23 results
The Parkes Pulsar Timing Array third data release
- Andrew Zic, Daniel J. Reardon, Agastya Kapur, George Hobbs, Rami Mandow, Małgorzata Curyło, Ryan M. Shannon, Jacob Askew, Matthew Bailes, N. D. Ramesh Bhat, Andrew Cameron, Zu-Cheng Chen, Shi Dai, Valentina Di Marco, Yi Feng, Matthew Kerr, Atharva Kulkarni, Marcus E. Lower, Rui Luo, Richard N. Manchester, Matthew T. Miles, Rowina S. Nathan, Stefan Osłowski, Axl F. Rogers, Christopher J. Russell, John M. Sarkissian, Mohsen Shamohammadi, Renée Spiewak, Nithyanandan Thyagarajan, Lawrence Toomey, Shuangqiang Wang, Lei Zhang, Songbo Zhang, Xing-Jiang Zhu
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- Journal:
- Publications of the Astronomical Society of Australia / Volume 40 / 2023
- Published online by Cambridge University Press:
- 19 July 2023, e049
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We present the third data release from the Parkes Pulsar Timing Array (PPTA) project. The release contains observations of 32 pulsars obtained using the 64-m Parkes ‘Murriyang’ radio telescope. The data span is up to 18 yr with a typical cadence of 3 weeks. This data release is formed by combining an updated version of our second data release with $\sim$3 yr of more recent data primarily obtained using an ultra-wide-bandwidth receiver system that operates between 704 and 4032 MHz. We provide calibrated pulse profiles, flux density dynamic spectra, pulse times of arrival, and initial pulsar timing models. We describe methods for processing such wide-bandwidth observations and compare this data release with our previous release.
Early developmental profiles of sensory features and links to school-age adaptive and maladaptive outcomes: A birth cohort investigation
- Yun-Ju Chen, John Sideris, Linda R. Watson, Elizabeth R. Crais, Grace T. Baranek
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- Journal:
- Development and Psychopathology / Volume 36 / Issue 1 / February 2024
- Published online by Cambridge University Press:
- 29 December 2022, pp. 291-301
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Sensory-based subtypes among autistic children have been well documented, but little is known about longitudinal sensory subtypes beyond autistic populations. This prospective study aimed to identify subtypes based on trajectories of parent-reported sensory features measured at 6–19 months, 3–4, and 6–7 years of age among a community-based birth cohort (N = 1,517), and to examine their associations with school-age clinical and adaptive/maladaptive outcomes on a subset sample (N = 389). Latent class growth analysis revealed five trajectory subtypes varying in intensity and change rates across three sensory domains. In contrast to an Adaptive-All Improving subtype (35%) with very low sensory features and overall better school-age outcomes, an Elevated-All Worsening subtype (3%), comprised of more boys and children of parents with less education, was associated with most elevated autistic traits and poorest adaptive/maladaptive outcomes. Three other subtypes (62% in total) were generally characterized by stable or improving patterns of sensory features at mild to moderate levels, and challenges in certain outcome domains. Our findings indicate that characterizing children based on early sensory trajectories may contribute to earlier detection of subgroups of children with sensory challenges who are more likely to experience developmental challenges by school age, followed by early targeted interventions for improved long-term outcomes.
Using polygenic scores and clinical data for bipolar disorder patient stratification and lithium response prediction: machine learning approach – CORRIGENDUM
- Micah Cearns, Azmeraw T. Amare, Klaus Oliver Schubert, Anbupalam Thalamuthu, Joseph Frank, Fabian Streit, Mazda Adli, Nirmala Akula, Kazufumi Akiyama, Raffaella Ardau, Bárbara Arias, JeanMichel Aubry, Lena Backlund, Abesh Kumar Bhattacharjee, Frank Bellivier, Antonio Benabarre, Susanne Bengesser, Joanna M. Biernacka, Armin Birner, Clara Brichant-Petitjean, Pablo Cervantes, HsiChung Chen, Caterina Chillotti, Sven Cichon, Cristiana Cruceanu, Piotr M. Czerski, Nina Dalkner, Alexandre Dayer, Franziska Degenhardt, Maria Del Zompo, J. Raymond DePaulo, Bruno Étain, Peter Falkai, Andreas J. Forstner, Louise Frisen, Mark A. Frye, Janice M. Fullerton, Sébastien Gard, Julie S. Garnham, Fernando S. Goes, Maria Grigoroiu-Serbanescu, Paul Grof, Ryota Hashimoto, Joanna Hauser, Urs Heilbronner, Stefan Herms, Per Hoffmann, Andrea Hofmann, Liping Hou, Yi-Hsiang Hsu, Stephane Jamain, Esther Jiménez, Jean-Pierre Kahn, Layla Kassem, Po-Hsiu Kuo, Tadafumi Kato, John Kelsoe, Sarah Kittel-Schneider, Sebastian Kliwicki, Barbara König, Ichiro Kusumi, Gonzalo Laje, Mikael Landén, Catharina Lavebratt, Marion Leboyer, Susan G. Leckband, Mario Maj, the Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Mirko Manchia, Lina Martinsson, Michael J. McCarthy, Susan McElroy, Francesc Colom, Marina Mitjans, Francis M. Mondimore, Palmiero Monteleone, Caroline M. Nievergelt, Markus M. Nöthen, Tomas Novák, Claire O'Donovan, Norio Ozaki, Vincent Millischer, Sergi Papiol, Andrea Pfennig, Claudia Pisanu, James B. Potash, Andreas Reif, Eva Reininghaus, Guy A. Rouleau, Janusz K. Rybakowski, Martin Schalling, Peter R. Schofield, Barbara W. Schweizer, Giovanni Severino, Tatyana Shekhtman, Paul D. Shilling, Katzutaka Shimoda, Christian Simhandl, Claire M. Slaney, Alessio Squassina, Thomas Stamm, Pavla Stopkova, Fasil TekolaAyele, Alfonso Tortorella, Gustavo Turecki, Julia Veeh, Eduard Vieta, Stephanie H. Witt, Gloria Roberts, Peter P. Zandi, Martin Alda, Michael Bauer, Francis J. McMahon, Philip B. Mitchell, Thomas G. Schulze, Marcella Rietschel, Scott R. Clark, Bernhard T. Baune
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- Journal:
- The British Journal of Psychiatry / Volume 221 / Issue 2 / August 2022
- Published online by Cambridge University Press:
- 04 May 2022, p. 494
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- August 2022
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Using polygenic scores and clinical data for bipolar disorder patient stratification and lithium response prediction: machine learning approach
- Micah Cearns, Azmeraw T. Amare, Klaus Oliver Schubert, Anbupalam Thalamuthu, Joseph Frank, Fabian Streit, Mazda Adli, Nirmala Akula, Kazufumi Akiyama, Raffaella Ardau, Bárbara Arias, Jean-Michel Aubry, Lena Backlund, Abesh Kumar Bhattacharjee, Frank Bellivier, Antonio Benabarre, Susanne Bengesser, Joanna M. Biernacka, Armin Birner, Clara Brichant-Petitjean, Pablo Cervantes, Hsi-Chung Chen, Caterina Chillotti, Sven Cichon, Cristiana Cruceanu, Piotr M. Czerski, Nina Dalkner, Alexandre Dayer, Franziska Degenhardt, Maria Del Zompo, J. Raymond DePaulo, Bruno Étain, Peter Falkai, Andreas J. Forstner, Louise Frisen, Mark A. Frye, Janice M. Fullerton, Sébastien Gard, Julie S. Garnham, Fernando S. Goes, Maria Grigoroiu-Serbanescu, Paul Grof, Ryota Hashimoto, Joanna Hauser, Urs Heilbronner, Stefan Herms, Per Hoffmann, Andrea Hofmann, Liping Hou, Yi-Hsiang Hsu, Stephane Jamain, Esther Jiménez, Jean-Pierre Kahn, Layla Kassem, Po-Hsiu Kuo, Tadafumi Kato, John Kelsoe, Sarah Kittel-Schneider, Sebastian Kliwicki, Barbara König, Ichiro Kusumi, Gonzalo Laje, Mikael Landén, Catharina Lavebratt, Marion Leboyer, Susan G. Leckband, Mario Maj, the Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Mirko Manchia, Lina Martinsson, Michael J. McCarthy, Susan McElroy, Francesc Colom, Marina Mitjans, Francis M. Mondimore, Palmiero Monteleone, Caroline M. Nievergelt, Markus M. Nöthen, Tomas Novák, Claire O'Donovan, Norio Ozaki, Vincent Millischer, Sergi Papiol, Andrea Pfennig, Claudia Pisanu, James B. Potash, Andreas Reif, Eva Reininghaus, Guy A. Rouleau, Janusz K. Rybakowski, Martin Schalling, Peter R. Schofield, Barbara W. Schweizer, Giovanni Severino, Tatyana Shekhtman, Paul D. Shilling, Katzutaka Shimoda, Christian Simhandl, Claire M. Slaney, Alessio Squassina, Thomas Stamm, Pavla Stopkova, Fasil Tekola-Ayele, Alfonso Tortorella, Gustavo Turecki, Julia Veeh, Eduard Vieta, Stephanie H. Witt, Gloria Roberts, Peter P. Zandi, Martin Alda, Michael Bauer, Francis J. McMahon, Philip B. Mitchell, Thomas G. Schulze, Marcella Rietschel, Scott R. Clark, Bernhard T. Baune
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- Journal:
- The British Journal of Psychiatry / Volume 220 / Issue 4 / April 2022
- Published online by Cambridge University Press:
- 28 February 2022, pp. 219-228
- Print publication:
- April 2022
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Background
Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.
AimsTo use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.
MethodThis study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi+Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework.
ResultsThe best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data.
ConclusionsUsing PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.
4277 Functional consequences of the juvenile idiopathic arthritis risk variant at 1q24.3
- Halima Moncrieffe, Katelyn Dunn, Yongbo Huang, Xiaoting Chen, Carl D. Langefeld, Matthew T. Weirauch, John B. Harley, Leah C. Kottyan, Susan D. Thompson, Juvenile Arthritis Consortium for the Immunochip
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- Journal:
- Journal of Clinical and Translational Science / Volume 4 / Issue s1 / June 2020
- Published online by Cambridge University Press:
- 29 July 2020, pp. 95-96
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OBJECTIVES/GOALS: Juvenile idiopathic arthritis (JIA) is the most common childhood rheumatologic disease childhood and a cause of pain and potential disability. JIA has a strong genetic component and no known cure. The goal of this study is to evaluate allele-dependent effects of a novel JIA risk variant at 1q24.3. METHODS/STUDY POPULATION: JIA patients meeting criteria for the two most common disease subtypes (oligoarticular and RF neg polyarthritis) were genotyped using the Immunochip, an Illumina array with dense coverage of the HLA region and 186 other loci previously reported in autoimmune diseases. Phase I association findings (Hinks, 2013) and Phase II analysis (unpublished) of an expanded cohort (4,271 JIA and 14,390 controls) identified new risk loci, including rs78037977 at 1q24.3. We prioritized rs78037977 and predicted possible impacted mechanisms based on Bayesian predictions of attributable risk, the surrounding chromatin landscape, and transcription factor binding data. A luciferase reporter assay was used to assess allele-dependent enhancer activity. RESULTS/ANTICIPATED RESULTS: rs78037977 is located between FASLG and TNFSF18 at chromosome 1q24.3 is associated with JIA (p = 6.3x10−09), and explains 94% of the posterior probability at this locus; no other SNPs in linkage disequilibrium (r2>0.6). The chromatin landscape around rs78037977 contains H3K4Me1 and H3K27Ac marks, which are indicative of enhancer activity. Further, >160 transcription factors have chromatin immunoprecipitation followed by sequencing (ChIP-seq) peaks overlapping rs78037977 in various cellular contexts. In luciferase reporter assays, the region around rs78037977 containing the reference A allele had ~2-fold increased enhancer activity compared to the non-reference allele. DISCUSSION/SIGNIFICANCE OF IMPACT: This work provides in vitro evidence to support allele-dependent enhancer activity of a novel JIA-risk variant at 1q24.3. Our ongoing work investigates the effect of the DNA-containing region of rs78037977 on gene expression and differential transcription factor binding at rs78037977.
Understanding Crystallization Pathways of MnOx Polymorph Formation via in-situ X-ray Scattering
- Bor-Rong Chen, Wenhao Sun, Daniil A. Kitchaev, John S. Mangum, Vivek Thampy, Lauren M. Garten, David G. Ginley, Brian P. Gorman, Kevin H. Stone, Gerbrand Ceder, Michael F. Toney, Laura T. Schelhas
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- Journal:
- Microscopy and Microanalysis / Volume 24 / Issue S1 / August 2018
- Published online by Cambridge University Press:
- 01 August 2018, pp. 1486-1487
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- August 2018
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Assessment of Groin Application of Junctional Tourniquets in a Manikin Model
- John F. Kragh, Jr., Matthew P. Lunati, Chetan U. Kharod, Cord W. Cunningham, Jeffrey A. Bailey, Zsolt T. Stockinger, Andrew P. Cap, Jacob Chen, James K. Aden, 3d, Leopoldo C. Cancio
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- Journal:
- Prehospital and Disaster Medicine / Volume 31 / Issue 4 / August 2016
- Published online by Cambridge University Press:
- 27 May 2016, pp. 358-363
- Print publication:
- August 2016
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Introduction
To aid in preparation of military medic trainers for a possible new curriculum in teaching junctional tourniquet use, the investigators studied the time to control hemorrhage and blood volume lost in order to provide evidence for ease of use.
HypothesisModels of junctional tourniquet could perform differentially by blood loss, time to hemostasis, and user preference.
MethodsIn a laboratory experiment, 30 users controlled simulated hemorrhage from a manikin (Combat Ready Clamp [CRoC] Trainer) with three iterations each of three junctional tourniquets. There were 270 tests which included hemorrhage control (yes/no), time to hemostasis, and blood volume lost. Users also subjectively ranked tourniquet performance. Models included CRoC, Junctional Emergency Treatment Tool (JETT), and SAM Junctional Tourniquet (SJT). Time to hemostasis and total blood loss were log-transformed and analyzed using a mixed model analysis of variance (ANOVA) with the users represented as random effects and the tourniquet model used as the treatment effect. Preference scores were analyzed with ANOVA, and Tukey’s honest significant difference test was used for all post-hoc pairwise comparisons.
ResultsAll tourniquet uses were 100% effective for hemorrhage control. For blood loss, CRoC and SJT performed best with least blood loss and were significantly better than JETT; in pairwise comparison, CRoC-JETT (P < .0001) and SJT-JETT (P = .0085) were statistically significant in their mean difference, while CRoC-SJT (P = .35) was not. For time to hemostasis in pairwise comparison, the CRoC had a significantly shorter time compared to JETT and SJT (P < .0001, both comparisons); SJT-JETT was also significant (P = .0087). In responding to the directive, “Rank the performance of the models from best to worst,” users did not prefer junctional tourniquet models differently (P > .5, all models).
ConclusionThe CRoC and SJT performed best in having least blood loss, CRoC performed best in having least time to hemostasis, and users did not differ in preference of model. Models of junctional tourniquet performed differentially by blood loss and time to hemostasis.
,Kragh JF Jr ,Lunati MP ,Kharod CU ,Cunningham CW ,Bailey JA ,Stockinger ZT ,Cap AP ,Chen J ,Aden JK 3d .Cancio LC Assessment of Groin Application of Junctional Tourniquets in a Manikin Model . Prehosp Disaster Med.2016 ;31 (4 ):358 –363 .
Contributors
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- By Jean Marie Abraham, Catherine Ayoub, Jessica Dym Bartlett, Karen L. Bierman, Paula A. Braveman, Robert H. Bruininks, Frances A. Campbell, Rachel Chazan-Cohen, Peggy Chen, Alyssa Crawford, Katina D’Onise, Celene E. Domitrovich, Greg J. Duncan, Susan Egerter, Michelle M. Englund, Temitope O. Erinosho, Kevin D. Frick, Michael K. Georgieff, Scott D. Gest, Bernard Guyer, Momoko Hayakawa, Ariel Kalil, Pinar Karaca-Mandic, Samuel A. Kleiner, Narayana Kocherlakota, John W. Lynch, Sai Ma, Laurie T. Martin, Robyn A. Mcdermott, Robin E. Mockenhaupt, Robert L. Nix, Helen Raikes, Arthur J. Reynolds, Arthur J. Rolnick, Sharon Rolnick, Lawrence J. Schweinhart, Amy Susman-Stillman, Judy A. Temple, Jim Thorp, Dianne S. Ward, Janet A. Welsh, Barry White, Sung J. Choi Yoo, Kathleen M. Ziol-Guest
- Edited by Arthur J. Reynolds, University of Minnesota, Arthur J. Rolnick, University of Minnesota, Judy A. Temple, University of Minnesota
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- Book:
- Health and Education in Early Childhood
- Published online:
- 05 February 2015
- Print publication:
- 19 February 2015, pp xiii-xiv
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- By Masoud Azodi, Patricia Baetens, Steven Bayer, Joel Bernstein, Jonathan D. Black, Christophe Blockeel, Carolien M. Boomsma, Birgit Borgström, Mark Bowman, Nicholas Brook, Elisabeth Carlsen, Peter Carne, Ying Cheong, Jen-Ruei Chen, Erin Clark, S. Alberto Dávila Garza, Sunita De Sousa, Michel De Vos, Leo Doherty, Patricio Donoso, Cindy M. P. Duke, Human M. Fatemi, Alison Fernbach, Juan A. Garcia-Velasco, Elizabeth S. Ginsburg, Dorothy A. Greenfeld, William M. Hague, Daniel Hajioff, Tristan Hardy, Catherine Henry, Outi Hovatta, John Hutton, Gordana Ivanovic, Sameer Jatkar, Shilpa Jesudason, Theo Joseph, Amanda Kallen, Sonal Karia, Bala Karunakaran, Jenneke C. Kasius, Ben Kroon, Dimitra Kyrou, Robert Lahoud, Jennifer M Levine, Inge Liebaers, Shane T. Lipskind, Derek Lok, Nick S. Macklon, Manveen (Manny) Mangat, Tom P. Manolitsas, S. McDowell, Cherise Mooy, Mark R. Morton, Andrew Murray, Robert J. Norman, Sara Ornaghi, Israel Ortega, Michael J. Paidas, Evaggelos Papanikolaou, Pasquale Patrizio, Sofie Piessens, Biljana Popovic Todorovic, Luk Rombauts, Katrina Rowan, Denny Sakkas, P. Sanhueza, Kirsten Tryde Schmidt, Mark Teoh, Hammed A. Tijani, Jelena Todorovic, Saioa Torrealday, Herman Tournaye, Geoffrey Trew, W. Verpoest, Veerle Vloeberghs, A. Yazdani
- Edited by Nick S. Macklon, University of Southampton, Human M. Fatemi, Robert J. Norman, University of Adelaide, Pasquale Patrizio
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- Book:
- Case Studies in Assisted Reproduction
- Published online:
- 05 February 2015
- Print publication:
- 22 January 2015, pp ix-xiv
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- By Linda S. Aglio, Cyrus Ahmadi Yazdi, Syed Irfan Qasim Ali, Caryn Barnet, Jessica Bauerle, Felicity Billings, Evan Blaney, Beverly Chang, Christopher Chen, Zinaida Chepurny, Hyung Sun Choi, Allison Clark, Lauren J. Cornella, Lisa Crossley, Michael D’Ambra, Galina Davidyuk, Whitney de Luna, Manisha S. Desai, Sukumar P. Desai, Kelly G. Elterman, Michaela K. Farber, Iuliu Fat, Jaida Fitzgerald, Devon Flaherty, John A. Fox, Gyorgy Frendl, Rejean Gareau, Joseph M. Garfield, Andrea Girnius, Laverne D. Gugino, J. Tasker Gundy, Carly C. Guthrie, Lisa M. Hammond, M. Tariq Hanifi, James Hardy, Philip M. Hartigan, Thomas Hickey, Richard Hsu, Mohab Ibrahim, David Janfaza, Yuka Kiyota, Suzanne Klainer, Benjamin Kloesel, Hanjo Ko, Bhavani Kodali, Vesela Kovacheva, J. Matthew Kynes, Robert W. Lekowski, Joyce Lo, Jeffrey Lu, Alvaro A. Macias, Zahra M. Malik, Erich N. Marks, Brendan McGinn, Jonathan R. Meserve, Annette Mizuguchi, Srdjan S. Nedeljkovic, Ju-Mei Ng, Michael Nguyen, Olutoyin Okanlawon, Jennifer Oliver, Krishna Parekh, Jessica Patterson, Christian Peccora, Pete Pelletier, Sujatha Pentakota, James H. Philip, Marc Philip T. Pimentel, Timothy D. Quinn, Elizabeth M. Rickerson, Susan L. Sager, Julia Serber, Shaheen Shaikh, Stanton Shernan, David Silver, Alissa Sodickson, Pingping Song, George P. Topulos, Agnieszka Trzcinka, Richard D. Urman, Rosemary Uzomba, Joshua Vacanti, Assia Valovska, Michael Vaninetti, Scott W. Vaughan, Kamen Vlassakov, Christopher Voscopoulos, Emily L. Wang, Laura Westfall, Zhiling Xiong, Stephanie Yacoubian, Dongdong Yao, Martin Zammert, Maksim Zayaruzny, Jose Luis Zeballos, Natthasorn Zinboonyahgoon, Jie Zhou
- Edited by Linda S. Aglio, Robert W. Lekowski, Richard D. Urman
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- Book:
- Essential Clinical Anesthesia Review
- Published online:
- 05 February 2015
- Print publication:
- 08 January 2015, pp xi-xvi
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- By Ainsworth Shaaron, Ayres Paul, Azevedo Roger, Bediou Benoit, Britt Anne, Kirsten R. Butcher, Chen Fei, Michelene T. H. Chi, Richard E. Clark, Ruth Colvin Clark, Sharon J. Derry, David F. Feldon, Fiorella Logan, J. D. Fletcher, Arthur C. Graesser, Hegarty Mary, HU Xiangen, Allison J. Jaeger, Janssen Jeroen, Cheryl I. Johnson, Ton De Jong, Kalyuga Slava, Kester Liesbeth, Kirschner Femke, Paul A. Kirschner, Susanne P. Lajoie, Ard W. Lazonder, Leutner Detlev, Low Renae, Richard K. Lowe, Richard E. Mayer, Benjamin D. Nye, Paas Fred, Pilegard Celeste, Jan L. Plass, Heather A. Priest, Renkl Alexander, Rouet Jean-FranÇois, Christopher A. Sanchez, Scheiter Katharina, Schmeck Annett, Schnotz Wolfgang, Ruth N. Schwartz, Bruce L. Sherin, Miriam Gamoran Sherin, Sweller John, Tobias Sigmund, Tamara Van Gog, Jeroen J. G. Van MerriËNboer, Jennifer Wiley, Alexander P. Wind, Ruth Wylie
- Edited by Richard E. Mayer, University of California, Santa Barbara
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- Book:
- The Cambridge Handbook of Multimedia Learning
- Published online:
- 05 August 2014
- Print publication:
- 28 July 2014, pp ix-x
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- By Alyssa Abo, Faiza Al Talaq, Alexander C. Arroyo, Laura J. Berg, Tony Berger, Lei Chen, Roberto Copetti, Stephanie J. Doniger, Mahmoud Elbarbary, Alaa A. Eldemerdash, Jason W. Fischer, John Christian Fox, Katja Goldflam, Beatrice Hoffmann, Jamie A. Jenkins, David Kessler, Heidi Ladner, Samuel H. F. Lam, Jason A. Levy, Resa E. Lewiss, Andrew S. Liteplo, Jennifer R. Marin, Arun Nagdev, Vicki E. Noble, Daniela Ramirez-Schrempp, Joshua Rempell, Randall T. Rhyne, Antonio Riera, Dana R. Sajed, Fernando Silva, Adam B. Sivitz, Dave Spear, Rebecca L. Vieira
- Edited by Stephanie J. Doniger
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- Pediatric Emergency Critical Care and Ultrasound
- Published online:
- 05 February 2015
- Print publication:
- 24 April 2014, pp x-xii
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61 - Squamous-cell carcinoma
- from Part 3.3 - Molecular pathology: cancers of the skin
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- By Carter Van Waes, Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda,MD, USA, Yansong Bian, Laboratory of Cell and Developmental Biology, National Institute of Dental and Craniofacial Research, NIH, Bethesda, MD, USA, Clint T. Allen, Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda,MD, USA, John C. Morris, Metabolism Branch, National Cancer Institute, NIH, Bethesda, MD, USA, Zhong Chen, Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda,MD, USA
- Edited by Edward P. Gelmann, Columbia University, New York, Charles L. Sawyers, Memorial Sloan-Kettering Cancer Center, New York, Frank J. Rauscher, III
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- Book:
- Molecular Oncology
- Published online:
- 05 February 2015
- Print publication:
- 19 December 2013, pp 686-692
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Summary
Introduction
Squamous-cell carcinomas (SCCs) form the predominant histological type of cancers arising from the head and neck (HNSCC; oral and nasal cavities, paranasal sinuses, pharynx, and larynx), uterine cervix, and skin; and a subset of carcinomas arising from the lung and esophagus (1). Those arising in the head and neck, lung, and esophagus are predominantly associated with tobacco and alcohol use, which contain polyaromatic hydrocarbons, sulphites, and acetaldehydes that can induce mutagenesis of key tumor-suppressor genes, such as CDKN2A and TP53, or mutagenesis or over-expression of oncogenes, such as EGFR, c-MET, or RAS. Most cervical SCC, and a subset of SCC arising in the oropharynx and skin of the anogential region, are associated with human papilloma viruses (HPVs). These viruses encode E6 and E7 oncogenes that inactivate important tumor-suppressor proteins TP53 and RB, and activate nuclear factor-kappaB (NF-κB). A subset of nasopharygeal carcinomas is associated with Epstein–Barr viruses (EBVs), which express LMP-1, an oncogene that also activates NF-κB. Most skin SCC arise in sun-exposed areas due to ultraviolet-light-induced carcinogenesis. Because much of what has been learned about the molecular pathogenesis of tobacco and HPV-related HNSCC applies to lung, esophageal, or cervical SCC, emphasis will be given to alterations common to HNSCC and SCC arising from these sites.
Tumor-suppressor genes in SCC
A genetic progression model for HNSCC has been defined by micro-satellite analysis for allelic loss at multiple loci (2). Important tumor-suppressor genes altered by genetic and epigenetic events and their consequences are illustrated in Figure 61.1, left side. A locus at 9p21 frequently undergoes loss of heterozygosity (LOH) during development of squamous hyperplasia and SCC (2). This locus encodes proteins p16INK4a and p14ARF, and is inactivated in the majority of HNSCC by homozygous deletion, mutation, or by methylation of the regulatory promoter region (3). The p16INK4a protein is a cyclin-dependent kinase (CDKN2A/MTS-1/INK4A) that inhibits cell-cycle progression. Re-expression of p16INK4a in HNSCC cells by gene transfer suppresses cell growth in vitro (4). p14ARF is an important activator of the TP53 tumor-suppressor pathway and repressor of the NF-κB pro-survival pathway (5,6). Re-expression of p14ARF has been shown to reactivate TP53, and repress NF-κB-mediated pro-survival gene expression and promote cell death in other cell lines (6). Thus, genetic or epigenetic alteration of this locus can result in loss of p16INK4a, causing increased proliferation, and p14ARF protein, causing decreased programmed cell death.
Contributors
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- By Arthur S. Abramson, Norhaida Aman, Virginie Attina, Sapna Bhat, B. Bhuvaneshwari, Denis Burnham, Brian Byrne, Hsin-Chin Chen, Shyamala K. Chengappa, Chris Davis, Jackson T. Gandour, Winston D. Goh, Thom Huebner, Lixian Jin, Jing Zhou, R. Malatesha Joshi, Benjawan Kasisopa, Jeesun Kim, Christine Kitamura, Ananthanarayan Krishnan, Lay Wah Lee, Elena Lieven, Sudaporn Luksaneeyanawin, Ramesh Mishra, Sonali Nag, Vishnu K. K. Nair, Loraine K. Obler, Tomasina Oh, Richard K. Olson, Prakash Padakannaya, Aparna Pandey, Avanthi Niranjan Paplikar, Shalmalee Pitale, Chaitra Rao, Theeraporn Ratitamkul, Nan Xu Rattanasone, Sunil Kumar Ravi, Rogayah A. Razak, Ronan Reilly, Susan Rickard Liow, Khazriyati Salehuddin, Stefan Samuelsson, Vaijayanthi M. Sarma, Yasuhiro Shirai, Shruti Sircar, John Song, Sabine Stoll, Lidia Suárez, Jennie Tran, Jie-Li Tsai, Kimiko Tsukada, Jyotsna Vaid, Heather Winskel, Janet Wright, Kelly Yeo
- Edited by Heather Winskel, Southern Cross University, Australia, Prakash Padakannaya, University of Mysore, India
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- Book:
- South and Southeast Asian Psycholinguistics
- Published online:
- 05 December 2013
- Print publication:
- 28 November 2013, pp xvii-xx
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- By Amy F.T. Arnsten, Darrick T. Balu, Anthony W. Bannon, James E. Barrett, Craig W. Berridge, David L. Braff, Jiang-Fan Chen, Guang Chen, Joseph T. Coyle, David M. Devilbiss, Wayne C. Drevets, Craig A. Erickson, Michael Gandal, Maciej Gasior, Charles F. Gillespie, Donald C. Goff, Swati Gupta, Ioline D. Henter, Tong Li, Farah D. Lubin, Christopher J. McDougle, Husseini K. Manji, Nicholas J. Maragakis, Charles P. O'Brien, Ryley Parrish, David J. Posey, Donald L. Price, Jorge A. Quiroz, Kerry J. Ressler, Timothy P.L. Roberts, Richard A. Rudick, Alfred W. Sandrock, Alena V. Savonenko, Brooke E. Schmeichel, Steven J. Siegel, Robert C. Spencer, Kimberly A. Stigler, Paulo Vianney-Rodrigues, John P. Welsh, Tamara Weiss, Frank Wiegand, Michael Williams, Philip C. Wong
- Edited by James E. Barrett, Joseph T. Coyle, Michael Williams
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- Book:
- Translational Neuroscience
- Published online:
- 05 July 2012
- Print publication:
- 28 June 2012, pp vi-viii
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Contributors
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- By Rose Teteki Abbey, K. C. Abraham, David Tuesday Adamo, LeRoy H. Aden, Efrain Agosto, Victor Aguilan, Gillian T. W. Ahlgren, Charanjit Kaur AjitSingh, Dorothy B E A Akoto, Giuseppe Alberigo, Daniel E. Albrecht, Ruth Albrecht, Daniel O. Aleshire, Urs Altermatt, Anand Amaladass, Michael Amaladoss, James N. Amanze, Lesley G. Anderson, Thomas C. Anderson, Victor Anderson, Hope S. Antone, María Pilar Aquino, Paula Arai, Victorio Araya Guillén, S. Wesley Ariarajah, Ellen T. Armour, Brett Gregory Armstrong, Atsuhiro Asano, Naim Stifan Ateek, Mahmoud Ayoub, John Alembillah Azumah, Mercedes L. García Bachmann, Irena Backus, J. Wayne Baker, Mieke Bal, Lewis V. Baldwin, William Barbieri, António Barbosa da Silva, David Basinger, Bolaji Olukemi Bateye, Oswald Bayer, Daniel H. Bays, Rosalie Beck, Nancy Elizabeth Bedford, Guy-Thomas Bedouelle, Chorbishop Seely Beggiani, Wolfgang Behringer, Christopher M. Bellitto, Byard Bennett, Harold V. Bennett, Teresa Berger, Miguel A. Bernad, Henley Bernard, Alan E. Bernstein, Jon L. Berquist, Johannes Beutler, Ana María Bidegain, Matthew P. Binkewicz, Jennifer Bird, Joseph Blenkinsopp, Dmytro Bondarenko, Paulo Bonfatti, Riet en Pim Bons-Storm, Jessica A. Boon, Marcus J. Borg, Mark Bosco, Peter C. Bouteneff, François Bovon, William D. Bowman, Paul S. Boyer, David Brakke, Richard E. Brantley, Marcus Braybrooke, Ian Breward, Ênio José da Costa Brito, Jewel Spears Brooker, Johannes Brosseder, Nicholas Canfield Read Brown, Robert F. Brown, Pamela K. Brubaker, Walter Brueggemann, Bishop Colin O. Buchanan, Stanley M. Burgess, Amy Nelson Burnett, J. Patout Burns, David B. Burrell, David Buttrick, James P. Byrd, Lavinia Byrne, Gerado Caetano, Marcos Caldas, Alkiviadis Calivas, William J. Callahan, Salvatore Calomino, Euan K. Cameron, William S. Campbell, Marcelo Ayres Camurça, Daniel F. Caner, Paul E. Capetz, Carlos F. Cardoza-Orlandi, Patrick W. Carey, Barbara Carvill, Hal Cauthron, Subhadra Mitra Channa, Mark D. Chapman, James H. Charlesworth, Kenneth R. Chase, Chen Zemin, Luciano Chianeque, Philip Chia Phin Yin, Francisca H. Chimhanda, Daniel Chiquete, John T. Chirban, Soobin Choi, Robert Choquette, Mita Choudhury, Gerald Christianson, John Chryssavgis, Sejong Chun, Esther Chung-Kim, Charles M. A. Clark, Elizabeth A. Clark, Sathianathan Clarke, Fred Cloud, John B. Cobb, W. Owen Cole, John A Coleman, John J. Collins, Sylvia Collins-Mayo, Paul K. Conkin, Beth A. Conklin, Sean Connolly, Demetrios J. Constantelos, Michael A. Conway, Paula M. Cooey, Austin Cooper, Michael L. Cooper-White, Pamela Cooper-White, L. William Countryman, Sérgio Coutinho, Pamela Couture, Shannon Craigo-Snell, James L. Crenshaw, David Crowner, Humberto Horacio Cucchetti, Lawrence S. Cunningham, Elizabeth Mason Currier, Emmanuel Cutrone, Mary L. Daniel, David D. Daniels, Robert Darden, Rolf Darge, Isaiah Dau, Jeffry C. Davis, Jane Dawson, Valentin Dedji, John W. de Gruchy, Paul DeHart, Wendy J. Deichmann Edwards, Miguel A. De La Torre, George E. Demacopoulos, Thomas de Mayo, Leah DeVun, Beatriz de Vasconcellos Dias, Dennis C. Dickerson, John M. Dillon, Luis Miguel Donatello, Igor Dorfmann-Lazarev, Susanna Drake, Jonathan A. Draper, N. Dreher Martin, Otto Dreydoppel, Angelyn Dries, A. J. Droge, Francis X. D'Sa, Marilyn Dunn, Nicole Wilkinson Duran, Rifaat Ebied, Mark J. Edwards, William H. Edwards, Leonard H. Ehrlich, Nancy L. Eiesland, Martin Elbel, J. Harold Ellens, Stephen Ellingson, Marvin M. Ellison, Robert Ellsberg, Jean Bethke Elshtain, Eldon Jay Epp, Peter C. Erb, Tassilo Erhardt, Maria Erling, Noel Leo Erskine, Gillian R. Evans, Virginia Fabella, Michael A. Fahey, Edward Farley, Margaret A. Farley, Wendy Farley, Robert Fastiggi, Seena Fazel, Duncan S. Ferguson, Helwar Figueroa, Paul Corby Finney, Kyriaki Karidoyanes FitzGerald, Thomas E. FitzGerald, John R. Fitzmier, Marie Therese Flanagan, Sabina Flanagan, Claude Flipo, Ronald B. Flowers, Carole Fontaine, David Ford, Mary Ford, Stephanie A. Ford, Jim Forest, William Franke, Robert M. Franklin, Ruth Franzén, Edward H. Friedman, Samuel Frouisou, Lorelei F. Fuchs, Jojo M. Fung, Inger Furseth, Richard R. Gaillardetz, Brandon Gallaher, China Galland, Mark Galli, Ismael García, Tharscisse Gatwa, Jean-Marie Gaudeul, Luis María Gavilanes del Castillo, Pavel L. Gavrilyuk, Volney P. Gay, Metropolitan Athanasios Geevargis, Kondothra M. George, Mary Gerhart, Simon Gikandi, Maurice Gilbert, Michael J. Gillgannon, Verónica Giménez Beliveau, Terryl Givens, Beth Glazier-McDonald, Philip Gleason, Menghun Goh, Brian Golding, Bishop Hilario M. Gomez, Michelle A. Gonzalez, Donald K. Gorrell, Roy Gottfried, Tamara Grdzelidze, Joel B. Green, Niels Henrik Gregersen, Cristina Grenholm, Herbert Griffiths, Eric W. Gritsch, Erich S. Gruen, Christoffer H. Grundmann, Paul H. Gundani, Jon P. Gunnemann, Petre Guran, Vidar L. Haanes, Jeremiah M. Hackett, Getatchew Haile, Douglas John Hall, Nicholas Hammond, Daphne Hampson, Jehu J. Hanciles, Barry Hankins, Jennifer Haraguchi, Stanley S. Harakas, Anthony John Harding, Conrad L. Harkins, J. William Harmless, Marjory Harper, Amir Harrak, Joel F. Harrington, Mark W. Harris, Susan Ashbrook Harvey, Van A. Harvey, R. Chris Hassel, Jione Havea, Daniel Hawk, Diana L. Hayes, Leslie Hayes, Priscilla Hayner, S. Mark Heim, Simo Heininen, Richard P. Heitzenrater, Eila Helander, David Hempton, Scott H. Hendrix, Jan-Olav Henriksen, Gina Hens-Piazza, Carter Heyward, Nicholas J. Higham, David Hilliard, Norman A. Hjelm, Peter C. Hodgson, Arthur Holder, M. Jan Holton, Dwight N. Hopkins, Ronnie Po-chia Hsia, Po-Ho Huang, James Hudnut-Beumler, Jennifer S. Hughes, Leonard M. Hummel, Mary E. Hunt, Laennec Hurbon, Mark Hutchinson, Susan E. Hylen, Mary Beth Ingham, H. Larry Ingle, Dale T. Irvin, Jon Isaak, Paul John Isaak, Ada María Isasi-Díaz, Hans Raun Iversen, Margaret C. Jacob, Arthur James, Maria Jansdotter-Samuelsson, David Jasper, Werner G. Jeanrond, Renée Jeffery, David Lyle Jeffrey, Theodore W. Jennings, David H. Jensen, Robin Margaret Jensen, David Jobling, Dale A. Johnson, Elizabeth A. Johnson, Maxwell E. Johnson, Sarah Johnson, Mark D. Johnston, F. Stanley Jones, James William Jones, John R. Jones, Alissa Jones Nelson, Inge Jonsson, Jan Joosten, Elizabeth Judd, Mulambya Peggy Kabonde, Robert Kaggwa, Sylvester Kahakwa, Isaac Kalimi, Ogbu U. Kalu, Eunice Kamaara, Wayne C. Kannaday, Musimbi Kanyoro, Veli-Matti Kärkkäinen, Frank Kaufmann, Léon Nguapitshi Kayongo, Richard Kearney, Alice A. Keefe, Ralph Keen, Catherine Keller, Anthony J. Kelly, Karen Kennelly, Kathi Lynn Kern, Fergus Kerr, Edward Kessler, George Kilcourse, Heup Young Kim, Kim Sung-Hae, Kim Yong-Bock, Kim Yung Suk, Richard King, Thomas M. King, Robert M. Kingdon, Ross Kinsler, Hans G. Kippenberg, Cheryl A. Kirk-Duggan, Clifton Kirkpatrick, Leonid Kishkovsky, Nadieszda Kizenko, Jeffrey Klaiber, Hans-Josef Klauck, Sidney Knight, Samuel Kobia, Robert Kolb, Karla Ann Koll, Heikki Kotila, Donald Kraybill, Philip D. W. Krey, Yves Krumenacker, Jeffrey Kah-Jin Kuan, Simanga R. Kumalo, Peter Kuzmic, Simon Shui-Man Kwan, Kwok Pui-lan, André LaCocque, Stephen E. Lahey, John Tsz Pang Lai, Emiel Lamberts, Armando Lampe, Craig Lampe, Beverly J. Lanzetta, Eve LaPlante, Lizette Larson-Miller, Ariel Bybee Laughton, Leonard Lawlor, Bentley Layton, Robin A. Leaver, Karen Lebacqz, Archie Chi Chung Lee, Marilyn J. Legge, Hervé LeGrand, D. L. LeMahieu, Raymond Lemieux, Bill J. Leonard, Ellen M. Leonard, Outi Leppä, Jean Lesaulnier, Nantawan Boonprasat Lewis, Henrietta Leyser, Alexei Lidov, Bernard Lightman, Paul Chang-Ha Lim, Carter Lindberg, Mark R. Lindsay, James R. Linville, James C. Livingston, Ann Loades, David Loades, Jean-Claude Loba-Mkole, Lo Lung Kwong, Wati Longchar, Eleazar López, David W. Lotz, Andrew Louth, Robin W. Lovin, William Luis, Frank D. Macchia, Diarmaid N. J. MacCulloch, Kirk R. MacGregor, Marjory A. MacLean, Donald MacLeod, Tomas S. Maddela, Inge Mager, Laurenti Magesa, David G. Maillu, Fortunato Mallimaci, Philip Mamalakis, Kä Mana, Ukachukwu Chris Manus, Herbert Robinson Marbury, Reuel Norman Marigza, Jacqueline Mariña, Antti Marjanen, Luiz C. L. Marques, Madipoane Masenya (ngwan'a Mphahlele), Caleb J. D. Maskell, Steve Mason, Thomas Massaro, Fernando Matamoros Ponce, András Máté-Tóth, Odair Pedroso Mateus, Dinis Matsolo, Fumitaka Matsuoka, John D'Arcy May, Yelena Mazour-Matusevich, Theodore Mbazumutima, John S. McClure, Christian McConnell, Lee Martin McDonald, Gary B. McGee, Thomas McGowan, Alister E. McGrath, Richard J. McGregor, John A. McGuckin, Maud Burnett McInerney, Elsie Anne McKee, Mary B. McKinley, James F. McMillan, Ernan McMullin, Kathleen E. McVey, M. Douglas Meeks, Monica Jyotsna Melanchthon, Ilie Melniciuc-Puica, Everett Mendoza, Raymond A. Mentzer, William W. Menzies, Ina Merdjanova, Franziska Metzger, Constant J. Mews, Marvin Meyer, Carol Meyers, Vasile Mihoc, Gunner Bjerg Mikkelsen, Maria Inêz de Castro Millen, Clyde Lee Miller, Bonnie J. Miller-McLemore, Alexander Mirkovic, Paul Misner, Nozomu Miyahira, R. W. L. Moberly, Gerald Moede, Aloo Osotsi Mojola, Sunanda Mongia, Rebeca Montemayor, James Moore, Roger E. Moore, Craig E. Morrison O.Carm, Jeffry H. Morrison, Keith Morrison, Wilson J. Moses, Tefetso Henry Mothibe, Mokgethi Motlhabi, Fulata Moyo, Henry Mugabe, Jesse Ndwiga Kanyua Mugambi, Peggy Mulambya-Kabonde, Robert Bruce Mullin, Pamela Mullins Reaves, Saskia Murk Jansen, Heleen L. Murre-Van den Berg, Augustine Musopole, Isaac M. T. Mwase, Philomena Mwaura, Cecilia Nahnfeldt, Anne Nasimiyu Wasike, Carmiña Navia Velasco, Thulani Ndlazi, Alexander Negrov, James B. Nelson, David G. Newcombe, Carol Newsom, Helen J. Nicholson, George W. E. Nickelsburg, Tatyana Nikolskaya, Damayanthi M. A. Niles, Bertil Nilsson, Nyambura Njoroge, Fidelis Nkomazana, Mary Beth Norton, Christian Nottmeier, Sonene Nyawo, Anthère Nzabatsinda, Edward T. Oakes, Gerald O'Collins, Daniel O'Connell, David W. Odell-Scott, Mercy Amba Oduyoye, Kathleen O'Grady, Oyeronke Olajubu, Thomas O'Loughlin, Dennis T. Olson, J. Steven O'Malley, Cephas N. Omenyo, Muriel Orevillo-Montenegro, César Augusto Ornellas Ramos, Agbonkhianmeghe E. Orobator, Kenan B. Osborne, Carolyn Osiek, Javier Otaola Montagne, Douglas F. Ottati, Anna May Say Pa, Irina Paert, Jerry G. Pankhurst, Aristotle Papanikolaou, Samuele F. Pardini, Stefano Parenti, Peter Paris, Sung Bae Park, Cristián G. Parker, Raquel Pastor, Joseph Pathrapankal, Daniel Patte, W. Brown Patterson, Clive Pearson, Keith F. Pecklers, Nancy Cardoso Pereira, David Horace Perkins, Pheme Perkins, Edward N. Peters, Rebecca Todd Peters, Bishop Yeznik Petrossian, Raymond Pfister, Peter C. Phan, Isabel Apawo Phiri, William S. F. Pickering, Derrick G. Pitard, William Elvis Plata, Zlatko Plese, John Plummer, James Newton Poling, Ronald Popivchak, Andrew Porter, Ute Possekel, James M. Powell, Enos Das Pradhan, Devadasan Premnath, Jaime Adrían Prieto Valladares, Anne Primavesi, Randall Prior, María Alicia Puente Lutteroth, Eduardo Guzmão Quadros, Albert Rabil, Laurent William Ramambason, Apolonio M. Ranche, Vololona Randriamanantena Andriamitandrina, Lawrence R. Rast, Paul L. Redditt, Adele Reinhartz, Rolf Rendtorff, Pål Repstad, James N. Rhodes, John K. Riches, Joerg Rieger, Sharon H. Ringe, Sandra Rios, Tyler Roberts, David M. Robinson, James M. Robinson, Joanne Maguire Robinson, Richard A. H. Robinson, Roy R. Robson, Jack B. Rogers, Maria Roginska, Sidney Rooy, Rev. Garnett Roper, Maria José Fontelas Rosado-Nunes, Andrew C. Ross, Stefan Rossbach, François Rossier, John D. Roth, John K. Roth, Phillip Rothwell, Richard E. Rubenstein, Rosemary Radford Ruether, Markku Ruotsila, John E. Rybolt, Risto Saarinen, John Saillant, Juan Sanchez, Wagner Lopes Sanchez, Hugo N. Santos, Gerhard Sauter, Gloria L. Schaab, Sandra M. Schneiders, Quentin J. Schultze, Fernando F. Segovia, Turid Karlsen Seim, Carsten Selch Jensen, Alan P. F. Sell, Frank C. Senn, Kent Davis Sensenig, Damían Setton, Bal Krishna Sharma, Carolyn J. Sharp, Thomas Sheehan, N. Gerald Shenk, Christian Sheppard, Charles Sherlock, Tabona Shoko, Walter B. Shurden, Marguerite Shuster, B. Mark Sietsema, Batara Sihombing, Neil Silberman, Clodomiro Siller, Samuel Silva-Gotay, Heikki Silvet, John K. Simmons, Hagith Sivan, James C. Skedros, Abraham Smith, Ashley A. Smith, Ted A. Smith, Daud Soesilo, Pia Søltoft, Choan-Seng (C. S.) Song, Kathryn Spink, Bryan Spinks, Eric O. Springsted, Nicolas Standaert, Brian Stanley, Glen H. Stassen, Karel Steenbrink, Stephen J. Stein, Andrea Sterk, Gregory E. Sterling, Columba Stewart, Jacques Stewart, Robert B. Stewart, Cynthia Stokes Brown, Ken Stone, Anne Stott, Elizabeth Stuart, Monya Stubbs, Marjorie Hewitt Suchocki, David Kwang-sun Suh, Scott W. Sunquist, Keith Suter, Douglas Sweeney, Charles H. Talbert, Shawqi N. Talia, Elsa Tamez, Joseph B. Tamney, Jonathan Y. Tan, Yak-Hwee Tan, Kathryn Tanner, Feiya Tao, Elizabeth S. Tapia, Aquiline Tarimo, Claire Taylor, Mark Lewis Taylor, Bishop Abba Samuel Wolde Tekestebirhan, Eugene TeSelle, M. Thomas Thangaraj, David R. Thomas, Andrew Thornley, Scott Thumma, Marcelo Timotheo da Costa, George E. “Tink” Tinker, Ola Tjørhom, Karen Jo Torjesen, Iain R. Torrance, Fernando Torres-Londoño, Archbishop Demetrios [Trakatellis], Marit Trelstad, Christine Trevett, Phyllis Trible, Johannes Tromp, Paul Turner, Robert G. Tuttle, Archbishop Desmond Tutu, Peter Tyler, Anders Tyrberg, Justin Ukpong, Javier Ulloa, Camillus Umoh, Kristi Upson-Saia, Martina Urban, Monica Uribe, Elochukwu Eugene Uzukwu, Richard Vaggione, Gabriel Vahanian, Paul Valliere, T. J. Van Bavel, Steven Vanderputten, Peter Van der Veer, Huub Van de Sandt, Louis Van Tongeren, Luke A. Veronis, Noel Villalba, Ramón Vinke, Tim Vivian, David Voas, Elena Volkova, Katharina von Kellenbach, Elina Vuola, Timothy Wadkins, Elaine M. Wainwright, Randi Jones Walker, Dewey D. Wallace, Jerry Walls, Michael J. Walsh, Philip Walters, Janet Walton, Jonathan L. Walton, Wang Xiaochao, Patricia A. Ward, David Harrington Watt, Herold D. Weiss, Laurence L. Welborn, Sharon D. Welch, Timothy Wengert, Traci C. West, Merold Westphal, David Wetherell, Barbara Wheeler, Carolinne White, Jean-Paul Wiest, Frans Wijsen, Terry L. Wilder, Felix Wilfred, Rebecca Wilkin, Daniel H. Williams, D. Newell Williams, Michael A. Williams, Vincent L. Wimbush, Gabriele Winkler, Anders Winroth, Lauri Emílio Wirth, James A. Wiseman, Ebba Witt-Brattström, Teofil Wojciechowski, John Wolffe, Kenman L. Wong, Wong Wai Ching, Linda Woodhead, Wendy M. Wright, Rose Wu, Keith E. Yandell, Gale A. Yee, Viktor Yelensky, Yeo Khiok-Khng, Gustav K. K. Yeung, Angela Yiu, Amos Yong, Yong Ting Jin, You Bin, Youhanna Nessim Youssef, Eliana Yunes, Robert Michael Zaller, Valarie H. Ziegler, Barbara Brown Zikmund, Joyce Ann Zimmerman, Aurora Zlotnik, Zhuo Xinping
- Edited by Daniel Patte, Vanderbilt University, Tennessee
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- Book:
- The Cambridge Dictionary of Christianity
- Published online:
- 05 August 2012
- Print publication:
- 20 September 2010, pp xi-xliv
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A lower bound using Hamilton-type circuits and its applications
- Part of
- John T. Chen
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- Journal:
- Journal of Applied Probability / Volume 40 / Issue 4 / September 2003
- Published online by Cambridge University Press:
- 14 July 2016, pp. 1121-1132
- Print publication:
- September 2003
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This paper presents a degree-two probability lower bound for the union of an arbitrary set of events in an arbitrary probability space. The bound is designed in terms of the first-degree Bonferroni summation and pairwise joint probabilities of events, which are represented as weights of edges in a Hamilton-type circuit in a connected graph. The proposed lower bound strengthens the Dawson–Sankoff lower bound in the same way that Hunter and Worsley's degree-two upper bound improves the degree-two Bonferroni-type optimal upper bound. It can be applied to statistical inference in time series and outlier diagnoses as well as the study of dose response curves.
De novo synthesis of minus strand RNA by the rotavirus RNA polymerase in a cell-free system involves a novel mechanism of initiation
- DAYUE CHEN, JOHN T. PATTON
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The replicase activity of rotavirus open cores has been used to study the synthesis of (−) strand RNA from viral (+) strand RNA in a cell-free replication system. The last 7 nt of the (+) strand RNA, 5′-UGUGACC-3′, are highly conserved and are necessary for efficient (−) strand synthesis in vitro. Characterization of the cell-free replication system revealed that the addition of NaCl inhibited (−) strand synthesis. By preincubating open cores with (+) strand RNA and ATP, CTP, and GTP prior to the addition of NaCl and UTP, the salt-sensitive step was overcome. Thus, (−) strand initiation, but not elongation, was a salt-sensitive process in the cell-free system. Further analysis of the requirements for initiation showed that preincubating open cores and the (+) strand RNA with GTP or UTP, but not with ATP or CTP, allowed (−) strand synthesis to occur in the presence of NaCl. Mutagenesis suggested that in the presence of GTP, (−) strand synthesis initiated at the 3′-terminal C residue of the (+) strand template, whereas in the absence of GTP, an aberrant initiation event occurred at the third residue upstream from the 3′ end of the (+) strand RNA. During preincubation with GTP, formation of the dinucleotides pGpG and ppGpG was detected; however, no such products were made during preincubation with ATP, CTP, or UTP. Replication assays showed that pGpG, but not GpG, pApG, or ApG, served as a specific primer for (−) strand synthesis and that the synthesis of pGpG may occur by a template-independent process. From these data, we conclude that initiation of rotavirus (−) strand synthesis involves the formation of a ternary complex consisting of the viral RNA-dependent RNA polymerase, viral (+) strand RNA, and possibly a 5′-phosphorylated dinucleotide, that is, pGpG or ppGpG.
Fabrication and Characterization of Calcium Phosphate / Porous Silicon / Silicon Structures Doped with Platinum Antitumor Compounds
- Jeffery L. Coffer, Xin Li, John St. John, Russell F. Pinizzotto, Yandong Chen, Jon Newey, Leigh T. Canham
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- Journal:
- MRS Online Proceedings Library Archive / Volume 599 / 1999
- Published online by Cambridge University Press:
- 10 February 2011, 61
- Print publication:
- 1999
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A process has been developed which permits the encapsulation of an established class of platinum anticancer drugs such as cis-Platin (cis-diammine-dichloroplatinum (II)) within synthetic biocompatible calcium phosphate films that are electrochemically-grown on porous Si/Si substrates. These platinum complex-doped hydroxyapatite / porous Si / Si materials have been characterized by scanning electron microscopy (SEM), energy dispersive x-ray spectroscopy (XEDS), and secondary ion mass spectrometry (SIMS). Upon immersion of these structures into aqueous media, the desired platinum species can be released into the surrounding environment. This study also focuses on the influence of initial platinum concentration for a given complex in the deposition process on the rate and resultant amount of platinum complex that can be delivered to the surroundings in vitro. Both inductively-coupled plasma (ICP) spectroscopy and uv-visible absorption spectrometry have been employed to monitor the release of the encapsulated drug from the calcium phosphate layers.
Biochemical and morphological analysis of non-NMDA receptor mediated excitotoxicity in chick embryo retina
- QUAN CHEN, JOHN W. OLNEY, MADELON T. PRICE, CARMELO ROMANO
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- Journal:
- Visual Neuroscience / Volume 16 / Issue 1 / January 1999
- Published online by Cambridge University Press:
- 01 January 1999, pp. 131-139
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Ionotropic glutamate receptors (iGluRs) are ligand-gated ion channels that mediate glutamatergic neurotransmission, and when pathologically overstimulated induce excitotoxic neuronal death. Of the two families of iGluRs, the non-NMDA receptors have received less experimental attention than the NMDA receptors as mediators of neuronal death in in vitro systems. We have demonstrated that non-NMDA receptor activation is highly lethal for neurons of the chick embryo retina, and further characterize this phenomenon here. Treatment of isolated retinas with any of the non-NMDA receptor agonists glutamate, AMPA, or KA, in the presence of the NMDA receptor antagonist MK-801, led to pathomorphology and cell death. KA was the most effective toxin. All of KA-induced toxicity could be blocked by selective AMPA receptor blockers. The toxicity of both AMPA and glutamate could be greatly increased using cyclothiazide, which blocks AMPA receptor desensitization. These results indicate that KA is the most powerful toxin because it is a non-desensitizing agonist at the AMPA receptors. Glutamate exhibited a paradoxical ability to prevent KA-induced toxicity as measured by a biochemical assay of cell death. Also, histological studies indicated that glutamate selectively blocked KA-induced pathomorphological changes in bipolar cells. This protective effect of glutamate was not mimicked by AMPA, NMDA, or any of several metabotropic receptor agonists, indicating that it may be mediated by a receptor of undescribed pharmacology.