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

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

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

Centrosomal Protein of 55 Regulates Glucose Metabolism, Proliferation and Apoptosis of Glioma Cells via the Akt/mTOR Signaling Pathway

PubMed Central

Wang, Guangzhi; Liu, Mingna; Wang, Hongjun; Yu, Shan; Jiang, Zhenfeng; Sun, Jiahang; Han, Ke; Shen, Jia; Zhu, Minwei; Lin, Zhiguo; Jiang, Chuanlu; Guo, Mian

2016-01-01

Introduction: Glioma is one of the most common and most aggressive brain tumors in humans. The molecular and cellular mechanisms responsible for the onset and the progression of glioma are elusive and controversial. Centrosomal protein of 55 (CEP55) was initially described as a highly coiled-coil protein that plays critical roles in cell division, but was recently identified as being overexpressed in many human cancers. The function of CEP55 has not previously been characterized in glioma. We aim to discover the effect and mechanism of CEP55 in glioma development. Method: qRT-PCR and immunohistochemistry were used to analyze CEP55 expression. Glucose uptake, western blot, MTS, CCK-8, Caspase-3 activity and TUNEL staining assays were performed to investigate the role and mechanism of CEP55 on glioma cell process. Results: We found that the levels of CEP55 expression were upregulated in glioma. In addition, CEP55 appeared to regulate glucose metabolism of glioma cells. Furthermore, knockdown of CEP55 inhibited cell proliferation and induced cell apoptosis in glioma. Finally, we provided preliminary evidence that knockdown of CEP55 inhibited glioma development via suppressing the activity of Akt/mTOR signaling. Conclusions: Our results demonstrated that CEP55 regulates glucose metabolism, proliferation and apoptosis of glioma cells via the Akt/mTOR signaling pathway, and its promotive effect on glioma tumorigenesis can be a potential target for glioma therapy in the future. PMID:27471559

2-(ω-Carboxyethyl)pyrrole Antibody as a New Inhibitor of Tumor Angiogenesis and Growth.

PubMed

Wu, Chunying; Wang, Xizhen; Tomko, Nicholas; Zhu, Junqing; Wang, William R; Zhu, Jinle; Wangf, Bin; Wang, Yanming; Salomon, Robert G

2017-01-01

Angiogenesis is a fundamental process in the progression, invasion, and metastasis of tumors. Therapeutic drugs such as bevacizumab and ranibuzumab have thus been developed to inhibit vascular endothelial growth factor (VEFG)-promoted angiogenesis. While these anti-angiogenic drugs have been commonly used in the treatment of cancer, patients often develop significant resistance that limits the efficacy of anti-VEGF therapies to a short period of time. This is in part due to the fact that an independent pathway of angiogenesis exists, which is mediated by 2-(ω-carboxyethyl)pyrrole (CEP) in a TLR2 receptor-dependent manner that can compensate for inhibition of the VEGF-mediated pathway. In this work, we evaluated a CEP antibody as a new tumor growth inhibitor that blocks CEP-induced angiogenesis. We first evaluated the effectiveness of a CEP antibody as a monotherapy to impede tumor growth in two human tumor xenograft models. We then determined the synergistic effects of bevacizumab and CEP antibody in a combination therapy, which demonstrated that blocking of the CEP-mediated pathway significantly enhanced the anti-angiogenic efficacy of bevacizumab in tumor growth inhibition indicating that CEP antibody is a promising chemotherapeutic drug. To facilitate potential translational studies of CEP-antibody, we also conducted longitudinal imaging studies and identified that FMISO-PET is a non-invasive imaging tool that can be used to quantitatively monitor the anti-angiogenic effects of CEP-antibody in the clinical setting. That treatment with CEP antibody induces hypoxia in tumor tissue WHICH was indicated by 43% higher uptake of [18F]FMISO in CEP antibody-treated tumor xenografs than in the control PBS-treated littermates. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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.

Sonic hedgehog protein promotes proliferation and chondrogenic differentiation of bone marrow-derived mesenchymal stem cells in vitro.

PubMed

Warzecha, Jörg; Göttig, Stephan; Brüning, Christian; Lindhorst, Elmar; Arabmothlagh, Mohammad; Kurth, Andreas

2006-10-01

Sonic hedgehog (Shh) protein is known to be an important signaling protein in early embryonic development. Also, Shh is involved in the induction of early cartilaginous differentiation of mesenchymal cells in the limb and in the spine. The impact of Shh on adult stem cells, human bone marrow-derived mesenchymal stem cells (MSCs), was tested. The MSCs were treated either with recombinant Sonic hedgehog protein (r-Shh) or with transforming growth factor-beta 1 (TGF-beta(1)) as a positive control in vitro for 3 weeks. The effects on cartilaginous differentiation and proliferation were assayed. MSCs when treated with either Shh or TGF-beta(1) showed expression of cartilage markers aggrecan, Sox9, CEP-68, and collagen type II and X within 3 weeks. Only r-Shh-treated cells showed a very strong cell proliferation and much higher BrdU incorporation in cell assay systems. These are the first data that indicate an important role of Shh for the induction of cartilage production by MSCs in vitro.

Antisense Oligonucleotide (AON)-based Therapy for Leber Congenital Amaurosis Caused by a Frequent Mutation in CEP290

PubMed Central

Collin, Rob WJ; den Hollander, Anneke I; van der Velde-Visser, Saskia D; Bennicelli, Jeannette; Bennett, Jean; Cremers, Frans PM

2012-01-01

Leber congenital amaurosis (LCA) is the most severe form of inherited retinal degeneration, with an onset in the first year of life. The most frequent mutation that causes LCA, present in at least 10% of individuals with LCA from North-American and Northern-European descent, is an intronic mutation in CEP290 that results in the inclusion of an aberrant exon in the CEP290 mRNA. Here, we describe a genetic therapy approach that is based on antisense oligonucleotides (AONs), small RNA molecules that are able to redirect normal splicing of aberrantly processed pre-mRNA. Immortalized lymphoblastoid cells of individuals with LCA homozygously carrying the intronic CEP290 mutation were transfected with several AONs that target the aberrant exon that is incorporated in the mutant CEP290 mRNA. Subsequent RNA isolation and reverse transcription-PCR analysis revealed that a number of AONs were capable of almost fully redirecting normal CEP290 splicing, in a dose-dependent manner. Other AONs however, displayed no effect on CEP290 splicing at all, indicating that the rescue of aberrant CEP290 splicing shows a high degree of sequence specificity. Together, our data show that AON-based therapy is a promising therapeutic approach for CEP290-associated LCA that warrants future research in animal models to develop a cure for this blinding disease. PMID:23343883

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.

CRITICAL EVALUATION OF MAGNETIC FIELD DETECTIONS REPORTED FOR PULSATING B-TYPE STARS IN LIGHT OF ESPaDOnS, NARVAL, AND REANALYZED FORS1/2 OBSERVATIONS

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

Shultz, M.; Wade, G. A.; Grunhut, J.

2012-05-01

Recent spectropolarimetric studies of seven slowly pulsating B (SPB) and {beta} Cep stars have suggested that photospheric magnetic fields are more common in B-type pulsators than in the general population of B stars, suggesting a significant connection between magnetic and pulsational phenomena. We present an analysis of new and previously published spectropolarimetric observations of these stars. New Stokes V observations obtained with the high-resolution ESPaDOnS and Narval instruments confirm the presence of a magnetic field in one of the stars ({epsilon} Lup), but find no evidence of magnetism in five others. A re-analysis of the published longitudinal field measurements obtainedmore » with the low-resolution FORS1/2 spectropolarimeters finds that the measurements of all stars show more scatter from zero than can be attributed to Gaussian noise, suggesting the presence of a signal and/or systematic underestimation of error bars. Re-reduction and re-measurement of the FORS1/2 spectra from the ESO archive demonstrates that small changes in reduction procedure lead to substantial changes in the inferred longitudinal field, and substantially reduces the number of field detections at the 3{sigma} level. Furthermore, we find that the published periods are not unique solutions to the time series of either the original or the revised FORS1/2 data. We conclude that the reported field detections, proposed periods, and field geometry models for {alpha} Pyx, 15 CMa, 33 Eri, and V1449 Aql are artifacts of the data analysis and reduction procedures, and that magnetic fields at the reported strength are no more common in SPB/{beta} Cep stars than in the general population of B stars.« less

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.

TLA-1: a new plasmid-mediated extended-spectrum beta-lactamase from Escherichia coli.

PubMed

Silva, J; Aguilar, C; Ayala, G; Estrada, M A; Garza-Ramos, U; Lara-Lemus, R; Ledezma, L

2000-04-01

Escherichia coli R170, isolated from the urine of an infected patient, was resistant to expanded-spectrum cephalosporins, aztreonam, ciprofloxacin, and ofloxacin but was susceptible to amikacin, cefotetan, and imipenem. This particular strain contained three different plasmids that encoded two beta-lactamases with pIs of 7.0 and 9.0. Resistance to cefotaxime, ceftazidime, aztreonam, trimethoprim, and sulfamethoxazole was transferred by conjugation from E. coli R170 to E. coli J53-2. The transferred plasmid, RZA92, which encoded a single beta-lactamase, was 150 kb in length. The cefotaxime resistance gene that encodes the TLA-1 beta-lactamase (pI 9.0) was cloned from the transconjugant by transformation to E. coli DH5alpha. Sequencing of the bla(TLA-1) gene revealed an open reading frame of 906 bp, which corresponded to 301 amino acid residues, including motifs common to class A beta-lactamases: (70)SXXK, (130)SDN, and (234)KTG. The amino acid sequence of TLA-1 shared 50% identity with the CME-1 chromosomal class A beta-lactamase from Chryseobacterium (Flavobacterium) meningosepticum; 48.8% identity with the VEB-1 class A beta-lactamase from E. coli; 40 to 42% identity with CblA of Bacteroides uniformis, PER-1 of Pseudomonas aeruginosa, and PER-2 of Salmonella typhimurium; and 39% identity with CepA of Bacteroides fragilis. The partially purified TLA-1 beta-lactamase had a molecular mass of 31.4 kDa and a pI of 9.0 and preferentially hydrolyzed cephaloridine, cefotaxime, cephalothin, benzylpenicillin, and ceftazidime. The enzyme was markedly inhibited by sulbactam, tazobactam, and clavulanic acid. TLA-1 is a new extended-spectrum beta-lactamase of Ambler class A.

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.

CEP295 interacts with microtubules and is required for centriole elongation.

PubMed

Chang, Ching-Wen; Hsu, Wen-Bin; Tsai, Jhih-Jie; Tang, Chieh-Ju C; Tang, Tang K

2016-07-01

Centriole duplication is a tightly ordered process during which procentrioles are assembled in G1-S and elongate during S and G2. Here, we show that human CEP295 (Drosophila Ana1) is not essential for initial cartwheel assembly, but is required to build distal half centrioles during S and G2. Using super-resolution and immunogold electron microscopy, we demonstrate that CEP295 is recruited to the proximal end of procentrioles in early S phase, when it is also localized at the centriolar microtubule wall that surrounds the human SAS6 cartwheel hub. Interestingly, depletion of CEP295 not only inhibits the recruitments of POC5 and POC1B to the distal half centrioles in G2, resulting in shorter centrioles, it also blocks the post-translational modification of centriolar microtubules (e.g. acetylation and glutamylation). Importantly, our results indicate that CEP295 directly interacts with microtubules, and that excess CEP295 could induce the assembly of overly long centrioles. Furthermore, exogenous expression of the N-terminal domain of CEP295 exerts a dominant-negative effect on centriole elongation. Collectively, these findings suggest that CEP295 is essential for building the distal half centrioles and for post-translational modification of centriolar microtubules. © 2016. Published by The Company of Biologists Ltd.

CEP295 interacts with microtubules and is required for centriole elongation

PubMed Central

Chang, Ching-Wen; Hsu, Wen-Bin; Tsai, Jhih-Jie; Tang, Chieh-Ju C.

2016-01-01

ABSTRACT Centriole duplication is a tightly ordered process during which procentrioles are assembled in G1-S and elongate during S and G2. Here, we show that human CEP295 (Drosophila Ana1) is not essential for initial cartwheel assembly, but is required to build distal half centrioles during S and G2. Using super-resolution and immunogold electron microscopy, we demonstrate that CEP295 is recruited to the proximal end of procentrioles in early S phase, when it is also localized at the centriolar microtubule wall that surrounds the human SAS6 cartwheel hub. Interestingly, depletion of CEP295 not only inhibits the recruitments of POC5 and POC1B to the distal half centrioles in G2, resulting in shorter centrioles, it also blocks the post-translational modification of centriolar microtubules (e.g. acetylation and glutamylation). Importantly, our results indicate that CEP295 directly interacts with microtubules, and that excess CEP295 could induce the assembly of overly long centrioles. Furthermore, exogenous expression of the N-terminal domain of CEP295 exerts a dominant-negative effect on centriole elongation. Collectively, these findings suggest that CEP295 is essential for building the distal half centrioles and for post-translational modification of centriolar microtubules. PMID:27185865

The novel GrCEP12 peptide from the plant-parasitic nematode Globodera rostochiensis suppresses flg22-mediated PTI.

PubMed

Chen, Shiyan; Chronis, Demosthenis; Wang, Xiaohong

2013-09-01

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, (1) nematode secreted effectors are becoming recognized as suppressors of plant immunity. (2)(-) (4) Recently we reported that the effector ubiquitin carboxyl extension protein (GrUBCEP12) from G. rostochiensis is processed into free ubiquitin and a 12-amino acid GrCEP12 peptide in planta. Transgenic potato lines overexpressing the derived GrCEP12 peptide showed increased susceptibility to G. rostochiensis and to an unrelated bacterial pathogen Streptomyces scabies, suggesting that GrCEP12 has a role in suppressing host basal defense or possibly pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) during the parasitic interaction. (3) To determine if GrCEP12 functions as a PTI suppressor we evaluated whether GrCEP12 suppresses flg22-induced PTI responses in Nicotiana benthamiana. Interestingly, we found that transient expression of GrCEP12 in N. benthamiana leaves suppressed reactive oxygen species (ROS) production and the induction of two PTI marker genes triggered by the bacterial PAMP flg22, providing direct evidence that GrCEP12 indeed has an activity in PTI suppression.

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.

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.

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

Examining the construct and known-group validity of a composite endpoint for The Older Persons and Informal Caregivers Survey Minimum Data Set (TOPICS-MDS); A large-scale data sharing initiative

PubMed Central

Hofman, Cynthia S.; Lutomski, Jennifer E.; Boter, Han; Buurman, Bianca M.; Donders, Rogier; Olde Rikkert, Marcel G. M.; Makai, Peter; Melis, René J. F.

2017-01-01

Background Preference-weighted multi-faceted endpoints have the potential to facilitate comparative effectiveness research that incorporates patient preferences. The Older Persons and Informal Caregivers Survey—Composite endpoint (TOPICS-CEP) is potentially a valuable outcome measure for evaluating interventions in geriatric care as it combines multiple outcomes relevant to older persons in a single metric. The objective of this study was to validate TOPICS-CEP across different study settings (general population, primary care and hospital). Methods Data were extracted from TOPICS Minimum Dataset (MDS), a pooled public-access national database with information on older persons throughout the Netherlands. Data of 17,603 older persons were used. Meta-correlations were performed between TOPICS-CEP indexed scores, EuroQol5-D utility scores and Cantril’s ladder life satisfaction scores. Mixed linear regression analyses were performed to compare TOPICS-CEP indexed scores between known groups, e.g. persons with versus without depression. Results In the complete sample and when stratified by study setting TOPICS-CEP and Cantril’s ladder were moderately correlated, whereas TOPICS-CEP and EQ-5D were highly correlated. Higher mean TOPICS-CEP scores were found in persons who were: married, lived independently and had an education at university level. Moreover, higher mean TOPICS-CEP scores were found in persons without dementia, depression, and dizziness with falls, respectively. Similar results were found when stratified by subgroup. Conclusion This study supports that TOPICS-CEP is a robust measure which can potentially be used in broad settings to identify the effect of intervention or of prevention in elderly care. PMID:28296910

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.

Single-shot carrier-envelope-phase-tagged ion-momentum imaging of nonsequential double ionization of argon in intense 4-fs laser fields

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

Johnson, Nora G.; Herrwerth, O.; Wirth, A.

2011-01-15

Single-shot carrier-envelope-phase (CEP) tagging is combined with a reaction mircoscope (REMI) to investigate CEP-dependent processes in atoms. Excellent experimental stability and data acquisition longevity are achieved. Using this approach, we study the CEP effects for nonsequential double ionization of argon in 4-fs laser fields at 750 nm and an intensity of 1.6x10{sup 14} W/cm{sup 2}. The Ar{sup 2+} ionization yield shows a pronounced CEP dependence which compares well with recent theoretical predictions employing quantitative rescattering theory [S. Micheau et al., Phys. Rev. A 79, 013417 (2009)]. Furthermore, we find strong CEP influences on the Ar{sup 2+} momentum spectra along themore » laser polarization axis.« less

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.

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.

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.

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

[beta]-Glucan Synthesis in the Cotton Fiber (III. Identification of UDP-Glucose-Binding Subunits of [beta]-Glucan Synthases by Photoaffinity Labeling with [[beta]-32P]5[prime]-N3-UDP-Glucose.

PubMed Central

Li, L.; Drake, R. R.; Clement, S.; Brown, R. M.

1993-01-01

Using differential product entrapment and photolabeling under specifying conditions, we identifIed a 37-kD polypeptide as the best candidate among the UDP-glucose-binding polypeptides for the catalytic subunit of cotton (Gossypium hirsutum) cellulose synthase. This polypeptide is enriched by entrapment under conditions favoring [beta]-1,4-glucan synthesis, and it is magnesium dependent and sensitive to unlabeled UDP-glucose. A 52-kD polypeptide was identified as the most likely candidate for the catalytic subunit of [beta]-1,3-glucan synthase because this polypeptide is the most abundant protein in the entrapment fraction obtained under conditions favoring [beta]-1,3-glucan synthesis, is coincident with [beta]-1,3-glucan synthase activity, and is calcium dependent. The possible involvement of other polypeptides in the synthesis of [beta]-1,3-glucan is discussed. PMID:12231766

Single-trial extraction of cognitive evoked potentials by combination of third-order correlation and wavelet denoising.

PubMed

Zhang, Z; Tian, X

2005-01-01

The application of a recently proposed denoising implementation for obtaining cognitive evoked potentials (CEPs) at the single-trial level is shown. The aim of this investigation is to develop the technique of extracting CEPs by combining both the third-order correlation and the wavelet denoising methods. First, the noisy CEPs was passed through a finite impulse response filter whose impulse response is matched with the shape of the noise-free signal. It was shown that it is possible to estimate the filter impulse response on basis of a select third-order correlation slice (TOCS) of the input noisy CEPs. Second, the output from the third-order correlation filter is decomposed with bi-orthogonal splines at 5 levels. The CEPs is reconstructed by wavelet final approximation a5. We study its performance in simulated data as well as in cognitive evoked potentials of normal rat and Alzheimer's disease (AD) model rat. For the simulated data, the method gives a significantly better reconstruction of the single-trial cognitive evoked potentials responses in comparison with the simulated data. Moreover, with this approach we obtain a significantly better estimation of the amplitudes and latencies of the simulated CEPs. For the real data, the method clearly improves the visualization of single-trial CEPs. This allows the calculation of better averages as well as the study of systematic or unsystematic variations between trials.

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.

A study of coronal X-ray emission from short-period Algol binaries

NASA Technical Reports Server (NTRS)

Singh, K. P.; Drake, S. A.; White, N. E.

1995-01-01

A study of X-ray emission from five short-period Algol-type binaries based on observations with Advanced Satellite for Cosmology and Astrophysics (ASCA) and ROSAT is presented. We have observed RZ Cas with both satellites, and beta Per, U Cep, delta Lib, and TW Dra with ROSAT. Significant intensity variations are seen in the X-ray emission from RZ Cas, U Cep, TW Dra, and delta Lib. These variations seem unrelated to the eclipsing behavior of these systems and are probably due to either rotational modulation of compact active regions on the surfaces of the chromospherically active secondary components or to flaring activity in the systems. The spectra of all but one of the systems require the presence of at least two discrete plasma components with different temperatures (0.6 - 0.7 keV, and approximately 2 keV) and the abundances of the medium-Z elements 20% - 50% of the solar photospheric values. The high resolving power and signal-to-noise ratio of the ASCA spectra allow us to individually constrain the coronal abundances of O, Ne, Mg, Si, S, and Fe in RZ Cas. We demonstrate that, if we use the elemental abundances and temperatures obtained from the analysis of their ASCA spectra as (fixed) inputs, to fit the ROSAT PSPC spectra well requires the presence of a third component (kT approximately 0.2 - 0.3 keV) in RZ Cas and beta Per. A continuous emission measure model of the power-law type (EM(T) variesas (T/T(sub max)(sup alpha)) generally gives a poor fit to the ASCA and ROSAT data on most sources. Circumstellar or circumbinary absorbing matter seems to be present in some of these systems, as indicated by the variable total column density needed to fit their X-ray spectra.

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

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.

Complete analog control of the carrier-envelope-phase of a high-power laser amplifier.

PubMed

Feng, C; Hergott, J-F; Paul, P-M; Chen, X; Tcherbakoff, O; Comte, M; Gobert, O; Reduzzi, M; Calegari, F; Manzoni, C; Nisoli, M; Sansone, G

2013-10-21

In this work we demonstrate the development of a complete analog feedback loop for the control of the carrier-envelope phase (CEP) of a high-average power (20 W) laser operating at 10 kHz repetition rate. The proposed method combines a detection scheme working on a single-shot basis at the full-repetition-rate of the laser system with a fast actuator based either on an acousto-optic or on an electro-optic crystal. The feedback loop is used to correct the CEP fluctuations introduced by the amplification process demonstrating a CEP residual noise of 320 mrad measured on a single-shot basis. The comparison with a feedback loop operating at a lower sampling rate indicates an improvement up to 45% in the residual noise. The measurement of the CEP drift for different integration times clearly evidences the importance of the single-shot characterization of the residual CEP drift. The demonstrated scheme could be efficiently applied for systems approaching the 100 kHz repetition rate regime.

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.

A community engagement process identifies environmental priorities to prevent early childhood obesity: the Children's Healthy Living (CHL) program for remote underserved populations in the US Affiliated Pacific Islands, Hawaii and Alaska.

PubMed

Fialkowski, Marie Kainoa; DeBaryshe, Barbara; Bersamin, Andrea; Nigg, Claudio; Leon Guerrero, Rachael; Rojas, Gena; Areta, Aufa'i Apulu Ropeti; Vargo, Agnes; Belyeu-Camacho, Tayna; Castro, Rose; Luick, Bret; Novotny, Rachel

2014-12-01

Underserved minority populations in the US Affiliated Pacific Islands (USAPI), Hawaii, and Alaska display disproportionate rates of childhood obesity. The region's unique circumstance should be taken into account when designing obesity prevention interventions. The purpose of this paper is to (a), describe the community engagement process (CEP) used by the Children's Healthy Living (CHL) Program for remote underserved minority populations in the USAPI, Hawaii, and Alaska (b) report community-identified priorities for an environmental intervention addressing early childhood (ages 2-8 years) obesity, and (c) share lessons learned in the CEP. Four communities in each of five CHL jurisdictions (Alaska, American Samoa, Commonwealth of the Northern Mariana Islands, Guam, Hawai'i) were selected to participate in the community-randomized matched-pair trial. Over 900 community members including parents, teachers, and community leaders participated in the CEP over a 14 month period. The CEP was used to identify environmental intervention priorities to address six behavioral outcomes: increasing fruit/vegetable consumption, water intake, physical activity and sleep; and decreasing screen time and intake of sugar sweetened beverages. Community members were engaged through Local Advisory Committees, key informant interviews and participatory community meetings. Community-identified priorities centered on policy development; role modeling; enhancing access to healthy food, clean water, and physical activity venues; and healthy living education. Through the CEP, CHL identified culturally appropriate priorities for intervention that were also consistent with the literature on effective obesity prevention practices. Results of the CEP will guide the CHL intervention design and implementation. The CHL CEP may serve as a model for other underserved minority island populations.

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

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

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.

Linkage study of nonsyndromic cleft lip with or without cleft palate using candidate genes and mapped polymorphic markers

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

Stein, J.D.; Nelson, L.D.; Conner, B.J.

1994-09-01

Nonsyndromic cleft lip with or without cleft palate (CL(P)) involves fusion or growth failure of facial primordia during development. Complex segregation analysis of clefting populations suggest that an autosomal dominant gene may play a role in this common craniofacial disorder. We have ascertained 16 multigenerational families with CL(P) and tested linkage to 29 candidate genes and 139 mapped short tandem repeat markers. The candidate genes were selected based on their expression in craniofacial development or were identified through murine models. These include: TGF{alpha}, TGF{beta}1, TGF{beta}2, TGF{beta}3, EGF, EGFR, GRAS, cMyc, FGFR, Jun, JunB, PDFG{alpha}, PDGF{beta}, IGF2R, GCR Hox7, Hox8, Hox2B,more » twirler, 5 collagen and 3 extracellular matrix genes. Linkage was tested assuming an autosomal dominant model with sex-specific decreased penetrance. Linkage to all of the candidate loci was excluded in 11 families. RARA was tested and was not informative. However, haplotype analysis of markers flanking RARA on 17q allowed exclusion of this candidate locus. We have previously excluded linkage to 61 STR markers in 11 families. Seventy-eight mapped short tandem repeat markers have recently been tested in 16 families and 30 have been excluded. The remaining are being analyzed and an exclusion map is being developed based on the entire study results.« less

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.

Non-Invasive Monitoring of Streptococcus pyogenes Vaccine Efficacy Using Biophotonic Imaging

PubMed Central

Alam, Faraz M.; Bateman, Colin; Turner, Claire E.; Wiles, Siouxsie; Sriskandan, Shiranee

2013-01-01

Streptococcus pyogenes infection of the nasopharynx represents a key step in the pathogenic cycle of this organism and a major focus for vaccine development, requiring robust models to facilitate the screening of potentially protective antigens. One antigen that may be an important target for vaccination is the chemokine protease, SpyCEP, which is cell surface-associated and plays a role in pathogenesis. Biophotonic imaging (BPI) can non-invasively characterize the spatial location and abundance of bioluminescent bacteria in vivo. We have developed a bioluminescent derivative of a pharyngeal S. pyogenes strain by transformation of an emm75 clinical isolate with the luxABCDE operon. Evaluation of isogenic recombinant strains in vitro and in vivo confirmed that bioluminescence conferred a growth deficit that manifests as a fitness cost during infection. Notwithstanding this, bioluminescence expression permitted non-invasive longitudinal quantitation of S. pyogenes within the murine nasopharynx albeit with a detection limit corresponding to approximately 105 bacterial colony forming units (CFU) in this region. Vaccination of mice with heat killed streptococci, or with SpyCEP led to a specific IgG response in the serum. BPI demonstrated that both vaccine candidates reduced S. pyogenes bioluminescence emission over the course of nasopharyngeal infection. The work suggests the potential for BPI to be used in the non-invasive longitudinal evaluation of potential S. pyogenes vaccines. PMID:24278474

Defining photon channels in strong-field physics: the photon-phase Fourier representation

NASA Astrophysics Data System (ADS)

Zeng, Shuo; Zohrabi, Mohammad; Berry, Ben; Ablikim, Utuq; Kling, Nora; Severt, Travis; Jochim, Bethany; Carnes, Kevin; Ben-Itzhak, Itzik; Esry, Brett

2014-05-01

In strong-field physics, complex atomic and molecular dynamics can be steered by the carrier-envelope phase (CEP). The general theory formulated in Refs., provides a rigorous foundation upon which this understanding might be built. By recognizing the underlying periodicity of the time-dependent Schrödinger equation--and thus its solutions--in the CEP, all CEP effects can be understood as the interference of different photon channels. We will show that this understanding can be turned around to extract information on the photon channel by examining the CEP dependence. In particular, by taking the Fourier transform with respect to the CEP, photon channel information can be extracted from both theory and experiment. Through several examples, we will also show that this technique can be applied to any system and provides knowledge of the net numbers of photons absorbed--even in few-cycle pulses--that is not available in any other way. This work was supported by the Chemical Sciences, Geosciences, and Biosciences Division, Office of Basic Energy Sciences, Office of Science, U.S. Department of Energy under Grant No. DE-FG02-86ER13491. The PULSAR laser was provided by Grant No. DE-FG02-09.

Basics and applications of stem cells in the pancreas.

PubMed

Sekine, Keisuke; Taniguchi, Hideki

2012-11-01

Enormous efforts have been made to establish pancreatic stem/progenitor cells as a source for regenerative medicine for the treatment of diabetes mellitus. In recent years, it has been recognized that the self-renewal of beta cells is the dominant process involved in postnatal beta-cell regeneration and expansion. Nevertheless, several in-vitro studies have suggested that ductal or as yet unidentified cells are candidates for pancreatic stem/progenitor cells that can differentiate into multilineage cells, including insulin(+) cells. The question remains as to whether beta cells are generated postnatally from stem/progenitor cells other than pre-existing beta cells. Furthermore, mutated pancreatic stem cells are considered to be prospective candidates for cancer stem cells or tumor-initiating cells. This review highlights recent progress in pancreatic stem/progenitor cell research.

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.

Tomography of the Red Supergiant Star MU Cep

NASA Astrophysics Data System (ADS)

Kravchenko, Kateryna

2018-04-01

We present a tomographic method allowing to recover the velocity field at different optical depths in a stellar atmosphere. It is based on the computation of the contribution function to identify the depth of formation of spectral lines in order to construct numerical masks probing different optical depths. These masks are cross-correlated with observed spectra to extract information about the average shape of lines forming at a given optical depth and to derive the velocity field projected on the line of sight. We applied this method to series of spectra of the red supergiant star mu Cep and derived velocities in different atmospheric layers. The resulting velocity variations reveal complex atmospheric dynamics and indicate that convective cells are present in the atmosphere of the mu Cep. The mu Cep velocities were compared with those obtained by applying the tomographic masks to series of snapshot spectra from 3D radiative-hydrodynamics CO5BOLD simulations.

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.

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

Delta-beta correlation as a candidate endophenotype of social anxiety: A two-generation family study.

PubMed

Harrewijn, Anita; van der Molen, Melle J W; van Vliet, Irene M; Houwing-Duistermaat, Jeanine J; Westenberg, P Michiel

2018-02-01

Social anxiety disorder (SAD) is characterized by an extreme and intense fear and avoidance of social situations. In this two-generation family study we examined delta-beta correlation during a social performance task as candidate endophenotype of SAD. Nine families with a target participant (diagnosed with SAD), their spouse and children, as well as target's siblings with spouse and children performed a social performance task in which they gave a speech in front of a camera. EEG was measured during resting state, anticipation, and recovery. Our analyses focused on two criteria for endophenotypes: co-segregation within families and heritability. Co-segregation analyses revealed increased negative delta-low beta correlation during anticipation in participants with (sub)clinical SAD compared to participants without (sub)clinical SAD. Heritability analyses revealed that delta-low beta and delta-high beta correlation during anticipation were heritable. Delta-beta correlation did not differ between participants with and without (sub)clinical SAD during resting state or recovery, nor between participants with and without SAD during all phases of the task. It should be noted that participants were seen only once, they all performed the EEG tasks in the same order, and some participants were too anxious to give a speech. Delta-low beta correlation during anticipation of giving a speech might be a candidate endophenotype of SAD, possibly reflecting increased crosstalk between cortical and subcortical regions. If validated as endophenotype, delta-beta correlation during anticipation could be useful in studying the genetic basis, as well as improving treatment and early detection of persons at risk for developing SAD. Copyright © 2017 Elsevier B.V. All rights reserved.

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

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.

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.

Hydrogen-bonded turns in proteins: the case for a recount.

PubMed

Panasik, Nick; Fleming, Patrick J; Rose, George D

2005-11-01

Beta-turns are sites at which proteins change their overall chain direction, and they occur with high frequency in globular proteins. The Protein Data Bank has many instances of conformations that resemble beta-turns but lack the characteristic N-H(i) --> O=C(i - 3) hydrogen bond of an authentic beta-turn. Here, we identify potential hydrogen-bonded beta-turns in the coil library, a Web-accessible database utility comprised of all residues not in repetitive secondary structure, neither alpha-helix nor beta-sheet (http://www.roselab.jhu.edu/coil). In particular, candidate turns were identified as four-residue segments satisfying highly relaxed geometric criteria but lacking a strictly defined hydrogen bond. Such candidates were then subjected to a minimization protocol to determine whether slight changes in torsion angles are sufficient to shift the conformation into reference-quality geometry without deviating significantly from the original structure. This approach of applying constrained minimization to known structures reveals a substantial population of previously unidentified, stringently defined, hydrogen-bonded beta-turns. In particular, 33% of coil library residues were classified as beta-turns prior to minimization. After minimization, 45% of such residues could be classified as beta-turns, with another 8% in 3(10) helixes (which closely resemble type III beta-turns). Of the remaining coil library residues, 37% have backbone dihedral angles in left-handed polyproline II structure.

Genetic and Proteomic Interrogation of Lower Confidence Candidate Genes Reveals Signaling Networks in beta-Catenin-Active Cancers | Office of Cancer Genomics

Cancer.gov

Genome-scale expression studies and comprehensive loss-of-function genetic screens have focused almost exclusively on the highest confidence candidate genes. Here, we describe a strategy for characterizing the lower confidence candidates identified by such approaches.

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

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

Coherent control at its most fundamental: carrier-envelope-phase-dependent electron localization in photodissociation of a H2(+) molecular ion beam target.

PubMed

Rathje, T; Sayler, A M; Zeng, S; Wustelt, P; Figger, H; Esry, B D; Paulus, G G

2013-08-30

Measurements and calculations of the absolute carrier-envelope-phase (CEP) effects in the photodissociation of the simplest molecule, H2(+), with a 4.5-fs Ti:sapphire laser pulse at intensities up to (4±2)×10(14)  W/cm2 are presented. Localization of the electron with respect to the two nuclei (during the dissociation process) is controlled via the CEP of the ultrashort laser pulses. In contrast to previous CEP-dependent experiments with neutral molecules, the dissociation of the molecular ions is not preceded by a photoionization process, which strongly influences the CEP dependence. Kinematically complete data are obtained by time- and position-resolved coincidence detection. The phase dependence is determined by a single-shot phase measurement correlated to the detection of the dissociation fragments. The experimental results show quantitative agreement with ab initio 3D time-dependent Schrödinger equation calculations that include nuclear vibration and rotation.

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

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.

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.

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.

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.

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...

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.

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.

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.

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.

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.

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

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.

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.

ON THE EVOLUTIONARY AND PULSATION MASS OF CLASSICAL CEPHEIDS. III. THE CASE OF THE ECLIPSING BINARY CEPHEID CEP0227 IN THE LARGE MAGELLANIC CLOUD

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

Prada Moroni, P. G.; Gennaro, M.; Bono, G.

2012-04-20

We present a new Bayesian approach to constrain the intrinsic parameters (stellar mass and age) of the eclipsing binary system-CEP0227-in the Large Magellanic Cloud (LMC). We computed several sets of evolutionary models covering a broad range in chemical compositions and in stellar mass. Independent sets of models were also constructed either by neglecting or by including a moderate convective core overshooting ({beta}{sub ov} = 0.2) during central hydrogen-burning phases. Sets of models were also constructed either by neglecting or by assuming a canonical ({eta} = 0.4, 0.8) or an enhanced ({eta} = 4) mass-loss rate. The most probable solutions weremore » computed in three different planes: luminosity-temperature, mass-radius, and gravity-temperature. By using the Bayes factor, we found that the most probable solutions were obtained in the gravity-temperature plane with a Gaussian mass prior distribution. The evolutionary models constructed by assuming a moderate convective core overshooting ({beta}{sub ov} = 0.2) and a canonical mass-loss rate ({eta} = 0.4) give stellar masses for the primary (Cepheid)-M = 4.14{sup +0.04}{sub -0.05} M{sub Sun }-and for the secondary-M = 4.15{sup +0.04}{sub -0.05} M{sub Sun }-that agree at the 1% level with dynamical measurements. Moreover, we found ages for the two components and for the combined system-t = 151{sup +4}{sub -3} Myr-that agree at the 5% level. The solutions based on evolutionary models that neglect the mass loss attain similar parameters, while those ones based on models that either account for an enhanced mass loss or neglect convective core overshooting have lower Bayes factors and larger confidence intervals. The dependence on the mass-loss rate might be the consequence of the crude approximation we use to mimic this phenomenon. By using the isochrone of the most probable solution and a Gaussian prior on the LMC distance, we found a true distance modulus-18.53{sup +0.02}{sub -0.02} mag-and a reddening value-E(B - V) = 0.142{sup +0.005}{sub -0.010} mag-that agree quite well with similar estimates in the literature.« less

Surrogate Endpoint Evaluation: Principal Stratification Criteria and the Prentice Definition.

PubMed

Gilbert, Peter B; Gabriel, Erin E; Huang, Ying; Chan, Ivan S F

2015-09-01

A common problem of interest within a randomized clinical trial is the evaluation of an inexpensive response endpoint as a valid surrogate endpoint for a clinical endpoint, where a chief purpose of a valid surrogate is to provide a way to make correct inferences on clinical treatment effects in future studies without needing to collect the clinical endpoint data. Within the principal stratification framework for addressing this problem based on data from a single randomized clinical efficacy trial, a variety of definitions and criteria for a good surrogate endpoint have been proposed, all based on or closely related to the "principal effects" or "causal effect predictiveness (CEP)" surface. We discuss CEP-based criteria for a useful surrogate endpoint, including (1) the meaning and relative importance of proposed criteria including average causal necessity (ACN), average causal sufficiency (ACS), and large clinical effect modification; (2) the relationship between these criteria and the Prentice definition of a valid surrogate endpoint; and (3) the relationship between these criteria and the consistency criterion (i.e., assurance against the "surrogate paradox"). This includes the result that ACN plus a strong version of ACS generally do not imply the Prentice definition nor the consistency criterion, but they do have these implications in special cases. Moreover, the converse does not hold except in a special case with a binary candidate surrogate. The results highlight that assumptions about the treatment effect on the clinical endpoint before the candidate surrogate is measured are influential for the ability to draw conclusions about the Prentice definition or consistency. In addition, we emphasize that in some scenarios that occur commonly in practice, the principal strata sub-populations for inference are identifiable from the observable data, in which cases the principal stratification framework has relatively high utility for the purpose of effect modification analysis, and is closely connected to the treatment marker selection problem. The results are illustrated with application to a vaccine efficacy trial, where ACN and ACS for an antibody marker are found to be consistent with the data and hence support the Prentice definition and consistency.

Surrogate Endpoint Evaluation: Principal Stratification Criteria and the Prentice Definition

PubMed Central

Gilbert, Peter B.; Gabriel, Erin E.; Huang, Ying; Chan, Ivan S.F.

2015-01-01

A common problem of interest within a randomized clinical trial is the evaluation of an inexpensive response endpoint as a valid surrogate endpoint for a clinical endpoint, where a chief purpose of a valid surrogate is to provide a way to make correct inferences on clinical treatment effects in future studies without needing to collect the clinical endpoint data. Within the principal stratification framework for addressing this problem based on data from a single randomized clinical efficacy trial, a variety of definitions and criteria for a good surrogate endpoint have been proposed, all based on or closely related to the “principal effects” or “causal effect predictiveness (CEP)” surface. We discuss CEP-based criteria for a useful surrogate endpoint, including (1) the meaning and relative importance of proposed criteria including average causal necessity (ACN), average causal sufficiency (ACS), and large clinical effect modification; (2) the relationship between these criteria and the Prentice definition of a valid surrogate endpoint; and (3) the relationship between these criteria and the consistency criterion (i.e., assurance against the “surrogate paradox”). This includes the result that ACN plus a strong version of ACS generally do not imply the Prentice definition nor the consistency criterion, but they do have these implications in special cases. Moreover, the converse does not hold except in a special case with a binary candidate surrogate. The results highlight that assumptions about the treatment effect on the clinical endpoint before the candidate surrogate is measured are influential for the ability to draw conclusions about the Prentice definition or consistency. In addition, we emphasize that in some scenarios that occur commonly in practice, the principal strata sub-populations for inference are identifiable from the observable data, in which cases the principal stratification framework has relatively high utility for the purpose of effect modification analysis, and is closely connected to the treatment marker selection problem. The results are illustrated with application to a vaccine efficacy trial, where ACN and ACS for an antibody marker are found to be consistent with the data and hence support the Prentice definition and consistency. PMID:26722639

LUMINOSITY FUNCTIONS OF SPITZER-IDENTIFIED PROTOSTARS IN NINE NEARBY MOLECULAR CLOUDS

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

Kryukova, E.; Megeath, S. T.; Allen, T. S.

2012-08-15

We identify protostars in Spitzer surveys of nine star-forming (SF) molecular clouds within 1 kpc: Serpens, Perseus, Ophiuchus, Chamaeleon, Lupus, Taurus, Orion, Cep OB3, and Mon R2, which combined host over 700 protostar candidates. These clouds encompass a variety of SF environments, including both low-mass and high-mass SF regions, as well as dense clusters and regions of sparsely distributed star formation. Our diverse cloud sample allows us to compare protostar luminosity functions in these varied environments. We combine near- and mid-infrared photometry from the Two Micron All Sky Survey and Spitzer to create 1-24 {mu}m spectral energy distributions (SEDs). Usingmore » protostars from the c2d survey with well-determined bolometric luminosities, we derive a relationship between bolometric luminosity, mid-IR luminosity (integrated from 1-24 {mu}m), and SED slope. Estimations of the bolometric luminosities for protostar candidates are combined to create luminosity functions for each cloud. Contamination due to edge-on disks, reddened Class II sources, and galaxies is estimated and removed from the luminosity functions. We find that luminosity functions for high-mass SF clouds (Orion, Mon R2, and Cep OB3) peak near 1 L{sub Sun} and show a tail extending toward luminosities above 100 L{sub Sun }. The luminosity functions of the low-mass SF clouds (Serpens, Perseus, Ophiuchus, Taurus, Lupus, and Chamaeleon) do not exhibit a common peak, however the combined luminosity function of these regions peaks below 1 L{sub Sun }. Finally, we examine the luminosity functions as a function of the local surface density of young stellar objects. In the Orion molecular clouds, we find a significant difference between the luminosity functions of protostars in regions of high and low stellar density, the former of which is biased toward more luminous sources. This may be the result of primordial mass segregation, although this interpretation is not unique. We compare our luminosity functions to those predicted by models and find that our observed luminosity functions are best matched by models that invoke competitive accretion, although we do not find strong agreement between the high-mass SF clouds and any of the models.« less

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

A polymorphic region in the human transcription factor AP-2beta gene is associated with specific personality traits.

PubMed

Damberg, M; Garpenstrand, H; Alfredsson, J; Ekblom, J; Forslund, K; Rylander, G; Oreland, L

2000-03-01

Transcription factor AP-2beta is implicated in playing an important role during embryonic development of different parts of the brain, eg, midbrain, hindbrain, spinal cord, dorsal and cranial root ganglia.1,2 The gene encoding AP-2beta contains a polymorphic region which includes a tetranucleotide repeat of [CAAA] four or five times, located in intron 2 between nucleotides 12593 and 12612.3 Since the midbrain contains structures important for variables such as mood and personality, we have investigated if the AP-2beta genotype is associated with personality traits estimated by the Karolinska Scales of Personality (KSP). Identification of transcription factor genes as candidate genes in psychiatric disorders is a novel approach to further elucidate the genetic factors that, together with environmental factors, are involved in the expression of specific psychiatric phenotypes. The AP-2beta genotype and KSP scores were determined for 137 Caucasian volunteers (73 females and 64 males). The personality traits muscular tension, guilt, somatic anxiety, psychastenia and indirect aggression were significantly associated with the specific AP-2beta genotype, albeit with significant difference between genders. Based on this result the human AP-2beta gene seems to be an important candidate gene for personality disorders. Moreover, the present results suggest that the structure of the intron 2 region of the AP-2beta gene is one factor that contributes to development of the constitutional component of specific personality traits.

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.

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

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).

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.

VizieR Online Data Catalog: OB association members in ACT+TRC Catalogs (Hoogerwerf, 2000)

NASA Astrophysics Data System (ADS)

Hoogerwerf, R.

2000-05-01

The Hipparcos Catalogue (Cat. I/239) contains members of nearby OB associations brighter than 12th magnitude in V. However, membership lists are complete only to magnitude V=7.3. In this paper we discuss whether proper motions listed in the `Astrographic Catalogue+Tycho' reference catalogue (ACT, Cat. I/246) and the Tycho Reference Catalogue (TRC, Cat. I/250), which are complete to V~10.5mag, can be used to find additional association members. Proper motions in the ACT/TRC have an average accuracy of ~3mas/yr. We search for ACT/TRC stars which have proper motions consistent with the spatial velocity of the Hipparcos members of the nearby OB associations already identified by de Zeeuw et al. (1999, Cat. J/AJ/117/354). These stars are first selected using a convergent-point method, and then subjected to further constraints on the proper-motion distribution, magnitude and colour to narrow down the final number of candidate members. Monte Carlo simulations show that the proper-motion distribution, magnitude, and colour constraints remove ~97% of the field stars, while at the same time retain more than 90% of the cluster stars. The procedure has been applied to five nearby associations: the three subgroups of Sco OB2, plus Per OB3 and Cep OB6. In all cases except Cep OB6, we find evidence for new association members fainter than the completeness limit of the Hipparcos Catalogue. However, narrow-band photometry and/or radial velocities are needed to pinpoint the cluster members, and to study their physical characteristics. (1 data file).

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

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.

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.

Clostridium perfringens enterotoxin is a superantigen reactive with human T cell receptors V beta 6.9 and V beta 22

PubMed Central

1992-01-01

Candidate superantigens were screened for their ability to induce lysis of human histocompatibility leukocyte antigen class II-positive targets by human CD8+ influenza-specific cytotoxic T cell (CTL) lines. Clostridium perfringens enterotoxin (CPET) induced major histocompatibility complex unrestricted killing by some but not all CTL lines. Using "anchored" polymerase chain reactions, CPET was shown to selectively stimulate peripheral blood lymphocytes bearing T cell receptor V beta 6.9 and V beta 22 in five healthy donors. V beta 24, V beta 21, V beta 18, V beta 5, and V beta 6.1-5 appeared to be weakly stimulated. Antigen processing was not required for CPET to induce proliferation. Like the staphylococcal enterotoxins, CPET is a major cause of food poisoning. These data suggest that superantigenic and enterotoxigenic properties may be closely linked. PMID:1512551

FOXM1 Upregulation Is an Early Event in Human Squamous Cell Carcinoma and it Is Enhanced by Nicotine during Malignant Transformation

PubMed Central

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

Background 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). Methodology/Principal Findings 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. Conclusions/Significance 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. PMID:19287496

A Better Lemon Squeezer? Maximum-Likelihood Regression with Beta-Distributed Dependent Variables

ERIC Educational Resources Information Center

Smithson, Michael; Verkuilen, Jay

2006-01-01

Uncorrectable skew and heteroscedasticity are among the "lemons" of psychological data, yet many important variables naturally exhibit these properties. For scales with a lower and upper bound, a suitable candidate for models is the beta distribution, which is very flexible and models skew quite well. The authors present…

Analysis of Novel Prostate Cancer Biomarkers and their Predictive Utility in an Active Surveillance Protocol

DTIC Science & Technology

2014-05-01

Shock Protein, Annexin A3, Sorbitol Dehydrogenase, Fibrinogen Beta Chain Precursor, Creatine Kinase B-Type, Annexin A1, Cystatin B, and AZI. We have...Shock Protein, Annexin A3, Sorbitol Dehydrogenase, Fibrinogen Beta Chain Precursor, and Creatine Kinase B-Type. After testing these candidates with

In Vitro Monitoring of the Mitochondrial Beta-Oxidation Flux of Palmitic Acid and Investigation of Its Pharmacological Alteration by Therapeutics.

PubMed

Murgasova, Renata; Tor Carreras, Ester; Bourgailh, Julien

2018-05-03

The present study was designed to validate the functional assay that enables rapid screening of therapeutic candidates for their effect on mitochondrial fatty acid oxidation. The two whole-cell systems (tissue homogenates and hepatocytes) have been evaluated to monitor the total beta-oxidation flux of physiologically important 3 H-palmitic acid by measurement of tritiated water enrichment in incubations using UPLC coupled on-line to radioactivity monitoring and mass spectrometry. Our results with several known inhibitors of fatty acid oxidation showed that this simple assay could correctly predict a potential in alteration of mitochondrial function by drug candidates. Since the beta-oxidation of palmitic acid takes place almost exclusively in mitochondria of human hepatocytes, this model can be also utilized to distinguish between the mitochondrial and peroxisomal routes of this essential metabolic pathway in some cases. The present work offers a new in vitro screen of changes in mitochondrial beta-oxidation by xenobiotics as well as a model to study the mechanism of this pathway.

Inhibitors and modulators of beta- and gamma-secretase.

PubMed

Schmidt, Boris; Baumann, Stefanie; Braun, Hannes A; Larbig, Gregor

2006-01-01

Most gene mutations associated with Alzheimer's disease point to the metabolism of amyloid precursor protein as potential cause. The beta- and gamma-secretases are two executioners of amyloid precursor protein processing resulting in amyloid beta. Significant progress has been made in the selective inhibition of both proteases, regardless of structural information for gamma-secretase. Several peptidic and non-peptidic leads were identified and first drug candidates are in clinical trials. This review focuses on the developments since 2003.

Optical isomer separation of potential analgesic drug candidates by using capillary electrophoresis.

PubMed

Ferrara, G; Santagati, N A; Aturki, Z; Fanali, S

1999-09-01

Using cyclodextrin capillary zone electrophoresis (CD-CZE), baseline separation of synthetic potential analgesic drug diastereoisomer candidates 6,11-dimethyl-1,2,3,4,5,6-hexahydro-3-[(2'-methoxycarbonyl-2'-phenylc yclopropyl)methyl]-2,6-methano-3-benzazocin-8-ol (MPCB) and 6,11-dimethyl-1,2,3,4,5,6-hexahydro-3-[[2'-methoxycarbonyl-2'(4-chloroph enyl)cyclopropyl]methyl]-2,6-methano-3-benzazocin-8-ol (CCB) was achieved. Among the cyclodextrins tested (hydroxypropyl-, carboxymethyl- and sulfobutyl-beta-cyclodextrin (HP-beta-CD, CM-beta-CD and SBE-beta-CD)) SBE-beta-CD was found to be the most effective complexing agent, allowing good optical isomer separation. Resolution was also influenced by the CD concentration, pH of the buffer and presence of organic modifier in the background electrolyte. The optimum experimental conditions for the separation of studied analgesic drugs were found using 25 mM borate buffer at pH 9 containing 40 mM of SBE-beta-CD and 20% v/v of methanol. Using the above-mentioned background electrolyte, it was also possible to separate, in the same run, the enantiomers of normetazocine (NMZ) as well as the optical isomers of (+/-)-cis-2-chloromethyl-1-phenyl cyclopropancarboxylic acid methyl ester (PCE) or (+/-)-cis-2-chloromethyl-1-(4-chlorophenyl)cyclopropancarboxylic acid methyl ester (CPCE) reagents used in the synthesis of the studied analgesic drugs).

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…

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.

[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.

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.

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.

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).

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

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.

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

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.

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-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.

Feasibility of commercial space manufacturing, production of pharmaceuticals. Volume 2: Technical analysis

NASA Technical Reports Server (NTRS)

1978-01-01

A technical analysis on the feasibility of commercial manufacturing of pharmaceuticals in space is presented. The method of obtaining pharmaceutical company involvement, laboratory results of the separation of serum proteins by the continuous flow electrophoresis process, the selection and study of candidate products, and their production requirements is described. The candidate products are antihemophilic factor, beta cells, erythropoietin, epidermal growth factor, alpha-1-antitrypsin and interferon. Production mass balances for antihemophelic factor, beta cells, and erythropoietin were compared for space versus ground operation. A conceptual description of a multiproduct processing system for space operation is discussed. Production requirements for epidermal growth factor of alpha-1-antitrypsin and interferon are presented.

Regenerative effect of basic fibroblast growth factor on periodontal healing in two-wall intrabony defects in dogs.

PubMed

Shirakata, Yoshinori; Taniyama, Katsuyoshi; Yoshimoto, Takehiko; Miyamoto, Motoharu; Takeuchi, Naoshi; Matsuyama, Takashi; Noguchi, Kazuyuki

2010-04-01

The aim of the present study was to evaluate the effect of a basic fibroblast growth factor (bFGF) candidate treatment on periodontal healing in two-wall intrabony defects in dogs. Two-wall intrabony defects (5 x 5 x 5 mm) were created surgically on the distal and mesial sides of bilateral mandibular second and fourth premolars in four Beagle dogs. bFGF, enamel matrix derivative (EMD) and platelet-derived growth factor with beta-tricalcium phosphate (PDGF/beta-TCP) treatments, and sham-surgery (OFD) were rotated among the four defects in each animal, EMD and PDGF/beta-TCP serving as benchmark controls. The animals were euthanized for radiographic and histologic evaluation at 8 weeks. Bone formation was significantly greater in the bFGF group (4.11 +/- 0.77 mm) than in the EMD (3.32 +/- 0.71 mm; p<0.05) and OFD (3.09 +/- 0.52 mm; p<0.01) groups. The EMD (4.59 +/- 1.19 mm) and PDGF/beta-TCP (4.66 +/- 0.7 mm) groups exhibited significantly greater cementum regeneration with periodontal ligament-like tissue than the OFD group (2.96 +/- 0.69 mm; p<0.01). No significant differences were observed between the bFGF and the PDGF/beta-TCP groups in any of the histometric parameters. The candidate bFGF treatment supported periodontal regeneration comparable with that of established benchmarks: EMD and PDGF/beta-TCP.

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.

Differing Efficacies of Lead Group A Streptococcal Vaccine Candidates and Full-Length M Protein in Cutaneous and Invasive Disease Models.

PubMed

Rivera-Hernandez, Tania; Pandey, Manisha; Henningham, Anna; Cole, Jason; Choudhury, Biswa; Cork, Amanda J; Gillen, Christine M; Ghaffar, Khairunnisa Abdul; West, Nicholas P; Silvestri, Guido; Good, Michael F; Moyle, Peter M; Toth, Istvan; Nizet, Victor; Batzloff, Michael R; Walker, Mark J

2016-06-14

Group A Streptococcus (GAS) is an important human pathogen responsible for both superficial infections and invasive diseases. Autoimmune sequelae may occur upon repeated infection. For this reason, development of a vaccine against GAS represents a major challenge, since certain GAS components may trigger autoimmunity. We formulated three combination vaccines containing the following: (i) streptolysin O (SLO), interleukin 8 (IL-8) protease (Streptococcus pyogenes cell envelope proteinase [SpyCEP]), group A streptococcal C5a peptidase (SCPA), arginine deiminase (ADI), and trigger factor (TF); (ii) the conserved M-protein-derived J8 peptide conjugated to ADI; and (iii) group A carbohydrate lacking the N-acetylglucosamine side chain conjugated to ADI. We compared these combination vaccines to a "gold standard" for immunogenicity, full-length M1 protein. Vaccines were adjuvanted with alum, and mice were immunized on days 0, 21, and 28. On day 42, mice were challenged via cutaneous or subcutaneous routes. High-titer antigen-specific antibody responses with bactericidal activity were detected in mouse serum samples for all vaccine candidates. In comparison with sham-immunized mice, all vaccines afforded protection against cutaneous challenge. However, only full-length M1 protein provided protection in the subcutaneous invasive disease model. This set of experiments demonstrates the inherent variability of mouse models for the characterization of GAS vaccine candidate protective efficacy. Such variability poses an important challenge for GAS vaccine development, as advancement of candidates to human clinical trials requires strong evidence of efficacy. This study highlights the need for an open discussion within the field regarding standardization of animal models for GAS vaccine development. Copyright © 2016 Rivera-Hernandez et al.

Association study of IL10, IL1beta, and IL1RN and schizophrenia using tag SNPs from a comprehensive database: suggestive association with rs16944 at IL1beta.

PubMed

Shirts, Brian H; Wood, Joel; Yolken, Robert H; Nimgaonkar, Vishwajit L

2006-12-01

Genetic association studies of several candidate cytokine genes have been motivated by evidence of immune dysfunction among patients with schizophrenia. Intriguing but inconsistent associations have been reported with polymorphisms of three positional candidate genes, namely IL1beta, IL1RN, and IL10. We used comprehensive sequencing data from the Seattle SNPs database to select tag SNPs that represent all common polymorphisms in the Caucasian population at these loci. Associations with 28 tag SNPs were evaluated in 478 cases and 501 unscreened control individuals, while accounting for population sub-structure using the genomic control method. The samples were also stratified by gender, diagnostic category, and exposure to infectious agents. Significant association was not detected after correcting for multiple comparisons. However, meta-analysis of our data combined with previously published association studies of rs16944 (IL1beta -511) suggests that the C allele confers modest risk for schizophrenia among individuals reporting Caucasian ancestry, but not Asians (Caucasians, n=819 cases, 1292 controls; p=0.0013, OR=1.24, 95% CI 1.09, 1.41).

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.

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.

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.

Spotlight on agalsidase beta in Fabry disease.

PubMed

Keating, Gillian M; Simpson, Dene

2007-01-01

Agalsidase beta (Fabrazyme) is a recombinant human alpha-galactosidase A enzyme approved for intravenous use in the treatment of Fabry disease. Fabry disease is a progressive, multisystemic, potentially life-threatening disorder caused by a deficiency of alpha-galactosidase A. This deficiency results in accumulation of glycosphingolipids, particularly globotriaosylceramide (GL-3), in the lysosomes of various tissues. This accumulation is the underlying driver of disease progression. Agalsidase beta provides an exogenous source of alpha-galactosidase A. Intravenous agalsidase beta is effective and well tolerated in patients with Fabry disease. In a phase III trial, agalsidase beta was shown to clear GL-3 from various target cells and, in a subsequent extension of this trial, prevent GL-3 reaccumulation. In a post-approval trial, agalsidase beta was shown to provide significant clinical benefit by reducing the risk of a major clinical event. Thus, agalsidase beta represents an important advance in the treatment of Fabry disease, and agalsidase beta therapy should be strongly considered in patients with Fabry disease who are suitable candidates.

Agalsidase Beta: a review of its use in the management of Fabry disease.

PubMed

Keating, Gillian M; Simpson, Dene

2007-01-01

Agalsidase beta (Fabrazyme) is a recombinant human alpha-galactosidase A enzyme approved for intravenous use in the treatment of Fabry disease. Fabry disease is a progressive, multisystemic, potentially life threatening disorder caused by a deficiency of alpha-galactosidase A. This deficiency results in accumulation of glycosphingolipids, particularly globotriaosylceramide (GL-3), in the lysosomes of various tissues. This accumulation is the underlying driver of disease progression. Agalsidase beta provides an exogenous source of alpha-galactosidase A.Intravenous agalsidase beta is effective and well tolerated in patients with Fabry disease. In a phase III trial, agalsidase beta was shown to clear GL-3 from various target cells and, in a subsequent extension of this trial, prevent GL-3 reaccumulation. In a post-approval trial, agalsidase beta was shown to provide significant clinical benefit by reducing the risk of a major clinical event. Thus, agalsidase beta represents an important advance in the treatment of Fabry disease, and agalsidase beta therapy should be strongly considered in patients with Fabry disease who are suitable candidates.

Differing Efficacies of Lead Group A Streptococcal Vaccine Candidates and Full-Length M Protein in Cutaneous and Invasive Disease Models

PubMed Central

Rivera-Hernandez, Tania; Pandey, Manisha; Henningham, Anna; Cole, Jason; Choudhury, Biswa; Cork, Amanda J.; Gillen, Christine M.; Ghaffar, Khairunnisa Abdul; West, Nicholas P.; Silvestri, Guido; Good, Michael F.; Moyle, Peter M.; Toth, Istvan; Nizet, Victor; Batzloff, Michael R.

2016-01-01

ABSTRACT Group A Streptococcus (GAS) is an important human pathogen responsible for both superficial infections and invasive diseases. Autoimmune sequelae may occur upon repeated infection. For this reason, development of a vaccine against GAS represents a major challenge, since certain GAS components may trigger autoimmunity. We formulated three combination vaccines containing the following: (i) streptolysin O (SLO), interleukin 8 (IL-8) protease (Streptococcus pyogenes cell envelope proteinase [SpyCEP]), group A streptococcal C5a peptidase (SCPA), arginine deiminase (ADI), and trigger factor (TF); (ii) the conserved M-protein-derived J8 peptide conjugated to ADI; and (iii) group A carbohydrate lacking the N-acetylglucosamine side chain conjugated to ADI. We compared these combination vaccines to a “gold standard” for immunogenicity, full-length M1 protein. Vaccines were adjuvanted with alum, and mice were immunized on days 0, 21, and 28. On day 42, mice were challenged via cutaneous or subcutaneous routes. High-titer antigen-specific antibody responses with bactericidal activity were detected in mouse serum samples for all vaccine candidates. In comparison with sham-immunized mice, all vaccines afforded protection against cutaneous challenge. However, only full-length M1 protein provided protection in the subcutaneous invasive disease model. PMID:27302756

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

Carrier-envelope phase-dependent atomic coherence and quantum beats

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

Wu Ying; State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan 430071; Yang Xiaoxue

2007-07-15

It is shown that the carrier-envelope phase (CEP) of few-cycle laser pulses has profound effects on the bound-state atomic coherence even in the weak-field regime where both tunneling and multiphoton ionization hardly take place. The atomic coherence thus produced is shown to be able to be mapped onto the CEP-dependent signal of quantum beats (and other quantum-interference phenomena) and hence might be used to extract information about and ultimately to measure the carrier-envelope phase.

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

Loss of function of ATXN1 increases amyloid beta-protein levels by potentiating beta-secretase processing of beta-amyloid precursor protein.

PubMed

Zhang, Can; Browne, Andrew; Child, Daniel; Divito, Jason R; Stevenson, Jesse A; Tanzi, Rudolph E

2010-03-19

Alzheimer disease (AD) is a devastating neurodegenerative disease with complex and strong genetic inheritance. Four genes have been established to either cause familial early onset AD (APP, PSEN1, and PSEN2) or to increase susceptibility for late onset AD (APOE). To date approximately 80% of the late onset AD genetic variance remains elusive. Recently our genome-wide association screen identified four novel late onset AD candidate genes. Ataxin 1 (ATXN1) is one of these four AD candidate genes and has been indicated to be the disease gene for spinocerebellar ataxia type 1, which is also a neurodegenerative disease. Mounting evidence suggests that the excessive accumulation of Abeta, the proteolytic product of beta-amyloid precursor protein (APP), is the primary AD pathological event. In this study, we ask whether ATXN1 may lead to AD pathogenesis by affecting Abeta and APP processing utilizing RNA interference in a human neuronal cell model and mouse primary cortical neurons. We show that knock-down of ATXN1 significantly increases the levels of both Abeta40 and Abeta42. This effect could be rescued with concurrent overexpression of ATXN1. Moreover, overexpression of ATXN1 decreased Abeta levels. Regarding the underlying molecular mechanism, we show that the effect of ATXN1 expression on Abeta levels is modulated via beta-secretase cleavage of APP. Taken together, ATXN1 functions as a genetic risk modifier that contributes to AD pathogenesis through a loss-of-function mechanism by regulating beta-secretase cleavage of APP and Abeta levels.

Frontal delta-beta cross-frequency coupling in high and low social anxiety: An index of stress regulation?

PubMed

Poppelaars, Eefje S; Harrewijn, Anita; Westenberg, P Michiel; van der Molen, Melle J W

2018-05-17

Cross-frequency coupling (CFC) between frontal delta (1-4 Hz) and beta (14-30 Hz) oscillations has been suggested as a candidate neural correlate of social anxiety disorder, a disorder characterized by fear and avoidance of social and performance situations. Prior studies have used amplitude-amplitude correlation (AAC) as a CFC measure and hypothesized it as a candidate neural mechanism of affective control. However, using this metric has yielded inconsistent results regarding the direction of CFC, and the functional significance of coupling strength is uncertain. To offer a better understanding of CFC in social anxiety, we compared frontal delta-beta AAC with phase-amplitude coupling (PAC) - a mechanism for information transfer through neural circuits. Twenty high socially anxious (HSA) and 32 low socially anxious (LSA) female undergraduates participated in a social performance task (SPT). Delta-beta PAC and AAC were estimated during the resting state, as well as the anticipation and recovery conditions. Results showed significantly more AAC in LSA than HSA participants during early anticipation, as well as significant values during all conditions in LSA participants only. PAC did not distinguish between LSA and HSA participants, and instead was found to correlate with state nervousness during early anticipation, but in LSA participants only. Together, these findings are interpreted to suggest that delta-beta AAC is a plausible neurobiological index of adaptive stress regulation and can distinguish between trait high and low social anxiety during stress, while delta-beta PAC might be sensitive enough to reflect mild state anxiety in LSA participants.

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.

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

Time-correlated coincidences at the sudbury neutrino observatory: An antineutrino search

NASA Astrophysics Data System (ADS)

Shokair, Timothy Milad

This dissertation presents a search for antineutrinos in all three phases of data from the Sudbury Neutrino Observatory. This work presents a new method for detecting time correlated coincidences in water detectors. There are two separate searches: an outside search for the inverse beta decay of antineutrinos on protons and an inside search for the inverse beta decay of antineutrinos on deuterons. The inside search found 3 antineutrino candidates in Phase I with an expected background of 3.83+0.71-0.72 events, 28 antineutrino candidates in Phase II with an expected background of 21.25+3.72-3.75 events, 4 antineutrino candidates in Phase III with an expected background of 6.06 +/- 1.14 events. The outside search found 4 antineutrino candidates in Phase I with an expected background of 1.21+0.14-0.17 events, 8 antineutrino candidates in Phase II with an expected background of 9.77+1.06-1.34 events, 0 antineutrino candidates in Phase III with an expected background of 0.46 +/- 0.29 events. Including the expected contribution of antineutrinos from nuclear reactors after oscillations, a limit on the solar antineutrino flux is computed to be F8Bn¯ ≤ 2.5 x 103 cm-2s -1. Taking the flux limit and the measured 8B solar neutrino flux, a limit on the neutrino to antineutrino conversion probability of P(nu → nu) ≤ 5.0 x 10-4. These limits are the best limits from a water detector.

Analysis of complex repeat sequences within the spinal muscular atrophy (SMA) candidate region in 5q13

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

Davies, K.E.; Morrison, K.E.; Daniels, R.I.

1994-09-01

We previously reported that the 400 kb interval flanked the polymorphic loci D5S435 and D5S557 contains blocks of a chromosome 5 specific repeat. This interval also defines the SMA candidate region by genetic analysis of recombinant families. A YAC contig of 2-3 Mb encompassing this area has been constructed and a 5.5 kb conserved fragment, isolated from a YAC end clone within the above interval, was used to obtain cDNAs from both fetal and adult brain libraries. We describe the identification of cDNAs with stretches of high DNA sequence homology to exons of {beta} glucuronidase on human chromosome 7. Themore » cDNAs map both to the candidate region and to an area of 5p using FISH and deletion hybrid analysis. Hybridization to bacteriophage and cosmid clones from the YACs localizes the {beta} glucuronidase related sequences within the 400 kb region of the YAC contig. The cDNAs show a polymorphic pattern on hybridization to genomic BamH1 fragments in the size range of 10-250 kb. Further analysis using YAC fragmentation vectors is being used to determine how these {beta} glucuronidase related cDNAs are distributed within 5q13. Dinucleotide repeats within the region are being investigated to determine linkage disequilibrium with the disease locus.« less

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.

Carrier-envelope-offset phase control of ultrafast optical rectification in resonantly excited semiconductors.

PubMed

Van Vlack, C; Hughes, S

2007-04-20

Ultrashort pulse light-matter interactions in a semiconductor are investigated within the regime of resonant optical rectification. Using pulse envelope areas of around 1.5-3.5 pi, a single-shot dependence on carrier-envelope-offset phase (CEP) is demonstrated for 5 fs pulse durations. A characteristic phase map is predicted for several different frequency regimes using parameters for thin-film GaAs. We subsequently suggest a possible technique to extract the CEP, in both sign and amplitude, using a solid state detector.

FIRST MAGNETIC FIELD MODELS FOR RECENTLY DISCOVERED MAGNETIC {beta} CEPHEI AND SLOWLY PULSATING B STARS

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

Hubrig, S.; Ilyin, I.; Schoeller, M.

2011-01-01

In spite of recent detections of magnetic fields in a number of {beta} Cephei and slowly pulsating B (SPB) stars, their impact on stellar rotation, pulsations, and element diffusion has not yet been sufficiently studied. The reason for this is the lack of knowledge of rotation periods, the magnetic field strength distribution and temporal variability, and the field geometry. New longitudinal field measurements of four {beta} Cephei and candidate {beta} Cephei stars, and two SPB stars were acquired with FORS 2 at the Very Large Telescope. These measurements allowed us to carry out a search for rotation periods and tomore » constrain the magnetic field geometry for four stars in our sample.« less

The CKM Matrix and The Unitarity Triangle: Another Look

NASA Astrophysics Data System (ADS)

Buras, Andrzej J.; Parodi, Fabrizio; Stocchi, Achille

2003-01-01

The unitarity triangle can be determined by means of two measurements of its sides or angles. Assuming the same relative errors on the angles (alpha,beta,gamma) and the sides (Rb,Rt), we find that the pairs (gamma,beta) and (gamma,Rb) are most efficient in determining (bar varrho,bar eta) that describe the apex of the unitarity triangle. They are followed by (alpha,beta), (alpha,Rb), (Rt,beta), (Rt,Rb) and (Rb,beta). As the set |Vus|, |Vcb|, Rt and beta appears to be the best candidate for the fundamental set of flavour violating parameters in the coming years, we show various constraints on the CKM matrix in the (Rt,beta) plane. Using the best available input we determine the universal unitarity triangle for models with minimal flavour violation (MFV) and compare it with the one in the Standard Model. We present allowed ranges for sin 2beta, sin 2alpha, gamma, Rb, Rt and DeltaMs within the Standard Model and MFV models. We also update the allowed range for the function Ftt that parametrizes various MFV-models.

Alpha-beta T cells provide protection against lethal encephalitis in the murine model of VEEV infection

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

Paessler, Slobodan; Yun, Nadezhda E.; Judy, Barbara M.

2007-10-25

We evaluated the safety and immunogenicity of a chimeric alphavirus vaccine candidate in mice with selective immunodeficiencies. This vaccine candidate was highly attenuated in mice with deficiencies in the B and T cell compartments, as well as in mice with deficient gamma-interferon responsiveness. However, the level of protection varied among the strains tested. Wild type mice were protected against lethal VEEV challenge. In contrast, alpha/beta ({alpha}{beta}) TCR-deficient mice developed lethal encephalitis following VEEV challenge, while mice deficient in gamma/delta ({gamma}{delta}) T cells were protected. Surprisingly, the vaccine potency was diminished by 50% in animals lacking interferon-gamma receptor alpha chain (R1)-chainmore » and a minority of vaccinated immunoglobulin heavy chain-deficient ({mu}MT) mice survived challenge, which suggests that neutralizing antibody may not be absolutely required for protection. Prolonged replication of encephalitic VEEV in the brain of pre-immunized mice is not lethal and adoptive transfer experiments indicate that CD3{sup +} T cells are required for protection.« less

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

The Beta Pictoris Phenomenon in Young Stars With Accreting Gas

NASA Technical Reports Server (NTRS)

Grady, Carol A.

1999-01-01

Program Hae2BPIC resulted in usable ISO spectra of three young, Herbig Ae stars: HR 5999 (A7e, t=0.6 Myr), SV Cep (al-2e, t=1-3 Myr), and MW Vul (Al-2e, t=1-3 Myr). While too small a sample to pursue our original goal of surveying the silicate emission in these young, protoplanetary disk systems, comparison of these data with ground-based IR spectra, and published ISO observations of other HAe stars (especially the posters at PPIV) reveals the following: The known binary stars in the sample show signatures of partially crystal line silicate features by t=0.6 Myr, at an epoch when ostensibly single Herbig Ae stars have substantially stronger silicate emission dominated by amorphous grains. The known binary stars also show deficits in the optically thick continuum flux relative to coeval single stars. Comparison of ISO spectra indicates that the flux deficit seen in WD 163296 over 10-100 microns relative to AB Aur reflects a real deficit of material interior to 300.

VizieR Online Data Catalog: BVIc light curves of SZ Cam (Tamajo+, 2012)

NASA Astrophysics Data System (ADS)

Tamajo, E.; Munari, U.; Siviero, A.; Tomasella, L.; Dallaporta, S.

2012-01-01

We present a spectroscopic and photometric analysis of the multiple system and early-type eclipsing binary SZ Cam (O9 IV + B0.5 V), which consists of an eclipsing SB2 pair of orbital period P=2.7-days in a long orbit (~55yrs) around a non-eclipsing SB1 pair of orbital period P=2.8-days. We have reconstructed the spectra of the individual components of SZ Cam from the observed composite spectra using the technique of spectral disentangling. We used them together with extensive and accurate BV IC CCD photometry to obtain an orbital solution. Our photometry revealed the presence of a beta Cep variable in the SZ Cam hierarchical system, probably located within the non-eclipsing SB1 pair. The pulsation period is 0.33265+/-0.00005-days and the observed total amplitude in the B band is 0.0105+/-0.0005mag. NLTE analysis of the disentangled spectra provided atmospheric parameters for all three components, consistent with those derived from orbital solution. (1 data file).

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/.

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.

Backscatter laser depolarization studies of simulated stratospheric aerosols - Crystallized sulfuric acid droplets

NASA Technical Reports Server (NTRS)

Sassen, Kenneth; Zhao, Hongjie; Yu, Bing-Kun

1989-01-01

The optical depolarizing properties of simulated stratospheric aerosols were studied in laboratory laser (0.633 micrometer) backscattering experiments for application to polarization lidar observations. Clouds composed of sulfuric acid solution droplets, some treated with ammonia gas, were observed during evaporation. The results indicate that the formation of minute ammonium sulfate particles from the evaporation of acid droplets produces linear depolarization ratios of beta equivalent to 0.02, but beta equivalent to 0.10 to 0.15 are generated from aged acid cloud aerosols and acid droplet crystalization effects following the introduction of ammonia gas into the chamber. It is concluded that partially crystallized sulfuric acid droplets are a likely candidate for explaining the lidar beta equivalent to 0.10 values that have been observed in the lower stratosphere in the absence of the relatively strong backscattering from homogeneous sulfuric acid droplet (beta equivalent to 0) or ice crystal (beta equivalent to 0.5) clouds.

Backscatter laser depolarization studies of simulated stratospheric aerosols: Crystallized sulfuric acid droplets

NASA Technical Reports Server (NTRS)

Sassen, Kenneth; Zhao, Hongjie; Yu, Bing-Kun

1988-01-01

The optical depolarizing properties of simulated stratospheric aerosols were studied in laboratory laser (0.633 micrometer) backscattering experiments for application to polarization lidar observations. Clouds composed of sulfuric acid solution droplets, some treated with ammonia gas, were observed during evaporation. The results indicate that the formation of minute ammonium sulfate particles from the evaporation of acid droplets produces linear depolarization ratios of beta equivalent to 0.02, but beta equivalent to 0.10 to 0.15 are generated from aged acid cloud aerosols and acid droplet crystallization effects following the introduction of ammonia gas into the chamber. It is concluded that partially crystallized sulfuric acid droplets are a likely candidate for explaining the lidar beta equivalent to 0.10 values that have been observed in the lower stratosphere in the absence of the relatively strong backscattering from homogeneous sulfuric acid droplet (beta equivalent to 0) or ice crystal (beta equivalent to 0.5) clouds.

First total-absorption spectroscopy measurement on the neutron-rich Cu isotopes

NASA Astrophysics Data System (ADS)

Naqvi, F.; Spyrou, A.; Liddick, S. N.; Larsen, A. C.; Guttormsen, M.; Bleuel, D. L.; Campo, L. C.; Couture, A.; Crider, B. P.; Dombos, A. C.; Ginter, T.; Lewis, R.; Mosby, S.; Perdikakis, G.; Prokop, C. P.; Quinn, S. J.; Renstrom, T.; Rubio, B.; Siem, S.

2015-10-01

The first beta-decay studies of 73-71Cu isotopes using the Total Absorption Spectroscopy (TAS) will be reported. The Cu isotopes have one proton outside the Z = 28 shell and hence are good candidates to probe the single-particle structure in the region.Theories predict weakening of the Z = 28 shell gap due to the tensor interaction between the valence πν single-particle orbitals. Comparing the beta-decay strength distributions in the daughter Zn isotopes to the theoretical calculations will provide a stringent test of the predictions. The experiment was performed at the National Superconducting Cyclotron Laboratory (NSCL) employing the TAS technique with the Summing NaI(Tl) detector, while beta decays were measured in the NSCL beta-counting system. The experimentally obtained total absorption spectra for the neutron-rich Cu isotopes will be presented and the implications of the extracted beta-feeding intensities will be discussed.

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

Regeneration of hyaline cartilage by cell-mediated gene therapy using transforming growth factor beta 1-producing fibroblasts.

PubMed

Lee, K H; Song, S U; Hwang, T S; Yi, Y; Oh, I S; Lee, J Y; Choi, K B; Choi, M S; Kim, S J

2001-09-20

Transforming growth factor beta (TGF-beta) has been considered as a candidate for gene therapy of orthopedic diseases. The possible application of cell-mediated TGF-beta gene therapy as a new treatment regimen for degenerative arthritis was investigated. In this study, fibroblasts expressing active TGF-beta 1 were injected into the knee joints of rabbits with artificially made cartilage defects to evaluate the feasibility of this therapy for orthopedic diseases. Two to 3 weeks after the injection there was evidence of cartilage regeneration, and at 4 to 6 weeks the cartilage defect was completely filled with newly grown hyaline cartilage. Histological analyses of the regenerated cartilage suggested that it was well integrated with the adjacent normal cartilage at the sides of the defect and that the newly formed tissue was indeed hyaline cartilage. Our findings suggest that cell-mediated TGF-beta 1 gene therapy may be a novel treatment for orthopedic diseases in which hyaline cartilage damage has occurred.

Candidate Gene Study of TRAIL and TRAIL Receptors: Association with Response to Interferon Beta Therapy in Multiple Sclerosis Patients

PubMed Central

Órpez-Zafra, Teresa; Pinto-Medel, María Jesús; Oliver-Martos, Begoña; Ortega-Pinazo, Jesús; Arnáiz, Carlos; Guijarro-Castro, Cristina; Varadé, Jezabel; Álvarez-Lafuente, Roberto; Urcelay, Elena; Sánchez-Jiménez, Francisca

2013-01-01

TRAIL and TRAIL Receptor genes have been implicated in Multiple Sclerosis pathology as well as in the response to IFN beta therapy. The objective of our study was to evaluate the association of these genes in relation to the age at disease onset (AAO) and to the clinical response upon IFN beta treatment in Spanish MS patients. We carried out a candidate gene study of TRAIL, TRAILR-1, TRAILR-2, TRAILR-3 and TRAILR-4 genes. A total of 54 SNPs were analysed in 509 MS patients under IFN beta treatment, and an additional cohort of 226 MS patients was used to validate the results. Associations of rs1047275 in TRAILR-2 and rs7011559 in TRAILR-4 genes with AAO under an additive model did not withstand Bonferroni correction. In contrast, patients with the TRAILR-1 rs20576-CC genotype showed a better clinical response to IFN beta therapy compared with patients carrying the A-allele (recessive model: p = 8.88×10−4, pc = 0.048, OR = 0.30). This SNP resulted in a non synonymous substitution of Glutamic acid to Alanine in position 228 (E228A), a change previously associated with susceptibility to different cancer types and risk of metastases, suggesting a lack of functionality of TRAILR-1. In order to unravel how this amino acid change in TRAILR-1 would affect to death signal, we performed a molecular modelling with both alleles. Neither TRAIL binding sites in the receptor nor the expression levels of TRAILR-1 in peripheral blood mononuclear cell subsets (monocytes, CD4+ and CD8+ T cells) were modified, suggesting that this SNP may be altering the death signal by some other mechanism. These findings show a role for TRAILR-1 gene variations in the clinical outcome of IFN beta therapy that might have relevance as a biomarker to predict the response to IFN beta in MS. PMID:23658636

No significant association between the genetic polymorphisms in the GSK-3 beta gene and schizophrenia in the Chinese population.

PubMed

Meng, Junwei; Shi, Yongyong; Zhao, Xinzhi; Zhou, Jian; Zheng, Yonglan; Tang, Ruqi; Ma, Gang; Zhu, Xuming; He, Zangdong; Wang, Zhe; Xu, Yifeng; Feng, Guoyin; He, Lin

2008-04-01

The GSK-3 beta gene encodes a protein kinase which is abundant in the brain, and its product is involved in signal transduction cascades of neuronal cell development, energy metabolism and body pattern formation. Previous studies have suggested that GSK-3 beta might act as a potential candidate locus for schizophrenia susceptibility. We genotyped six SNPs within the gene and conducted a case-control study involving 329 schizophrenic patients and 288 healthy subjects in the Chinese population. We examined allele and genotype frequencies and haplotype distributions in the subtype of paranoid schizophrenic patients as well as schizophrenic subjects in general. Our results fail to replicate the association of the GSK-3 beta gene with susceptibility to schizophrenia in the Chinese population.

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.

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.

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.

Maintained activity of glycogen synthase kinase-3{beta} despite of its phosphorylation at serine-9 in okadaic acid-induced neurodegenerative model

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

Lim, Yong-Whan; Yoon, Seung-Yong, E-mail: ysy@amc.seoul.kr; Institute for Biomacromolecules, University of Ulsan College of Medicine, Seoul

2010-04-30

Glycogen synthase kinase-3{beta} (GSK3{beta}) is recognized as one of major kinases to phosphorylate tau in Alzheimer's disease (AD), thus lots of AD drug discoveries target GSK3{beta}. However, the inactive form of GSK3{beta} which is phosphorylated at serine-9 is increased in AD brains. This is also inconsistent with phosphorylation status of other GSK3{beta} substrates, such as {beta}-catenin and collapsin response mediator protein-2 (CRMP2) since their phosphorylation is all increased in AD brains. Thus, we addressed this paradoxical condition of AD in rat neurons treated with okadaic acid (OA) which inhibits protein phosphatase-2A (PP2A) and induces tau hyperphosphorylation and cell death. Interestingly,more » OA also induces phosphorylation of GSK3{beta} at serine-9 and other substrates including tau, {beta}-catenin and CRMP2 like in AD brains. In this context, we observed that GSK3{beta} inhibitors such as lithium chloride and 6-bromoindirubin-3'-monoxime (6-BIO) reversed those phosphorylation events and protected neurons. These data suggest that GSK3{beta} may still have its kinase activity despite increase of its phosphorylation at serine-9 in AD brains at least in PP2A-compromised conditions and that GSK3{beta} inhibitors could be a valuable drug candidate in AD.« less

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.

Physical properties of gas disks around shell stars with and without dust

NASA Technical Reports Server (NTRS)

Grady, Carol A.

1992-01-01

Analysis of archival IRAS and IUE data has resulted in: (1) identification of 8 new A star proto-planetary candidates; (2) detection of a mass outflow event around Beta Pic (subsequently confirmed by the 1991 July HST observation); and (3) confirmation of the suggestion by Waters et al. (1988) that 51 Oph is a protoplanetary system similar to beta Pic with the detection of high density, high velocity, collisionally ionized accreting gas in the line of sight toward this star.

Feasibility of commercial space manufacturing, production of pharmaceuticals. Volume 1: Executive summary

NASA Technical Reports Server (NTRS)

1978-01-01

The feasibility of the commercial manufacturing of pharmaceuticals in space is examined. The method of obtaining pharmaceutical company involvement, laboratory results of the separation of serum proteins by the continuous flow electrophoresis process, the selection and study of candidate products, and their production requirements is presented. Antihemophilic factor, beta cells, erythropoietin, epidermal growth factor, alpha-1-antitrypsin and interferon were studied. Production mass balances for antihemophilic factor, beta cells, and erythropoietin were compared for space verus ground operation.

The quest for fragile X biomarkers.

PubMed

Westmark, Cara J

2014-12-01

Fragile X is the most common form of inherited intellectual disability and the leading known genetic cause of autism. There is currently no cure or approved medication for fragile X although various drugs target specific disease symptoms and a large number of therapeutics are in various stages of clinical development. Multiple recent clinical trials have failed on their primary endpoints indicating that there is a compelling need for validated biomarkers and outcome measures in fragile X. There are currently no validated blood-based biomarkers to assess disease severity or to monitor drug efficacy in fragile X syndrome. Herein, we review candidate blood protein biomarkers including extracellular-regulated kinase, phosphoinositide 3-kinase, matrix metalloproteinase 9, amyloid-beta and amyloid-beta protein precursor. Bench-to-bedside plans for fragile X syndrome are severely limited by the lack of validated outcome measures. The reviewed candidate biomarkers are at early stages of validation and deserve further investigation.

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.

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

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.

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

Lymphotoxin beta receptor (Lt betaR): dual roles in demyelination and remyelination and successful therapeutic intervention using Lt betaR-Ig protein.

PubMed

Plant, Sheila R; Iocca, Heather A; Wang, Ying; Thrash, J Cameron; O'Connor, Brian P; Arnett, Heather A; Fu, Yang-Xin; Carson, Monica J; Ting, Jenny P-Y

2007-07-11

Inflammation mediated by macrophages is increasingly found to play a central role in diseases and disorders that affect a myriad of organs, prominent among these are diseases of the CNS. The neurotoxicant-induced, cuprizone model of demyelination is ideally suited for the analysis of inflammatory events. Demyelination on exposure to cuprizone is accompanied by predictable microglial activation and astrogliosis, and, after cuprizone withdrawal, this activation reproducibly diminishes during remyelination. This study demonstrates enhanced expression of lymphotoxin beta receptor (Lt betaR) during the demyelination phase of this model, and Lt betaR is found in areas enriched with microglial and astroglial cells. Deletion of the Lt betaR gene (Lt betaR-/-) resulted in a significant delay in demyelination but also a slight delay in remyelination. Inhibition of Lt betaR signaling by an Lt betaR-Ig fusion decoy protein successfully delayed demyelination in wild-type mice. Unexpectedly, this Lt betaR-Ig decoy protein dramatically accelerated the rate of remyelination, even after the maximal pathological disease state had been reached. This strongly indicates the beneficial role of Lt betaR-Ig in the delay of demyelination and the acceleration of remyelination. The discrepancy between remyelination rates in these systems could be attributed to developmental abnormalities in the immune systems of Lt betaR-/- mice. These findings bode well for the use of an inhibitory Lt betaR-Ig as a candidate biological therapy in demyelinating disorders, because it is beneficial during both demyelination and remyelination.

Status of double beta decay experiments using isotopes other than 136Xe

NASA Astrophysics Data System (ADS)

Pandola, L.

2014-09-01

Neutrinoless double beta decay is a lepton-number violating process predicted by many extensions of the standard model. It is actively searched for in several candidate isotopes within many experimental projects. The status of the experimental initiatives which are looking for the neutrinoless double beta decay in isotopes other than 136Xe is reviewed, with special emphasis given to the projects that passed the R&D phase. The results recently released by the experiment GERDA are also summarized and discussed. The GERDA data give no positive indication of neutrinoless double beta decay of 76Ge and disfavor in a model-independent way the long-standing observation claim on the same isotope. The lower limit reported by GERDA for the half-life of neutrinoless double beta decay of 76Ge is T1/20ν > 2.1 ṡ1025 yr (90% C.L.), or T1/20ν > 3.0 ṡ1025 yr, when combined with the results of other 76Ge predecessor experiments.

[beta][sup +] decay and cosmic-ray half-life of [sup 91]Nb

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

Hindi, M.M.; Sur, B.; Wedding, K.L.

1993-06-01

In the laboratory, [sup 91]Nb decays by electron capture with a 680-yr half-life. However, as a high energy cosmic ray, it would be stripped of its atomic electrons and would be able to undergo only [beta][sup +] decay. We produced and chemically purified a sample of [sup 91]Nb and observed its decay with an array of Ge and NaI detectors. By following the [beta][sup +] annihilation radiation, we were able to determine the [beta][sup +] branching ratios of both the 105-keV, 61-d isomer and the ground state of [sup 91]Nb. The ground-state branch is (7.7[plus minus]0.8)[times]10[sup [minus]3]% leading to amore » [beta][sup +] partial half-like of (8.8[plus minus]1.9)[times]10[sup 6] yr. Such a value of the half-life makes [sup 91]Nb a good candidate for determining the confinement time of this secondary component of the cosmic rays.« less

Radionuclide development at BNL for nuclear medicine therapy.

PubMed

Mausner, L F; Kolsky, K L; Joshi, V; Srivastava, S C

1998-04-01

Radionuclides with medium energy beta emission and a several day half-life have often been viewed as attractive candidates for radioimmunotherapy. Among the most promising in this category are 47Sc, 67Cu, 153Sm, 188Re, and 199Au. The production of 67Cu, 153Sm, 199Au at BNL is summarized and the development of the latest candidate for this application, 47Sc, is described in detail. We also summarize the development of another important therapeutic radionuclide, 117mSn for bone pain palliation.

Benefit evaluation of space processing of biological materials

NASA Technical Reports Server (NTRS)

1977-01-01

A rational analytical basis for the evaluation of potential benefits of space processing of biological materials is described. A preliminary evaluation of three candidate space processed biological materials was accomplished. Materials investigated were human lymphocytes, urokinase, and Beta cells. Separation of lymphocyte groups was considered in order to improve the matching of donors and recipients for kidney transplantation, while urokinase was examined in regard to treatment of thromboembolic diseases. Separation of Beta cells was studied since it could provide a highly effective means for the treatment of juvenile-onset diabetes.

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.

An siRNA-based functional genomics screen for the identification of regulators of ciliogenesis and ciliopathy genes

PubMed Central

Racher, Hilary; Phelps, Ian G.; Toedt, Grischa; Kennedy, Julie; Wunderlich, Kirsten A.; Sorusch, Nasrin; Abdelhamed, Zakia A.; Natarajan, Subaashini; Herridge, Warren; van Reeuwijk, Jeroen; Horn, Nicola; Boldt, Karsten; Parry, David A.; Letteboer, Stef J.F.; Roosing, Susanne; Adams, Matthew; Bell, Sandra M.; Bond, Jacquelyn; Higgins, Julie; Morrison, Ewan E.; Tomlinson, Darren C.; Slaats, Gisela G.; van Dam, Teunis J. P.; Huang, Lijia; Kessler, Kristin; Giessl, Andreas; Logan, Clare V.; Boyle, Evan A.; Shendure, Jay; Anazi, Shamsa; Aldahmesh, Mohammed; Al Hazzaa, Selwa; Hegele, Robert A.; Ober, Carole; Frosk, Patrick; Mhanni, Aizeddin A.; Chodirker, Bernard N.; Chudley, Albert E.; Lamont, Ryan; Bernier, Francois P.; Beaulieu, Chandree L.; Gordon, Paul; Pon, Richard T.; Donahue, Clem; Barkovich, A. James; Wolf, Louis; Toomes, Carmel; Thiel, Christian T.; Boycott, Kym M.; McKibbin, Martin; Inglehearn, Chris F.; Stewart, Fiona; Omran, Heymut; Huynen, Martijn A.; Sergouniotis, Panagiotis I.; Alkuraya, Fowzan S.; Parboosingh, Jillian S.; Innes, A Micheil; Willoughby, Colin E.; Giles, Rachel H.; Webster, Andrew R.; Ueffing, Marius; Blacque, Oliver; Gleeson, Joseph G.; Wolfrum, Uwe; Beales, Philip L.; Gibson, Toby

2015-01-01

Defects in primary cilium biogenesis underlie the ciliopathies, a growing group of genetic disorders. We describe a whole genome siRNA-based reverse genetics screen for defects in biogenesis and/or maintenance of the primary cilium, obtaining a global resource. We identify 112 candidate ciliogenesis and ciliopathy genes, including 44 components of the ubiquitin-proteasome system, 12 G-protein-coupled receptors, and three pre-mRNA processing factors (PRPF6, PRPF8 and PRPF31) mutated in autosomal dominant retinitis pigmentosa. The PRPFs localise to the connecting cilium, and PRPF8- and PRPF31-mutated cells have ciliary defects. Combining the screen with exome sequencing data identified recessive mutations in PIBF1/CEP90 and C21orf2/LRRC76 as causes of the ciliopathies Joubert and Jeune syndromes. Biochemical approaches place C21orf2 within key ciliopathy-associated protein modules, offering an explanation for the skeletal and retinal involvement observed in individuals with C21orf2-variants. Our global, unbiased approaches provide insights into ciliogenesis complexity and identify roles for unanticipated pathways in human genetic disease. PMID:26167768

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.

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.

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

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.

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

Gene-gene interactions among genetic variants from obesity candidate genes for nonobese and obese populations in type 2 diabetes.

PubMed

Lin, Eugene; Pei, Dee; Huang, Yi-Jen; Hsieh, Chang-Hsun; Wu, Lawrence Shih-Hsin

2009-08-01

Recent studies indicate that obesity may play a key role in modulating genetic predispositions to type 2 diabetes (T2D). This study examines the main effects of both single-locus and multilocus interactions among genetic variants in Taiwanese obese and nonobese individuals to test the hypothesis that obesity-related genes may contribute to the etiology of T2D independently and/or through such complex interactions. We genotyped 11 single nucleotide polymorphisms for 10 obesity candidate genes including adrenergic beta-2-receptor surface, adrenergic beta-3-receptor surface, angiotensinogen, fat mass and obesity associated gene, guanine nucleotide binding protein beta polypeptide 3 (GNB3), interleukin 6 receptor, proprotein convertase subtilisin/kexin type 1 (PCSK1), uncoupling protein 1, uncoupling protein 2, and uncoupling protein 3. There were 389 patients diagnosed with T2D and 186 age- and sex-matched controls. Single-locus analyses showed significant main effects of the GNB3 and PCSK1 genes on the risk of T2D among the nonobese group (p = 0.002 and 0.047, respectively). Further, interactions involving GNB3 and PCSK1 were suggested among the nonobese population using the generalized multifactor dimensionality reduction method (p = 0.001). In addition, interactions among angiotensinogen, fat mass and obesity associated gene, GNB3, and uncoupling protein 3 genes were found in a significant four-locus generalized multifactor dimensionality reduction model among the obese population (p = 0.001). The results suggest that the single nucleotide polymorphisms from the obesity candidate genes may contribute to the risk of T2D independently and/or in an interactive manner according to the presence or absence of obesity.

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.

Using Complex Event Processing (CEP) and vocal synthesis techniques to improve comprehension of sonified human-centric data

NASA Astrophysics Data System (ADS)

Rimland, Jeff; Ballora, Mark

2014-05-01

The field of sonification, which uses auditory presentation of data to replace or augment visualization techniques, is gaining popularity and acceptance for analysis of "big data" and for assisting analysts who are unable to utilize traditional visual approaches due to either: 1) visual overload caused by existing displays; 2) concurrent need to perform critical visually intensive tasks (e.g. operating a vehicle or performing a medical procedure); or 3) visual impairment due to either temporary environmental factors (e.g. dense smoke) or biological causes. Sonification tools typically map data values to sound attributes such as pitch, volume, and localization to enable them to be interpreted via human listening. In more complex problems, the challenge is in creating multi-dimensional sonifications that are both compelling and listenable, and that have enough discrete features that can be modulated in ways that allow meaningful discrimination by a listener. We propose a solution to this problem that incorporates Complex Event Processing (CEP) with speech synthesis. Some of the more promising sonifications to date use speech synthesis, which is an "instrument" that is amenable to extended listening, and can also provide a great deal of subtle nuance. These vocal nuances, which can represent a nearly limitless number of expressive meanings (via a combination of pitch, inflection, volume, and other acoustic factors), are the basis of our daily communications, and thus have the potential to engage the innate human understanding of these sounds. Additionally, recent advances in CEP have facilitated the extraction of multi-level hierarchies of information, which is necessary to bridge the gap between raw data and this type of vocal synthesis. We therefore propose that CEP-enabled sonifications based on the sound of human utterances could be considered the next logical step in human-centric "big data" compression and transmission.

Double Charge Exchange Reactions and Double Beta Decay

NASA Astrophysics Data System (ADS)

Auerbach, N.

2018-05-01

The subject of this presentation is at the forefront of nuclear physics, namely double beta decay. In particular one is most interested in the neutrinoless process of double beta decay, when the decay proceeds without the emission of two neutrinos. The observation of such decay would mean that the lepton conservation symmetry is violated and that the neutrinos are of Majorana type, meaning that they are their own anti-particles. The life time of this process has two unknowns, the mass of the neutrino and the nuclear matrix element. Determining the nuclear matrix element and knowing the cross-section well will set limits on the neutrino mass. There is a concentrated effort among the nuclear physics community to calculate this matrix element. Usually these matrix elements are a very small part of the total strength of the transition operators involved in the process. There is no simple way to “calibrate” the nuclear double beta decay matrix element. The double beta decay is a double charge exchange process, therefore it is proposed that double charge exchange reactions using ion projectiles on nuclei that are candidates for double beta decay, will provide additional necessary information about the nuclear matrix elements.

ADHD Candidate Gene Study in a Population-Based Birth Cohort: Association with DBH and DRD2

ERIC Educational Resources Information Center

Nyman, Emma S.; Ogdie, Matthew N.; Loukola, Anu; Varilo, Teppo; Taanila, Anja; Hurtig, Tuula; Moilanen, Irma K.; Loo, Sandra K.; McGough, James J.; Jarvelin, Marjo-Riitta; Smalley, Susan L.

2007-01-01

A study aims to examine the genetic contribution if any to attention-deficit/hyperactivity disorder (ADHD). The results confirm the hypothesis and the association of dopamine [beta]-hydroxylase and dopamine receptor D2 genes with ADHD.

Somatostatin regulates brain amyloid beta peptide Abeta42 through modulation of proteolytic degradation.

PubMed

Saito, Takashi; Iwata, Nobuhisa; Tsubuki, Satoshi; Takaki, Yoshie; Takano, Jiro; Huang, Shu-Ming; Suemoto, Takahiro; Higuchi, Makoto; Saido, Takaomi C

2005-04-01

Expression of somatostatin in the brain declines during aging in various mammals including apes and humans. A prominent decrease in this neuropeptide also represents a pathological characteristic of Alzheimer disease. Using in vitro and in vivo paradigms, we show that somatostatin regulates the metabolism of amyloid beta peptide (Abeta), the primary pathogenic agent of Alzheimer disease, in the brain through modulating proteolytic degradation catalyzed by neprilysin. Among various effector candidates, only somatostatin upregulated neprilysin activity in primary cortical neurons. A genetic deficiency of somatostatin altered hippocampal neprilysin activity and localization, and increased the quantity of a hydrophobic 42-mer form of Abeta, Abeta(42), in a manner similar to presenilin gene mutations that cause familial Alzheimer disease. These results indicate that the aging-induced downregulation of somatostatin expression may be a trigger for Abeta accumulation leading to late-onset sporadic Alzheimer disease, and suggest that somatostatin receptors may be pharmacological-target candidates for prevention and treatment of Alzheimer disease.

Physiological and chemical analysis of neurotransmitter candidates at a fast excitatory synapse in the jellyfish Cyanea capillata (Cnidaria, Scyphozoa).

PubMed

Anderson, Peter A V; Trapido-Rosenthal, H G

2009-12-01

Motor nerve net (MNN) neurons in the jellyfish Cyanea capillata communicate with one another by way of fast, bidirectional excitatory chemical synapses. As is the case with almost all identified chemical synapses in cnidarians, the identity of the neurotransmitter at these synapses is unclear. MNN neurons are large enough for stable intracellular recordings. This, together with the fact that they can be exposed, providing unlimited access to them and to their synapses, prompted a study of the action of a variety of neurotransmitter candidates, including those typically associated with fast synapses in higher animals. Only the amino acids taurine and beta-alanine produced physiological responses consistent with those of the normal EPSP in these cells. Moreover, chemical analysis revealed that both taurine and beta-alanine are present in the neurons and released by depolarization. These various findings strongly suggest that either or both of these amino acids, or a closely related compound is the neurotransmitter at the fast chemical synapses between MNN neurons.

Alpha-beta T cells provide protection against lethal encephalitis in the murine model of VEEV infection

PubMed Central

Paessler, Slobodan; Yun, Nadezhda E.; Judy, Barbara M.; Dziuba, Natallia; Zacks, Michele A.; Grund, Anna H.; Frolov, Ilya; Campbell, Gerald A.; Weaver, Scott C.; Estes, D. Mark

2007-01-01

We evaluated the safety and immunogenicity of a chimeric alphavirus vaccine candidate in mice with selective immunodeficiencies. This vaccine candidate was highly attenuated in mice with deficiencies in the B and T cell compartments, as well as in mice with deficient gamma-interferon responsiveness. However, the level of protection varied among the strains tested. Wild type mice were protected against lethal VEEV challenge. In contrast, alpha/beta (αβ) TCR-deficient mice developed lethal encephalitis following VEEV challenge, while mice deficient in gamma/delta ( γδ) T cells were protected. Surprisingly, the vaccine potency was diminished by 50% in animals lacking interferon-gamma receptor alpha chain (R1)-chain and a minority of vaccinated immunoglobulin heavy chain-deficient (μMT) mice survived challenge, which suggests that neutralizing antibody may not be absolutely required for protection. Prolonged replication of encephalitic VEEV in the brain of pre-immunized mice is not lethal and adoptive transfer experiments indicate that CD3+ T cells are required for protection. PMID:17610927

Evaluation of suitable porosity for sintered porous {beta}-tricalcium phosphate as a bone substitute

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

Park, Jin-Hong; Bae, Ji-Yong; Shim, Jaebum

2012-09-15

Structural and mechanical characterization is performed for sintered porous beta tricalcium phosphate ({beta}-TCP) to determine the appropriate porosity for use as a bone substitute. Four different types of porous {beta}-TCP specimen with different porosities are fabricated through a sintering process. For structural characterization, scanning electron microscopy and a Microfocus X-ray computed tomography system are used to investigate the pore openings on the specimen's surface, pore size, pore distribution, and pore interconnections. Compression tests of the specimens are performed, and mechanical properties such as the elastic modulus and compressive strength are obtained. Also, the geometric shape and volume of the {beta}-TCPmore » around the contact region of two pores, which need to be initially resolved after implantation in order to increase the size of the pore openings, are evaluated through simple calculations. The results show that porous {beta}-TCP with 42.1% porosity may be a suitable bone substitute candidate in terms of sustaining external loads, and inducing and cultivating bone cells. - Highlights: Black-Right-Pointing-Pointer Structural and mechanical characterization was performed for sintered porous {beta}-TCP specimens. Black-Right-Pointing-Pointer For structural characterization, SEM and Microfocus X-ray CT system were used. Black-Right-Pointing-Pointer For mechanical characterization, compression tests were performed. Black-Right-Pointing-Pointer Porous {beta}-TCP with 42.1% porosity may be a suitable bone substitute.« less

Localization of beta and gamma subunits of ENaC in sensory nerve endings in the rat foot pad.

PubMed

Drummond, H A; Abboud, F M; Welsh, M J

2000-11-24

The molecular mechanisms underlying mechanoelectrical transduction and the receptors that detect light touch remain uncertain. Studies in Caenorhabditis elegans suggest that members of the DEG/ENaC cation channel family may be mechanoreceptors. Therefore, we tested the hypothesis that subunits of the mammalian epithelial Na(+) channel (ENaC) family are expressed in touch receptors in rat hairless skin. We detected betaENaC and gammaENaC, but not alphaENaC transcripts in cervical and lumbar dorsal root ganglia (DRG). Using immunofluorescence, we found betaENaC and gammaENaC expressed in medium to large lumbar DRG neurons. Moreover, we detected these two subunits in Merkel cell-neurite complexes, Meissner-like corpuscles, and small lamellated corpuscles, specialized mechanosensory structures of the skin. Within these structures, betaENaC and gammaENaC were localized in the nerve fibers believed to contain the sensors responsive to mechanical stress. Thus beta and gammaENaC subunits are good candidates as components of the molecular sensor that detects touch.

1-Methyl-beta-carboline (harmane), a potent endogenous inhibitor of benzodiazepine receptor binding.

PubMed

Rommelspacher, H; Nanz, C; Borbe, H O; Fehske, K J; Müller, W E; Wollert, U

1980-10-01

The interaction of several beta-carbolines with specific [3H]-flunitrazepam binding to benzodiazepine receptors in rat brain membranes was investigated. Out of the investigated compounds, harmane and norharmane were the most potent inhibitors of specific [3H]-flunitrazepam binding, with IC50-values in the micromolar range. All other derivatives, including harmine, harmaline, and several tetrahydroderivatives were at least ten times less potent. Harmane has been previously found in rat brain and human urine, so it is the most potent endogenous inhibitor of specific [3H]-flunitrazepam binding known so far, with a several fold higher affinity for the benzodiazepine receptor than inosine and hypoxanthine. Thus, we suggest that harmane or other related beta-carbolines could be potential candidates as endogenous ligands of the benzodiazepine receptor.

Maize arabinoxylan gels as protein delivery matrices.

PubMed

Berlanga-Reyes, Claudia M; Carvajal-Millán, Elizabeth; Lizardi-Mendoza, Jaime; Rascón-Chu, Agustin; Marquez-Escalante, Jorge A; Martínez-López, Ana Luisa

2009-04-08

The laccase induced gelation of maize bran arabinoxylans at 2.5% (w/v) in the presence of insulin or beta-lactoglobulin at 0.1% (w/v) was investigated. Insulin and beta-lacto-globulin did not modify either the gel elasticity (9 Pa) or the cross-links content (0.03 and 0.015 microg di- and triferulic acids/mg arabinoxylan, respectively). The protein release capability of the gel was also investigated. The rate of protein release from gels was dependent on the protein molecular weight. The apparent diffusion coefficient was 0.99 x 10(-7) and 0.79 x 10(-7) cm(2)/s for insulin (5 kDa) and beta-lactoglobulin (18 kDa), respectively. The results suggest that maize bran arabinoxylan gels can be potential candidates for the controlled release of proteins.

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.

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

CUORE and beyond: Bolometric techniques to explore inverted neutrino mass hierarchy

DOE PAGES

Artusa, D. R.; Avignone, F. T.; Azzolini, O.; ...

2015-03-24

The CUORE (Cryogenic Underground Observatory for Rare Events) experiment will search for neutrinoless double beta decay of 130Te. With 741 kg of TeO 2 crystals and an excellent energy resolution of 5 keV (0.2%) at the region of interest, CUORE will be one of the most competitive neutrinoless double beta decay experiments on the horizon. With five years of live time, CUORE projected neutrinoless double beta decay half-life sensitivity is 1.6 × 10 26 y at 1σ (9.5 × 10 25 y at the 90% confidence level), which corresponds to an upper limit on the effective Majorana mass in themore » range 40–100 meV (50–130 meV). Further background rejection with auxiliary light detector can significantly improve the search sensitivity and competitiveness of bolometric detectors to fully explore the inverted neutrino mass hierarchy with 130Te and possibly other double beta decay candidate nuclei.« less

Perpendicular and Parallel Ion Stochastic Heating by Kinetic Alfvén Wave Turbulence in the Solar Wind

NASA Astrophysics Data System (ADS)

Hoppock, I. W.; Chandran, B. D. G.

2017-12-01

The dissipation of turbulence is a prime candidate to explain the heating of collisionless plasmas like the solar wind. We consider the heating of protons and alpha particles using test particle simulations with a broad spectrum of randomly phased kinetic Alfvén waves (KAWs). Previous research extensively simulated and analytically considered stochastic heating at low plasma beta for conditions similar to coronal holes and the near-sun solar wind. We verify the analytical models of proton and alpha particle heating rates, and extend these simulations to plasmas with beta of order unity like in the solar wind at 1 au. Furthermore, we consider cases with very large beta of order 100, relevant to other astrophysical plasmas. We explore the parameter dependency of the critical KAW amplitude that breaks the gyro-center approximation and leads to stochastic gyro-orbits of the particles. Our results suggest that stochastic heating by KAW turbulence is an efficient heating mechanisms for moderate to high beta plasmas.

PGE(2) inhibition of TGF-beta1-induced myofibroblast differentiation is Smad-independent but involves cell shape and adhesion-dependent signaling.

PubMed

Thomas, Peedikayil E; Peters-Golden, Marc; White, Eric S; Thannickal, Victor J; Moore, Bethany B

2007-08-01

Myofibroblasts are pathogenic in pulmonary fibrotic disease due to their exuberant production of matrix rich in collagen that interferes with gas exchange and the ability of these cells to contract and distort the alveolar space. Transforming growth factor-beta1 (TGF-beta1) is a well-known inducer of myofibroblast differentiation. TGF-beta1-induced transformation of fibroblasts to apoptosis-resistant myofibroblasts is adhesion-dependent and focal adhesion kinase (FAK)-mediated. Prostaglandin E(2) (PGE(2)) inhibits this differentiation via E prostanoid receptor 2 (EP2) signaling and cAMP elevation, but whether PGE(2) does so by interfering with TGF-beta1 signaling is unknown. Thus we examined the effects of PGE(2) in the presence and absence of TGF-beta1 stimulation on candidate signaling pathways in human lung fibroblasts. We now demonstrate that PGE(2) does not interfere with TGF-beta1-induced Smad phosphorylation or its translocation to the nucleus. Rather, PGE(2) has dramatic effects on cell shape and cytoskeletal architecture and disrupts the formation of appropriate focal adhesions. PGE(2) treatment diminishes TGF-beta1-induced phosphorylation of paxillin, STAT-3, and FAK and, in turn, limits activation of the protein kinase B (PKB/Akt) pathway. These alterations do not, however, result in increased apoptosis within the first 24 h of treatment. Interestingly, the effects of PGE(2) stimulation alone do not always mirror the effects of PGE(2) in the presence of TGF-beta1, indicating that the context for EP2 signaling is different in the presence of TGF-beta1. Taken together, our results demonstrate that PGE(2) has the potential to limit TGF-beta1-induced myofibroblast differentiation via adhesion-dependent, but Smad-independent, pathways.

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

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.

The EndoC-βH1 cell line is a valid model of human beta cells and applicable for screenings to identify novel drug target candidates.

PubMed

Tsonkova, Violeta Georgieva; Sand, Fredrik Wolfhagen; Wolf, Xenia Asbæk; Grunnet, Lars Groth; Kirstine Ringgaard, Anna; Ingvorsen, Camilla; Winkel, Louise; Kalisz, Mark; Dalgaard, Kevin; Bruun, Christine; Fels, Johannes Josef; Helgstrand, Charlotte; Hastrup, Sven; Öberg, Fredrik Kryh; Vernet, Erik; Sandrini, Michael Paolo Bastner; Shaw, Allan Christian; Jessen, Carsten; Grønborg, Mads; Hald, Jacob; Willenbrock, Hanni; Madsen, Dennis; Wernersson, Rasmus; Hansson, Lena; Jensen, Jan Nygaard; Plesner, Annette; Alanentalo, Tomas; Petersen, Maja Borup Kjær; Grapin-Botton, Anne; Honoré, Christian; Ahnfelt-Rønne, Jonas; Hecksher-Sørensen, Jacob; Ravassard, Philippe; Madsen, Ole D; Rescan, Claude; Frogne, Thomas

2018-02-01

To characterize the EndoC-βH1 cell line as a model for human beta cells and evaluate its beta cell functionality, focusing on insulin secretion, proliferation, apoptosis and ER stress, with the objective to assess its potential as a screening platform for identification of novel anti-diabetic drug candidates. EndoC-βH1 was transplanted into mice for validation of in vivo functionality. Insulin secretion was evaluated in cells cultured as monolayer and as pseudoislets, as well as in diabetic mice. Cytokine induced apoptosis, glucolipotoxicity, and ER stress responses were assessed. Beta cell relevant mRNA and protein expression were investigated by qPCR and antibody staining. Hundreds of proteins or peptides were tested for their effect on insulin secretion and proliferation. Transplantation of EndoC-βH1 cells restored normoglycemia in streptozotocin induced diabetic mice. Both in vitro and in vivo, we observed a clear insulin response to glucose, and, in vitro, we found a significant increase in insulin secretion from EndoC-βH1 pseudoislets compared to monolayer cultures for both glucose and incretins. Apoptosis and ER stress were inducible in the cells and caspase 3/7 activity was elevated in response to cytokines, but not affected by the saturated fatty acid palmitate. By screening of various proteins and peptides, we found Bombesin (BB) receptor agonists and Pituitary Adenylate Cyclase-Activating Polypeptides (PACAP) to significantly induce insulin secretion and the proteins SerpinA6, STC1, and APOH to significantly stimulate proliferation. ER stress was readily induced by Tunicamycin and resulted in a reduction of insulin mRNA. Somatostatin (SST) was found to be expressed by 1% of the cells and manipulation of the SST receptors was found to significantly affect insulin secretion. Overall, the EndoC-βH1 cells strongly resemble human islet beta cells in terms of glucose and incretin stimulated insulin secretion capabilities. The cell line has an active cytokine induced caspase 3/7 apoptotic pathway and is responsive to ER stress initiation factors. The cells' ability to proliferate can be further increased by already known compounds as well as by novel peptides and proteins. Based on its robust performance during the functionality assessment assays, the EndoC-βH1 cell line was successfully used as a screening platform for identification of novel anti-diabetic drug candidates. Copyright © 2017 Novo Nordisk A/S. Published by Elsevier GmbH.. All rights reserved.

Comparative Genomics of Regulation of Fatty Acid and Branched-chain Amino Acid Utilization in Proteobacteria

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

Kazakov, Alexey E.; Rodionov, Dmitry A.; Arkin, Adam Paul

2008-10-31

Bacteria can use branched-chain amino acids (ILV, i.e. isoleucine, leucine, valine) and fatty acids (FA) as sole carbon and energy sources convering ILV into acetyl-CoA, propanoyl-CoA and propionyl-CoA, respectively. In this work, we used the comparative genomic approach to identify candidate transcriptional factors and DNA motifs that control ILV and FA utilization pathways in proteobacteria. The metabolic regulons were characterized based on the identification and comparison of candidate transcription factor binding sites in groups of phylogenetically related genomes. The reconstructed ILV/FA regulatory network demonstrates considerable variability and involves six transcriptional factors from the MerR, TetR and GntR families binding tomore » eleven distinct DNA motifs. The ILV degradation genes in gamma- and beta-proteobacteria are mainly regulated by anovel regulator from the MerR family (e.g., LiuR in Pseudomonas aeruginosa) (40 species), in addition, the TetR-type regulator LiuQ was identified in some beta-proteobacteria (8 species). Besides the core set of ILV utilization genes, the LiuR regulon in some lineages is expanded to include genes from other metabolic pathways, such as the glyoxylate shunt and glutamate synthase in the Shewanella species. The FA degradation genes are controlled by four regulators including FadR in gamma-proteobacteria (34 species), PsrA in gamma- and beta-proteobacteria (45 species), FadP in beta-proteobacteria (14 species), and LiuR orthologs in alpha-proteobacteria (22 species). The remarkable variability of the regulatory systems associated with the FA degradation pathway is discussed from the functional and evolutionary points of view.« less

On the origin of biological chirality via natural beta-decay

NASA Technical Reports Server (NTRS)

Noyes, H. P.; Bonner, W. A.; Tomlin, J. A.

1977-01-01

An hypothesis to account for the chirality (handedness) of some biological molecules is given. Experimental evidence suggests that longitudinally polarized electrons having the chirality of terrestrial beta-decay electrons remove dextro-leucine from a racemic mixture. If, by a similar mechanism, the terrestrial environment provided more levo- than dextro-amino acids, that would account for the chirality now observed in organic molecules. An isotope of potassium has been proposed as the natural beta-emitter responsible for biomolecular chirality; however, Carbon 14 may be an even more plausible candidate. Ready availability of the carbon isotope in the terrestrial environment of 4.5 aeons ago, and the role of leucine in protein synthesis indicate that these two agents may have been chief factors in the evolution of biomolecular chirality. Suggestions for further research in this area are made.

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.

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.

[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.

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.

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

Heat Shock Protein Beta-1 Modifies Anterior to Posterior Purkinje Cell Vulnerability in a Mouse Model of Niemann-Pick Type C Disease.

PubMed

Chung, Chan; Elrick, Matthew J; Dell'Orco, James M; Qin, Zhaohui S; Kalyana-Sundaram, Shanker; Chinnaiyan, Arul M; Shakkottai, Vikram G; Lieberman, Andrew P

2016-05-01

Selective neuronal vulnerability is characteristic of most degenerative disorders of the CNS, yet mechanisms underlying this phenomenon remain poorly characterized. Many forms of cerebellar degeneration exhibit an anterior-to-posterior gradient of Purkinje cell loss including Niemann-Pick type C1 (NPC) disease, a lysosomal storage disorder characterized by progressive neurological deficits that often begin in childhood. Here, we sought to identify candidate genes underlying vulnerability of Purkinje cells in anterior cerebellar lobules using data freely available in the Allen Brain Atlas. This approach led to the identification of 16 candidate neuroprotective or susceptibility genes. We demonstrate that one candidate gene, heat shock protein beta-1 (HSPB1), promoted neuronal survival in cellular models of NPC disease through a mechanism that involved inhibition of apoptosis. Additionally, we show that over-expression of wild type HSPB1 or a phosphomimetic mutant in NPC mice slowed the progression of motor impairment and diminished cerebellar Purkinje cell loss. We confirmed the modulatory effect of Hspb1 on Purkinje cell degeneration in vivo, as knockdown by Hspb1 shRNA significantly enhanced neuron loss. These results suggest that strategies to promote HSPB1 activity may slow the rate of cerebellar degeneration in NPC disease and highlight the use of bioinformatics tools to uncover pathways leading to neuronal protection in neurodegenerative disorders.

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.

Targeted next-generation sequencing identification of mutations in disease resistance gene anologs (RGAs) in wild and cultivated beets

USDA-ARS?s Scientific Manuscript database

Resistance gene analogs (RGAs) were searched bioinformatically in the sugar beet (Beta vulgaris L.) genome as potential candidates for improving resistance against different diseases. In the present study, Ion Torrent sequencing technology was used to identify mutations in 21 RGAs. The DNA samples o...

Beta-manganese dioxide nanorods for sufficient high-temperature electromagnetic interference shielding in X-band

NASA Astrophysics Data System (ADS)

Song, Wei-Li; Cao, Mao-Sheng; Hou, Zhi-Ling; Lu, Ming-Ming; Wang, Chan-Yuan; Yuan, Jie; Fan, Li-Zhen

2014-09-01

As the development of electronic and communication technology, electromagnetic interference (EMI) shielding and attenuation is an effective strategy to ensure the operation of the electronic devices. Among the materials for high-performance shielding in aerospace industry and related high-temperature working environment, the thermally stable metal oxide semiconductors with narrow band gap are promising candidates. In this work, beta-manganese dioxide ( β-MnO2) nanorods were synthesized by a hydrothermal method. The bulk materials of the β-MnO2 were fabricated to evaluate the EMI shielding performance in the temperature range of 20-500 °C between 8.2 and 12.4 GHz (X-band). To understand the mechanisms of high-temperature EMI shielding, the contribution of reflection and absorption to EMI shielding was discussed based on temperature-dependent electrical properties and complex permittivity. Highly sufficient shielding effectiveness greater than 20 dB was observed over all the investigated range, suggesting β-MnO2 nanorods as promising candidates for high-temperature EMI shielding. The results have also established a platform to develop high-temperature EMI shielding materials based on nanoscale semiconductors.

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 ...

Genome-Wide Identification of Differentially Expressed Genes Associated with the High Yielding of Oleoresin in Secondary Xylem of Masson Pine (Pinus massoniana Lamb) by Transcriptomic Analysis

PubMed Central

Liu, Qinghua; Zhou, Zhichun; Wei, Yongcheng; Shen, Danyu; Feng, Zhongping; Hong, Shanping

2015-01-01

Masson pine is an important timber and resource for oleoresin in South China. Increasing yield of oleoresin in stems can raise economic benefits and enhance the resistance to bark beetles. However, the genetic mechanisms for regulating the yield of oleoresin were still unknown. Here, high-throughput sequencing technology was used to investigate the transcriptome and compare the gene expression profiles of high and low oleoresin-yielding genotypes. A total of 40,690,540 reads were obtained and assembled into 137,499 transcripts from the secondary xylem tissues. We identified 84,842 candidate unigenes based on sequence annotation using various databases and 96 unigenes were candidates for terpenoid backbone biosynthesis in pine. By comparing the expression profiles of high and low oleoresin-yielding genotypes, 649 differentially expressed genes (DEGs) were identified. GO enrichment analysis of DEGs revealed that multiple pathways were related to high yield of oleoresin. Nine candidate genes were validated by QPCR analysis. Among them, the candidate genes encoding geranylgeranyl diphosphate synthase (GGPS) and (-)-alpha/beta-pinene synthase were up-regulated in the high oleoresin-yielding genotype, while tricyclene synthase revealed lower expression level, which was in good agreement with the GC/MS result. In addition, DEG encoding ABC transporters, pathogenesis-related proteins (PR5 and PR9), phosphomethylpyrimidine synthase, non-specific lipid-transfer protein-like protein and ethylene responsive transcription factors (ERFs) were also confirmed to be critical for the biosynthesis of oleoresin. The next-generation sequencing strategy used in this study has proven to be a powerful means for analyzing transcriptome variation related to the yield of oleoresin in masson pine. The candidate genes encoding GGPS, (-)-alpha/beta-pinene, tricyclene synthase, ABC transporters, non-specific lipid-transfer protein-like protein, phosphomethylpyrimidine synthase, ERFs and pathogen responses may play important roles in regulating the yield of oleoresin. These DEGs are worthy of special attention in future studies. PMID:26167875

Targeted next generation sequencing identifies functionally deleterious germline mutations in novel genes in early-onset/familial prostate cancer.

PubMed

Paulo, Paula; Maia, Sofia; Pinto, Carla; Pinto, Pedro; Monteiro, Augusta; Peixoto, Ana; Teixeira, Manuel R

2018-04-01

Considering that mutations in known prostate cancer (PrCa) predisposition genes, including those responsible for hereditary breast/ovarian cancer and Lynch syndromes, explain less than 5% of early-onset/familial PrCa, we have sequenced 94 genes associated with cancer predisposition using next generation sequencing (NGS) in a series of 121 PrCa patients. We found monoallelic truncating/functionally deleterious mutations in seven genes, including ATM and CHEK2, which have previously been associated with PrCa predisposition, and five new candidate PrCa associated genes involved in cancer predisposing recessive disorders, namely RAD51C, FANCD2, FANCI, CEP57 and RECQL4. Furthermore, using in silico pathogenicity prediction of missense variants among 18 genes associated with breast/ovarian cancer and/or Lynch syndrome, followed by KASP genotyping in 710 healthy controls, we identified "likely pathogenic" missense variants in ATM, BRIP1, CHEK2 and TP53. In conclusion, this study has identified putative PrCa predisposing germline mutations in 14.9% of early-onset/familial PrCa patients. Further data will be necessary to confirm the genetic heterogeneity of inherited PrCa predisposition hinted in this study.

LIF is more potent than BDNF in promoting neurite outgrowth of mammalian auditory neurons in vitro.

PubMed

Gillespie, L N; Clark, G M; Bartlett, P F; Marzella, P L

2001-02-12

Neurotrophic factors are known to play a crucial role in the elongation and guidance of auditory nerve fibres to their targets within the organ of Corti. Maintenance of these neural connections following deafness would clearly influence the efficacy of therapies for hearing recovery. The growth factors leukaemia inhibitory factor (LIF), brain-derived neurotrophic factor (BDNF) and transforming growth factor-beta 5 (TGF-beta5) were tested for their efficacy in promoting neurite outgrowth from dissociated cultures of early postnatal rat auditory neurons. Our results indicate that while BDNF enhances neurite outgrowth in a strong fashion, LIF is more potent; moreover, the combined administration of both factors has even greater neuritogenic capacities. TGF-beta5, although neurotrophic, has no neuritogenic activity on cultured auditory neurons. LIF and BDNF may therefore be potential candidates when developing pharmacological therapies for hearing recovery.

Search for pair production of scalar top quarks decaying to a tau lepton and a b quark in pp over collisions at sqrt s=1.96 TeV.

PubMed

Aaltonen, T; Adelman, J; Akimoto, T; Albrow, M G; Alvarez González, B; Amerio, S; Amidei, D; Anastassov, A; Annovi, A; Antos, J; Aoki, M; Apollinari, G; Apresyan, A; Arisawa, T; Artikov, A; Ashmanskas, W; Attal, A; Aurisano, A; Azfar, F; Azzi-Bacchetta, P; Azzurri, P; Bacchetta, N; Badgett, W; Barbaro-Galtieri, A; Barnes, V E; Barnett, B A; Baroiant, S; Bartsch, V; Bauer, G; Beauchemin, P-H; Bedeschi, F; Bednar, P; Behari, S; Bellettini, G; Bellinger, J; Belloni, A; Benjamin, D; Beretvas, A; Beringer, J; Berry, T; Bhatti, A; Binkley, M; Bisello, D; Bizjak, I; Blair, R E; Blocker, C; Blumenfeld, B; Bocci, A; Bodek, A; Boisvert, V; Bolla, G; Bolshov, A; Bortoletto, D; Boudreau, J; Boveia, A; Brau, B; Bridgeman, A; Brigliadori, L; Bromberg, C; Brubaker, E; Budagov, J; Budd, H S; Budd, S; Burkett, K; Busetto, G; Bussey, P; Buzatu, A; Byrum, K L; Cabrera, S; Campanelli, M; Campbell, M; Canelli, F; Canepa, A; Carlsmith, D; Carosi, R; Carrillo, S; Carron, S; Casal, B; Casarsa, M; Castro, A; Catastini, P; Cauz, D; Cavalli-Sforza, M; Cerri, A; Cerrito, L; Chang, S H; Chen, Y C; Chertok, M; Chiarelli, G; Chlachidze, G; Chlebana, F; Cho, K; Chokheli, D; Chou, J P; Choudalakis, G; Chuang, S H; Chung, K; Chung, W H; Chung, Y S; Ciobanu, C I; Ciocci, M A; Clark, A; Clark, D; Compostella, G; Convery, M E; Conway, J; Cooper, B; Copic, K; Cordelli, M; Cortiana, G; Crescioli, F; Cuenca Almenar, C; Cuevas, J; Culbertson, R; Cully, J C; Dagenhart, D; Datta, M; Davies, T; de Barbaro, P; De Cecco, S; Deisher, A; De Lentdecker, G; De Lorenzo, G; Dell'Orso, M; Demortier, L; Deng, J; Deninno, M; De Pedis, D; Derwent, P F; Di Giovanni, G P; Dionisi, C; Di Ruzza, B; Dittmann, J R; D'Onofrio, M; Donati, S; Dong, P; Donini, J; Dorigo, T; Dube, S; Efron, J; Erbacher, R; Errede, D; Errede, S; Eusebi, R; Fang, H C; Farrington, S; Fedorko, W T; Feild, R G; Feindt, M; Fernandez, J P; Ferrazza, C; Field, R; Flanagan, G; Forrest, R; Forrester, S; Franklin, M; Freeman, J C; Furic, I; Gallinaro, M; Galyardt, J; Garberson, F; Garcia, J E; Garfinkel, A F; Genser, K; Gerberich, H; Gerdes, D; Giagu, S; Giakoumopolou, V; Giannetti, P; Gibson, K; Gimmell, J L; Ginsburg, C M; Giokaris, N; Giordani, M; Giromini, P; Giunta, M; Glagolev, V; Glenzinski, D; Gold, M; Goldschmidt, N; Golossanov, A; Gomez, G; Gomez-Ceballos, G; Goncharov, M; González, O; Gorelov, I; Goshaw, A T; Goulianos, K; Gresele, A; Grinstein, S; Grosso-Pilcher, C; Grundler, U; Guimaraes da Costa, J; Gunay-Unalan, Z; Haber, C; Hahn, K; Hahn, S R; Halkiadakis, E; Hamilton, A; Han, B-Y; Han, J Y; Handler, R; Happacher, F; Hara, K; Hare, D; Hare, M; Harper, S; Harr, R F; Harris, R M; Hartz, M; Hatakeyama, K; Hauser, J; Hays, C; Heck, M; Heijboer, A; Heinemann, B; Heinrich, J; Henderson, C; Herndon, M; Heuser, J; Hewamanage, S; Hidas, D; Hill, C S; Hirschbuehl, D; Hocker, A; Hou, S; Houlden, M; Hsu, S-C; Huffman, B T; Hughes, R E; Husemann, U; Huston, J; Incandela, J; Introzzi, G; Iori, M; Ivanov, A; Iyutin, B; James, E; Jayatilaka, B; Jeans, D; Jeon, E J; Jindariani, S; Johnson, W; Jones, M; Joo, K K; Jun, S Y; Jung, J E; Junk, T R; Kamon, T; Kar, D; Karchin, P E; Kato, Y; Kephart, R; Kerzel, U; Khotilovich, V; Kilminster, B; Kim, D H; Kim, H S; Kim, J E; Kim, M J; Kim, S B; Kim, S H; Kim, Y K; Kimura, N; Kirsch, L; Klimenko, S; Klute, M; Knuteson, B; Ko, B R; Koay, S A; Kondo, K; Kong, D J; Konigsberg, J; Korytov, A; Kotwal, A V; Kraus, J; Kreps, M; Kroll, J; Krumnack, N; Kruse, M; Krutelyov, V; Kubo, T; Kuhlmann, S E; Kuhr, T; Kulkarni, N P; Kusakabe, Y; Kwang, S; Laasanen, A T; Lai, S; Lami, S; Lammel, S; Lancaster, M; Lander, R L; Lannon, K; Lath, A; Latino, G; Lazzizzera, I; LeCompte, T; Lee, J; Lee, J; Lee, Y J; Lee, S W; Lefèvre, R; Leonardo, N; Leone, S; Levy, S; Lewis, J D; Lin, C; Lin, C S; Linacre, J; Lindgren, M; Lipeles, E; Liss, T M; Lister, A; Litvintsev, D O; Liu, T; Lockyer, N S; Loginov, A; Loreti, M; Lovas, L; Lu, R-S; Lucchesi, D; Lueck, J; Luci, C; Lujan, P; Lukens, P; Lungu, G; Lyons, L; Lys, J; Lysak, R; Lytken, E; Mack, P; MacQueen, D; Madrak, R; Maeshima, K; Makhoul, K; Maki, T; Maksimovic, P; Malde, S; Malik, S; Manca, G; Manousakis, A; Margaroli, F; Marino, C; Marino, C P; Martin, A; Martin, M; Martin, V; Martínez, M; Martínez-Ballarín, R; Maruyama, T; Mastrandrea, P; Masubuchi, T; Mattson, M E; Mazzanti, P; McFarland, K S; McIntyre, P; McNulty, R; Mehta, A; Mehtala, P; Menzemer, S; Menzione, A; Merkel, P; Mesropian, C; Messina, A; Miao, T; Miladinovic, N; Miles, J; Miller, R; Mills, C; Milnik, M; Mitra, A; Mitselmakher, G; Miyake, H; Moed, S; Moggi, N; Moon, C S; Moore, R; Morello, M; Movilla Fernandez, P; Mülmenstädt, J; Mukherjee, A; Muller, Th; Mumford, R; Murat, P; Mussini, M; Nachtman, J; Nagai, Y; Nagano, A; Naganoma, J; Nakamura, K; Nakano, I; Napier, A; Necula, V; Neu, C; Neubauer, M S; Nielsen, J; Nodulman, L; Norman, M; Norniella, O; Nurse, E; Oh, S H; Oh, Y D; Oksuzian, I; Okusawa, T; Oldeman, R; Orava, R; Osterberg, K; Griso, S Pagan; Pagliarone, C; Palencia, E; Papadimitriou, V; Papaikonomou, A; Paramonov, A A; Parks, B; Pashapour, S; Patrick, J; Pauletta, G; Paulini, M; Paus, C; Pellett, D E; Penzo, A; Phillips, T J; Piacentino, G; Piedra, J; Pinera, L; Pitts, K; Plager, C; Pondrom, L; Portell, X; Poukhov, O; Pounder, N; Prakoshyn, F; Pronko, A; Proudfoot, J; Ptohos, F; Punzi, G; Pursley, J; Rademacker, J; Rahaman, A; Ramakrishnan, V; Ranjan, N; Redondo, I; Reisert, B; Rekovic, V; Renton, P; Rescigno, M; Richter, S; Rimondi, F; Ristori, L; Robson, A; Rodrigo, T; Rogers, E; Rolli, S; Roser, R; Rossi, M; Rossin, R; Roy, P; Ruiz, A; Russ, J; Rusu, V; Saarikko, H; Safonov, A; Sakumoto, W K; Salamanna, G; Saltó, O; Santi, L; Sarkar, S; Sartori, L; Sato, K; Savoy-Navarro, A; Scheidle, T; Schlabach, P; Schmidt, E E; Schmidt, M A; Schmidt, M P; Schmitt, M; Schwarz, T; Scodellaro, L; Scott, A L; Scribano, A; Scuri, F; Sedov, A; Seidel, S; Seiya, Y; Semenov, A; Sexton-Kennedy, L; Sfyrla, A; Shalhout, S Z; Shapiro, M D; Shears, T; Shepard, P F; Sherman, D; Shimojima, M; Shochet, M; Shon, Y; Shreyber, I; Sidoti, A; Sinervo, P; Sisakyan, A; Slaughter, A J; Slaunwhite, J; Sliwa, K; Smith, J R; Snider, F D; Snihur, R; Soderberg, M; Soha, A; Somalwar, S; Sorin, V; Spalding, J; Spinella, F; Spreitzer, T; Squillacioti, P; Stanitzki, M; St Denis, R; Stelzer, B; Stelzer-Chilton, O; Stentz, D; Strologas, J; Stuart, D; Suh, J S; Sukhanov, A; Sun, H; Suslov, I; Suzuki, T; Taffard, A; Takashima, R; Takeuchi, Y; Tanaka, R; Tecchio, M; Teng, P K; Terashi, K; Thom, J; Thompson, A S; Thompson, G A; Thomson, E; Tipton, P; Tiwari, V; Tkaczyk, S; Toback, D; Tokar, S; Tollefson, K; Tomura, T; Tonelli, D; Torre, S; Torretta, D; Tourneur, S; Trischuk, W; Tu, Y; Turini, N; Ukegawa, F; Uozumi, S; Vallecorsa, S; van Remortel, N; Varganov, A; Vataga, E; Vázquez, F; Velev, G; Vellidis, C; Veszpremi, V; Vidal, M; Vidal, R; Vila, I; Vilar, R; Vine, T; Vogel, M; Volobouev, I; Volpi, G; Würthwein, F; Wagner, P; Wagner, R G; Wagner, R L; Wagner-Kuhr, J; Wagner, W; Wakisaka, T; Wallny, R; Wang, S M; Warburton, A; Waters, D; Weinberger, M; Wester, W C; Whitehouse, B; Whiteson, D; Wicklund, A B; Wicklund, E; Williams, G; Williams, H H; Wilson, P; Winer, B L; Wittich, P; Wolbers, S; Wolfe, C; Wright, T; Wu, X; Wynne, S M; Yagil, A; Yamamoto, K; Yamaoka, J; Yamashita, T; Yang, C; Yang, U K; Yang, Y C; Yao, W M; Yeh, G P; Yoh, J; Yorita, K; Yoshida, T; Yu, G B; Yu, I; Yu, S S; Yun, J C; Zanello, L; Zanetti, A; Zaw, I; Zhang, X; Zheng, Y; Zucchelli, S

2008-08-15

We search for pair production of supersymmetric top quarks (t over1), followed by R-parity violating decay t over1-->taub with a branching ratio beta, using 322 pb(-1) of pp over collisions at sqrt s=1.96 TeV collected by the upgraded Collider Detector at Fermilab. Two candidate events pass our final selection criteria, consistent with the standard model expectation. We set upper limits on the cross section sigma(t over1t over1) x beta2 as a function of the top-squark mass m(t over1). Assuming beta=1, we set a 95% confidence level limit m(t over1)>153 GeV/c2. The limits are also applicable to the case of a third-generation scalar leptoquark (LQ3) decaying LQ3-->taub.

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

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.

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.

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

A short synthesis and biological evaluation of potent and nontoxic antimalarial bridged bicyclic beta-sulfonyl-endoperoxides.

PubMed

Bachi, Mario D; Korshin, Edward E; Hoos, Roland; Szpilman, Alex M; Ploypradith, Poonsakdi; Xie, Suji; Shapiro, Theresa A; Posner, Gary H

2003-06-05

The syntheses and in vitro antimalarial screening of 50 bridged, bicyclic endoperoxides of types 9-13 are reported. In contrast to antimalarial trioxanes of the artemisinin family, but like yingzhaosu A and arteflene, the peroxide function of compounds 9-13 is contained in a 2,3-dioxabicyclo[3.3.1]nonane system 6. Peroxides 9 and 10 (R(1) = OH) are readily available through a multicomponent, sequential, free-radical reaction involving thiol-monoterpenes co-oxygenation (a TOCO reaction). beta-Sulfenyl peroxides 9 and 10 (R(1) = OH) are converted into beta-sulfinyl and beta-sulfonyl peroxides of types 11-13 by controlled S-oxidation and manipulation of the tert-hydroxyl group through acylation, alkylation, or dehydration followed by selective hydrogenation. Ten enantiopure beta-sulfonyl peroxides of types 12 and 13 exhibit in vitro antimalarial activity comparable to that of artemisinin (IC(50) = 6-24 nM against Plasmodium falciparum NF54). In vivo testing of a few selected peroxides against Plasmodium berghei N indicates that the antimalarial efficacies of beta-sulfonyl peroxides 39a, 46a, 46b, and 50a are comparable to those of some of the best antimalarial drugs and are higher than artemisinin against chloroquine-resistant Plasmodium yoelii ssp. NS. In view of the nontoxicity of beta-sulfonyl peroxides 39a, 46a, and 46b in mice, at high dosing, these compounds are regarded as promising antimalarial drug candidates.

Monooxygenase, a Novel Beta-Cypermethrin Degrading Enzyme from Streptomyces sp

PubMed Central

Xiao, Ying; Deng, Yinyue; Chang, Changqing; Zhong, Guohua; Hu, Meiying; Zhang, Lian-Hui

2013-01-01

The widely used insecticide beta-cypermethrin has become a public concern because of its environmental contamination and toxic effects on mammals. In this study, a novel beta-cypermethrin degrading enzyme designated as CMO was purified to apparent homogeneity from a Streptomyces sp. isolate capable of utilizing beta-cypermethrin as a growth substrate. The native enzyme showed a monomeric structure with a molecular mass of 41 kDa and pI of 5.4. The enzyme exhibited the maximal activity at pH 7.5 and 30°C. It was fairly stable in the pH range from 6.5–8.5 and at temperatures below 10°C. The enzyme activity was significantly stimulated by Fe2+, but strongly inhibited by Ag+, Al3+, and Cu2+. The enzyme catalyzed the degradation of beta-cypermethrin to form five products via hydroxylation and diaryl cleavage. A novel beta-cypermethrin detoxification pathway was proposed based on analysis of these products. The purified enzyme was identified as a monooxygenase by matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometry analysis (MALDI-TOF-MS) and N-terminal protein sequencing. Given that all the characterized pyrethroid-degrading enzymes are the members of hydrolase family, CMO represents the first pyrethroid-degrading monooxygenase identified from environmental microorganisms. Taken together, our findings depict a novel pyrethroid degradation mechanism and indicate that the purified enzyme may be a promising candidate for detoxification of beta-cypermethrin and environmental protection. PMID:24098697

Aspartic proteases involved in Alzheimer's disease.

PubMed

Schmidt, Boris

2003-05-09

Alzheimer's disease afflicts every tenth human aged over 65. Despite the dramatic progress that has been made in understanding the disease, the exact cause of Alzheimer's disease is still unknown. Most gene mutations associated with Alzheimer's disease point at the same culprits: amyloid precursor protein and ultimately amyloid beta. The enigmatic proteases alpha-,beta-, and gamma-secretase are the three executioners of amyloid precursor protein processing, and disruption of their delicate balance is suspected to result in Alzheimer's disease. Significant progress has been made in the selective control of these proteases, regardless of the availability of structural information. Not even the absence of a robust cell-free assay for gamma-secretase could hamper the identification of nonpeptidic inhibitors of this enzyme for long. Within five years, four distinctly different structural moieties were developed and the first drug candidates are in clinical trials. Unfortunately, selective inhibition of amyloid beta formation remains a crucial issue because fundamental fragments of the gamma-secretase complex are important for other signaling events. This problem makes beta-secretase inhibition and alpha-secretase induction even more appealing.

Translocation of arrestin induced by human A(3) adenosine receptor ligands in an engineered cell line: comparison with G protein-dependent pathways.

PubMed

Gao, Zhan-Guo; Jacobson, Kenneth A

2008-04-01

Structurally diverse ligands were studied in A(3) adenosine receptor (AR)-mediated beta-arrestin translocation in engineered CHO cells. The agonist potency and efficacy were similar, although not identical, to their G protein signaling. However, differences have also been found. MRS542, MRS1760, and other adenosine derivatives, A(3)AR antagonists in cyclic AMP assays, were partial agonists in beta-arrestin translocation, indicating possible biased agonism. The xanthine 7-riboside DBXRM, a full agonist, was only partially efficacious in beta-arrestin translocation. DBXRM was shown to induce a lesser extent of desensitization compared with IB-MECA. In kinetic studies, MRS3558, a potent and selective A(3)AR agonist, induced beta-arrestin translocation significantly faster than IB-MECA and Cl-IB-MECA. Non-nucleoside antagonists showed similar inhibitory potencies as previously reported. PTX pretreatment completely abolished ERK1/2 activation, but not arrestin translocation. Thus, lead candidates for biased agonists at the A(3)AR have been identified with this arrestin-translocation assay, which promises to be an effective tool for ligand screening.

Abnormalities of peptide metabolism in Alzheimer disease.

PubMed

Panchal, Maï; Rholam, Mohamed; Brakch, Noureddine

2004-10-01

The steady-state level of peptide hormones represents a balance between their biosynthesis and proteolytic processing by convertases and their catabolism by proteolytic enzymes. Low levels of neuropeptide Y, somatostatin and corticotropin-releasing factor, described in Alzheimer disease (AD), were related to a defect in proteolytic processing of their protein precursors. In contrast the abundance of beta-amyloid peptides, the major protein constituents of senile plaques is likely related to inefficient catabolism. Therefore, attention is mainly focused on convertases that generate active peptides and counter-regulatory proteases that are involved in their catabolism. Some well-described proteases such as NEP are thought to be involved in beta-amyloid catabolism. The search of other possible candidates represents a primary effort in the field. A variety of vascular risk factors such as diabetes, hypertension and arteriosclerosis suggest that the functional vascular defect contributes to AD pathology. It has also been described that beta-amyloid peptides potentiate endothelin-1 induced vasoconstriction. In this review, we will critically evaluate evidence relating proteases implicated in amyloid protein precursor proteolytic processing and beta-amyloid catabolism.

Novel estrogens and their radical scavenging effects, iron-chelating, and total antioxidative activities: 17 alpha-substituted analogs of delta 9(11)-dehydro-17 beta-estradiol.

PubMed

Römer, W; Oettel, M; Menzenbach, B; Droescher, P; Schwarz, S

1997-11-01

Antioxidant effects of N,N-dimethyl-p-toluidine, p-cresol, and p-(hydroxy)thioanisol 17 alpha-substituted analogs of 17 beta-estradiol and their delta 9(11)-dehydro homologs were investigated using four different in vitro models: rat synaptosomal lipid peroxidation induced by Fenton's reagent, Fe(II)-chelating activities, the formation of superoxide anion radicals, and total antioxidative activity. Whereas the classical estrogen 17 beta-estradiol as well as selected phenolic compounds was only moderately inhibiting iron-dependent lipid peroxidation and stimulating total antioxidative activity, besides delta 9(11)-dehydro-17 beta-estradiol (J 1213), novel estrogens such as C-17-oriented side chain analogs of 17 beta-estradiol (J 843, J 872, and J 897) and delta 9(11)-dehydro homologs (J 844, J 864, and J 898) directly altered the iron redox chemistry and diminished the formation of superoxide anion radicals generated by a xanthine/xanthine oxidase-dependent luminescence reaction to a great extent. These results suggest that definite modifications in the chemical structure of 17 beta-estradiol, e.g., the introduction of a delta 9(11)-double bond and/or p-cresol as well as p-(hydroxy)thioanisol C-17 substitution, may result in substantial changes in their antioxidant behavior. These compounds may be drug candidates for treating pathologies related to free radical formation.

Identification of an active acidic residue in the catalytic site of beta-hexosaminidase.

PubMed

Tse, R; Vavougios, G; Hou, Y; Mahuran, D J

1996-06-11

Human beta-hexosaminidases A and B (EC 3.2.1.52) are dimeric lysosomal glycosidases composed of evolutionarily related alpha and/or beta subunits. Both isozymes hydrolyze terminal beta-linked GalNAc or GlcNAc residues from numerous artificial and natural substrates; however, in vivo GM2 ganglioside is a substrate for only the heterodimeric A isozyme. Thus, mutations in either gene encoding its alpha or beta subunits can result in GM2 ganglioside storage and Tay-Sachs or Sandhoff disease, respectively. All glycosyl hydrolases ae believed to have one or more acidic residues in their catalytic site. We demonstrate that incubation of hexosaminidase with a chemical modifier specific for carboxyl side chains produces a time-dependent loss of activity, and that this effect can be blocked by the inclusion of a strong competitive inhibitor in the reaction mix. We hypothesized that the catalytic acid residue(s) should be located in a region of overall homology and be invariant within the aligned deduced primary sequences of the human alpha and beta subunits, as well as hexosaminidases from other species, including bacteria. Such a region is encoded by exons 5-6 of the HEXA and HEXB genes. This region includes beta Arg211 (invariant in 15 sequences), which we have previously shown to be an active residue. This region also contains two invariant and one conserved acidic residues. A fourth acidic residue, Asp alpha 258, beta 290, in exon 7 was also investigated because of its association with the B1 variant of Tay-Sachs disease. Conservative substitutions were made at each candidate residue by in vitro mutagenesis of a beta cDNA, followed by cellular expression. Of these, only the beta Asp196Asn substitution decreased the kcat (350-910-fold) without any noticeable effect on the K(m). Mutagenesis of either beta Asp240 or beta Asp290 to Asn decreased kcat by 10- or 1.4-fold but also raised the K(m) of the enzyme 11- of 3-fold, respectively. The above results strongly suggest that beta Asp196 is a catalytic acid residue in beta-hexosaminidase.

Impact of a pharmacist-driven beta-lactam allergy interview on inpatient antimicrobial therapy: A pilot project.

PubMed

Sigona, Nicholas S; Steele, Jeffrey M; Miller, Christopher D

To determine the impact of a pharmacist-driven beta-lactam allergy interview on antimicrobial therapy. Tertiary care academic medical center. Clarification of beta-lactam allergy may expand treatment options for patients and potentially improve outcomes, reduce toxicity, and reduce costs. At our institution, a pilot service using a pharmacy resident and infectious diseases clinical pharmacist was implemented to clarify beta-lactam allergy information and, where appropriate, recommend a change to the patient's antibiotic therapy. Adult patients with a documented beta-lactam allergy who had received non-penicillin antibiotics and who had undergone a beta-lactam allergy interview were identified via pharmacy intervention data. A pharmacist interviewed these patients with the use of an internally developed allergy questionnaire. Recommendations for beta-lactam therapy were made to the patient's primary medical team based on the results of the allergy interview and factors including infection type and culture results. The primary objectives were to determine the percentage of patients successfully switched to beta-lactam therapy as a result of the drug allergy interview, to identify allergy discrepancies between the electronic medical record (EMR) and pharmacist's interview, and to quantify the acceptance rate of the pharmacist's antimicrobial recommendations after drug allergy clarification. Thirty-two patients were interviewed, and 24 were candidates for a beta-lactam recommendation. As a result of the interview, 21 patients (65.6%) were successfully switched from a non-penicillin antibiotic to a cephalosporin, carbapenem, or penicillin. A discrepancy between the EMR-reported allergy and history obtained on interview was identified in 11 patients (34.4%). Medical providers accepted 87.5% of pharmacists' antimicrobial recommendations. A pharmacist-driven beta-lactam allergy interview was effective in switching eligible patients to beta-lactam therapy and identifying discrepancies between EMR-documented allergies and confirmed allergies. Antimicrobial recommendations were well received by medical providers with a high acceptance rate. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Lipid oxidation in algae oil-in-water emulsions stabilized by bovine and caprine caseins

USDA-ARS?s Scientific Manuscript database

Caseins (alpha S1-, alpha S2-, and beta-casein) are phosphoproteins that are capable of binding transition metals and scavenging free radicals, these properties make them good candidates to be used as natural antioxidants in oil-in-water emulsions. Caprine casein exhibits variability in aS1-casein c...

Searching for new white dwarf pulsators for TESS observations at Konkoly Observatory

NASA Astrophysics Data System (ADS)

Bognár, Zs; Kalup, Cs; Sódor, Á.; Charpinet, S.; Hermes, J. J.

2018-07-01

We present the results of our survey searching for new white dwarf pulsators for observations by the TESS space telescope. We collected photometric time-series data on 14 white dwarf variable candidates at Konkoly Observatory, and found two new bright ZZ Ceti stars, namely EGGR 120 and WD 1310+583. We performed a Fourier analysis of the datasets. In the case of EGGR 120, which was observed on one night only, we found one significant frequency at 1332μHz with 2.3 mmag amplitude. We successfully observed WD 1310+583 on eight nights, and determined 17 significant frequencies in the whole dataset. Seven of them seem to be independent pulsation modes between 634 and 2740μHz, and we performed preliminary asteroseismic investigations of the star utilizing six of these periods. We also identified three new light variables on the fields of white dwarf candidates: an eclipsing binary, a candidate delta Scuti/beta Cephei and a candidate W UMa-type star.

Meta-analysis of genetic studies from journals published in China of ischemic stroke in the Han Chinese population.

PubMed

Xu, Xiaowei; Li, Jiejie; Sheng, Wenli; Liu, Lin

2008-01-01

The aim of this study was to confirm the nature and number of genes contributing to stroke risk and qualify the genetic risk of each susceptibility gene in the Han Chinese population. After collecting all case-control studies related to DNA polymorphism of any candidate gene for ischemic stroke in Han Chinese, strict selection criteria and exclusion criteria were determined and different effect models were used according to the difference in heterogeneity. Meta-analyses were carried out by Revman 4.0 software and the publication bias was further evaluated through calculation of fail-safe numbers in the included gene polymorphisms. Seventy-six studies were included in the meta-analyses which were all published in mainland China and referred to 6 candidate genes and 7 polymorphisms. Among the gene polymorphisms tested in the study, association of gene polymorphisms with increasing risk of ischemic stroke was confirmed in 6 polymorphisms including angiotensin-converting enzyme insertion/deletion (ACE I/D; OR = 1.87, 95% CI = 1.45-2.42), methylenetetrahydrofolate reductase (MTHFR) C677T (OR = 1.55, 95% CI = 1.26-1.90), plasminogen activator inhibitor 1 (PAI-1) 4G/5G (OR = 1.79, 95% CI = 1.20-2.67), beta-fibrinogen (beta-Fg) -455A/G (OR = 1.48, 95% CI = 1.14-1.92), beta-Fg -148T/C (OR = 1.72, 95% CI = 1.42-2.07), apolipoprotein E (ApoE) epsilon2-4 (OR = 2.39, 95% CI = 1.94-2.95). Because of the obvious publication bias, the association between paraoxonase 1 (PON-1) polymorphisms and stroke risk was not established although the OR of the meta-analysis suggested a positive result (OR = 1.14, 95% CI = 1.01-1.35). ACE D/I, MTHFR C677T, beta-Fg -455A/G, beta-Fg -148T/C, PAI-1 4G/5G, and ApoE epsilon2-4 were associated with risk of ischemic stroke in Han Chinese. (c) 2008 S. Karger AG, Basel

Islet-selectivity of G-protein coupled receptor ligands evaluated for PET imaging of pancreatic {beta}-cell mass

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

Cline, Gary W., E-mail: gary.cline@yale.edu; Zhao, Xiaojian; Jakowski, Amy B.

2011-09-02

Highlights: {yields} We screened G-protein coupled receptors for imaging pancreatic. {yields} Database mining and immunohistochemistry identified GPCRs enriched in {beta}-cells. {yields} In vitro and in vivo assays were used to determine exocrine vs endocrine specificity. {yields} GPCR candidates for imaging of {beta}-cell mass are Prokineticin-1R, mGluR5, and GLP-1R. -- Abstract: A critical unmet need exists for methods to quantitatively measure endogenous pancreatic {beta}-cell mass (BCM) for the clinical evaluation of therapies to prevent or reverse loss of BCM and diabetes progression. Our objective was to identify G-protein coupled receptors (GPCRs) that are expressed with a high degree of specificity tomore » islet {beta}-cells for receptor-targeted imaging of BCM. GPCRs enriched in pancreatic islets relative to pancreas acinar and hepatic tissue were identified using a database screen. Islet-specific expression was confirmed by human pancreas immunohistochemistry (IHC). In vitro selectivity assessment was determined from the binding and uptake of radiolabeled ligands to the rat insulinoma INS-1 832/13 cell line and isolated rat islets relative to the exocrine pancreas cell-type, PANC-1. Tail-vein injections of radioligands into rats were used to determine favorable image criteria of in vivo biodistribution to the pancreas relative to other internal organs (i.e., liver, spleen, stomach, and lungs). Database and IHC screening identified four candidate receptors for further in vitro and in vivo evaluation for PET imaging of BCM: prokineticin-1 receptor (PK-1R), metabotropic glutamate receptor type-5 (mGluR5), neuropeptide Y-2 receptor (NPY-2R), and glucagon-like peptide 1 receptor (GLP-1R). In vitro specificity ratios gave the following receptor rank order: PK-1R > GLP-1R > NPY-2R > mGluR5. The biodistribution rank order of selectivity to the pancreas was found to be PK-1R > VMAT2 {approx} GLP-1R > mGluR5. Favorable islet selectivity and biodistribution characteristics suggest several GPCRs as potential targets for PET imaging of pancreatic BCM.« less

Pharmacogenetics of the β2-Adrenergic Receptor Gene

PubMed Central

Ortega, Victor E.; Hawkins, Gregory A.; Peters, Stephen P.; Bleecker, Eugene R.

2009-01-01

Asthma is a complex genetic disease with multiple genetic and environmental determinants contributing to the observed variability in response to common anti-asthma therapies. Asthma pharmacogenetic research has focused on multiple candidate genes including the β2-adrenergic receptor gene (ADRβ2) and its effect on individual responses to beta agonist therapy. At present, knowledge about the effects of ADRβ2 variation on therapeutic responses is evolving and should not alter current Asthma Guideline approaches consisting of the use of short acting beta agonists for as-needed symptom based therapy and the use of a regular long-acting beta agonist in combination with inhaled corticosteroid therapy for optimal control of asthma symptoms in those asthmatics who are not controlled on inhaled corticosteroid alone. This approach is based upon studies showing a consistent pharmacogenetic response to regular use of short acting beta agonists (SABA) and less consistent findings in studies evaluating long acting beta agonist (LABA). While emerging pharmacogenetic studies are provocative and should lead to functional approaches, conflicting data with responses to LABA therapy may be caused by factors that include small sample sizes of study populations and differences in experimental design that may limit the conclusions that may be drawn from these clinical trials at the present time. PMID:17996583

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

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.

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

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.

Gonadal Identity in the Absence of Pro-Testis Factor SOX9 and Pro-Ovary Factor Beta-Catenin in Mice1

PubMed Central

Nicol, Barbara; Yao, Humphrey H.-C.

2015-01-01

Sex-reversal cases in humans and genetic models in mice have revealed that the fate of the bipotential gonad hinges upon the balance between pro-testis SOX9 and pro-ovary beta-catenin pathways. Our central query was: if SOX9 and beta-catenin define the gonad's identity, then what do the gonads become when both factors are absent? To answer this question, we developed mouse models that lack either Sox9, beta-catenin, or both in the somatic cells of the fetal gonads and examined the morphological outcomes and transcriptome profiles. In the absence of Sox9 and beta-catenin, both XX and XY gonads progressively lean toward the testis fate, indicating that expression of certain pro-testis genes requires the repression of the beta-catenin pathway, rather than a direct activation by SOX9. We also observed that XY double knockout gonads were more masculinized than their XX counterpart. To identify the genes responsible for the initial events of masculinization and to determine how the genetic context (XX vs. XY) affects this process, we compared the transcriptomes of Sox9/beta-catenin mutant gonads and found that early molecular changes underlying the XY-specific masculinization involve the expression of Sry and 21 SRY direct target genes, such as Sox8 and Cyp26b1. These results imply that when both Sox9 and beta-catenin are absent, Sry is capable of activating other pro-testis genes and drive testis differentiation. Our findings not only provide insight into the mechanism of sex determination, but also identify candidate genes that are potentially involved in disorders of sex development. PMID:26108792

A supramolecular complex between proteinases and beta-cyclodextrin that preserves enzymatic activity: physicochemical characterization.

PubMed

Denadai, Angelo M L; Santoro, Marcelo M; Lopes, Miriam T P; Chenna, Angélica; de Sousa, Frederico B; Avelar, Gabriela M; Gomes, Marco R Túlio; Guzman, Fanny; Salas, Carlos E; Sinisterra, Rubén D

2006-01-01

Cyclodextrins are suitable drug delivery systems because of their ability to subtly modify the physical, chemical, and biological properties of guest molecules through labile interactions by formation of inclusion and/or association complexes. Plant cysteine proteinases from Caricaceae and Bromeliaceae are the subject of therapeutic interest, because of their anti-inflammatory, antitumoral, immunogenic, and wound-healing properties. In this study, we analyzed the association between beta-cyclodextrin (betaCD) and fraction P1G10 containing the bioactive proteinases from Carica candamarcensis, and described the physicochemical nature of the solid-state self-assembled complexes by Fourier transform infrared (FTIR) spectroscopy, thermogravimetry (TG), differential scanning calorimetry (DSC), X-ray powder diffraction (XRD), and nuclear magnetic resonance (NMR), as well as in solution by circular dichroism (CD), isothermal titration calorimetry (ITC), and amidase activity. The physicochemical analyses suggest the formation of a complex between P1G10 and betaCD. Higher secondary interactions, namely hydrophobic interactions, hydrogen bonding and van der Waals forces were observed at higher P1G10 : betaCD mass ratios. These results provide evidence of the occurrence of strong solid-state supramolecular non-covalent interactions between P1G10 and betaCD. Microcalorimetric analysis demonstrates that complexation results in a favorable enthalpic contribution, as has already been described during formation of similar betaCD inclusion compounds. The amidase activity of the complex shows that the enzyme activity is not readily available at 24 hours after dissolution of the complex in aqueous buffer; the proteinase becomes biologically active by the second day and remains stable until day 16, when a gradual decrease occurs, with basal activity attained by day 29. The reported results underscore the potential for betaCDs as candidates for complexing cysteine proteinases, resulting in supramolecular arrays with sustained proteolytic activity.

FAMIAS User Manual

NASA Astrophysics Data System (ADS)

Zima, Wolfgang

2008-10-01

The excitation of pulsation modes in Beta Cephei and Slowly Pulsating B stars is known to be very sensitive to opacity changes in the stellar interior where T ~ 2 x 10E5 K. In this region differences in opacity up to ~ 50% can be induced by the choice between OPAL and OP opacity tables, and between two different metal mixtures (Grevesse & Noels 1993 and Asplund et al. 2005). We have extended the non-adiabatic computations presented in Miglio et al. (2007) towards models of higher mass and pulsation modes of degree l = 3, and we present here the instability domains in the HR- and log P-log Teff diagrams resulting from different choices of opacity tables, and for three different metallicities. FAMIAS (Frequency Analysis and Mode Identification for AsteroSeismology) is a collection of state-of-the-art software tools for the analysis of photometric and spectroscopic time series data. It is one of the deliverables of the Work Package NA5: Asteroseismology of the European Coordination Action in Helio-and Asteroseismology (HELAS). Two main sets of tools are incorporated in FAMIAS. The first set allows to search for periodicities in the data using Fourier and non-linear least-squares fitting algorithms. The other set allows to carry out a mode identification for the detected pulsation frequencies to determine their pulsational quantum numbers, the harmonic degree, m. The types of stars to which famias is applicable are main-sequence pulsators hotter than the Sun. This includes the Gamma Dor stars, Delta Sct stars, the slowly pulsating B stars and the Beta Cep stars - basically all pulsating main-sequence stars, for which empirical mode identification is required to successfully carry out asteroseismology. This user manual describes how to use the different features of FAMIAS and provides two tutorials that demonstrate the usage of FAMIAS for spectroscopic and photometric mode identification.

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.

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

Discovery of DNA dyes Hoechst 34580 and 33342 as good candidates for inhibiting amyloid beta formation: in silico and in vitro study

NASA Astrophysics Data System (ADS)

Thai, Nguyen Quoc; Tseng, Ning-Hsuan; Vu, Mui Thi; Nguyen, Tin Trung; Linh, Huynh Quang; Hu, Chin-Kun; Chen, Yun-Ru; Li, Mai Suan

2016-08-01

Combining Lipinski's rule with the docking and steered molecular dynamics simulations and using the PubChem data base of about 1.4 million compounds, we have obtained DNA dyes Hoechst 34580 and Hoechst 33342 as top-leads for the Alzheimer's disease. The binding properties of these ligands to amyloid beta (Aβ) fibril were thoroughly studied by in silico and in vitro experiments. Hoechst 34580 and Hoechst 33342 prefer to locate near hydrophobic regions with binding affinity mainly governed by the van der Waals interaction. By the Thioflavin T assay, it was found that the inhibition constant IC50 ≈ 0.86 and 0.68 μM for Hoechst 34580 and Hoechst 33342, respectively. This result qualitatively agrees with the binding free energy estimated using the molecular mechanic-Poisson Boltzmann surface area method and all-atom simulations with the AMBER-f99SB-ILDN force field and water model TIP3P. In addition, DNA dyes have the high capability to cross the blood brain barrier. Thus, both in silico and in vitro experiments have shown that Hoechst 34580 and 33342 are good candidates for treating the Alzheimer's disease by inhibiting Aβ formation.

Candidate genes for Alzheimer's disease are associated with individual differences in plasma levels of beta amyloid peptides in adults with Down syndrome.

PubMed

Schupf, Nicole; Lee, Annie; Park, Naeun; Dang, Lam-Ha; Pang, Deborah; Yale, Alexander; Oh, David Kyung-Taek; Krinsky-McHale, Sharon J; Jenkins, Edmund C; Luchsinger, José A; Zigman, Warren B; Silverman, Wayne; Tycko, Benjamin; Kisselev, Sergey; Clark, Lorraine; Lee, Joseph H

2015-10-01

We examined the contribution of candidates genes for Alzheimer's disease (AD) to individual differences in levels of beta amyloid peptides in adults with Down syndrom, a population at high risk for AD. Participants were 254 non-demented adults with Down syndrome, 30-78 years of age. Genomic deoxyribonucleic acid was genotyped using an Illumina GoldenGate custom array. We used linear regression to examine differences in levels of Aβ peptides associated with the number of risk alleles, adjusting for age, sex, level of intellectual disability, race and/or ethnicity, and the presence of the APOE ε4 allele. For Aβ42 levels, the strongest gene-wise association was found for a single nucleotide polymorphism (SNP) on CAHLM1; for Aβ40 levels, the strongest gene-wise associations were found for SNPs in IDE and SOD1, while the strongest gene-wise associations with levels of the Aβ42/Aβ40 ratio were found for SNPs in SORCS1. Broadly classified, variants in these genes may influence amyloid precursor protein processing (CALHM1, IDE), vesicular trafficking (SORCS1), and response to oxidative stress (SOD1). Copyright © 2015 Elsevier Inc. All rights reserved.

S1 certification of alpha-endosulfan, beta-endosulfan, and endosulfan sulfate in a candidate certified reference material (organochlorine pesticides in tea) by isotope dilution gas chromatography-mass spectrometry.

PubMed

Sin, Della Wai-Mei; Wong, Yee-Lok; Cheng, Eddie Chung-Chin; Lo, Man-Fung; Ho, Clare; Mok, Chuen-Shing; Wong, Siu-Kay

2015-04-01

This paper presents the certification of alpha-endosulfan, beta-endosulfan, and endosulfan sulfate in a candidate tea certified reference material (code: GLHK-11-03) according to the requirements of the ISO Guide 30 series. Certification of GLHK-11-03 was based on an analytical method purposely developed for the accurate measurement of the mass fraction of the target analytes in the material. An isotope dilution mass spectrometry (IDMS) method involving determination by (i) gas chromatography-negative chemical ionization-mass spectrometry (GC-NCI-MS) and (ii) gas chromatography-electron ionization-high-resolution mass spectrometry (GC-EI-HRMS) techniques was employed. The performance of the described method was demonstrated through participation in the key comparison CCQM-K95 "Mid-Polarity Analytes in Food Matrix: Mid-Polarity Pesticides in Tea" organized by the Consultative Committee for Amount of Substance-Metrology in Chemistry in 2012, where the study material was the same as the certified reference material (CRM). The values reported by using the developed method were in good agreement with the key comparison reference value (KCRV) assigned for beta-endosulfan (727 ± 14 μg kg(-1)) and endosulfan sulfate (505 ± 11 μg kg(-1)), where the degree of equivalence (DoE) values were 0.41 and 0.40, respectively. The certified values of alpha-endosulfan, beta-endosulfan, and endosulfan sulfate in dry mass fraction in GLHK-11-03 were 350, 730, and 502 μg kg(-1), respectively, and the respective expanded uncertainties, due to sample inhomogeneity, long-term and short-term stability, and variability in the characterization procedure, were 27 μg kg(-1) (7.8 %), 48 μg kg(-1) (6.6 %), and 33 μg kg(-1) (6.6 %).

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

Uptake of particulate vaccine adjuvants by dendritic cells activates the NALP3 inflammasome.

PubMed

Sharp, Fiona A; Ruane, Darren; Claass, Benjamin; Creagh, Emma; Harris, James; Malyala, Padma; Singh, Manomohan; O'Hagan, Derek T; Pétrilli, Virginie; Tschopp, Jurg; O'Neill, Luke A J; Lavelle, Ed C

2009-01-20

Many currently used and candidate vaccine adjuvants are particulate in nature, but their mechanism of action is not well understood. Here, we show that particulate adjuvants, including biodegradable poly(lactide-co-glycolide) (PLG) and polystyrene microparticles, dramatically enhance secretion of interleukin-1beta (IL-1beta) by dendritic cells (DCs). The ability of particulates to promote IL-1beta secretion and caspase 1 activation required particle uptake by DCs and NALP3. Uptake of microparticles induced lysosomal damage, whereas particle-mediated enhancement of IL-1beta secretion required phagosomal acidification and the lysosomal cysteine protease cathepsin B, suggesting a role for lysosomal damage in inflammasome activation. Although the presence of a Toll-like receptor (TLR) agonist was required to induce IL-1beta production in vitro, injection of the adjuvants in the absence of TLR agonists induced IL-1beta production at the injection site, indicating that endogenous factors can synergize with particulates to promote inflammasome activation. The enhancement of antigen-specific antibody production by PLG microparticles was independent of NALP3. However, the ability of PLG microparticles to promote antigen-specific IL-6 production by T cells and the recruitment and activation of a population of CD11b(+)Gr1(-) cells required NALP3. Our data demonstrate that uptake of microparticulate adjuvants by DCs activates the NALP3 inflammasome, and this contributes to their enhancing effects on innate and antigen-specific cellular immunity.

Perturbative search for dead-end CFTs

DOE PAGES

Nakayama, Yu

2015-05-08

To explore the possibility of self-organized criticality, we look for CFTs without any relevant scalar deformations (a.k.a. dead-end CFTs) within power-counting renormalizable quantum field theories with a weakly coupled Lagrangian description. In three dimensions, the only candidates are pure (Abelian) gauge theories, which may be further deformed by Chern-Simons terms. In four dimensions, we show that there are infinitely many non-trivial candidates based on chiral gauge theories. Using the three-loop beta functions, we compute the gap of scaling dimensions above the marginal value, and it can be as small as O(10 –5) and robust against the perturbative corrections. These classesmore » of candidates are very weakly coupled and our perturbative conclusion seems difficult to refute. Furthermore, the hypothesis that non-trivial dead-end CFTs do not exist is likely to be false in four dimensions.« less

Perturbative search for dead-end CFTs

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

Nakayama, Yu

To explore the possibility of self-organized criticality, we look for CFTs without any relevant scalar deformations (a.k.a. dead-end CFTs) within power-counting renormalizable quantum field theories with a weakly coupled Lagrangian description. In three dimensions, the only candidates are pure (Abelian) gauge theories, which may be further deformed by Chern-Simons terms. In four dimensions, we show that there are infinitely many non-trivial candidates based on chiral gauge theories. Using the three-loop beta functions, we compute the gap of scaling dimensions above the marginal value, and it can be as small as O(10 –5) and robust against the perturbative corrections. These classesmore » of candidates are very weakly coupled and our perturbative conclusion seems difficult to refute. Furthermore, the hypothesis that non-trivial dead-end CFTs do not exist is likely to be false in four dimensions.« less

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

Qian, Jinping P.; Garofalo, Andrea M.; Gong, Xianzu Z.

Recent EAST/DIII-D joint experiments on the high poloidal betamore » $${{\\beta}_{\\text{P}}}$$ regime in DIII-D have extended operation with internal transport barriers (ITBs) and excellent energy confinement (H 98y2 ~ 1.6) to higher plasma current, for lower q 95 ≤ 7.0, and more balanced neutral beam injection (NBI) (torque injection < 2 Nm), for lower plasma rotation than previous results. Transport analysis and experimental measurements at low toroidal rotation suggest that the E × B shear effect is not key to the ITB formation in these high $${{\\beta}_{\\text{P}}}$$ discharges. Experiments and TGLF modeling show that the Shafranov shift has a key stabilizing effect on turbulence. Extrapolation of the DIII-D results using a 0D model shows that with the improved confinement, the high bootstrap fraction regime could achieve fusion gain Q = 5 in ITER at $${{\\beta}_{\\text{N}}}$$ ~ 2.9 and q 95 ~ 7. With the optimization of q(0), the required improved confinement is achievable when using 1.5D TGLF-SAT1 for transport simulations. Furthermore, results reported in this paper suggest that the DIII-D high $${{\\beta}_{\\text{P}}}$$ scenario could be a candidate for ITER steady state operation.« less

Neutron induced radio-isotopes and background for Ge double beta decay experiments

NASA Astrophysics Data System (ADS)

Chu, Pinghan; Majorana Collaboration

2015-10-01

Environmental neutrons, mostly produced by muons in the cosmic rays, might contribute backgrounds to the search for neutrinoless double beta decays. These neutrons can interact with materials and generate radio-isotopes, which can decay and produce radioactive backgrounds. Some of these neutron-induced isotopes have a signature of a time-delayed coincidence, allowing us to study these infrequent events. For example, such isotopes can decay by beta decay to metastable states and then decay by gamma decay to the ground state. Considering the time-delayed coincidence of these two processes, we can determine candidates for these neutron-induced isotopes in the data and estimate the flux of neutrons in the deep underground environment. In this report, we will list possible neutron-induced isotopes and the methodology to detect them, especially those that can affect the search for neutrinoless double beta decays in 76Ge. This material is based upon work supported by the U.S. Department of Energy, Office of Science, Office of Nuclear Physics, the Particle Astrophysics Program of the National Science Foundation, and the Sanford Underground Research Facility. We acknowledge the support of the U.S. Department of Energy through the LANL/LDRD Program.

Molecular genetics of Alzheimer disease.

PubMed

St George-Hyslop, P H

1999-01-01

Epidemiological and individual case studies indicate that genetic factors play a significant role in the genesis of Alzheimer Disease (AD). To date, molecular genetic studies in families multiply affected with AD have identified three genes (Presenilin 1-PS1, Presenilin 2-PS2, and beta-amyloid precursor protein--betaAPP) associated with highly penetrant early onset AD, and one gene (Apolipoprotein E) associated with late onset AD. A fifth potential AD susceptibility locus has been mapped to a broad region of chromosome 12, but the responsible gene defect has not yet been identified. Case-control studies comparing the frequency of alleles in numerous other candidate genes have identified a number of additional potential AD genes. However, methodological difficulties and conflicting results in follow-up studies, make it unclear whether allelic variations in these genes are truly pathogenic. Nevertheless, analysis of the biochemical effects of mutations in PS1, PS2, betaAPP at least, suggest a common biochemical effect-namely disturbances in the processing of betaAPP protein. In addition to utility in defining potential therapeutic targets, in some circumstances these genes can also potentially be used as adjunctives in clinical presymptomatic, symptomatic or pharmacogenomic diagnosis.

Periodontal wound healing/regeneration following implantation of recombinant human growth/differentiation factor-5 in a beta-tricalcium phosphate carrier into one-wall intrabony defects in dogs.

PubMed

Lee, Jung-Seok; Wikesjö, Ulf M E; Jung, Ui-Won; Choi, Seong-Ho; Pippig, Susanne; Siedler, Michael; Kim, Chong-Kwan

2010-04-01

Recombinant human growth/differentiation factor-5 (rhGDF-5) is being evaluated as a candidate therapy in support of periodontal regeneration. The objective of this study was to evaluate periodontal wound healing/regeneration following the application of rhGDF-5 on a particulate beta-tricalcium phosphate (beta-TCP) carrier using an established defect model. Bilateral 4 x 5 mm (width x depth), one-wall, critical-size, intrabony periodontal defects were surgically created at the mandibular second and fourth pre-molar teeth in 15 Beagle dogs. Unilateral defects in five animals received rhGDF-5/beta-TCP (Scil Technology GmbH); five animals received beta-TCP solo; and five animals served as sham-surgery controls. Contralateral sites received treatments reported elsewhere. The animals were sacrificed following an 8-week healing interval for histological examination. Clinical healing was generally uneventful. Sites implanted with rhGDF-5/beta-TCP exhibited greater enhanced cementum and bone formation compared with beta-TCP and sham-surgery controls; cementum regeneration averaged (+/- SD) 3.83 +/- 0.73 versus 1.65 +/- 0.82 and 2.48 +/- 1.28 mm for the controls (p<0.05). Corresponding values for bone regeneration height averaged 3.26 +/- 0.30 versus 1.70 +/- 0.66 and 1.68 +/- 0.49 mm (p<0.05), and bone area 10.45 +/- 2.26 versus 6.31 +/- 2.41 and 3.00 +/- 1.97 mm(2) (p<0.05). Cementum regeneration included cellular/acellular cementum with or without a functionally oriented periodontal ligament. A non-specific connective tissue attachment was evident in the sham-surgery control. Controls exhibited mostly woven bone with primary osteons, whereas rhGDF-5/beta-TCP sites showed a noticeable extent of lamellar bone. Sites receiving rhGDF-5/beta-TCP or beta-TCP showed some residual beta-TCP granules apparently undergoing biodegradation without obvious differences between the sites. Sites receiving beta-TCP alone commonly showed residual beta-TCP granules sequestered in the connective tissue or fibrovascular marrow. rhGDF-5/beta-TCP has a greater potential to support the regeneration of the periodontal attachment. Long-term studies are necessary to confirm the uneventful maturation of the regenerated tissues.

[Obesity studies in candidate genes].

PubMed

Ochoa, María del Carmen; Martí, Amelia; Martínez, J Alfredo

2004-04-17

There are more than 430 chromosomic regions with gene variants involved in body weight regulation and obesity development. Polymorphisms in genes related to energy expenditure--uncoupling proteins (UCPs), related to adipogenesis and insulin resistance--hormone-sensitive lipase (HLS), peroxisome proliferator-activated receptor gamma (PPAR gamma), beta adrenergic receptors (ADRB2,3), and alfa tumor necrosis factor (TNF-alpha), and related to food intake--ghrelin (GHRL)--appear to be associated with obesity phenotypes. Obesity risk depends on two factors: a) genetic variants in candidate genes, and b) biographical exposure to environmental risk factors. It is necessary to perform new studies, with appropriate control groups and designs, in order to reach relevant conclusions with regard to gene/environmental (diet, lifestyle) interactions.

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...

EANM guidelines for radionuclide therapy of bone metastases with beta-emitting radionuclides.

PubMed

Handkiewicz-Junak, Daria; Poeppel, Thorsten D; Bodei, Lisa; Aktolun, Cumali; Ezziddin, Samer; Giammarile, Francesco; Delgado-Bolton, Roberto C; Gabriel, Michael

2018-05-01

The skeleton is the most common metastatic site in patients with advanced cancer. Pain is a major healthcare problem in patients with bone metastases. Bone-seeking radionuclides that selectively accumulate in the bone are used to treat cancer-induced bone pain and to prolong survival in selected groups of cancer patients. The goals of these guidelines are to assist nuclear medicine practitioners in: (a) evaluating patients who might be candidates for radionuclide treatment of bone metastases using beta-emitting radionuclides such as strontium-89 ( 89 Sr), samarium-153 ( 153 Sm) lexidronam ( 153 Sm-EDTMP), and phosphorus-32 ( 32 P) sodium phosphate; (b) performing the treatments; and ©) understanding and evaluating the treatment outcome and side effects.

20 mJ, 1 ps Yb:YAG Thin-disk Regenerative Amplifier

PubMed Central

Alismail, Ayman; Wang, Haochuan; Brons, Jonathan; Fattahi, Hanieh

2017-01-01

This is a report on a 100 W, 20 mJ, 1 ps Yb:YAG thin-disk regenerative amplifier. A homemade Yb:YAG thin-disk, Kerr-lens mode-locked oscillator with turn-key performance and microjoule-level pulse energy is used to seed the regenerative chirped-pulse amplifier. The amplifier is placed in airtight housing. It operates at room temperature and exhibits stable operation at a 5 kHz repetition rate, with a pulse-to-pulse stability less than 1%. By employing a 1.5 mm-thick beta barium borate crystal, the frequency of the laser output is doubled to 515 nm, with an average power of 70 W, which corresponds to an optical-to-optical efficiency of 70%. This superior performance makes the system an attractive pump source for optical parametric chirped-pulse amplifiers in the near-infrared and mid-infrared spectral range. Combining the turn-key performance and the superior stability of the regenerative amplifier, the system facilitates the generation of a broadband, CEP-stable seed. Providing the seed and pump of the optical parametric chirped-pulse amplification (OPCPA) from one laser source eliminates the demand of active temporal synchronization between these pulses. This work presents a detailed guide to set up and operate a Yb:YAG thin-disk regenerative amplifier, based on chirped-pulse amplification (CPA), as a pump source for an optical parametric chirped-pulse amplifier. PMID:28745636

Central auditory processing and migraine: a controlled study.

PubMed

Agessi, Larissa Mendonça; Villa, Thaís Rodrigues; Dias, Karin Ziliotto; Carvalho, Deusvenir de Souza; Pereira, Liliane Desgualdo

2014-11-08

This study aimed to verify and compare central auditory processing (CAP) performance in migraine with and without aura patients and healthy controls. Forty-one volunteers of both genders, aged between 18 and 40 years, diagnosed with migraine with and without aura by the criteria of "The International Classification of Headache Disorders" (ICDH-3 beta) and a control group of the same age range and with no headache history, were included. Gaps-in-noise (GIN), Duration Pattern test (DPT) and Dichotic Digits Test (DDT) tests were used to assess central auditory processing performance. The volunteers were divided into 3 groups: Migraine with aura (11), migraine without aura (15), and control group (15), matched by age and schooling. Subjects with aura and without aura performed significantly worse in GIN test for right ear (p = .006), for left ear (p = .005) and for DPT test (p < .001) when compared with controls without headache, however no significant differences were found in the DDT test for the right ear (p = .362) and for the left ear (p = .190). Subjects with migraine performed worsened in auditory gap detection, in the discrimination of short and long duration. They also presented impairment in the physiological mechanism of temporal processing, especially in temporal resolution and temporal ordering when compared with controls. Migraine could be related to an impaired central auditory processing. Research Ethics Committee (CEP 0480.10) - UNIFESP.

Integrin {alpha}{beta}1, {alpha}{sub v}{beta}, {alpha}{sub 6}{beta} effectors p130Cas, Src and talin regulate carcinoma invasion and chemoresistance

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

Sansing, Hope A.; Sarkeshik, Ali; Yates, John R.

2011-03-11

Research highlights: {yields} Proteomics of clustered integrin {alpha}{beta}1, {alpha}{sub v}{beta}, {alpha}{sub 6}{beta} receptors in oral carcinoma. {yields} p130Cas, Dek, Src and talin regulate oral carcinoma invasion. {yields} p130Cas, talin, Src and zyxin regulate oral carcinoma resistance to cisplatin. -- Abstract: Ligand engagement by integrins induces receptor clustering and formation of complexes at the integrin cytoplasmic face that controls cell signaling and cytoskeletal dynamics critical for adhesion-dependent processes. This study searches for a subset of integrin effectors that coordinates both tumor cell invasion and resistance to the chemotherapeutic drug cisplatin in oral carcinomas. Candidate integrin effectors were identified in a proteomicsmore » screen of proteins recruited to clustered integrin {alpha}{beta}1, {alpha}{sub v}{beta} or {alpha}{sub 6}{beta} receptors in oral carcinomas. Proteins with diverse functions including microtubule and actin binding proteins, and factors involved in trafficking, transcription and translation were identified in oral carcinoma integrin complexes. Knockdown of effectors in the oral carcinoma HN12 cells revealed that p130Cas, Dek, Src and talin were required for invasion through Matrigel. Disruption of talin or p130Cas by RNA interference increased resistance to cisplatin, whereas targeting Dek, Src or zyxin reduced HN12 resistance to cisplatin. Analysis of the spreading of HN12 cells on collagen I and laminin I revealed that a decrease in p130Cas or talin expression inhibited spreading on both matrices. Interestingly, a reduction in zyxin expression enhanced spreading on laminin I and inhibited spreading on collagen I. Reduction of Dek, Src, talin or zyxin expression reduced HN12 proliferation by 30%. Proliferation was not affected by a reduction in p130Cas expression. We conclude that p130Cas, Src and talin function in both oral carcinoma invasion and resistance to cisplatin.« less

Feasibility of commercial space manufacturing, production of pharmaceuticals. Volume 3: Product data

NASA Technical Reports Server (NTRS)

1978-01-01

The feasibility of commercial manufacturing of pharmaceuticals in space is analyzed and the study results are presented. The chronology of the study process is discussed. The separation of serum proteins by the continuous flow electrophoresis process is investigated. The production requirements of twelve candidate products including antihemophilic factor, beta cells, erythropoietin, epidermal growth factor, alpha-1-antitrypsin, and interferon are evaluated.

3beta-taraxerol of Mangifera indica, a PI3K dependent dual activator of glucose transport and glycogen synthesis in 3T3-L1 adipocytes.

PubMed

Sangeetha, Kadapakkam Nandabalan; Sujatha, Sundaresan; Muthusamy, Velusamy Shanmuganathan; Anand, Singaravel; Nithya, Nirmal; Velmurugan, Devadasan; Balakrishnan, Arun; Lakshmi, Baddireddi Subhadra

2010-03-01

The present study focuses on identifying and developing an anti-diabetic molecule from plant sources that would effectively combat insulin resistance through proper channeling of glucose metabolism involving glucose transport and storage. Insulin-stimulated glucose uptake formed the basis for isolation of a bioactive molecule through column chromatography followed by its characterization using NMR and mass spectroscopic analysis. Mechanism of glucose transport and storage was evaluated based on the expression profiling of signaling molecules involved in the process. The study reports (i) the isolation of a bioactive compound 3beta-taraxerol from the ethyl acetate extract (EAE) of the leaves of Mangifera indica (ii) the bioactive compound exhibited insulin-stimulated glucose uptake through translocation and activation of the glucose transporter (GLUT4) in an IRTK and PI3K dependent fashion. (iii) the fate of glucose following insulin-stimulated glucose uptake was ascertained through glycogen synthesis assay that involved the activation of PKB and suppression of GSK3beta. This study demonstrates the dual activity of 3beta-taraxerol and the ethyl acetate extract of Mangifera indica as a glucose transport activator and stimulator of glycogen synthesis. 3beta-taraxerol can be validated as a potent candidate for managing the hyperglycemic state. Copyright (c) 2009 Elsevier B.V. All rights reserved.

Expression of the growth factor pleiotrophin and its receptor protein tyrosine phosphatase beta/zeta in the serum, cartilage and subchondral bone of patients with osteoarthritis.

PubMed

Kaspiris, Angelos; Mikelis, Constantinos; Heroult, Melanie; Khaldi, Lubna; Grivas, Theodoros B; Kouvaras, Ioannis; Dangas, Spyridon; Vasiliadis, Elias; Lioté, Frédéric; Courty, José; Papadimitriou, Evangelia

2013-07-01

Pleiotrophin is a heparin-binding growth factor expressed in embryonic but not mature cartilage, suggesting a role in cartilage development. Elucidation of the molecular changes observed during the remodelling process in osteoarthritis is of paramount importance. This study aimed to investigate serum pleiotrophin levels and expression of pleiotrophin and its receptor protein tyrosine phosphatase beta/zeta in the cartilage and subchondral bone of osteoarthritis patients. Serum samples derived from 16 osteoarthritis patients and 18 healthy donors. Pleiotrophin and receptor protein tyrosine phosphatase beta/zeta in the cartilage and subchondral bone were studied in 29 patients who had undergone total knee or hip replacement for primary osteoarthritis and in 10 control patients without macroscopic osteoarthritis changes. Serum pleiotrophin levels and expression of pleiotrophin in chondrocytes and subchondral bone osteocytes significantly increased in osteoarthritis patients graded Ahlback II to III. Receptor protein tyrosine phosphatase beta/zeta was mainly detected in the subchondral bone osteocytes of patients with moderate osteoarthritis and as disease severity increased, in the osteocytes and bone lining cells of the distant trabeculae. These data render pleiotrophin and receptor protein tyrosine phosphatase beta/zeta promising candidates for further studies towards developing targeted therapeutic schemes for osteoarthritis. Copyright © 2012 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

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…

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.

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.

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

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

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.

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

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.

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

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.

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.

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.

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.

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

Concurrent evolution of feature extractors and modular artificial neural networks

NASA Astrophysics Data System (ADS)

Hannak, Victor; Savakis, Andreas; Yang, Shanchieh Jay; Anderson, Peter

2009-05-01

This paper presents a new approach for the design of feature-extracting recognition networks that do not require expert knowledge in the application domain. Feature-Extracting Recognition Networks (FERNs) are composed of interconnected functional nodes (feurons), which serve as feature extractors, and are followed by a subnetwork of traditional neural nodes (neurons) that act as classifiers. A concurrent evolutionary process (CEP) is used to search the space of feature extractors and neural networks in order to obtain an optimal recognition network that simultaneously performs feature extraction and recognition. By constraining the hill-climbing search functionality of the CEP on specific parts of the solution space, i.e., individually limiting the evolution of feature extractors and neural networks, it was demonstrated that concurrent evolution is a necessary component of the system. Application of this approach to a handwritten digit recognition task illustrates that the proposed methodology is capable of producing recognition networks that perform in-line with other methods without the need for expert knowledge in image processing.

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.

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

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.

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.

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.

Synthesis, Characterization, In Vitro Evaluation, and Preclinical Profiling of beta-Cyclodextrin Polyrotaxane Families for Use As Potential Niemann-Pick Type C Therapeutics

NASA Astrophysics Data System (ADS)

Collins, Christopher J.

Niemann-Pick Disease Type C (NPC) is a rare, autosomal recessive genetic disorder featuring a loss of proteins responsible for unesterified cholesterol (UC) trafficking through the late endosomes/lysosomes (LE/LY) of every cell of the body. Disruption of this pathway leads to abnormal accumulation and storage of UC and other lipids. A broad range of visceral and neurological symptoms result from this accumulation exhibiting a variable age of onset and a disease progression that is ultimately fatal. The disease has an incidence of approximately 1 in 120,000 live births and has no known effective treatment. beta-Cyclodextrin (beta-CD) are natural small molecules macrocycles composed of glucose units with a hydrophobic inner cavity and hydrophilic outer rims. beta-CD derivatives have recently been shown to be effective therapeutics for NPC in cellular and animal models. In the mouse model of the disease, beta-CD therapy increases overall lifetime by as much as 50% and slows the progression of neurodegeneration. The progress has led to the initiation of a National Institutes of Health phase I clinical trial. A main drawback of beta-CD administration is the poor pharmacokinetic profile characterized by rapid renal clearance of the drug through the urine. Libraries of beta-CD derivative carrying high molecular weight polyrotaxane (PR) systems have been designed to prevent glomerular filtration of the injected beta-CD dose. An initial family of unmodified beta-CD PRs was synthesized, characterized, and their therapeutic efficacy was tested in NPC fibroblasts. This was followed by screening of PRs consisting of mixed beta-CD derivative threading featuring charged sulfobutylether beta-CD. Finally, we sought to define PR structure-property effects on in vivo pharmacokinetics, biodistribution, toxicity, immunogenicity, and protein hard corona composition. This was accomplished using a family of gadolinium carrying PRs composed of triblock Pluronic co-polymers of varying molecular weights and hydrophilic/lipophilic ratios. The effect of varying threaded beta-CD derivative surface chemistry on PR mediated hemolysis and hard protein corona was also studied. Knowing if structure-property relationships exist in the in vivo performances of PR materials will help with building pre-clinical profile, selecting candidate materials for a given application, and understanding therapeutic outcomes.

Electrical screening procedure for solid ionic conductors

NASA Technical Reports Server (NTRS)

Kautz, H. E.; Singer, J.; Fielder, W. L.; Fordyce, J. S.

1973-01-01

An electrical screening method has been developed for preliminary evaluation of polycrystalline specimens of candidates for use as solid ionic conductive electrolytes in batteries. The procedure measures dielectric loss and capacitance, from which are calculated an ac conductivity attributed provisionally to ions and an activation energy for that conductivity. Electronic conductivity is directly measured. The screening procedure applied to sodium beta-alumina yielded acceptable values for conductivity and activation energy.

Pharmacogenetics: Implications of Race and Ethnicity on Defining Genetic Profiles for Personalized Medicine

PubMed Central

Ortega, Victor E.; Meyers, Deborah A.

2014-01-01

Pharmacogenetics is being used to develop personalized therapies specific to individuals from different ethnic or racial groups. Pharmacogenetic studies to date have been primarily performed in trial cohorts consisting of non-Hispanic whites of European descent. A “bottleneck” or collapse of genetic diversity associated with the first human colonization of Europe during the Upper Paleolithic period, followed by the recent mixing of African, European, and Native American ancestries has resulted in different ethnic groups with varying degrees of genetic diversity. Differences in genetic ancestry may introduce genetic variation which has the potential to alter the therapeutic efficacy of commonly used asthma therapies, for example β2-adrenergic receptor agonists (beta agonists). Pharmacogenetic studies of admixed ethnic groups have been limited to small candidate gene association studies of which the best example is the gene coding for the receptor target of beta agonist therapy, ADRB2. Large consortium-based sequencing studies are using next-generation whole-genome sequencing to provide a diverse genome map of different admixed populations which can be used for future pharmacogenetic studies. These studies will include candidate gene studies, genome-wide association studies, and whole-genome admixture-based approaches which account for ancestral genetic structure, complex haplotypes, gene-gene interactions, and rare variants to detect and replicate novel pharmacogenetic loci. PMID:24369795

Nitrophenols isolated from diesel exhaust particles regulate steroidogenic gene expression and steroid synthesis in the human H295R adrenocortical cell line

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

Furuta, Chie; Laboratory of Veterinary Physiology, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Tokyo 183-8509; Noda, Shiho

2008-05-15

Studies of nitrophenols isolated from diesel exhaust particles (DEPs), 3-methyl-4-nitrophenol (PNMC) and 4-nitro-3-phenylphenol (PNMPP) have revealed that these chemicals possess estrogenic and anti-androgenic activity in vitro and in vivo and that PNMC accumulate in adrenal glands in vivo. However, the impacts of exposure to these compounds on adrenal endocrine disruption and steroidogenesis have not been investigated. To elucidate the non-receptor mediated effects of PNMC and PNMPP, we investigated the production of the steroid hormones progesterone, cortisol, testosterone, and estradiol-17{beta} and modulation of nine major enzyme genes involved in the synthesis of steroid hormones (CYP11A, CYP11B1, CYP17, CYP19, 17{beta}HSD1, 17{beta}HSD4, CYP21,more » 3{beta}HSD2, StAR) in human adrenal H295R cells supplied with cAMP. Exposure to 10{sup -7} to 10{sup -5} M PNMC and 1 mM 8-Br-cAMP for 48 h decreased testosterone, cortisol, and estradiol-17{beta} levels and increased progesterone secretion. At 10{sup -5} M, PNMC with 1 mM 8-Br-cAMP significantly stimulated expression of the 17{beta}HSD4 and significantly suppressed expression of 3{beta}HSD2. In comparison, 10{sup -7} to 2 x 10{sup -5} M PNMPP with 1 mM 8-Br-cAMP for 48 h decreased concentrations of estradiol-17{beta}, increased progesterone levels, but did not affect testosterone and cortisol secretion due to the significant suppression of CYP17 and the non-significant but obvious suppression of CYP19. Our results clarified steroidogenic enzymes as candidates responsible for the inhibition or stimulation for the production of steroid hormones in the steroidogenic pathway, thus providing the first experimental evidence for multiple mechanisms of disruption of endocrine pathways by these nitrophenols.« less

Design, Synthesis, and Crystal Structures of 6-Alkylidene-2 -Substituted Penicillanic Acid Sulfones as Potent Inhibitors of Acinetobacter baumannii OXA-24 Carbapenemase

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

Bou, G.; Santillana, E; Sheri, A

Class D {beta}-lactamases represent a growing and diverse class of penicillin-inactivating enzymes that are usually resistant to commercial {beta}-lactamase inhibitors. As many such enzymes are found in multi-drug resistant (MDR) Acinetobacter baumannii and Pseudomonas aeruginosa, novel {beta}-lactamase inhibitors are urgently needed. Five unique 6-alkylidene-2{prime}-substituted penicillanic acid sulfones (1-5) were synthesized and tested against OXA-24, a clinically important {beta}-lactamase that inactivates carbapenems and is found in A. baumannii. Based upon the roles Tyr112 and Met223 play in the OXA-24 {beta}-lactamase, we also engineered two variants (Tyr112Ala and Tyr112Ala,Met223Ala) to test the hypothesis that the hydrophobic tunnel formed by these residues influencesmore » inhibitor recognition. IC{sub 50} values against OXA-24 and two OXA-24 {beta}-lactamase variants ranged from 10 {+-} 1 (4 vs WT) to 338 {+-} 20 nM (5 vs Tyr112Ala, Met223Ala). Compound 4 possessed the lowest K{sub i} (500 {+-} 80 nM vs WT), and 1 possessed the highest inactivation efficiency (k{sub inact}/K{sub i} = 0.21 {+-} 0.02 {micro}M{sup -1}s{sup -1}). Electrospray ionization mass spectrometry revealed a single covalent adduct, suggesting the formation of an acyl-enzyme intermediate. X-ray structures of OXA-24 complexed to four inhibitors (2.0-2.6 {angstrom}) reveal the formation of stable bicyclic aromatic intermediates with their carbonyl oxygen in the oxyanion hole. These data provide the first structural evidence that 6-alkylidene-2{prime}-substituted penicillin sulfones are effective mechanism-based inactivators of class D {beta}-lactamases. Their unique chemistry makes them developmental candidates. Mechanisms for class D hydrolysis and inhibition are discussed, and a pathway for the evolution of the BlaR1 sensor of Staphylococcus aureus to the class D {beta}-lactamases is proposed.« 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…

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).

Cytochrome P450 induction by rifampicin in healthy subjects: determination using the Karolinska cocktail and the endogenous CYP3A4 marker 4beta-hydroxycholesterol.

PubMed

Kanebratt, K P; Diczfalusy, U; Bäckström, T; Sparve, E; Bredberg, E; Böttiger, Y; Andersson, T B; Bertilsson, L

2008-11-01

The Karolinska cocktail, comprising caffeine, losartan, omeprazole, and quinine, was given before and after administration of rifampicin (20, 100, or 500 mg daily) to measure induction of cytochrome P450 (P450) enzymes. Rifampicin was given for 14 days to eight healthy subjects (all of whom possessed at least one wild-type CYP2C9 and one wild-type CYP2C19 gene) in each dose group. 4beta-hydroxycholesterol was assessed as an endogenous marker of CYP3A4 induction. A fourfold induction of CYP3A4 was seen at the highest dose by both quinine:3'-hydroxyquinine and 4beta-hydroxycholesterol measurements (P < 0.001). CYP3A4 was also induced at the two lower doses of rifampicin when measured by these two markers (P < 0.01 or P < 0.001). CYP1A2, CYP2C9, and CYP2C19 were induced after 500 mg rifampicin daily (1.2-fold, P < 0.05; 1.4-fold, P < 0.05; and 4.2-fold, P < 0.01, respectively). In conclusion, we have shown that the Karolinska cocktail and 4beta-hydroxycholesterol can be used for an initial screening of the induction properties of a drug candidate.

A small molecule fusion inhibitor of dengue virus.

PubMed

Poh, Mee Kian; Yip, Andy; Zhang, Summer; Priestle, John P; Ma, Ngai Ling; Smit, Jolanda M; Wilschut, Jan; Shi, Pei-Yong; Wenk, Markus R; Schul, Wouter

2009-12-01

The dengue virus envelope protein plays an essential role in viral entry by mediating fusion between the viral and host membranes. The crystal structure of the envelope protein shows a pocket (located at a "hinge" between Domains I and II) that can be occupied by ligand n-octyl-beta-D-glucoside (betaOG). Compounds blocking the betaOG pocket are thought to interfere with conformational changes in the envelope protein that are essential for fusion. Two fusion assays were developed to examine the anti-fusion activities of compounds. The first assay measures the cellular internalization of propidium iodide upon membrane fusion. The second assay measures the protease activity of trypsin upon fusion between dengue virions and trypsin-containing liposomes. We performed an in silico virtual screening for small molecules that can potentially bind to the betaOG pocket and tested these candidate molecules in the two fusion assays. We identified one compound that inhibits dengue fusion in both assays with an IC(50) of 6.8 microM and reduces viral titers with an EC(50) of 9.8 microM. Time-of-addition experiments showed that the compound was only active when present during viral infection but not when added 1h later, in agreement with a mechanism of action through fusion inhibition.

ENU mutagenesis identifies mice with cardiac fibrosis and hepatic steatosis caused by a mutation in the mitochondrial trifunctional protein beta-subunit.

PubMed

Kao, Hsiao-Jung; Cheng, Ching-Feng; Chen, Yen-Hui; Hung, Shuen-Iu; Huang, Cheng-Chih; Millington, David; Kikuchi, Tateki; Wu, Jer-Yuarn; Chen, Yuan-Tsong

2006-12-15

Using the metabolomics-guided screening coupled to N-ethyl-N-nitrosourea-mediated mutagenesis, we identified mice that exhibited elevated levels of long-chain acylcarnitines. Whole genome homozygosity mapping with 262 SNP markers mapped the disease gene to chromosome 5 where candidate genes Hadha and Hadhb, encoding the mitochondria trifunctional protein (MTP) alpha- and beta-subunits, respectively, are located. Direct sequencing revealed a normal alpha-subunit, but detected a nucleotide T-to-A transversion in exon 14 (c.1210T>A) of beta-subunit (Hadhb) which resulted in a missense mutation of methionine to lysine (M404K). Western blot analysis showed a significant reduction of both the alpha- and beta-subunits, consistent with reduced enzyme activity in both the long-chain 3-hydroxyacyl-CoA dehydrogenase and the long-chain 3-ketoacyl-CoA thiolase activities. These mice had a decreased weight gain and cardiac arrhythmias which manifested from a prolonged PR interval to a complete atrio-ventricular dissociation, and died suddenly between 9 and 16 months of age. Histopathological studies showed multifocal cardiac fibrosis and hepatic steatosis. This mouse model will be useful to further investigate the mechanisms underlying arrhythmogenesis relating to lipotoxic cardiomyopathy and to investigate pathophysiology and treatment strategies for human MTP deficiency.

Advances in the high bootstrap fraction regime on DIII-D towards the Q = 5 mission of ITER steady state

DOE PAGES

Qian, Jinping P.; Garofalo, Andrea M.; Gong, Xianzu Z.; ...

2017-03-20

Recent EAST/DIII-D joint experiments on the high poloidal betamore » $${{\\beta}_{\\text{P}}}$$ regime in DIII-D have extended operation with internal transport barriers (ITBs) and excellent energy confinement (H 98y2 ~ 1.6) to higher plasma current, for lower q 95 ≤ 7.0, and more balanced neutral beam injection (NBI) (torque injection < 2 Nm), for lower plasma rotation than previous results. Transport analysis and experimental measurements at low toroidal rotation suggest that the E × B shear effect is not key to the ITB formation in these high $${{\\beta}_{\\text{P}}}$$ discharges. Experiments and TGLF modeling show that the Shafranov shift has a key stabilizing effect on turbulence. Extrapolation of the DIII-D results using a 0D model shows that with the improved confinement, the high bootstrap fraction regime could achieve fusion gain Q = 5 in ITER at $${{\\beta}_{\\text{N}}}$$ ~ 2.9 and q 95 ~ 7. With the optimization of q(0), the required improved confinement is achievable when using 1.5D TGLF-SAT1 for transport simulations. Furthermore, results reported in this paper suggest that the DIII-D high $${{\\beta}_{\\text{P}}}$$ scenario could be a candidate for ITER steady state operation.« less

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

Zhang Yueyang; Deng Licai; Liu Chao

A total of {approx}640, 000 objects from the LAMOST pilot survey have been publicly released. In this work, we present a catalog of DA white dwarfs (DAWDs) from the entire pilot survey. We outline a new algorithm for the selection of white dwarfs (WDs) by fitting Sersic profiles to the Balmer H{beta}, H{gamma}, and H{delta} lines of the spectra, and calculating the equivalent width of the Ca II K line. Two thousand nine hundred sixty-four candidates are selected by constraining the fitting parameters and the equivalent width of the Ca II K line. All the spectra of candidates are visuallymore » inspected. We identify 230 DAWDs (59 of which are already included in the Villanova and SDSS WD catalogs), 20 of which are DAWDs with non-degenerate companions. In addition, 128 candidates are classified as DAWDs/subdwarfs, which means the classifications are ambiguous. The result is consistent with the expected DAWD number estimated based on the LEGUE target selection algorithm.« less

Alternative Pathways for Production of Beta-Amyloid Peptides of Alzheimer’s Disease

PubMed Central

Hook, Vivian; Schechter, Israel; Demuth, Hans-Ulrich; Hook, Gregory

2009-01-01

This highlight article describes three Alzheimer’s disease (AD) presentations made at the 5th General Meeting of the International Proteolysis Society that address enzymatic mechanisms that produce neurotoxic beta-amyloid (Aβ) peptides. One group described the poor kinetic properties of the BACE 1 β-secretase for cleaving the wild-type β-secretase site in the APP found in most AD patients. They demonstrated that cathepsin D displays BACE 1-like specificity, is 280-fold more abundant in human brain than BACE 1, and pepstatin A inhibits cleavage of β-secretase site peptides by brain extracts and cathepsin D, but not by BACE 1. Nevertheless, as BACE 1 and cathepsin D show poor activity towards the wild type β-secretase site, they suggested continuing the search for additional β-secretase candidate(s). The second group reported that cathepsin B is such an alternative β-secretase candidate possessing excellent kinetic efficiency and specificity for cleaving the wild-type β-secretase site. Significantly, they demonstrated that inhibitors of cathepsin B improved memory function with reduced amyloid plaque neuropathology and decreased brain Aβ(40/42) and β-secretase activity in AD animal models expressing APP containing the wild-type β-secretase site. The third group addressed isoaspartate and pyroglutamate (pGlu) posttranslational modifications of Aβ that are present in AD brains, with evidence that cathepsin B, but not BACE 1, efficiently cleaves the wild-type β-secretase site containing isoaspartate. They also found that cyclization of N-terminal Glu by glutaminyl cyclase generates pGluAβ(3-40/42) peptides that are highly amyloidogenic. These presentations suggested that cathepsin B and glutaminyl cyclase are potential new AD therapeutic targets. PMID:18979625

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…

The Leptospiral Antigen Lp49 is a Two-Domain Protein with Putative Protein Binding Function

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

Oliveira Giuseppe,P.; Oliveira Neves, F.; Nascimento, A.

2008-01-01

Pathogenic Leptospira is the etiological agent of leptospirosis, a life-threatening disease that affects populations worldwide. Currently available vaccines have limited effectiveness and therapeutic interventions are complicated by the difficulty in making an early diagnosis of leptospirosis. The genome of Leptospira interrogans was recently sequenced and comparative genomic analysis contributed to the identification of surface antigens, potential candidates for development of new vaccines and serodiagnosis. Lp49 is a membrane-associated protein recognized by antibodies present in sera from early and convalescent phases of leptospirosis patients. Its crystal structure was determined by single-wavelength anomalous diffraction using selenomethionine-labelled crystals and refined at 2.0 Angstromsmore » resolution. Lp49 is composed of two domains and belongs to the all-beta-proteins class. The N-terminal domain folds in an immunoglobulin-like beta-sandwich structure, whereas the C-terminal domain presents a seven-bladed beta-propeller fold. Structural analysis of Lp49 indicates putative protein-protein binding sites, suggesting a role in Leptospira-host interaction. This is the first crystal structure of a leptospiral antigen described to date.« less

Novel donepezil-based inhibitors of acetyl- and butyrylcholinesterase and acetylcholinesterase-induced beta-amyloid aggregation.

PubMed

Camps, Pelayo; Formosa, Xavier; Galdeano, Carles; Gómez, Tània; Muñoz-Torrero, Diego; Scarpellini, Michele; Viayna, Elisabet; Badia, Albert; Clos, M Victòria; Camins, Antoni; Pallàs, Mercè; Bartolini, Manuela; Mancini, Francesca; Andrisano, Vincenza; Estelrich, Joan; Lizondo, Mònica; Bidon-Chanal, Axel; Luque, F Javier

2008-06-26

A novel series of donepezil-tacrine hybrids designed to simultaneously interact with the active, peripheral and midgorge binding sites of acetylcholinesterase (AChE) have been synthesized and tested for their ability to inhibit AChE, butyrylcholinesterase (BChE), and AChE-induced A beta aggregation. These compounds consist of a unit of tacrine or 6-chlorotacrine, which occupies the same position as tacrine at the AChE active site, and the 5,6-dimethoxy-2-[(4-piperidinyl)methyl]-1-indanone moiety of donepezil (or the indane derivative thereof), whose position along the enzyme gorge and the peripheral site can be modulated by a suitable tether that connects tacrine and donepezil fragments. All of the new compounds are highly potent inhibitors of bovine and human AChE and BChE, exhibiting IC50 values in the subnanomolar or low nanomolar range in most cases. Moreover, six out of the eight hybrids of the series, particularly those bearing an indane moiety, exhibit a significant A beta antiaggregating activity, which makes them promising anti-Alzheimer drug candidates.

New Low-Mass Members of Nearby Young Moving Groups

NASA Astrophysics Data System (ADS)

Schlieder, Joshua; Simon, Michal; Rice, Emily; Lepine, Sebastien

2012-08-01

We are now ready to expand our program to identify new low-mass members of nearby young moving groups (NYMGs) to stars of mass ≤0.3 M_⊙. This is important to: (1) complete the census of low-mass stars near the Sun, (2) provide high priority targets for disk and exoplanet studies by direct imaging, and (3) provide a well- characterized sample of nearby, young stars for detailed study of their physical and kinematic properties. Our proven technique starts with a proper motion selection algorithm, proceeds to vet the sample for indicators of youth, and requires as its last step the measurement of candidate member radial velocities (RVs). So far, we have measured more than 100 candidate RVs using CSHELL on the NASA-IRTF and PHOENIX on Gemini-South, yielding more than 50 likely new moving group members. Here we propose to continue our RV follow-up of candidate NYMG members using PHOENIX on the KPNO 4m. We aim to measure RVs and determine spectral types of 23 faint (V≥15, H≥9), late-type (≥M4) candidates of the (beta) Pic (10 Myrs), AB Dor (70 Myrs), Tuc/Hor (30 Myrs), and TW Hydrae (8 Myrs) moving groups.

Chemokine expression in rheumatoid arthritis (RA): evidence of RANTES and macrophage inflammatory protein (MIP)-1 beta production by synovial T cells.

PubMed Central

Robinson, E; Keystone, E C; Schall, T J; Gillett, N; Fish, E N

1995-01-01

Earlier studies from this laboratory provided evidence for restricted cytokine expression in the T cell population in RA tissues. Specifically, IL-2, IL-4, IL-6 and interferon-gamma (IFN-gamma) gene expression levels were low. The selective chemoattractant and activation effects of chemokines on leucocytes identify them as potentially ideal candidates in mediating selective inflammatory processes in RA. Accordingly, we undertook studies to examine constitutive chemokine gene expression in RA tissues. RANTES, monocyte chemotactic protein-1 (MCP-1) and MIP-1 beta gene expression was examined in both the T and non-T cell populations in RA peripheral blood (PB), synovial fluid (SF) and synovial tissues (ST). Our results identified elevated levels of both RANTES and MIP-1 beta gene expression in circulating RA PB and SF T cells. By contrast, MCP-1 expression was virtually absent in RA PB, yet elevated MCP-1 mRNA levels were detected primarily in the non-T cell populations of the SF and ST samples. Histological examination of affected rheumatoid joints revealed extensive RANTES and MIP-1 beta expression in sites of lymphocyte infiltration and cell proliferation, namely the synovial lining and sublining layers. Fractionation or RA ST patient samples revealed that RANTES expression was restricted to the T cells, whereas MIP-1 beta expression was detected in both T and non-T fractions. These data suggest that MCP-1, MIP-1 beta and RANTES may have a central role in the trafficking of reactive molecules involved in immunoregulation and in the inflammatory processes in RA. Images Fig. 4 PMID:7545093

Role of integrin-linked kinase in regulating phosphorylation of Akt and fibroblast survival in type I collagen matrices through a beta1 integrin viability signaling pathway.

PubMed

Nho, Richard Seonghun; Xia, Hong; Kahm, Judy; Kleidon, Jill; Diebold, Deanna; Henke, Craig A

2005-07-15

A beta1 integrin phosphatidylinositol 3-kinase/Akt pathway regulates fibroblast survival in collagen matrices. When fibroblasts attach to collagen, Akt becomes phosphorylated, providing a survival signal. In contrast, in response to mechanical forces generated during collagen contraction, Akt is dephosphorylated and fibroblasts undergo apoptosis. The kinase(s) responsible for regulating Akt phosphorylation in response to matrix-derived mechanical signals are unclear. Integrin-linked kinase (ILK) is associated with the beta1 integrin in the focal adhesion complex and as such is a candidate kinase that may regulate Akt phosphorylation and fibroblast viability. Nevertheless, there is no direct evidence that matrix-derived mechanical forces regulate cell viability by modulating ILK activity. Here, we show that ILK activity decreased in response to collagen matrix contraction, which correlated with Akt dephosphorylation and induction of fibroblast apoptosis. In contrast, enforced activation of beta1 integrin by activating antibody preserved ILK and Akt activity during collagen matrix contraction, and this is associated with protection from collagen contraction-induced apoptosis. Knock-down of ILK by small, interfering RNA (siRNA) attenuated Akt phosphorylation in response to ligation of beta1 integrin by collagen or activating antibody and enhanced fibroblast apoptosis in response to collagen contraction. Kinase dead ILK attenuated Akt phosphorylation and enhanced fibroblast apoptosis, whereas hyperactive and wild type ILK augmented Akt phosphorylation and protected fibroblasts from apoptosis. Constitutively active Akt preserved Akt activity and rescued ILK siRNA-treated fibroblasts from collagen contraction-induced apoptosis. These data establish that matrix-derived mechanical forces sensed by beta1 integrin are capable of modulating ILK activity which regulates fibroblast viability via an Akt-dependent mechanism.