) of the ultrashort pulse. Constructive and destructive interferences in the HHG spectrum resulting from coherent superpositions of electronic states in the H+-H2+ system are interpreted in terms of multiple electron trajectories extracted from a time profile analysis.

Carrier-envelope phase stabilization with sub-10 as residual timing jitter.

PubMed

Borchers, B; Koke, S; Husakou, A; Herrmann, J; Steinmeyer, G

2011-11-01

We demonstrate carrier-envelope phase (CEP) stabilization of a mode-locked Ti:sapphire oscillator with unprecedented timing jitter of eight attoseconds. The stabilization performance is obtained by a combination of two different stabilization approaches. In a first step the drift of the CEP is stabilized with a conventional feedback loop by means of controlling the oscillator pump power with an acousto-optic modulator (AOM). In a second step we utilize a recently developed feed-forward type stabilization scheme which has a much higher control bandwith. Here an acousto-optic frequency shifter (AOFS) produces the stabilized output in the first diffraction order. Moreover, we present numerical results on the optimization of the length of the photonic crystal fiber, which is used to generate an octave-spanning spectrum, in order to optimize the sensitivity in the f-to-2f interferometers.

Sub-cycle steering of the deprotonation of acetylene by intense few-cycle mid-infrared laser fields.

PubMed

Li, H; Kling, Nora G; Gaumnitz, T; Burger, C; Siemering, R; Schötz, J; Liu, Q; Ban, L; Pertot, Y; Wu, J; Azzeer, A M; de Vivie-Riedle, R; Wörner, H J; Kling, M F

2017-06-26

Directional breaking of the C-H/C-D molecular bond is manipulated in acetylene (C 2 H 2 ) and deuterated acetylene (C 2 D 2 ) by waveform controlled few-cycle mid-infrared laser pulses with a central wavelength around 1.6 μm at an intensity of about 8 × 10 13 W/cm 2 . The directionality of the deprotonation of acetylene is controlled by changing the carrier-envelope phase (CEP). The CEP-control can be attributed to the laser-induced superposition of vibrational modes, which is sensitive to the sub-cycle evolution of the laser waveform. Our experiments and simulations indicate that near-resonant, intense mid-infrared pulses permit a higher degree of control of the directionality of the reaction compared to those obtained in near-infrared fields, in particular for the deuterated species.

EE Cep Winks in Full Color (Abstract)

NASA Astrophysics Data System (ADS)

Walker, G.

2015-06-01

(Abstract only) We observe the long period (5.6 years) Eclipsing Binary Variable Star EE Cep during its 2014 eclipse. It was observed on every clear night from the Maria Mitchell Observatory as well as remote sites for a total of 25 nights. Each night consisted of a detailed time series in BVRI looking for short term variations for a total of >10,000 observations. The data was transformed to the Standard System. In addition, a time series was captured during the night of the eclipse. This data provides an alternate method to determine Time of Minimum than traditionally performed. The TOM varied with color. Several strong correlations are seen between colors substantiating the detection of variations on a time scale of hours. The long term light curve shows five interesting and different Phases with different characteristics.

Climate windows for Polynesian voyaging to New Zealand and Easter Island.

PubMed

Goodwin, Ian D; Browning, Stuart A; Anderson, Atholl J

2014-10-14

Debate about initial human migration across the immense area of East Polynesia has focused upon seafaring technology, both of navigation and canoe capabilities, while temporal variation in sailing conditions, notably through climate change, has received less attention. One model of Polynesian voyaging observes that as tradewind easterlies are currently dominant in the central Pacific, prehistoric colonization canoes voyaging eastward to and through central East Polynesia (CEP: Society, Tuamotu, Marquesas, Gambier, Southern Cook, and Austral Islands) and to Easter Island probably had a windward capacity. Similar arguments have been applied to voyaging from CEP to New Zealand against prevailing westerlies. An alternative view is that migration required reliable off-wind sailing routes. We investigate the marine climate and potential voyaging routes during the Medieval Climate Anomaly (MCA), A.D. 800-1300, when the initial colonization of CEP and New Zealand occurred. Paleoclimate data assimilation is used to reconstruct Pacific sea level pressure and wind field patterns at bidecadal resolution during the MCA. We argue here that changing wind field patterns associated with the MCA provided conditions in which voyaging to and from the most isolated East Polynesian islands, New Zealand, and Easter Island was readily possible by off-wind sailing. The intensification and poleward expansion of the Pacific subtropical anticyclone culminating in A.D. 1140-1260 opened an anomalous climate window for off-wind sailing routes to New Zealand from the Southern Austral Islands, the Southern Cook Islands, and Tonga/Fiji Islands.

Climate windows for Polynesian voyaging to New Zealand and Easter Island

PubMed Central

Goodwin, Ian D.; Browning, Stuart A.; Anderson, Atholl J.

2014-01-01

Debate about initial human migration across the immense area of East Polynesia has focused upon seafaring technology, both of navigation and canoe capabilities, while temporal variation in sailing conditions, notably through climate change, has received less attention. One model of Polynesian voyaging observes that as tradewind easterlies are currently dominant in the central Pacific, prehistoric colonization canoes voyaging eastward to and through central East Polynesia (CEP: Society, Tuamotu, Marquesas, Gambier, Southern Cook, and Austral Islands) and to Easter Island probably had a windward capacity. Similar arguments have been applied to voyaging from CEP to New Zealand against prevailing westerlies. An alternative view is that migration required reliable off-wind sailing routes. We investigate the marine climate and potential voyaging routes during the Medieval Climate Anomaly (MCA), A.D. 800–1300, when the initial colonization of CEP and New Zealand occurred. Paleoclimate data assimilation is used to reconstruct Pacific sea level pressure and wind field patterns at bidecadal resolution during the MCA. We argue here that changing wind field patterns associated with the MCA provided conditions in which voyaging to and from the most isolated East Polynesian islands, New Zealand, and Easter Island was readily possible by off-wind sailing. The intensification and poleward expansion of the Pacific subtropical anticyclone culminating in A.D. 1140–1260 opened an anomalous climate window for off-wind sailing routes to New Zealand from the Southern Austral Islands, the Southern Cook Islands, and Tonga/Fiji Islands. PMID:25267611

Health-Related Quality of Life Measures for Physically Active Elderly in Community Exercise Programs in Catalonia: Comparative Analysis with Sedentary People

PubMed Central

Fortuño-Godes, Jesús; Guerra-Balic, Myriam; Cabedo-Sanromà, Josep

2013-01-01

Objective. To evaluate Health-Related Quality of Life (HRQoL), medication used, and Stock of Health Capital (SHC) in physically active elderly participants in Community Exercise Programs (CEPs) compared to a sedentary group. Methods. EuroQol standardized instrument was completed by physically active elderly (n = 2,185) who participated in CEPs. Common items were compared to HRQoL data of 1,874 sedentary elderly people, taken from the Catalan Health Survey 2006 (CHS'06). Visual Analogue Scale (VAS) outcomes and medication used were assessed through parametric statistics. Dimensions of health conditions were compared, between sedentary people and physically active elderly participants in CEPs. SHC results were obtained combining the EuroQol scores and Life Expectancy (LE) values. An economic value of €34,858.70 was assigned to these years of LE. Results. Physically active subjects had better HRQoL values (75.36 in males and 70.71 in females) than CHS'06 sedentary subjects (58.35 in males and 50.59 in females). Medication used was different between physically active subjects (1.89 in males and 2.87 in females) and CHS'06 sedentary subjects (4.34 in males and 4.21 in females). SHC data for physically active elderly (€465,988.31/QALY in males and €522,550.31/QALY in females) were higher than for CHS'06 sedentary subjects (€363,689.33/QALY in males and €346,615.91/QALY in females). PMID:24454357

TW-class hollow-fiber compressor with tunable pulse duration (Conference Presentation)

NASA Astrophysics Data System (ADS)

Boehle, Frederik; Vernier, Aline; Kretschmar, Martin; Jullien, Aurélie; Kovacs, Mate; Romero, Rosa M.; Crespo, Helder M.; Simon, Peter; Nagy, Tamas; Lopez-Martens, Rodrigo

2017-05-01

CEP-stable few-cycle light pulses find numerous applications in attosecond science, most notably the production of isolated attosecond pulses for studying ultrafast electronic processes in matter [1]. Scaling up the pulse energy of few-cycle pulses could extend the scope of applications to even higher intensity processes, such as attosecond dynamics of relativistic plasma mirrors [2]. Hollow fiber compressors are widely used to produce few-cycle pulses with excellent spatiotemporal quality [3], where octave-spanning broadened spectra can be temporally compressed to sub-2-cycle duration [4,5]. Several tricks help increase the output energy: using circularly polarized light [6], applying a pressure gradient along the fiber [7] or even temporal multiplexing [8]. The highest pulse energy of 5 mJ at 5 fs pulse duration was achieved by using a hollow fiber in pressure gradient mode [9] but in this case no CEP stabilization was achieved, which is crucial for most applications of few-cycle pulses. Nevertheless, it did show that in order to scale up the peak power, the effective length and area mode of the fiber had to be increased proportionally, thereby requiring the use of longer waveguides with larger apertures. Thanks to an innovative design utilizing stretched flexible capillaries [10], we recently demonstrated the generation CEP-stable sub-4fs pulses with 3mJ energy using a 2m length 450mm bore hollow fiber in pressure gradient mode [11]. Here, we show that a stretched hollow-fiber compressor operated in pressure gradient mode can generate relativistic intensity pulses with continuously tunable waveform down to almost a single cycle (3.5fs at 750nm central wavelength). The pulses are characterized online using an integrated d-scan device directly under vacuum [12]. While the pulse shape is tuned, all other pulse characteristics, such as energy, pointing stability and focal distribution remain the same on target, making it possible to explore the dynamics of plasma mirrors using controllable relativistic-intensity light waveforms at 1kHz. [1] Krausz and Ivanov, Rev. Mod. Phys. 81, 163 (2009). [2] Borot et al., Nature Phys. 8, 417-421 (2012). [3] Nisoli et al., Appl. Phys. Lett. 68, 2793-2795 (1996). [4] Park et al., Opt. Lett. 34, 2342-2344 (2009). [5] Schweinberger et al., Opt. Lett. 37, 3573-5 (2012). [6] Chen et al., Opt. Lett. 34, 1588-1590 (2009). [7] Suda et al., Appl. Phys. Lett. 86, 111116 (2005). [8] Jacqmin et al., Opt. Lett. 40, 709-712 (2015) [9] Bohman et al., Opt. Lett. 35, 1887-9 (2010). [10] Nagy et al., Appl. Opt. 47, 3264-3268 (2008). [11] Boehle et al., Las. Phys. Lett. 11, 095401 (2014). [12] Miranda et al., Opt. Express 20, 18732-43 (2012)

A Mass for γ Cep Ab

NASA Astrophysics Data System (ADS)

Benedict, G. Fritz; Harrison, Thomas E.; Endl, M.; Torres, G.

2018-04-01

Not Available Based on observations made with the NASA/ESA Hubble Space Telescope, obtained at the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., under NASA contract NAS5-26555.

A search for spectroscopic binaries among the runaway O type stars

NASA Technical Reports Server (NTRS)

Stone, R. C.

1982-01-01

Numerous radial velocity measurements of medium dispersion were made for the 10 brighter stars given in Stone's list of very probable O type runaways. All plates were measured with the KPNO PDS microdensitometer, and a new iterative reductional analysis was used to derive plate velocities, which are estimated to be 1.6 times more accurate internally than those found by using the traditional method. Of thse stars, psi Per, alpha Cam, HD 188209, and 26 Cep are identified as probable velocity variables, while 9 Sge, lambda Cep, and HD 218915 are classed as possible variables. If the source of this variability is Keplerian rather than atmospheric, which cannot be established unequivocally from the observations of this paper, psi Per could be a spectroscopic binary with a black hole companion, and at least 1.2 solar mass. The detection of runaway binary systems from radial velocity measurements is discussed.

Effective Gene Therapy of Mice with Congenital Erythropoietic Porphyria Is Facilitated by a Survival Advantage of Corrected Erythroid Cells

PubMed Central

Robert-Richard, Elodie; Moreau-Gaudry, François; Lalanne, Magalie; Lamrissi-Garcia, Isabelle; Cario-André, Muriel; Guyonnet-Dupérat, Véronique; Taine, Laurence; Ged, Cécile; de Verneuil, Hubert

2008-01-01

Achieving long-term expression of a therapeutic gene in a given hematopoietic lineage remains an important goal of gene therapy. Congenital erythropoietic porphyria (CEP) is a severe autosomal-recessive disorder characterized by a deficiency in uroporphyrinogen III synthase (UROS), the fourth enzyme of the heme biosynthetic pathway. We used a recently obtained murine model to check the feasibility of gene therapy in this disease. Lentivirus-mediated transfer of the human UROS cDNA into hematopoietic stem cells (HSCs) from Urosmut248 mice resulted in a complete and long-term enzymatic, metabolic, and phenotypic correction of the disease, favored by a survival advantage of corrected red blood cells. These results demonstrate that the cure of this mouse model of CEP at a moderate transduction level supports the proof of concept of a gene therapy in this disease by transplantation of genetically modified hematopoietic stem cells. PMID:18179890

Secret Lives of Cepheids: beta Dor as a Test of Cepheid X-ray Heating Mechanisms

NASA Astrophysics Data System (ADS)

Engle, Scott

2017-09-01

We propose two 40 ksec phase-constrained ACIS-I observations of the 9.8 day Cepheid beta Dor. This will fill its uncharted 0.9-0.2 phase gap to confirm and define (Lx, kT) its pulsation-driven X-ray variations and help identify the mechanism (shocks, magnetic fields, turbulent dynamos) responsible, in complement to our recent confirmation of pulsation-induced X-ray variations from delta Cep (Engle et al. 2017). Beta Dor has different properties than delta Cep (P = 9.8/5.4d; R = 61/44Rsun), and the proposed visits are crucial to combine with existing X-ray and FUV data and test the X-ray heating mechanisms. This program is the culmination of several years of work, and the resulting nearly complete phase coverage of beta Dor makes this Cepheid the timeliest and most promising target.

Determination of the absolute carrier-envelope phase by angle-resolved photoelectron spectra of Ar by intense circularly polarized few-cycle pulses

NASA Astrophysics Data System (ADS)

Fukahori, Shinichi; Ando, Toshiaki; Miura, Shun; Kanya, Reika; Yamanouchi, Kaoru; Rathje, Tim; Paulus, Gerhard G.

2017-05-01

The angle-resolved photoelectron spectra of Ar are recorded using intense circularly polarized near-infrared few-cycle laser pulses, and the effect of the depletion of Ar atoms by the ionization and the effect of the Coulombic potential are examined by the classical trajectory Monte Carlo simulations. On the basis of the comparison between the experimental and theoretical photoelectron spectra, a procedure for estimating the absolute carrier-envelope phase (CEP) of the few-cycle laser pulses interacting with atoms and molecules is proposed. It is confirmed that the absolute CEP can securely be estimated without any numerical calculations once the angular distribution of the yield of photoelectrons having the kinetic energy larger than 30 eV is measured with the peak laser intensity in the range between 1 ×1014 and 5 ×1014W /c m2 .

Design and analysis of a low actuation voltage electrowetting-on-dielectric microvalve for drug delivery applications.

PubMed

Samad, Mst Fateha; Kouzani, Abbas Z

2014-01-01

This paper presents a low actuation voltage microvalve with optimized insulating layers that manipulates a conducting ferro-fluid droplet by the principle of electrowetting-on-dielectric (EWOD). The proposed EWOD microvalve contains an array of chromium (Cr) electrodes on the soda-lime glass substrate, covered by both dielectric and hydrophobic layers. Various dielectric layers including Su-8 2002, Polyvinylidenefluoride (PVDF) and Cyanoethyl pullulan (CEP), and thin (50 nm) hydrophobic Teflon and Cytonix are used to analyze the EWOD microvalves at different voltages. The Finite Element Method (FEM) based software, Coventorware is used to carry out the simulation analysis. It is observed that the EWOD microvalve having a CEP dielectric layer with dielectric constant of about 20 and thickness of 1 μm, and a Cytonix hydrophobic layer with thickness of 50 nm operated the conducting ferro-fluid droplet at the actuation voltage as low as 7.8 V.

Theoretical exploration of control factors for the high-order harmonic generation (HHG) spectrum in two-color field.

PubMed

Huang, Xinting; Yang, Dapeng; Yao, Li

2014-09-15

In this work, the laser-parameter effects on the high-order harmonic generation (HHG) spectrum and attosecond trains by mixing two-color laser field, a visible light field of 800 nm and a mid-infrared (mid-IR) laser pulses of 2400 nm, are theoretically demonstrated for the first time. Different schemes are applied to discuss the function of intensity, carrier-envelope phase (CEP) and pulse duration on the generation of an isolated attosecond pulse. As a consequence, an isolated 16as pulse is obtained by Fourier transforming an ultrabroad XUV continuum of 208 eV with the fundamental field of duration of 6 fs, 9×10(14)W/cm2 of intensity, the duration of 12 fs, the CEPs of the two driving pulses of -π and the relative strength ratio √R=0.2. Copyright © 2014 Elsevier B.V. All rights reserved.

Oxidation-Induced Increase In Photoreactivity of Bovine Retinal Lipid Extract.

PubMed

Koscielniak, A; Serafin, M; Duda, M; Oles, T; Zadlo, A; Broniec, A; Berdeaux, O; Gregoire, S; Bretillon, L; Sarna, T; Pawlak, A

2017-12-01

The mammalian retina contains a high level of polyunsaturated fatty acids, including docosahexaenoic acid (22:6) (DHA), which are highly susceptible to oxidation. It has been shown that one of the products of DHA oxidation-carboxyethylpyrrole (CEP), generated in situ, causes modifications of retinal proteins and induces inflammation response in the outer retina. These contributing factors may play a role in the development of age-related macular degeneration (AMD). It is also possible that some of the lipid oxidation products are photoreactive, and upon irradiation with blue light may generate reactive oxygen species. Therefore, in this work we analysed oxidation-induced changes in photoreactivity of lipids extracted from bovine neural retinas. Lipid composition of bovine neural retinas closely resembles that of human retinas making the bovine tissue a convenient model for studying the photoreactivity and potential phototoxicity of oxidized human retinal lipids. Lipid composition of bovine neural retinas Folch' extracts (BRex) was determined by gas chromatography (GC) and liquid chromatography coupled to an electrospray ionization source-mass spectrometer (LC-ESI-MS) analysis. Liposomes prepared from BRex, equilibrated with air, were oxidized in the dark at 37 °C for up to 400 h. The photoreactivity of BRex at different stages of oxidation was studied by EPR-oximetry and EPR-spin trapping. Photogeneration of singlet oxygen ( 1 O 2 , 1 Δ g ) by BRex was measured using time-resolved detection of the characteristic phosphorescence at 1270 nm. To establish contribution of lipid components to the analysed photoreactivity of Folch' extract of bovine retinas, a mixture of selected synthetic lipids in percent by weight (w/w %) ratio resembling that of the BRex has been also studied. Folch's extraction of bovine neural retinas was very susceptible to oxidation despite the presence of powerful endogenous antioxidants such as α-tocopherol and zeaxanthin. Non-oxidized and oxidized BRex photogenerated singlet oxygen with moderate quantum yield. Blue-light induced generation of superoxide anion by Folch' extract of bovine neural retinas strongly depended on the oxidation time. The observed photoreactivity of the studied extract gradually increased during its in vitro oxidation.

A CHANDRA OBSERVATION OF THE ECLIPSING WOLF-RAYET BINARY CQ Cep

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

Skinner, Stephen L.; Zhekov, Svetozar A.; Güdel, Manuel

The short-period (1.64 d) near-contact eclipsing WN6+O9 binary system CQ Cep provides an ideal laboratory for testing the predictions of X-ray colliding wind shock theory at close separation where the winds may not have reached terminal speeds before colliding. We present results of a Chandra X-ray observation of CQ Cep spanning ∼1 day during which a simultaneous Chandra optical light curve was acquired. Our primary objective was to compare the observed X-ray properties with colliding wind shock theory, which predicts that the hottest shock plasma (T ≳ 20 MK) will form on or near the line-of-centers between the stars. The X-raymore » spectrum is strikingly similar to apparently single WN6 stars such as WR 134 and spectral lines reveal plasma over a broad range of temperatures T ∼ 4-40 MK. A deep optical eclipse was seen as the O star passed in front of the Wolf-Rayet star and we determine an orbital period P {sub orb} = 1.6412400 d. Somewhat surprisingly, no significant X-ray variability was detected. This implies that the hottest X-ray plasma is not confined to the region between the stars, at odds with the colliding wind picture and suggesting that other X-ray production mechanisms may be at work. Hydrodynamic simulations that account for such effects as radiative cooling and orbital motion will be needed to determine if the new Chandra results can be reconciled with the colliding wind picture.« less

Noncovalent interaction of polyethylene glycol with copper complex of ethylenediaminetetraacetic acid and its application in constructing inorganic nanomaterials.

PubMed

Pan, Shu Zhen; Song, Le Xin; Chen, Jie; Du, Fang Yun; Yang, Jing; Xia, Juan

2011-10-21

In this study, we try to answer a fundamental question: what is the consequence of the noncovalent interaction between a polymer and a coordination compound? Here, polyethylene glycol (PEG-4000, PEG-b) and copper complex of ethylenediaminetetraacetic acid (H(2)CuY) were employed to solve this problem. A novel adduct (CEP) between H(2)CuY and PEG-b was prepared. Our results indicated several interesting findings. First, the introduction of H(2)CuY had no effect on the stacking structure of PEG-b but led to a large change in surface structure of the polymer. Second, there was a significant difference (117 K) in the maximum degradation temperature between the PEG and the CEP, suggesting that the noncovalent interaction can drastically improve the thermal stability of the PEG. Third, sintering experiments showed that H(2)CuY and CEP produced completely different decomposition products. The former formed Cu crystals in nitrogen and CuO in air, but the latter generated Cu and CuCl crystals with good crystallinity, respectively. Finally, three independent measurements: viscosity, conductivity and nuclear magnetic resonance in solution, provided useful information and insights from both sides of the noncovalent interaction. Probable interaction mechanisms and interaction sites were proposed. We consider that the current research could create the foundation for a new understanding of how the noncovalent adduct interaction between a metallic complex and a polymer relates to the change in physical and chemical properties of the adducted components. This journal is © The Royal Society of Chemistry 2011

Materials Data on Ce(P3Ru)4 (SG:204) by Materials Project

DOE Data Explorer

Kristin Persson

2015-02-09

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

78 FR 67018 - Airworthiness Directives; Embraer S.A. Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-08

... dos Campos, Sao Paulo, Brasil; phone: (+55 12) 3927-1000; Fax: (+55 12) 3927-6600, Ext. 1448; email..., CEP: 12227-901, Sao Jose dos Campos, Sao Paulo, Brasil; phone: (+55 12) 3927-1000; Fax: (+55 12) 3927...

Hubble’s View of a Changing Fan

NASA Image and Video Library

2017-12-08

The Universe is rarely static, although the timescales involved can be very long. Since modern astronomical observations began we have been observing the birthplaces of new stars and planets, searching for and studying the subtle changes that help us to figure out what is happening within. The bright spot located at the edge of the bluish fan-shaped structure in this Hubble image is a young star called V* PV Cephei, or PV Cep. It is a favorite target for amateur astronomers because the fan-shaped nebulosity, known as GM 1-29 or Gyulbudaghian’s Nebula, changes over a timescale of months. The brightness of the star has also varied over time. Images of PV Cep taken in 1952 showed a nebulous streak, similar to a comet’s tail. However, this had vanished when new images of the star were obtained some twenty-five years later. Instead, the blue fan-shaped nebula had appeared. Twenty-five years is a very short period on cosmic timescales, so astronomers think that the mysterious streak may have been a temporary phenomenon, such as the remnants of a massive stellar flare — similar to the solar flares we are used to seeing in the solar system. At the same time as this was happening, the star itself was brightening. This provided the light to illuminate the newly formed fan-shaped nebula. This brightening might be related to the start of the hydrogen-burning phase of the star, which would mean that it was reaching maturity. PV Cep is thought to be surrounded by a disc of gas and dust, which would stop light from escaping in all directions. The fan-like appearance is therefore probably a result of starlight escaping from the dust disc and projecting onto the nebula. PV Cep is located in the northern constellation of Cepheus at a distance of over 1600 light-years from Earth. European Space Agency/NASA Hubble NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

Ethanol precipitation for purification of recombinant antibodies.

PubMed

Tscheliessnig, Anne; Satzer, Peter; Hammerschmidt, Nikolaus; Schulz, Henk; Helk, Bernhard; Jungbauer, Alois

2014-10-20

Currently, the golden standard for the purification of recombinant humanized antibodies (rhAbs) from CHO cell culture is protein A chromatography. However, due to increasing rhAbs titers alternative methods have come into focus. A new strategy for purification of recombinant human antibodies from CHO cell culture supernatant based on cold ethanol precipitation (CEP) and CaCl2 precipitation has been developed. This method is based on the cold ethanol precipitation, the process used for purification of antibodies and other components from blood plasma. We proof the applicability of the developed process for four different antibodies resulting in similar yield and purity as a protein A chromatography based process. This process can be further improved using an anion-exchange chromatography in flowthrough mode e.g. a monolith as last step so that residual host cell protein is reduced to a minimum. Beside the ethanol based process, our data also suggest that ethanol could be replaced with methanol or isopropanol. The process is suited for continuous operation. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Optimizing SIEM Throughput on the Cloud Using Parallelization.

PubMed

Alam, Masoom; Ihsan, Asif; Khan, Muazzam A; Javaid, Qaisar; Khan, Abid; Manzoor, Jawad; Akhundzada, Adnan; Khan, Muhammad Khurram; Farooq, Sajid

2016-01-01

Processing large amounts of data in real time for identifying security issues pose several performance challenges, especially when hardware infrastructure is limited. Managed Security Service Providers (MSSP), mostly hosting their applications on the Cloud, receive events at a very high rate that varies from a few hundred to a couple of thousand events per second (EPS). It is critical to process this data efficiently, so that attacks could be identified quickly and necessary response could be initiated. This paper evaluates the performance of a security framework OSTROM built on the Esper complex event processing (CEP) engine under a parallel and non-parallel computational framework. We explain three architectures under which Esper can be used to process events. We investigated the effect on throughput, memory and CPU usage in each configuration setting. The results indicate that the performance of the engine is limited by the number of events coming in rather than the queries being processed. The architecture where 1/4th of the total events are submitted to each instance and all the queries are processed by all the units shows best results in terms of throughput, memory and CPU usage.

BIOAFFINITY SENSORS BASED ON CONDUCTING POLYMERS: A SHORT REVIEW. (R825323)

EPA Science Inventory

The development of new electrode materials has expanded the range and classes of detectable compounds using electroanalytical methods. Conducting electroactive polymers (CEPs) have been demonstrated to have remarkable sensing applications through their ability to be reversibly ox...

The Two Components of the Evolved Massive Binary LZ Cephei: Testing the Effects of Binarity on Stellar Evolution

NASA Technical Reports Server (NTRS)

Mahy, L.; Martins, F.; Donati, J.-F.; Bouret, J.-C.

2011-01-01

We present an in-dep(h study of the two components of the binary system LZ Cep to constrain the effects of binarity on the evolution of massive stars. Methods. We analyzed a set of high-resolution, high signal-to-noise ratio optical spectra obtained over the orbital period of the system to perform a spectroscopic disentangling and derive an orbital solution. We subsequently determine the stellar properties of each component by means of an analysis with the CMFGEN atmosphere code. Finally, with the derived stellar parameters, we model the Hipparcos photometric light curve using the program NIGHTFALL to obtain the orbit inclination and the stellar masses. Results.LZ Cep is a O9III+ON9.7V binary. It is as a semi-detailed system in which either the primary or the secondary star almost fills up its Roche lobe. The dynamical masses are about 16.0 Stellar Mass (primary) and 6.5 Stellar Mass (secondary). The latter is lower than the typical mass of late-type O stars. The secondary component is chemically more evolved than the primary (which barely shows any sign of CNO processing), with strong helium and nitrogen enhancements as well as carbon and oxygen depletions. These properties (surface abundances and mass) are typical of Wolf-Rayet stars, although the spectral type is ON9.7V. The luminosity of the secondary is consistent with that of core He-burning objects. The preferred, tentative evolutionary scenario to explain abe observed properties involves mass transfer from the secondary - which was initially more massive- towards the primary. The secondary is now almost a core He-burning object, probably with only a thin envelope of H-rich and CNO processed material. A very inefficient mass transfer is necessary to explain the chemical appearance of the primary. Alternative scenarios are discussed but they are affected by greater uncertainties.

The two components of the evolved massive binary LZ Cephei. Testing the effects of binarity on stellar evolution

NASA Astrophysics Data System (ADS)

Mahy, L.; Martins, F.; Machado, C.; Donati, J.-F.; Bouret, J.-C.

2011-09-01

Aims: We present an in-depth study of the two components of the binary system LZ Cep to constrain the effects of binarity on the evolution of massive stars. Methods: We analyzed a set of high-resolution, high signal-to-noise ratio optical spectra obtained over the orbital period of the system to perform a spectroscopic disentangling and derive an orbital solution. We subsequently determine the stellar properties of each component by means of an analysis with the CMFGEN atmosphere code. Finally, with the derived stellar parameters, we model the Hipparcos photometric light curve using the program NIGHTFALL to obtain the orbit inclination and the stellar masses. Results: LZ Cep is a O 9III+ON 9.7V binary. It is as a semi-detached system in which either the primary or the secondary star almost fills up its Roche lobe. The dynamical masses are about 16.0 M⊙ (primary) and 6.5 M⊙ (secondary). The latter is lower than the typical mass of late-type O stars. The secondary component is chemically more evolved than the primary (which barely shows any sign of CNO processing), with strong helium and nitrogen enhancements as well as carbon and oxygen depletions. These properties (surface abundances and mass) are typical of Wolf-Rayet stars, although the spectral type is ON 9.7V. The luminosity of the secondary is consistent with that of core He-burning objects. The preferred, tentative evolutionary scenario to explain the observed properties involves mass transfer from the secondary - which was initially more massive- towards the primary. The secondary is now almost a core He-burning object, probably with only a thin envelope of H-rich and CNO processed material. A very inefficient mass transfer is necessary to explain the chemical appearance of the primary. Alternative scenarios are discussed but they are affected by greater uncertainties.

Herbig Haro-Emission in zwei bipolaren Reflexionsnebeln

NASA Astrophysics Data System (ADS)

Staude, H. J.; Neckel, Th.; Sarcander, M.; Birkle, K.

Der mit PV Cep assoziierte Reflexionsnebel hat sich auf CCD-Aufnahmen als bipolar erwiesen. Die Spektroskopie dieses Nebels sowie des bipolaren Boomerang-Nebels zeigt niedrig angeregte Herbig-Haro-Emission und macht die Anwesenheit kollimierter Hochgeschwindigkeitsflüsse entlang der Polachsen beider Objekte wahrscheinlich.

LUXEMBOURG INCOME STUDY (LIS)

EPA Science Inventory

The LIS database is a collection of household income surveys. The LIS project began in 1983 under the joint sponsorship of the government of the Grand Duchy of Luxembourg and the Center for Population, Poverty and Policy Studies (CEPS). The project is mainly funded by the nationa...

Comprehensive Education Portfolio with a Career Focus

ERIC Educational Resources Information Center

Kruger, Evonne J.; Holtzman, Diane M.; Dagavarian, Debra A.

2013-01-01

There are many types of student portfolios used within academia: the prior learning portfolio, credentialing portfolio, developmental portfolio, capstone portfolio, individual course portfolio, and the comprehensive education portfolio. The comprehensive education portfolio (CEP), as used by the authors, is a student portfolio, developed over…

Central exclusive production at RHIC

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

Adamczyk, Leszek; Guryn, Włodek; Turnau, Jacek

The present status and future plans of the physics program of Central Exclusive Production (CEP) at RHIC are described. The measurements are based on the detection of the forward protons from the Double Pomeron Exchange (DPE) process in the Roman Pot system and of the recoil system of charged particles from the DPE process measured in the STAR experiment’s Time Projection Chamber (TPC). The data described here were taken using polarized proton-proton collisions at ps = 200 GeV. The preliminary spectra of two pion and four pion invariant mass reconstructed by STAR TPC in central region of pseudo-rapidity | |more » < 1, are presented. Near future plans to take data with the current system at center-of-mass energy ps = 200 GeV and plans to upgrade the forward proton tagging sys- tem are presented. Also a possible addition of the Roman Pots to the sPHENIX detector is discussed.« less

The VMC Survey - XIII. Type II Cepheids in the Large Magellanic Cloud

NASA Astrophysics Data System (ADS)

Ripepi, V.; Moretti, M. I.; Marconi, M.; Clementini, G.; Cioni, M.-R. L.; de Grijs, R.; Emerson, J. P.; Groenewegen, M. A. T.; Ivanov, V. D.; Muraveva, T.; Piatti, A. E.; Subramanian, S.

2015-01-01

The VISTA (Visible and Infrared Survey Telescope for Astronomy) survey of the Magellanic Clouds System (VMC) is collecting deep Ks-band time-series photometry of the pulsating variable stars hosted in the system formed by the two Magellanic Clouds and the Bridge connecting them. In this paper, we have analysed a sample of 130 Large Magellanic Cloud (LMC) Type II Cepheids (T2CEPs) found in tiles with complete or near-complete VMC observations for which identification and optical magnitudes were obtained from the OGLE III (Optical Gravitational Lensing Experiment) survey. We present J and Ks light curves for all 130 pulsators, including 41 BL Her, 62 W Vir (12 pW Vir) and 27 RV Tau variables. We complement our near-infrared photometry with the V magnitudes from the OGLE III survey, allowing us to build a variety of period-luminosity (PL), period-luminosity-colour (PLC) and period-Wesenheit (PW) relationships, including any combination of the V, J, Ks filters and valid for BL Her and W Vir classes. These relationships were calibrated in terms of the LMC distance modulus, while an independent absolute calibration of the PL(Ks) and the PW(Ks, V) was derived on the basis of distances obtained from Hubble Space Telescope parallaxes and Baade-Wesselink technique. When applied to the LMC and to the Galactic globular clusters hosting T2CEPs, these relations seem to show that (1) the two Population II standard candles RR Lyrae and T2CEPs give results in excellent agreement with each other; (2) there is a discrepancy of ˜0.1 mag between Population II standard candles and classical Cepheids when the distances are gauged in a similar way for all the quoted pulsators. However, given the uncertainties, this discrepancy is within the formal 1σ uncertainties.

Cascade Error Projection: A Learning Algorithm for Hardware Implementation

NASA Technical Reports Server (NTRS)

Duong, Tuan A.; Daud, Taher

1996-01-01

In this paper, we workout a detailed mathematical analysis for a new learning algorithm termed Cascade Error Projection (CEP) and a general learning frame work. This frame work can be used to obtain the cascade correlation learning algorithm by choosing a particular set of parameters. Furthermore, CEP learning algorithm is operated only on one layer, whereas the other set of weights can be calculated deterministically. In association with the dynamical stepsize change concept to convert the weight update from infinite space into a finite space, the relation between the current stepsize and the previous energy level is also given and the estimation procedure for optimal stepsize is used for validation of our proposed technique. The weight values of zero are used for starting the learning for every layer, and a single hidden unit is applied instead of using a pool of candidate hidden units similar to cascade correlation scheme. Therefore, simplicity in hardware implementation is also obtained. Furthermore, this analysis allows us to select from other methods (such as the conjugate gradient descent or the Newton's second order) one of which will be a good candidate for the learning technique. The choice of learning technique depends on the constraints of the problem (e.g., speed, performance, and hardware implementation); one technique may be more suitable than others. Moreover, for a discrete weight space, the theoretical analysis presents the capability of learning with limited weight quantization. Finally, 5- to 8-bit parity and chaotic time series prediction problems are investigated; the simulation results demonstrate that 4-bit or more weight quantization is sufficient for learning neural network using CEP. In addition, it is demonstrated that this technique is able to compensate for less bit weight resolution by incorporating additional hidden units. However, generation result may suffer somewhat with lower bit weight quantization.

Targets Fishing and Identification of Calenduloside E as Hsp90AB1: Design, Synthesis, and Evaluation of Clickable Activity-Based Probe

PubMed Central

Wang, Shan; Tian, Yu; Zhang, Jing-Yi; Xu, Hui-Bo; Zhou, Ping; Wang, Min; Lu, Sen-Bao; Luo, Yun; Wang, Min; Sun, Gui-Bo; Xu, Xu-Dong; Sun, Xiao-Bo

2018-01-01

Calenduloside E (CE), a natural triterpenoid compound isolated from Aralia elata, can protect against ox-LDL-induced human umbilical vein endothelial cell (HUVEC) injury in our previous reports. However, the exact targets and mechanisms of CE remain elusive. For the sake of resolving this question, we designed and synthesized a clickable activity-based probe (CE-P), which could be utilized to fish the functional targets in HUVECs using a gel-based strategy. Based on the previous studies of the structure-activity relationship (SAR), we introduced an alkyne moiety at the C-28 carboxylic group of CE, which kept the protective and anti-apoptosis activity. Via proteomic approach, one of the potential proteins bound to CE-P was identified as Hsp90AB1, and further verification was performed by pure recombinant Hsp90AB1 and competitive assay. These results demonstrated that CE could bind to Hsp90AB1. We also found that CE could reverse the Hsp90AB1 decrease after ox-LDL treatment. To make our results more convincing, we performed SPR analysis and the affinity kinetic assay showed that CE/CE-P could bind to Hsp90AB1 in a dose-dependent manner. Taken together, our research showed CE could probably bind to Hsp90AB1 to protect the cell injury, which might provide the basis for the further exploration of its cardiovascular protective mechanisms. For the sake of resolving this question, we designed and synthesized a clickable activity-based probe (CE-P), which could be utilized to fish the functional targets in HUVECs using a gel-based strategy. PMID:29875664

Structure‐function relationships at the human spinal disc‐vertebra interface

PubMed Central

Berg‐Johansen, Britta; Fields, Aaron J.; Liebenberg, Ellen C.; Li, Alfred

2017-01-01

ABSTRACT Damage at the intervertebral disc‐vertebra interface associates with back pain and disc herniation. However, the structural and biomechanical properties of the disc‐vertebra interface remain underexplored. We sought to measure mechanical properties and failure mechanisms, quantify architectural features, and assess structure‐function relationships at this vulnerable location. Vertebra‐disc‐vertebra specimens from human cadaver thoracic spines were scanned with micro‐computed tomography (μCT), surface speckle‐coated, and loaded to failure in uniaxial tension. Digital image correlation (DIC) was used to calculate local surface strains. Failure surfaces were scanned using scanning electron microscopy (SEM), and adjacent sagittal slices were analyzed with histology and SEM. Seventy‐one percent of specimens failed initially at the cartilage endplate‐bone interface of the inner annulus region. Histology and SEM both indicated a lack of structural integration between the cartilage endplate (CEP) and bone. The interface failure strength was increased in samples with higher trabecular bone volume fraction in the vertebral endplates. Furthermore, failure strength decreased with degeneration, and in discs with thicker CEPs. Our findings indicate that poor structural connectivity between the CEP and vertebra may explain the structural weakness at this region, and provide insight into structural features that may contribute to risk for disc‐vertebra interface injury. The disc‐vertebra interface is the site of failure in the majority of herniation injuries. Here we show new structure‐function relationships at this interface that may motivate the development of diagnostics, prevention strategies, and treatments to improve the prognosis for many low back pain patients with disc‐vertebra interface injuries. © 2017 The Authors. Journal of Orthopaedic Research® Published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 36:192–201, 2018. PMID:28590060

Pressure profiles of sport compression stockings.

PubMed

Reich-Schupke, Stefanie; Surhoff, Stefan; Stücker, Markus

2016-05-01

While sport compression stockings (SCS) have become increasingly popular, there is no regulatory norm as exists for medical compression stockings (MCS). The objective of this pilot study was to compare five SCS with respect to their pressure profiles ex vivo and in vivo, and in relation to German standards for MCS (RAL norm). In vivo (10 competitive athletes; standardized procedure using the Kikuhime pressure monitor) and ex vivo (tested at the Hohenstein Institute) pressure profiles were tested for the following products: CEP Running Progressive Socks, Falke Running Energizing, Sigvaris Performance, X-Socks Speed Metal Energizer, and 2XU Compression Race Socks. Ex vivo ankle pressures of CEP (25.6 mmHg) and 2XU (23.2 mmHg) corresponded to class 2 MCS; that of Sigvaris (20.8 mmHg), to class 1 MCS. The remaining SCS achieved lower pressure values. The pressure gradients showed marked differences, and did not meet MCS standards. Average in vivo pressures were higher for 2XU, CEP, and Sigvaris than for Falke and X-Socks. However, in vivo values for all SCS were below those of class 1 MCS. None of the SCS showed the decreasing pressure gradient (from distal to proximal) required for MCS. In vivo and ex vivo pressure profiles of all SCS examined showed marked heterogeneity, and did not meet MCS standards. Consequently, the clinical and practical effects of SCS cannot be compared, either. It would therefore be desirable to establish a classification that allows for the categorization and comparison of various SCS as well as their selection based on individual preferences and needs (high vs. low pressure, progressive vs. degressive profile). © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

Correlation between SiO v = 3 J = 1 → 0 maser excitation and the light curve of a long-period variable star

NASA Astrophysics Data System (ADS)

Oyadomari, Miyako; Imai, Hiroshi; Nagayama, Takumi; Oyama, Tomoaki; Matsumoto, Naoko; Nakashima, Jun-ichi; Cho, Se-Hyung

2018-06-01

In order to understand the excitation mechanisms of silicon monoxide (SiO) masers around long-period variables (LPVs), we have investigated distributions of the SiO v = 2 and v = 3 J = 1 → 0 masers around 12 LPVs by very long baseline interferometry (VLBI) observations with the VLBI Exploration of Radio Astrometry (VERA) and the Nobeyama 45 m telescopes. VLBI fringes of the v = 3 maser emission were detected for five LPVs. The composite maps of the v = 2 and v = 3 masers were made for T Cep, W Hya, WX Psc, and R Leo using the spectral line phase-referencing technique. The v = 2 maser spots were distributed in a ring-like form around the central stars, while it is difficult to recognize any specific morphology in the v = 3 maser distributions due to the small number of v = 3 spots detected. However in T Cep, we find that the distribution of the v = 3 maser spots correlates well with the v = 2 masers within a few milliarcseconds (0.2-0.3 au) in position and 1 km s-1 in line-of-sight velocity at the light curve phase of ϕ = 0.28 (ϕ = 0.0 and 1.0 correspond to the visible light maxima). This correlation implies that the mechanism of line-overlapping between the mid-infrared lines of H2O and SiO molecules works in T Cep at ϕ = 0.28. We discuss the possibility that the line-overlapping may work at the limited duration from the maximum to the minimum of the stellar light curve.

Prognostic Value of CD109+ Circulating Endothelial Cells in Recurrent Glioblastomas Treated with Bevacizumab and Irinotecan

PubMed Central

Cuppini, Lucia; Calleri, Angelica; Bruzzone, Maria Grazia; Prodi, Elena; Anghileri, Elena; Pellegatta, Serena; Mancuso, Patrizia; Porrati, Paola; Di Stefano, Anna Luisa; Ceroni, Mauro; Bertolini, Francesco; Finocchiaro, Gaetano; Eoli, Marica

2013-01-01

Background Recent data suggest that circulating endothelial and progenitor cells (CECs and CEPs, respectively) may have predictive potential in cancer patients treated with bevacizumab, the antibody recognizing vascular endothelial growth factor (VEGF). Here we report on CECs and CEPs investigated in 68 patients affected by recurrent glioblastoma (rGBM) treated with bevacizumab and irinotecan and two Independent Datasets of rGBM patients respectively treated with bevacizumab alone (n=32, independent dataset A: IDA) and classical antiblastic chemotherapy (n=14, independent dataset B: IDB). Methods rGBM patients with KPS ≥50 were treated until progression, as defined by MRI with RANO criteria. CECs expressing CD109, a marker of tumor endothelial cells, as well as other CEC and CEP subtypes, were investigated by six-color flow cytometry. Results A baseline count of CD109+ CEC higher than 41.1/ml (1st quartile) was associated with increased progression free survival (PFS; 20 versus 9 weeks, P=0.008) and overall survival (OS; 32 versus 23 weeks, P=0.03). Longer PFS (25 versus 8 weeks, P=0.02) and OS (27 versus 17 weeks, P=0.03) were also confirmed in IDA with CD109+ CECs higher than 41.1/ml but not in IDB. Patients treated with bevacizumab with or without irinotecan that were free from MRI progression after two months of treatment had significant decrease of CD109+ CECs: median PFS was 19 weeks; median OS 29 weeks. The presence of two non-contiguous lesions (distant disease) at baseline was an independent predictor of shorter PFS and OS (P<0.001). Conclusions Data encourage further studies on the predictive potential of CD109+ CECs in GBM patients treated with bevacizumab. PMID:24069296

SOFIA EXES Observations of Herschel’s Garnet Star and the two α Red Supergiants

NASA Astrophysics Data System (ADS)

Harper, Graham M.; DeWitt, Curtis N.; Richter, Matthew; Guinan, Edward F.; Montiel, Edward; Bennett, Philip D.; EXES Instrument Team

2018-06-01

We report EXES Cycle 4 and 5 observations of M supergiants, made at high spectral resolution (R > 50,000), and obtained from NASA-DLR SOFIA.Emission profiles from Herschel’s Garnet Star (μ Cephei: M2 Ia) show distinct structure and asymmetry in the [S I] 25.25 micron and [Fe II] 25.99 micron lines. These profiles are unlike the remarkably symmetric [Fe II] profile observed from Betelgeuse (α Orionis: M2 Iab) at R=65,000. These diagnostics both arise from upper energy levels with Eup ≈ 550 K and they probe the inner circumstellar envelope. The flux ratios of [S I]/[Fe II] are very different for μ Cep, α Ori, and Antares (α Scorpii: M1.5 Iab), suggesting that the intrinsic far ultraviolet photoionization field of μ Cep is weaker than that of α Ori, and that α Sco’s hot companion may contribute to ionizing neutral sulfur. We find that the mid-IR emission from μ Cep is centered close to the optical radial velocity of V(LSR)=33.0 km s-1 [V(Helio)=19.3 km s-1] reported in the General Catalogue of Stellar Radial Velocities (Wilson 1953), and which is substantially different to that inferred from low-J CO radio emission, i.e. V(LSR)=25 km s-1. It appears that Herschel's Garnet Star has undergone discrete events of asymmetric mass loss.Acknowledgements: This work has made extensive use of the SAO/NASA ADS and VizieR search tools, and the ASTRAL and SIMBAD databases. Financial support has been provided by NASA SOFIA Cycle 4 and 5 grants SOF 04-0136 and 05-0073 issued by USRA.

The Practical Integration of Action Research into Building Climate Literacy and Partnership with Key Influentials

NASA Astrophysics Data System (ADS)

Estrada, M.

2015-12-01

Climate Education Partners (CEP) has been using an action research approach to build climate literacy and partnership with key influential (KI) leaders in the San Diego community. After identifying 6 key sectors that either (a) could reduce green house gas emissions and adapt to impacts, or (b) would be highly vulnerable to the impacts of climate change, we conducted 89 interviews with KIs from the San Diego region -- including elected officials, academics, laborers, and representatives from local businesses, non-profits, ethnic and cultural communities, faith-based groups, and special interest groups -- to assess their science knowledge and opinions about climate change and the impacts of climate change. Other questions asked were about KIs' personal efficacy, identity, values and engagement in pro-environmental behaviors related to climate change. The results of the interviews contributed to CEP's action research approach in two ways: 1) it provided critical data regarding which leaders wanted further engagement with CEP and what that engagement should entail (e.g., being a connector to other leaders, a spokesperson, or a participant in future educational activities), and 2) it provided key information about the extent to which "knowledge deficit" is related to use of climate change knowledge to inform engagement in mitigation and adaptive behaviors. Practically, the results were used to create a database that is being used to inform the contact and education of KIs. We were able to show, consistent with previous research and identity theory, that liberal leaders were more likely than conservatives to believe in, feel concern for, and be knowledgeable about climate change. However, engagement in mitigation behaviors- specifically making decisions that would reduce electricity, gas, or water use- were similar for both groups. These results are being used to create resources and direct climate education activities going forward.

Analytic theory of high-order-harmonic generation by an intense few-cycle laser pulse

NASA Astrophysics Data System (ADS)

Frolov, M. V.; Manakov, N. L.; Popov, A. M.; Tikhonova, O. V.; Volkova, E. A.; Silaev, A. A.; Vvedenskii, N. V.; Starace, Anthony F.

2012-03-01

We present a theoretical model for describing the interaction of an electron, weakly bound in a short-range potential, with an intense, few-cycle laser pulse. General definitions for the differential probability of above-threshold ionization and for the yield of high-order-harmonic generation (HHG) are presented. For HHG we then derive detailed analytic expressions for the spectral density of generated radiation in terms of the key laser parameters, including the number N of optical cycles in the pulse and the carrier-envelope phase (CEP). In particular, in the tunneling approximation, we provide detailed derivations of the closed-form formulas presented briefly by M. V. Frolov [Phys. Rev. APLRAAN1050-294710.1103/PhysRevA.83.021405 83, 021405(R) (2011)], which were used to describe key features of HHG by both H and Xe atom targets in an intense, few-cycle laser pulse. We then provide a complete analysis of the dependence of the HHG spectrum on both N and the CEP φ of an N-cycle laser pulse. Most importantly, we show analytically that the structure of the HHG spectrum stems from interference between electron wave packets originating from electron ionization from neighboring half-cycles near the peak of the intensity envelope of the few-cycle laser pulse. Such interference is shown to be very sensitive to the CEP. The usual HHG spectrum for a monochromatic driving laser field (comprising harmonic peaks at odd multiples of the carrier frequency and spaced by twice the carrier frequency) is shown analytically to occur only in the limit of very large N, and begins to form, as N increases, in the energy region beyond the HHG plateau cutoff.

Correlation between SiO v = 3 J = 1 → 0 maser excitation and the light curve of a long-period variable star

NASA Astrophysics Data System (ADS)

Oyadomari, Miyako; Imai, Hiroshi; Nagayama, Takumi; Oyama, Tomoaki; Matsumoto, Naoko; Nakashima, Jun-ichi; Cho, Se-Hyung

2018-03-01

In order to understand the excitation mechanisms of silicon monoxide (SiO) masers around long-period variables (LPVs), we have investigated distributions of the SiO v = 2 and v = 3 J = 1 → 0 masers around 12 LPVs by very long baseline interferometry (VLBI) observations with the VLBI Exploration of Radio Astrometry (VERA) and the Nobeyama 45 m telescopes. VLBI fringes of the v = 3 maser emission were detected for five LPVs. The composite maps of the v = 2 and v = 3 masers were made for T Cep, W Hya, WX Psc, and R Leo using the spectral line phase-referencing technique. The v = 2 maser spots were distributed in a ring-like form around the central stars, while it is difficult to recognize any specific morphology in the v = 3 maser distributions due to the small number of v = 3 spots detected. However in T Cep, we find that the distribution of the v = 3 maser spots correlates well with the v = 2 masers within a few milliarcseconds (0.2-0.3 au) in position and 1 km s-1 in line-of-sight velocity at the light curve phase of ϕ = 0.28 (ϕ = 0.0 and 1.0 correspond to the visible light maxima). This correlation implies that the mechanism of line-overlapping between the mid-infrared lines of H2O and SiO molecules works in T Cep at ϕ = 0.28. We discuss the possibility that the line-overlapping may work at the limited duration from the maximum to the minimum of the stellar light curve.

Assessment of the NPOESS/VIIRS Nighttime Infrared Cloud Optical Properties Algorithms

NASA Astrophysics Data System (ADS)

Wong, E.; Ou, S. C.

2008-12-01

In this paper we will describe two NPOESS VIIRS IR algorithms used to retrieve microphysical properties for water and ice clouds during nighttime conditions. Both algorithms employ four VIIRS IR channels: M12 (3.7 μm), M14 (8.55 μm), M15 (10.7 μm) and M16 (12 μm). The physical basis for the two algorithms is similar in that while the Cloud Top Temperature (CTT) is derived from M14 and M16 for ice clouds the Cloud Optical Thickness (COT) and Cloud Effective Particle Size (CEPS) are derived from M12 and M15. The two algorithms depart in the different radiative transfer parameterization equations used for ice and water clouds. Both the VIIRS nighttime IR algorithms and the CERES split-window method employ the 3.7 μm and 10.7 μm bands for cloud optical properties retrievals, apparently based on similar physical principles but with different implementations. It is reasonable to expect that the VIIRS and CERES IR algorithms produce comparable performance and similar limitations. To demonstrate the VIIRS nighttime IR algorithm performance, we will select a number of test cases using NASA MODIS L1b radiance products as proxy input data for VIIRS. The VIIRS retrieved COT and CEPS will then be compared to cloud products available from the MODIS, NASA CALIPSO, CloudSat and CERES sensors. For the MODIS product, the nighttime cloud emissivity will serve as an indirect comparison to VIIRS COT. For the CALIPSO and CloudSat products, the layered COT will be used for direct comparison. Finally, the CERES products will provide direct comparison with COT as well as CEPS. This study can only provide a qualitative assessment of the VIIRS IR algorithms due to the large uncertainties in these cloud products.

Copy number variation in CEP57L1 predisposes to congenital absence of bilateral ACL and PCL ligaments.

PubMed

Liu, Yichuan; Li, Yun; March, Michael E; Nguyen, Kenny; Kenny, Nguyen; Xu, Kexiang; Wang, Fengxiang; Guo, Yiran; Keating, Brendan; Glessner, Joseph; Li, Jiankang; Ganley, Theodore J; Zhang, Jianguo; Deardorff, Matthew A; Xu, Xun; Hakonarson, Hakon

2015-11-11

Absence of the anterior (ACL) or posterior cruciate ligament (PCL) are rare congenital malformations that result in knee joint instability, with a prevalence of 1.7 per 100,000 live births and can be associated with other lower-limb abnormalities such as ACL agnesia and absence of the menisci of the knee. While a few cases of absence of ACL/PCL are reported in the literature, a number of large familial case series of related conditions such as ACL agnesia suggest a potential underlying monogenic etiology. We performed whole exome sequencing of a family with two individuals affected by ACL/PCL. We identified copy number variation (CNV) deletion impacting the exon sequences of CEP57L1, present in the affected mother and her affected daughter based on the exome sequencing data. The deletion was validated using quantitative PCR (qPCR), and the gene was confirmed to be expressed in ACL ligament tissue. Interestingly, we detected reduced expression of CEP57L1 in Epstein-Barr virus (EBV) cells from the two patients in comparison with healthy controls. Evaluation of 3D protein structure showed that the helix-binding sites of the protein remain intact with the deletion, but other functional binding sites related to microtubule attachment are missing. The specificity of the CNV deletion was confirmed by showing that it was absent in ~700 exome sequencing samples as well as in the database of genomic variations (DGV), a database containing large numbers of annotated CNVs from previous scientific reports. We identified a novel CNV deletion that was inherited through an autosomal dominant transmission from an affected mother to her affected daughter, both of whom suffered from the absence of the anterior and posterior cruciate ligaments of the knees.

Variants of CEP68 Gene Are Associated with Acute Urticaria/Angioedema Induced by Multiple Non-Steroidal Anti-Inflammatory Drugs

PubMed Central

Cornejo-García, José Antonio; Flores, Carlos; Plaza-Serón, María C.; Acosta-Herrera, Marialbert; Blanca-López, Natalia; Doña, Inmaculada; Torres, María J.; Mayorga, Cristobalina; Guéant-Rodríguez, Rosa M.; Ayuso, Pedro; Fernández, Javier; Laguna, José J.; Agúndez, José A. G.; García-Martín, Elena; Guéant, Jean-Louis; Canto, Gabriela; Blanca, Miguel

2014-01-01

Non-steroidal anti-inflammatory drugs (NSAIDs) are the most consumed drugs worldwide because of their efficacy and utility in the treatment of pain and inflammatory diseases. However, they are also responsible for an important number of adverse effects including hypersensitivity reactions. The most important group of these reactions is triggered by non-immunological, pharmacological mechanisms catalogued under the denomination of cross-intolerance (CRI), with acute urticaria/angioedema induced by multiple NSAIDs (MNSAID-UA) the most frequently associated clinical entity. A recent genome-wide association study identified the gene encoding the centrosomal protein of 68 KDa (CEP68) as the major locus associated with aspirin intolerance susceptibility in asthmatics. In this study, we aimed to assess the role of this locus in susceptibility to CRI to NSAIDs by examining 53 common gene variants in a total of 635 patients that were classified as MNSAID-UA (n = 399), airway exacerbations (n = 110) or blended pattern (n = 126), and 425 controls. We found in the MNSAID-UA group a number of variants (17) associated (lowest p-value = 1.13×10−6), including the non-synonymous Gly74Ser variant (rs7572857) previously associated with aspirin intolerance susceptibility in asthmatics. Although not being significant in the context of multiple testing, eight of these variants were also associated with exacerbated respiratory disease or blended reactions. Our results suggest that CEP68 gene variants may play an important role in MNSAID-UA susceptibility and, despite the different regulatory mechanisms involved depending on the specific affected organ, in the development of hypersensitivity reactions to NSAIDs. PMID:24618698

First Progress Report--Victorian Country Education Project.

ERIC Educational Resources Information Center

Victoria Education Dept. (Australia).

The Victorian Country Education Project (CEP), a pilot project searching for new ways of bringing beneficial educational experiences to disadvantaged rural areas, successfully achieved its aims of establishing community-based programs involving varied groups and people in developing solutions to local educational problems. A central Planning…

Enterprise Measures. Evaluation Report.

ERIC Educational Resources Information Center

European Social Fund, Dublin (Ireland).

In Ireland, four government programs have traditionally been available to help individuals wishing to establish an enterprise: (1) Enterprise Training; (2) local training initiatives (LTI); (3) the Enterprise Scheme; and (4) the Community Enterprise Programme (CEP). In 1988, the four enterprise measures were combined to form the Training and…

76 FR 52220 - Airworthiness Directives; Embraer-Empresa Brasileira de Aeronautica S.A. (EMBRAER) Model EMB-500...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-22

... Support, Av. Brig. Farina Lima, 2170, Sao Jose dos Campos--SP, CEP: 12227-901--PO Box: 36/2, BRASIL..., BRASIL; telephone: ++55 12 3927-5383; fax: ++55 12 3927-2619; e-mail: embraer.com .br">phenom.reliability...

76 FR 26959 - Airworthiness Directives; Embraer-Embraer-Empresa Brasileira de Aeronautica S.A. (EMBRAER) Model...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-10

...-- SP, CEP: 12227-901--PO Box: 36/2, Brasil; telephone: ++55 12 3927-5383; fax: ++55 12 3927-2619; E...: 36/2, Brasil; telephone: ++55 12 3927-5383; fax: ++55 12 3927-2619; E- mail: phenom.reliability...

General Achievement Trends: Alabama

ERIC Educational Resources Information Center

Center on Education Policy, 2009

2009-01-01

This general achievement trends profile includes information that the Center on Education Policy (CEP) and the Human Resources Research Organization (HumRRO) obtained from states from fall 2008 through April 2009. Included herein are: (1) Bullet points summarizing key findings about achievement trends in that state at three performance…

In-Situ NDE Characterization of Kevlar and Carbon Composite Micromechanics for Improved COPV Health Monitoring

NASA Technical Reports Server (NTRS)

Waller, Jess M.; Saulsberry, Regor L.

2009-01-01

This project is a subtask of a multi-center project to advance the state-of-the-art by developing NDE techniques that are capable of evaluating stress rupture (SR) degradation in Kevlar/epoxy (K/Ep) composite overwrapped pressure vessels (COPVs), and damage progression in carbon/epoxy (C/Ep) COPVs. In this subtask, acoustic emission (AE) data acquired during intermittent load hold tensile testing of K/Ep and C/Ep composite tow materials-of-construction used in COPV fabrication were analyzed to monitor progressive damage during the approach to tensile failure. Insight into the progressive damage of composite tow was gained by monitoring AE event rate, energy, source location, and frequency. Source location based on arrival time data was used to discern between significant AE attributable to microstructural damage and spurious AE attributable to background and grip noise. One of the significant findings was the observation of increasing violation of the Kaiser effect (Felicity ratio < 1.0) with damage accumulation.

Optimization of infrared two-color multicycle field synthesis for intense-isolated-attosecond-pulse generation

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

Lan Pengfei; Takahashi, Eiji J.; Midorikawa, Katsumi

2010-11-15

We present the optimization of the two-color synthesis method for generating an intense isolated attosecond pulse (IAP) in the multicycle regime. By mixing an infrared assistant pulse with a Ti:sapphire main pulse, we show that an IAP can be produced using a multicycle two-color pulse with a duration longer than 30 fs. We also discuss the influence of the carrier-envelope phase (CEP) and the relative intensity on the generation of IAPs. By optimizing the wavelength of the assistant field, IAP generation becomes insensitive to the CEP slip. Therefore, the optimized two-color method enables us to relax the requirements of pulsemore » duration and easily produce the IAP with a conventional multicycle laser pulse. In addition, it enables us to markedly suppress the ionization of the harmonic medium. This is a major advantage for efficiently generating intense IAPs from a neutral medium by applying the appropriate phase-matching and energy-scaling techniques.« less

Doppler Imaging with FUSE: The Partially Eclipsing Binary VW Cep

NASA Technical Reports Server (NTRS)

Sonneborn, George (Technical Monitor); Brickhouse, Nancy

2003-01-01

This report covers the FUSE Guest Observer program. This project involves the study of emission line profiles for the partially eclipsing, rapidly rotating binary system VW Cep. Active regions on the surface of the star(s) produce observable line shifts as the stars move with respect to the observer. By studying the time-dependence of the line profile changes and centroid shifts, one can determine the location of the activity. FUSE spectra were obtained by the P.I. 27 Sept 2002 and data reduction is in progress. Since we are interested in line profile analysis, we are now investigating the wavelength scale calibration in some detail. We have also obtained and are analyzing Chandra data in order to compare the X-ray velocities with the FUV velocities. A complementary project comparing X-ray and Far UltraViolet (FUV) emission for the similar system 44i Boo is also underway. Postdoctoral fellow Ronnie Hoogerwerf has joined the investigation team and will perform the data analysis, once the calibration is optimized.

Single-shot velocity-map imaging of attosecond light-field control at kilohertz rate.

PubMed

Süssmann, F; Zherebtsov, S; Plenge, J; Johnson, Nora G; Kübel, M; Sayler, A M; Mondes, V; Graf, C; Rühl, E; Paulus, G G; Schmischke, D; Swrschek, P; Kling, M F

2011-09-01

High-speed, single-shot velocity-map imaging (VMI) is combined with carrier-envelope phase (CEP) tagging by a single-shot stereographic above-threshold ionization (ATI) phase-meter. The experimental setup provides a versatile tool for angle-resolved studies of the attosecond control of electrons in atoms, molecules, and nanostructures. Single-shot VMI at kHz repetition rate is realized with a highly sensitive megapixel complementary metal-oxide semiconductor camera omitting the need for additional image intensifiers. The developed camera software allows for efficient background suppression and the storage of up to 1024 events for each image in real time. The approach is demonstrated by measuring the CEP-dependence of the electron emission from ATI of Xe in strong (≈10(13) W/cm(2)) near single-cycle (4 fs) laser fields. Efficient background signal suppression with the system is illustrated for the electron emission from SiO(2) nanospheres. © 2011 American Institute of Physics

Scaling functions for the Inverse Compressibility near the QCD critical point

NASA Astrophysics Data System (ADS)

Lacey, Roy

2017-09-01

The QCD phase diagram can be mapped out by studying fluctuations and their response to changes in the temperature and baryon chemical potential. Theoretical studies indicate that the cumulant ratios Cn /Cm used to characterize the fluctuation of conserved charges, provide a valuable probe of deconfinement and chiral dynamics, as well as for identifying the position of the critical endpoint (CEP) in the QCD phase diagram. The ratio C1 /C2 , which is linked to the inverse compressibility, vanishes at the CEP due to the divergence of the net quark number fluctuations at the critical point belonging to the Z(2) universality class. Therefore, it's associated scaling function can give insight on the location of the critical end point, as well as the critical exponents required to assign its static universality class. Scaling functions for the ratio C1 /C2 , obtained from net-proton multiplicity distributions for a broad range of collision centralities in Au+Au (√{sNN} = 7.7 - 200 GeV) collisions will be presented and discussed.

STAR Online Framework: from Metadata Collection to Event Analysis and System Control

NASA Astrophysics Data System (ADS)

Arkhipkin, D.; Lauret, J.

2015-05-01

In preparation for the new era of RHIC running (RHIC-II upgrades and possibly, the eRHIC era), the STAR experiment is expanding its modular Message Interface and Reliable Architecture framework (MIRA). MIRA allowed STAR to integrate meta-data collection, monitoring, and online QA components in a very agile and efficient manner using a messaging infrastructure approach. In this paper, we briefly summarize our past achievements, provide an overview of the recent development activities focused on messaging patterns and describe our experience with the complex event processor (CEP) recently integrated into the MIRA framework. CEP was used in the recent RHIC Run 14, which provided practical use cases. Finally, we present our requirements and expectations for the planned expansion of our systems, which will allow our framework to acquire features typically associated with Detector Control Systems. Special attention is given to aspects related to latency, scalability and interoperability within heterogeneous set of services, various data and meta-data acquisition components coexisting in STAR online domain.

Sub-50-as isolated extreme ultraviolet continua generated by 1.6-cycle near-infrared pulse combined with double optical gating scheme

NASA Astrophysics Data System (ADS)

Oguri, Katsuya; Mashiko, Hiroki; Ogawa, Tatsuya; Hanada, Yasutaka; Nakano, Hidetoshi; Gotoh, Hideki

2018-04-01

We demonstrate the generation of ultrabroad bandwidth attosecond continua extending to sub-50-as duration in the extreme ultraviolet (EUV) region based on a 1.6-cycle Ti:sapphire laser pulse. The combination of the amplitude gating scheme with a sub-two-cycle driver pulse and the double optical gating scheme achieves the continuum generation with a bandwidth of 70 eV at the full width at half maximum near the peak photon energy of 140 eV, which supports a Fourier-transform-limited pulse duration as short as 32 as. The carrier-envelope-phase (CEP) dependence of the attosecond continua shows a single-peak structure originating from the half-cycle cut-off at appropriate CEP values, which strongly indicates the generation of a single burst of an isolated attosecond pulse. Our approach suggests a possibility for isolated sub-50-as pulse generation in the EUV region by compensating for the intrinsic attosecond chirp with a Zr filter.

General Achievement Trends: New Hampshire

ERIC Educational Resources Information Center

Center on Education Policy, 2009

2009-01-01

This general achievement trends profile includes information that the Center on Education Policy (CEP) and the Human Resources Research Organization (HumRRO) obtained from states from fall 2008 through April 2009. Included herein are: (1) Bullet points summarizing key findings about achievement trends in that state at three performance…

Measurement of spectral phase noise in a cryogenically cooled Ti:Sa amplifier (Conference Presentation)

NASA Astrophysics Data System (ADS)

Nagymihaly, Roland S.; Jójárt, Péter; Börzsönyi, Ádám.; Osvay, Károly

2017-05-01

In most of cases the drift of the carrier envelope phase (CEP) of a chirped pulse amplifier (CPA) system is determined only [1], being the relevant parameter at laser-matter interactions. The need of coherent combination of multiple amplifier channels to further increase the peak power of pulses requires interferometric precision [2]. For this purpose, the stability of the group delay of the pulses may become equally important. Further development of amplifier systems requires the investigation of phase noise contributions of individual subsystems, like amplifier stages. Spectrally resolved interferometry (SRI), which is a completely linear optical method, makes the measurement of spectral phase noise possible of basically any part of a laser system [3]. By utilizing this method, the CEP stability of water-cooled Ti:Sa based amplifiers was investigated just recently, where the effects of seed and pump energy, repetition rate, and the cooling crystal mounts were thoroughly measured [4]. We present a systematic investigation on the noise of the spectral phase, including CEP, of laser pulses amplified in a cryogenically-cooled Ti:Sa amplifier of a CPA chain. The double-pass amplifier was built in the sample arm of a compact Michelson interferometer. The Ti:Sa crystal was cooled below 30 °K. The inherent phase noise was measured for different operation modes, as at various repetition rates, and pump depletion. Noise contributions of the vacuum pumps and the cryogenic refrigerator were found to be 43 and 47 mrad, respectively. We have also identified CEP noise having thermal as well as mechanical origin. Both showed a monotonically decreasing tendency towards higher repetition rates. We found that the widths of the noise distributions are getting broader towards lower repetition rates. Spectral phase noise with and without amplification was measured, and we found no significant difference in the phase noise distributions. The mechanical vibration was also measured in the setup by using an accelerometer synchronously with the optical measurements. The noise spectra of phase and vibration measurements were compared and the sources of individual noise components were identified. References [1] Sebastian Koke et al, Opt. Lett. 33, 2545-2547 (2008). [2] J. Limpert et al, IEEE J. of Sel. Top. in Quant. El. 20, 0901810 (2014). [3] A. Borzsonyi, A.P. Kovacs, K. Osvay, Appl. Sci. 3, 515-544 (2013). [4] A. Borzsonyi, R.S. Nagymihaly, K. Osvay, Las. Phys. Lett. 13, 015301 (2016).

The Secret Lives of Cepheids: Evolutionary Changes and Pulsation-induced Shock Heating in the Prototype Classical Cepheid δ Cep

NASA Astrophysics Data System (ADS)

Engle, Scott G.; Guinan, Edward F.; Harper, Graham M.; Neilson, Hilding R.; Remage Evans, Nancy

2014-10-01

Over the past decade, the Secret Lives of Cepheids (SLiC) program has been carried out at Villanova University to study aspects and behaviors of classical Cepheids that are still not well understood. In this, the first of several planned papers on program Cepheids, we report the current results for δ Cep, the Cepheid prototype. Ongoing photometry has been obtained to search for changes in the pulsation period, light-curve morphology, and amplitude. Combining our photometry with the times of maximum light compilation by Berdnikov et al. returns a small period change of dP/dt ≈-0.1006 ± 0.0002 s yr-1. There is also evidence for a gradual light amplitude increase of ~0.011 mag (V band) and ~0.012 mag (B band) per decade over the last ~50 years. In addition, Hubble Space Telescope (HST) Cosmic Origins Spectrograph (COS) UV spectrophotometry and XMM-Newton X-ray data were carried out to investigate the high-temperature plasmas present above the Cepheid photospheres. In total, from the five visits (eight exposures) with XMM-Newton, δ Cep is found to be a soft X-ray source (L X (0.3-2 keV) ≈4.5-13 × 1028 erg s-1) with peak flux at kT = 0.6-0.9 keV. The X-ray activity is found to vary, possibly in phase with the stellar pulsations. From 2010-2013, nine observations of δ Cep were carried out with HST-COS. The UV emissions are also variable and well phased with the stellar pulsations. Maximum UV line emissions occur near, or slightly before, maximum optical light, varying by as much as 20 times. This variability shows that pulsation-induced shock heating plays a significant role in Cepheid atmospheres, possibly in addition to a quiescent, magnetic heating. The results of this study show Cepheid atmospheres to be rather complex and dynamic. Based on observations made with the NASA/ESA Hubble Space Telescope, obtained at the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., under NASA contract NAS 5-26555. These observations are associated with programs #11726, #12302, and #13019. This work is also based on observations obtained with XMM-Newton, an ESA science mission with instruments and contributions directly funded by ESA Member States and the USA (NASA).

The stream of experience when watching artistic movies. Dynamic aesthetic effects revealed by the Continuous Evaluation Procedure (CEP).

PubMed

Muth, Claudia; Raab, Marius H; Carbon, Claus-Christian

2015-01-01

Research in perception and appreciation is often focused on snapshots, stills of experience. Static approaches allow for multidimensional assessment, but are unable to catch the crucial dynamics of affective and perceptual processes; for instance, aesthetic phenomena such as the "Aesthetic-Aha" (the increase in liking after the sudden detection of Gestalt), effects of expectation, or Berlyne's idea that "disorientation" with a "promise of success" elicits interest. We conducted empirical studies on indeterminate artistic movies depicting the evolution and metamorphosis of Gestalt and investigated (i) the effects of sudden perceptual insights on liking; that is, "Aesthetic Aha"-effects, (ii) the dynamics of interest before moments of insight, and (iii) the dynamics of complexity before and after moments of insight. Via the so-called Continuous Evaluation Procedure (CEP) enabling analogous evaluation in a continuous way, participants assessed the material on two aesthetic dimensions blockwise either in a gallery or a laboratory. The material's inherent dynamics were described via assessments of liking, interest, determinacy, and surprise along with a computational analysis on the variable complexity. We identified moments of insight as peaks in determinacy and surprise. Statistically significant changes in liking and interest demonstrated that: (i) insights increase liking, (ii) interest already increases 1500 ms before such moments of insight, supporting the idea that it is evoked by an expectation of understanding, and (iii) insights occur during increasing complexity. We propose a preliminary model of dynamics in liking and interest with regard to complexity and perceptual insight and discuss descriptions of participants' experiences of insight. Our results point to the importance of systematic analyses of dynamics in art perception and appreciation.

Global Characterization of Protein-Altering Mutations in Prostate Cancer

DTIC Science & Technology

2013-08-01

abnormal signals are marked as horizontal dashed lines on each plot. (A) Average number of AR per nucleus. (B) Average PTEN/CEP10 ratio. doi:10.1371...1060. 20. Hankinson SE, Manson JE, Spiegelman D, Willett WC, Longcope C, et al. (1995) Reproducibility of plasma hormone levels in postmenopausal

A Historical Review of "Contemporary Educational Psychology" from 1995 to 2010

ERIC Educational Resources Information Center

Mitchell, Anita Witt; McConnell, John Robert, III

2012-01-01

The major themes and trends represented by the articles published in "Contemporary Educational Psychology" (CEP) from 1995 to 2010 are reviewed in this paper. Included are the major topics, theoretical perspectives, participant characteristics, research methods and statistics used, and highly cited papers. The most frequently occurring topic…

Disciplinary Action Committee (DAC)

ERIC Educational Resources Information Center

Notar, Charles; Riley, Gena; Thornburg, Roland; Owens, Lynetta; Harper, Cynthia

2009-01-01

The College of Education and Professional Studies (CEPS) provides an environment in which all students can learn. The term "students" encompasses anyone enrolled in a course provided by the College. The DAC was formed to protect the health, safety, and general welfare of students, educators, and those who participate in conjunction with…

Cepheus

NASA Astrophysics Data System (ADS)

Murdin, P.

2000-11-01

(abbrev. Cep, gen. Cephei; area 588 sq. deg.) A northern constellation which lies between Draco and Cassiopeia, and culminates at midnight in late August. It is named after King Cepheus, husband of Queen Cassiopeia and father of Andromeda in Greek mythology. Its brightest stars were cataloged by Ptolemy (c. AD 100-175) in the Almagest....

CEP's Eleven Principles of Effective Character Education

ERIC Educational Resources Information Center

Lickona, Tom; Schaps, Eric; Lewis, Catherine

2007-01-01

There is no single script for effective character education, but there are some important basic principles. This document presents eleven principles that schools and other groups can use to plan a character education effort and to evaluate available character education programs: (1) Promotes core ethical values and supportive performance values as…

Russian Operational Art in the Russo-Georgian War of 2008

DTIC Science & Technology

2009-03-25

Conflicting Reports on their Mission”, Moscow RIA-Novosti” (August 10, 2008), CEP20080810950050 in OpenSource (January 8, 2009). Russia claimed that the...Paris AFP (North American Service) in English, August 13, 2008, in OpenSource Center (accessed January 9, 2009). 55“Georgia, Russia: The Cyberwarfare

Humanistic Teacher Education: An Experiment in Systematic Curriculum Innovation.

ERIC Educational Resources Information Center

Wass, Hannelore; And Others

The Florida Childhood Education Program (CEP) at the University of Florida is an innovative teacher education program whose theoretical base lies in 12 years of research in effective teaching combined with modern thinking from perceptual-humanistic psychology. This theory was given practical expression in an experimental program designed and…

"Teaching to Teach" Literacy. CEP Discussion Paper No. 1425

ERIC Educational Resources Information Center

Machin, Stephen; McNally, Sandra; Viarengo, Martina

2016-01-01

Significant numbers of people have very low levels of literacy in many OECD countries and, because of this, face significant labour market penalties. Despite this, it remains unclear what teaching strategies are most useful for actually rectifying literacy deficiencies. The subject remains hugely controversial amongst educationalists and has…

Optimizing SIEM Throughput on the Cloud Using Parallelization

PubMed Central

Alam, Masoom; Ihsan, Asif; Javaid, Qaisar; Khan, Abid; Manzoor, Jawad; Akhundzada, Adnan; Khan, M Khurram; Farooq, Sajid

2016-01-01

Processing large amounts of data in real time for identifying security issues pose several performance challenges, especially when hardware infrastructure is limited. Managed Security Service Providers (MSSP), mostly hosting their applications on the Cloud, receive events at a very high rate that varies from a few hundred to a couple of thousand events per second (EPS). It is critical to process this data efficiently, so that attacks could be identified quickly and necessary response could be initiated. This paper evaluates the performance of a security framework OSTROM built on the Esper complex event processing (CEP) engine under a parallel and non-parallel computational framework. We explain three architectures under which Esper can be used to process events. We investigated the effect on throughput, memory and CPU usage in each configuration setting. The results indicate that the performance of the engine is limited by the number of events coming in rather than the queries being processed. The architecture where 1/4th of the total events are submitted to each instance and all the queries are processed by all the units shows best results in terms of throughput, memory and CPU usage. PMID:27851762

The Common Core Takes Hold

ERIC Educational Resources Information Center

Rothman, Robert

2014-01-01

A survey administered in the spring of 2013 by the Center on Education Policy (CEP) inquired into the implementation of Common Core State Standards at that time. Based on self-reports by state officials, the survey found that curricula aligned to the common core were already being taught in at least some districts or grade levels. All states…

Racial Segregation Patterns in Selective Universities. CEP Discussion Paper No. 1219

ERIC Educational Resources Information Center

Arcidiacono, Peter; Aucejo, Esteban; Hussey, Andrew; Spenner, Kenneth

2013-01-01

This paper examines sorting into interracial friendships at selective universities. We show significant friendship segregation, particularly for blacks. Indeed, black friendships are no more diverse in college than in high school despite the colleges blacks attend having substantially smaller black populations. We show that part of the reason for…

The novel GrCEP12 peptide from the plant-parasitic nematode Globodera rostochiensis suppresses flg22-mediated PTI

USDA-ARS?s Scientific Manuscript database

The potato cyst nematode Globodera rostochiensis is a biotrophic pathogen that secretes effector proteins into host root cells to promote successful plant parasitism. In addition to the role in generating within root tissue the feeding cells essential for nematode development, nematode secreted effe...

"High" Achievers? Cannabis Access and Student Performance. CEP Discussion Paper No. 1340

ERIC Educational Resources Information Center

Marie, Olivier; Zölitz, Ulf

2015-01-01

This paper investigates how legal cannabis access affects student performance. Identification comes from an exceptional policy introduced in the city of Maastricht which discriminated legal access based on individuals' nationality. We apply a difference-in-difference approach using administrative panel data on over 54,000 course grades of local…

"School for Life" in Ghana: Promoting Literate Opportunities for Rural Youth

ERIC Educational Resources Information Center

Sherris, Arieh; Sulemana, Osama Saaka; Alhassan, Andani; Abudu, Grace; Karim, Abdul-Rahaman

2014-01-01

Sociocultural and socio-economic conditions (e.g. subsistence family farming needs) as well as the absence of nearby public schools result in Ghanaian youth, primarily from rural areas, not receiving formal schooling. Because of this, children may never learn to read and write. One solution is a complementary education programme (CEP) that…

Investigation of Times of Minima of Selected Early-Type Eclipsing Binaries

NASA Astrophysics Data System (ADS)

Mayer, Pavel; Wolf, Marek; Niarchos, P. G.; Gazeas, K. D.; Manimanis, V. N.; Chochol, Drahomír

2006-08-01

New precise times of minimum light for several early-type eclipsing binaries were obtained at three observatories. The changes of period of the following measured binaries are discussed: V1182 Aql, LY Aur, SZ Cam, FZ CMa, QZ Car, LZ Cen, V606 Cen, AH Cep and TU~Mus.

Character Counts: Don't Leave Home without It!

ERIC Educational Resources Information Center

Education Digest: Essential Readings Condensed for Quick Review, 2011

2011-01-01

Orrs Elementary School in Griffin-Spalding County, Georgia, was selected as a 2010 National School of Character by the Character Education Partnership (CEP) and was honored at the National Forum of Character Education awards ceremony in San Francisco, California. According to Principal Dexter Martin, character education is more than a phrase or a…

Consultants, Consultancy and Consultocracy in Education Policymaking in England

ERIC Educational Resources Information Center

Gunter, Helen M.; Hall, David; Mills, Colin

2015-01-01

The role and contribution of consultants and consultancy in public services has grown rapidly and the power of consultants suggests the emergence of a "consultocracy". We draw on research evidence from the social sciences and critical education policy (CEP) studies to present an examination of the state of the field. We deploy a…

Academies 2: The New Batch. CEP Discussion Paper No. 1370

ERIC Educational Resources Information Center

Eyles, Andrew; Machin, Stephen; Silva, Olmo

2015-01-01

The English education system has undergone a large restructuring programme through the introduction of academy schools. The most salient feature of these schools is that, despite remaining part of the state sector, they operate with more autonomy than the predecessor schools they replace. Two distinct time periods of academy school introduction…

Nonlinear Dichroism in Back-to-Back Double Ionization of He by an Intense Elliptically Polarized Few-Cycle Extreme Ultraviolet Pulse.

PubMed

Ngoko Djiokap, J M; Manakov, N L; Meremianin, A V; Hu, S X; Madsen, L B; Starace, Anthony F

2014-11-28

Control of double ionization of He by means of the polarization and carrier-envelope phase (CEP) of an intense, few-cycle extreme ultraviolet (XUV) pulse is demonstrated numerically by solving the six-dimensional two-electron, time-dependent Schrödinger equation for He interacting with an elliptically polarized XUV pulse. Guided by perturbation theory (PT), we predict the existence of a nonlinear dichroic effect (∝I^{3/2}) that is sensitive to the CEP, ellipticity, peak intensity I, and temporal duration of the pulse. This dichroic effect (i.e., the difference of the two-electron angular distributions for opposite helicities of the ionizing XUV pulse) originates from interference of first- and second-order PT amplitudes, allowing one to probe and control S- and D-wave channels of the two-electron continuum. We show that the back-to-back in-plane geometry with unequal energy sharing is an ideal one for observing this dichroic effect that occurs only for an elliptically polarized, few-cycle attosecond pulse.

THE BANANA PROJECT. III. SPIN-ORBIT ALIGNMENT IN THE LONG-PERIOD ECLIPSING BINARY NY CEPHEI

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

Albrecht, Simon; Winn, Joshua N.; Carter, Joshua A.

Binaries are not always neatly aligned. Previous observations of the DI Her system showed that the spin axes of both stars are highly inclined with respect to one another and the orbital axis. Here, we report on a measurement of the spin-axis orientation of the primary star of the NY Cep system, which is similar to DI Her in many respects: it features two young early-type stars ({approx}6 Myr, B0.5V+B2V), in an eccentric and relatively long-period orbit (e = 0.48, P = 15fd3). The sky projections of the rotation vector and the spin vector are well aligned ({beta}{sub p} =more » 2{sup 0} {+-} 4{sup 0}), in strong contrast to DI Her. Although no convincing explanation has yet been given for the misalignment of DI Her, our results show that the phenomenon is not universal, and that a successful theory will need to account for the different outcome in the case of NY Cep.« less

JICA support of NGO project succeeds.

PubMed

2000-05-01

In 1997, the Japan International Cooperation Agency (JICA) started the Community Empowerment Program (CEP) to directly help people at the grassroots level in developing countries. It was created to directly benefit people in developing countries by improving their livelihood and welfare. Under the program, model projects are implemented together with local nongovernmental organizations (NGOs). The Capacity Building for Sustainable Reproductive Health Care Project in Jessore District in Bangladesh, is a pioneer of JICA and NGO cooperation under CEP, and it aims to develop the capacity of service providers to deliver sustainable reproductive health (RH) services in rural areas through community involvement. To achieve this, training for community health promoters (CHPs) is provided to enable them to deliver an Essential Services Package (ESP) of integrated health and RH services to rural beneficiaries. So far, a total of 125 people have been trained, including 75 CHPs, 10 health assistants, and 40 family welfare assistants. Midterm evaluation of the project indicated that the project had pioneered the development of 17 ESP modules and has established the strong potential to link with government programs for future sustainability.

Phase I/II study of the novel proteasome inhibitor delanzomib (CEP-18770) for relapsed and refractory multiple myeloma.

PubMed

Vogl, Dan T; Martin, Thomas G; Vij, Ravi; Hari, Parameswaran; Mikhael, Joseph R; Siegel, David; Wu, Ka Lung; Delforge, Michel; Gasparetto, Cristina

2017-08-01

Delanzomib (CEP-18770), a reversible P2 threonine boronic acid proteasome (β5/β1 subunits) inhibitor that showed promising anti-myeloma effects in preclinical studies, was investigated in a single-agent multicenter phase I/II study in patients with relapsed/refractory myeloma. Sixty-one patients (17 during dose escalation; 44 in the expansion cohort) received delanzomib on days 1, 8, and 15 in 28-d cycles; 47 received the maximum tolerated dose (MTD), 2.1 mg/m 2 . Dose-limiting toxicities (DLTs) at 2.4 mg/m 2 were rash and thrombocytopenia. At the MTD, the most prominent adverse events were nausea, vomiting, anorexia, fatigue, and pyrexia; grade 3/4 thrombocytopenia and neutropenia occurred in 53 and 23% of patients, respectively. Peripheral neuropathy (21%) was limited to grades 1/2. At the MTD, 26 patients (55%) had stable disease and four (9%) had a partial response (PR). Median time to progression (TTP) was 2.5 months across the cohort. Based upon the efficacy results, development of delanzomib for myeloma was discontinued.

Synergistic Effects Induced by a Low Dose of Diesel Particulate Extract and Ultraviolet-A in Caenorhabditis elegans: DNA Damage-Triggered Germ Cell Apoptosis

PubMed Central

2015-01-01

Diesel exhaust has been classified as a potential carcinogen and is associated with various health effects. A previous study showed that the doses for manifesting the mutagenetic effects of diesel exhaust could be reduced when coexposed with ultraviolet-A (UVA) in a cellular system. However, the mechanisms underlying synergistic effects remain to be clarified, especially in an in vivo system. In the present study, using Caenorhabditis elegans (C. elegans) as an in vivo system we studied the synergistic effects of diesel particulate extract (DPE) plus UVA, and the underlying mechanisms were dissected genetically using related mutants. Our results demonstrated that though coexposure of wild type worms at young adult stage to low doses of DPE (20 μg/mL) plus UVA (0.2, 0.5, and 1.0 J/cm2) did not affect worm development (mitotic germ cells and brood size), it resulted in a significant induction of germ cell death. Using the strain of hus-1::gfp, distinct foci of HUS-1::GFP was observed in proliferating germ cells, indicating the DNA damage after worms were treated with DPE plus UVA. Moreover, the induction of germ cell death by DPE plus UVA was alleviated in single-gene loss-of-function mutations of core apoptotic, checkpoint HUS-1, CEP-1/p53, and MAPK dependent signaling pathways. Using a reactive oxygen species (ROS) probe, it was found that the production of ROS in worms coexposed to DPE plus UVA increased in a time-dependent manner. In addition, employing a singlet oxygen (1O2) trapping probe, 2,2,6,6-tetramethyl-4-piperidone, coupled with electron spin resonance analysis, we demonstrated the increased 1O2 production in worms coexposed to DPE plus UVA. These results indicated that UVA could enhance the apoptotic induction of DPE at low doses through a DNA damage-triggered pathway and that the production of ROS, especially 1O2, played a pivotal role in initiating the synergistic process. PMID:24841043

High-Density Proximity Mapping Reveals the Subcellular Organization of mRNA-Associated Granules and Bodies.

PubMed

Youn, Ji-Young; Dunham, Wade H; Hong, Seo Jung; Knight, James D R; Bashkurov, Mikhail; Chen, Ginny I; Bagci, Halil; Rathod, Bhavisha; MacLeod, Graham; Eng, Simon W M; Angers, Stéphane; Morris, Quaid; Fabian, Marc; Côté, Jean-François; Gingras, Anne-Claude

2018-02-01

mRNA processing, transport, translation, and ultimately degradation involve a series of dedicated protein complexes that often assemble into large membraneless structures such as stress granules (SGs) and processing bodies (PBs). Here, systematic in vivo proximity-dependent biotinylation (BioID) analysis of 119 human proteins associated with different aspects of mRNA biology uncovers 7424 unique proximity interactions with 1,792 proteins. Classical bait-prey analysis reveals connections of hundreds of proteins to distinct mRNA-associated processes or complexes, including the splicing and transcriptional elongation machineries (protein phosphatase 4) and the CCR4-NOT deadenylase complex (CEP85, RNF219, and KIAA0355). Analysis of correlated patterns between endogenous preys uncovers the spatial organization of RNA regulatory structures and enables the definition of 144 core components of SGs and PBs. We report preexisting contacts between most core SG proteins under normal growth conditions and demonstrate that several core SG proteins (UBAP2L, CSDE1, and PRRC2C) are critical for the formation of microscopically visible SGs. Copyright © 2017 Elsevier Inc. All rights reserved.

Foundations for Streaming Model Transformations by Complex Event Processing.

PubMed

Dávid, István; Ráth, István; Varró, Dániel

2018-01-01

Streaming model transformations represent a novel class of transformations to manipulate models whose elements are continuously produced or modified in high volume and with rapid rate of change. Executing streaming transformations requires efficient techniques to recognize activated transformation rules over a live model and a potentially infinite stream of events. In this paper, we propose foundations of streaming model transformations by innovatively integrating incremental model query, complex event processing (CEP) and reactive (event-driven) transformation techniques. Complex event processing allows to identify relevant patterns and sequences of events over an event stream. Our approach enables event streams to include model change events which are automatically and continuously populated by incremental model queries. Furthermore, a reactive rule engine carries out transformations on identified complex event patterns. We provide an integrated domain-specific language with precise semantics for capturing complex event patterns and streaming transformations together with an execution engine, all of which is now part of the Viatra reactive transformation framework. We demonstrate the feasibility of our approach with two case studies: one in an advanced model engineering workflow; and one in the context of on-the-fly gesture recognition.

Efficient Sub-Bandgap Light Absorption and Signal Amplification in Silicon Photodetectors

NASA Astrophysics Data System (ADS)

Liu, Yu-Hsin

This thesis focuses on two areas in silicon photodetectors, the first being enhancing the sub-bandgap light absorption of IR wavelenghts in silicon, and the second being intrinsic signal amplification in silicon photodetectors. Both of these are achieved using heavily doped p-n junction devices which create localized states that relax the k-selection rule of indirect bandgap material. The probability of transitions between impurity band and the conduction/valence band would be much more efficient than the one between band-to-band transition. The waveguide-coupled epitaxial p-n photodetector was demonstrated for 1310 nm wavelength detection. Incorporated with the Franz-Keldysh effect and the quasi-confined epitaxial layer design, an absorption coefficient around 10 cm-1 has been measured and internal quantum efficiency nearly 100% at -2.5V. The absorption coefficient is calculated from the wave function of the electron and hole in p-n diode. The heavily doped impurity wave function can be formulated as a delta function, and the quasi-confined conduction band energy states, and the wave function on each level can be obtained from the Silvaco software. The calculated theoretical absorption coefficient increases with the increasing applied bias and the doping concentration, which matches the experimental results. To solve the issues of large excess noise and high operation bias for avalanche photodiodes based on impact ionization, I presented a detector using the Cycling Excitation Process (CEP) for signal amplification. This can be realized in a heavily doped and highly compensated Si p-n junction, showing ultra high gain about 3000 at very low bias (<4 V), and possessing an intrinsic, phonon-mediated regulation process to keep the device stable without any quenching device required in today's Geiger-mode avalanche detectors. The CEP can be formulated with the rate equations in conduction bands and impurity states. The gain expression, which is a function of the primary photocurrent and related to the phonon absorption time, predicts the same trend of the gain increasing with temperature and decreasing with increasing primary photocurrent.

Reactions of VX, HD, and their simulants with NaY and AgY zeolites. Desulfurization of VX on AgY

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

Wagner, G.W.; Bartram, P.W.

1999-11-09

The room-temperature reactions of the chemical warfare agents VX (O-ethyl S-2-(diisopropylamino)-ethyl methylphosphonothioate), HD (2,2{prime}-dichloroethyl sulfide, or mustard), and their common simulants, O,S-diethyl phenylphosphonothioate (DEPPT) and 2-chloroethyl phenyl sulfide (CEPS), with NaY and silver-exchanged (AgY) zeolites have been studied using solid-state magic angle spinning NMR. VX hydrolyzes via exclusive cleavage of the P{single{underscore}bond}S bond on both NaY and AgY to yield ethyl methylphosphonate (EMPA). The reaction is significantly faster on AgY than on NaY, suggesting catalysis by silver. On AgY, an intermediate silver salt of EMPA is apparently formed which is slowly converted to ethyl 2-(diisopropylamino)ethyl methylphosphonate (QB, the desulfurized analoguemore » of VX) in about a 78% yield. DEPPT similarly hydrolyzes via P{single{underscore}bond}S cleavage on AgY to yield an apparent silver salt of ethyl phenylphosphonate, which does not undergo further reaction to the desulfurized analogue. No reaction is observed for DEPPT on NaY. HD on AgY forms both vinyl sulfide and the cyclic ether 1,4-thioxane. HD reacts faster on NaY to exclusively form the CH-TG sulfonium ion (HOCH{sub 2}CH{sub 2}SCH{sub 2}CH{sub 2}S{sup +}[CH{sub 2}CH{sub 2}OH]{sub 2}). CEPS also reacts faster on NaY, forming 2-hydroxyethyl phenyl sulfide. On AgY, CEPS does not give the vinyl product, but does yield the ether product PhSCH{sub 2}CH{sub 2}OCH{sub 2}CH{sub 2}SPh. A mechanism is proposed for the silver-catalyzed hydrolysis of VX, the desulfurization of the cleaved thiol, and the formation of QB.« less

A highly selective, orally active inhibitor of Janus kinase 2, CEP-33779, ablates disease in two mouse models of rheumatoid arthritis

PubMed Central

2011-01-01

Introduction Janus kinase 2 (JAK2) is involved in the downstream activation of signal transducer and activator of transcription 3 (STAT3) and STAT5 and is responsible for transducing signals for several proinflammatory cytokines involved in the pathogenesis of rheumatoid arthritis (RA), including interleukin (IL)-6, interferon γ (IFNγ) and IL-12. In this paper, we describe the efficacy profile of CEP-33779, a highly selective, orally active, small-molecule inhibitor of JAK2 evaluated in two mouse models of RA. Methods Collagen antibody-induced arthritis (CAIA) and collagen type II (CII)-induced arthritis (CIA) were established before the oral administration of a small-molecule JAK2 inhibitor, CEP-33779, twice daily at 10 mg/kg, 30 mg/kg, 55 mg/kg or 100 mg/kg over a period of 4 to 8 weeks. Results Pharmacodynamic inhibition of JAK2 reduced mean paw edema and clinical scores in both CIA and CAIA models of arthritis. Reduction in paw cytokines (IL-12, IFNγ and tumor necrosis factor α) and serum cytokines (IL-12 and IL-2) correlated with reduced spleen CII-specific T helper 1 cell frequencies as measured by ex vivo IFNγ enzyme-linked immunosorbent spot assay. Both models demonstrated histological evidence of disease amelioration upon treatment (for example, reduced matrix erosion, subchondral osteolysis, pannus formation and synovial inflammation) and reduced paw phosphorylated STAT3 levels. No changes in body weight or serum anti-CII autoantibody titers were observed in either RA model. Conclusions This study demonstrates the utility of using a potent and highly selective, orally bioavailable JAK2 inhibitor for the treatment of RA. Using a selective inhibitor of JAK2 rather than pan-JAK inhibitors avoids the potential complication of immunosuppression while targeting critical signaling pathways involved in autoimmune disease progression. PMID:21510883

Spectrally resolved interferometric observations of α Cephei and physical modeling of fast rotating stars

NASA Astrophysics Data System (ADS)

Delaa, O.; Zorec, J.; Domiciano de Souza, A.; Mourard, D.; Perraut, K.; Stee, Ph.; Frémat, Y.; Monnier, J.; Kraus, S.; Che, X.; Bério, Ph.; Bonneau, D.; Clausse, J. M.; Challouf, M.; Ligi, R.; Meilland, A.; Nardetto, N.; Spang, A.; McAlister, H.; ten Brummelaar, T.; Sturmann, J.; Sturmann, L.; Turner, N.; Farrington, C.; Goldfinger, P. J.

2013-07-01

Context. When a given observational quantity depends on several stellar physical parameters, it is generally very difficult to obtain observational constraints for each of them individually. Therefore, we studied under which conditions constraints for some individual parameters can be achieved for fast rotators, knowing that their geometry is modified by the rapid rotation which causes a non-uniform surface brightness distribution. Aims: We aim to study the sensitivity of interferometric observables on the position angle of the rotation axis (PA) of a rapidly rotating star, and whether other physical parameters can influence the determination of PA, and also the influence of the surface differential rotation on the determination of the β exponent in the gravity darkening law that enters the interpretation of interferometric observations, using α Cep as a test star. Methods: We used differential phases obtained from observations carried out in the Hα absorption line of α Cep with the VEGA/CHARA interferometer at high spectral resolution, R = 30 000 to study the kinematics in the atmosphere of the star. Results: We studied the influence of the gravity darkening effect (GDE) on the determination of the PA of the rotation axis of α Cep and determined its value, PA = -157-10°+17°. We conclude that the GDE has a weak influence on the dispersed phases. We showed that the surface differential rotation can have a rather strong influence on the determination of the gravity darkening exponent. A new method of determining the inclination angle of the stellar rotational axis is suggested. We conclude that differential phases obtained with spectro-interferometry carried out on the Hα line can in principle lead to an estimate of the stellar inclination angle i. However, to determine both i and the differential rotation parameter α, lines free from the Stark effect and that have collision-dominated source functions are to be preferred.

Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update.

PubMed

Wolff, Antonio C; Hammond, M Elizabeth Hale; Allison, Kimberly H; Harvey, Brittany E; Mangu, Pamela B; Bartlett, John M S; Bilous, Michael; Ellis, Ian O; Fitzgibbons, Patrick; Hanna, Wedad; Jenkins, Robert B; Press, Michael F; Spears, Patricia A; Vance, Gail H; Viale, Giuseppe; McShane, Lisa M; Dowsett, Mitchell

2018-05-30

- To update key recommendations of the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) human epidermal growth factor receptor 2 (HER2) testing in breast cancer guideline. - Based on the signals approach, an Expert Panel reviewed published literature and research survey results on the observed frequency of less common in situ hybridization (ISH) patterns to update the recommendations. - Two recommendations addressed via correspondence in 2015 are included. First, immunohistochemistry (IHC) 2+ is defined as invasive breast cancer with weak to moderate complete membrane staining observed in >10% of tumor cells. Second, if the initial HER2 test result in a core needle biopsy specimen of a primary breast cancer is negative, a new HER2 test may (not "must") be ordered on the excision specimen based on specific clinical criteria. The HER2 testing algorithm for breast cancer is updated to address the recommended workup for less common clinical scenarios (approximately 5% of cases) observed when using a dual-probe ISH assay. These scenarios are described as ISH group 2 ( HER2/chromosome enumeration probe 17 [CEP17] ratio ≥2.0; average HER2 copy number <4.0 signals per cell), ISH group 3 ( HER2/CEP17 ratio <2.0; average HER2 copy number ≥6.0 signals per cell), and ISH group 4 ( HER2/CEP17 ratio <2.0; average HER2 copy number ≥4.0 and <6.0 signals per cell). The diagnostic approach includes more rigorous interpretation criteria for ISH and requires concomitant IHC review for dual-probe ISH groups 2 to 4 to arrive at the most accurate HER2 status designation (positive or negative) based on combined interpretation of the ISH and IHC assays. The Expert Panel recommends that laboratories using single-probe ISH assays include concomitant IHC review as part of the interpretation of all single-probe ISH assay results.

Assessment of accuracy, fix success rate, and use of estimated horizontal position error (EHPE) to filter inaccurate data collected by a common commercially available GPS logger.

PubMed

Morris, Gail; Conner, L Mike

2017-01-01

Global positioning system (GPS) technologies have improved the ability of researchers to monitor wildlife; however, use of these technologies is often limited by monetary costs. Some researchers have begun to use commercially available GPS loggers as a less expensive means of tracking wildlife, but data regarding performance of these devices are limited. We tested a commercially available GPS logger (i-gotU GT-120) by placing loggers at ground control points with locations known to < 30 cm. In a preliminary investigation, we collected locations every 15 minutes for several days to estimate location error (LE) and circular error probable (CEP). Using similar methods, we then investigated the influence of cover on LE, CEP, and fix success rate (FSR) by constructing cover over ground control points. We found mean LE was < 10 m and mean 50% CEP was < 7 m. FSR was not significantly influenced by cover and in all treatments remained near 100%. Cover had a minor but significant effect on LE. Denser cover was associated with higher mean LE, but the difference in LE between the no cover and highest cover treatments was only 2.2 m. Finally, the most commonly used commercially available devices provide a measure of estimated horizontal position error (EHPE) which potentially may be used to filter inaccurate locations. Using data combined from the preliminary and cover investigations, we modeled LE as a function of EHPE and number of satellites. We found support for use of both EHPE and number of satellites in predicting LE; however, use of EHPE to filter inaccurate locations resulted in the loss of many locations with low error in return for only modest improvements in LE. Even without filtering, the accuracy of the logger was likely sufficient for studies which can accept average location errors of approximately 10 m.

RAI1 Alternate Probe Identifies Additional Breast Cancer Cases as Amplified Following Equivocal HER2 Fluorescence In Situ Hybridization Testing: Experience From a National Reference Laboratory.

PubMed

Hui, Ling; Geiersbach, Katherine B; Downs-Kelly, Erinn; Gulbahce, H Evin

2017-02-01

-In 2013 the American Society of Clinical Oncology and College of American Pathologists updated the HER2 guidelines and changed the equivocal category for HER2 in situ hybridization testing to an average HER2 copy number of 4.0 to 5.9 with a HER2:CEP17 ratio of less than 2.0 and proposed retesting, with an option of using another control probe to avoid false-negative results. RAI1, located at band position 17p11.2, is a popular alternate probe locus for retesting equivocal changes. -To review experience with the RAI1 alternate probe in HER2 fluorescence in situ hybridization equivocal breast cancers. -Primary and metastatic breast cancers with equivocal HER2 fluorescence in situ hybridization, retested with an alternate (RAI1) probe, were identified. HER2, RAI1, and CEP17 copy numbers, HER2 to control probe ratios, and genetic heterogeneity were recorded. Hematoxylin-eosin-stained slides were reviewed for type and grade of cancer. -Of 876 cases tested with CEP17 as the reference probe, 97 (11.1%) had equivocal HER2 fluorescence in situ hybridization results. Additional testing with the RAI1 probe classified 39.2% cases (38 of 97) as amplified with a HER2:RAI1 ratio ranging from 2.0 to 3.2 (mean, 2.37); 3.1% (3 of 97) were still unclassifiable because of a deletion of RAI1. -RAI1 identified close to 40% of original HER2 fluorescence in situ hybridization equivocal cases as amplified, making these patients eligible for targeted therapies. It is not known whether guidelines for US Food and Drug Administration-approved probes can be extrapolated to alternate probes when an alternate control probe shows losses or gains. Because of the lack of guidelines for reporting HER2 status with alternate probes, laboratories face challenges in interpreting results.

Analysis of HER2 status in breast carcinoma by fully automated HER2 fluorescence in situ hybridization (FISH): comparison of two immunohistochemical tests and manual FISH.

PubMed

Yoon, Nara; Do, In-Gu; Cho, Eun Yoon

2014-09-01

Easy and accurate HER2 testing is essential when considering the prognostic and predictive significance of HER2 in breast cancer. The use of a fully automated, quantitative FISH assay would be helpful to detect HER2 amplification in breast cancer tissue specimens with reduced inter-laboratory variability. We compared the concordance of HER2 status as assessed by an automated FISH staining system to manual FISH testing. Using 60 formalin-fixed paraffin-embedded breast carcinoma specimens, we assessed HER2 immunoexpression with two antibodies (DAKO HercepTest and CB11). In addition, HER2 status was evaluated with automated FISH using the Leica FISH System for BOND and a manual FISH using the Abbott PathVysion DNA Probe Kit. All but one specimen were successfully stained using both FISH methods. When the data were divided into two groups according to HER2/CEP17 ratio, positive and negative, the results from both the automated and manual FISH techniques were identical for all 59 evaluable specimens. The HER2 and CEP17 copy numbers and HER2/CEP17 ratio showed great agreement between both FISH methods. The automated FISH technique was interpretable with signal intensity similar to those of the manual FISH technique. In contrast with manual FISH, the automated FISH technique showed well-preserved architecture due to low membrane digestion. HER2 immunohistochemistry and FISH results showed substantial significant agreement (κ = 1.0, p < 0.001). HER2 status can be reliably determined using a fully automated HER2 FISH system with high concordance to the well-established manual FISH method. Because of stable signal intensity and high staining quality, the automated FISH technique may be more appropriate than manual FISH for routine applications. © 2013 APMIS. Published by John Wiley & Sons Ltd.

Prognostic significance of myocardial energy expenditure and myocardial efficiency in patients with heart failure with reduced ejection fraction.

PubMed

Cetin, Mehmet S; Ozcan Cetin, Elif H; Canpolat, Ugur; Sasmaz, Hatice; Temizhan, Ahmet; Aydogdu, Sinan

2018-02-01

In heart failure with reduced ejection fraction (HFrEF) patients, myocardial blood flow (MBF), myocardial energy expenditure (MEE), myocardial efficiency has been poorly evaluated because of the necessity of invasive procedures in the determination of these parameters. Transthoracic echocardiography (TTE) can provide reliable data for MEE, MBF (via coronary sinus (CS) flows). Also, myocardial efficiency can be evaluated by the MEE to MBF ratio. We aim to assess MBF, MEE and energy efficiency and the prognostic value of these parameters in HFrEF. In this prospective study, a total of 80 patients with HFrEF due to either ischemic or non-ischemic etiology and 20 healthy control subjects were included. Median follow-up duration was 901 (27-1004) days. MBF was calculated via coronary sinus blood flow. MEE was measured from circumferential end-systolic stress, stroke volume and left ventricular ejection time. MEE to MBF ratio was determined as MEf. Primary composite end-point (CEP) was cardiovascular mortality, heart transplantation or mechanical circulatory support. MEE and MEf were lower and MBF per minute was higher in HF group compared to control subjects whereas MBF per 100 g left ventricular mass was not different. MEE and MEf have significantly negative correlation with troponin I, BNP, uric acid and positive correlation with epicardial fat thickness. In Cox regression analysis, per one calorie decrease of MEE was associated 4.3 times increased risk [HR 4.396 (95% CI 1.230-15.716)] and per one percent decrease of MEf was associated 3.3 times increased risk of CEP [HR 3.343 (95% CI 1.025-10.905)]. Our study demonstrated that while MEE and MEf diminished in HFrEF, MBF preserved with the symptomatic progression of HF. MEE and MEf were found to be associated with important prognostic markers and independent predictors of CEP in HFrEF. Evaluation of MEE, MBF and MEf with echocardiography may provide an additional data regarding prognostic assessment of HFrEF population.

Utility of cytopathological specimens and an automated image analysis for the evaluation of HER2 status and intratumor heterogeneity in breast carcinoma.

PubMed

Arihiro, Koji; Oda, Miyo; Ogawa, Katsunari; Kaneko, Yoshie; Shimizu, Tomomi; Tanaka, Yuna; Marubashi, Yukari; Ishida, Katsunari; Takai, Chikako; Taoka, Chie; Kimura, Shuji; Shiroma, Noriyuki

2016-12-01

Although updated HER2 testing guidelines have been improved by a collaboration between the American Society of Clinical Oncology (ASCO) and the College of American Pathologists (CAP) in 2013, HER2 evaluation is still problematic because of issues involving CEP17 polysomy, heterogeneity, and HER2 score 2+ cases. The aim of this retrospective study was to evaluate the relationship between HER2 gene heterogeneity, or so called CEP17 polysomy, using breast carcinoma cells sampled by scraping and the IHC score graded by automated image analysis using whole slide image. We randomly selected 23 breast carcinoma cases with a HER2 score 0, 24 cases with a HER2 score 1+, 24 cases with HER2 score 2+, and 23 cases with HER2 score 3+ from the records of patients with breast cancer at Hiroshima University Hospital. We compared the results of fluorescent in situ hybridization (FISH) using formalin-fixed, paraffin-embedded (FFPE) tissues and cytological samples and compared the HER2 score calculated using an automated image analysis using wholly scanned slide images and visual counting. We successfully performed the FISH assay in 78 of 94 cases (83%) using FFPE tissues and in all 94 (100%) cases using cytological samples. Frequency of both HER2 amplification and CEP17 polysomy was higher when cytological samples were used than when FFPE tissue was used. Frequency of HER2 heterogeneity using cytological samples was higher that than using FFPE tissue, except for the IHC score 3+ cases. When assessment of HER2 status based on FISH using FFPE tissue cannot be accomplished, FISH using cytological samples should be considered. When intensity of HER2 is heterogeneous in the tumor tissue, particularly in cases regarded as score 2+, they should be evaluated by automated image analysis using the whole slide image. Copyright © 2016 Elsevier GmbH. All rights reserved.

Interferometric view of the circumstellar envelopes of northern FU Orionis-type stars

NASA Astrophysics Data System (ADS)

Fehér, O.; Kóspál, Á.; Ábrahám, P.; Hogerheijde, M. R.; Brinch, C.

2017-11-01

Context. FU Orionis-type objects are pre-main sequence, low-mass stars with large outbursts in visible light that last for several years or decades. They are thought to represent an evolutionary phase during the life of every young star when accretion from the circumstellar disk is enhanced during recurring time periods. These outbursts are able to rapidly build up the star while affecting the physical conditions inside the circumstellar disk and thus the ongoing or future planet formation. In many models, infall from a circumstellar envelope seems to be necessary to trigger the outbursts. Aims: We characterise the morphology and the physical parameters of the circumstellar material around FU Orionis-type stars using the emission of millimetre-wavelength molecular tracers. The high-spatial-resolution study provides insight into the evolutionary state of the objects, the distribution of parameters in the envelopes and the physical processes forming the environment of these stars. Methods: We observed the J = 1-0 rotational transition of 13CO and C18O towards eight northern FU Orionis-type stars (V1057 Cyg, V1515 Cyg, V2492 Cyg, V2493 Cyg, V1735 Cyg, V733 Cep, RNO 1B and RNO 1C) and determine the spatial and velocity structure of the circumstellar gas on a scale of a few thousand AU. We derive temperatures and envelope masses and discuss the kinematics of the circumstellar material. Results: We detected extended CO emission associated with all our targets. Smaller-scale CO clumps were found to be associated with five objects with radii of 2000-5000 AU and masses of 0.02-0.5 M⊙; these are clearly heated by the central stars. Three of these envelopes are also strongly detected in the 2.7 mm continuum. No central CO clumps were detected around V733 Cep and V710 Cas which can be interpreted as envelopes but there are many other clumps in their environments. Traces of outflow activity were observed towards V1735 Cyg, V733 Cep and V710 Cas. Conclusions: The diversity of the observed envelopes enables us to set up an evolutionary sequence between the objects. We find their evolutionary state to range from early, embedded Class I stage to late, Class II-type objects with very-low-mass circumstellar material. We also find evidence of larger-scale circumstellar material influencing the detected spectral features in the environment of our targets. These results reinforce the idea of FU Orionis-type stars as representatives of a transitory stage between embedded Class I young stellar objects and classical T Tauri stars.

Cattle Sex-Specific Recombination and Genetic Control from a Large Pedigree Analysis.

PubMed

Ma, Li; O'Connell, Jeffrey R; VanRaden, Paul M; Shen, Botong; Padhi, Abinash; Sun, Chuanyu; Bickhart, Derek M; Cole, John B; Null, Daniel J; Liu, George E; Da, Yang; Wiggans, George R

2015-11-01

Meiotic recombination is an essential biological process that generates genetic diversity and ensures proper segregation of chromosomes during meiosis. From a large USDA dairy cattle pedigree with over half a million genotyped animals, we extracted 186,927 three-generation families, identified over 8.5 million maternal and paternal recombination events, and constructed sex-specific recombination maps for 59,309 autosomal SNPs. The recombination map spans for 25.5 Morgans in males and 23.2 Morgans in females, for a total studied region of 2,516 Mb (986 kb/cM in males and 1,085 kb/cM in females). The male map is 10% longer than the female map and the sex difference is most pronounced in the subtelomeric regions. We identified 1,792 male and 1,885 female putative recombination hotspots, with 720 hotspots shared between sexes. These hotspots encompass 3% of the genome but account for 25% of the genome-wide recombination events in both sexes. During the past forty years, males showed a decreasing trend in recombination rate that coincided with the artificial selection for milk production. Sex-specific GWAS analyses identified PRDM9 and CPLX1 to have significant effects on genome-wide recombination rate in both sexes. Two novel loci, NEK9 and REC114, were associated with recombination rate in both sexes, whereas three loci, MSH4, SMC3 and CEP55, affected recombination rate in females only. Among the multiple PRDM9 paralogues on the bovine genome, our GWAS of recombination hotspot usage together with linkage analysis identified the PRDM9 paralogue on chromosome 1 to be associated in the U.S. Holstein data. Given the largest sample size ever reported for such studies, our results reveal new insights into the understanding of cattle and mammalian recombination.

Cattle Sex-Specific Recombination and Genetic Control from a Large Pedigree Analysis

PubMed Central

Ma, Li; O'Connell, Jeffrey R.; VanRaden, Paul M.; Shen, Botong; Padhi, Abinash; Sun, Chuanyu; Bickhart, Derek M.; Cole, John B.; Null, Daniel J.; Liu, George E.; Da, Yang; Wiggans, George R.

2015-01-01

Meiotic recombination is an essential biological process that generates genetic diversity and ensures proper segregation of chromosomes during meiosis. From a large USDA dairy cattle pedigree with over half a million genotyped animals, we extracted 186,927 three-generation families, identified over 8.5 million maternal and paternal recombination events, and constructed sex-specific recombination maps for 59,309 autosomal SNPs. The recombination map spans for 25.5 Morgans in males and 23.2 Morgans in females, for a total studied region of 2,516 Mb (986 kb/cM in males and 1,085 kb/cM in females). The male map is 10% longer than the female map and the sex difference is most pronounced in the subtelomeric regions. We identified 1,792 male and 1,885 female putative recombination hotspots, with 720 hotspots shared between sexes. These hotspots encompass 3% of the genome but account for 25% of the genome-wide recombination events in both sexes. During the past forty years, males showed a decreasing trend in recombination rate that coincided with the artificial selection for milk production. Sex-specific GWAS analyses identified PRDM9 and CPLX1 to have significant effects on genome-wide recombination rate in both sexes. Two novel loci, NEK9 and REC114, were associated with recombination rate in both sexes, whereas three loci, MSH4, SMC3 and CEP55, affected recombination rate in females only. Among the multiple PRDM9 paralogues on the bovine genome, our GWAS of recombination hotspot usage together with linkage analysis identified the PRDM9 paralogue on chromosome 1 to be associated in the U.S. Holstein data. Given the largest sample size ever reported for such studies, our results reveal new insights into the understanding of cattle and mammalian recombination. PMID:26540184

"Educational Regionalization" and the Gated Global: The Construction of the Caribbean Educational Policy Space

ERIC Educational Resources Information Center

Jules, Tavis D.

2015-01-01

This article draws on "regime theory," particularly on the concepts of cooperation, compatibility of interests, and proclivity to compromise, to examine the rise of the Caribbean Educational Policy Space (CEPS). In making this argument, with the aid of a content analysis of 26 educational policies from the 15 member states of the…

Wrestling the Devil in the Details: An Early Look at Restructuring in California

ERIC Educational Resources Information Center

Scott, Caitlin

2006-01-01

To learn more about district and school decision making for No Child Left Behind (NCLB) restructuring, the Center on Education Policy (CEP) turned to California, a state with a substantial number of schools in restructuring and several state and regional supports for making decisions about restructuring. In the summer and fall of 2005, CEP…

Student Motivation: An Overlooked Piece of School Reform. Summary

ERIC Educational Resources Information Center

Usher, Alexandra; Kober, Nancy

2012-01-01

This summary report by the Center on Education Policy (CEP) pulls together findings from a wide array of studies on student motivation by scholars in a range of disciplines, as well as lessons from programs around the country intended to increase motivation. It is intended to start a conversation about the importance of motivation and the policies…

It's Unanimous: "Effective Character Education Is Not Quick or Superficial, and It Begins with Caring Relationships"

ERIC Educational Resources Information Center

Sojourner, Russ

2014-01-01

Russ Sojourner is the Schools of Character Director for the Character Education Partnership (CEP) in Washington, DC. In this article he begins by saying that Daniel Lapsley and Charles Murray's articles presented in this issue of "Journal of Character Education" are clearly concerned about the compelling (and daunting) challenges facing…

Contribution of the Visual Perception and Graphic Production Systems to the Copying of Complex Geometrical Drawings: A Developmental Study

ERIC Educational Resources Information Center

Bouaziz, Serge; Magnan, Annie

2007-01-01

The aim of this study was to determine the contribution of the visual perception and graphic production systems [Van Sommers, P. (1989). "A system for drawing and drawing-related neuropsychology." "Cognitive Neuropsychology," 6, 117-164] to the manifestation of the "Centripetal Execution Principle" (CEP), a graphic…

Benchmarking Attosecond Physics with Atomic Hydrogen

DTIC Science & Technology

2015-05-25

theoretical simulations are available in this regime. We provided accurate reference data on the photoionization yield and the CEP-dependent...this difficulty. This experiment claimed to show that, contrary to current understanding, the photoionization of an atomic electron is not an... photoion yield and transferrable intensity calibration. The dependence of photoionization probability on laser intensity is one of the most

77 FR 42273 - Solid Urea From the Russian Federation: Preliminary Results of Antidumping Duty Administrative...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-18

.... Although the HTSUS subheading is provided for convenience and customs purposes, the written description of... or exporter's records kept in the ordinary course of business, as the date of sale. The regulation... that of the starting-price sales in the home market. For CEP, the level of trade is that of the...

Testing Means-Tested Aid. CEP Discussion Paper No. 1396. Revised

ERIC Educational Resources Information Center

Murphy, Richard; Wyness, Gill

2016-01-01

Inequalities do not end once students enter higher education. Yet, the majority of papers on the effectiveness of higher education aid examine its impact on college enrolment. In this paper, we provide evidence on the causal impact of means-tested but otherwise unconditional financial aid on the outcomes of students who have already enrolled in…

76 FR 76128 - Diamond Sawblades and Parts Thereof From the Republic of Korea: Preliminary Results of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-06

... trade, as discussed in the ``Cost of Production Analysis'' section, below. Product Comparisons In... in a pattern of consistent price differences between the sales on which NV is based and comparison... Department bases its CEP LOT analysis on the sale to the producer/ exporter's U.S. affiliate and, thus...

Quality in Early Years Settings and Children's School Achievement. CEP Discussion Paper No. 1468

ERIC Educational Resources Information Center

Blanden, Jo; Hansen, Kirstine; McNally, Sandra

2017-01-01

Childcare quality is often thought to be important for influencing children's subsequent attainment at school. The English Government regulates the quality of early education by setting minimum levels of qualifications for workers and grading settings based on a national Inspectorate (OfSTED). This paper uses administrative data on over two…

Explaining Cross-Racial Differences in the Educational Gender Gap. CEP Discussion Paper No. 1220

ERIC Educational Resources Information Center

Aucejo, Esteban

2013-01-01

The sizable gender gap in college enrolment, especially among African Americans, constitutes a puzzling empirical regularity that may have serious consequences on marriage markets, male labor force participation and the diversity of college campuses. For instance, only 35.7 percent of all African American undergraduate students were men in 2004.…

The Employment Situation in Selected Communities on the Lower Eastern Shore of Maryland.

ERIC Educational Resources Information Center

Thaxton, Louis C.; Tuthill, Dean F.

This is an illustrated report on some findings of the Citizens Education Project (CEP), a 1979 survey of the employment situation of communities in five Maryland counties. The study was conducted by the Maryland Cooperative Extension Service, University of Maryland, College Park and Eastern Shore, with funding from Extension Program 1890. The…

Raman Investigation of Structural Photoinduced Irreversible Changes of Ga(10)Ge(25)S(65) Chalcogenide Glasses

DTIC Science & Technology

2001-06-01

Brazil cDepto de Quimica - Universidade Federal de Juiz de Fora, Juiz de Fora, MG- Brazil dEscola de Engenharia de Sao Carlos- - Universidade de Sao Paulo...Inorganic Materials IIC ASCR and ICT, Pelleova 24, Prague 6, Czech Republic blnstituto de Quimica - UNESP- C.P. 355, CEP: 14801-970, Araraquara, SP

Virtual Reality Transfer Protocol (VRTP): Implementing a Monitor Application for the Real-Time Transport Protocol (RTP) Using the JAVA Media Framework (JMF)

DTIC Science & Technology

1999-09-01

application, a complete specification will require one or more companion documents, as follows. 1. Profile Specification Documents A Profile...Rio de Janeiro - RJ - Brazil 21. Diretoria de Sistemas de Armas da Marinha Rua Primeiro de Marco, 118 Rio de Janeiro - RJ - Brazil CEP 20010 22

What Now? Lessons from Michigan about Restructuring Schools and Next Steps under NCLB

ERIC Educational Resources Information Center

Scott, Caitlin

2007-01-01

Because federal law offers little guidance for continually-failing schools, the Center on Education Policy (CEP) conducted a study from August 2006 to January 2007 in Michigan to explore questions of what happens after restructuring, particularly to schools that continue to fail to meet achievement targets. Because it had an accountability system…

Schools of Character: Reclaiming America's Values for Tomorrow's Workforce. The 1998 Ninth Annual "Business Week" Awards for Instructional Innovation.

ERIC Educational Resources Information Center

McGraw-Hill Companies, New York, NY. Educational and Professional Publishing Group.

This booklet profiles 10 schools that have successfully integrated character education into the lives of their students. The Character Education Partnership (CEP), in its "Eleven Principles of Effective Character Education," has articulated the kinds of efforts that its members believe have proven successful in helping young people…

Fatigue study of ultra-runners: Presentation of a new approach for the separation of GRF signals components

NASA Astrophysics Data System (ADS)

Zakaria, F. A.; El Badaoui, M.; Lamraoui, M.; Khalil, M.

2016-06-01

In recent years, ultra-marathon running has become increasingly popular in many countries around the world. The ability to run for long hours has played a role in human evolution. It is known that the etiology of fatigue depends upon the exercise under consideration. In order to characterize and find a full description of the fatigue and its effects on the human locomotion mechanics, and to extract the relevant parameters and information for diagnosis, we have investigated the changes in running mechanics. More specifically, the ground reaction force (GRF) manifestations of fatigue, have been investigated by using advanced signal processing tools. GRF signals are composed of two parts: an active peak representing the propulsive force and a passive peak that represents the impact force. The impact force is the major factor indicating the reaction of muscle, that may reflects the fatigue state and performance of the muscle. In this article, we focused on the treatment of biomechanical signals for the purpose of GRF components separation where the aim is to separate the contribution of the active components and the passive components. For this reason, we proposed a new algorithm, based on the Gaussian decomposition and non-linear least squares method that will achieve the desired goal. We then compare the results of separation with a proposed BSS based method i.e. "FastICA algorithm". We also compare the results with that obtained by Sabri et al. [1-3] who used different BSS techniques which gave bad and fair results. The separated passive signal is then proved to contain a mixture of a deterministic phenomenon and a stationary random phenomenon, where both phenomena are separated using the cepstral editing procedure (CEP) method. CEP is applied after signal synchronization using method with maximization of the inter-correlation function. The random part is then proved to be cyclostationary of order 2. A real application examined the biomechanical changes occurring in the GRF signals of ten experienced ultra- runners during 24 h of continuous running. The aim was to characterize and better understand the mechanical phenomena behind the GRF signals' behavior and also to analyze and characterize the runner's step in order to quantify the degree of fatigue. This could allow a better characterization and a full innovative description of the different fatigue states of a runner. Moreover, we introduce some parameters which were measured in these subjects during the 24 h of running, such as the cyclic autocorrelation function, the cyclic frequency and the energy of the integrated autocorrelation function at alpha equal to zero and at the first cyclic frequency α1. The results quantify the changes induced by runners over time, where after an extreme ultra-long duration of running, could lead to significant insights into the evolution of fatigue.

Mechanisms and pathways of growth failure in primordial dwarfism.

PubMed

Klingseisen, Anna; Jackson, Andrew P

2011-10-01

The greatest difference between species is size; however, the developmental mechanisms determining organism growth remain poorly understood. Primordial dwarfism is a group of human single-gene disorders with extreme global growth failure (which includes Seckel syndrome, microcephalic osteodysplastic primordial dwarfism I [MOPD] types I and II, and Meier-Gorlin syndrome). Ten genes have now been identified for microcephalic primordial dwarfism, encoding proteins involved in fundamental cellular processes including genome replication (ORC1 [origin recognition complex 1], ORC4, ORC6, CDT1, and CDC6), DNA damage response (ATR [ataxia-telangiectasia and Rad3-related]), mRNA splicing (U4atac), and centrosome function (CEP152, PCNT, and CPAP). Here, we review the cellular and developmental mechanisms underlying the pathogenesis of these conditions and address whether further study of these genes could provide novel insight into the physiological regulation of organism growth.

Application of alternative fixatives to formalin in diagnostic pathology

PubMed Central

Gatta, L. Benerini; Cadei, M.; Balzarini, P.; Castriciano, S.; Paroni, R.; Verzeletti, A.; Cortellini, V.; De Ferrari, F.; Grigolato, P.

2012-01-01

Fixation is a critical step in the preparation of tissues for histopathology. The aim of this study was to investigate the effects of different fixatives vs formalin on proteins and DNA, and to evaluate alternative fixation for morphological diagnosis and nucleic acid preservation for molecular methods. Forty tissues were fixed for 24 h with six different fixatives: the gold standard fixative formalin, the historical fixatives Bouin and Hollande, and the alternative fixatives Greenfix, UPM and CyMol. Tissues were stained (Haematoxylin-Eosin, Periodic Acid Schiff, Trichromic, Alcian-blue, High Iron Diamine stainings), and their antigenicity was determined by immunohistochemistry (performed with PAN-CK, CD31, Ki-67, S100, CD68, AML antibodies). DNA extraction, KRAS sequencing, FISH for CEP-17, and flow cytometry analysis of nuclear DNA content were applied. For cell morphology the alternative fixatives (Greenfix, UPM, CyMol) were equivalent to formalin. As expected, Hollande proved to be the best fixative for morphology. The morphology obtained with Bouin was comparable to the one with formalin. Hollande was the best fixative for histochemistry. Bouin proved to be equivalent to formalin. The alternative fixatives were equivalent to formalin, although with greater variability in haematoxylin-eosin staining. It proved the possibility to obtain immunohistochemical staining largely equivalent to that following formalin-fixation with the following fixatives: Greenfix, Hollande, UPM and CyMol. The tissues fixed in Bouin did not provide results comparable to those obtained with formalin. The DNA extracted from samples fixed with alternative fixatives was found to be suitable for molecular analysis. PMID:22688293

Who Decided College Access in Chinese Secondary Education? Rural-Urban Inequality of Basic Education in Contemporary China

ERIC Educational Resources Information Center

Li, Jian

2016-01-01

This paper investigates the rural-urban inequalities in basic education of contemporary China. The China Education Panel Survey (2013-2014) (CEPS) was utilized to analyze the gaps between rural and urban inequality in junior high schools in terms of three domains, which include the equalities of access, inputs, and outcomes. From the sociocultural…

The Effects of Resources across School Phases: A Summary of Recent Evidence. CEP Discussion Paper No. 1226

ERIC Educational Resources Information Center

Gibbons, Stephen; McNally, Sandra

2013-01-01

This report provides an overview and discussion of the past decade of academic evidence on the causal effects of resources in schooling on students' outcomes. Early evidence lacked good strategies for estimating the effects of schools resources, leading many people to conclude that spending more on schools had no effect. More recent evidence using…

Unexpected School Reform: Academisation of Primary Schools in England. CEP Discussion Paper No. 1455

ERIC Educational Resources Information Center

Eyles, Andrew; Machin, Stephen; McNally, Sandra

2016-01-01

The change of government in 2010 provoked a large structural change in the English education landscape. Unexpectedly, the new government offered primary schools the chance to have "the freedom and the power to take control of their own destiny", with better performing schools given a green light to convert to become an academy school on…

STEM Graduates and Secondary School Curriculum: Does Early Exposure to Science Matter? CEP Discussion Paper No. 1443

ERIC Educational Resources Information Center

De Philippis, Marta

2016-01-01

Increasing the number of Science, Technology, Engineering and Math (STEM) university graduates is considered a key element for long-term productivity and competitiveness in the global economy. Still, little is known about what actually drives and shapes students' choices. This paper focusses on secondary school students at the very top of the…

Application of Logistic Regression and Survival Analysis to the Study of CEP, Manpower Performance and Attrition

DTIC Science & Technology

1993-09-01

compared to the male counterparts, the study does not discriminate between the two sexes . Out of the total of about 17000 records, about 30% of them are...few naval officers and pilots. Almost all the officers are in the Army. Hence, for the support vocations and sevice groups effects the study does not

Multitask Agents and Incentives: The Case of Teaching and Research for University Professors. CEP Discussion Paper No. 1386

ERIC Educational Resources Information Center

De Philippis, Marta

2015-01-01

This paper evaluates the behavioural responses of multitask agents to the provision of incentives skewed towards one task only. In particular it studies the case of strong research incentives for university professors and it analyzes their effects on the way university faculty members allocate effort between teaching and quantity and quality of…

The Introduction of Academy Schools to England's Education. CEP Discussion Paper No. 1368

ERIC Educational Resources Information Center

Eyles, Andrew; Machin, Stephen

2015-01-01

We study the origins of what has become one of the most radical and encompassing programmes of school reform seen in the recent past amongst advanced countries--the introduction of academy schools to English secondary education. Academies are state schools that are allowed to run in an autonomous manner which is free from local authority control.…

Development of the 2007 Chemical Decontaminant Source Document

DTIC Science & Technology

2009-03-01

Chemical Agent Simulant Specific DEM diethyl malonate MeS methyl salicylate PEG200 Polyethylene glycol 200 TEP triethyl phosphate Group 6...simulants • H-agent simulants o Methyl salicylate (MeS) o Chloroethyl phenyl sulfide (CEPS) o Chloroethyl ethyl sulfide (CEES) • VX simulants... Methyl bromide Ethyl phosphonothioic dichloride Sulfur dioxide Methyl chloroformate Ethyl phosphonic dichloride Sulfuric acid Methyl chlorosilane

"It's Different Now:" How Exit Exams Are Affecting Teaching and Learning in Jackson and Austin

ERIC Educational Resources Information Center

Zabala, Dalia; Minnici, Angela; Kober, Nancy, Ed.

2007-01-01

Since much of the previous research on exit exams, including CEP's own work, has looked at national patterns of implementation and passing rates, this study aimed to benefit policy and practice by focusing on the local level. Specifically, case studies were conducted in Jackson, MS and Austin, TX that examined how classroom instruction and other…

Student Achievement since 2005: On State Tests and State-Level NAEP

ERIC Educational Resources Information Center

Education Digest: Essential Readings Condensed for Quick Review, 2010

2010-01-01

This article reports on a new study released by the Center on Education Policy (CEP) of states with five years of comparable test data which finds that student achievement in reading and math rose between 2005 and 2009 on state tests as well as on National Assessment of Education Progress (NAEP). The report also finds overlapping achievement gains…

School Districts' Perspectives on the Economic Stimulus Package: School Improvement Grants Present Uncertainty and Opportunity

ERIC Educational Resources Information Center

Scott, Caitlin

2010-01-01

The information in this report is drawn from the responses of a nationally representative sample of school districts to a broader Center on Education Policy (CEP) survey on American Recovery and Reinvestment Act of 2009 (ARRA) administered in the spring of 2010. Survey responses were weighted to draw conclusions for all districts in the 50 states…

Paying out and Crowding out? The Globalisation of Higher Education. CEP Discussion Paper No. 1299

ERIC Educational Resources Information Center

Machin, Stephen; Murphy, Richard

2014-01-01

We investigate the rapid influx of overseas students into UK higher education and the impact on the number of domestic students. Using administrative data since 1994/5, we find no evidence of crowd out of domestic undergraduate students and indications of increases in the domestic numbers of postgraduate students as overseas enrolments have grown.…

Assessing the Effect of School Days and Absences on Test Score Performance. CEP Discussion Paper No. 1302

ERIC Educational Resources Information Center

Aucejo, Esteban M.; Romano, Teresa Foy

2014-01-01

While instructional time is viewed as crucial to learning, little is known about the effectiveness of reducing absences relative to increasing the number of school days. In this regard, this paper jointly estimates the effect of absences and length of the school calendar on test score performance. Using administrative data from North Carolina…

Exploiting the Immunological Effects of Standard Treatments in Prostate Cancer

DTIC Science & Technology

2009-03-01

GTG CCT 1114 In progress PTMA F: CAC CAT GTC AGA CGC AGC CGT A R: GTC ATC CTC GTC GGT CTT CT 331 Cloned successfully CEP78 F: CAC CAT GAT CGA CTC CGT...Mde L, Gray A, Hubby B, Kast WM. In vivo effects of vaccination with six-transmembrane epithelial antigen of the prostate: a candidate antigen for

A Novel INS and Doppler Sensors Calibration Method for Long Range Underwater Vehicle Navigation

PubMed Central

Tang, Kanghua; Wang, Jinling; Li, Wanli; Wu, Wenqi

2013-01-01

Since the drifts of Inertial Navigation System (INS) solutions are inevitable and also grow over time, a Doppler Velocity Log (DVL) is used to aid the INS to restrain its error growth. Therefore, INS/DVL integration is a common approach for Autonomous Underwater Vehicle (AUV) navigation. The parameters including the scale factor of DVL and misalignments between INS and DVL are key factors which limit the accuracy of the INS/DVL integration. In this paper, a novel parameter calibration method is proposed. An iterative implementation of the method is designed to reduce the error caused by INS initial alignment. Furthermore, a simplified INS/DVL integration scheme is employed. The proposed method is evaluated with both river trial and sea trial data sets. Using 0.03°/h(1σ) ring laser gyroscopes, 5 × 10−5 g(1σ) quartz accelerometers and DVL with accuracy 0.5% V ± 0.5 cm/s, INS/DVL integrated navigation can reach an accuracy of about 1‰ of distance travelled (CEP) in a river trial and 2‰ of distance travelled (CEP) in a sea trial. PMID:24169542

Molecular genetics of human primary microcephaly: an overview

PubMed Central

2015-01-01

Autosomal recessive primary microcephaly (MCPH) is a neurodevelopmental disorder that is characterised by microcephaly present at birth and non-progressive mental retardation. Microcephaly is the outcome of a smaller but architecturally normal brain; the cerebral cortex exhibits a significant decrease in size. MCPH is a neurogenic mitotic disorder, though affected patients demonstrate normal neuronal migration, neuronal apoptosis and neural function. Twelve MCPH loci (MCPH1-MCPH12) have been mapped to date from various populations around the world and contain the following genes: Microcephalin, WDR62, CDK5RAP2, CASC5, ASPM, CENPJ, STIL, CEP135, CEP152, ZNF335, PHC1 and CDK6. It is predicted that MCPH gene mutations may lead to the disease phenotype due to a disturbed mitotic spindle orientation, premature chromosomal condensation, signalling response as a result of damaged DNA, microtubule dynamics, transcriptional control or a few other hidden centrosomal mechanisms that can regulate the number of neurons produced by neuronal precursor cells. Additional findings have further elucidated the microcephaly aetiology and pathophysiology, which has informed the clinical management of families suffering from MCPH. The provision of molecular diagnosis and genetic counselling may help to decrease the frequency of this disorder. PMID:25951892

Theory and computer simulation of hard-core Yukawa mixtures: thermodynamical, structural and phase coexistence properties.

PubMed

Mkanya, Anele; Pellicane, Giuseppe; Pini, Davide; Caccamo, Carlo

2017-09-13

We report extensive calculations, based on the modified hypernetted chain (MHNC) theory, on the hierarchical reference theory (HRT), and on Monte Carlo simulations, of thermodynamical, structural and phase coexistence properties of symmetric binary hard-core Yukawa mixtures (HCYM) with attractive interactions at equal species concentration. The obtained results are throughout compared with those available in the literature for the same systems. It turns out that the MHNC predictions for thermodynamic and structural quantities are quite accurate in comparison with the MC data. The HRT is equally accurate for thermodynamics, and slightly less accurate for structure. Liquid-vapor (LV) and liquid-liquid (LL) consolute coexistence conditions as emerging from simulations, are also highly satisfactorily reproduced by both the MHNC and HRT for relatively long ranged potentials. When the potential range reduces, the MHNC faces problems in determining the LV binodal line; however, the LL consolute line and the critical end point (CEP) temperature and density turn out to be still satisfactorily predicted within this theory. The HRT also predicts with good accuracy the CEP position. The possibility of employing liquid state theories HCYM for the purpose of reliably determining phase equilibria in multicomponent colloidal fluids of current technological interest, is discussed.

Theory and computer simulation of hard-core Yukawa mixtures: thermodynamical, structural and phase coexistence properties

NASA Astrophysics Data System (ADS)

Mkanya, Anele; Pellicane, Giuseppe; Pini, Davide; Caccamo, Carlo

2017-09-01

We report extensive calculations, based on the modified hypernetted chain (MHNC) theory, on the hierarchical reference theory (HRT), and on Monte Carlo simulations, of thermodynamical, structural and phase coexistence properties of symmetric binary hard-core Yukawa mixtures (HCYM) with attractive interactions at equal species concentration. The obtained results are throughout compared with those available in the literature for the same systems. It turns out that the MHNC predictions for thermodynamic and structural quantities are quite accurate in comparison with the MC data. The HRT is equally accurate for thermodynamics, and slightly less accurate for structure. Liquid-vapor (LV) and liquid-liquid (LL) consolute coexistence conditions as emerging from simulations, are also highly satisfactorily reproduced by both the MHNC and HRT for relatively long ranged potentials. When the potential range reduces, the MHNC faces problems in determining the LV binodal line; however, the LL consolute line and the critical end point (CEP) temperature and density turn out to be still satisfactorily predicted within this theory. The HRT also predicts with good accuracy the CEP position. The possibility of employing liquid state theories HCYM for the purpose of reliably determining phase equilibria in multicomponent colloidal fluids of current technological interest, is discussed.

[The French medecine pricing committee].

PubMed

Giorgi, D

2017-09-01

The French medicine pricing committee (CEPS) has to reconcile several major constraints, including optimal patient access to medicines and a good control of expenditures on reimbursable medicines. From 2013 to 2015, drug price decreases and discounts obtained by CEPS contributed more than € 5 billion to the balance of the health insurance accounts. As for price setting, there is a significant drop in the prices of medicines in France once they are registered for reimbursement. France is affected by a limited, but costly, flow of innovative medicines, whose prices are higher than those of previous generations, a reflection of an international gradient to which France is obviously subject, despite prices that remain at the low end of the range in Western Europe. The provision of innovative medicines for all patients who need them has been ensured in France over the last fifteen years at a controlled cost. But with the arrival of new expensive products, a resolute policy of control of expenditures must take over from the fall in prices, and original financing channels will have to be explored. Copyright © 2017 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.

Chandra Observations of the Eclipsing Wolf-Rayet Binary CQ CepOver a Full Orbital Cycle

NASA Astrophysics Data System (ADS)

Skinner, Steve L.; Guedel, Manuel; Schmutz, Werner; Zhekov, Svetozar

2018-06-01

We present results of Chandra X-ray observations and simultaneous optical light curves of the short-period (1.64 d) eclipsing WN6+O9 binary system CQ Cep obtained in 2013 and 2017 covering a full binary orbit. Our primary objective was to compare the observed X-ray properties with colliding wind shock theory, which predicts that the hottest shock plasma (T > 20 MK) will form on or near the line-of-centers between the stars. Thus, X-ray variability is expected during eclipses when the hottest plasma is occulted. The X-ray spectrum is strikingly similar to apparently single WN6 stars such as WR 134 and spectral lines reveal plasma over a broad range of temperatures T ~ 4 - 40 MK. Both primary and secondary optical eclipses were clearly detected and provide an accurate orbital period determination (P = 1.6412 d). The X-ray emission remained remarkably steady throughout the orbit and statistical tests give a low probability of variability. The lack of significant X-ray variabililty during eclipses indicates that the X-ray emission is not confined along the line-of-centers but is extended on larger spatial scales, contrary to colliding wind predictions.

ALK inhibitors in non-small cell lung cancer: the latest evidence and developments

PubMed Central

Sullivan, Ivana; Planchard, David

2016-01-01

The treatment of patients with advanced non-small cell lung cancer (NSCLC) harbouring chromosomal rearrangements of ALK (anaplastic lymphoma kinase) was revolutionized by crizotinib, a small molecule inhibitor of ALK, ROS1 and MET. Unfortunately, the disease progressed within the first 12 months in most of the patients because of the development of crizotinib resistance in the majority of patients and the emergence of acquired resistance mutations in most of them. Many of them had been reported even before its approval leading to the rapid development of second-generation ALK inhibitors for crizotinib-resistant NSCLC. In the last few years, novel potent ALK inhibitors with promising results and a good toxicity profile have become available: ceritinib (LDK378), alectinib (RG7853/AF-802/RO5424802/CH5424802), brigatinib (AP26113), entrectinib (RXDX-101, NMS-E628), PF-06463922, ASP3026, TSR-011, X-376/X-396 and CEP-28122/CEP-37440. Moreover, HSP90 (90 kDa heat shock protein) inhibitors have demonstrated clinical activity in patients with ALK+ NSCLC. This review focuses on the molecular and clinical properties of this new generation of ALK inhibitors under development in the clinic. PMID:26753004

Symmetry-controlled time structure of high-harmonic carrier fields from a solid

PubMed Central

Langer, F.; Hohenleutner, M.; Huttner, U.; Koch, S. W.; Kira, M.; Huber, R.

2017-01-01

High-harmonic (HH) generation in crystalline solids1–6 marks an exciting development, with potential applications in high-efficiency attosecond sources7, all-optical bandstructure reconstruction8,9, and quasiparticle collisions10,11. Although the spectral1–4 and temporal shape5 of the HH intensity has been described microscopically1–6,12, the properties of the underlying HH carrier wave have remained elusive. Here we analyse the train of HH waveforms generated in a crystalline solid by consecutive half cycles of the same driving pulse. Extending the concept of frequency combs13–15 to optical clock rates, we show how the polarization and carrier-envelope phase (CEP) of HH pulses can be controlled by crystal symmetry. For some crystal directions, we can separate two orthogonally polarized HH combs mutually offset by the driving frequency to form a comb of even and odd harmonic orders. The corresponding CEP of successive pulses is constant or offset by π, depending on the polarization. In the context of a quantum description of solids, we identify novel capabilities for polarization- and phase-shaping of HH waveforms that cannot be accessed with gaseous sources. PMID:28572835

Use of Statistical Analysis of Acoustic Emission Data on Carbon-Epoxy COPV Materials-of-Construction for Enhanced Felicity Ratio Onset Determination

NASA Technical Reports Server (NTRS)

Abraham, Arick Reed A.; Johnson, Kenneth L.; Nichols, Charles T.; Saulsberry, Regor L.; Waller, Jess M.

2012-01-01

Broadband modal acoustic emission (AE) data were acquired during intermittent load hold tensile test profiles on Toray T1000G carbon fiber-reinforced epoxy (C/Ep) single tow specimens. A novel trend seeking statistical method to determine the onset of significant AE was developed, resulting in more linear decreases in the Felicity ratio (FR) with load, potentially leading to more accurate failure prediction. The method developed uses an exponentially weighted moving average (EWMA) control chart. Comparison of the EWMA with previously used FR onset methods, namely the discrete (n), mean (n (raised bar)), normalized (n%) and normalized mean (n(raised bar)%) methods, revealed the EWMA method yields more consistently linear FR versus load relationships between specimens. Other findings include a correlation between AE data richness and FR linearity based on the FR methods discussed in this paper, and evidence of premature failure at lower than expected loads. Application of the EWMA method should be extended to other composite materials and, eventually, composite components such as composite overwrapped pressure vessels. Furthermore, future experiments should attempt to uncover the factors responsible for infant mortality in C/Ep strands.

Generation of single-cycle mid-infrared pulses via coherent synthesis.

PubMed

Ma, Fen; Liu, Hongjun; Huang, Nan; Sun, Qibing

2012-12-17

A new approach for the generation of single-cycle mid-infrared pulses without complicated control systems is proposed, which is based on direct coherent synthesis of two idlers generated by difference frequency generation (DFG) processes. It is found that the waveform of synthesized pulses is mainly determined by the spectra superposition, the carrier-envelope phase (CEP) difference, the relative timing and the chirp ratio between the idlers. The influences of these parameters on the synthesized waveform are also numerically calculated and analyzed via second-order autocorrelation, which offers general guidelines for the waveform optimization. The single-cycle synthesized mid-infrared pulses, which are centered at 4233 nm with the spectrum spanning from 3000 nm to 7000 nm, are achieved by carefully optimizing these parameters. The single-cycle mid-infrared laser source presents the possibility of investigating and controlling the strong field light-matter interaction.

Mechanisms and pathways of growth failure in primordial dwarfism

PubMed Central

Klingseisen, Anna; Jackson, Andrew P.

2011-01-01

The greatest difference between species is size; however, the developmental mechanisms determining organism growth remain poorly understood. Primordial dwarfism is a group of human single-gene disorders with extreme global growth failure (which includes Seckel syndrome, microcephalic osteodysplastic primordial dwarfism I [MOPD] types I and II, and Meier-Gorlin syndrome). Ten genes have now been identified for microcephalic primordial dwarfism, encoding proteins involved in fundamental cellular processes including genome replication (ORC1 [origin recognition complex 1], ORC4, ORC6, CDT1, and CDC6), DNA damage response (ATR [ataxia-telangiectasia and Rad3-related]), mRNA splicing (U4atac), and centrosome function (CEP152, PCNT, and CPAP). Here, we review the cellular and developmental mechanisms underlying the pathogenesis of these conditions and address whether further study of these genes could provide novel insight into the physiological regulation of organism growth. PMID:21979914

Nonlinear Wave Propagation

DTIC Science & Technology

2009-02-12

describes the mode- locking and dynamics of solitons . A characteristic of short pulse lasers is the carrier-envelope phase (CEP) slip which is the change in...and evolution of pulses in mode- locked lasers that are operating in the soliton regime. To describe our research in more detail, we fix typical...solutions with mode- locking evolution. Otherwise the solitons are found to be unstable; either dispersing to radiation or evolving into nonlocalized

Education and Health Knowledge: Evidence from UK Compulsory Schooling Reform. CEP Discussion Paper No. 1297

ERIC Educational Resources Information Center

Johnston, David W.; Lordon, Grace; Shields, Michael A.; Suziedelyte, Agne

2014-01-01

We investigate if there is a causal link between education and health knowledge using data from the 1984/85 and 1991/92 waves of the UK Health and Lifestyle Survey (HALS). Uniquely, the survey asks respondents what they think are the main causes of ten common health conditions, and we compare these answers to those given by medical professionals…

State Test Score Trends through 2008-09, Part 4: Is Achievement Improving and Are Gaps Narrowing for Title I Students?

ERIC Educational Resources Information Center

Kober, Nancy; McMurrer, Jennifer; Silva, Malini R.

2011-01-01

Title I provides extra instructional services designed to raise achievement for low-performing students in schools with relatively high poverty rates, and for all students in many of the nation's highest-poverty schools. To learn more about how well Title I students are performing academically, the Center on Education Policy (CEP) compared…

State Test Score Trends through 2008-09, Part 5: Progress Lags in High School, Especially for Advanced Achievers

ERIC Educational Resources Information Center

McMurrer, Jennifer; Kober, Nancy

2011-01-01

This report by the Center on Education Policy (CEP), an independent nonprofit organization, examines trends in the achievement of high school students on the state reading/English language arts (ELA) and mathematics tests used for accountability under the No Child Left Behind Act (NCLB). In most states, these tests are first administered in grade…

Economic Uncertainty, Parental Selection and the Criminal Activity of the "Children of the Wall." CEP Discussion Paper No. 1256

ERIC Educational Resources Information Center

Chevalier, Arnaud; Marie, Olivier

2014-01-01

We study the link between parental selection and children criminality in a new context. After the fall of the Berlin Wall, East Germany experienced an unprecedented temporary drop in fertility driven by economic uncertainty. We exploit this natural experiment to estimate that the children from these (smaller) cohorts are 40 percent more likely to…

Higher Education Funding Reforms: A Comprehensive Analysis of Educational and Labour Market Outcomes in England. CEP Discussion Paper No. 1529

ERIC Educational Resources Information Center

Azmat, Ghazala; Simion, Stefania

2018-01-01

This paper investigates the impact of changes in the funding of higher education in England on students' choices and outcomes. Over the last two decades--through three major reforms in 1998, 2006 and 2012--undergraduate university education in public universities moved from being free to students and state funded to charging substantial tuition…

What's in a Name? Expectations, Heuristics and Choice during a Period of Radical School Reform. CEP Discussion Paper No. 1477

ERIC Educational Resources Information Center

Bertoni, Marco; Gibbons, Stephen; Silva, Olmo

2017-01-01

Education policy worldwide has sought to incentivize school improvement and facilitate pupil-school matching by introducing reforms that promote autonomy and choice. Understanding the way in which families form preferences during these periods of reform is crucial for evaluating the impact of such policies. We study the effects on choice of a…

Giving a Little Help to Girls? Evidence on Grade Discrimination and Its Effect on Students' Achievement. CEP Discussion Paper No. 1341

ERIC Educational Resources Information Center

Terrier, Camille

2015-01-01

This paper tests if gender-discrimination in grading affects pupils' achievements and course choices. I use a unique dataset containing grades given by teachers, scores obtained anonymously by pupils at different ages, and their course choice during high school. Based on double-differences, the identification of the gender bias in grades suggests…

Precision Strike 2008 Summer Forum

DTIC Science & Technology

2008-01-11

extended ranges, 360--mounted and dismounted Technical fire direction and limited tactical fire direction on all delivery systems Delivery systems that...can rapidly emplace/displace with high rates of fire Accurate on demand, meteorological data to delivery system ranges All munitions with less than 50M...CEP at all ranges Munitions that provide a variety of effects in any environment To achieve this, Field Artillery needs these “enablers” Target

Einstein observations of three classical Cepheids

NASA Technical Reports Server (NTRS)

Bohm-Vitense, E.; Parsons, S. B.

1983-01-01

We have looked for X-ray emission from the classical Cepheids delta Cep, beta Dor, and zeta Gem during phases when the latter two stars show emission in low excitation chromospheric lines. No X-ray flux was detected except possibly from zeta Gem at phase 0.26. Derived upper limits are in line with emission flux or upper limits obtained for other F and G supergiants.

5-fs, Multi-mJ, CEP-locked parametric chirped-pulse amplifier pumped by a 450-nm source at 1 kHz.

PubMed

Adachi, S; Ishii, N; Kanai, T; Kosuge, A; Itatani, J; Kobayashi, Y; Yoshitomi, D; Torizuka, K; Watanabe, S

2008-09-15

We report on the development of an optical parametric chirpedpulse amplifier at a 1-kHz repetition rate with a 5.5-fs pulse duration, a 2.7-mJ pulse energy and carrier-envelope phase-control. The amplifier is pumped by a 450-nm pulse from a frequency-doubled Ti:sapphire laser.

Graduate Returns, Degree Class Premia and Higher Education Expansion in the UK. CEP Discussion Paper No. 1392

ERIC Educational Resources Information Center

Naylor, Robin; Smith, Jeremy; Telhaj, Shqiponja

2015-01-01

We investigate the extent to which graduate returns vary according to the class of degree achieved by UK university students and examine changes over time in estimated degree class premia. Using a variety of complementary datasets for individuals born in Britain around 1970 and aged between 30 and 40, we estimate an hourly wage premium for a…

Cleft Lip and Palate Repair.

PubMed

Gatti, Gian Luca; Freda, Nicola; Giacomina, Alessandro; Montemagni, Marina; Sisti, Andrea

2017-11-01

Cleft lip and palate is the most frequent congenital craniofacial deformity. In this article, the authors describe their experience with cleft lip and palate repair. Data regarding patients presenting with primary diagnosis of cleft lip and/or palate, between 2009 and 2015, were reviewed. Details including demographics, type of cleft, presence of known risk factors, surgical details, and follow-up visits were collected. Documented complications were reported. Caregivers' satisfaction was assessed with a survey. The survey used to assess satisfaction with cleft-related features was based on the cleft evaluation profile (CEP). In addition, 4 assessors used visual analog scale (VAS) to assess the aesthetic satisfaction. Seven hundred fifty-two patients with primary diagnosis of cleft lip and/or palate underwent surgical correction at "S. Chiara" Hospital, 432 (57.45%) male and 320 (42.55%) female. The most common cleft types in our study were incomplete cleft palate (152 patients) and left unilateral complete cleft lip and palate (152 patients). Associated syndromes were found in 46 patients (6.12%). Cleft lip was repaired using a modified Tennison-Randall technique when the defect was unilateral, whereas a modified Mulliken technique was used for bilateral cleft lip. Cleft palate was repaired using the Bardach technique or Von Langenbeck technique at 5 to 6 months of age. Cleft lip and palate was repaired in several surgical steps. In total, complications were reported in 81 of 752 patients (14.16%). Average fathers' satisfaction score assessed using CEP was 4.5 (lip), 4.8 (nose), 4.7 (teeth), 4.8 (bite), 4.2 (breathing), 4.6 (profile). Average mothers' satisfaction score assessed using CEP was 4.3 (lip), 4.6 (nose), 4.4 (teeth), 4.5 (bite), 4.1 (breathing), 4.4 (profile). Average level of aesthetic satisfaction, assessed using VAS, was 8.7 (fathers), 8.1 (mothers), 7.9 (lay person), and 8.0 (senior cleft surgeon). The multidisciplinary management of children with oral cleft determinated good results, in terms of satisfaction and aesthetic appearance. From our experience, periosteoplasty and lip-adhesion are key surgical techniques.

Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update.

PubMed

Wolff, Antonio C; Hammond, M Elizabeth Hale; Allison, Kimberly H; Harvey, Brittany E; Mangu, Pamela B; Bartlett, John M S; Bilous, Michael; Ellis, Ian O; Fitzgibbons, Patrick; Hanna, Wedad; Jenkins, Robert B; Press, Michael F; Spears, Patricia A; Vance, Gail H; Viale, Giuseppe; McShane, Lisa M; Dowsett, Mitchell

2018-05-30

Purpose To update key recommendations of the American Society of Clinical Oncology/College of American Pathologists human epidermal growth factor receptor 2 (HER2) testing in breast cancer guideline. Methods Based on the signals approach, an Expert Panel reviewed published literature and research survey results on the observed frequency of less common in situ hybridization (ISH) patterns to update the recommendations. Recommendations Two recommendations addressed via correspondence in 2015 are included. First, immunohistochemistry (IHC) 2+ is defined as invasive breast cancer with weak to moderate complete membrane staining observed in > 10% of tumor cells. Second, if the initial HER2 test result in a core needle biopsy specimen of a primary breast cancer is negative, a new HER2 test may (not "must") be ordered on the excision specimen based on specific clinical criteria. The HER2 testing algorithm for breast cancer is updated to address the recommended work-up for less common clinical scenarios (approximately 5% of cases) observed when using a dual-probe ISH assay. These scenarios are described as ISH group 2 ( HER2/chromosome enumeration probe 17 [CEP17] ratio ≥ 2.0; average HER2 copy number < 4.0 signals per cell), ISH group 3 ( HER2/CEP17 ratio < 2.0; average HER2 copy number ≥ 6.0 signals per cell), and ISH group 4 ( HER2/CEP17 ratio < 2.0; average HER2 copy number ≥ 4.0 and < 6.0 signals per cell). The diagnostic approach includes more rigorous interpretation criteria for ISH and requires concomitant IHC review for dual-probe ISH groups 2 to 4 to arrive at the most accurate HER2 status designation (positive or negative) based on combined interpretation of the ISH and IHC assays. The Expert Panel recommends that laboratories using single-probe ISH assays include concomitant IHC review as part of the interpretation of all single-probe ISH assay results. Find additional information at www.asco.org/breast-cancer-guidelines .

Searching for Cool Dust in the Mid-to-far Infrared: The Mass-loss Histories of the Hypergiants μ Cep, VY CMa, IRC+10420, and ρ Cas

NASA Astrophysics Data System (ADS)

Shenoy, Dinesh; Humphreys, Roberta M.; Jones, Terry J.; Marengo, Massimo; Gehrz, Robert D.; Helton, L. Andrew; Hoffmann, William F.; Skemer, Andrew J.; Hinz, Philip M.

2016-03-01

We present mid- and far-IR imaging of four famous hypergiant stars: the red supergiants μ Cep and VY CMa, and the warm hypergiants IRC +10420 and ρ Cas. Our 11-37 μm SOFIA/FORCAST imaging probes cool dust not detected in visual and near-IR imaging studies. Adaptive optics 8-12 μm imaging of μ Cep and IRC +10420 with MMT/MIRAC reveals extended envelopes that are the likely sources of these stars’ strong silicate emission features. We find μ Cep’s mass-loss rate to have declined by about a factor of five over a 13,000 year history, ranging from 5 × 10-6 down to ˜1× 10-6 M⊙ yr-1. The morphology of VY CMa indicates a cooler dust component coincident with the highly asymmetric reflection nebulae seen in the visual and near-IR. The lack of cold dust at greater distances around VY CMa indicates that its mass-loss history is limited to the last ˜1200 years, with an average rate of 6 × 10-4 M⊙ yr-1. We find two distinct periods in the mass-loss history of IRC +10420 with a high rate of 2 × 10-3 M⊙ yr-1 until approximately 2000 years ago, followed by an order of magnitude decrease in the recent past. We interpret this change as evidence of its evolution beyond the RSG stage. Our new infrared photometry of ρ Cas is consistent with emission from the expanding dust shell ejected in its 1946 eruption, with no evidence of newer dust formation from its more recent events. Based on observations obtained with: (1) the NASA/DLR Stratospheric Observatory for Infrared Astronomy (SOFIA). SOFIA is jointly operated by the Universities Space Research Association, Inc. (USRA), under NASA contract NAS2-97001, and the Deutsches SOFIA Institut (DSI) under DLR contract 50 OK 0901 to the University of Stuttgart; and (2) the MMT Observatory on Mt. Hopkins, AZ, a joint facility of the Smithsonian Institution and the University of Arizona.

FOXM1 upregulation is an early event in human squamous cell carcinoma and it is enhanced by nicotine during malignant transformation.

PubMed

Gemenetzidis, Emilios; Bose, Amrita; Riaz, Adeel M; Chaplin, Tracy; Young, Bryan D; Ali, Muhammad; Sugden, David; Thurlow, Johanna K; Cheong, Sok-Ching; Teo, Soo-Hwang; Wan, Hong; Waseem, Ahmad; Parkinson, Eric K; Fortune, Farida; Teh, Muy-Teck

2009-01-01

Cancer associated with smoking and drinking remains a serious health problem worldwide. The survival of patients is very poor due to the lack of effective early biomarkers. FOXM1 overexpression is linked to the majority of human cancers but its mechanism remains unclear in head and neck squamous cell carcinoma (HNSCC). FOXM1 mRNA and protein expressions were investigated in four independent cohorts (total 75 patients) consisting of normal, premalignant and HNSCC tissues and cells using quantitative PCR (qPCR), expression microarray, immunohistochemistry and immunocytochemistry. Effect of putative oral carcinogens on FOXM1 transcriptional activity was dose-dependently assayed and confirmed using a FOXM1-specific luciferase reporter system, qPCR, immunoblotting and short-hairpin RNA interference. Genome-wide single nucleotide polymorphism (SNP) array was used to 'trace' the genomic instability signature pattern in 8 clonal lines of FOXM1-induced malignant human oral keratinocytes. Furthermore, acute FOXM1 upregulation in primary oral keratinocytes directly induced genomic instability. We have shown for the first time that overexpression of FOXM1 precedes HNSCC malignancy. Screening putative carcinogens in human oral keratinocytes surprisingly showed that nicotine, which is not perceived to be a human carcinogen, directly induced FOXM1 mRNA, protein stabilisation and transcriptional activity at concentrations relevant to tobacco chewers. Importantly, nicotine also augmented FOXM1-induced transformation of human oral keratinocytes. A centrosomal protein CEP55 and a DNA helicase/putative stem cell marker HELLS, both located within a consensus loci (10q23), were found to be novel targets of FOXM1 and their expression correlated tightly with HNSCC progression. This study cautions the potential co-carcinogenic effect of nicotine in tobacco replacement therapies. We hypothesise that aberrant upregulation of FOXM1 may be inducing genomic instability through a program of malignant transformation involving the activation of CEP55 and HELLS which may facilitate aberrant mitosis and epigenetic modifications. Our finding that FOXM1 is upregulated early during oral cancer progression renders FOXM1 an attractive diagnostic biomarker for early cancer detection and its candidate mechanistic targets, CEP55 and HELLS, as indicators of malignant conversion and progression.

Correlation Between Quantitative HER-2 Protein Expression and Risk for Brain Metastases in HER-2+ Advanced Breast Cancer Patients Receiving Trastuzumab-Containing Therapy

PubMed Central

Duchnowska, Renata; Biernat, Wojciech; Szostakiewicz, Barbara; Sperinde, Jeff; Piette, Fanny; Haddad, Mojgan; Paquet, Agnes; Lie, Yolanda; Czartoryska-Arłukowicz, Bogumiła; Wysocki, Piotr; Jankowski, Tomasz; Radecka, Barbara; Foszczyńska-Kłoda, Małgorzata; Litwiniuk, Maria; Dȩbska, Sylwia; Weidler, Jodi; Huang, Weidong; Buyse, Marc; Bates, Michael

2012-01-01

Background. Patients with human epidermal growth factor receptor (HER)-2+ breast cancer are at particularly high risk for brain metastases; however, the biological basis is not fully understood. Using a novel HER-2 assay, we investigated the correlation between quantitative HER-2 expression in primary breast cancers and the time to brain metastasis (TTBM) in HER-2+ advanced breast cancer patients treated with trastuzumab. Methods. The study group included 142 consecutive patients who were administered trastuzumab-based therapy for HER-2+ metastatic breast cancer. HER-2/neu gene copy number was quantified as the HER-2/centromeric probe for chromosome 17 (CEP17) ratio by central laboratory fluorescence in situ hybridization (FISH). HER-2 protein was quantified as total HER-2 protein expression (H2T) by the HERmark® assay (Monogram Biosciences, Inc., South San Francisco, CA) in formalin-fixed, paraffin-embedded tumor samples. HER-2 variables were correlated with clinical features and TTBM was measured from the initiation of trastuzumab-containing therapy. Results. A higher H2T level (continuous variable) was correlated with shorter TTBM, whereas HER-2 amplification by FISH and a continuous HER-2/CEP17 ratio were not predictive (p = .013, .28, and .25, respectively). In the subset of patients that was centrally determined by FISH to be HER-2+, an above-the-median H2T level was significantly associated with a shorter TTBM (hazard ratio, [HR], 2.4; p = .005), whereas this was not true for the median HER-2/CEP17 ratio by FISH (p = .4). Correlation between a continuous H2T level and TTBM was confirmed on multivariate analysis (HR, 3.3; p = .024). Conclusions. These data reveal a strong relationship between the quantitative HER-2 protein expression level and the risk for brain relapse in HER-2+ advanced breast cancer patients. Consequently, quantitative assessment of HER-2 protein expression may inform and facilitate refinements in therapeutic treatment strategies for selected subpopulations of patients in this group. PMID:22234627

Correlation between quantitative HER-2 protein expression and risk for brain metastases in HER-2+ advanced breast cancer patients receiving trastuzumab-containing therapy.

PubMed

Duchnowska, Renata; Biernat, Wojciech; Szostakiewicz, Barbara; Sperinde, Jeff; Piette, Fanny; Haddad, Mojgan; Paquet, Agnes; Lie, Yolanda; Czartoryska-Arłukowicz, Bogumiła; Wysocki, Piotr; Jankowski, Tomasz; Radecka, Barbara; Foszczynska-Kłoda, Małgorzata; Litwiniuk, Maria; Debska, Sylwia; Weidler, Jodi; Huang, Weidong; Buyse, Marc; Bates, Michael; Jassem, Jacek

2012-01-01

Patients with human epidermal growth factor receptor (HER)-2+ breast cancer are at particularly high risk for brain metastases; however, the biological basis is not fully understood. Using a novel HER-2 assay, we investigated the correlation between quantitative HER-2 expression in primary breast cancers and the time to brain metastasis (TTBM) in HER-2+ advanced breast cancer patients treated with trastuzumab. The study group included 142 consecutive patients who were administered trastuzumab-based therapy for HER-2+ metastatic breast cancer. HER-2/neu gene copy number was quantified as the HER-2/centromeric probe for chromosome 17 (CEP17) ratio by central laboratory fluorescence in situ hybridization (FISH). HER-2 protein was quantified as total HER-2 protein expression (H2T) by the HERmark® assay (Monogram Biosciences, Inc., South San Francisco, CA) in formalin-fixed, paraffin-embedded tumor samples. HER-2 variables were correlated with clinical features and TTBM was measured from the initiation of trastuzumab-containing therapy. A higher H2T level (continuous variable) was correlated with shorter TTBM, whereas HER-2 amplification by FISH and a continuous HER-2/CEP17 ratio were not predictive (p = .013, .28, and .25, respectively). In the subset of patients that was centrally determined by FISH to be HER-2+, an above-the-median H2T level was significantly associated with a shorter TTBM (hazard ratio, [HR], 2.4; p = .005), whereas this was not true for the median HER-2/CEP17 ratio by FISH (p = .4). Correlation between a continuous H2T level and TTBM was confirmed on multivariate analysis (HR, 3.3; p = .024). These data reveal a strong relationship between the quantitative HER-2 protein expression level and the risk for brain relapse in HER-2+ advanced breast cancer patients. Consequently, quantitative assessment of HER-2 protein expression may inform and facilitate refinements in therapeutic treatment strategies for selected subpopulations of patients in this group.

After the Tests: How States Share Assessment Data. A Special Report in the Series, "Planning for Progress: States Reflect on Year One Implementation of ESSA"

ERIC Educational Resources Information Center

Frizzell, Matthew; Rentner, Diane Stark; Kober, Nancy

2018-01-01

In September and October of 2017, the Center on Education Policy conducted a survey of state deputy superintendents of education or their designees to learn about states' early efforts in implementing the Every Student Succeeds Act (ESSA). Most of those survey findings are described in the CEP publication "Planning for Progress: States…

Universal Pre-School Education: The Case of Public Funding with Private Provision. CEP Discussion Paper No. 1352

ERIC Educational Resources Information Center

Blanden, Joanne; Del Bono, Emilia; McNally, Sandra; Rabe, Birgitta

2015-01-01

This paper studies the effect of free pre-school education on child outcomes in primary school. We exploit the staggered implementation of free part-time pre-school for three-year-olds across Local Education Authorities in England in the early 2000s. The policy led to small improvements in attainment at age five, with no apparent benefits by age…

Aerospace Power: The Case for Indivisible Application

DTIC Science & Technology

1986-09-01

missile, used with such impact by Argentina during the Falklands battle, will be seen as just a modest beginning . The CEP of new weapons will likely be... Argentina to the Soviet Union, to accomplish a spectrum of combat missions with rapidly increasing effectiveness . The mixed nature of the "blessings of...aerospace forces according to their capabilities and the elimination of the rigid strategic and tactical stereotypes . 60 AEROSPACEPOWER These global

When the Cat Is Near, the Mice Won't Play: The Effect of External Examiners in Italian Schools. CEP Discussion Paper No. 1191

ERIC Educational Resources Information Center

Bertoni, Marco; Brunello, Giorgio; Rocco, Lorenzo

2013-01-01

We use a natural experiment to show that the presence of an external examiner has both a direct and an indirect negative effect on the performance of monitored classes in standardized educational tests. The direct effect is the difference in the test performance between classes of the same school with and without external examiners. The indirect…